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Enantioselective Synthesis of Spiro‐oxiranes: An Asymmetric Addition/Aldol/Spirocyclization Domino Cascade
Author(s) -
Choo KenLoon,
Mirabi Bijan,
Demmans Karl Z.,
Lautens Mark
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202105562
Subject(s) - stereocenter , aldol reaction , enantioselective synthesis , domino , chemistry , nucleophile , combinatorial chemistry , cascade , epoxide , cascade reaction , alkyne , derivatization , substrate (aquarium) , rhodium , stereochemistry , organic chemistry , catalysis , oceanography , chromatography , geology , high performance liquid chromatography
Abstract Enantioenriched spiro‐oxiranes bearing three contiguous stereocenters were synthesized using a rhodium‐catalyzed asymmetric addition/aldol/spirocyclization sequence. Starting from a linear substrate, the cascade enabled the formation of a spirocyclic framework in a single step. sp 2 ‐ and sp‐hybridized carbon nucleophiles were found to be competent initiators for this cascade, giving arylated or alkynylated products, respectively. Derivatization studies demonstrated the synthetic versatility of both the epoxide and the alkyne moieties of the products. DFT calculations were used to reconcile spectroscopic discrepancies observed between the solution‐ and solid‐state structures of the products.