Vinyl cuprate addition

Corey and Fuchs (39) noted the vinyl cuprate addition on J15 to produce 116 stereospecifically. Clark and Heathcock (40) observed the lithium dime-thylcopper addition on 117 which yielded 118 while Trost, Taber, and Alper (41) reported the conversion of 119 into 120 with the same reagent. 

Vinyl cuprates.17 Vinyl cuprates can be prepared conveniently by in situ trans-metallation of vinylstannanes, available by hydrostannylation of alkynes, with a cuprate such as (CH3)2Cu(CN)Li2 (equation I). Reagents prepared in this way effect conjugate addition of the vinyl group to an enone with essentially no transfer of the methyl group. 

The initial reports in 1982-83 by Westmijze et. al. [25a] and Piers [25b] on the addition of stannylcopper and cuprate reagents to simple alkynes were followed by full studies [76] and reports from several laboratories [14b, 16b-e, 25c, 77-78]. In the earlier studies, the vinylcopper species could only be trapped with a proton. Marino achieved success in the addition to cyclohexenone of the vinyl cuprate generated by addition of BusSnCuCNLi to acetylene [79a-b], and Fleming [79c]... 

ESR and CIDNP studies intended to detect the radical intermediates failed [63], Conjugate addition of a vinylcuprate reagent to an enone takes place with retention of the vinyl geometry indicating that no vinyl radical intermediate is involved [64, 65], Kinetic isotope effects and substituent effects in cuprate addition to benzophenone indicate that C-C bond formation is rate-determining, which is not consistent with the involvement of a radical ion pair intermediate [66]. 

The formed vinylic cuprates readily perform conjugate addition to a,)3-unsaturated carbonyl compounds giving 8-vinyl-substituted ketones. 

Details of the Janda-Chen synthesis were as follows. A tetrahydropyran (THP) linker was attached to the NCPS support enabling attachment of alcohols via THP ether formation.13 The THP-NCPS resin 1 is derivatized with / -(+)-4-hydroxy-2-cyclopentanone 2, giving the THP ether-based resin 3, followed by coupling of the C13 20 fragment by enone-cuprate addition. The cuprate required was generated from the corresponding E-vinyl stannane 4. The resulting enolate was trapped as the silyl end ether... 

The is-olefin was prepared as a trans-amide bond replacement. A number of compounds incorporating substituents to mimic both natural and unnatural amino acid sidechains were prepared by adapting chemistry developed by Ibuka for the synthesis of Zs-olefin peptide isosteres (see Scheme l).40,41 The key step involved anti-SN2 displacement of vinyl mesylate 8 by boron trifluoride-activated cuprate addition. Compounds containing butyl, propyl, and benzyl substituents at the allylic positions to mimic the aj and sidechains produced potent FTase inhibitors (Table 4). 

Conjugate addition of vinyl cuprate and dimethyl malonate to 4,4-dimethylcyclo-hexa-2,5-dienones has allowed facile access to mono- and bis-adducts in good yields. Whereas the high diastereoselectivity to afford trans-bis-adducts was predictable,... 

The stannylcupration of alkynes has been widely studied. Reaction of alkynes with lithium bis(tributylstannyl) cuprate leads to r -2-(tri butyl stannyl) vinyl cuprates, which are synthetically equivalent to cis- 1,2-ethylene dianions. Addition of the tin-copper reagent across the triple bond occurs i>7/-stereospecifically, thus providing Z-vinylstannanes. Phenylacetylene reacts with the tin cuprate with a regiochemistry opposite to that of 1-decyne.294 The intermediate cuprates react well with the various electrophiles.295 For example, the reaction with ethylene oxide gives primary alcohols, and further treatment of their />-toluenesulfonates with butyllithium gives 1-substituted cyclobutenes (Equation (120)) 294... 

This reaction illustrates a stereoselective preparation of (Z)-vinylic cuprates, 5 which are very useful synthetic Intermediates. They react with a variety of electrophiles such as carbon dioxide,5,6 epoxides,5,6 aldehydes,6 allylic halides,7 alkyl halides,7 and acetylenic halides 7 they undergo conjugate addition to a,6-unsaturated esters,5 6 ketones,6 aldehydes,6 and sulfones.8 Finally they add smoothly to activated triple bonds6 such as HCSC-OEt, HC3C-SEt, HC=C-CH(0Et)2. In most cases these cuprates transfer both alkenyl groups. The uses and applications of the carbocupration reaction have been reviewed recently.9 The configurational purity in the final product 1s at least 99.951 Z in the above transformations. 

Ethyl acrylate will react with vinylic cuprates, but at a much slower rate than a, -unsaturated ketones and ethyl propynoates 205). Complex-ation with trimethyl phosphite is advantageous because the reactivities of the cuprate and resulting carbanion are increased. Glutarate esters are important by-products from the reaction of the intermediate carbanion with another molecule of the acrylate the primary addition product was obtained in yields from 3.4% to 38% and the glutarate ester in 7.1-31% yield. 

Lithium divinyl cuprates.5 The addition of vinylic cuprates to chiral y-alkoxy-a,P-unsaturated ketones and esters proceeds with high diastereoselectivity the major product is that in which the vinyl group is anti to the ally lie alkoxyl group. The geometry of the unsaturated system does not affect the stereochemistry of the addition. 

Z)-Viuylic iodides. These iodides can be prepared by reaction of iodine with (Z)-vinylic cuprates, prepared by addition of lithium dialkylcuprates to acetylene (equation I). ... 

Methyl-a-D-mannopyranoside and methyl-a-D-galactopyranoside have also been used as chiral auxiliaries for conjugate additions of organocuprates to crotonyl esters. For the galactosyl derivative, the crotonyl ester was attached to the 3-hydroxyl group of the galactopyranoside. The addition of vinyl cuprate to ester 191 proceeded with high yield and stereoselectivity (Scheme 10.63). In this case, the diastereomeric esters 192 and 193 delivered the enantiomeric benzyl esters 194 and 195 with 96% ee. 

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