more than 750 bromine - containing 
 compounds have been isolated from laurencia species 
 of marine algae , making them the single 
 largest source of brominated natural products yet known . while there have been a vast number of innovative 
 approaches to access the most abundant halogenated natural products , 
 the c15-acetogenins , other classes have served less often 
 as synthetic targets . take , for instance , the second largest family 
 of halogenated sesquiterpenes isolated from laurencia , the snyderanes ( figure 1 ) . characterized by a bromocyclohexane ring with halogen incorporation 
 at c10 , this family of compounds includes members with acyclic side 
 chains ( 1 and 2 ) as well as a variety of 
 ring fusions , including 6,5- , 6,6- and 6,7-fused compounds ( 36 ) . their biogenesis likely involves 
 an asymmetric brominative cyclization of nerolidol ( 7 ) followed by postcyclization modifications . examples 
 of snyderane natural products . despite the synthetic attractiveness of such a simple approach , 
 the enantioselective electrophilic bromination of unactivated alkenes 
 remains a major challenge in organic chemistry . for instance , no catalytic methods exist for the enantioselective 
 electrophilic brominative cyclization of polyenes . several strategies 
 have been employed to circumvent this limitation , and there is one report of a stoichiometric brominating 
 reagent capable of delivering moderate levels of enantioselectivity . it is therefore unsurprising that only a handful 
 of reports utilizing electrophilic brominative approaches to the snyderanes 
 have been disclosed . the parent - and -snyderols 
 ( 1 and 2 ) have been synthesized in ca a similar strategy was used to synthesize the 6,6-fused 8-bromo - epi - capirrappi oxide ( 4 ) in a more palatable 
 30% yield . an electrophilic brominative 
 strategy to the 6,7-fused compound aplysistatin ( 5 ) gave the desired compound in ca . consequently , 
 total syntheses of aplysistatin ( 5 ) and palisadin ( 6 ) using 
 tin- and mercury - based methods , respectively , have been reported . to the best of our knowledge , there are no reports detailing the synthesis 
 of 6,5-fused snyderanes by electrophilic bromination or any other 
 means . this paper details our first foray into the chemistry of snyderane 
 natural products , the total synthesis of the 6,5-fused snyderane luzofuran 
 ( 3 ) . luzofuran ( 3 ) was isolated from 
 an okinawan collection 
 of the red alga laurencia luzonensis by kuniyoshi 
 and co - workers in 2005 . with only 3.8 mg being isolated from 1.1 kg of the predried alga , it is unsurprising 
 that there are as yet no literature reports regarding any biological 
 activities of the compound . we elected to employ a biomimetically 
 inspired brominative cyclization 
 to access the 6,5-fused ring system . we anticipated that the electrophilic 
 brominating reagent could be generated in situ from an unreactive 
 but economical bromonium source and engage in a diastereoselective 
 cyclization . our approach was inspired by two considerations : ( 1 ) 
 the seminal work of ishihara and co - workers who developed a stoichiometric brominating reagent and ( 2 ) the highly conserved histidine and arginine - rich active 
 site of the vanadium haloperoxidase class of enzymes that are responsible 
 for in vivo brominative cyclizations . we sought to combine the attributes from both systems to give a 
 catalytically active molecule that could function as a bromonium shuttle 
 in the manner depicted in figure 2 . phosphoramidites chelate to metal 
 centers exclusively via the tetrahedral 
