Acetates 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. ... 

Scheme 8.1 gives several examples of the use of coupling reactions of organocuprate reagents with halides and acetates. Entries 1 to 3 are examples of the... 

Reaction of complex (90) with methyllithium followed by acid and carbon monoxide affords a mixture of acylated complexes (Scheme 149). Reaction of an oxime complex with organocuprates followed by acetic anhydride, carbon monoxide, and potassium carbonate gives meta-acylaniline derivatives (Scheme 150). In both cases, the nucleophile probably initially adds to the metal followed by an acyl transfer. 

Valuable preparative applications are rare and especially in ring-forming reactions other stereochemical factors such as ring strain and conformational effects will determine the stereochemistry. However the use of metal compounds to influence regio- and stereo-selectivity continues to excite interest. For C—C bond formation the coupling of allylic acetates with organocuprates offers broad synthetic potential as it generally seems to proceed with double bond shift. ... 

The scope of regio- and stereo-selective synthesis of vinylallenes by 1,5-(>S )-substitution of enyne acetates and oxiranes with organocuprates has been explored the products are usually obtained as mixtures of E- and Z-isomers (Scheme 12), ° Optimum conditions for stereoselective alkynylation of trans-2,3-epoxy sulfides at C(2), with double inversion of configuration, on reaction with alkynylaluminiums (Scheme 13) have been sought. 

Numerous other nucleophiles participate in highly diastereoselective reactions with chiral acetals (Scheme 6.9). A few selected examples include the introduction of acetylene [30] and of cyanide [31] to give the chiral pro-pargylic alcohol 45 and the optically active cyanohydrins 46 and 47, respectively. Furthermore, Alexakis and Mangenay observed that diastereoselective acetal cleavages can be carried out with organocuprates to give 48 with 95 5 diastereoselectivity [32]. 

Organocuprates react rapidly with allylic halides (or acetates), propargyl halides (or acetates), and vinyloxiranes, frequently with 5 2 regioselectivity. The reaction ordinarily takes place with anti (with respect to the leaving group) stereochemistry. 

Alkanes can also be prepared from alkyl halides by reduction, directly with Zn and acetic acid (AcOH) (see Section 5.7.14) or via the Grignard reagent formation followed by hydrolytic work-up (see Section 5.7.15). The coupling reaction of alkyl halides with Gilman reagent (R 2CuLi, lithium organocuprates) also produces alkanes (see Section 5.5.2). 

Organocuprates and a few other carbon nucleophiles sometimes react with allylic halides (or acetates) to give the product of what looks like an SN2 reaction. However, the mechanism is completely different— preliminary coordination by the copper or other transition metal to the C=C n bond is the first step, and the coordination of the copper changes from rj-2 to rj-1 or rj-3 before a reductive elimination step establishes the C—C bond.394 Each of these steps affects the overall regiochemistry (and the stereochemistry discussed in the next chapter), which may look like an SN2 or an SN2 reaction, while mechanistically being neither. 

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