Lithium enolates, copper chloride

Reaction of the lithium enolate 2 with prochiral aldehydes at low temperature proceeds with little selectivity, producing all four possible diastereomers 3, 4, 5, and 6 in similar amounts50. Transmetalation of the lithium enolate by treatment with three equivalents of diethylaluminum chloride or with one equivalent of copper cyanide generates the corresponding cthylaluminum and copper enolates which react at — 100°C with prochiral aldehydes to produce selectively diastereomers 1 and 2, respectively50. The reactivity of tin enolates of iron- propanoyl complexes has not been described. 

In contrast, transmetalation of the lithium enolate at —40 C by treatment with one equivalent of copper cyanide generated a species 10b (M = Cu ) that reacted with acetaldehyde to selectively provide a 25 75 mixture of diastereomers 11 and 12 (R = CH3) which are separable by chromatography on alumina. Other diastereomers were not observed. Similar transmetalation of 10a (M = Li0) with excess diethylaluminum chloride, followed by reaction with acetaldehyde, produced a mixture of the same two diastereomers, but with a reversed ratio (80 20). Similar results were obtained upon aldol additions to other aldehydes (see the following table)49. 

The ultimate in the three-component coupling approach to prostaglandins has now been achieved by Noyori (48). As illustrated in Fig. 15, the cuprate derived from iodide [82] was added to enone [80] in the usual fashion. Then, after addition of hexamethylphosphoramide, triphenyltin chloride was used to effect enolate interchange. As opposed to lithium (or copper) enolates, the tin enolate is cleanly alkylated with allylic iodide [81]. The protected PGE2 [83] was obtained in 78% yield. Two-step deprotection to PGEj was straightforward. 

Addition of aldehydes to the lithium enolate derived from propanoyl complex 6 requires prior transmetallation for optimum results. In particular, the use of diethylaluminium chloride has proved to be most valuable when the anti-aldol adduct 14 is required, whilst copper cyanide is the transmetallation reagent of choice when the syn-aldol adduct 15 is the target (Scheme 4.8). Oxidative cleavage and formation of the threo and erythro -hydroxy acids, respectively, is easily achieved by treatment with aqueous bromine solution or CAN. The aluminium(III)-mediated sequence has been employed in the synthesis of an enantiomerically pure degradation product of a marine cyclic peroxide, thereby proving its absolute configuration. ... 

Chiral carboxyamides derived from acid chlorides and A-chiral cA-aminoindanol can be protonated and Li Cu transmetallated to generate copper enolates which react with A-lithium derivative of A-Boc-O-tosylhydroxylamine (LiBTOC) 31 to give a-A-Boc amino carboxamides in high yields and enantiomeric excess (Scheme 38) . The chiral auxiliary can be removed by acidic hydrolysis to obtain the a-aminocarboxylic acid. 

House and Fischer (38) have found that lithium dimethyl cuprate reacts with enone 108 and yields a mixture of trans and cis 3,5-dimethyl-cyclohexanones 109 and 110 in a 98 2 ratio. Similar results were observed by Allinger and Riew (39) using methylmagnesium iodide in the presence of copper(I) chloride. In another case, Heathcock and co-workers (AO) observed the exclusive formation of the trans isomer V[2 from enone 111 no cis isomer was detected. Thus, the preferred mode of approach by cuprate reagent is also 76 + 78 which leads to a chair-like enolate ion. 

With this end in view, phenyldimcthylsilyl tri-n-butylstannane was added under the influence of zero-valent palladium compound with high regioselectivity and in excellent yield to the acetylene 386 to give the metallated olefin 387 (Scheme 56). The vinyl lithium carbanion 388 generated therefrom, was then converted by reaction with cerium(lll) chloride into an equilibrium mixture (1 1) of the cerium salts 389 and 390 respectively. However, the 1,2-addition of 389 to the caibonyl of 391, which in principle would have eventually led to ( )-pretazettine, did not occur due to steric reasons — instead, only deprotonation of 391 was observed. On the other hand, 390 did function as a suitable nucleophile to provide the olefinic product 392. Exposure of 392 to copper(II) triflate induced its transformation via the nine membered enol (Scheme 55) to the requisite C-silyl hydroindole 393. On treatment with tetrafluoroboric acid diethyl ether complex in dichloromethane, compound 393 suffered... 

Compounds with acidic hydrogen atoms react rapidly with cuprates. Phenylacetylene has been mentioned as one example (223). Another is diethyl phenylmalonate (144), which on addition to lithium dimethylcuprate gave a rapid evolution of methane and the formation of a methyl-copper-like precipitate which did not redissolve. Subsequent to the addition of benzoyl chloride and the customary work-up, only acetophenone and the phenylmalonate were isolated. The reaction may be summarized by Eq. (23). The failure to isolate the acylated product may be ascribed to the formation of the enolate, (II). 

Ibrning to structurally more complex applications of 100, it has been shown that it can function as a Michael acceptor. For example, when the enolate of 2,4-dimethyl-cyclo-hexen-3-one (152) is treated with 100 in the presence of lithium hexamethyldisilazane (LiHMDS), dichlorovinylation takes place and 153 is formed. On the other hand, with lithium diisopropylamide (LDA) as base, the 1-chloroacetylene derivative 151 is produced [98-100] (Scheme 2-15). The reaction, which also takes place with other 1-chloroacetylenes, most likely involves the Michael intermediate 154 which — depending on reaction conditions — is either protonated or loses a chloride ion. On treatment with copper powder in tetrahydro-furan/acetic acid, 151 is dechlorinated the resulting terminal acetylene has been used for further transformations. 

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