 phosphorus atom , and they likewise protonate 
 on phosphorus , so a binol - based phosphoramidite 
 seemed the most appropriate molecule to function as a bromonium shuttle . to this end , we recently 
 reported the development of a library of n - heterocycle - substituted 
 phosphoramidites . the required balance between 
 oxidative stability versus catalytic activity led us to settle upon 
 the 2,4,5-trichlorophenyltriazole ( tcpt)-flanked catalyst 8 for this work ( figure 3 ) . as shown in scheme 1 , our synthesis began 
 with the organometallic union of the geranyl fragment 9 and the furan fragment 10 . organobarium reagents are 
 well - known to give extremely high levels of -selectivity in 
 reaction with aldehydes , and polyene - containing organobarium 
 reagents can be made with complete retention of alkene geometry . as such , reaction of geranyl chloride 9 with activated barium gave an organobarium reagent , which 
 reacted with 3-furancarboxaldehyde 10 to give alcohol 11 . treatment of 11 with 1 equiv of the cheap 
 and readily available n - bromosuccinimide ( nbs ) and 
 a catalytic amount of tcpt 8 furnished ( )-luzofuran 
 ( 3 ) in 17% yield and ( )-4-epi - luzofuran 
 ( epi-3 ) in 4% yield . the relative stereochemistry 
 of synthetic ( )-luzofuran ( 3 ) was assigned on the 
 basis of the noe enhancements between 
 the hydrogens shown in scheme 1 ( see the supporting information ) , which necessitates the 
 relative configuration depicted . this is in excellent agreement with 
 kuniyoshi s assignment of the natural product stereochemistry . however , a comparison of the h and c nmr shifts for naturally occurring luzofuran and our synthetic 
 ( )-luzofuran revealed an anomaly ( table 1 ) . as depicted graphically in figure 4 , the h nmr shifts were in almost perfect agreement , 
 differing by 
 no more than 0.08 ppm . similarly , the c nmr shifts differed 
 by no more than 0.08 ppm with the exception of c7 . at that center there was a marked difference between our observed chemical shift 
 ( 80.15 ppm ) and the reported value ( 78.1 ppm ) . we could not easily 
 reconcile this unexpected outcome with the noe data shown in scheme 1 . chemical shift comparison between natural and synthetic 
 ( )-luzofuran 
 ( 3 ) . h or c = [ reported shift][observed 
 shift ] ( ppm ) . we therefore performed 
 a j - value comparison using 
 the reported data , our observed values , 
 and those predicted for the low energy conformations of all diastereomers 
 about the luzofuran core ( see the supporting information ) . we anticpated that any alteration 
 in the chemical environment of c7 would affect the ring conformation 
 such that the coupling constants around the bicyclic structure would 
 be perturbed . the diagnostic signal for the hydrogen appended to c4 
 was most useful for monitoring this process . of the available possibilities 
 ( see the supporting information ) , the only 
 diastereomer that had matching ( predicted ) coupling constants and 
 that could possess the observed noe interactions was the ( 4s*,6s*,7s*,10s * ) isomer . unambiguous confirmation of the relative stereochemistry was secured 
 by conversion of 3 ( and epi-3 ) into known compounds ( vide infra ) . the structure of the 
 minor product , ( )-epi - luzofuran ( epi-3 ) differs from the 
 natural product at c4 only ( scheme 2 ) . eschenmoser 
 scenario in which cyclization occurs more readily when the acyclic 
 precursor is in the appropriate conformation . although a single enantiomer 
 of tcpt 8 was employed in the cyclization , the production 
