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Carbamoyl Anion Addition to N‑Sulfinyl Imines: Highly Diastereoselective Synthesis of α‑Amino Amides

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posted on 17.04.2013, 00:00 by Jonathan T. Reeves, Zhulin Tan, Melissa A. Herbage, Zhengxu S. Han, Maurice A. Marsini, Zhibin Li, Guisheng Li, Yibo Xu, Keith R. Fandrick, Nina C. Gonnella, Scot Campbell, Shengli Ma, Nelu Grinberg, Heewon Lee, Bruce Z. Lu, Chris H. Senanayake
Carbamoyl anions, generated from N,N-disubstituted formamides and lithium diisopropylamide, add with high diastereoselectivity to chiral N-sulfinyl aldimines and ketimines to provide α-amino amides. The methodology enables the direct introduction of a carbonyl group without the requirement of unmasking steps as with other nucleophiles. The products may be converted to α-amino esters or 1,2-diamines. Iterative application of the reaction enabled the stereoselective synthesis of a dipeptide. Spectroscopic and computational studies support an anion structure with η2 coordination of lithium by the carbonyl group.