sphingoid - type bases 
 that contain vicinal amino alcohols are key 
 structural and functional components of the plasma membranes of nearly 
 all eukaryotic cells . the sphingolipids that they form play a crucial 
 role in many physiological processes and 
 are implicated in many common human diseases , including diabetes , cancer , and various 
 neurological syndromes . d - erythro - sphingosine ( 1 ) and d - erythro - sphinganine ( 2 ) both strongly 
 inhibit protein kinase c , whereas d - ribo - phytosphingosine ( 3 ) is 
 a potential heat - stress signal in yeast cells . more simple structures from this family of natural products also 
 display potent biological properties . spisulosine ( 4 ) , 
 originally isolated from the clam spisula polynyma , has been shown to have significant cytotoxic activity by the disassembly 
 of actin stress fibers . because 
 of their biological significance and the complicated isolation 
 of sphingolipids from natural sources , methods for the asymmetric 
 synthesis of these compounds and their derivatives have received considerable 
 attention . a common approach involves the preparation of the anti - vicinal amino - alcohol motif using starting materials from the chiral 
 pool , such as carbohydrates and amino acids . in particular , several 
 members of the sphingoid family of natural products have been synthesized 
 by the stereoselective addition of nucleophiles to aldehydes derived 
 from serine . recently , 
 more specific methods , including the addition of allenylzinc complexes 
 to chiral sulfinyl imines , an asymmetric 
 henry reaction involving a chiral copper complex , and the nucleophilic ring opening of chiral aziridine - derived 
 sulfamates , have all been used as the 
 key step for the preparation of the anti - vicinal 
 amino - alcohol moiety in these natural products . d - erythro - sphingosine ( 1 ) , d - erythro - sphinganine ( 2 ) , d - ribo - phytosphingosine 
 ( 3 ) , and ( + ) -spisulosine ( 4 ) . in 2005 , we reported a new approach for the preparation 
 of anti - vicinal amino alcohols using a palladium(ii)-catalyzed 
 ether - directed overman rearrangement . mechanistic studies with a range of substrates showed that an ether 
 oxygen atom adjacent to an allylic trichloroacetimidate can direct 
 the facial complexation of the pd(ii)-catalyst and the subsequent 
 rearrangement , resulting in the preparation of allylic anti - vicinal amino alcohols in high diastereoselectivity ( scheme 1 ) . since then , we have 
 shown that the products of this process can be transformed into various 
 natural products , including -hydroxy--amino acids , the alkaloids -conhydrine and ( + ) -monanchorin as well as several members of the clavaminol family . in our continuing studies of how the stereogenic 
 centers within a molecule can influence the outcome of rearrangement 
 reactions , we were interested in investigating the use of directed 
 overman rearrangements for the general preparation of sphingoid - type 
 bases . we now report the synthesis of d - erythro - sphinganine ( 2 ) and the antitumor agent ( + ) -spisulosine 
 ( 4 ) using a mom ether - directed pd(ii)-catalyzed 
 overman rearrangement to create the key anti - vicinal 
 amino - alcohol moiety . we also describe a novel strategy for the preparation 
 of d - ribo - phytosphingosine ( 3 ) and l - arabino - phytosphingosine ( 35 ) using an overman rearrangement of a chiral allylic trichloroacetimidate . our investigation began with 
 the preparation of a suitable allylic - alcohol 
 substrate for the ether - directed overman rearrangement that would 
 ultimately yield both d - erythro - sphinganine 
 ( 2 ) and ( + ) -spisulosine ( 4 ) . initially , 
 a chiral diol was prepared by a sharpless asymmetric dihydroxylation 
 of 1-heptadecene . as with other long - chain 
 terminal alkenes , dihydroxylation of 5 gave diol 6 in only modest enantiomeric excess ( 86% ) . however , recrystallization from ethyl acetate allowed isolation 
 of 6 in > 99% enantiomeric excess and in 87% yield . the 
 primary and secondary hydroxyl groups of 6 were then 
 selectively protected using tbdms and mom ethers , respectively , under 
 standard conditions , giving 7 in quantitative yield . removal of the tbdms protecting group was followed by a one - pot swern 
 oxidation / horner  wadsworth  emmons reaction of 8 with triethyl phosphonoacetate under masamune dibal - h 
 reduction of 9 completed the seven - step synthesis of 
 allylic alcohol 10 in 68% overall yield ( scheme 2 ) . allylic alcohol 10 was transformed into corresponding 
 allylic trichloroacetimidate 11 using trichloroacetonitrile 
 and dbu , and this was treated with bis(acetonitrile)palladium(ii ) 
 chloride ( 10 mol % ) to affect the key overman rearrangement ( scheme 3).p - benzoquinone was also added to the directed rearrangement reaction 
 because previous studies have shown that this prevents the side reaction 
 that forms the -product via a pd(0)-catalyzed process . analysis of the h nmr spectrum of the crude material 
 from this reaction showed the presence of the erythro- and threo - allylic trichloroacetamides in a 28:1 
 diastereomeric ratio , respectively . purification by column chromatography 
 allowed the isolation of major erythro - diastereomer 12 in 78% yield from allylic alcohol 10 . to complete 
 the synthesis of d - erythro - sphinganine ( 2 ) , alkene 12 was subjected to ozonolysis followed 
 by a reductive workup , which gave alcohol 13 in 78% yield . removal of both protecting groups under acid - mediated 
 conditions completed the 11-step synthesis of d - erythro - sphinganine ( 2 ) in 41% overall yield . alcohol 13 was 
 also used as an intermediate for the 
 synthesis of the antitumor agent ( + ) -spisulosine ( 4 ) 
 ( scheme 4 ) . activation of the primary alcohol 
 as the mesylate followed by displacement with sodium bromide gave 
 bromide 14 in good yield . br 
 bond by hydrogenation also resulted in the reduction of the trichloromethyl 
 group to give n - acetyl derivative 15 in 68% yield . hydrolysis of the n - acetyl group 
 and removal of the mom protecting group by treatment with 6 m hydrochloric 
 acid gave ( + ) -spisulosine ( 4 ) in quantitative yield . having successfully completed the synthesis 
 of d - erythro - sphinganine ( 2 ) and ( + ) -spisulosine 
 ( 4 ) using a highly diastereoselective mom ether - directed 
 overman rearrangement as the key step , a similar strategy was proposed 
 for the synthesis of d - ribo - phytosphingosine 
 ( 3 ) . a nine - step synthesis was developed from d - ribose ( 16 ) to allylic alcohol 24 ( a precursor 
 deemed suitable for a directed overman rearrangement ; scheme 5 ) . d - ribose ( 16 ) was converted 
 under standard conditions to 2,3-isopropylidine-1-methoxy - d - ribofuranoside ( 17 ) . iodination 
 of 17 then allowed vasella fragmentation in the presence 
 of zinc and acetic acid to give aldehyde 19 . attempts at the isolation of 19 led to the formation of a mixture of diastereomers as well as substantial 
 decomposition . therefore , before isolation the aldehyde was reduced 
 at 0 c with sodium borohydride to give alcohol 20 in 89% yield over the two steps . installation of the lipid side 
 chain was then achieved by cross metathesis of 20 with 
 1-tetradecene using grubbs second - generation catalyst ( 5 mol % ) . hydrogenation 
 of the resulting alkene and purification gave 22 in 82% 
 yield over the two steps . the synthesis of allylic alcohol 24 was then completed using a one - pot swern oxidation / horner  wadsworth emmons 
 reaction of alcohol 22 , followed by dibal - h reduction 
 of the ester . optimization of this nine - step route allowed the scalable 
 synthesis of allylic alcohol 24 in 40% overall yield . with allylic alcohol 24 in hand , initially , allylic alcohol 24 was converted to allylic trichloroacetimidate 25 using 
 trichloroacetonitrile and dbu ( scheme 6 ) . the h nmr spectrum of the crude material from this reaction confirmed 
 a complete conversion . however , the attempted rearrangement using 
 various pd(ii ) catalysts , including bis(acetonitrile)palladium(ii ) 
 chloride , gave none of the desired allylic trichloroacetamide products . instead , substantial decomposition of the starting material was observed 
 resulting from the loss of the acetonide protecting group . the steric 
 bulk surrounding the alkene moiety of 25 likely results 
 in a slow rearrangement and allows other competing pathways to come 
 to prominence , such as the pd(ii)-mediated hydrolysis of the acetonide 
 group . although this process did 
 give allylic trichloroacetamides 26 and 27 in 70% yield over the two steps , the reaction took 60 h to complete 
 and gave undesired diastereomer 26 as the major product 
 ( 26/27 , 1.7:1 ) . scheme 6 shows the proposed chairlike intermediates in which the side 
 chains adopt a conformation that minimizes allylic 1,3-strain . inspection of the intermediate leading to allylic 
 trichloroacetamide 26 shows that a hydrogen bond between 
 the imidate hydrogen atom and the adjacent acetonide oxygen may account 
 for its preferred formation . because of the problems 
 associated with the rearrangement of allylic 
 trichloroacetimidate 25 , an alternative approach for 
 the synthesis of d - ribo - phytosphingosine 
 ( 3 ) was devised . it was proposed that the chiral amino 
 group could be incorporated via an overman rearrangement of a chiral 
 allylic secondary alcohol . this was prepared in a two - stage approach 
