Zinc ( d )-Tartrate Catalyzed Asymmetric Epoxide Ring Opening: Access to Enantioenriched β-Hydroxy Thiols and ADC Linker Compounds

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).