The designed discovery, development, and mechanistic elucidation of novel reactions which have significant potential for synthesis is proposed. The focus is on reactions which can stimulate the development of new synthetic strategies and provide conceptual guidance for research on more efficient synthetic methods. The proposed studies are generally based on pevious discoveries from our laboratory and should provide new and more efficient methods for the preparation of a wide variety of chemotherapeutic agents. Two new cyclopentane syntheses which are based on our recent work in amide-directed remote lithiations are proposed. We also show how the methodology of ortho lithiation of tertiary aromatic amides and Beta and Beta prime lithiation of unsaturated amides provides new approaches to annelations and novel substitutions. The concept of dipole-stabilized carbanions is the basis for a proposed preparation of Alpha-lithioamine synthetic equivalents from primary and secondary amines. We discuss the development of displacement on the nitrogen of alkoxy amides as a novel and useful synthetic process. Thiophilic addition to thiocarbonyl compounds is the basis for a proposed new homologation sequence. We outline model studies of tautomerically driven enzymatic decarboxylations, and investigations of protomeric structures which are believed to model biochemically important ractions.
| Lee, Suk Joong; Beak, Peter (2006) Asymmetric synthesis of 4,5,6- and 3,4,5,6-substituted azepanes by a highly diastereoselective and enantioselective lithiation-conjugate addition sequence. J Am Chem Soc 128:2178-9 |
