Aldehydes, reaction with organocuprates

Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

C-Trapping. Alkylation or hydroxy alkylation (i.e., reaction with RCHO) of enolates derived from conjugate addition of organocuprates affords vicinal dialkylated products. However, the reaction is confined to highly reactive alkylating agents such as methyl, allyl, propargyl, benzyl, and a-halocarbonyl compounds or aldehydes. 

Several procedures are available for the preparation of the requisite p-hydroxysi-lanes such as addition of a-silyl carbanions to aldehydes and ketones, reaction of organocuprates with a,P-epoxysilanes, reduction of P-ketosilanes, and addition of organometallic regents to P-ketosilanes. The selection of a particular procedure is dictated by the structure and stereochemistry of the desired alkene. 

Other asymmetric substrates can be used with organocuprates. One example is Scolastico s report that reaction of 470 with di-n-butylcuprate gave a 70% yield of 471 (78-98 % ee). 32 Using this auxiliary, alkylated ester 471 was converted to aldehyde 472 in 80% yield with 91% asymmetric induction. 32... 

Stereoselective alkene synthesis starts from the reaction of triethylsilyloxirane 117 with an organocuprate reagent and is concluded by oxidation of the formed P-silyl alcohol to the aldehyde, whose reaction with Grignard reagent and elimination of [EtjSi/OH] leads to either the ( )- or the (Z)-alkene (118 or 119) by using different reagents (Schane 7.45). 

The reaction of carbon nucleophiles with ketones or aldehydes proceeds by acyl addition, as described in Chapter 18. The reaction of carbon nucleophiles with acid derivatives proceeds by acyl substitution, as described in Chapter 20. Carbon nucleophiles included cyanide, alkyne anions, Grignard reagents, organolithium reagents, and organocuprates. Alkyne anions are formed by an acid-base reaction with terminal alkynes (RC=C-H RCsCr). In this latter transformation, it is clear that formation of the alkyne anion relies on the fact that a terminal alkyne is a weak carbon acid. Other carbon acids specifically involve the proton on an a-carbon in aldehydes, ketones, or esters. With a siiitable base, these carbonyl compounds generate a new type of carbon nucleophile called an enolate anion. 

The scope of the reaction is very large, thus /3-disubstituted enones that are frequently less reactive with organocuprates readily react with Cu-catalyzed organo-manganese reagents. The reaction has also been extended to a,/3-ethylenic esters (Scheme 13.39) and to a,/3-ethylenic aldehydes (Scheme 13.40). 

An interesting observation from organocuprate chemistry is that the initial step in 1,4-addition to enones may be electron transfer. Thus the relative reactivity of enones toward conjugate addition parallels their ease of reduction. One problem with any reaction between a ketone or aldehyde and a metal alkyl is deprotonation, when a hydrogens are present, to yield an enolate. Given the considerable basicity of metal alkyls, this side reaction should be anticipated. 

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