 of a racemate convinced us that the level of diastereoselection was 
 substrate rather than catalyst - controlled , and that the ratio of products 
 reflected the thermodynamic preference for the furyl unit to be pseudoaxial , 
 as in 12 , rather than pseudoequatorial as in 13 . the most direct way to probe this hypothesis was to generate the 
 cyclization precursor as a single enantiomer and measure the diastereomeric 
 ratio of the ensuing product mixture . the enantioselective synthesis 
 of ( + ) -luzofuran ( + ) -3 required the corresponding ( s)-configured alcohol 
 ( + ) -11 . we anticipated that this could be generated by 
 an enantioselective reduction of the corresponding ketone 14 ( scheme 3 ) . enantioselective transfer hydrogenation 
 with noyori s ( s , s)-rutsdpen 
 catalyst proceeded in excellent yield . the enantiomeric ratio was determined by h nmr analysis 
 of the corresponding o - methyl mandalate 15 to be 95:5 . compound ( + ) -11 was treated with 1 equiv of nbs and 
 a catalytic amount of tcpt 8 to furnish ( + ) -luzofuran 
 ( + ) -(3 ) in 29% yield and ( 4s,6r,7r,10r)-epi - luzofuran ( + ) -(epi-3 ) in 7% yield . comparison of product ratio of luzofuran and 4-epi - luzofuran revealed that the cyclization was indeed immune to the 
 absolute stereochemistry of the c4 center , ruling out a matched , mis - matched 
 catalyst rather , that unaltered product ratio lends weight to the hypothesized 
 stork  eschenmoser cyclization depicted in scheme 2 . the value of optical rotation for this synthetic sample 
 of luzofuran 
 was identical in both magnitude and direction to that reported for 
 the natural product . this necessitates the absolute stereochemistry 
 of naturally occurring luzofuran to be ( 4s,6s,7s,10s ) . final confirmation 
 of the relative and absolute stereochemistry of the products was attained 
 by conversion into the known compounds ( )-epi - ancistrofuran 16 and ( )-ancistrofuran 17 . ancistrofuran was isolated from the defensive secretions 
 of the 
 west african termite ancistrotermes cavithorax by 
 baker , evans and co - workers . a combination 
 of spectroscopic techniques and chemical derivatization was employed 
 to elucidate the gross structure of ancistrofuran . several total syntheses 
 have subsequently confirmed the relative stereochemistry of the natural 
 product , and although the absolute stereochemistry remains undetermined 
 both enantiomers of ancistrofuran have been synthesized . as depicted in scheme 4 , radical - mediated 
 debromination of ( )-luzofuran ( )-(3 ) gave 
 ( )-epi - ancistrofuran ( )-16 . employing the same protocol on ( 4s,6r,7r,10r)-epi - luzofuran 
 ( epi-3 ) gave ( )-ancistrofuran , 
 but the sample was contaminated with traces of an inseparable byproduct . we were pleased to find that debromination of ( 4s,6r,7r,10r)-epi - luzofuran ( epi-3 ) with 
 activated magnesium smoothly gave ( )-ancistrofuran ( 17 ) in good yield . as shown in table 2 and table 3 , comparison 
 of the nmr chemical shifts of 16 and 17 with 
 the literaure values showed excellent agreement . the successful synthesis 
 of ( )-epi - ancistrofuran ( )-16 and ( )-ancistrofuran ( 17 ) confirms the relative 
 stereochemistry of epi - luzofuran ( epi-3 ) and luzofuran ( 3 ) . our attention then turned to gaining a mechanistic understanding 
 of how the tcpt catalyst ( 8) affects the brominative 
 cyclization . the importance of the catalyst structure was illustrated 
 by the observations that are summarized in scheme 5 . first , the cyclization of substrate 11 did 
 not proceed in the absence of tcpt ( 8) . second , attempted 
