Key result
Benzophenone imine with catalytic Y(OTf)3 enabled the selective preparation of primary 1,2-amino alcohols from epoxides in up to 79% isolated yield over three steps.
Demonstrates a novel chemical methodology for the selective preparation of primary 1,2-amino alcohols from epoxides using benzophenone imine and Y(OTf)3 catalysis.
Provides selective access to primary 1,2-amino alcohols; leaves open translation to scalable process chemistry.
Benzophenone imine was found to be an effective ammonia surrogate for the selective preparation of primary 1,2-amino alcohols from epoxides, including enantiopure epichlorohydrin, in the presence of catalytic Y(OTf) 3 . High-throughput screening of 48 Lewis acids quickly identified Y(OTf) 3 as an effective mediator of the addition reaction under mild conditions. Following acidic hydrolysis, the primary amino alcohol salt is revealed and partitions into the aqueous solution, while the benzophenone byproduct is easily removed by simple extraction with ethyl acetate. These ammonium salts can be directly Boc-protected or further derivatized without isolation to form benzamides and sulfonamides under Schotten–Baumann-type conditions in up to 79% isolated yield over three steps. This methodology has been used to prepare key intermediates for the synthesis of PRMT5 inhibitors with high enantiopurity as well as numerous other amide and sulfonamide derivatives.
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Lim et al. (2018) studied this question. Benzophenone imine and catalytic Y(OTf)3 was evaluated on Yield of primary 1,2-amino alcohols and derivatives. Benzophenone imine with catalytic Y(OTf)3 enabled the selective preparation of primary 1,2-amino alcohols from epoxides in up to 79% isolated yield over three steps.
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