Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis
Author(s)Nguyen, Thach T.; Koh, Ming Joo; Mann, Tyler J.; Hoveyda, Amir H.; Schrock, Richard Royce
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Catalytic cross-metathesis is a central transformation in chemistry, yet corresponding methods for the stereoselective generation of acyclic trisubstituted alkenes in either the E or the Z isomeric forms are not known. The key problems are a lack of chemoselectivity—namely, the preponderance of side reactions involving only the less hindered starting alkene, resulting in homo-metathesis by-products—and the formation of short-lived methylidene complexes. By contrast, in catalytic cross-coupling, substrates are more distinct and homocoupling is less of a problem. Here we show that through cross-metathesis reactions involving E- or Z-trisubstituted alkenes, which are easily prepared from commercially available starting materials by cross-coupling reactions, many desirable and otherwise difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to 98 per cent E or 95 per cent Z). The utility of the strategy is demonstrated by the concise stereoselective syntheses of biologically active compounds, such as the antifungal indiacen B and the anti-inflammatory coibacin D.
DepartmentMassachusetts Institute of Technology. Department of Chemistry
Nature Publishing Group
Nguyen, Thach T. et al. “Synthesis of E- and Z-Trisubstituted Alkenes by Catalytic Cross-Metathesis.” Nature 552, 7685 (December 2017): 347–354
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