Acid-Catalyzed Tandem Process for the One-Pot Synthesis of Oxazolidines

Dedicated to Prof. Victor Snieckus on the occasion of his 80^th birthday

Abstract

A simple protocol for the synthesis of oxazolidines from aziridines and allylic alcohols is reported. The solid-supported sulfonic acid catalyst can be easily removed after the reaction by a simple filtration leading to the oxazolidine reaction products in good to excellent yields.

Key words

aziridines - cyclization - oxazolidines - rearrangement - ring opening

• References and Notes

• 1 Hu XE. Tetrahedron 2004; 60: 2701
• 2a Williams RM. Glinka T. Flanagan ME. Gallegos R. Coffman H. Pei D. J. Am. Chem. Soc. 1992; 114: 733
• 2b Tomita F. Takahashi K. Tamaoki T. J. Antibiot. 1984; 37: 1268
• 3a Yadav JS. Reddy BV. S. Balanarsaiah E. Raghavendra S. Tetrahedron Lett. 2002; 43: 5105
• 3b Ghorai MK. Das K. Shukla D. J. Org. Chem. 2007; 72: 5859
• 4 Lu Z. Stahl SS. Org. Lett. 2012; 14: 1234
• 5 Kang B. Miller AW. Goyal S. Nguyen ST. Chem. Commun. 2009; 3928
• 6 Compound 4: Yar M. McGarrigle EM. Aggarwal VK. Angew. Chem. Int. Ed. 2008; 47: 3784
• 7a Singh FV. Rehbein J. Wirth T. ChemistryOpen 2012; 1: 245
• 7b Aldmairi AH. Griffiths-Jones C. Dupauw A. Henderson L. Knight DW. Tetrahedron Lett. 2017; 58: 3690
• 8 Javorskis T. Sriubaitė S. Bagdžiūnas G. Orentas E. Chem. Eur. J. 2015; 21: 9157
• 9 Coles SJ. Gale PA. Chem. Sci. 2012; 3: 683 . CCDC 1576825 ( cis-6d) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures
• 10 General Procedure A mixture of N-tosylaziridine (1 mmol), the allylic alcohol (1.1 mmol) in dry CH₂Cl₂ (20 mL) was stirred at 0 °C for 10 min, then dry Amberlyst-15 (0.5 g) was added. The mixture was left to warm up to room temperature for 2 h. The reaction mixture was filtered and washed with CH₂Cl₂ (2 × 10 mL). The combined organic layers were concentrated in vacuo and purified by column chromatography on silica gel to afford the oxazolidine as a clear oil. 2-Isopropyl-3-tosyloxazolidine (6a) ¹H NMR (500 MHz, CDCl₃): δ = 7.67 (d, J = 7.6 Hz, 2 H), 7.26 (d, J = 7.6 Hz, 2 H), 4.85 (d, J = 5.5 Hz, 1 H), 3.71 (ddd, J = 8.0, 6.9, 3.4 Hz, 1 H), 3.54 (ddd, J = 11.6, 6.8, 3.4 Hz, 1 H), 3.27 (ddd, J = 11.6, 8.6, 6.9 Hz, 1 H), 3.06 (td, J = 8.3, 6.9 Hz, 1 H), 2.36 (s, 3 H), 1.96–1.78 (m, 1 H), 0.93 (d, J = 6.1 Hz, 3 H), 0.88 (d, J = 6.7 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 144.1, 134.8, 129.9 (2 C), 127.8 (2 C), 95.85, 65.2, 46.8, 33.0, 21.6, 18.2, 16.3. IR (neat): ν = 2965, 2875, 1470, 1346, 1092 cm^–1. HRMS (APCI): m/z calcd for C₁₃H₂₀NO₃S [M + H]⁺: 270.1164; found: 270.1151. 