Methods of Reactivity Umpolung

TLDR

The past decade of organic chemistry has seen rapid development of new synthetic methods and a systematization of synthetic strategy analysis. The paper demonstrates that reactivity umpolung functions as a heuristic principle, classification scheme, and tool for locating strategic bonds. The authors describe six principal umpolung strategies—n‑oxidation, heteroatom exchange/modification, homologation and its reversal, the cyclopropane trick, acetylenes, and redox reactions—and note that direct umpolung can sometimes replace them, marking normal reactivity in green and umpolung in red.

Abstract

Abstract The past decade of organic chemistry may be charcterized as a period of violent development of new synthetic methods. This was accompained by a systematization of the analysis of synthetic problems (synthetic strategy). The planning of the synthesis of an organic target molecule is greatly facilitated by distinguishing between reagents X(C) n … with normal reactivity (acceptor properties at C 1,3,5… , donor properties at X, C 2,4… ) and with reactivity umpolung (acceptor properties at X, C 2,4… , donor properties at C 1,3,5… ). In this context, reactivity umpolung turned out to be useful as a heuristic principle, as a classification scheme, and as an aid for locating so‐called strategic bonds (synthon, transform, and antithesis according to E. J. Corey ). There are six principal methods of umpolung: 1 2 n ‐oxidation, heteroatom exchange and modification, homologation and its reversal, the cyclopropane “trick”, use of acetylenes, and redox reactions; under certain circumstances none of these techniques is necessary in cases where direct umpolung is possible. Throughout the article, normal reactivity is indicated by green print; reactivity umpolung by red print.