Diastereodivergent Synthesis of (+)‐α‐Conhydrine and (−)‐β‐Conhydrine from a η,γ‐Dibromo‐β‐ketosulfoxide

Abstract

Diastereodivergent syntheses of the enantiopure hemlock alkaloid (+)‐α‐conhydrine and its diastereomer (−)‐β‐conhydrine are reported. Our approach relies on efficient Crystallization‐Induced Diastereomer Transformation (CIDT) of an epimeric mixture of a η,γ‐dibromo‐β‐ketosulfoxide, optically pure only at the sulfur atom, that provided a stable α‐bromoketone, and diastereoselective β‐ketosulfoxide reduction that led to the corresponding anti and syn‐bromohydrins with high level of asymmetric induction.

Stereochemical switch driven by crystallization: Interplay between stoichiometry and configuration of the products

“…In the realms of stereoselective synthesis, the option of driving a reaction equilibrium towards a selectively crystallizing stereoisomer appears to be particularly appealing. Supposing that these reactions provide diastereomeric species, the phenomenon is termed crystallization-induced diastereomer transformation (CIDT) (for reviews, see Kolarovic ˇand Jakubec 9 and Brands and Davies 10 and for the most up-to-date examples, see previous studies [11][12][13][14][15][16][17][18] ). A thermodynamic nature of the process typically allows for a straightforward reaction setup, and even syntheses featuring complex reaction equilibria can furnish crystalline products in very good yields and high purities.…”