Enantioselective Synthesis of Oxazolidinones from N,N-Dibenzylamino Epoxides

Abstract

Enantiomerically pure oxazolidinones are easily prepared from N,N-dibenzylamino epoxides through a one-pot procedure involving monodeprotection of the amino group and treatment with NaHCO₃.

Key words

amino epoxides - cyclization - oxazolidinones - heterocycles

References and Notes

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General Experimental Procedure for the Preparation of Oxazolidinones from N , N -Dibenzyl Amino Epoxides
To a 0.05 M solution of the amino epoxide in MeCN-H₂O (5:1) was added CAN (2.1 equiv) and the reaction was stirred at r.t., following the progress by TLC (approx. 12 h). Then a sat. aq soln of NaHCO₃ was added, and the mixture was vigorously stirred for 10 min. After extraction with Et₂O, drying over Na₂SO₄ and concentration, the crude reaction mixture was purified by chromatography to give the pure oxazolidinone.

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Representative Data
Oxazolidinone 4: [α]_D ^²0 -67.9 (c 1.2, CHCl₃). IR: ν_max = 3415, 2927, 1731, 1424, 1052 cm^-¹. ^¹H NMR (400 MHz, C₆D₆): δ = 7.27 (m, 5 H), 4.75 (d, J = 15.3 Hz, 1 H), 3.91 (dt, J = 5.0, 8.3 Hz, 1 H), 3.80 (d, J = 15.3 Hz, 1 H), 3.37 (d, J = 5.0 Hz, 2 H), 3.16 (dq, J = 6.6, 8.3 Hz, 1 H), 0.68 (d, J = 6.6 Hz, 1 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 157.7 (s), 135.7 (s), 128.8 (d), 128.0 (d), 127.9 (d), 76.7 (d), 60.8 (t), 51.8 (d), 45.6 (t), 12.5 (c). LRMS (EI): m/z (%) = 221 (29)[M⁺], 91 (100). HRMS (EI): m/z calcd for C₁₂H₁₅NO₃: 221.1052; found: 221.1043.

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Each possible isomer was subjected to a conformational search using Molecular Mechanics (PCMODEL v7, Serena Software, Bloomington, IN). The coupling constants in each conformer were calculated and the Boltzmann weighted average was used for the comparison with the experimental values.