Vanadium-Catalyzed Oxidation of tert-Butyl N-Hydroxycarbamate to tert-Butyl Nitrosoformate and Its Diels–Alder Reaction with Simple and Functionalized Dienes

Abstract

A general and efficient vanadium-catalyzed oxidation of tert-butyl N-hydroxycarbamate to tert-butyl nitrosoformate using alkyl hydroperoxides as terminal oxidants has been developed. The intermediate nitroso compound was trapped by in situ Diels–Alder reaction with simple and functionalized dienes, providing general access to a variety of functionalized 3,6-dihydro-2H-1,2-oxazines.

Key words

nitroso Diels–Alder reaction - catalysis - oxidation - functionalized dienes - vanadium catalyst

• References and Notes

• 1a Kirby GW. Chem. Soc. Rev. 1977; 6: 1
• 1b Yamamoto Y, Yamamoto H. Eur. J. Org. Chem. 2006; 2031
• 2a Kirby GW, Sweeny JG. J. Chem. Soc., Chem. Commun. 1973; 704
• 2b Bodnar BS, Miller MJ. Angew. Chem. Int. Ed. 2011; 50: 5630
• 2c Li F, Yang B, Miller MJ, Zajicek J, Noll BC, Möllmann U, Dahse H.-M, Miller PA. Org. Lett. 2007; 9: 2923
• 2d Vogt PF, Miller MJ. Tetrahedron 1998; 54: 1317
• 2e Iwasa S, Fakhruddin A, Nishiyama H. Mini-Rev. Org. Chem. 2005; 2: 157
• 3 Kirby GW, Sweeny JG. J. Chem. Soc., Perkin Trans. 1 1981; 3250
• 4 Jenkins NE, Ware RW. Jr, Atkinson RN, King SB. Synth. Commun. 2000; 30: 947
• 5 Martin SF, Hartmann M, Josey JA. Tetrahedron Lett. 1992; 33: 3583
• 6 Dao LH, Dust JM, Mackay D, Watson KN. Can. J. Chem. 1979; 57: 1712
• 7a Flower KR, Lightfoot AP, Wan H, Whiting A. Chem. Commun. 2001; 1812
• 7b Iwasa S, Tajima K, Tsushima S, Nishiyama H. Tetrahedron Lett. 2001; 42: 5897
• 7c Chaiyaveij D, Cleary L, Batsanov AS, Marder TB, Shea KJ, Whiting A. Org. Lett. 2011; 13: 3442
• 7d Howard JA. K, Ilyashenko G, Sparkes HA, Whiting A, Wright AR. Adv. Synth. Catal. 2008; 350: 869
• 7e Howard JA. K, Ilyashenko G, Sparkes HA, Whiting A. Dalton Trans. 2007; 2108
• 7f Adamo MF. A, Bruschi S. J. Org. Chem. 2007; 72: 2666
• 7g Chow CP, Shea KJ. J. Am. Chem. Soc. 2005; 127: 3678
• 7h Pulacchini S, Sibbons KF, Shastri K, Motevalli M, Watkinson M, Wan H, Whiting A, Lightfoot AP. Dalton Trans. 2003; 2043
• 7i Flower KR, Lightfoot AP, Wan H, Whiting A. J. Chem. Soc., Perkin Trans. 1 2002; 2058
• 7j Iwasa S, Fakhruddin A, Tsukamoto Y, Kameyama M, Nishiyama H. Tetrahedron Lett. 2002; 43: 6159
• 8a Streith J, Defoin A. Synthesis 1994; 1107
