Cyclizations of Alkoxyallenes: Mechanisms, Intermediates, ­Products – A Personal Account on Solved and Unsolved Problems with Unique Allene Building Blocks

Abstract

The additions of lithiated alkoxyallenes to electrophiles, such as carbonyl compounds, thioketones, imines, and nitrones, provide the expected primary addition products. These alkoxyallene intermediates undergo ring-closure reactions under quite different conditions. Whereas allenyl hydroxylamine derivatives spontaneously cyclize to 1,2-oxazine derivatives, the related allenyl amines, thiols, and alcohols require, with distinct exceptions, promotion by acids, base, silver(I), or gold(I). The different mechanisms of these processes are discussed in this account. The serendipitous discovery of a novel three-component reaction of lithiated alkoxyallenes, nitriles, and carboxylic acids followed by a cyclization to pyridine derivatives is also reported and the mechanism involved is illustrated. This account also compiles exemplary examples of natural products and other compounds prepared by subsequent reactions of alkoxyallene-based cyclization products, but the fascinating ring-closing event of the allenyl intermediates is the main focus of this report.1 Introduction2 Cyclizations of Allenyl Hydroxylamines to 1,2-Oxazine Derivatives3 Cyclizations of Allenyl Amines to Dihydropyrrole Derivatives4 Cyclizations of Allenyl Imines to Pyrroles – Discovery of a New Three-Component Synthesis of Pyridines5 Cyclizations of Allenyl Thiols to Vinylthiiranes and Dihydrothiophene Derivatives6 Cyclizations of Allenyl Alcohols to Dihydrofuran Derivatives7 Conclusions