coupling reactions with organoboron compounds 
 are among the most 
 strategically significant processes in chemical synthesis . robust ( pinacolato)boron [ b(pin ) ] derivatives 
 are utilized frequently , and alkenylboron species represent one of 
 the more attractive substrate classes ; the resulting olefin - containing products , particularly if generated 
 stereoselectively , can be functionalized in a number of ways . b(pin ) 
 reagents therefore carry substantial value , and their development 
 constitutes a compelling research objective . one recent line 
 of study in these laboratories has led to the design 
 of enantioselective processes with different types of b - containing 
 starting materials . c bonds 
 while delivering alkenyl groups of varying substitution patterns that might contain sensitive functionality ( e.g. , a carbonyl group ) . the significance 
 of such attributes becomes evident through comparison with the alternative 
 catalytic transformations that entail alkenylaluminum species ( scheme 1a and b ) . although the latter nucleophile set can 
 be prepared through reaction of a terminal alkyne ( uncatalyzed or 
 promoted by a ni - based complex ) with diisobutylaluminum hydride ( dibal  h ) , a number of shortcomings accompany their use . one issue is the sensitivity 
 of the metal  hydride reagent 
 as well as the resulting alkenylmetal complex to air and moisture . the relatively high reactivity of the latter species with commonly 
 used functional units , such as a carbonyl unit ( unless it is conjugated 
 with the reacting  system ) , also detracts from 
 the approach . moreover , direct preparation of several types of alkenylaluminum 
 reagents would be challenging ( e.g. , z - disubstituted 
 or vinylboron compounds ) , and it would not be a given that the stereochemical 
 identity of the organometallic reagent would be retained in the course 
 of the ensuing eas . we have previously reported a sequence involving 
 silyl - substituted alkenylaluminum compounds ( scheme 1b ) , accessed via a silyl - alkyne and its site - selective hydroalumination . the catalytic eas reactions proved to be high 
 yielding , and the expected 1,4-dienes were formed in up to > 98% 
 sn2 selectivity and > 99:1 enantiomeric ratio 
 ( er ) ; nonetheless , 
 silylated alkynes had to be prepared initially , and the desired z alkenes were revealed after protodesilylation . it would 
 be more efficient if z - alkenylboron reagents were 
 to be employed , especially if accessed through a catalytic stereoselective 
 process ; the need for transitory incorporation of a silyl unit would 
 thus be obviated . what is more , reactions of silyl - substituted alkenylaluminum 
 species and sterically demanding electrophiles are inefficient , a limitation more likely to be resolved with 
 nonsilylated nucleophilic components . addition of an unsubstituted 
 alkene can be more easily accomplished by means of a vinyl b(pin ) 
 reagent ; as far as we are aware , catalytic eas reactions involving 
 a vinyl group have not been previously disclosed . a significant 
 recent advance by carreira illustrates that a variety 
 of secondary allylic alcohols react with alkenyl(trifluoro)boron potassium 
 salts to generate eas products in the presence of a chiral phosphoramidite transformations are efficient and proceed in 75:25 to > 98:2 branched : linear 
 ( sn2:sn2 ) ratios and up to > 99:1 
 er . a distinguishing feature of the approach is that unsaturated alcohols 
 serve as starting materials ( vs a more activated derivative ) . substrates are limited 
 to aryl - substituted allylic alcohols with a terminal olefin , affording 
 1,4-dienes bearing a monosubstituted alkene . the need for 2 equiv 
 of hydrogen fluoride detracts from the practicality of the approach . the protocol requires the use of fluoroboryl compounds , which are 
 typically accessed via alkenyl bf3k species employed did not contain a carbonyl - based moiety ; 