 cyclization using a phosphine catalyst was unsuccessful . phosphoramidite lacking 
 only the pendant n - heterocycles ( morfphos ) was completely 
 ineffective . even when a stoichiometric quantity of morfphos was employed 
 for extended reaction times ( 3 h ) , the reaction was extremely low 
 yielding ( < 5% ) . and finally , in line with snyder s observations , 
 the unprotected alcohol of compound 11 rendered it incompatible 
 with the potently electrophilic reagent bdsb . quantum mechanical calculations at the m06 - 2x/6 - 311+g(3df,2p)//m05 - 2x/6 - 31g(d ) 
 level of theory with the inclusion of solvation effects using the 
 smd continuum model ( see the supporting information ) show that the bromine atom is indeed transferred from nbs onto 
 the phosphorus atom of the tcpt catalyst ( figure 5 ) . subsequent transfer of the catalyst - bound bromine onto 
 the alkene is acompanied by succinimide deprotonation of the alcohol 
 which assists cyclization . the involvement of the bromonium shuttle 
 in the delivery of the bromine atom to the alkene renders the process 
 substantially more energetically favorable than the uncatalyzed process . calculated schematic energy profiles for the catalyzed 
 brominative 
 cyclization of ( + ) -11 . we report the first synthesis of the 6,5-fused 
 snyderane , luzofuran 
 ( 3 ) , in both racemic and enantioenriched form . excision 
 of the halogen from epi-3 gave the insect - derived 
 natural product ( )-ancistrofuran ( 17 ) , while 
 debromination of ( )-luzofuran ( 3 ) gave the known 
 compound ( )-epi - ancistrofuran ( )-16 . the heightened nucleophilicity of the n - heterocycle - flanked phosphoramidite 8 enabled us to 
 perform a diastereoselective brominative cyclization using the common 
 laboratory reagent nbs . we anticipate that this strategy will provide 
 general access to the snyderane class of natural products . to a suspension 
 of anhydrous barium iodide ( 3.12 
 g , 7.97 mmol , 4.5 equiv ) in thf ( 30 ml ) was added a solution of lithium 
 biphenylide , prepared by stirring ( 2 h ) freshly cut lithium pieces 
 ( 110 mg , 15.9 mmol , 9.0 equiv ) and biphenyl ( 2.44 g , 15.8 mmol , 9.0 
 equiv ) in thf ( 30 ml ) . this mixture was stirred ( 1 h ) and then cooled 
 to 78 c , and a solution of ( e)-geranyl 
 chloride ( 9 ) ( 620 mg , 3.59 mmol , 1.0 equiv ) in thf ( 20 ml ) was added 
 over 1.5 h. the resulting mixture was stirred ( 1 h ) at 78 
 c , and then a solution of 3-furancarboxaldehyde ( 310 l , 
 3.58 mmol , 1.0 equiv ) in thf ( 10 ml ) added over 10 min . the mixture 
 was stirred ( 0.5 h ) at 78 c and then quenched via the 
 addition of hydrochloric acid ( 0.2 m , 100 ml ) . the aqueous phase was 
 extracted with et2o ( 2  50 ml ) , and the organic extracts 
 were combined with the organic partition of the reaction mixture , 
 washed with water ( 2  200 ml ) and brine ( 100 ml ) , dried over 
 sodium sulfate , and concentrated . column chromatography ( ethyl acetate / light 
 petroleum 5/95 ) gave 11 ( 494 mg , 2.11 mmol , 58% ) as a 
 colorless oil : rf 0.50 
 ( ethyl acetate / hexanes 1/9 ) ; ir ( cm ) 3383 , 2917 , 
 1108 , 1024 , 787 ; h nmr ( 300 mhz ; cdcl3 ) 7.39 
 ( 2 h , m ) , 6.41 ( 1 h , m ) , 5.16 ( 1 h , ddd , j 7.9 , 6.8 , 
 0.9 ) , 5.06 ( 1 h , m ) , 4.66 ( 1 h , ddd , j 7.2 , 5.8 , 
 3.9 ) , 2.452.49 ( 2 h , m ) , 2.032.10 ( 4 h , m ) , 1.91 ( 1 
 h , d , j 4.0 ) , 1.68 ( 3 h , s ) , 1.64 ( 3 h , s ) , 1.60 
 ( 3 h , s ) ; c nmr ( 75 mhz ; cdcl3 ) 143.3 ( ch ) , 
 139.7 ( ch ) , 139.2 ( c ) , 131.9 ( c ) , 128.8 ( c ) , 124.2 ( ch ) , 119.5 ( ch ) , 
