α-Oxymethyl Ketone Enolates for the Asymmetric Mannich Reaction. From Acetylene and N-Alkoxycarbonylimines to β-Amino Acids

✍ Scribed by Claudio Palomo; Mikel Oiarbide; M. Concepción González-Rego; Arun K. Sharma; Jesús M. García; Alberto González; Cristina Landa; Anthony Linden

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 94 KB
• Volume: 112
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/(sici)1521-3757(20000317)112:6<1105::aid-ange1105>3.0.co;2-h

✦ Synopsis

The reactions of enolizable carbonyl compounds with azomethine functions, usually referred to as Mannich-type reactions (also termed aza ± aldol reactions), result in the formation of b-amino acids, ketones, or aldehydes. [1] These reactions are conceptually equivalent to the aldol reactions, but, in sharp contrast, they have been substantially less developed. [2,3, 4] There are two reasons that can justify this situation: firstly, the poorer electrophilicity of the azomethine function relative to that of the carbonyl function, and secondly, the preference of enolizable azomethines to undergo a-deprotonation rather than addition. [5] To date, there are two main ways to approach these problems. One strategy lies in the use of activated forms of azomethines, [1, 2] and the other in the use of trialkylsilylenol ethers or O-(trialkylsilyl)ketene acetals as nucleophiles. [3, 6] The later strategy has led to outstanding advances in enantioselective Mannich reactions [7] catalyzed by chiral ruthenium, [8a±b] palladium, [8c±e] and copper [8e±g] complexes. Some highly diastereoselective methods involving chiral azomethines are also known, [6, 9] but in most