 eas with vinylboron entities or alkenylboron reagents that carry a 
 trisubstituted heterocyclic unit were not reported . a notable 2011 
 disclosure by hayashi and shintani focused on nhc  cu - catalyzed 
 eas processes with arylboronic acid neopentyl glycol esters ; this 
 study included an example of the addition of cyclohexenyl - derived 
 species , which furnished the desired product in 84% yield and complete 
 site selectivity ( > 99:1 sn2:sn2 ) 
 and 
 in 86.5:13.5 er . herein , we put 
 forth a broadly applicable method for catalytic 
 eas reactions of easily accessible di- or trisubstituted allylic phosphates 
 and alkenyl b(pin ) reagents , resulting in the formation of 
 tertiary c  c bonds ( scheme 2 ) ; only 
 the carboxylic ester and acetal - containing alkenylboron reagents have 
 previously been employed in eas reactions that furnish quaternary 
 carbon centers . products are obtained 
 in 52% to > 98% yield , 93:7 to > 98:2 sn2:sn2 selectivity , and 83:1799:1 er . a key attribute of 
 the approach 
 is that , in many cases , products are obtained in high enantiomeric 
 purity despite containing a sensitive stereogenic center ( cf . , highlighted 
 acidic protons in scheme 2 ) ; such a challenge 
 was not germane to the previously investigated transformations leading 
 to quaternary carbon stereogenic centers , nor did it pose a complication in those performed with allenyl an assortment of alkenylboron 
 compounds can be used , including those containing a carbonyl , an acetal , 
 or an o- or n - substituted heterocyclic unit . in all cases , except 
 one . disubstituted 
 ( e or z ) , trisubstituted ( linear 
 or cyclic ) variants , as well as vinyl , there are no 
 existing descriptions of catalytic eas processes with heterocyclic 
 alkenylboron or vinyl  b(pin ) compounds . b(pin ) reagents are prepared by catalytic site- or 
 stereoselective processes , such as z - selective cross - metathesis 
 ( cm ) with commercially available vinyl catalysts are derived from 
 sulfonate - containing chiral imidazolinium salts synthesized in four 
 steps and are converted to n - heterocyclic carbene ( nhc ) copper complexes through deprotonation 
 and reaction with commercially available cucl . utility is illustrated 
 through approaches to enantioselective syntheses of several natural 
 products ( cf . we began by examining 
 the ability of a selection of chiral nhc  cu complexes to promote 
 the eas involving allylic phosphate 1a and commercially 
 available n - alkyl - substituted alkenyl the transformation carried out 
 in the presence of c2-symmetric 4 and with c1-symmetric species 
 derived from imidazolinium salt 5 proceeded to 38% and 
 76% conversion , respectively , generating the desired product with 
 low site and enantioselectivity ( entries 1,2 , table 1 ) . similarly low efficiency was observed with phenyl glycinol - derived 6(14 ) ( entry 3 ) ; while site selectivity 
 improved substantially , underlining the crucial ability of cuprate 
 complexes ( vs monodentate nhc 1,4-diene 3 was formed with reasonable efficiency ( 91% conv ) and complete 
 site selectivity ( > 98% sn2 ) but only in 41:59 
 er 
 when imidazolinium salt 7 was utilized ( entry 4 ) . particularly 
 noteworthy sulfonate 8 , which proved to be the most effective for eas with 2 and the corresponding trisubstituted allylic phosphate leading 
 to a quaternary carbon stereogenic center , promoted a minimally enantioselective reaction ( entry 5 ) . finally , 
 we established that bidentate copper complexes generated from 9a , b ( entries 6,7 ) , containing a 3,5-disubstituted 
 nar moiety , deliver 3 efficiently and selectively ; the 
 complex derived from 9b afforded the desired product 
 in 97% yield , 98:2 sn2:sn2 selectivity , 
 and 92:8 er ( entry 7 , table 1 ) . reaction at 
 lower temperatures resulted in reduced efficiency and similar selectivity . 
