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Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Zinc (d)-Tartrate Catalyzed Asymmetric Epoxide Ring Opening: Access to Enantioenriched β-Hydroxy Thiols and ADC
Anupam Karmakar1, Omkar Revu1, Maksim Vasilev1
1TCG GreenChem, Inc., 701 Charles Ewing Blvd, Ewing, New Jersey 08628, United States.
Abstract:
We report a zinc (d)-tartrate catalyzed asymmetric ring opening of epoxides with thiols, affording β-hydroxy sulfides with high enantioselectivity up to 98:2 er after crystallization. The process enables fast reaction in 10-15 min under continuous flow conditions and demonstrates efficient catalyst recyclability over multiple cycles. The implementation of a dual-purpose thiol methyl 3-mercaptopropanoate provides a cost-effective strategy for enantiomeric enrichment via crystallization, eliminating enzymatic resolution. Overall, this methodology represents a practical platform for chiral β-hydroxy sulfides synthesis for antibody-drug conjugates (ADC).
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