Book Review, Encyclopedia of Reagents for Organic Synthesis

Abstract

Acetaldehyde serves as an electrophilic partner in the aldol condensation with a wide array of enolates. 13 Knoevenagel condensation of acetaldehyde with active methylene compounds in the presence of base provides good yields of the ethylidene substituted compounds. 14 Addition of two equivalents of an active methylene compound to acetaldehyde results in a Michael addition of the second equivalent to the initially formed ethylidene. 15 Tollens reaction of acetaldehyde with formaldehyde gives pentaerythritol. 16 The addition of acetaldehyde in a Baylis-Hillman condensation with Ethyl Acrylate using 1,4-Diazabicyclo[2.2.2]octane (DABCO) as catalyst gives a 90% yield of the allylic alcohol. 17 The stereoselective aldol reaction of acetaldehyde with achiral 18 and chiral 19 imide enolates has received much attention and is a proven method for controlling acyclic relative and absolute stereochemistry. 13 For example, the boron enolate of a norephedrine-derived propionyloxazolidine reacts with acetaldehyde to afford in 90% yield and >98% de the syn aldol product (eq 2). 19a Acetaldehyde also smoothly undergoes nitro-aldol condensation to the corresponding nitro alcohols. 20 The lithium enolates of a variety of heterocycles react with acetaldehyde to give good yields of product alcohols. 21 In addition, the zinc, 22 copper, 23 and boron 24 enolates of esters and ketones provide aldol products with acetaldehyde. Mannich and Mannich-Type Reactions. Although not as commonly used as Formaldehyde, acetaldehyde undergoes many synthetically useful Mannich reactions. Intramolecular Mannich reaction of acetaldehyde has been utilized to produce the natural product myrtine (eq 3). 25 The intramolecular Mannich reaction has also been used in the synthesis of proline derivatives. 26 Nucleophiles as diverse as dialkyl phosphites 27 and amines 28 or aryl radicals 29 may also add to the intermediate imine of acetaldehyde in Mannich-type reactions. A historically significant reaction of acetaldehyde in this mode is the Strecker synthesis of alanine, whereby cyanide is added to the adduct of ammonia and acetaldehyde followed by hydrolysis of the intermediate α-aminonitrile. 30 The Pictet-Spengler reaction utilizing acetaldehyde is an important ring-forming reaction.