 at this point , we turned to examining eas where the more synthetically 
 versatile organoboron reagents are used . reactions performed under n2 atm . conversion ( allylic phosphate consumption ) 
 and site selectivity ( 2% ) were determined by analysis of 400 
 mhz h nmr spectra of product mixtures prior to purification . the nhc  cu - catalyzed eas involving p - nitrophenyl - substituted allylic phosphate 1b and commercially available alkenylboron species 10 proceeded 
 to > 98% conv , affording 11 in 90% yield , 96% site 
 selectivity , 
 and 93:7 er ( scheme 3 ) . hydrolysis of the acetal 
 group , achieved by subjection of 11 to a suspension of 
 silica gel in et2o , delivered enal 12b in 
 quantitative yield without detectable loss of enantiomeric purity 
 [ 93:7 er ; > 98% enantiospecificity ( es ) ] despite an acidic benzylic 
 proton . two involve additions to a disubstituted allylic phosphate , 
 followed by hydrolysis to afford ,-unsaturated aldehydes 12a and 12c ; the latter case entails eas with 
 a sterically demanding substrate containing an o - bromophenyl 
 moiety . also shown is a reaction with a trisubstituted allylic phosphate , 
 furnishing unsaturated ester 13 , with the acetal unit 
 preserved , in 52% yield , > 98:2 sn2:sn2 selectivity , and 92:8 er . the discrepancy between the conversion 
 level and yield of the desired product in the last case might be due 
 to sensitivity of the acetal group to adventitious hydrolysis upon 
 purification . reactions performed 
 under n2 atm ; conversion ( allylic phosphate consumption ) 
 and site 
 selectivities ( 2% ) were determined by analysis of 400 mhz h nmr spectra of product mixtures prior to purification ; yields 
 ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . the catalytic 
 processes involving the commercially available ethyl ester - substituted 14 present a more notable challenge in relation to retention 
 of the kinetically generated stereoisomeric purity ( scheme 4 ) . here , the resulting stereogenic center must survive 
 the basic conditions needed for eas reactions for 24 h ( vs mild acidic 
 conditions needed for hydrolysis of the acetal - containing products 
 in scheme 3 ) . the 
 most sensitive 1,4-diene generated through the transformations illustrated 
 in scheme 4 relates to the eas with m - trifluoromethylphenyl - substituted allylic phosphate 1c ; nonetheless , 15c was formed in 61% yield , > 98% sn2 selectivity , 
 and 
 96:4 er ; undesired 1,3-diene 16 was obtained in 39% yield . consistent with the aforementioned complication , synthesis of 15a proceeded in an improved 95% yield with 97% site selectivity 
 and 92.5:7.5 er ( scheme 4 ) . addition to the 
 sterically demanding o - tolyl substrate leading to 15d ( 95% yield , 96:4 sn2:sn2 , 
 92:8 er ) illustrates that nhc  cu - catalyzed eas can be performed 
 with sterically demanding electrophiles . alkyl - substituted allylic 
 phosphates are suitable starting materials as well , underscored by 
 the efficient and highly selective formation of 17 ( > 98% 
 conv , 95% sn2 , 92.5:7.5 er ) ; subsequent treatment 
 with meli delivered the tertiary alcohol , and concomitant removal 
 of the acyl group revealed an irregular monoterpene derived from artemisia annua l. , from which the potent antimalarial 
 artemisinin was isolated . reactions performed 
 under n2 atm ; conversion ( allylic phosphate consumption ) 
 and site 
 selectivities ( 2% ) were determined by analysis of 400 mhz h nmr spectra of product mixtures prior to purification ; yields 
 ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . we wished to introduce a catalytic eas protocol that leads 
 to incorporation of z alkenes and is of broad scope . moreover , we aimed to establish a catalytic eas protocol with the 
 more readily accessible ( in many cases through a catalytic stereoselective 
 process ) and robust alkenyl what renders such a task challenging is the reduced lewis 
 acidity of the boron center and the larger size of the pinacol moiety , 
 attributes that diminish the rate of transmetalation leading to the 
 nhc  cu  alkenyl intermediate of the catalytic cycle ; 
 such a complication is exacerbated by the increased steric hindrance 
 of a z alkenyl we first 
 investigated transformations involving 
