Carbocupration reaction

In case of 3-substituted 1,2-allenyl sulfones, e.g. 210, the carbocupration reaction exhibits Z-selectivity, indicating that the nucleophile attacks from the less hindered... 

Chiral homoallylic alcohols and amines were prepared by using a four-component condensation reaction based on a zinc homologation followed by a trapping with an aldehyde or an imine.301 A regio- and stereospecific carbocupration reaction on alkynyl sulfoxide provides the corresponding metallated /3,/3-dialkylated a,/ -ethylenic sufoxide 98. Addition of aldehydes or imines, followed by addition of the bis(iodomethyl)zinc carbenoid, provides adducts 99 in good overall yield and with very high diastereoselectivity (Scheme 36). 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

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. 

The conjugate addition of various propargyl alcohols [57] or propargyl amines [58] to gem-diactivated olefins such as 47 can be used in tandem with the intramolecular carbocupration reaction (Scheme 20). This sequential... 

They continue to serve synthetic practitioners who have come to rely on their ability to mainly effect substitution, conjugate addition, and to a lesser extent, carbocupration reactions (Scheme 1). 

Taylor has nicely controlled the double carbocupration reaction of... 

Complex 69, formed via n-complexation of an organocuprate with an unsaturated carbonyl compound, is the common starting point in both pathways (Scheme 26). jr-Complexation is followed by either (1) a formal oxidative addition to the p-carbon of the carbonyl compound to afford o-complex 70 (Cu(lll)-intermediate) that after a reductive elimination step affords the it-adduct 72 or (2) a carbocupration reaction affording compound 71 that upon rearrangement leads to jr-adduct 72 [105-108]. 

On the other hand, it was possible to observe vinyl copper species derived from carbocupration reactions, when an a,p-unsaturated carbonyl compound bearing an alkynyl moiety underwent addition to a Lipshutz-type organocuprate [121, 122]. Krause et al. were the first to show NMR spectroscopic evidence of such intermediates during their studies of the reaction between methyl phenylpropiolate 77 and lBuCu(CN)Li 78 (Scheme 29) [123]. 

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