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. 2022 Mar 2;144(8):3353-3359.
doi: 10.1021/jacs.1c13299. Epub 2022 Feb 21.

Excited-State Palladium-Catalyzed Radical Migratory Mizoroki-Heck Reaction Enables C2-Alkenylation of Carbohydrates

Wang Yao  1 , Gaoyuan Zhao  1 , Yue Wu  2 , Lin Zhou  2 , Upasana Mukherjee  1 , Peng Liu  2   3 , Ming-Yu Ngai  1   4
Affiliations

Excited-State Palladium-Catalyzed Radical Migratory Mizoroki-Heck Reaction Enables C2-Alkenylation of Carbohydrates

Wang Yao et al. J Am Chem Soc. .

Abstract

Excited-state palladium catalysis has emerged as a promising strategy for developing novel and valuable reactions. Herein, we report the first excited-state Pd-catalyzed 1,2-radical migratory Mizoroki-Heck reaction that enables C2-alkenylation of carbohydrates using readily available 1-bromosugars and alkenes. The reaction tolerates a wide variety of functional groups and complex molecular architectures, including derivatives of natural products and marketed drugs. Preliminary mechanistic studies and DFT calculations suggest the involvement of visible-light-induced photoexcitation of Pd species, 1,2-spin-centered-shift (SCS) process, and Heck-type cross-coupling reaction. The reaction expands the reactivity profile of excited-state Pd catalysis and provides a streamlined protocol for the preparation of a wide variety of C2-alkenylated carbohydrate mimetics to aid the discovery and development of new therapeutics, agrochemicals, and materials.

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Figures

Figure 1.
Figure 1.
Excited-state Pd-catalyzed radical migratory Mizoroki-Heck reaction via 1,2-SCS pathway enabling C2-alkenylation of carbohydrates. PG = protecting group.
Figure 2.
Figure 2.
Mechanistic studies and a proposed reaction mechanism. aDFT calculations were performed at the M06/SDD-6-311+G(d,p)/SMD//B3LYP-D3/SDD-6-31G(d) level of theory using a simplified model of the glucosyl radical(1), where the OMe groups were used in place of the OAc groups at the C3, C4, and C6 of the pyranose ring.
See this image and copyright information in PMC

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