 methyl - substituted reagent 18 , a compound that can be 
 purchased in the purely z form ( < 2% e ; scheme 5 ) . we established that 
 the cu - catalyzed process involving 1a and 18 proceeds to 90% conversion at ambient temperature within 8 h ( scheme 5 ) ; z-1,4-diene 19a was obtained in 76% yield , with > 98% sn2 selectivity , 
 without any isomerization to the e isomer ( > 98% z ) and in 95:5 er . an assortment of allylic phosphates can 
 be employed : electrophilic alkenes attached to electron - deficient 
 ( cf . , 19b ) , electron - rich ( cf . , 19c ) , or 
 sterically demanding ( cf . , 19d ) aryl groups were transformed 
 to the desired products in 7682% yield , exceptional site selectivity 
 ( > 98% sn2 ) , and 97:398:2 er . reactions 
 with electrophilic components containing a trisubstituted alkene , 
 previously determined to be a relatively challenging and more sparsely 
 examined substrate class , whether it 
 is a methyl group ( 20a  c ) or a carboxylic 
 ester ( 21a  c ) , remained reasonably 
 efficient ( 7496% yield ) , generating little or none of the 
 achiral linear product isomer ( 2% sn2 ) . reactions performed 
 under n2 atm ; reaction times are 8.0 h for 19a  d , and 24 h for the other cases . conversion 
 ( allylic phosphate 
 consumption ) and site selectivities ( 2% ) were determined by 
 analysis of 400 mhz h nmr spectra of product mixtures 
 prior to purification ; yields ( 5% ) are of products after purification ; 
 enantioselectivities ( 2% ) were determined by hplc analysis . b(pin ) reagents allows for a two - stage 
 catalytic process that begins with a z - selective 
 cm . regarding the first stage , cm transformations promoted by mo monopyrrolide 
 aryloxide catalysts involving commercially available vinyl b(pin ) 
 ( 22 ) were recently shown to proceed efficiently and with 
 high z selectivity . conversion ( allylic phosphate consumption ) and site selectivities 
 ( 2% ) were determined by analysis of 400 mhz h nmr 
 spectra of unpurified product mixtures ; yields ( 5% ) are of products 
 after purification ; enantioselectivities ( 2% ) were determined 
 by hplc analysis . conditions were the same as those used for 25 , except 1.0 equiv of z - alkenyl b(pin ) , 
 1.25 equiv of allylic phosphate , and 1.25 equiv of naome were used . b(pin ) reagent 
 used consisted of a 96:4 z : e and 
 > 98% z samples for 25 and 27c , respectively ( in each case , the pure z isomer 
 of the eas product was isolated after silica gel chromatography ) . the transformation culminating in the formation 
 of enal 26 demonstrates the effectiveness of the catalytic 
 cm / eas sequence 
 ( scheme 6 ) . z - selective cm 
 of commercially available 22 and a readily accessible 
 silyl ether in the presence of 5.0 mol % mo complex 23a , generated and used in situ , afforded z - alkenyl the ensuing 
 eas with allylic phosphate 1d delivered z-1,4-diene 25 in 81% yield as its pure z isomer with > 98% site selectivity 
 and 
 in 99:1 er . unmasking of the allylic alcohol and subsequent oxidation 
 afforded enantiomerically enriched 26 in 78% overall 
 yield with complete retention of diastereo- and enantiomeric purity 
 ( > 98% z and 99:1 er ) . as demonstrated through 
 syntheses 
 of 27a  c and 28 , a variety 
 of 1,4-dienes can be accessed efficiently and with 95% sn2 selectivity and 96:499:1 er , and as 93% z isomers . when 
 the z - alkenylboron reagent carries a sizable group , 
 eas processes proceed with lower site- and enantioselectivity with 
 imidazolinium salt 9b serving as the catalyst precursor . one example ( scheme 7 ) is the transformation 
 involving the cyclohexyl - containing allylic phosphate 29a and phenyl - substituted alkenylboron species 30 ( obtained 
 through z - selective cm);31 was obtained in 74:26 sn2:sn2 and er . to address the above issue , we returned to 
 the stereochemical model for catalytic eas reactions ( i , scheme 7 ) . we considered the possibility 
 that the large group of the z - alkenylcopper intermediate 
 ( g ) might elevate the energy of complex i due to steric 
 interactions involving the tri - i - propylphenyl moiety 
 in 9b . accordingly , modes of transformation involving 
 substrate  catalyst association through the alternative enantiotopic 
