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Direct Asymmetric α‐Selective Mannich Reaction of β,γ‐Unsaturated Ketones with Cyclic α‐Imino Ester: Divergent Synthesis of Cyclocanaline and Tetrahydro Pyridazinone Derivatives
Author(s) -
Geng YuHuan,
Hua YuanZhao,
Jia ShiKun,
Wang MinCan
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202100284
Subject(s) - chemistry , stereocenter , enantioselective synthesis , mannich reaction , diastereomer , catalysis , lewis acids and bases , adduct , organic chemistry , brønsted–lowry acid–base theory , medicinal chemistry
The first regio‐, diastereo‐, and enantioselective direct Mannich reaction of β,γ,‐unsaturated ketones with benzoxazinone cyclic imines was enabled by Lewis acid/Brønsted base cooperative catalysis. The dinuclear zinc complex catalyzed the reaction of a broad range of β,γ‐unsaturated ketones to proceed at the α‐site exclusively, leading to corresponding adducts with two consecutive tertiary carbon stereocenters in diastereomeric ratios of up to >20:1 and enantioselectivities generally in the 90–99 % ee range. These products were used as general intermediates in the synthesis of multisubstituted cyclocanalines, tetrahydro pyridazinones, and 4 H ‐furo[2,3‐ b ][1,4]benzoxazine derivatives.