Ring Opening Reactions of N-Alkyl Oxazolidinones with Organolithium Reagents

Abstract

Addition of primary, secondary and aryl organolithium reagents to N-methyl and N-benzyl oxazolidin-2-ones give N-acyl amino alcohols in 30-93% yields. Application to the synthesis of an imidazoyl oxazoline is demonstrated.

Key words

acylations - amides - amino alcohols - organometallic ­reagents - rearrangements

References

• 2a Myers AG. Yang BH. Chen H. Gleason JL. J. Am. Chem. Soc.  1994,  116:  9361 
• 2b Micouin L. Schanen V. Riche C. Chiaroni A. Quirion J.-C. Husson H.-P. Tetrahedron Lett.  1994,  35:  7223 
• 2c Myers AG. Gleason JL. Yoon T. J. Am. Chem. Soc.  1995,  117:  8488 
• 2d Myers AG. Yoon T. Tetrahedron Lett.  1995,  36:  9429 
• 2e Micouin L. Jullian V. Quirion J.-C. Husson H.-P. Tetrahedron: Asymmetry  1996,  7:  2839 
• 3 Bull S. D., Davies S. G., Jones S., Sanganee H. J.; J. Chem. Soc., Perkin Trans. 1; 1999, 387
• 6 Jullian V. Quirion J.-C. Husson H.-P. Synthesis  1997,  1091 
• 7 Jarowicki K. Kocienski PJ. Qun L. Org. Synth.  2002,  79:  11 
• 8 Phillips AJ. Uto Y. Wipf P. Reno MJ. Williams DR. Org. Lett.  2000,  2:  1165 

1

Current address: Department of Chemistry, University of Sheffield, Dainton Building, Brook Hill, Sheffield S3 7HF, UK.

4

Analytical samples were prepared by column chromatography and/or recrystallisation. All new compounds reported had satisfactory analytical data that will be reported in full in due course.

5

Typical Experimental Procedure: n-BuLi (1.6 M, 0.44 mL, 0.70 mmol) was added to a solution of N-methyl 4(S)-iso-propyl oxazolidin-2-one (0.1 g, 0.70 mmol) at -78 °C. The reaction was warmed to 0 °C and after 2 h quenched with H₂O (2 mL) and extracted with EtOAc (5 × 10 mL). The organic extracts were combined and washed with NH₄Cl (5 mL), dried over NaSO₄ and the solvent removed under vacuum to give a pale yellow oil as the crude product
(0.157 g) which was purified using flash column chromatography (EtOAc) to give a clear oil (0.131 g, 93%); [α]_D ²⁵ -23.1 (c 2.5, CHCl₃); ratio of rotamers A/B = 1.7:1. Rotamer A: ¹H NMR (500 MHz, CDCl₃): δ = 0.80 (d, J = 6.4 Hz, 3 H, CH ₃ CH), 0.86 (t, J = 7.3 Hz, 3 H, CH ₃ CH₂), 0.93 (d, J = 6.4 Hz, 3 H, CH ₃ CH), 1.29 (m, 2 H, CH₃CH ₂ ), 1.55 (m, 2 H, CH₃CH₂CH ₂ ), 1.84 [m, 1 H, (CH₃)₂CH], 2.33 (m, 2 H, CH₃CH₂CH₂CH ₂ ), 2.84 (s, 3 H, NCH ₃ ), 3.24 (s, br d, 1 H, OH), 3.97-3.42 (range of multiplets, 3 H, HOCH ₂ CH). ¹³C NMR (125 MHz, CDCl₃): δ = 22.7 (CH₃CH), 27.6 [(CH₃)CH₂ CH₂], 27.7 [(CH₃)₂ CH], 34.1 [CH₃(CH₂)₂ CH₂], 61.9 (HOCH₂), 65.6 (HOCH₂ CH), 175.4 [C(O)N]. Rotamer B: ¹H NMR (500 MHz, CDCl₃): δ = 0.77 (d, J = 6.7 Hz, 3 H, CH ₃ CH), 0.85(t, J = 7.3 Hz, 3 H, CH ₃ CH₂), 0.91(d, J = 6.4 Hz, 3 H, CH ₃ CH), 1.68 [m, 1 H, (CH₃)₂CH], 2.28 (m, 2 H, CH₃CH₂CH₂CH ₂ ), 2.68 (s, 3 H, NCH ₃ ), 3.24 (s, br d, 1 H, OH), 3.97-3.42 (range of multiplets, 3 H, HOCH ₂ CH). ¹³C NMR (125 MHz, CDCl₃): δ = 14.0 (CH₃CH), 26.8 [(CH₃)₂ CH], 27.3 (CH₃CH₂ CH₂), 32.1 (N-CH₃), 33.4 [CH₃(CH₂)₂ CH₂], 60.8 (HOCH₂), 63.3 (HOCH₂ CH), 175.1 [C(O)N]. MS (EI): m/z calcd [M⁺] for C₁₁H₂₃NO₂: 201.1729; found: 201.1719. MS (EI): m/z (%) = 201 (1) [C₁₁H₂₃NO₂ ⁺], 183 (2), 170 (1) [C₁₀H₂₀N⁺], 86 (100), 74 (44).