 from previously synthesized alcohol 22 . emmons reaction with 
 dimethyl 2-oxopropylphosphonate gave e-,-unsaturated 
 ketone 28 in 79% yield ( scheme 7 ) . the reduction of 28 using 1 equiv of ( r)-cbs - me in the presence of borane  thf gave ( 2s)-allylic alcohol 29 as a single diastereomer in 99% 
 yield . alternatively , the reduction of 28 under the same 
 conditions using ( s)-cbs - me gave ( 2r)-allylic alcohol 30 in 64% yield . the stereogenic center formed by reduction of ketone 28 was then used to install the amino group required for d - ribo - phytosphingosine ( 3 ) ( scheme 8) . ( 2s)-allylic alcohol 29 was converted to the corresponding allylic trichloroacetimidate , 
 and various conditions were explored for the overman rearrangement . it was found that standard thermal conditions 
 ( k2co3 , p - xylene , and 140 c ) 
 gave after 12 h allylic trichloroacetamide 31 as a single 
 diastereomer in 71% yield over the two steps . however , the use of 
 microwave heating at the same temperature allowed the preparation 
 of 31 in similar yield after only 15 min . the ozonolysis 
 of 31 followed by a reductive workup with sodium borohydride 
 gave alcohol 32 in 73% yield . the synthesis of d - ribo - phytosphingosine ( 3 ) was then 
 completed using a two - step approach involving the basic hydrolysis 
 of the trichloroacetamide group and acid - mediated removal of the acetonide 
 protecting group . this gave d - ribo - phytosphingosine ( 3 ) after 13-steps 
 in 19% overall yield . using ( 2r)-allylic alcohol 30 , the formation of the allylic trichloroacetimidate and 
 overman rearrangement using microwave heating gave ( 4r)-diastereomer 33 in a similar manner ( scheme 8) . conversion to alcohol 34 by ozonolysis 
 was then followed by the two - step deprotection approach , which completed 
 the synthesis of l - arabino - phytosphingosine 
 ( 35 ) after 13-steps in 12% overall yield . new synthetic routes have been developed 
 for the preparation of 
 allylic alcohols bearing chiral hydroxyl side chains , and these have 
 been used to study the diastereoselective outcome of the overman rearrangement 
 for the selective preparation of anti - vicinal amino 
 alcohols . in particular , the use of a mom ether - directed palladium(ii)-catalyzed 
 overman rearrangement gave the corresponding ( 3s,4r)-allylic trichloroacetamide in a diastereomeric ratio 
 of 28:1 , and this synthetic intermediate was converted to the natural 
 products d - erythro - sphinganine ( 2 ) and ( + ) -spisulosine ( 4 ) . alternatively , the asymmetric 
 reduction of an ,-unsaturated methyl ketone using the 
 cbs oxazaborolidines followed by overman rearrangement of the resulting 
 allylic trichloroacetimidate under microwave heating allowed rapid 
 access to both d - ribo - phytosphingosine ( 3 ) and l - arabino - phytosphingosine 
 ( 35 ) . this work has generated further insight into the 
 scope and limitations of the overman rearrangement of allylic trichloroacetimidates 
 bearing stereogenic centers using either metal - catalyzed or thermal 
 conditions . current studies are underway to investigate additional 
 applications of these highly selective rearrangements for use in natural 
 product synthesis . all reagents and starting materials were obtained from commercial 
 sources and used as received . aluminum - backed 
 plates precoated with silica gel 60f254 were used for thin 
 layer chromatography and were visualized with a uv lamp or by staining 
 with potassium permanganate . h nmr spectra were recorded 
 on a nmr spectrometer at either 400 or 500 mhz , and data are reported 
 as follows : chemical shift in ppm relative to tetramethylsilane as 
 the internal standard , multiplicity ( s = singlet , d = doublet , t = 
 triplet , q = quartet , m = multiplet or overlap of nonequivalent resonances , 
 integration ) . c nmr spectra were recorded on a nmr spectrometer 
 at either 101 or 126 mhz , and data are reported as follows : chemical 
 shift in ppm relative to tetramethylsilane or the solvent as the internal 
 standard ( cdcl3 ,  77.0 ppm or cd3od , 
  44.0 ppm ) , multiplicity with respect to proton ( deduced from 
 dept experiments , c , ch , ch2 or ch3 ) . the infrared 
 spectra were recorded on a ftir spectrometer ; wavenumbers are indicated 
 in cm . mass spectra were recorded using electron - impact , 
 chemical - ionization , electrospray , or fast - atom - bombardment techniques . the optical rotations 
 were determined as solutions irradiating with the sodium d line (  
 = 589 nm ) using a polarimeter . the [ ]d values are 
 given in units of 10 deg cm g. the chiral hplc method was calibrated with the corresponding 
 racemic mixture . the microwave reactions were conducted using a cem 
 discover explorer synthesis unit and performed in glass tubes ( capacity 
 10 ml ) sealed with a septum . temperatures of the reaction mixtures 
 were monitored by an internal infrared temperature - control probe . a solution of ad - mix- ( 6.00 
 g ) in tert - butanol / water ( 1:1 ) ( 150 ml ) was stirred 
 vigorously at room temperature for 0.5 h. the reaction mixture was 
 cooled to 0 c , and 1-heptadecene ( 5 ) ( 1.16 g , 4.86 
 mmol ) was added . the reaction mixture was then stirred vigorously 
 for 40 h. the reaction was quenched by the addition of sodium sulfite 
 ( 6.00 g ) , stirred for 1 h , and extracted with ethyl acetate ( 3  
 100 ml ) . the combined extracts were dried ( na2so4 ) and concentrated to give a solid residue . this was purified by 
 dry flash column chromatography using hexane / ethyl acetate ( 2:1 ) ( 300 
 ml ) . recrystallization from ethyl acetate 
 gave ( 2r)-heptadecane-1,2-diol ( 6 ) as 
 a crystalline white solid ( 1.15 g , 87% ) . chiral hplc ( chiralcel ib 
 column ) analysis using 10% isopropanol in hexane as the elution solvent 
 indicated > 99% ee : mp 7880 c ( lit . mp 77.878.2 c ) ; [ ]d23 1.5 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.88 ( t , 3h , j 6.8 hz ) , 1.251.44 
 ( m , 28h ) , 1.81 ( dd , 1h , j 6.4 , 5.2 hz ) , 1.95 ( d , 
 1h , j 4.4 hz ) , 3.44 ( ddd , 1h , j 10.8 , 
 7.6 , 5.2 hz ) , 3.66 ( ddd , 1h , j 10.8 , 6.4 , 3.2 hz ) , 
 3.683.74 ( m , 1h ) ; c nmr ( 101 mhz , cdcl3 )  14.1 ( ch3 ) , 22.7 ( ch2 ) , 25.5 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.5 ( 2  ch2 ) , 29.6 ( 3  ch2 ) , 29.7 ( 3  ch2 ) , 
 31.9 ( ch2 ) , 33.3 ( ch2 ) , 66.9 ( ch2 ) , 72.3 ( ch ) ; ms ( ci ) m / z 273 ( mh , 3 ) , 255 ( 100 ) , 237 ( 5 ) , 123 ( 5 ) , 69 ( 6 ) . a mixture of ( 2r)-heptadecane-1,2-diol ( 6 ) ( 5.40 g , 19.85 mmol ) , tert - butyldimethylsilyl 
 chloride ( 4.49 g , 29.78 mmol ) , and imidazole ( 2.02 g , 29.78 mmol ) 
 was dissolved in tetrahydrofuran ( 300 ml ) , and the solution was stirred 
 overnight at room temperature . a white precipitate was removed by 
 filtration and washed with diethyl ether ( 200 ml ) . the combined filtrate 
 was concentrated and purified by flash column chromatography using 
 ( diethyl ether / petroleum ether 1:15 ) , which gave ( 2r)-1-(tert - butyldimethylsilyloxy)heptadecan-2-ol 
 ( 7.80 g , 100% ) as a colorless oil : ir ( nacl ) 3449 , 2925 , 1464 , 1254 , 
 1097 , 836 , 778 cm ; [ ]d23 5.9 ( c 1.2 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.07 ( s , 6h ) , 0.88 ( t , 3h , j 7.2 hz ) , 
 0.91 ( s , 9h ) , 1.241.47 ( m , 28h ) , 2.40 ( d , 1h , j 3.2 hz ) , 3.39 ( dd , 1h , j 10.4 , 8.4 hz ) , 3.593.65 
 ( m , 2h ) ; c nmr ( 101 mhz , cdcl3 )  5.4 
 ( ch3 ) , 5.3 ( ch3 ) , 14.1 ( ch3 ) , 18.3 ( c ) , 22.7 ( ch2 ) , 25.6 ( ch2 ) , 25.9 ( 3 
  ch3 ) , 29.4 ( ch2 ) , 29.6 ( 3  ch2 ) , 29.6 ( ch2 ) , 29.7 ( 3  ch2 ) , 
 29.7 ( ch2 ) , 31.9 ( ch2 ) , 32.8 ( ch2 ) , 67.3 ( ch2 ) , 71.9 ( ch ) ; ms ( ci ) m / z 387 ( mh , 100 ) , 369 ( 49 ) , 329 ( 19 ) , 295 ( 3 ) , 
 111 ( 2 ) . anal . calcd for c23h50o2si : c , 71.50 ; h , 12.95 . found : c , 71.51 ; h , 13.10 . a solution of ( 2r)-1-(tert - butyldimethylsilyloxy)heptadecan-2-ol ( 8.59 g , 22.2 
 mmol ) was dissolved in dichloromethane ( 400 ml ) , and the solution 
 was cooled to 0 c . diisopropylethylamine ( 11.6 ml , 66.7 mmol ) 
 was added followed by bromomethyl methyl ether ( 3.72 ml , 45.6 mmol ) . the solution was stirred for 0.5 h at 0 c and then heated under 
 reflux overnight . the reaction mixture was cooled to room temperature , 
 acidified with 1.0 m hydrochloric acid ( 15 ml ) , and extracted with 
 dichloromethane ( 3  200 ml ) . after removal of the solvent under 
 reduced pressure , the resulting material was purified by flash column 
 chromatography ( petroleum ether / diethyl ether 25:1 ) to give ( 2r)-1-(tert - butyldimethylsilyloxy)-2-(methoxymethoxy)heptadecane 
 ( 7 ) as a colorless oil ( 9.48 g , 100% ) : ir ( nacl ) 2923 , 
 1463 , 1250 , 1105 , 1036 , 835 , 774 cm ; [ ]d23 + 17.1 ( c 1.3 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.05 ( s , 6h ) , 0.850.91 ( m , 12h ) , 1.241.52 
 ( m , 28h ) , 3.38 ( s , 3h ) , 3.543.64 ( m , 3h ) , 4.65 ( d , 1h , j 6.8 hz ) , 4.78 ( d , 1h , j 6.8 hz ) ; c nmr ( 101 mhz , cdcl3 )  5.4 ( ch3 ) , 5.3 ( ch3 ) , 14.1 ( ch3 ) , 18.3 
 ( c ) , 22.7 ( ch2 ) , 25.4 ( ch2 ) , 25.9 ( 3  
 ch3 ) , 29.4 ( ch2 ) , 29.6 ( 3  ch2 ) , 29.6 ( ch2 ) , 29.7 ( 3  ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 31.8 ( ch2 ) , 31.9 ( ch2 ) , 55.4 ( ch3 ) , 65.9 ( ch2 ) , 78.3 ( ch ) , 
 96.3 ( ch2 ) ; ms m / z 431 
 ( mh , 41 ) , 399 ( 100 ) , 369 ( 72 ) , 343 ( 12 ) , 285 ( 5 ) , 161 
 ( 8) , 107 ( 10 ) , 73 ( 21 ) ; hrms ( ci ) calcd for c25h55o3si ( mh ) , 431.3920 ; found , 431.3922 . a solution of tetrabutylammonium fluoride ( 1.0 
