Organocatalytic Asymmetric Cascade Reaction of 2-Hydroxyphenyl-Substituted Enones and Isocyanates To Construct 1,3-Benzoxazin-2-ones

Abstract

The development of a new bisguanidinium salt as a multifunctional organocatalyst for asymmetric cascade esterification/aza-Michael reaction between 2-hydroxyphenyl-substituted enones and isocyanates is reported. A high level of enantioinduction and excellent isolated yields were achieved under mild reaction conditions. Enantiomerically enriched 1,3-benzoxazin-2-ones were constructed, and a possible catalytic model was suggested based on the mechanism-driven experiments.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…Feng and co‐workers recently reported the utilization of bisguanidinium salt 528 as a multifunctional organocatalyst in an asymmetric domino esterification/aza‐Michael reaction between 2‐hydroxyphenyl‐substituted enones 477 and isocyanates 525 for the synthesis of enantioenriched 1,3‐benzoxazin‐2‐ones 527 in high yields and ee values via the intermediates 526 (Scheme ) . Both the guanidinium salt and the amide moieties of the catalyst were found to be necessary to trigger the intramolecular aza‐Michael reaction …”

Recent Advances in Chiral Guanidine‐Catalyzed Enantioselective Reactions

“…Most substrates could provide products with dr >19:1 and excellent enantioselectivities (up to 99 % ee values). Liu and co‐workers also discovered the cascade esterification/aza‐Michael reaction catalyzed by bisguanidinium salt 24 a ⋅HBAr F 4 (Scheme ) . Excellent yields (73–99 %) and ee values (85–95 %) were achieved for the 1,3‐benzoxazin‐2‐ones adducts.…”

3,4-Dihydro-2H-1,3-benzoxazines and their oxo-derivatives - Chemistry and bioactivities

“…On the other hand, by condensation of amino-alkylnaphthols with phosgene 93 or carbonyl di-imidazole 94 in the presence of triethylamine, the 1,3-oxazin-2-one derivatives were produced in moderate yields.Also, the 1,3-benzoxazin-2-ones (8) were prepared by reaction of 2-hydroxyphenyl-substituted enones and isocyanates using bisguanidinium salt as catalyst. 95 Additionally, the 1,3-benzoxazine-2-one was synthesized from the reaction of substituted slicyladehyde with primary amine and aldehyde. As example, the spiropyrans based on benzoxazinone [4] were synthesizedfrom the reaction of compound (A) with compound (B) using protonated acetic acid [MeC (OH)2] + ClO4as catalyst, as indicated in Scheme 11.…”