 face of the allylic phosphate could become competitive , leading to 
 lowering of er . ii ) , with the protruding group of the nar group at its ortho 
 position , might be better able to accommodate the sizable alkenyl 
 substituent . we therefore prepared chiral 
 imidazolinium salt 9c and probed the ability of the derived 
 nhc  cu complex in catalyzing the formation of 1,4-diene 31 , which was accordingly obtained in quantitative yield and 
 significantly improved > 98% sn2 selectivity 
 and 
 91:9 er . reactions 
 performed under n2 atm ; all alkenyl b(pin ) reagents 
 were obtained through 
 mo - catalyzed z - selective cross - metathesis ( cm ) . conversion 
 ( allylic phosphate consumption ) , site- , and z / e selectivities ( 2% ) were determined by analysis of 
 400 mhz h nmr spectra of product mixtures prior to purification ; 
 yields ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . , we carried out a concise , 
 diastereo- and 
 enantioselective synthesis of nyasol ( scheme 8) . b(pin ) reagent 32 was prepared 
 in 69% yield and 93% stereoselectivity through mo - catalyzed cm performed 
 with 3.0 mol % 23b and 1.5 equiv of p - methoxystyrene . subsequent nhc  cu - catalyzed eas with 1e afforded 33 in 92% yield , with complete site 
 selectivity , as a single alkene isomer ( > 98% z after 
 purification ) and in 97:3 er . nyasol was generated after removal of 
 the methoxy and tosyl groups in 79% overall yield . in contrast to 
 a route reported previously , also involving an nhc  cu - catalyzed 
 eas , preparation and use of a silyl - substituted 
 alkenylaluminum reagent and subsequent desilylation was not needed . 
 additionally , unlike the recent route to nyasol involving a phosphine  ir - catalyzed 
 eas reaction , complete site selectivity 
 was attained ( vs 74:26 sn2:sn2 ) , the 
 presence of hydrogen fluoride was not necessary ( see scheme 1c ) , and the z - alkenyl b(pin ) 
 compound could be employed directly without the multistep 
 procedures needed for the formation of the corresponding trifluoroborate 
 salts . the possibility of a succinct route for enantioselective 
 synthesis 
 of diol 38 ( scheme 9 ) , used to 
 prepare different members of the heliannuol family of natural products as well as the structurally related heliespirones , presented us with an opportunity to explore 
 further the scope of the catalytic protocol with a more sterically 
 demanding z - alkenyl we established 
 that reaction of 1d with allylic t - butyldimethylsilyl 
 ether 34(27 ) promoted by 5.0 
 mol % of the nhc cu complex derived from 9c furnishes 
 1,4-diene 35 in > 98:2 sn2:sn2 selectivity and 98:2 er ( > 98% z ) . that 
 is , the 
 highly encumbered boron center of alkenyl alkenyl complex 
 undergoes reasonably efficient addition to generate 35 ; although 18% of the allylic phosphate was recovered , the expected 
 product was isolated in 79% yield ( 82% conv ) . when performed on ca . 0.5 g scale , the reaction proceeded to 79% conv , affording 35 in 71% yield ( ca . desilylation , oxidation , and alkylation of the resulting ketone delivered 
 tertiary alcohol 36 in 60% overall yield ( no detectable 
 change in stereoisomeric purity ) . b(pin ) containing the tertiary alcohol 
 or the derived silyl ether moiety ( obviating the above deprotection / oxidation / alkylation 
 sequence ) by hydroboration of the appropriate terminal alkyne proved unsuccessful . site- ( chemo- ) and diastereoselective 
 epoxidation , in the presence of excess 
 ti(oi - pr)4 likely needed due to steric 
 hindrance at the hydroxyl directing group or competitive coordination 
 to lewis basic ome groups , afforded 37 in 92:8 diastereomeric ratio ( dr ) , which was isolated as 
 a single diastereomer in 76% yield ( 15% epoxide derived from the terminal 
 alkene was also isolated after chromatography ) . reductive cleavage 
 of the epoxide proceeded with > 98% site selectivity through a ti - mediated 
 procedure , furnishing 38 in 55% yield . the latter diol has been utilized in the enantioselective 
 synthesis of heliespirone a and c ( only 
 the former shown in scheme 9 ) and heliannuol 
 e. reactions performed under n2 atm ; conversion ( allylic phosphate consumption ) , site selectivities , 