 m in tetrahydrofuran , 22.00 ml , 22.00 mmol ) was added to a solution 
 of ( 2r)-1-(tert - butyldimethylsilyloxy)-2-(methoxymethoxy)heptadecane 
 ( 7 ) ( 7.88 g , 18.32 mmol ) in tetrahydrofuran ( 400 ml ) 
 at 0 c . the reaction mixture was concentrated , and 
 the resulting residue was resuspended in diethyl ether ( 200 ml ) . the 
 solution was washed with water ( 100 ml ) , and the aqueous layer was 
 extracted with diethyl ether ( 3  150 ml ) . the combined organic 
 extracts were dried ( mgso4 ) , concentrated , and purified 
 by flash column chromatography ( petroleum ether / diethyl ether 7:2 ) 
 to give ( 2r)-2-(methoxymethoxy)heptadecane-1-ol ( 8) as a white solid ( 5.91 g , 91% ) : mp 3234 c ; 
 ir ( nacl ) 2929 , 1216 , 1032 , 753 , 667 cm ; [ ]d23 27.6 
 ( c 1.2 , chcl3 ) ; h nmr ( 400 
 mhz , cdcl3 )  0.88 ( t , 3h , j 6.8 
 hz ) , 1.251.53 ( m , 28h ) , 3.04 ( dd , 1h , j 8.8 , 
 3.6 hz ) , 3.43 ( s , 3h ) , 3.463.62 ( m , 3h ) , 4.69 ( d , 1h , j 6.8 hz ) , 4.74 ( d , 1h , j 6.8 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.1 ( ch3 ) , 22.7 ( ch2 ) , 25.6 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.6 ( 2  ch2 ) , 29.6 ( 4  ch2 ) , 29.7 ( 2  ch2 ) , 31.7 ( ch2 ) , 31.9 ( ch2 ) , 55.6 ( ch3 ) , 65.7 ( ch2 ) , 82.4 ( ch ) , 
 97.0 ( ch2 ) ; ms ( ci ) m / z 317 ( mh , 9 ) , 285 ( 93 ) , 255 ( 80 ) , 181 ( 2 ) , 139 ( 3 ) , 97 
 ( 4 ) . anal . dimethyl sulfoxide ( 2.52 ml , 35.6 mmol ) 
 was added to a stirred solution of oxalyl chloride ( 1.74 ml , 19.93 
 mmol ) in dichloromethane ( 350 ml ) at 78 c . the reaction 
 mixture was stirred for 0.3 h before ( 2r)-2-(methoxymethoxy)heptadecane-1-ol 
 ( 8) ( 4.50 g , 14.24 mmol ) in dichloromethane ( 50 ml ) was 
 slowly added . the reaction mixture was stirred for an additional 0.3 
 h before triethylamine ( 9.90 ml , 71.20 mmol ) was added . this reaction 
 mixture was stirred for 0.5 h at 78 c , allowed to warm 
 to room temperature , and stirred for another 2 h. meanwhile , a solution 
 of lithium chloride ( 1.10 g , 25.63 mmol ) , triethyl phosphonoacetate 
 ( 4.23 ml , 21.36 mmol ) , and 1,8-diazabicycloundec-7-ene ( 3.22 
 ml , 21.36 mmol ) in acetonitrile ( 350 ml ) was prepared and stirred 
 for 1.0 h. the swern solution was concentrated in vacuo , the horner emmons 
 solution was added , and the reaction mixture was stirred at room temperature 
 overnight . the reaction was quenched by the addition of a saturated 
 solution of ammonium chloride ( 50 ml ) and concentrated to give an 
 orange residue , which was extracted with diethyl ether ( 4  100 
 ml ) . the organic layers were combined , dried ( mgso4 ) , and 
 concentrated to give an orange oil . purification by flash column chromatography 
 ( diethyl ether / petroleum ether 1:20 ) gave ethyl ( 2e,4r)-4-(methoxymethoxy)nonadecan-2-enoate ( 9 ) ( 5.48 g , 100% ) as a yellow oil : ir ( nacl ) 2922 , 1723 , 1265 , 
 1152 , 1030 , 921 cm ; [ ]d23 + 40.6 ( c 1.2 , 
 chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  
 0.88 ( t , 3h , j 6.8 hz ) , 1.251.68 ( m , 31h ) , 
 3.38 ( s , 3h ) , 4.164.23 ( m , 3h ) , 4.58 ( d , 1h , j 6.8 hz ) , 4.63 ( d , 1h , j 6.8 hz ) , 5.97 ( dd , 1h , j 15.6 , 1.2 hz ) , 6.81 ( dd , 1h , j 15.6 , 
 6.4 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.1 
 ( ch3 ) , 14.2 ( ch3 ) , 22.7 ( ch2 ) , 25.2 
 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.5 ( 3  ch2 ) , 29.6 ( 3  ch2 ) , 29.7 ( 2  ch2 ) , 31.9 ( ch2 ) , 34.9 ( ch2 ) , 55.6 ( ch3 ) , 60.5 ( ch2 ) , 75.3 ( ch ) , 94.6 ( ch2 ) , 121.8 
 ( ch ) , 148.0 ( ch ) , 166.3 ( c ) ; ms ( ci ) m / z 385 ( mh , 11 ) , 355 ( 33 ) , 323 ( 100 ) , 283 ( 47 ) , 173 ( 12 ) , 
 109 ( 4 ) . ethyl ( 2e,4r)-4-(methoxymethoxy)nonadecan-2-enoate ( 9 ) ( 4.7 g , 12.24 
 mmol ) was dissolved in diethyl ether ( 350 ml ) , and the solution was 
 cooled to 78 c . dibal - h ( 1 m in hexane , 27 ml , 27.00 
 mmol ) was added dropwise , and the reaction mixture was stirred at 
 78 c for 3 h before warming to room temperature . the 
 solution was cooled to 0 c , quenched by the addition of a saturated 
 solution of ammonium chloride ( 50 ml ) , and warmed to room temperature 
 with vigorous stirring over 1 h , producing a white precipitate . the 
 precipitate was filtered through a pad of celite and washed with diethyl 
 ether ( 400 ml ) . flash chromatography ( diethyl ether / petroleum ether 2:5 ) 
 gave ( 2e,4r)-4-(methoxymethoxy)nonadecan-2-ene-1-ol 
 ( 10 ) ( 3.60 g , 86% ) as a white solid : mp 3840 
 c ; ir ( nacl ) 3390 , 2913 , 2849 , 1471 , 1093 , 1002 , 914 , 716 cm ; [ ]d23 + 61.2 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.88 ( t , 
 3h , j 6.8 hz ) , 1.241.62 ( m , 29h ) , 3.37 ( s , 
 3h ) , 4.02 ( q , 1h , j 7.2 hz ) , 4.16 ( td , 2h , j 5.6 , 1.6 hz ) , 4.53 ( d , 1h , j 6.8 hz ) , 
 4.70 ( d , 1h , j 6.8 hz ) , 5.57 ( ddt , 1h , j 15.6 , 7.2 , 1.6 hz ) , 5.81 ( dt , 1h , j 15.6 , 5.6 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.1 ( ch3 ) , 22.7 ( ch2 ) , 25.4 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.6 ( 3  ch2 ) , 29.6 ( 2  ch2 ) , 29.7 ( 3  ch2 ) , 31.9 ( ch2 ) , 35.6 ( ch2 ) , 55.4 ( ch3 ) , 63.0 ( ch2 ) , 76.2 ( ch ) , 
 93.7 ( ch2 ) , 131.7 ( ch ) , 131.9 ( ch ) ; ms ( ci ) m / z 343 ( mh , 3 ) , 319 ( 11 ) , 281 ( 81 ) , 
 263 ( 14 ) , 157 ( 8) , 113 ( 7 ) , 85 ( 100 ) . ( 2e,4r)-4-(methoxymethoxy)nonadecan-2-ene-1-ol ( 10 ) ( 3.01 
 g , 8.80 mmol ) was dissolved in dichloromethane ( 300 ml ) , and the solution 
 was cooled to 0 c . 1,8-diazabicyclo[5.4.0]undec-7-ene ( 0.33 
 ml , 2.20 mmol ) was added to the solution followed by trichloroacetonitrile 
 ( 1.32 ml , 13.20 mmol ) . the reaction mixture was warmed to room temperature , 
 stirred for 2 h , filtered through a short pad of silica gel , and washed 
 with diethyl ether ( 200 ml ) . the resulting filtrate was concentrated 
 to give allylic trichloroacetimidate 11 , which was used 
 without further purification . resulting allylic trichloroacetimidate 11 was dissolved in toluene ( 300 ml ) , and bis(acetonitrile)palladium(ii ) 
 chloride ( 0.22 g , 0.88 mmol ) and p - benzoquinone ( 1.90 
 g , 17.60 mmol ) were added . the reaction mixture was stirred at 45 
 c for 24 h , concentrated , and purified by flash column chromatography 
 ( diethyl ether / petroleum ether 1:30 ) to give ( 3s,4r)-3-(2,2,2-trichloromethylcarbonylamino)-4-(methoxymethoxy)nonadecan-1-ene 
 ( 12 ) as a yellow oil ( 3.22 g , 78% over 2 steps ) : ir ( nacl ) 
 3292 , 2922 , 1717 , 1516 , 1465 , 1236 , 1033 , 819 , 721 cm ; [ ]d23 5.1 ( c 1.1 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.88 ( t , 3h , j 6.8 hz ) , 1.231.65 ( m , 28h ) , 3.43 ( s , 3h ) , 3.56 ( ddd , 1h , j 8.4 , 4.8 , 2.0 hz ) , 4.354.42 ( m , 1h ) , 4.65 ( d , 
 1h , j 6.8 hz ) , 4.74 ( d , 1h , j 6.8 
 hz ) , 5.305.36 ( m , 2h ) , 5.85 ( ddd , 1h , j 17.2 , 
 10.4 , 6.8 hz ) , 8.28 ( br d , 1h , j 7.6 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.1 ( ch3 ) , 
 22.7 ( ch2 ) , 25.7 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.5 ( 3  ch2 ) , 29.5 ( ch2 ) , 
 29.6 ( 2  ch2 ) , 29.7 ( 2  ch2 ) , 31.9 
 ( ch2 ) , 33.0 ( ch2 ) , 55.9 ( ch ) , 56.7 ( ch3 ) , 83.8 ( ch ) , 93.0 ( c ) , 98.1 ( ch2 ) , 118.9 ( ch2 ) , 131.6 ( ch ) , 161.4 ( c ) ; ms ( ci ) m / z 486 ( mh , 42 ) , 454 ( 100 ) , 416 ( 31 ) , 392 ( 23 ) , 356 ( 18 ) , 
 263 ( 38 ) , 214 ( 28 ) , 113 ( 17 ) , 85 ( 71 ) . calcd for c23h42cl3no3 : c , 56.79 ; h , 8.64 ; n , 
 2.88 . found : c , 56.87 ; h , 8.75 ; n , 2.79 . ( 3s,4r)-3-(2,2,2-trichloromethylcarbonylamino)-4-(methoxymethoxy)nonadecan-1-ene 
 ( 12 ) ( 1.46 g , 3.00 mmol ) was dissolved in a mixture of 
 dichloromethane ( 60 ml ) and methanol ( 20 ml ) , and the solution was 
 cooled to 78 c . after excess ozone 
 was purged with argon , sodium borohydride ( 0.11 g , 3.00 mmol ) was 
 added in portions . the solution was stirred for 1.5 h at 0 c 
 and acidified with 1 m hydrochloric acid ( 10 ml ) . the reaction was 
 quenched by the addition of water ( 20 ml ) and extracted with diethyl 
 ether ( 4  75 ml ) . the organic layers were combined , dried ( mgso4 ) , and concentrated to give an orange oil . purification by 
 flash column chromatography using ( diethyl ether / petroleum ether 1:1 ) 
 yielded ( 2s,3r)-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecan-1-ol 
 ( 13 ) ( 1.15 g , 78% over 2 steps ) as a colorless oil : ir 
 ( nacl ) 2922 , 1705 , 1521 , 1467 , 1030 , 819 , 822 cm ; [ ]d23 24.4 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.88 ( t , 3h , j 6.8 hz ) , 1.241.70 ( m , 28h ) , 2.69 ( dd , 1h , j 9.2 , 3.4 hz ) , 3.43 ( s , 3h ) , 3.703.81 ( m , 2h ) , 3.92 ( dq , 
 1h , j 8.4 , 3.4 hz ) , 4.03 ( dt , 1h , j 12.0 , 3.4 hz ) , 4.63 ( d , 1h , j 6.8 hz ) , 4.71 ( d , 
 1h , j 6.8 hz ) , 7.96 ( br d , 1h , j 8.4 hz ) ; c nmr ( 101 mhz , cdcl3 )  
 14.1 ( ch3 ) , 22.7 ( ch2 ) , 25.7 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.5 ( 2  ch2 ) , 
 29.6 ( 4  ch2 ) , 29.7 ( ch2 ) , 30.3 ( ch2 ) , 31.9 ( ch2 ) , 32.9 ( ch2 ) , 54.8 ( ch ) , 
 56.1 ( ch3 ) , 61.2 ( ch2 ) , 82.5 ( ch ) , 92.7 ( c ) , 
 97.9 ( ch2 ) , 162.2 ( c ) ; ms ( ci ) m / z 490 ( mh , 21 ) , 458 ( 18 ) , 428 ( 12 ) , 372 ( 100 ) , 
 340 ( 22 ) , 255 ( 5 ) , 137 ( 6 ) , 73 ( 16 ) calcd for c22h42cl3no4 : c , 53.87 ; h , 8.57 ; n , 
 2.85 . found : c , 53.93 ; h , 8.71 ; n , 2.95 . ( 2s,3r)-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecan-1-ol 
 ( 13 ) ( 0.06 g , 0.12 mmol ) was dissolved in 6 m hydrochloric 
 acid ( 10 ml ) , and the solution was heated at 60 c for 24 h. 
