Organocuprates, addition with aldehydes

Hydroboration of (5) with an excess of pinacolborane at room temperature for 3 days in the absence of solvent followed by oxidation with PDC in the presence of an excess of TMSC1 led to the aldehyde (4h) and the ketone (4i) (75 % and 50 % from (5h) and (5i) respectively after bulb to bulb purification) l2,13, Several other (3-kcto vinylboronates were obtained in good yields via the addition of organozinc or organocuprates to the aldehyde (4h) followed by a PCC oxidation of the corresponding allylic alcohols14. 

Evans synthesis of the polyether antibiotic X-206 (93) provides notable documentation of the use of organocuprate reagents in stereocontrolled additions to C=0 (Scheme 2.12) [73]. In the crucial coupling event, selective addition of organocuprate 91 to aldehyde 90 led to the formation of the 1,2-anti diastereomer 92 (dr=98 2). The observed preference for 92 is consistent with the intervention of a chelate intermediate. In a control experiment, the addition of the corresponding organolithium to aldehyde 90 furnished products with dramatically altered selectivity (dr= 33 67), a result consistent with the absence of chelation control in the organolithium addition. 

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. 

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. 

The effect of trimethylchlorosilane on the conjugate addition of organocuprates has been investigated with a,/ -unsaturated esters and amides7 in addition to the already discussed a,/ -unsaturated aldehydes and enones. 

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. 

Organocuprates add at the p position of a,p-unsaturated aldehydes, ketones, esters, and A,A-dialkylamides using trimethylchlorosilane as an activator [24]. The example shown in Equation 7.13 uses transmetallation of the initially formed organozinc to generate an organocuprate that contains an ester moiety. The enolate anion formed by addition to the P carbon is trapped with trimethylchlorosilane, which is then removed with tetrabutylammonium fluoride [25]. 

The Cu-catalyzed conjugate addition of organomanganese reagents to a,/3-ethyle-nic aldehydes gives similar results than those obtained via lithium organocuprates in the presence of trimethylchlorosilane (Scheme 13.41) [36]. However, the reaction is easier to carry out since the aldehyde is obtained in one step instead of the two steps required with an organocuprate. It is important since the partial aldoli-... 

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