Photoinduced Efficient Catalytic α-Alkylation Reactions of Active Methylene and Methine Compounds with Nonactivated Alkenes

Abstract

In catalytic α-alkylation reactions of carbonyl compounds, although S N 2-type substitution reactions of enolates with alkyl halides are a conventional methodology, addition reactions with alkenes are more desirable because of their atom-economical character; however, reactions with nonactivated alkenes are challenging. Here, we developed highly efficient catalytic α-alkylation reactions of active methylene and methine compounds with nonactivated alkenes such as 1-decene using an organophotocatalyst and lithium thiophenoxide as a Lewis acid/Brønsted base/hydrogen atom transfer (HAT) multifunctional catalyst under blue-light irradiation. The reaction was also performed with a higher degree of efficiency under a continuous-flow system to obtain the products in multigram scales. The present reaction system enables highly efficient and practical α-alkylation reactions of active methylene and methine compounds to be achieved.

Efficient Radical‐Mediated Intermolecular α‐Alkylation Reactions of Carbonyl Compounds with Nonactivated Alkenes

“…In 2023, Yamashita and Kobayashi et al developed catalytic α-alkylation reactions of active methylene and methine compounds with nonactivated alkenes using 2,4,5,6-tetrakis(9Hcarbazol-9-yl)isophthalonitrile (4CzIPN, 60) and lithium thiophenoxide (LiSPh) as a simple Lewis acid/Brønsted base/HAT catalyst (Scheme 20). [76] The alkylation reactions proceeded smoothly under mild reaction conditions under blue-light irradiation, and the desired products were obtained in high yields. The catalyst system was found to be very active, and only 0.5 mol% of the photocatalyst and 2 mol% of LiSPh were used in most cases.…”

Photoinduced Generation of Active Intermediates from Unmodified 1,3‐Dicarbonyl Compounds for Organic Transformations

“…In 2023, as a more recent example, Yamashita, Kobayashi, and co‐workers introduced a novel approach featuring highly efficient catalytic α‐alkylation reactions of methylene and methine compounds with non‐activated alkenes (Scheme 20). [30] This innovative methodology utilizes an organophotocatalyst and lithium thiophenoxide (LiSPh) as a versatile catalyst, functioning as a Lewis acid/Brønsted base/HAT agent, all under the influence of blue‐light irradiation. Numerous examples of extensive substrate expansion involved the modification of various non‐activated alkenes and diverse 1,3‐dicarbonyl compounds, resulting in the corresponding products in moderate to excellent yields.…”