Alkylation of Carbon by Conjugate Addition

The previous sections have dealt primarily with reactions in which the new carbon-carbon bond is formed in an Sn2 reaction between the nucleophilic carbon species and the alkylating reagent. There is another general and important method for alkylation of carbon that should be discussed at this point. This reaction involves the addition of a nucleophilic carbon species to an electrophilic multiple bond. The reaction is applicable to a wide variety of enolates and enamines. The electrophilic 

Enamines of cyclic ketones react with acrolein to give bicyclic ketones 

Several steps are involved in this reaction, including the transfer of the enamine function to the aldehyde carbonyl. The reaction begins with conjugate addition  

The precise mechanism of this reaction beyond the addition is difficult to specify. 

Presumably, the transfer of the amino function occurs by partial hydrolysis and re-formation of the enamine at the aldehyde group. The method is a convenient way of constructing certain bicyclic ring systems. 

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SECTION 1.10. ALKYLATION OF CARBON NUCLEOPHILES BY CONJUGATE ADDITION... 

Acyclic stereocontrol remains a challenging problem in synthesis. While enan-tiomerically pure sulfoxides are valuable synthetic intermediates for enantiocon-trolled carbon-carbon bond formation by conjugate addition in cyclic cases, their usefulness for such alkylations in acyclic cases has not been firmly established. Moreover, most sulfoxide directed alkylation protocols utilize the valuable sulfur auxiliary just once, which limits the synthetic versatility of the process. Marino et al. have recently reported SN2 displacements of acyclic allylic mesyloxy vinyl sulfoxides with organocopper reagents (Scheme 10).33 In addition to the excellent observed stereoselectivities, the newly created chiral center is adjacent to a vinyl sulfoxide which should allow for subsequent chirality transfer operations. On treatment with organocopper nucleophiles, both sulfoxide diastereoisomers 40b and 43b underwent SN2 displacements with high Z selectivity to yield products 42b and 45b, respectively (Table 2). The oxidation state on the sulfur was varied... 

There are two major reactions of organocuprates, and both give products reminiscent of a carbon nucleophile (1) reaction with alkyl halides and (2) conjugate addition with a,p-unsaturated ketones. Conjugate addition to a, 3-unsaturated ketones is promoted when ether is used as a solvent.381 The substitution reaction is promoted by the use of THF or ether-HMPA as a solvent. l As mentioned earlier, the mechanism of these reactions probably involves a one-electron transfer, although other mechanistic proposals are in the literature,but the synthetic result is that expected of a carbon nucleophile. 85 The general reactivity of organocuprates with electrophiles follows the order ... 

Alkylation of Carbon Nucleophiles by Conjugate Addition General References... 

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