Michael addition/enolate trapping sequence

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... 

Shibasaki also disclosed an application that incorporates an asymmetric tandem Michael addition-aldol reaction sequence with this family of bimetallic catalysts [117], as shown for the synthesis of the prostaglandin 11-deoxy-PGF (132, Scheme 12.16) [119]. In this route, the first two stereo-genic centers in the cyclopentane ring are installed in the course of an asymmetric Michael addition of malonate 128, followed by trapping of the resulting enolate 129 with aldehyde 130. The sequence provided the trans-cyclo-pentanone 131 in 92% ee. The stereoinduction at Cy was observed to range from dr 6 1 to dr 17 1, although this was inconsequential, as the secondary alcohol at C7 was later excised. 

Domino transformations combining two consecutive anionic steps exist in several variants, but the majority of these reactions is initiated by a Michael addition [1]. Due to the attack of a nucleophile at the 4-position of usually an enone, a reactive enolate is formed which can easily be trapped in a second anionic reaction by, for example, another n,(5-urisalurated carbonyl compound, an aldehyde, a ketone, an inline, an ester, or an alkyl halide (Scheme 2.1). Accordingly, numerous examples of Michael/Michael, Michael/aldol, Michael/Dieckmann, as well as Michael/SN-type sequences have been found in the literature. These reactions can be considered as very reliable domino processes, and are undoubtedly of great value to today s synthetic chemist... 

A powerful tandem 1,4-addition/cyclization was reported by Danishefsky in the total synthesis of avermectin A,., (15, Scheme 12.2) [53-55]. In the sequence, conjugate addition of thiophenoxide to enal 12 generates an intermediate enolate that is trapped by addition to the resident ketone. Subsequent oxidation of the sulfide in 13 to the corresponding sulfoxide and thermolysis provided the desired oxahydrindene 14 in 76% overall yield [54]. From advanced intermediate 14, only a few steps were required to complete the synthesis of the anthelmintic agent avermectin Aj (15) [54, 55], Fukumoto developed a stereoselective double Michael sequence for the construction of substituted bicyclo[2.2.2]octanes (Scheme 12.3) [56, 57]. The intramolecular transformation was conducted by treatment of 16 with base and afforded 17 as a single isomer in 58% yield. The sequence is no-... 

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