Reactions of Carbon Nucleophiles with Carbonyl Compounds

Abstract

Ph 3 P + (CH 3) 2 S + aldol or acylation olefination cyclization nucleophilic component electrophilic component Z = ; ; ; ; O – C ; (RO) 2 P O A second important reaction type considered in this chapter is conjugate addition, which involves addition of nucleophiles to electrophilic double or triple bonds. A crucial requirement for this reaction is an electron-withdrawing group (EWG) that can stabilize the negative charge on the intermediate. We focus on reactions between enolates and ,-unsaturated carbonyl compounds and other electrophilic alkenes such as nitroalkenes. O – Y H R CH 2 CH EWG O R Y EWG H + O R Y EWG + – enolate conjugate addition The retrosynthetic dissection is at a bond that is to a carbonyl and to an anion-stabilizing group. O R Y EWG O Y R CH 2 CH EWG + 2.1. Aldol Addition and Condensation Reactions 2.1.1. The General Mechanism The general mechanistic features of the aldol addition and condensation reactions of aldehydes and ketones were discussed in Section 7.7 of Part A, where these general mechanisms can be reviewed. That mechanistic discussion pertains to reactions occurring in hydroxylic solvents and under thermodynamic control. These conditions are useful for the preparation of aldehyde dimers (aldols) and certain ,-unsaturated aldehydes and ketones. For example, the mixed condensation of aromatic aldehydes with aliphatic aldehydes and ketones is often done under these conditions. The conju-gation in the -aryl enones provides a driving force for the elimination step. ArCH CCR′