 the reaction mixture was cooled to room temperature and washed with 
 diethyl ether ( 3  10 ml ) . the aqueous layer was concentrated 
 to give ( 2r,3s)-2-aminooctadecane-1,3-diol 
 hydrochloride ( 2 ) ( 0.038 g , 100% ) as a colorless oil : 
 ir ( nacl ) 3348 , 2924 , 1600 , 1467 , 1051 cm ; [ ]d23 + 8.4 ( c 3.0 , meoh ) , lit . [ ]d25 + 8.1 ( c 1.0 , meoh ) ; h nmr ( 400 mhz , cd3od )  0.80 ( t , 3h , j 6.8 hz ) , 1.171.46 
 ( m , 28h ) , 3.10 ( dt , 1h , j 8.6 , 4.4 hz ) , 3.60 ( dd , 
 1h , j 11.6 , 8.6 hz ) , 3.653.72 ( m , 1h ) , 3.74 
 ( dd , 1h , j 11.6 , 4.4 hz ) ; c nmr ( 101 
 mhz , cd3od )  14.5 ( ch3 ) , 23.8 ( ch2 ) , 27.0 ( ch2 ) , 30.5 ( 2  ch2 ) , 
 30.6 ( 3  ch2 ) , 30.7 ( 3  ch2 ) , 30.7 
 ( ch2 ) , 30.8 ( ch2 ) , 33.1 ( ch2 ) , 34.2 
 ( ch2 ) , 58.5 ( ch ) , 58.9 ( ch2 ) , 70.3 ( ch ) ; ms 
 ( ci ) m / z 302 ( mh , 90 ) , 
 282 ( 17 ) , 267 ( 23 ) , 241 ( 36 ) , 137 ( 11 ) , 107 ( 22 ) , 73 ( 100 ) . a solution of ( 2s,3r)-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecan-1-ol 
 ( 13 ) ( 1.08 g , 2.20 mmol ) was dissolved in dichloromethane 
 ( 50 ml ) . methanesulfonyl chloride ( 0.37 ml , 3.30 mmol ) , triethylamine 
 ( 0.67 ml , 4.84 mmol ) , and 4-dimethylaminopyridine ( 0.03 g , 0.22 mmol ) 
 were added at 0 c , and the solution was stirred at room temperature 
 for 24 h. the reaction mixture was washed with water ( 20 ml ) and extracted 
 with dichloromethane ( 3  40 ml ) . the organic layer was dried 
 ( mgso4 ) and concentrated to give the crude product . purification 
 by flash column chromatography ( diethyl ether / petroleum ether 2:3 ) 
 gave ( 2s,3r)-1-methanesulfonate-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecane 
 ( 1.17 g , 93% ) as a colorless oil : ir ( nacl ) 3343 , 2916 , 1686 , 1521 , 
 1349 , 1171 , 1034 , 895 cm ; [ ]d23 22.0 
 ( c 0.9 , chcl3 ) ; h nmr ( 400 
 mhz , cdcl3 )  0.88 ( t , 3h , j 7.2 
 hz ) , 1.241.68 ( m , 28h ) , 3.06 ( s , 3h ) , 3.45 ( s , 3h ) , 3.62 ( ddd , 
 1h , j 8.0 , 4.6 , 2.8 hz ) , 4.234.29 ( m , 1h ) , 
 4.34 ( dd , 1h , j 10.8 , 7.6 hz ) , 4.50 ( dd , 1h , j 10.8 , 4.6 hz ) , 4.63 ( dd , 1h , j 6.8 hz ) , 
 4.73 ( d , 1h , j 6.8 hz ) , 8.13 ( br d , 1h , j 8.4 hz ) ; c nmr ( 101 mhz , cdcl3 )  
 14.1 ( ch3 ) , 22.7 ( ch2 ) , 25.9 ( ch2 ) , 29.4 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.5 ( 2 
  ch2 ) , 29.6 ( 2  ch2 ) , 29.7 ( ch2 ) , 30.0 ( 2  ch2 ) , 31.9 ( ch2 ) , 
 32.9 ( ch2 ) , 37.8 ( ch3 ) , 53.2 ( ch ) , 56.0 ( ch3 ) , 66.4 ( ch2 ) , 82.3 ( ch ) , 92.6 ( c ) , 98.2 ( ch2 ) , 162.2 ( c ) ; ms ( ci ) m / z 568 ( mh , 4 ) , 536 ( 10 ) , 502 ( 8) , 474 ( 20 ) , 438 ( 100 ) , 
 404 ( 89 ) , 370 ( 31 ) , 356 ( 21 ) , 241 ( 9 ) , 137 ( 15 ) , 97 ( 19 ) . anal . calcd 
 for c23h44cl3no6s : c , 
 48.59 ; h , 7.74 ; n , 2.46 . found : c , 48.64 ; h , 7.85 ; n , 2.58 . ( 2s,3r)-1-methanesulfonate-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecane 
 ( 0.20 g , 0.35 mmol ) was dissolved in dimethyl sulfoxide ( 10 ml ) , and 
 sodium bromide ( 0.18 g , 1.76 mmol ) was added . the resulting residue was dissolved in 
 diethyl ether ( 20 ml ) and washed with water ( 2  30 ml ) . purification by 
 column chromatography ( petroleum ether / diethyl ether 14:1 ) gave ( 2r,3r)-1-bromo-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecane 
 ( 14 ) ( 0.14 g , 73% ) as a colorless oil : ir ( nacl ) 3330 , 
 2921 , 1718 , 1517 , 1030 , 819 cm ; [ ]d23 + 30.3 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.88 ( t , 3h , j 6.8 hz ) , 1.251.62 
 ( m , 28h ) , 3.44 ( s , 3h ) , 3.57 ( dd , 1h , j 11.2 , 7.6 
 hz ) , 3.633.68 ( m , 2h ) , 4.26 ( ddt , 1h , j 9.2 , 
 7.6 , 4.0 hz ) , 4.65 ( d , 1h , j 6.8 hz ) , 4.73 ( d , 1h , j 6.8 hz ) , 7.69 ( br d , 1h , j 9.2 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.1 ( ch3 ) , 22.7 ( ch2 ) , 25.4 ( ch2 ) , 29.4 ( 2  ch2 ) , 29.5 ( 2  ch2 ) , 29.5 ( ch2 ) , 
 29.6 ( 2  ch2 ) , 29.7 ( 2  ch2 ) , 29.7 
 ( ch2 ) , 31.4 ( ch2 ) , 31.9 ( ch2 ) , 32.4 
 ( ch2 ) , 54.6 ( ch ) , 56.0 ( ch3 ) , 81.6 ( ch ) , 92.7 
 ( c ) , 97.8 ( ch2 ) , 161.8 ( c ) ; ms m / z 552 ( mh , 10 ) , 522 ( 71 ) , 492 ( 38 ) , 472 ( 16 ) , 
 438 ( 24 ) , 285 ( 100 ) , 239 ( 33 ) , 189 ( 12 ) , 151 ( 12 ) , 117 ( 11 ) ; hrms 
 ( ci ) calcd for c22h42brcl3no3 ( mh ) , 552.1414 ; found , 552.1416 . to a solution of ( 2r,3r)-1-bromo-2-(2,2,2-trichloromethylcarbonylamino)-3-(methoxymethoxy)octadecane 
 ( 14 ) ( 0.02 g , 0.04 mmol ) in methanol ( 5 ml ) was added 
 10% palladium on carbon ( 0.03 g ) and triethylamine ( 0.03 ml , 0.21 
 mmol ) . the reaction mixture was allowed to stir under an atmosphere 
 of hydrogen at room temperature for 18 h. the reaction mixture was 
 filtered through a short pad of celite , which was washed with methanol 
 ( 50 ml ) and concentrated in vacuo . purification by 
 flash column chromatography ( petroleum ether / diethyl ether 1:6 ) gave 
 ( 2s,3r)-2-acetylamino-3-(methoxymethoxy)octadecane 
 ( 15 ) ( 0.01 g , 68% ) as a white solid : mp 3537 
 c ; ir ( nacl ) 3370 , 2925 , 1647 , 1540 , 1372 , 1034 , 920 cm ; [ ]d23 45.3 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.81 
 ( t , 3h , j 6.4 hz ) , 1.02 ( d , 3h , j 6.8 hz ) , 1.181.51 ( m , 28h ) , 1.93 ( s , 3h ) , 3.353.38 
 ( m , 4h ) , 3.903.97 ( m , 1h ) , 4.55 ( d , 1h , j 6.8 hz ) , 4.65 ( d , 1h , j 6.8 hz ) , 6.69 ( br s , 1h ) ; c nmr ( 101 mhz , cdcl3 )  13.9 ( ch3 ) , 14.1 ( ch3 ) , 22.7 ( ch2 ) , 23.5 ( ch3 ) , 25.9 ( ch2 ) , 29.3 ( ch2 ) , 29.5 ( 2  ch2 ) , 29.5 ( 4  ch2 ) , 29.6 ( 2  ch2 ) , 29.7 ( ch2 ) , 31.9 ( ch2 ) , 32.7 ( ch2 ) , 47.2 ( ch ) , 55.7 ( ch3 ) , 84.4 ( ch ) , 98.1 ( ch2 ) , 169.1 ( c ) ; ms m / z 372 ( mh , 100 ) , 340 ( 31 ) , 310 ( 4 ) , 174 ( 3 ) , 113 ( 4 ) , 71 ( 10 ) ; hrms 
 ( ci ) calcd for c22h46no3 ( mh ) , 372.3478 ; found , 372.3475 . ( 2s,3r)-2-acetylamino-3-(methoxymethoxy)octadecane 
 ( 15 ) ( 0.01 g , 0.03 mmol ) was dissolved in 6 m hydrochloric 
 acid ( 1.5 ml ) , and the solution was heated at 60 c for 48 h. 