 and diastereoselectivities ( 2% ) were determined by analysis 
 of 400 mhz h nmr spectra of product mixtures prior to 
 purification ; yields ( 5% ) are of products after purification ; 
 enantioselectivities ( 2% ) were determined by hplc analysis . another class of nucleophiles that have been used 
 less commonly in catalytic eas reactions involves those that contain 
 a trisubstituted alkene . as far as we are aware , there are no reported examples involving 
 transformations with heterocyclic alkenyl moieties . the eas 
 shown in eq 1 delivers natural product santolina 
 alcohol in 65% yield ( some loss due to 
 product volatility ) , complete sn2 selectivity , 
 and 96:4 er . the catalytic process involves alkyl - substituted substrate 39 , which contains a hydroxyl - substituted quaternary carbon 
 center immediately next to the reactive site . although the transformation 
 involves the sterically demanding reagent 40 ( commercially 
 available ) , enantioselective addition proceeds readily . it is equally 
 noteworthy that protection of the tertiary alcohol , a measure adopted 
 to curtail the competitive and adventitious protonation of the intermediate 
 alkenyl  cu complex , is not necessary here . such an advantage 
 is likely the result of the inability of the sterically encumbered 
 hydroxyl unit to approach the nhc alkene species ; 
 however , use of 2.5 equiv of 40 is needed for achieving 
 complete conversion ( vs 1.52.0 equiv ) , perhaps because the 
 above - mentioned complication does remain operative to a limited extent.1 various heterocyclic alkenyl b(pin ) compounds 
 can be either purchased or prepared by catalytic protocols , including ring - closing metathesis procedures . the nhc  cu - catalyzed eas reactions in 
 scheme 10 involve commercially available heterocyclic 
 organoboron reagents , affording products that contain unsaturated 
 nboc- or o - containing unsaturated rings in 5298% yield , 93% 
 to > 98% site selectivity , and 91:998:2 er . a range of allylic 
 phosphates serve as competent reaction partners , and a ( pinacolato)boron - bearing 
 trisubstituted cyclic allylic ether ( e.g. , 4446 , scheme 10 ) or enol ether ( e.g. , 47a , b , 48 ) readily undergoes addition 
 with high site- and enantioselectivity . aryl - substituted variants 
 may contain a sterically demanding ortho group ( e.g. , 42 , 45 , or 47b , scheme 10 ) , electron - withdrawing ( e.g. , 42 , 44 , 47a ) , or electron - donating units ( e.g. , 45 ) . transformations with alkyl - substituted allylic phosphates ( e.g. , 43b , 46 , 48 ) , those containing a 
 trisubstituted olefin with a methyl ( e.g. , 43a , b , 46 ) , or a carboxylic ester group ( e.g. , 44 , 47a , b , 48 ) proceed 
 efficiently and with high site- and enantioselectively . processes 
 involving unsaturated esters ( scheme 9 ) were 
 carried out with 2.5 mol % catalyst loading ( vs 5.0 mol % for other 
 cases ) . except for heterocyclic alkenyl b(pin ) 49 ( cf . , scheme 11 ) where silica gel chromatography 
 is required for optimal results , the commercially available organoboron 
 reagents can be used as received in eas reactions to generate products 
 with reasonable efficiency and similarly high site- and enantioselectivity 
 as would be observed with the materials that have been purified . reactions performed under n2 atm ; conversion ( allylic phosphate consumption ) and site 
 selectivities ( 2% ) were determined by analysis of 400 mhz h nmr spectra of product mixtures prior to purification ; yields 
 ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . reaction performed at 60 c 
 under otherwise identical conditions as shown for the formation of 42 . reaction performed 
 at 60 c with 2.5 mol % 9b ( for 47a and 48 ) or 9c ( for 47b ) and 
 25 mol % cucl under otherwise identical conditions as shown for the 
 formation of 42 . the route in scheme 11 includes a key nhc  cu - catalyzed stereoselective 
 conjugate reduction developed to complement the eas process . formation 
 of unsaturated pyran 50 from reaction of alkyl - substituted 
 allylic phosphate and organoboron reagent 49 is efficient 
 ( > 98% yield ) and site - selective 
 ( 97% sn2 ) ; nevertheless , the desired product is 
 generated in moderate enantioselectivity ( 83:17 er ) ; examination of 
