The intramolecular tandem Michael/Mannich-type reaction of α,β-unsaturated carbonyl compounds with acyliminium ions provides access to chiral indolizidines

The intramolecular tandem Michael/Mannich-type (Michael addition/halo-Mannich-type) reaction using TiCl4/n-Bu4NI system between the α,β-unsaturated carbonyl compounds possessing an Evans oxazolidinone as a chiral auxiliary and N-acyliminium ion intermediates is described. The reaction was promoted in a mixed solvent of AcOEt–CH2Cl2 to afford indolizidine compounds with three stereogenic centers.

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[7S,8R,8(4S),8aS]-7-Iodo-8-(2-oxo-4-phenyloxazolidine-3- carbonyl)hexahydroindorizin-3-oneC18H19IN2O4[α]D = +42.3 (c 1.01, CHCl3)Source of chirality: (S)-phenylglycineAbsolute configuration: [7S,8R,8(4S),8aS]

[7S,8R,8(4S),8aR]-7-Iodo-8-(2-oxo-4-phenyloxazolidine-3- carbonyl)hexahydroindorizin-3-oneC18H19IN2O4[α]D = +209.4 (c 1.01, CHCl3)Source of chirality: (S)-phenylglycineAbsolute configuration: [7S,8R,8(4S),8aR]

[7S,8R,8(4S),8aS]-8-(4-Benzyl-2-oxooxazolidine-3- carbonyl)-7-iodohexahydroindorizin-3-oneC19H21IN2O4[α]D = +52.2 (c 1.01, CHCl3)Source of chirality: (S)-phenylalanineAbsolute configuration: [7S,8R,8(4S),8aS]