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Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes
Published on: September 12, 2018
Chemo- and Stereoselective Semireduction of Alkynes to E-Alkenes Catalyzed by Nonheme Iron Enzymes
Zicong Wan1, Wenxuan Zhang1, Yang Sun1
1Department of Chemistry, Zhejiang Key Laboratory of Low-Carbon Synthesis of Value-Added Chemicals, Zhejiang University, Hangzhou310058, China.
Abstract:
The semireduction of alkynes represents a powerful yet challenging transformation that requires simultaneous control of stereoselectivity and chemoselectivity. Currently, synthetic methods for the trans-reduction of alkynes to E-alkenes remain limited, particularly in the realm of biocatalysis. Herein, we report the repurposing of a nonheme iron dioxygenase for the trans-reduction of alkynes. Through screening and directed evolution, we obtained variants of gentisate 1,2-dioxygenase that enable the preparation of structurally diverse E-alkenes in high yields (up to 99% yield) with excellent stereoselectivity (16 examples with E/Z ratios of 99/1) and chemoselectivity (21 cases with 0% alkane). Mechanistic studies suggest a pathway involving hydride attack to generate a trans anion intermediate, followed by protonation to directly furnish the E-alkene. This metalloenzymatic trans-reduction pathway is mechanistically distinct from the classical syn-addition/isomerization pathway typically observed in transition-metal catalysis.
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