 108.8 ( ch ) , 68.9 ( ch ) , 40.0 ( ch2 ) , 36.9 ( ch2 ) , 26.6 ( ch2 ) , 25.8 ( ch3 ) , 17.8 ( ch3 ) , 16.5 ( ch3 ) ; ms ( ei ) m / e ( relative intensity ) 216 ( 25 ) , 201 ( 16 ) , 147 ( 100 ) , 129 ( 70 ) , 95 
 ( 81 ) , 91 ( 64 ) ; hrms ( esi ) m / e [ m 
 + na ] calcd for c15h22o2na 257.15120 , 
 obsd 257.15130 . sodium hydrogen 
 carbonate ( 200 mg , 
 2.38 mmol , 3.46 equiv ) was added to a solution of the dess martin 
 periodinane ( 335 mg , 789 mol , 1.15 equiv ) in ch2cl2 ( 5 ml ) and the mixture stirred ( 5 min ) with cooling 
 to 0 c . a solution of 11 ( 150 mg , 687 mol , 
 1.00 equiv ) in ch2cl2 ( 5 ml ) was added slowly , 
 and the mixture was stirred and allowed to warm to 15 c . stirring was continued ( 1 h ) , a solution of sodium sulfite ( 5% in water , 20 
 ml ) was added , the aqueous phase was extracted with ch2cl2 ( 2  5 ml ) , and the organic extracts combined 
 with the organic partition of the reaction mixture and washed with 
 water ( 2  50 ml ) , brine ( 50 ml ) , dried over sodium sulfate , 
 and concentrated . column chromatography ( ether / light petroleum 5/95 ) 
 gave 14 ( 137 mg , 92% ) as a slightly yellow oil : rf 0.48 ( ether / hexanes 1/9 ) ; 
 ir ( cm ) 2947 , 1678 , 1154 , 873 , 743 ; h nmr ( 300 mhz ; cdcl3 ) 8.02 ( 1 h , m ) , 7.41 ( 1 h , m ) , 6.75 
 ( 1 h , m ) , 5.40 ( 1 h , app t j 7.0 ) , 5.04 ( 1 h , m ) , 
 3.44 ( 2 h , d j 7.0 ) , 1.962.11 ( 4 h , m ) , 1.67 
 ( 3 h , s ) , 1.64 ( 3 h , s ) , 1.57 ( 3 h , s ) ; c nmr ( 75 mhz ; 
 cdcl3 ) 193.4 ( c ) , 147.3 ( ch ) , 144.1 ( ch ) , 139.2 ( c ) , 131.7 
 ( c ) , 127.5 ( c ) , 124.0 ( ch ) , 116.2 ( ch ) , 108.9 ( ch ) , 40.5 ( ch2 ) , 39.7 ( ch2 ) , 26.5 ( ch2 ) , 25.7 ( ch3 ) , 17.7 ( ch3 ) , 16.6 ( ch3 ) ; ms ( esi ) m / e ( relative intensity ) 271 ( 100 , mk ) ; hrms ( esi ) m / e [ m + na ] 
 calcd for c15h20o2na 255.13555 , obsd 
 255.13551 . dichloro(p - cymene)ruthenium(ii ) 
 dimer ( 36 mg , 59 mol , 0.051 equiv ) and ( s , s)-tsdpen ( 51 mg , 0.14 mmol , 0.12 equiv ) were heated to reflux ( 1 
 h ) in degassed ch2cl2 ( 20 ml ) . the solvent was 
 removed under a stream of argon , and a solution of sodium formate 
 ( 800 mg , 11.8 mmol , 10 equiv ) in degassed , deionized water ( 15 ml ) 
 and then a solution of cetyltrimethylammonium bromide ( 16 mg , 44 mol , 
 0.04 equiv ) and 14 ( 250 mg , 1.16 mmol , 1.0 equiv ) in 
 degassed ethyl acetate ( 8 ml ) were added . the mixture was stirred 
 at room temperature ( 16 h ) and then poured onto water ( 100 ml ) , and 
 saturated aqueous ammonium chloride ( 100 ml ) was added . the mixture 
 was extracted with ether / hexanes 1/1 ( 3  50 ml ) , the combined 
 organic extracts were passed through a plug of celite , washing with 
 ether / hexanes:1/1 ( 100 ml ) , and the filtrate was concentrated . column 
 chromatography ( ethyl acetate / light petroleum : 5/95 ) gave ( s)-11 ( 199 mg , 79% ) as a colorless oil : [ ]d206.2 ( c 2.1 , thf ) . to a solution of ( s)-11 ( 20 mg , 85 mol , 1.0 equiv ) 
 in ch2cl2 ( 5 ml ) were added dcc ( 18 mg , 87 mol , 
 1.0 equiv ) , then ( s)-(+)--methoxyphenylacetic 
 acid ( 14.5 mg , 8.73 mol , 1.0 equiv ) , and then 4-dimethylaminopyridine 
 ( 1.0 mg , 8.2 mol , 0.10 equiv ) . the mixture was stirred ( 8 h ) 
 and then filtered , washing with ch2cl2 ( 5 ml ) , 
 and the filtrate concentrated . column chromatography ( ether / light 
 petroleum 7/93 ) gave 15 ( 30 mg , 92% ) : [ ]d20 + 2.2 ( c 0.054 , chcl3 ) ; rf 0.35 ( ether / hexanes 1/9 ) ; ir ( cm ) 2924 , 1747 , 1171 , 1106 , 1023 , 874 ; h nmr ( 500 mhz ; 
 cdcl3 ) 7.427.44 ( 2 h , m ) , 7.327.37 ( 5 h , 
 m ) , 6.36 ( 1 h , m ) , 5.79 ( 1 h , app t j 6.8 ) , 5.00 
