Michael addition, deconjugative

The next extension of preparatively useful ester enolate chemistry was the deconjugative a-alkylation of a./J-unsaturatcd esters20,21. A Michael addition of LDA was avoided by the use of one equivalent of HMPA21, which forms a non-nucleophilic complex with the former. The yields of the mono- and disubstituted products are all in the region of 90% 21,22. 

The Jorgensen group also applied the parent cinchona alkaloids as catalysts to the aza-Michael addition of hydrazones 8 to cyclic enones 9 [4] and the asymmetric deconjugative Michael reaction of alkylidene cyanoacetates 10 with acrolein (11) [5], However, only a moderate level of enantioselectivity was obtained in both reactions (Scheme 9.4). Of note, for the deconjugative Michael reaction, the delocalized allylic anion 12 could be generated via the deprotonation of 10 by the cinchona base and might attack the electrophilic enal at either the a- or the y-position. However, in this study, only the a-adducts were produced. 

Reductive deconjugation of 2-bromo-2-alkenoates. The process probably involves Michael addition, debromination, and phosphite elimination prior to the kinetic protonation of the ester enolates. Triethylamine is required as base to promote the reaction. 

In this chapter, asymmetric organocatalyzed umpolung conjugate additions are considered. Particular emphasis on deconjugative Michael additions with a,a-dicyanoalkenes, the intramolecular Rauhut-Currier reaction, and the Stetter reaction is placed. These are very efficient transformations in the synthetic chemist s arsenal, but they are also challenging to control. 

A different kind of vinylogous Michael addition of y-substituted deconjugated buteno-lides (444) to -nitrostyrenes was catalysed by the modified cinchona-derived thiourea (440). The reaction proceeded at -36 C and gave the adducts (445) with >20 1 dr and <98% ec.294... 

The standard method of introducing a functionality at the la-position of steroids is to prepare a A -3-ketone and then to carry out an appropriate Michael-type addition reaction which gives the adduct of proper la-stereochemistry. One complication of this method when working toward the preparation of A -sterols is that the usual conditions of the conjugate addition to the unsaturated ketone are sufficient to equilibrate the A -double bond to the more stable A" -3-ketone. Conversely, conditions for deconjugation of the resulting A -3-ketones are unsuitable for retaining substituents at C-1 which can be eliminated by P-elimination. The methods outlined below are adaptations which have been devised to circumvent these difficulties. 

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