• 8b Kibayashi C, Aoyagi S. Synlett 1995; 873
• 9 Recently, copper-catalyzed aerobic oxidation of N-hydroxy-carbamates to nitrosoformates and their nitroso ene reaction with functionalized olefins was reported, see: Frazier CP, Engelking JR, Read de Alaniz J. J. Am. Chem. Soc. 2011; 133: 10430
• 10 Typical Procedure for the Vanadium-Catalyzed Oxidation of tert-Butyl N-Hydroxycarbamate and in situ Diels–Alder Reaction with (E,E)-Hexa-2,4-dien-1-ol (1a) To a solution of tert-butyl N-hydroxycarbamate (0.564 g, 4.1 mmol), (E,E)-hexa-2,4-dien-1-ol (0.246 mL, 2.1 mmol), and VO(Oi-Pr)₃ (5.0 μL, 0.021 mmol) in CH₂Cl₂ (4.2 mL) was added 80% CHP (0.39 mL, 2.1 mmol) at ambient temper-ature. After stirring for 1 h, H₂O (2 mL) was added to the mixture. A sat. Na₂SO₃ solution was slowly added to the resulting mixture. After stirring for 1 h, the reaction mixture was transferred to a separatory funnel, and the aqueous phase was extracted with CH₂Cl₂ (5 × 5 mL). The combined organic phases were washed with brine, dried over anhyd Na₂SO₄, filtered, and concentrated under reduced pressure. Flash chromatographic purification (eluent: hexane–Et₂O = 3:1 to 2:1) of the residue provided 2a and 3a (0.480 g, 99%) as a mixture of two regioisomers. The mixture was separated by column chromatography on silica gel (hexane–EtOAc = 9:1) to give pure 2a and 3a. The structure was deduced from two-dimensional NMR spectroscopy (HMBC and HMQC).¹³ (3R*,6R*)-N-tert-Butoxycarbonyl-6-hydroxymethyl-3-methyl-3,6-dihydro-2H-1,2-oxazine (2a) ¹³ TLC: R_f  = 0.26 (hexane–EtOAc = 1:1). IR (neat): 3407, 2978, 1698, 1369, 1169, 1119, 1066 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.32 (d, J = 9.0 Hz, 3 H), 1.47–1.49 (m, 1 H), 1.50 (s, 9 H), 3.67 (dd, J = 6.6, 12.6 Hz, 1 H), 3.77 (dd, J = 3.0, 12.3 Hz, 1 H), 4.41–4.46 (m, 1 H), 4.64–4.68 (m, 1 H), 5.69 (dt, J = 10.2, 1.8 Hz, 1 H), 5.92 (ddd, J = 10.2, 4.5, 2.4 Hz, 1 H). (3S*,6S*)-N-tert-Butoxycarbonyl-3-hydroxymethyl-6-methyl-3,6-dihydro-2H-1,2-oxazine (3a) ¹³ TLC: R_f  = 0.38 (hexane–EtOAc = 1:1). IR (neat): 3445, 2979, 1704, 1369, 1166, 1113, 1088 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.26 (d, J = 6.6 Hz, 3 H), 1.50 (s, 9 H), 1.65 (s, 1 H), 3.72–3.77 (m, 2 H), 4.47–4.52 (m, 1 H), 4.65–4.68 (m, 1 H), 5.78 (ddd, J = 10.2, 4.2, 2.1 Hz, 1 H), 5.85 (td, J = 1.5, 10.2 Hz, 1 H).
