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One‐Pot Catalytic Enantioselective Synthesis of 2‐Pyrazolines
Author(s) -
Thomson Connor J.,
Barber David M.,
Dixon Darren J.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201811471
Subject(s) - enantioselective synthesis , bifunctional , catalysis , hydrazine (antidepressant) , hydrazone , chemistry , aldehyde , combinatorial chemistry , organic chemistry , reagent , reactivity (psychology) , chromatography , medicine , alternative medicine , pathology
A scalable, one‐pot, enantioselective catalytic synthesis of 2‐pyrazolines from beta‐substituted enones and hydrazines is described. Pivoting on a two‐stage catalytic Michael addition/condensation strategy, the use of an aldehyde to generate a suitable hydrazone derivative of the hydrazine was found to be key for curtailing background reactivity and tuning the catalyst‐controlled enantioselectivity. The new synthetic method is easy to perform, uses a new and readily prepared cinchona‐derived bifunctional catalyst, is broad in scope, and tolerates a range of functionalities with high enantioselectivity (up to >99:1 e.r.). The significant scalability of this methodology was demonstrated with the synthesis of more than 80 grams of a pyrazoline product with 89 % catalyst recovery.