Recent contributions from the asymmetric aza-Michael reaction to alkaloids total synthesis

• Published in: Natural product reports 2013-09, Vol.3 (9), p.1211-1225
• Main Authors: Amara, Zacharias, Caron, Joachim, Joseph, Delphine
• Format: Article
• Language: English
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Biological Products - chemical synthesis; Biological Products - chemistry; Molecular Structure
• ISSN: 0265-0568; 1460-4752
• DOI: 10.1039/c3np20121j

Covering: 2005 to 2013 This review focuses on recent applications of the aza-Michael reaction in alkaloids total synthesis with a special emphasis on stereoselectivity. The report highlights achievements and challenges over the past five years and describes stereoselective intra- and inter-molecular conjugate addition of nitrogen-containing nucleophiles, including tandem and cascade processes. Total asymmetric syntheses of natural scaffolds, such as pyrrolidine, piperidine and "izidine" families, are depicted. Multi-step syntheses of highly challenging natural products are further detailed, assessing the scope of the stereocontrolled aza-Michael reaction as a powerful tool in alkaloid chemistry. This review deals with the aza-Michael reaction in the particular context of alkaloids total synthesis. This conjugate addition emerges as one of the most convenient methods to selectively incorporate nitrogen into simple to more sophisticated molecules. We highlight the crucial role of aza-Michael reactions in alkaloids total synthesis, showing its efficiency, versatility and wide chemo-compatibility.