 the reaction mixture was cooled and washed with diethyl ether ( 3  
 10 ml ) . the aqueous layer was concentrated to give ( 2s,3r)-2-aminooctadecan-3-ol hydrochloride ( 4 ) ( 0.008 g , 100% ) as a white solid : mp 6466 c ; 
 [ ]d23 + 7.5 ( c 0.3 , meoh ) , lit . [ ]d25 + 7.15 ( c 0.42 , meoh ) ; h nmr ( 400 mhz , 
 cd3od )  0.80 ( t , 3h , j 5.6 hz ) , 
 1.12 ( d , 3h , j 5.2 hz ) , 1.191.35 ( m , 28h ) , 
 3.143.20 ( m , 1h ) , 3.573.62 ( m , 1h ) ; c 
 nmr ( 101 mhz , cd3od )  12.1 ( ch3 ) , 14.5 
 ( ch3 ) , 23.8 ( ch2 ) , 27.0 ( ch2 ) , 30.5 
 ( ch2 ) , 30.7 ( ch2 ) , 30.7 ( 2  ch2 ) , 30.8 ( 4  ch2 ) , 30.8 ( 2  ch2 ) , 
 33.1 ( ch2 ) , 34.0 ( ch2 ) , 52.6 ( ch ) , 71.7 ( ch ) ; 
 ms ( ci ) m / z 286 ( mh , 
 100 ) , 268 ( 16 ) , 241 ( 8) , 197 ( 12 ) , 113 ( 100 ) , 85 ( 41 ) . concentrated hydrochloric 
 acid ( 3436% , 0.02 ml ) was added to a stirred solution of d - ribose ( 16 ) ( 0.20 g , 1.34 mmol ) in acetone ( 3 
 ml ) and methanol ( 3 ml ) . the solution was heated under reflux for 
 2 h and cooled to room temperature . the reaction was neutralized by 
 the addition of a saturated solution of sodium hydrogen carbonate 
 ( 10 ml ) and extracted with ethyl acetate ( 2  50 ml ) . the organic 
 layers were combined and washed with water ( 40 ml ) and brine ( 40 ml ) , 
 dried ( mgso4 ) , and concentrated in vacuo to yield 2,3-isopropylidine-1-methoxy - d - ribofuranoside ( 17 ) ( 0.23 g , 84% ) as a colorless 
 oil ( the spectroscopic data were as reported in the literature ) : [ ]d25 52.8 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  1.32 
 ( s , 3h ) , 1.48 ( s , 3h ) , 3.24 ( dd , 1h , j 10.5 , 2.7 
 hz ) , 3.43 ( s , 3h ) , 3.61 ( ddd , 1h , j 12.8 , 10.5 , 2.7 
 hz ) , 3.70 ( dt , 1h , j 12.8 , 2.7 hz ) , 4.43 ( t , 1h , j 2.7 hz ) , 4.59 ( d , 1h , j 5.9 hz ) , 4.84 
 ( d , 1h , j 5.9 hz ) , 4.97 ( s , 1h ) ; c nmr 
 ( 101 mhz , cdcl3 )  24.7 ( ch3 ) , 26.3 ( ch3 ) , 55.5 ( ch3 ) , 64.0 ( ch2 ) , 81.5 ( ch ) , 
 85.8 ( ch ) , 88.4 ( ch ) , 110.0 ( ch ) , 112.1 ( c ) ; ms ( ci ) m / z 205 ( mh , 14 ) , 173 ( 100 ) , 113 ( 5 ) , 
 85 ( 10 ) , 69 ( 14 ) . iodine ( 0.34 
 g , 1.34 mmol ) was added to a stirred solution of 2,3-isopropylidine-1-methoxy - d - ribofuranoside ( 17 ) ( 0.23 g , 1.12 mmol ) , imidazole 
 ( 0.11 g , 1.68 mmol ) , and triphenylphosphine ( 0.35 g , 1.34 mmol ) in 
 toluene ( 15 ml ) and acetonitrile ( 5 ml ) . the solution was heated under 
 reflux for 0.1 h and cooled to room temperature . iodine was added 
 in 10 mg portions until the solution remained dark - brown . the solution 
 was diluted with diethyl ether ( 40 ml ) and washed with a saturated 
 solution of sodium thiosulfate ( 80 ml ) , water ( 100 ml ) , and brine 
 ( 70 ml ) . the organic layer was dried ( mgso4 ) , concentrated 
 in vacuo , and filtered through a short plug of silica ( ethyl acetate / petroleum 
 ether 1:20 ) to yield 5-deoxy-5-iodo-2,3-isopropylidine-1-methoxy - d - ribofuranoside ( 18 ) ( 0.33 g , 94% ) as a colorless 
 oil : [ ]d25 65.7 ( c 1.0 , chcl3 ) , lit . [ ]d25 68.3 ( c 0.1 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  1.33 
 ( d , 3h , j 0.4 hz ) , 1.48 ( d , 3h , j 0.4 hz ) , 3.16 ( t , 1h , j 10.0 hz ) , 3.29 ( dd , 1h , j 10.0 , 6.0 hz ) , 3.37 ( s , 3h ) , 4.44 ( ddd , 1h , j 10.0 , 6.0 , 0.7 hz ) , 4.63 ( d , 1h , j 5.9 hz ) , 4.76 
 ( dd , 1h , j 5.9 , 0.7 hz ) , 5.05 ( s , 1h ) ; c nmr ( 101 mhz , cdcl3 )  6.8 ( ch2 ) , 25.2 
 ( ch3 ) , 26.6 ( ch3 ) , 55.4 ( ch3 ) , 83.2 
 ( ch ) , 85.5 ( ch ) , 87.6 ( ch ) , 109.9 ( ch ) , 112.8 ( c ) ; ms ( ci ) m / z 315 ( mh , 8) , 279 ( 7 ) , 127 
 ( 8) , 113 ( 38 ) , 85 ( 52 ) , 73 ( 100 ) . zinc ( 2.44 
 g , 35.66 mmol ) was added 
 to a solution of 5-deoxy-5-iodo-2,3-isopropylidine-1-methoxy - d - ribofuranoside ( 18 ) ( 2.24 g , 7.14 mmol ) and a catalytic 
 amount of glacial acetic acid ( 12 drops ) in methanol ( 40 ml ) . the 
 suspension was heated under reflux for 1 h and cooled to 0 c . 
 a saturated solution of sodium borohydride in ethanol ( 140 ml ) was 
 added dropwise with stirring to the reaction mixture , stirred at 0 
 c for 0.5 h , and warmed to room temperature over 3 h. the mixture 
 was concentrated in vacuo . the resulting residue was dissolved in 
 diethyl ether ( 50 ml ) and filtered through celite . the organic layer 
 was washed with water ( 2  50 ml ) and brine ( 2  50 ml ) , 
 dried ( mgso4 ) , and concentrated in vacuo to yield ( 2s,3r)-2,3-(o - isopropylidene)pent-4-ene-1,2,3-triol 
 ( 20 ) ( 1.01 g , 89% ) as a colorless oil : [ ]d25 40.0 
 ( c 1.5 , chcl3 ) , lit . [ ]d24 45.7 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  1.40 ( d , 3h , j 0.4 hz ) , 1.51 ( d , 3h , j 0.4 hz ) , 1.81 
 ( t , 1h , j 6.2 hz ) , 3.59 ( dd , 2h , j 6.2 , 5.9 hz ) , 4.26 ( dt , 1h , j 6.6 , 5.9 hz ) , 4.65 
 ( tt , 1h , j 6.6 , 1.1 hz ) , 5.28 ( ddd , 1h , j 10.3 , 1.5 , 1.1 hz ) , 5.40 ( ddd , 1h , j 17.5 , 1.5 , 
 1.1 hz ) , 5.87 ( ddd , 1h , j 17.5 , 10.3 , 6.6 hz ) ; c nmr ( 101 mhz , cdcl3 )  25.3 ( ch3 ) , 27.8 ( ch3 ) , 62.1 ( ch2 ) , 78.3 ( ch ) , 78.4 
 ( ch ) , 108.9 ( c ) , 119.0 ( ch2 ) , 133.1 ( ch ) ; ms ( ci ) m / z 159 ( mh , 71 ) , 141 ( 11 ) , 
 101 ( 100 ) , 83 ( 12 ) . a solution of grubbs second - generation catalyst ( 0.14 
 g , 0.17 mmol ) 
 in dichloromethane ( 20 ml ) was added to a solution of ( 2s,3r)-2,3-(o - isopropylidene)pent-4-ene-1,2,3-triol 
 ( 20 ) ( 0.54 g , 3.41 mmol ) and 1-tetradecene ( 1.01 g , 5.12 
 mmol ) in dichloromethane ( 20 ml ) and heated under reflux for 16 h. 
 the reaction mixture was then concentrated in vacuo and filtered through 
 a plug of silica first with petroleum ether ( 500 ml ) followed by 25% 
 ethyl acetate in petroleum ether ( 1000 ml ) . the second wash was concentrated 
 in vacuo to yield cross metathesis product 21 as a clear 
 oil , which was used without further purification . alkene 21 was dissolved in ethyl acetate ( 40 ml ) , and a suspension of 10% 
 palladium on carbon ( 0.16 g , 30% w / w ) in ethyl acetate ( 10 ml ) was 
 added . the mixture was degassed , purged with hydrogen gas , and left 
 to stir at room temperature under a hydrogen atmosphere for 2 h. the 
 suspension was filtered through celite with ethyl acetate ( 100 ml ) 
 and purified by column chromatography ( ethyl acetate / petroleum ether 
 1:5 ) to yield ( 2s,3r)-2,3-(o - isopropylidene)heptadecane-1,2,3-triol ( 22 ) ( 0.92 g , 82% over two steps ) as a colorless oil : ir ( neat ) 3437 , 
 2923 , 2854 , 1466 , 1379 , 1217 , 1042 cm ; [ ]d24 10.4 
 ( c 1.0 , chcl3 ) ; h nmr ( 400 
 mhz , cdcl3 )  0.87 ( t , 3h , j 6.8 
 hz ) , 1.211.53 ( m , 32h ) , 1.95 ( br s , 1h ) , 3.553.63 
 ( m , 2h ) , 4.104.19 ( m , 2h ) ; c nmr ( 101 mhz , cdcl3 )  14.3 ( ch3 ) , 22.8 ( ch2 ) , 25.7 
 ( ch3 ) , 26.8 ( ch3 ) , 28.4 ( ch2 ) , 29.0 
 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.7 
 ( ch2 ) , 29.8 ( 3  ch2 ) , 29.8 ( 2  ch2 ) , 29.8 ( ch2 ) , 32.1 ( ch2 ) , 62.0 ( ch2 ) , 77.2 ( ch ) , 78.1 ( ch ) , 108.2 ( c ) ; ms m / z 329 ( mh , 100 ) , 313 ( 13 ) , 271 ( 60 ) , 253 ( 10 ) , 
 235 ( 5 ) , 159 ( 3 ) , 69 ( 7 ) ; hrms ( ci ) calcd for c20h41o3 ( mh ) , 329.3056 ; found , 329.3051 . dimethyl sulfoxide ( 0.68 g , 8.66 mmol ) 
 was added to a stirred solution of oxalyl chloride ( 0.56 g , 4.34 mmol ) 
 in dichloromethane ( 15 ml ) at 78 c . the reaction mixture 
 was stirred for 0.3 h , and ( 2s,3r)-2,3-(o - isopropylidene)heptadecane-1,2,3-triol 
 ( 22 ) ( 0.95 g , 2.89 mmol ) in dichloromethane ( 15 ml ) was 
 slowly added . the mixture was stirred for an additional 0.3 h , and 
 triethylamine ( 1.46 g , 14.44 mmol ) was added . this reaction mixture 
 was stirred for 0.5 h at 78 c and warmed to room temperature 