 ( 1 h , app tt , j 10.4 , 1.4 ) , 4.81 ( 1 h , dddd j 7.2 , 7.0 , 1.3 , 1.2 ) , 4.73 ( 1 h , s ) , 3.39 ( 3 h , s ) , 2.47 
 ( 1 h , ddd , j 14.5 , 7.2 , 6.8 ) , 2.40 ( 1 h , ddd , j 14.5 , 6.8 , 6.4 ) , 1.901.96 ( 2 h , m ) , 1.82 ( 2 h , 
 app t , j 7.66 ) , 1.67 ( 3 h , s ) , 1.57 ( 3 h , s ) , 1.46 
 ( 3 h , s ) ; c nmr ( 75 mhz ; cdcl3 ) 170.3 ( c ) , 
 143.2 ( ch ) , 140.5 ( ch ) , 138.6 ( c ) , 136.5 ( c ) , 131.6 ( c ) , 128.8 ( ch ) , 
 128.7 ( ch ) , 128.7 , ( ch ) , 127.4 ( ch ) , 127.4 ( ch ) , 124.6 ( c ) , 124.2 
 ( ch ) , 118.3 ( ch ) , 109.2 ( ch ) , 82.8 ( ch ) , 69.6 ( ch ) , 57.5 ( ch ) , 39.7 
 ( ch2 ) , 33.3 ( ch2 ) , 26.6 ( ch2 ) , 25.8 
 ( ch3 ) , 17.8 ( ch3 ) , 16.3 ( ch3 ) ; ms 
 ( esi ) m / e ( relative intensity ) 787 
 ( 100 ) , 405 ( mna+ , 30 ) ; hrms ( esi ) m / e [ m + na ] calcd for c24h30o4na 405.20363 , 
 obsd 405.20367 . a diasteromeric mixture was synthesized according 
 to the above procedure , using ( )-11 . ( s)-((r , e)-1-(furan-3-yl)-4,8-dimethylnona-3,7-dien-1-yl ) 
 2-methoxy-2-phenyl acetate ( epi-15 ) 
 showed key signals : ir ( cm ) 2915 , 1732 , 1197 , 
 1108 , 1023 , 874 , 791 , 726 ; h nmr ( 500 mhz ; cdcl3 ) 7.09 ( 1 h , m ) , 6.11 ( 1 h , m ) , 5.79 ( 1 h , app t , j 6.8 ) , 4.76 ( 1 h , s ) , 3.40 ( 3 h , s ) ; c nmr ( 125 mhz ; 
 cdcl3 ) 170.1 ( c ) , 143.0 ( ch ) , 140.0 ( ch ) , 138.6 ( c ) , 136.3 
 ( c ) , 131.5 ( c ) , 128.8 ( ch ) , 128.7 ( 2 c , ch ) , 127.4 ( 2 c , ch ) , 124.5 
 ( c ) , 124.2 ( ch ) , 118.5 ( ch ) , 108.8 ( ch ) , 82.8 ( ch ) , 69.7 ( ch ) , 57.4 
 ( ch ) , 39.8 ( ch2 ) , 33.7 ( ch2 ) , 26.6 ( ch2 ) , 25.8 ( ch3 ) , 17.8 ( ch3 ) , 16.4 ( ch3 ) . integration of the peaks of the major and minor diastereomers 
 in the h nmr spectrum of 15 indicated a 95:5 diasteromeric 
 ratio of esters . a solution of ( )-11 ( 120 mg , 512 mol , 
 1.00 equiv ) and ( s)-tcpt catalyst 8 ( 90 
 mg , 0.10 mmol , 0.200 equiv ) in ch2cl2 ( 10 ml ) 
 was stirred ( 7 h ) over activated 4  molecular sieves ( 0.5 g ) . the mixture was cooled to 78 c , and a solution of n - bromosuccinimide ( 92 mg , 517 mol , 1.01 equiv ) in 
 ch2cl2 ( 7 ml ) was added over 5 min . the solution 
 was stirred ( 10 min ) at 78 c then quenched via the addition 
 of a solution of sodium sulfite ( 5% in water , 20 ml ) and allowed to 
 warm to room temperature . the aqueous phase was extracted with ch2cl2 ( 2  5 ml ) , and the organic extracts were 
 combined with the organic partition of the reaction mixture , washed 
 with water ( 50 ml ) and brine ( 50 ml ) , dried over sodium sulfate , and 
 concentrated . column chromatography ( ether / light petroleum 7/93 ) gave 
 ( )-luzofuran ( 3 ) as a colorless oil ( 27 mg , 17% ) 
 and ( 4s*,6r*,7r*,10r*)-2-(furan-3-yl)-7,11,11-trimethyloctahydrobenzofuran 
 ( 4-epi-3 ) as a colorless solid ( 8.0 
 mg , 4% ) . a solution of ( s)-11 ( 200 mg , 853 mol , 1.00 equiv ) and ( s)-tcpt catalyst 8 ( 161 mg , 183 mol , 0.200 equiv ) 
 in ch2cl2 ( 14 ml ) was stirred ( 7 h ) over activated 
 4  molecular sieves ( 0.5 g ) . the mixture was cooled to 78 c , and a solution of n - bromosuccinimide ( 165 
 mg , 927 mol , 1.01 equiv ) in ch2cl2 ( 10 
 ml ) was added over 5 min . the solution was stirred ( 10 min ) at 78 
 c , quenched via the addition of a solution of sodium sulfite 
 ( 5% in water , 20 ml ) , and allowed to warm to room temperature . the 
 aqueous phase was extracted with ch2cl2 ( 2  
 5 ml ) , and the organic extracts were combined with the organic partition 
 of the reaction mixture , washed with water ( 50 ml ) and brine ( 50 ml ) , 