4-Ethyl-2-isopropyl-3-tosyloxazolidine (6c) Major isomer: ¹H NMR (400 MHz, CDCl₃): δ = 7.74 (d, J = 8.3 Hz, 2 H), 7.35 (d, J = 8.3 Hz, 2 H), 4.76 (d, J = 6.1 Hz, 1 H), 3.61–3.54 (m, 2 H), 3.11–2.94 (m, 1 H), 2.45 (s, 3 H), 2.10–2.00 (m, 1 H), 1.87–1.74 (m, 1 H), 1.62–1.51 (m, 1 H), 1.07 (d, J = 7.0 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H), 0.94 (d, J = 7.0 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 144.6, 134.5, 129.8 (2 C), 128.0 (2 C), 96.9, 69.6, 60.8, 32.5, 21.6, 18.7, 16.4, 10.6. Minor isomer: ¹H NMR (400 MHz, CDCl₃): δ = 4.94 (d, J = 4.4 Hz, 1 H), 3.40–3.30 (m, 2 H), 2.93–2.87 (m, 1 H), 2.45 (s, 3 H), 2.05–1.95 (m, 1 H), 1.45–1.35 (m, 1 H), 1.01 (d, J = 6.9 Hz, 3 H), 0.95 (d, J = 6.9 Hz, 3 H), 0.82 (t, 6.7 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 144.0, 135.1, 129.9 (2 C), 127.7 (2 C), 95.4, 50.7, 33.7, 25.8, 18.0, 16.7, 15.5. IR (neat): ν = 2965, 2875, 2153, 1350, 1092 cm^–1. HRMS (APCI): m/z calcd for C₁₅H₂₄NO₃S [M + H]⁺: 298.1477; found: 298.1466. 2-Isopropyl-3-tosyloctahydrobenzo[d]oxazole (6e) ¹H NMR (300 MHz, CDCl₃): δ = 7.70 (d, J = 8.0, 2 H), 7.36 (d, J = 8.0, 2 H), 4.70 (d, J = 3.8 Hz, 1 H), 3.51 (ddd, J = 11.5, 10.6, 3.7 Hz, 5 H), 2.46 (s, 3 H), 2.35 (ddd, J = 11.5, 9.7, 3.7 Hz, 1 H), 2.32–2.23 (m, 1 H), 2.07–1.97 (m, 1 H), 1.85–1.73 (m, 2 H), 1.55–1.40 (m, 1 H), 1.24–1.13 (m, 4 H), 1.06 (d, J = 6.9 Hz, 3 H), 1.01 (d, J = 6.9 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 144.0, 132.1, 129.9 (2 C), 128.3 (2 C), 95.8, 81.4, 65.0, 33.8, 29.5 (2 C), 23.8, 23.2, 21.5, 18.9, 16.1. IR (neat): ν = 2941, 2874, 1458, 1350, 1109 cm^–1. HRMS (APCI): m/z calcd for C₁₇H₂₆NO₃S [M + H]⁺: 324.1633; found: 324.1617. 2-Cyclohexyl-3-tosyloxazolidine (6f) ¹H NMR (400 MHz, CDCl₃): δ = 7.67 (d, J = 8.1 Hz, 2 H), 7.28 (d, J = 8.1 Hz, 2 H), 4.88 (d, J = 6.0 Hz, 1 H), 3.69 (td, J = 7.5, 3.6 Hz, 1 H), 3.56–3.49 (m, 1 H), 3.31–3.22 (m, 1 H), 3.05 (ddd, J = 15.5, 8.1, 6.6 Hz, 1 H), 2.36 (s, 3 H), 1.80–1.65 (m, 4 H), 1.62–1.55 (m, 1 H), 1.20–1.07 (m, 3 H), 1.07–0.95 (m, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 144.0, 134.8, 130.0 (2 C), 127.9 (2 C), 95.2, 65.7, 48.1, 42.4, 28.6, 27.0, 26.3, 25.9, 25.7, 21.6. IR (neat): ν = 2926, 2855, 1450, 1350, 1090 cm^–1. HRMS (APCI): m/z calcd for C₁₅H₂₄NO₃S [M + H]⁺: 310.1477; found: 310.1477.

Synthesis of 1a and 1b:
• 11a Ye W. Leow D. Goh SL. M. Tan C. Chian C. Tan C. Tetrahedron Lett. 2006; 47: 1007

Synthesis of 1c:
• 11b Ando T. Kano D. Minakata S. Ryu I. Komatsu M. Tetrahedron 1998; 54: 13485

Synthesis of 1d:
• 11c Kano D. Minakata S. Komatsu M. J. Chem. Soc., Perkin Trans. 1 2001; 3186

Synthesis of 2b:
• 11d Trost BM. King SA. J. Am. Chem. Soc. 1990; 112: 408

Synthesis of 2d:
• 11e Hazelden IR. Ma X. Langer T. Bower JF. Angew. Chem. Int. Ed. 2016; 55: 11198