 various cu complexes and silyl ether derivatives did not lead to identification 
 of superior conditions . oxidation of the heterocyclic moiety to ,-unsaturated 
 lactone 51 proceeded in 78% yield . at this point , a diastereoselective 
 1,4-reduction of the cyclic enoate investigation of 
 different cu complexes reported previously to be effective for reductions 
 involving polymethylhydrosiloxane as the hydride source led to either inefficient and/or minimally selective 
 reactions . as an example , when the ( achiral ) 
 nhc  cu complex reported to be effective for such transformations 
 was used , the desired saturated lactone 
 was obtained in 81% yield and 45:55 dr ( in favor of the undesired 
 isomer ) . we therefore probed a number of chiral imidazolinium salts 
 prepared previously in the context of catalytic enantioselective processes . we determined that with the cu complex derived 
 from c1-symmetric enantiomerically pure 
 heterocyclic salt 52 , lactone 53 can be obtained in 92% yield and 78:22 dr . removal of the 
 silyl unit , reduction of the ester group , and cyclization to the desired 
 bicyclic acetal delivered diastereomerically pure semburin in 65% 
 overall yield and 96:4 er after silica gel chromatography . reactions performed under n2 atm ; conversion ( allylic phosphate consumption ) , site- , and 
 diastereoselectivities ( 2% ) were determined by analysis of 400 
 mhz h nmr spectra of product mixtures prior to purification ; 
 yields ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . in addition to catalytic z - selective 
 cm reactions ( cf . , schemes 68 ) , another set of processes that can be combined 
 with catalytic eas processes is nhc  cu - catalyzed site - selective 
 protyl - boron additions to terminal alkynes . b(pin ) compounds that can be accessed directly through 
 efficient and -selective alkyne protoborations in the presence 
 of 1.0 mol % of a cu complex derived from a commercially available imidazolinium salt . alkenyl - b(pin ) 56 , formed through a transformation with nhc  cu complex 55 in 91% yield and > 98:2 : selectivity , was used to prepare 1,4-diene 57a in 89% yield , > similarly , allylsilane 57b was isolated in 93% yield , > 98:2 sn2:sn2 selectivity , and 97:3 er . because the b - based reagents are 
 relatively unhindered , the cu complex derived from 9b was used ( cf . , schemes 7 and 8) . it should be noted that alkenyl reagents such as 56 ( scheme 12 ) can not be synthesized 
 alternatively through hydrometalation reactions due to rapid substrate 
 decomposition . elevated temperatures ( 60 
 c ) were required for complete conversion to 57a , perhaps as a result of diminution of reactivity as a result of 
 intramolecular amide chelation to the cu center , which is absent in 
 the case of 57b , formation of which proceeds to > 98% 
 conversion at 22 c . the catalytic eas leading to 57a was significantly more sluggish at 22 c , while delivering 
 identical enantioselectivity ( e.g. , 37% conv after 24 h formed in 
 98:2 er ) . reactions performed under n2 atm ; conversion ( allylic phosphate consumption ) and site 
 selectivities ( 2% ) were determined by analysis of 400 mhz h nmr spectra of product mixtures prior to purification ; yields 
 ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . another noteworthy class of eas transformations involves the use 
 of robust and commercially available vinyl an assortment 
 of allylic phosphates , including those that contain a sterically demanding , 
 electron - withdrawing , or electron - donating aryl group ( 59a  d , scheme 13 ) , undergo 
 eas in the presence of 2.5 mol % 9b and 25 mol % cucl 
 to afford the desired products bearing an ,-unsaturated 
 ester in 6885% yield , complete sn2 selectivity , 
 and 98:2 er . addition of a vinyl group can be performed with 
 an alkyl - substituted allylic phosphate , delivering 61 in 66% yield , > 98% site selectivity , and 94:6 er . the use of 
 excess 
 cucl in the reactions in scheme 13 merits note . initial screening indicated that in the presence of 10 mol % 9b and 10 mol % cucl , > 98% conversion can be achieved with 
 er values similar to those shown ; subsequent investigations revealed 
 that with 1025 mol % of cucl present , the amount of the more 