 for a further 2 h. meanwhile , a solution of lithium chloride ( 0.24 
 g , 5.78 mmol ) , triethyl phosphonoacetate ( 0.75 g , 4.91 mmol ) , and 
 1,8-diazabicyclo[5.4.0]undec-7-ene ( 1.10 g , 4.91 mmol ) in acetonitrile 
 ( 30 ml ) was prepared and stirred for 1.0 h. the swern solution was 
 concentrated in vacuo and the horner  wadsworth the reaction mixture was stirred at room temperature 
 overnight , quenched by the addition of a saturated solution of ammonium 
 chloride ( 20 ml ) , and concentrated to give an orange residue that 
 was extracted with diethyl ether ( 2  30 ml ) . the organic layers 
 were combined , washed with water ( 50 ml ) and brine ( 50 ml ) , dried 
 ( mgso4 ) , and concentrated to give a yellow oil . purification 
 by filtration through a pad of silica ( ethyl acetate / petroleum ether 
 1:5 ) gave ethyl ( 2e,4s,5r)-4,5-(o - isopropylidene)-4,5-dihydroxynonadec-2-enoate 
 ( 23 ) ( 0.95 g , 83% ) as a clear yellow oil : ir ( neat ) 2924 , 
 2853 , 1722 , 1466 , 1370 , 1252 , 1161 , 1038 cm ; [ ]d26 5.1 ( c 1.0 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.88 ( t , 3h , j 6.9 hz ) , 1.231.33 
 ( m , 27h ) , 1.351.49 ( m , 8h ) , 4.164.26 ( m , 3h ) , 4.63 
 ( td , 1h , j 6.3 , 1.4 hz ) , 6.06 ( dd , 1h , j 15.6 , 1.4 hz ) , 6.84 ( dd , 1h , j 15.6 , 6.3 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.3 ( ch3 ) , 14.4 ( ch3 ) , 22.8 ( ch2 ) , 25.7 ( ch3 ) , 26.5 ( ch2 ) , 28.2 ( ch3 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( 2  ch2 ) , 29.8 ( 2 
  ch2 ) , 30.6 ( ch2 ) , 32.1 ( ch2 ) , 60.6 ( ch2 ) , 77.6 ( ch ) , 78.7 ( ch ) , 108.9 ( c ) , 123.2 
 ( ch ) , 144.0 ( ch ) , 166.2 ( c ) ; ms ( ci ) m / z 397 ( mh , 88 ) , 379 ( 12 ) , 339 ( 100 ) , 293 ( 8) , 143 ( 13 ) , 
 81 ( 12 ) . diisobutylaluminium hydride ( 0.55 ml , 5.50 
 mmol , 1 m in hexanes ) was added dropwise to a stirred solution of 
 ethyl ( 2e,4s,5r)-4,5-(o - isopropylidene)-4,5-dihydroxynonadec-2-enoate 
 ( 23 ) ( 0.95 g , 2.39 mmol ) in diethyl ether ( 50 ml ) at 
 78 c . the solution was stirred at 78 c 
 for 3 h and warmed to room temperature over 18 h. the reaction mixture 
 was quenched with a saturated solution of ammonium chloride ( 30 ml ) , 
 filtered through a pad of celite , and extracted with diethyl ether 
 ( 30 ml ) . the organic layer was washed with water ( 50 ml ) and brine 
 ( 50 ml ) . the organic layer was dried ( mgso4 ) and concentrated 
 in vacuo to give a colorless oil . purification by column chromatography 
 ( ethyl acetate / petroleum ether 1:5 ) gave ( 2e,4s,5r)-4,5-(o - isopropylidene)nonadec-2-ene-1,4,5-triol 
 ( 24 ) ( 0.71 g , 83% ) as a colorless oil : ir ( neat ) 3417 , 
 2922 , 2853 , 1456 , 1369 , 1216 , 1095 , 1027 , 974 cm ; [ ]d24  42.0 ( c 1.1 , chcl3 ) ; h nmr ( 500 mhz , cdcl3 )  0.87 ( t , 3h , j 7.0 hz ) , 1.221.52 ( m , 32h ) , 1.62 ( br s , 1h ) , 4.12 ( ddd , 
 1h , j 8.7 , 6.3 , 4.7 hz ) , 4.16 ( dd , 2h , j 5.2 , 1.5 hz ) , 4.50 ( dd , 1h , j 7.9 , 6.3 hz ) , 5.68 
 ( ddt , 1h , j 15.5 , 7.9 , 1.5 hz ) , 5.88 ( dtd , 1h , j 15.5 , 5.2 , 0.6 hz ) ; c nmr ( 126 mhz , cdcl3 )  14.2 ( ch3 ) , 22.8 ( ch2 ) , 25.8 
 ( ch3 ) , 26.4 ( ch2 ) , 28.4 ( ch3 ) , 29.5 
 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 
 ( ch2 ) , 29.8 ( 2  ch2 ) , 29.8 ( 3  ch2 ) , 30.5 ( ch2 ) , 32.1 ( ch2 ) , 63.0 ( ch2 ) , 78.5 ( ch ) , 79.1 ( ch ) , 108.2 ( c ) , 127.5 ( ch ) , 133.5 ( ch ) ; 
 ms m / z 355 ( mh , 26 ) , 
 337 ( 20 ) , 297 ( 41 ) , 279 ( 100 ) , 251 ( 23 ) , 225 ( 90 ) , 111 ( 69 ) , 73 ( 71 ) ; 
 hmrs ( ci ) calcd for c22h43o3 ( mh ) , 355.3212 ; found , 355.3211 . 1,8-diazabicycloundec-7-ene ( 0.07 g , 0.49 mmol ) was added 
 to a stirred solution of ( 2e,4s,5r)-4,5-(o - isopropylidene)nonadec-2-en-1,4,5-triol 
 ( 24 ) ( 0.19 g , 0.54 mmol ) and trichloroacetonitrile ( 0.12 
 g , 0.82 mmol ) at 0 c in dichloromethane ( 30 ml ) . the solution 
 was stirred at 0 c for 0.5 h and warmed to room temperature 
 over 3 h. the reaction mixture was filtered through a pad of silica 
 with dichloromethane ( 200 ml ) and concentrated in vacuo to yield crude 
 allylic trichloroacetimidate 25 , which was used without 
 further purification . allylic trichloroacetimidate 25 was dissolved in p - xylene ( 4 ml ) , and the solution 
 was added to a pressure tube loaded with a stirrer bar and potassium 
 carbonate ( 0.01 g , 0.72 mmol ) . the tube was sealed under argon and 
 heated with stirring at 160 c for 60 h. the reaction mixture 
 was cooled and filtered through celite to yield a yellow viscous oil . purification by column chromatography ( ethyl acetate / petroleum ether 
 1:20 ) gave ( 3r,4s,5r)-3-(2,2,2-trichloromethylcarbonylamino)-4,5-(o - isopropylidene)nonadec-1-ene-4,5-diol ( 26 ) ( 0.12 g , 44% ) as a colorless oil followed by ( 3s,4s,5r)-3-(2,2,2-trichloromethylcarbonylamino)-4,5-(o - isopropylidene)nonadec-1-ene-4,5-diol ( 27 ) ( 0.07 g , 26% ) as a colorless oil . for 26 : ir ( neat ) 
 3427 , 2922 , 2853 , 1721 , 1496 , 1211 , 819 cm ; [ ]d27 10.5 
 ( c 1.4 , chcl3 ) ; h nmr ( 500 
 mhz , cdcl3 )  0.88 ( t , 3h , j 7.0 
 hz ) , 1.221.33 ( m , 24h ) , 1.38 ( s , 3h ) , 1.461.58 ( m , 
 5h ) , 4.214.27 ( m , 2h ) , 4.374.42 ( m , 1h ) , 5.27 ( d , 
 1h , j 10.4 hz ) , 5.30 ( d , 1h , j 17.1 
 hz ) , 5.83 ( ddd , 1h , j 17.1 , 10.4 , 5.8 hz ) , 7.19 ( d , 
 1h , j 7.7 hz ) ; c nmr ( 126 mhz , cdcl3 )  14.3 ( ch3 ) , 22.9 ( ch2 ) , 24.3 
 ( ch3 ) , 27.2 ( ch3 ) , 27.3 ( ch2 ) , 29.4 
 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.6 
 ( ch2 ) , 29.7 ( 2  ch2 ) , 29.8 ( 2  ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 32.1 ( ch2 ) , 53.2 ( ch ) , 77.6 ( ch ) , 78.4 ( ch ) , 92.9 ( c ) , 108.1 ( c ) , 117.2 
 ( ch2 ) , 134.8 ( ch ) , 160.8 ( c ) ; ms m / z 498 ( mh , 14 ) , 440 ( 31 ) , 406 ( 28 ) , 297 ( 18 ) , 
 161 ( 35 ) , 113 ( 52 ) , 73 ( 100 ) ; hrms ( ci ) calcd for c24h43cl3no3 ( mh ) , 498.2309 ; found , 498.2307 . for 27 : ir ( neat ) 3324 , 
 2922 , 2853 , 1694 , 1515 , 1370 , 1217 , 1056 , 822 cm ; [ ]d27 48.0 ( c 0.8 , chcl3 ) ; h nmr ( 500 mhz , cdcl3 )  0.88 ( t , 3h , j 7.0 hz ) , 1.241.33 ( m , 24h ) , 1.36 ( s , 3h ) , 1.48 ( s , 3h ) , 
 1.501.64 ( m , 2h ) , 4.13 ( dd , 1h , j 6.3 , 3.8 
 hz ) , 4.23 ( ddd , 1h , j 9.7 , 6.3 , 3.8 hz ) , 4.55 ( dddt , 
 1h , j 8.7 , 5.2 , 3.8 , 1.7 hz ) , 5.265.33 ( m , 
 2h ) , 6.00 ( ddd , 1h , j 17.4 , 10.5 , 5.2 hz ) , 6.92 ( d , 
 1h , j 8.7 hz ) ; c nmr ( 126 mhz , cdcl3 )  14.3 ( ch3 ) , 22.8 ( ch2 ) , 25.3 
 ( ch3 ) , 27.0 ( ch3 ) , 27.1 ( ch2 ) , 29.0 
 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.7 
 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 29.8 
 ( 2  ch2 ) , 29.8 ( ch2 ) , 29.9 ( ch2 ) , 32.1 ( ch2 ) , 54.2 ( ch ) , 77.6 ( ch ) , 79.0 ( ch ) , 92.8 ( c ) , 
 108.7 ( c ) , 118.0 ( ch2 ) , 134.0 ( ch ) , 161.2 ( c ) ; ms m / z 498 ( mh , 5 ) , 464 ( 13 ) , 
 440 ( 100 ) , 406 ( 81 ) , 394 ( 22 ) , 329 ( 21 ) , 297 ( 20 ) , 271 ( 9 ) , 113 ( 7 ) , 
 73 ( 12 ) ; hrms ( ci ) calcd for c24h43cl3no3 ( mh ) , 498.2309 ; found , 498.2304 . dimethyl sulfoxide ( 0.68 g , 8.66 mmol ) 
 was added to a stirred solution of oxalyl chloride ( 0.56 g , 4.34 mmol ) 
 in dichloromethane ( 15 ml ) at 78 c . the reaction mixture 
 was stirred for 0.3 h , and ( 2s,3r)-2,3-(o - isopropylidene)heptadecane-1,2,3-triol 
 ( 22 ) ( 0.95 g , 2.89 mmol ) in dichloromethane ( 15 ml ) was 
 slowly added . the mixture was stirred for an additional 0.3 h , and 
 triethylamine ( 1.46 g , 14.44 mmol ) was added . this reaction mixture 
 was stirred for 0.5 h at 78 c , allowed to warm to room 
 temperature , and stirred for a further 2 h. meanwhile , a solution 
 of lithium chloride ( 0.24 g , 5.78 mmol ) , dimethyl 2-oxopropylphosphonate 
