Conjugate addition-enolate trapping

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential a-alkoxyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford as-fused tetrahydrofurans, while acyclic systems give complex mixtures of diastereomers. a-Alkoxyalkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

Review Taylor has reviewed the conjugate addition-enolate trapping reactions of organocopper reagents, in particular of lithium dialkylcuprates (131 references). 

The general reaction sequence has been named more specifically as tandem vicinal dialkylation, nucleophilic-electrophilic carbacondensation,11 dicarbacondensation1213 or conjugate addition-enolate trapping,14 usually in reference to the fact that most of the reaction examples available create two new vicinal carbon-carbon bonds. Many noncarbon nucleophiles and electrophiles also are known, resulting... 

For the most part, alkynic and allenic ketones have found limited use in conjugate addition-enolate trapping sequences 69,81-83 their analogous esters have been used with far greater frequency (vide infra). Alkynic ketones, in particular, have found use in development of a new anionic polycyclizadon method consisting of intramolecular Michael addition followed by intramolecular alkylation (equation 15).84... 

Scheme 12.3. Synthesis of prostaglandin Et using a three-component conjugate addition/enolate trapping on cyclopentenones, by Noyori and co-workers [10], TBS = t-butyldimethylsilyl, THF = tetrahydrofuran,...

Scheme 12.4. Multiple metal variant of the conjugate addition/ enolate trapping 3CR on cyclopentenones, by Lipshutz and Wood [13]. THF = tetrahydrofuran, TBS = t-butyldimethylsilyl.

A synthesis of this compound was devised by Ohmizu, Iwasaki and co-workers and featured a three-component tandem conjugate addition/enolate trapping as key step (Scheme 12.24) [82]. In this synthesis, the acyl anion equivalent cyanohydrin 165 was first treated with LDA and allowed to react with methyl crotonate 166. The resulting enolate was trapped with 2,3,5-trimethoxy benzylbromide 168 to afford crude intermediate 169, which was immediately deprotected in situ to afford ketone product 170. Both the ester and the ketone functionalities were then reduced at low temperature to afford the corresponding diol 171. Upon treatment with trifluoroacetic acid, the desired Friedel-Craft cyclization adduct 172 was obtained. The latter tricyclic compound was then further elaborated to the final target 164 through a short sequence of standard transformations. 

The reaction has been further extended into a tandem conjugate addition/ enolate trapping sequence, whereby the in situ generated zinc enolate was trapped with benzaldehyde. This resulted in an approximately 3 7 mixture of trans-erythro trans-threo aldol adducts, isolated in 88% yield. Subsequent oxidation of these products gave a single isomer of the corresponding diketone with 95% ee. 

R. J. K. Taylor, Organocopper Conjugate Addition-Enolate Trapping Reactions, Synthesis 1985, 364. 

Alcoholysis of epoxides. FeCl.i is an effective catalyst for the transformation. Oxidative cleavage of trimethylsiloxycyclopropanes. This method of enone generation, in combination with conjugate addition, enolate trapping, and Simmons-Smith reaction, complete the sequence of ring expansion that also incorporates a substituent at the y-position of a lower homolog. Thus 4-alkyl-2-cyclohexenones are readily prepared from cyclopentenone. 

Feringa and co-workers reported a new enantioselective Cu(I)/Tol-BINAP-cata-lyzed tandem conjugate addition-enolate trapping reaction of Grignard reagents with 4-chloro-a,p-unsaturated esters, thioesters, and ketones to yield tran -l-alkyl-2-substituted cyclopropanes in up to 92% yield and up to 98% ee (Scheme 38)... 

Keto-esters of tetrahydroindanone are obtained by a sulphur-mediated regio-controlled alkylation sequence. A re-investigation of the condensation reaction between 2-methyl-4-(carboxyethyl)oxazole and ethyl acetate has revealed that the product is the keto-ester (108). Keto-esters of the general structure (109) are prepared in reasonable yield by a conjugate addition-enolate trapping sequence. ... 

Intermediates similar to (170) are generated by conjugate addition, enolate trapping, and mercury-mediated cyclization by cleavage of a cyclopropane... 

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