A Rare Alder‐ene Cycloisomerization of 1,6‐Allenynes

Abstract

Thermally induced cycloisomerization reactions of 1,6-allenynes gives α-methylene-γ-lactams via intramolecular Alder-ene reactions. The mechanism is supported by computational and deuterium labelling studies. This thermal, non-radical method enables the discovery of a hitherto unknown route that proceeds via a divergent mechanism distinct from the previous [2 + 2] cycloisomerization manifold.

My 37 years of working with nitrogen heterocycles and alkaloids

“…These substrates were found to undergo intramolecular Alder-ene reactions upon heating at 110°C to give α-methylene-γlactams 119 in yields ranging from 69 to 92% with dr values ranging from 4.2:1 to 4.9:1. [75] These reactions occurred via a mechanism distinct from previous [2 + 2] cycloisomerization reactions of related systems. The mechanism involves an unusual transfer of the allene-hydrogen and is favored by the electron-deficient nature of the propiolamide moiety.…”

Diastereoselective Synthesis of Highly Functionalized Proline Derivatives

“…Such a thermal ene-type reaction, in which the terminal allene acts as the ene-component and the alkene as the enophile, has not been previously described. The closest literature analogy includes the Alder-ene cycloisomerization of 1,6-allenynes, namely α-allenyl propiolamides [ 45 ].…”

Cobalt-Catalyzed Chemo- and Stereoselective Arylative Carbocyclization of 1,6-Allenynes

“…In comparison to the widely investigated enynes, transition-metal-catalyzed carbocyclization reactions of allenynes are more capricious as a result of the unique structure and versatile reactivity of allenes . Since the pioneering work on cobalt-mediated cycloisomerizations of 1,6-allenynes by Malacria and co-workers, transition-metal-catalyzed cycloisomerization, , cycloaddition, and intramolecular Pauson–Khand reactions of allenynes have been well-established. Recently, much attention has been drawn to the carbocyclization reactions of allenynes in combination with additional coupling partners, and this reaction type is of great benefit to the development of new carbocyclization modes and structural diversity of cyclic products.…”