 ( 0.82 g , 4.91 mmol ) , and 1,8-diazabicyclo[5.4.0]undec-7-ene ( 1.10 
 g , 4.91 mmol ) in acetonitrile ( 30 ml ) was prepared and stirred for 
 1.0 h. the swern solution was concentrated in vacuo , and the horner  wadsworth the reaction mixture was stirred at room temperature 
 overnight , quenched by the addition of a saturated solution of ammonium 
 chloride ( 20 ml ) , and concentrated to give an orange residue that 
 was extracted with diethyl ether ( 2  30 ml ) . the organic layers 
 were combined , washed with water ( 50 ml ) and brine ( 50 ml ) , dried 
 ( mgso4 ) , and concentrated to give a yellow oil . purification 
 by filtration through a pad of silica ( ethyl acetate / petroleum ether 
 1:5 ) gave ( 3e,5s,6r)-5,6-(o - isopropylidene)-5,6-dihydroxyicos-3-en-2-one 
 ( 28 ) ( 0.84 g , 79% ) as a colorless oil : ir ( neat ) 2916 , 
 2848 , 1697 , 1676 , 1632 , 1373 , 1246 , 1217 , 1102 , 1036 cm ; [ ]d21 2.3 ( c 1.3 , chcl3 ) ; h nmr ( 400 mhz , cdcl3 )  0.87 ( t , 3h , j 6.9 hz ) , 1.211.34 ( m , 24h ) , 1.38 ( s , 3h ) , 1.411.49 
 ( m , 2h ) , 1.51 ( s , 3h ) , 2.28 ( s , 3h ) , 4.23 ( ddd , 1h , j 8.7 , 6.4 , 4.6 hz ) , 4.64 ( td , 1h , j 6.4 , 1.3 hz ) , 
 6.28 ( dd , 1h , j 15.9 , 1.3 hz ) , 6.65 ( dd , 1h , j 15.9 , 6.4 hz ) ; c nmr ( 101 mhz , cdcl3 )  14.3 ( ch3 ) , 22.8 ( ch2 ) , 25.6 ( ch3 ) , 26.4 ( ch2 ) , 27.7 ( ch3 ) , 28.2 ( ch3 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( 2  
 ch2 ) , 29.8 ( 2  ch2 ) , 30.7 ( ch2 ) , 32.1 ( ch2 ) , 77.8 ( ch ) , 78.6 ( ch ) , 109.0 ( c ) , 131.9 
 ( ch ) , 142.6 ( ch ) , 198.0 ( c ) ; ms m / z 367 ( mh , 71 ) , 349 ( 17 ) , 309 ( 45 ) , 239 ( 4 ) , 141 ( 100 ) , 
 113 ( 16 ) , 81 ( 16 ) ; hrms ( ci ) calcd for c23h43o3 ( mh ) , 367.3212 ; found , 367.3216 . ( r)-(+)-2-methyl - cbs - oxazaborolidine 
 ( 0.60 ml , 0.60 mmol , 1 m solution in toluene ) was added dropwise with 
 stirring to a solution of ( 3e,5s,6r)-5,6-(o - isopropylidene)-5,6-dihydroxyicos-3-en-2-one 
 ( 28 ) ( 0.20 g , 0.55 mmol ) in dry tetrahydrofuran ( 20 ml ) 
 at 0 c . the solution was stirred for 0.5 h at 0 c , borane 
 ( 1.64 ml , 1.64 mmol , 1 m in tetrahydrofuran ) was added dropwise , and 
 stirring was continued at 0 c for 7.5 h. the reaction was quenched 
 with methanol ( 10 ml ) , warmed to room temperature , and concentrated 
 in vacuo . the resulting residue was dissolved in diethyl ether ( 30 
 ml ) and washed with 1 m citric acid ( 3  50 ml ) , water ( 50 ml ) , 
 and brine ( 50 ml ) . the organic layer was dried ( mgso4 ) 
 and purified by column chromatography ( ethyl acetate / petroleum ether 
 1:6 , 1% triethylamine ) to yield ( 2s,3e,5s,6r)-5,6-(o - isopropylidene)icos-3-ene-2,5,6-triol ( 29 ) ( 0.20 g , 
 99% ) as a colorless oil : ir ( neat ) 3397 , 2982 , 2922 , 1456 , 1368 , 1215 , 
 1032 cm ; [ ]d22 + 4.5 ( c 1.1 , chcl3 ) ; h nmr ( 500 mhz , cdcl3 )  0.88 
 ( t , 3h , j 7.0 hz ) , 1.231.32 ( m , 27h ) , 1.36 
 ( s , 3h ) , 1.381.53 ( m , 5h ) , 4.12 ( ddd , 1h , j 8.6 , 6.3 , 4.7 hz ) , 4.35 ( quin , 1h , j 5.9 hz ) , 4.49 
 ( dd , 1h , j 7.9 , 6.3 hz ) , 5.65 ( ddd , 1h , j 15.5 , 7.9 , 1.2 hz ) , 5.81 ( ddd , 1h , j 15.5 , 5.9 , 
 0.7 hz ) ; c nmr ( 126 mhz , cdcl3 )  14.3 
 ( ch3 ) , 22.8 ( ch2 ) , 23.4 ( ch3 ) , 25.8 
 ( ch3 ) , 26.3 ( ch2 ) , 28.4 ( ch3 ) , 29.5 
 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 
 ( ch2 ) , 29.8 ( 2  ch2 ) , 29.8 ( ch2 ) , 29.8 ( 2  ch2 ) , 30.6 ( ch2 ) , 32.1 ( ch2 ) , 68.2 ( ch ) , 78.5 ( ch ) , 79.0 ( ch ) , 108.2 ( c ) , 125.9 ( ch ) , 
 138.4 ( ch ) ; hrms ( esi ) calcd for c23h44nao3 ( mna ) , 391.3183 ; found , 391.3169 . the reaction was carried out according 
 to the procedure described above using ( 3e,5s,6r)-5,6-(o - isopropylidene)-5,6-dihydroxyicos-3-ene-2-one 
 ( 28 ) ( 0.10 g , 0.28 mmol ) and ( s)-()-2-methyl - cbs - oxazaborolidine 
 ( 0.30 ml , 0.30 mmol , 1 m solution in tetrahydrofuran ) , yielding ( 2r,3e,5s,6r)-5,6-(o - isopropylidene)icos-3-en-2,5,6-triol ( 30 ) ( 0.065 g , 64% ) as a colorless oil : ir ( neat ) 3414 , 2922 , 
 2853 , 1458 , 1370 , 1217 , 1044 , 756 cm ; [ ]d24 3.7 ( c 1.0 , chcl3 ) ; h nmr ( 500 mhz , cdcl3 )  0.88 ( t , 3h , j 6.9 hz ) , 1.201.31 
 ( m , 27h ) , 1.35 ( s , 3h ) , 1.381.48 ( s , 5h ) , 4.084.15 
 ( m , 1h ) , 4.33 ( quintet of doublets , 1h , j 6.5 , 0.9 
 hz ) , 4.47 ( dd , 1h , j 8.0 , 6.2 hz ) , 5.62 ( ddd , 1h , j 15.5 , 8.0 , 0.9 hz ) , 5.78 ( ddd , 1h , j 15.5 , 
 6.5 , 0.6 hz ) ; c nmr ( 126 mhz , cdcl3 )  
 14.3 ( ch3 ) , 22.8 ( ch2 ) , 23.3 ( ch3 ) , 25.8 ( ch3 ) , 26.2 ( ch2 ) , 28.4 ( ch3 ) , 29.5 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( 3  ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 30.4 ( ch2 ) , 30.5 ( ch2 ) , 32.1 ( ch2 ) , 68.3 ( ch ) , 78.5 ( ch ) , 79.0 ( ch ) , 108.2 ( c ) , 126.1 ( ch ) , 
 138.5 ( ch ) ; ms m / z 369 ( mh , 21 ) , 351 ( 37 ) , 309 ( 14 ) , 293 ( 100 ) , 225 ( 28 ) , 183 ( 39 ) , 125 ( 88 ) ; 
 hrms ( ci ) calcd for c23h45o3 ( mh ) , 369.3369 ; found , 369.3366 . 1,8-diazabicycloundec-7-ene ( 0.011 g , 0.07 mmol ) was added to a 
 stirred solution of ( 2s,3e,5s,6r)-5,6-(o - isopropylidene)icos-3-ene-2,5,6-triol 
 ( 29 ) ( 0.053 g , 0.14 mmol ) and trichloroacetonitrile ( 0.031 
 g , 0.21 mmol ) at 0 c in dichloromethane ( 3 ml ) . the solution 
 was stirred at 0 c for 0.5 h and warmed to room temperature 
 over 3 h. the solution was filtered through a pad of silica with dichloromethane 
 ( 200 ml ) and concentrated in vacuo to yield the allylic trichloroacetimidate 
 as a yellow oil , which was used without further purification . the 
 allylic trichloroacetimidate was dissolved in p - xylene 
 ( 2 ml ) and added to a microwave vial loaded with a silicon carbide 
 bar and potassium carbonate ( 0.012 g , 6 mg / ml ) . the vial was sealed 
 under argon and heated at 140 c for 0.25 h in a microwave reactor . 
 after the reaction purification by column chromatography ( diethyl 
 ether / petroleum ether 1:10 ) gave ( 2e,4s,5s,6r)-4-(2,2,2-trichloromethylcarbonylamino)-5,6-(o - isopropylidene)icos-2-ene-5,6-diol ( 31 ) ( 0.053 
 g , 72% ) as a white solid : mp 5358 c ; ir ( neat ) 3356 , 
 2918 , 2851 , 1688 , 1516 , 1219 , 959 , 818 cm ; [ ]d22 28.5 
 ( c 1.0 , chcl3 ) ; h nmr ( 500 
 mhz , cdcl3 )  0.88 ( t , 3h , j 6.9 
 hz ) , 1.231.38 ( m , 27h ) , 1.48 ( s , 3h ) , 1.571.69 ( m , 
 2h ) , 1.72 ( dd , 3h , j 6.4 , 1.4 hz ) , 4.11 ( dd , 1h , j 6.3 , 3.8 hz ) , 4.21 ( ddd , 1h , j 9.6 , 6.3 , 
 3.7 hz ) , 4.474.51 ( m , 1h ) , 5.60 ( ddd , 1h , j 15.5 , 5.7 , 1.4 hz ) , 5.74 ( dqd , 1h , j 15.5 , 6.4 , 
 1.1 hz ) , 6.90 ( d , 1h , j 8.7 hz ) ; c nmr 
 ( 126 mhz , cdcl3 )  14.3 ( ch3 ) , 18.2 ( ch3 ) , 22.9 ( ch2 ) , 25.3 ( ch3 ) , 27.0 ( ch3 ) , 27.1 ( ch2 ) , 29.0 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( 2  ch2 ) , 
 29.9 ( 2  ch2 ) , 32.1 ( ch2 ) , 53.8 ( ch ) , 
 77.6 ( ch ) , 79.1 ( ch ) , 92.9 ( c ) , 108.5 ( c ) , 126.7 ( ch ) , 129.4 ( ch ) , 
 161.0 ( c ) ; hrms ( esi ) calcd for c25h44cl3nnao3 ( mh ) , 534.2279 ; found , 
 534.2265 . ( 2e,4s,5s,6r)-4-(2,2,2-trichloromethylcarbonylamino)-5,6-(o - isopropylidene)icos-2-ene-5,6-diol ( 31 ) ( 0.057 
 g , 0.11 mmol ) was dissolved in a mixture of dichloromethane ( 10 ml ) 
 and methanol ( 10 ml ) , and the solution was cooled to 78 c . after excess ozone was purged with oxygen gas , a 
 solution of sodium borohydride ( 0.013 g , 0.32 mmol ) in ethanol ( 10 
 ml ) was added dropwise with vigorous stirring . the reaction mixture 
 was allowed to slowly return to room temperature over 5 h. the reaction 
 mixture was quenched with a saturated solution of ammonium chloride 
 ( 10 ml ) , concentrated in vacuo to an aqueous solution , and extracted 
 with diethyl ether ( 3  15 ml ) . the combined organic layers were 