 valuable chiral imidazolinium salt can be decreased . the precise reason 
 for the need for excess cucl might be attributed to association of 
 the lewis acidic salt with the carbonyl unit of the ester moiety to 
 facilitate eas . reactions performed under n2 atm ; conversion ( allylic phosphate consumption ) and site 
 selectivities ( 2% ) were determined by analysis of 400 mhz h nmr spectra of product mixtures prior to purification ; yields 
 ( 5% ) are of products after purification ; enantioselectivities 
 ( 2% ) were determined by hplc analysis . we have developed a 
 generally applicable class of catalytic eas 
 transformations involving the use of an assortment of readily accessible 
 and/or commercially available alkenyl b(pin ) reagents that 
 possess a number of noteworthy attributes : ( 1 ) the nhc  cu - catalyzed 
 c  c bond - forming processes 
 have a reasonably general scope . monosubstituted , e- and z-1,2-disubstituted , 1,1-disubstituted , as 
 well as acyclic and cyclic trisubstituted alkenyl b(pin ) compounds 
 can be reacted with aryl- or alkyl - containing allylic electrophiles 
 efficiently to afford the desired products in high branched : linear 
 ( sn2:sn2 ) and enantiomeric ratios . the 
 scope of the approach and the range of ways through which enantiomerically 
 enriched eas products can be functionalized are underscored through 
 applications to enantioselective synthesis of several small molecule 
 natural products . ( 2 ) catalytic transformations require an abundant and inexpensive 
 metal salt 
 and proceed readily with alkenyl b(pin ) compounds , robust reagents 
 that can be purchased or prepared through catalytic processes . the 
 strategy of combining mo - catalyzed z - selective cm 
 or cu - catalyzed protoboration of terminal alkynes and nhc  cu - catalyzed 
 eas is notable . ( 3 ) alkenyl moieties bearing conjugated carbonyl 
 units can be added 
 efficiently under conditions that are sufficiently mild to allow the 
 isolation of 1,4-dienes that contain a sensitive stereogenic tertiary 
 carbon center in 6195% yield and 92:896:4 er . collectively , the nhc  cu - catalyzed transformations described 
 above allow access to a considerable range of versatile enantiomerically 
 enriched 1,4-dienes , the synthesis of which would have otherwise been 
 less efficient and concise . design and development of catalytic methods 
 for efficient eas processes involving other versatile classes of boron - based 
 reagents and their applications to synthesis of natural products are 
 in progress .
a set 
 of protocols for catalytic enantioselective allylic substitution 
 ( eas ) reactions that allow for additions of alkenyl units to readily 
 accessible allylic electrophiles is disclosed . 
 transformations afford 
 1,4-dienes that contain a tertiary carbon stereogenic site and are 
 promoted by 1.05.0 mol % of a copper complex of an n - heterocyclic carbene ( nhc ) . 
 aryl- as well as alkyl - substituted 
 electrophiles bearing a di- or trisubstituted alkene may be employed . 
 reactions can involve a variety of robust alkenyl(pinacolatoboron ) 
 [ alkenyl  b(pin ) ] compounds that can be either purchased or 
 prepared by various efficient , site- , and/or stereoselective catalytic 
 reactions , such as cross - metathesis or proto - boryl additions to terminal 
 alkynes . 
 vinyl- , e- , or z - disubstituted 
 alkenyl- , 1,1-disubstituted alkenyl- , acyclic , or heterocyclic trisubstituted 
 alkenyl groups may be added in up to > 98% yield , > 98:2 sn2:sn2 , and 99:1 enantiomeric ratio ( er ) . 
 nhc  cu - catalyzed 
 eas with alkenyl 
 b(pin ) reagents containing a conjugated carboxylic 
 ester or aldehyde group proceed to provide the desired 1,4-diene products 
 in good yield and with high enantioselectivity despite the presence 
 of a sensitive stereogenic tertiary carbon center that could be considered 
 prone to epimerization . in most instances , the alternative approach 
 of utilizing an alkenylmetal reagent ( e.g. , an al - based species ) represents 
 an incompatible option . 
 the utility of the approach is illustrated 
 through applications to enantioselective synthesis of natural products 
 such as santolina alcohol , semburin , nyasol , heliespirone a , and heliannuol 
 e.