N-Heterocyclic Carbene-Catalyzed 1,4-Alkylacylation of 1,3-Enynes

Abstract

The radical relay coupling reaction recently emerged as a powerful synthetic strategy for producing tetrasubstituted allenes. However, bond-forming processes involving the allenyl radical intermediate are mostly limited to those promoted by transition metals. In this report, we describe that a ketyl radical generated from single-electron oxidation of the Breslow intermediate is an excellent coupling partner of allenyl radicals. An organocatalytic 1,4-alkylacylation of 1,3-enynes occurred smoothly in the presence of an aldehyde, a radical precursor, and an N-heterocyclic carbene catalyst. This transformation showed remarkable tolerance to both aromatic and aliphatic aldehydes, enyne substitution, and diversified radical precursors.

NHC and visible light-mediated photoredox co-catalyzed 1,4-sulfonylacylation of 1,3-enynes for tetrasubstituted allenyl ketones

“…Despite those innovative approaches, NHC catalyzed radical transformations have mainly been focused on coupling with alkyl radical species, while cross-coupling between highly active vinyl radicals and ketyl radicals though being extremely attractive is still largely underdeveloped. 11 …”

“…In this regard, in situ generated allene radicals undergo cyanation, 15 a – d arylation, 15 e – i halogenation, 15 j alkynylation, 15 k trifluoromethylation, 15 l or intramolecular cyclization 15 m to afford functionalized allenes. Radical acylation of 1,3-enynes may provide straightforward access to value-added allenyl ketone units, 11 which are a crucial core in important nature products 16 and synthetic intermediates. 17 However, radical acylation of 1,3-enynes has been much less developed and is limited to carboacylation, 11 mainly due to the lack of an efficient acyl transfer approach.…”

Radical modulated regioselective difunctionalization of vinyl enynes: tunable access to naphthalen-1(2H)-ones and allenic alcohols

“…Based on the mechanistic investigations and previous reports, 6,7,9,15 a plausible mechanism for the regio-tunable difunctionalization process was proposed as illustrated in Scheme 5. First, in the presence of NBS, ˙OH is generated from H 2 O followed by addition to the double bond of 1a , affording propargylic radical [ A ].…”

“…Later on, Lu's group revealed a regiodivergent sulfonylarylation of 1,3-enynes via nickel/photoredox dual catalysis rendering multifunctional propargylic compounds, allenes and 1,3-dienes. 5 g In spite of the above advances, transition metals have been predominantly used to intercept the transient radical intermediates, and only limited approaches have been reported based on organic radicals; 6 moreover, the control of regioselectivity in the radical addition process is still a long-standing challenge but also highly desirable.…”

“…In contrast, gem-dialkyl terminated enynes delivered only trace amounts of products ( 3p ), which might be rationalized by alkyl groups not being sufficient to stabilize radical intermediates. 6 a …”