 dried over sodium sulfate , and concentrated . column chromatography 
 ( ether / light petroleum 7/93 ) gave ( + ) -luzofuran ( 3 ) as 
 a colorless oil ( 44 mg , 15% ) : [ ]d20 + 5.1 ( c 0.18 , chcl3 ) ; rf 0.53 ( ethyl 
 acetate / hexanes 1/9 ) ; ir ( neat ) max / cm 2955 , 1458 , 1157 , 1023 , 896 , 599 ; h nmr ( 500 mhz ; cdcl3 ) 7.38 ( 1 h , m ) , 7.35 ( 1 h , m ) , 6.32 ( 1 h , m ) , 5.08 ( 1 h , 
 dd j 9.2 , 2.4 ) , 3.94 , ( 1 h , dd j 12.5 , 4.6 ) , 2.212.33 ( 2 h , m ) , 2.08 ( 1 h , dddd j 14.4 , 13.6 , 12.5 , 4.0 ) , 1.91 ( 1 h , ddd j 12.4 , 
 4.0 , 3.1 ) , 1.81 ( 1 h , ddd j 9.8 , 7.0 , 2.6 ) , 1.70 
 ( 1 h , dd j 13.2 , 7.0 ) , 1.60 ( 1 h , dddd j 13.5 , 12.5 , 4.4 , 0.9 ) , 1.25 ( 3 h , d j 0.9 ) , 1.05 
 ( 3 h , s ) , 0.98 ( 3 h , s ) ; c nmr ( 125 mhz ; cdcl3 ) 143.5 ( ch ) , 138.9 ( ch ) , 128.8 ( c ) , 108.5 ( ch ) , 80.2 ( c ) , 70.5 ( ch ) , 
 65.6 ( ch ) , 55.1 ( ch ) , 39.6 ( ch2 ) , 38.7 ( ch2 ) , 
 32.8 ( c ) , 32.7 ( ch2 ) , 30.3 ( ch3 ) , 20.4 ( ch3 ) , 17.0 ( ch3 ) ; ms ( ei ) m / e ( relative intensity ) 299 ( 6 ) , 297 ( 6 ) , 219 ( 12 ) , 217 ( 12 ) , 
 137 ( 64 ) , 121 ( 57 ) , 95 ( 48 ) , 81 ( 100 ) ; hrms ( esi ) m / e [ m + na ] calcd for c15h21bro2na 335.06171 , obsd 335.06174 , calcd for 
 c15h21bro2na 337.05967 , 
 obsd 337.05968 . ( 4s,6r,7r,10r)-2-(furan-3-yl)-7,11,11-trimethyloctahydrobenzofuran 
 ( 4-epi-3 ) was also obtained as a colorless 
 solid ( 11 mg , 4% ) : 26120 4.38 ( thf ) ; mp 4044 c ; rf 0.45 ( ethyl acetate / hexanes 
 1/9 ) ; ir ( neat ) max / cm 2922 , 
 1488 , 1185 , 1161 , 956 , 752 , 687 ; h nmr ( 300 mhz ; cdcl3 ) 7.367.39 ( 2 h , m ) , 6.37 ( 1 h , m ) , 4.99 ( 1 h , ddd , j 9.2 , 6.8 , 0.95 ) , 3.94 ( 1 h , dd , j 12.5 , 
 4.8 ) , 2.212.32 ( 2 h , m ) , 2.07 ( 1 h , dddd , j 14.3 , 13.5 , 12.5 , 4.1 ) , 1.76 ( 1 h , dd , j 13.4 , 
 5.2 ) , 1.58 ( 1 h , dddd j 13.5 , 12.5 , 4.3 , 0.95 ) , 1.20 
 ( 3 h , d j 0.95 ) , 1.12 ( 3 h , s ) , 0.98 ( 3 h , s ) ; c nmr ( 75 mhz ; cdcl3 ) 143.4 ( ch ) , 139.0 ( ch ) , 
 128.9 ( c ) , 109.0 ( ch ) , 80.1 ( c ) , 72.8 ( ch ) , 65.6 ( ch ) , 57.0 ( ch ) , 
 40.2 ( ch2 ) , 39.0 ( c ) , 33.2 ( ch2 ) , 32.7 ( ch2 ) , 30.6 ( ch3 ) , 23.6 ( ch3 ) , 17.7 ( ch3 ) ; ms ( ei ) m / e ( relative 
 intensity ) 299 ( 32 ) , 297 ( 29 ) , 219 ( 16 ) , 217 ( 16 ) , 137 ( 62 ) , 121 ( 74 ) , 
 95 ( 53 ) , 81 ( 100 ) ; ms ( esi ; meoh / licl ) m / e ( relative intensity ) 241 ( 100 ) , 257 ( 48 ) , 319 ( 20 ) , 321 
 ( 21 ) ; hrms ( esi ) m / e [ m + li ] calcd 
 for c15h21bro2li 319.08795 , obsd 319.08811 , calcd for c15h21bro2li 321.08590 , obsd 321.08603 . elution with ethyl acetate allowed recovery of the catalyst as the 
 phosphoramidate ( 160 mg , 98% recovery ) . when the catalyst / substrate 
 system is prepared by addition of a solution of the ( s)-tcpt catalyst 8 in ch2cl2 ( 2 
 ml ) to a solution of the substrate in nitroethane ( 20 ml ) , followed 
 by drying over activated 4  molecular sieves and proceeding 
 as above the reaction gives luzofuran ( 3 ) ( 84 mg , 29% ) 
 and 4-epi-3 ( 21 mg , 7% ) with recovery 
 of the unreacted substrate ( 65 mg , 33% ) . to 
 a solution of ( )-3 ( 7.0 mg , 22 mol , 1.0 
 equiv ) in fluorobenzene ( 1 ml ) 
 was added tributyltin hydride ( 13 l , 48 mol , 2.1 equiv ) 
 and the mixture heated to 50 c . a solution of va-044 ( 7.1 mg , 
 22 mol , 1.0 equiv ) in methanol ( 1 ml ) was added over 10 h. 
 after the solution was stirred at 50 c ( 6 h ) tlc analysis showed 
 incomplete conversion . tributyltin hydride ( 5.0 l , 19 mol , 
 2 equiv ) and va-044 ( 2.0 mg , 6.2 mol , 0.28 equiv ) in methanol 
 ( 0.5 ml ) were added , and stirring was continued at 50 c ( 8 h ) . 
