Oxone-Mediated Radical Bicyclization of 1,6-Enynes through Dual α-C(sp³)–H Functionalization of Ketones under Catalyst- and Base-Free Conditions

Abstract

Without employing any catalyst and base, an economical, practical, and efficient protocol has been first developed for the one-pot synthesis of various functionalized polycyclic γ-lactams from easily accessible ketones and 1,6enynes in the presence of oxone. This method proceeds through C(sp 3 )−H bond functionalization, acetmethylation, intramolecular cyclization, 1,5-H shift, radical cyclization, and hydrogen abstraction. This transformation features mild reaction conditions, broad substrate scope, good yields, and ease of scale-up. In addition, the experimental result indicates that this bicyclization transformation contains a radical process.

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…Remarkably, alkyl sulfonyl hydrazide (R=Et) was also efficient radical source, providing the product in 56% yield. Recently, the Wei group has developed a series of cascade reactions about 1,6‐enynes with similar mechanism. The Guo group reported one example of radical triggered 6‐exo‐dig cyclization for the synthesis of 3,4‐dihydroquinolin‐2(1H)‐ones (Eq.…”

Radical Cyclization of 1,n‐Enynes and 1,n‐Dienes for the Synthesis of 2‐Pyrrolidone

“…In the presence of oxone, an α ‐carbonyl radical was formed on the ketone substrate, which then reacted with the 1,6‐enyne substrate (Scheme 8). [20] This synthetic approach did not require a catalyst or a base, was trivial to conduct, utilized abundant and cheap materials, and had an excellent substrate tolerance, all of which are attractive features for synthetic chemistry. We speculated that this reaction mechanism involved a radical cyclization process (Scheme 9).…”

Recent Advances in the Oxone-Mediated Synthesis of Heterocyclic Compounds

“…Despite the low reaction selectivity, the present protocol is important, once NO 2 -containing isatin derivatives 16 are satisfactorily afforded, which is not an easy task, from the synthetic point of view. In 2019, Wei and co-workers reported an Oxone-mediated base-free radical bicyclization of 1,6-enynes 17, in the presence of ketones 18, affording several functionalized polycyclic γ-lactams 19 (Scheme 11) [21]. Under the optimal conditions, aliphatic ketones, such as acetone 18a and cyclobutanone 18b, reacted satisfactorily with 1,6-enyne 17a, yielding the respective products 19a and 19b in 82% and 56% yield, respectively.…”