 washed with water ( 20 ml ) and brine ( 20 ml ) , dried ( mgso4 ) , and concentrated in vacuo to yield the crude product . purification 
 by column chromatography ( diethyl ether / petroleum ether 1:1 ) gave 
 ( 2s,3s,4r)-2-(2,2,2-trichloromethylcarbonylamino)-3,4-(o - isopropylidene)octadecane-1,3,4-triol ( 32 ) ( 0.041 g , 73% ) as a colorless oil : ir ( neat ) 3307 , 2918 , 2849 , 
 1687 , 1533 , 1221 , 1047 , 822 cm ; [ ]d20 + 4.8 ( c 1.1 , chcl3 ) ; h nmr ( 500 mhz , cdcl3 )  0.88 ( t , 3h , j 7.0 hz ) , 1.171.33 
 ( m , 24h ) , 1.36 ( s , 3h ) , 1.49 ( s , 3h ) , 1.521.58 ( m , 2h ) , 3.73 
 ( dd , 1h , j 11.4 , 3.2 hz ) , 4.01 ( dd , 1h , j 11.4 , 3.2 hz ) , 4.05 ( ddt , 1h , j 8.4 , 5.6 , 3.2 hz ) , 
 4.194.26 ( m , 2h ) , 7.18 ( d , 1h , j 8.4 hz ) ; c nmr ( 126 mhz , cdcl3 )  14.2 ( ch3 ) , 22.8 ( ch2 ) , 25.1 ( ch3 ) , 26.9 ( ch2 ) , 27.6 ( ch3 ) , 29.4 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.6 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( 2  ch2 ) , 32.1 ( ch2 ) , 52.1 ( ch ) , 
 62.5 ( ch2 ) , 77.8 ( ch ) , 77.8 ( ch ) , 92.7 ( c ) , 108.6 ( c ) , 
 161.7 ( c ) ; ms m / z 502 ( mh , 16 ) , 444 ( 100 ) , 410 ( 41 ) , 329 ( 80 ) , 313 ( 60 ) , 271 ( 46 ) , 257 ( 38 ) , 
 219 ( 31 ) , 172 ( 27 ) , 148 ( 26 ) , 73 ( 59 ) ; hrms ( ci ) calcd for c23h43cl3no4 ( mh ) , 502.2258 ; found , 502.2264 . ( 2s,3s,4r)-2-(2,2,2-trichloromethylcarbonylamino)-3,4-(o - isopropylidene)octadecane-1,3,4-triol ( 32 ) ( 0.026 g , 0.05 mmol ) was dissolved in a mixture of dichloromethane 
 ( 2 ml ) and methanol ( 2 ml ) . sodium hydroxide ( 4 m , 4 ml ) was added , 
 and the reaction mixture was stirred for 60 h. the solution was extracted 
 with dichloromethane ( 3  20 ml ) , washed with water ( 3  
 20 ml ) , and concentrated in vacuo . the crude oil was dissolved in 
 a mixture of dichloromethane ( 2 ml ) and methanol ( 2 ml ) . to this solution was added 6 m hydrochloric acid ( 2 ml ) , and the resulting solution 
 was stirred for 3 h at room temperature . the reaction was concentrated 
 in vacuo and washed with petroleum ether ( 3  10 ml ) to yield 
 ( 2s,3s,4r)-2-aminooctadecane-1,3,4-triol 
 hydrochloride ( 3 ) as a white solid ( 0.015 g , 82% ) ( the 
 spectroscopic data were as previously reported ) : ir ( neat ) 3304 ( oh ) , 2916 ( ch ) , 2849 ( ch ) , 1688 , 1470 , 
 1015 cm ; [ ]d21 + 4.8 ( c 0.8 , meoh ) ; h nmr ( 500 mhz , cd3od )  0.90 ( t , 3h , j 7.0 hz ) , 1.281.42 ( m , 24h ) , 1.501.57 ( m , 
 1h ) , 1.641.72 ( m , 1h ) , 3.383.45 ( m , 2h ) , 4.11 ( ddd , 
 1h , j 8.8 , 5.9 , 3.2 hz ) , 4.39 ( t , 1h , j 8.8 hz ) , 4.46 ( dd , 1h , j 8.8 , 5.9 hz ) ; c nmr ( 126 mhz , cd3od )  14.3 ( ch3 ) , 
 23.6 ( ch2 ) , 26.6 ( ch2 ) , 30.4 ( ch2 ) , 30.7 ( 2  ch2 ) , 30.7 ( 5  ch2 ) , 
 30.8 ( ch2 ) , 33.0 ( ch2 ) , 34.8 ( ch2 ) , 55.6 ( ch ) , 67.4 ( ch2 ) , 74.0 ( ch ) , 75.8 ( ch ) ; hrms ( esi ) 
 calcd for c18h40no3 ( mh ) , 318.3003 ; found , 318.2990 . the reactions were carried out according to the procedure described 
 for ( 2e,4s,5s,6r)-4-(2,2,2-trichloromethylcarbonylamino)-5,6-(o - isopropylidene)icos-2-ene-5,6-diol ( 31 ) using 
 ( 2r,3e,5s,6r)-5,6-(o - isopropylidene)icos-3-ene-2,5,6-triol 
 ( 30 ) ( 0.029 g , 0.08 mmol ) . this yielded ( 2e,4r,5s,6r)-4-(2,2,2-trichloromethylcarbonylamino)-5,6-(o - isopropylidene)icos-2-ene-5,6-diol ( 33 ) ( 0.029 
 g , 71% ) as a yellow oil : ir ( neat ) 3426 , 2922 , 2853 , 1719 , 1495 , 1213 , 
 964 , 820 cm ; [ ]d22 12.6 ( c 0.9 , 
 chcl3 ) ; h nmr ( 500 mhz , cdcl3 ) 0.88 ( t , 3h , j 7.0 hz ) , 1.201.33 ( m , 24h ) , 
 1.38 ( s , 3h ) , 1.451.57 ( m , 5h ) , 1.72 ( ddd , 3h , j 6.5 , 1.6 , 0.9 hz ) , 4.164.24 ( m , 2h ) , 4.304.37 ( m , 
 1h ) , 5.45 ( ddq , 1h , j 15.3 , 7.3 , 1.6 hz ) , 5.75 ( dqd , 
 1h , j 15.3 , 6.5 , 0.9 hz ) , 7.18 ( d , 1h , j 7.0 hz ) ; c nmr ( 126 mhz , cdcl3 )  
 14.3 ( ch3 ) , 18.0 ( ch3 ) , 22.9 ( ch2 ) , 24.4 ( ch3 ) , 27.2 ( ch3 ) , 27.3 ( ch2 ) , 29.3 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.6 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( 2  ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 32.1 ( ch2 ) , 52.8 ( ch ) , 77.6 ( ch ) , 78.9 ( ch ) , 
 93.0 ( c ) , 108.0 ( c ) , 127.8 ( ch ) , 129.0 ( ch ) , 160.6 ( c ) ; ms m / z 512 ( mh , 32 ) , 478 ( 84 ) , 
 442 ( 100 ) , 408 ( 55 ) , 297 ( 20 ) , 189 ( 34 ) , 113 ( 14 ) ; hrms ( ci ) calcd 
 for c25h45cl3no3 ( mh ) , 512.2465 ; found , 512.2458 . the reactions were carried out according to the procedure 
 described for ( 2s,3s,4r)-2-(2,2,2-trichloromethylcarbonylamino)-3,4-(o - isopropylidene)octadecane-1,3,4-triol ( 32 ) using ( 2e,4r,5s,6r)-4-(2,2,2-trichloromethylcarbonylamino)-5,6-(o - isopropylidene)icos-2-ene-5,6-diol ( 33 ) ( 0.09 
 g , 0.18 mmol ) . this yielded ( 2r,3s,4r)-2-(2,2,2-trichloromethylcarbonylamino)-3,4-(o - isopropylidene)octadecane-1,3,4-triol ( 34 ) ( 0.058 g , 66% ) as a colorless oil : ir ( neat ) 3419 , 2922 , 2853 , 
 1717 , 1502 , 1211 , 1050 , 820 cm ; [ ]d26 20.5 
 ( c 1.0 , chcl3 ) ; h nmr ( 500 
 mhz , cdcl3 )  0.90 ( t , 3h , j 6.9 
 hz ) , 1.211.33 ( m , 24h ) , 1.40 ( s , 3h ) , 1.411.60 ( m , 
 5h ) , 3.75 ( dd , 1h , j 11.1 , 6.4 hz ) , 3.81 ( dd , 1h , j 11.1 , 5.1 hz ) , 3.913.99 ( m , 1h ) , 4.224.30 
 ( m , 1h ) , 4.42 ( dd , 1h , j 7.1 , 1.4 hz ) , 7.27 ( d , 1h , j 7.4 hz ) ; c nmr ( 126 mhz , cdcl3 )  14.2 ( ch3 ) , 22.8 ( ch2 ) , 24.5 ( ch3 ) , 27.2 ( ch2 ) , 27.2 ( ch3 ) , 29.4 ( ch2 ) , 29.5 ( ch2 ) , 29.5 ( ch2 ) , 29.6 ( ch2 ) , 29.6 ( ch2 ) , 29.7 ( ch2 ) , 29.7 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 29.8 ( ch2 ) , 32.1 ( ch2 ) , 52.7 ( ch ) , 63.9 ( ch2 ) , 
 76.0 ( ch ) , 77.7 ( ch ) , 92.9 ( c ) , 108.3 ( c ) , 161.9 ( c ) ; ms m / z 502 ( mh , 18 ) , 486 ( 14 ) , 444 ( 100 ) , 
 419 ( 34 ) , 391 ( 42 ) , 342 ( 37 ) , 297 ( 68 ) , 149 ( 11 ) ; hrms ( ci ) calcd 
 for c23h43cl3no4 ( mh ) , 502.2258 ; found , 502.2252 . the reactions were carried out as 
 described for d - ribo - phytosphingosine hydrochloride 
 ( 3 ) using ( 2r,3s,4r)-2-(2,2,2-trichloromethylcarbonylamino)-3,4-(o - isopropylidene)octadecane-1,3,4-triol ( 34 ) ( 0.033 g , 0.07 mmol ) . this gave ( 2r,3s,4r)-2-aminooctadecane-1,3,4-triol hydrochloride 
 ( 35 ) as a white solid ( 0.020 g , 87% ) ( the spectroscopic 
 data were as previously reported ) : ir 
 ( neat ) 3335 ( nh / oh ) , 2916 ( ch ) , 2849 ( ch ) , 1472 , 1418 , 1034 , 718 cm ; [ ]d20 12.2 ( c 0.9 , meoh ) ; h nmr ( 500 mhz , cd3od )  0.90 ( t , 3h , j 7.0 hz ) , 1.271.40 ( m , 24h ) , 1.491.58 ( m , 
 1h ) , 1.75 ( td , 1h , j 9.4 , 3.4 hz ) , 3.19 ( dd , 1h , j 8.1 , 4.2 hz ) , 3.42 ( td , 1h , j 8.1 , 3.4 
 hz ) , 4.13 ( ddd , 1h , j 8.9 , 6.3 , 4.2 hz ) , 4.29 ( dd , 
 1h , j 8.9 , 6.3 hz ) , 4.48 ( t , 1h , j 8.9 hz ) ; c nmr ( 126 mhz , cd3od )  
 14.3 ( ch3 ) , 23.6 ( ch2 ) , 26.5 ( ch2 ) , 30.4 ( ch2 ) , 30.7 ( ch2 ) , 30.7 ( ch2 ) , 30.7 ( 5  ch2 ) , 30.8 ( ch2 ) , 33.0 ( ch2 ) , 35.1 ( ch2 ) , 55.9 ( ch ) , 69.2 ( ch2 ) , 
 73.9 ( ch ) , 76.3 ( ch ) ; hrms ( esi ) calcd for c18h40no3 ( mh ) , 318.3003 ; found , 318.2990 .
two 
 variations of the overman rearrangement have been developed 
 for the highly selective synthesis of anti - vicinal 
 amino alcohol natural products . 
 a mom ether - directed palladium(ii)-catalyzed 
 rearrangement of an allylic trichloroacetimidate was used as the key 
 step for the preparation of the protein kinase c inhibitor d - erythro - sphinganine and the antitumor agent ( + ) -spisulosine , 
 whereas the overman rearrangement of chiral allylic trichloroacetimidates 
 generated by the asymmetric reduction of an ,-unsaturated 
 methyl ketone allowed rapid access both to d - ribo - phytosphingosine and l - arabino - phytosphingosine .