 the solution was cooled to room temperature and partitioned between 
 ether ( 10 ml ) and a solution of potassium fluoride ( 5% in water , 10 
 ml ) , and then the aqueous partition was extracted with ether ( 10 ml ) . the combined organic extracts were washed with water ( 50 ml ) , a solution 
 of potassium fluoride ( 5% in water , 10 ml ) , and a saturated solution 
 of ammonium chloride ( 10 ml ) , dried over sodium sulfate , and concentrated . column chromatography with 10% potassium carbonate on silica ( ethyl 
 acetate / light petroleum 1/19 ) gave ( )-16 ( 4.1 mg , 
 84% ) as a colorless oil : rf 0.25 ( ether / hexanes 1/19 ) ; ir ( neat ) max / cm 2931 , 1461 , 1261 , 1158 , 1025 , 874 ; h nmr ( 300 mhz ; cdcl3 ) 7.357.37 ( 2 h , m ) , 6.34 
 ( 1 h , m ) , 5.03 ( 1 h , ddd , j 9.2 , 2.5 , 0.4 ) , 2.16 
 ( 1 h , ddd , j 13.6 , 11.6 , 9.3 ) 1.881.95 ( 1 
 h , m ) , 1.75 ( 1 h , dddd , j 11.6 , 7.0 , 2.7 , 0.5 ) , 1.31.65 
 ( 6 h , m ) , 1.16 ( 3 h , d , j 0.6 ) , 0.93 ( 3 h , s ) , 0.89 
 ( 3 h , s ) ; c nmr ( 75 mhz ; cdcl3 ) 143.4 ( ch ) , 
 139.1 ( ch ) , 129.5 ( c ) , 108.8 ( ch ) , 81.4 ( c ) , 69.5 ( ch ) , 55.6 ( ch ) , 
 41.2 ( ch2 ) , 39.0 ( ch2 ) , 33.3 ( c ) , 32.9 ( ch3 ) , 31.7 ( ch2 ) , 21.3 ( ch2 ) , 20.5 ( ch3 ) , 20.1 ( ch3 ) ; ms ( esi ; meoh / licl ) m / e ( relative intensity ) 241 ( 100 ) ; hrms ( esi ) m / e [ m + li ] calcd for c15h22o2li 241.17744 , obsd 241.17763 , calcd 
 for c30h44o4li 475.33942 , 
 obsd 475.33942 . lithium ( 5.0 mg , 
 0.72 mmol , 23 equiv ) , 
 anhydrous magnesium chloride ( 30 mg , 0.32 mmol , 10 equiv ) , and naphthalene 
 ( 13 mg , 0.10 mmol , 3.3 equiv ) were taken up in thf ( 1.5 ml ) and stirred 
 vigorously ( 3 h ) . the resulting black suspension of active magnesium 
 was cooled to 78 c , and a solution of ( s)-4-epi-3 ( 10 mg , 3.1 mol , 1.0 
 equiv ) in thf ( 1.0 ml ) added over 0.5 h. the solution was stirred , 
 allowing to warm to 65 c ( 16 h ) . a solution of tert - butyl alcohol ( 10% in thf , 3.0 ml ) was added slowly 
 and the solution stirred at 65 c ( 0.5 h ) . isopropyl 
 alcohol ( 5 ml ) was added , the reaction partitioned between ether ( 10 
 ml ) and water ( 50 ml ) , and the aqueous partition extracted with ether 
 ( 10 ml ) . the combined organic extracts were washed with water ( 3  
 50 ml ) , dried over sodium sulfate , and concentrated . column chromatography 
 ( ether / light petroleum 7/93 ) gave ( s)-()-17 ( 6.4 mg , 86% ) as a colorless oil : rf 0.35 ( ether / hexanes 1/19 ) ; [ ]d20 2.6 ( c 0.20 , chcl3 ) ; ir ( neat ) max / cm 2865 , 1458 , 1374 , 1259 , 1156 , 1049 , 1024 ; h nmr ( 300 mhz ; cdcl3 ) 7.37 ( 2 h , m ) , 6.38 ( 1 h , 
 m ) , 4.91 ( 1 h , dd , j 9.1 , 6.8 ) , 2.20 ( 1 h , dddd , j 11.6 , 6.4 , 4.8 , 0.7 ) 1.871.94 ( 1 h , m ) , 1.80 ( 1 
 h , ddd , j 13.7 , 11.2 , 9.1 ) , 1.63 ( 1 h , dd , j 13.7 , 5.2 ) , 1.261.74 ( 6 h , m ) , 1.14 ( 3 h , d , j 0.7 ) , 0.99 ( 3 h , s ) , 0.87 ( 3 h , s ) ; c nmr 
 ( 75 mhz ; cdcl3 ) 143.1 ( ch ) , 138.8 ( ch ) , 129.3 ( c ) , 109.1 
 ( ch ) , 81.0 ( c ) , 71.6 ( ch ) , 57.4 ( ch ) , 40.9 ( ch2 ) , 39.2 
 ( ch2 ) , 33.2 ( c ) , 32.9 ( ch3 ) , 31.5 ( ch2 ) , 23.4 ( ch3 ) , 21.4 ( ch2 ) , 20.5 ( ch3 ) ; ms ( esi ; meoh / licl ) m / e ( relative 
 intensity ) 241 ( 100 ) ; hrms ( esi ) m / e [ m + li ] calcd for c15h22o2li 241.17744 , obsd 241.17764 , calcd for c30h44o4li 475.33942 , obsd 475.33948 .
the first synthesis of the furan - containing 
 snyderane , ( + ) -luzofuran , 
 is reported . 
 the key step in this approach was an electrophilic brominative 
 cyclization , which was accomplished using a nucleophilic n - heterocycle - flanked phosphoramidite catalyst in combination with 
 the common laboratory reagent n - bromosuccinimide .