• 11a Sharpless KB, Michaelson RC. J. Am. Chem. Soc. 1973; 95: 6136
• 11b Sharpless KB, Verhoeven TR. Aldrichimica Acta 1979; 12: 63
• 11c Michaelson RC, Palermo RE, Sharpless KB. J. Am. Chem. Soc. 1977; 96: 1990
• 12 Zeng W, Ballard TE, Melander C. Tetrahedron Lett. 2006; 47: 5923
• 13 Calvet G, Blanchard N, Kouklovsky C. Synthesis 2005; 3346
• 14 N-tert-Butoxycarbonyl-2-oxa-3-azabicyclo[2.2.1]hept-5-ene (2b) ¹⁶ TLC: R_f  = 0.33 (hexane–Et₂O = 1:2). IR (neat): 2978, 1739, 1702, 1165 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.47 (s, 9 H), 1.73 (d, J = 8.6 Hz, 1 H), 1.99 (td, J = 2.4, 8.6 Hz, 1 H), 4.98 (br s, 1 H), 5.21 (br s, 1 H), 6.40–6.42 (m, 2 H). N-tert-Butoxycarbonyl-2-oxa-3-azabicyclo[2.2.2]oct-5-ene (2c) ¹⁶ TLC: R_f  = 0.51 (hexane–EtOAc = 3:1). IR (neat): 2976, 2936, 1736, 1695, 1158, 1073 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.27–1.54 (m, 2 H), 1.47 (s, 9 H), 2.06–2.23 (m, 2 H), 4.73–4.75 (m, 2 H), 6.50–6.59 (m, 2 H). (3S*,6R*)-N-tert-Butoxycarbonyl-3,6-diphenyl-3,6-dihydro-2H-1,2-oxazine (2d) TLC: R_f  = 0.39 (hexane–EtOAc = 5:1). IR (neat): 2978, 1700, 1392, 1368, 1166, 1094, 699 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.49 (s, 9 H), 5.56 (br s, 1 H), 5.59 (br s, 1 H), 6.09 (d, J = 10.5 Hz, 1 H), 6.16 (ddd, J = 10.8, 4.5, 2.1 Hz, 1 H), 7.26–7.53 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.4, 79.0, 81.7, 126.4, 127.7, 127.8, 128.2, 128.5, 128.7, 129.0, 137.2, 139.2, 154.2. N-tert-Butoxycarbonyl-1,8-dimethyl-15-oxa-16-azatetracyclo[6.6.2.0^2,7.0^9,14]hexadec-2,4,6,9,11,13-hexaene (2e) ⁴ Mp 106–109 °C. TLC: R_f  = 0.33 (hexane–EtOAc = 5:1). IR (KBr): 2981, 1707, 1460, 1288, 1159, 748 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.21 (s, 9 H), 2.23 (s, 3 H), 2.56 (s, 3 H), 7.23–7.27 (m, 4 H), 7.34–7.38 (m, 2 H), 7.43–7.46 (m, 2 H). A 1:1 Mixture of N-tert-Butoxycarbonyl-4-methyl-3,6-dihydro-2H-1,2-oxazine (2f) and N-tert-Butoxycarbonyl-5-methyl-3,6-dihydro-2H-1,2-oxazine (3f) ¹³ TLC: R_f  = 0.66 (hexane–EtOAc = 6:1). IR (neat): 2978, 2933, 1705, 1683, 1392, 1368, 1243, 1166, 1102 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.50 [s, 9 H, 3 × CH₃ (3f)], 1.51 (s, 9 H, 3 × CH₃), 1.67 [br s, 3 H, CH₃-5 (3f)], 1.74 (br s, 3 H, CH₃-4), 3.94 (br s, 2 H, H-3), 4.02–4.05 [m, 2 H, H-3 (3f)], 4.26 [br s, 2 H, H-6 (3f)], 4.35–4.38 (m, 2 H, H-6), 5.51–5.55 [m, 1 H + 1 H, overlapped with H-5 and H-4 (3f)]. A 1:1 Mixture of N-tert-Butoxycarbonyl-4-(4-methyl-pent-3-enyl)-3,6-dihydro-2H-1,2-oxazine (2g) and N-tert-Butoxycarbonyl-5-(4-methylpent-3-enyl)-3,6-dihydro-2H-1,2-oxazine (3g) TLC: R_f  = 0.64 (hexane–EtOAc = 6:1). IR (neat): 2976, 2929, 1727, 1703, 1366, 1162, 1092 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.50 (s, 9 H + 9 H), 1.60 (s, 3 H + 3 H), 1.69 (s, 3 H + 3 H), 1.98–2.12 (m, 4 H + 4 H), 3.97 (br s, 2 H), 4.05 (br s, 2 H), 4.29 (br s, 2 H), 4.39 (br s, 2 H), 5.05–5.12 (m, 1 H + 1 H), 5.52 (br s, 1 H + 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 17.7, 25.6, 25.8, 25.9, 28.3, 32.7, 33.9, 44.9, 47.6, 68.0, 70.4, 81.4, 116.0, 117.6, 123.3, 132.3, 134.2, 135.5, 155.0. N-tert-Butoxycarbonyl-6-carboxy-3-methyl-3,6-dihydro-2H-1,2-oxazine (2h) TLC: R_f  = 0.68 (MeOH). IR (KBr): 2977, 1748, 1686, 1370, 1156, 1121 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.36 (d, J = 6.6 Hz, 3 H), 1.51 (s, 9 H), 4.43 (br s, 1 H), 5.16 (s, 1 H), 5.93–6.03 (m, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 17.9, 28.3, 50.8, 75.9, 82.8, 121.9, 130.6 154.5, 170.5. N-tert-Butoxycarbonyl-6-ethoxycarbonyl-3-methyl-3,6-dihydro-2H-1,2-oxazine (2i) ¹⁷ TLC: R_f  = 0.63 (hexane–EtOAc = 6:1). IR (neat): 2980, 1760, 1738, 1705, 1369, 1312, 1196, 1169, 1076, 1032, 716 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.32 (t, J = 7.1 Hz, 3 H), 1.36 (d, J = 6.8 Hz, 3 H), 1.50 (s, 9 H), 4.27 (q, J = 7.2 Hz, 2 H), 4.46–4.48 (m, 1 H), 5.14–5.16 (m, 1 H), 5.90 (td, J = 1.3, 10.4 Hz, 1 H), 5.98 (ddd, J = 10.2, 4.3, 2.5 Hz, 1 H). N-tert-Butoxycarbonyl-6-methoxycarbonyl-3-hydroxy-methyl-3,6-dihydro-2H-1,2-oxazine (2j) TLC: R_f  = 0.24 (hexane–EtOAc = 1:1). IR (neat): 3446, 2979, 1737, 1707, 1475, 1251, 1157, 1071, 1024 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.50 (s, 9 H), 3.73–3.88 (m, 2 H), 3.82 (s, 3 H), 4.51–4.55 (m, 1 H), 5.52 (s, 1 H), 6.00 (ddd, J = 10.2, 3.9, 2.1 Hz, 1 H), 6.06 (td, J = 1.5, 10.5 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 28.2, 52.8, 56.6, 63.0, 74.3, 82.8, 124.3, 125.7, 155, 167.6. N-tert-Butoxycarbonyl-3-[(triisopropylsilyloxy)methyl]-6-methoxycarbonyl-3,6-dihydro-2H-1,2-oxazine (2k) TLC: R_f  = 0.77 (hexane–EtOAc = 1:1). IR (neat): 2943, 2867, 1766, 1740, 1710, 1367, 1109, 881, 681 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.02–1.13 (m, 3 H), 1.06 (d, J = 3.9 Hz, 18 H), 1.49 (s, 9 H), 3.80 (s, 3 H), 3.82 (dd, J = 9.6, 7.8 Hz, 1 H), 3.97 (dd, J = 9.3, 6.6 Hz, 1 H), 4.48–4.49 (m, 1 H), 5.16–5.19 (m, 1 H), 6.02 (td, J = 1.8, 10.2 Hz, 1 H), 6.16 (ddd, J = 10.2, 4.2, 2.7 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 11.9, 17.9, 28.3, 52.6, 55.8, 64.1, 74.7, 82.1, 123.2, 127.3, 154.1, 167.9. N-tert-Butoxycarbonyl-6-(N′-methoxy-N′-methyl-carbamoyl)-3-methyl-3,6-dihydro-2H-1,2-oxazine (2l) TLC: R_f  = 0.25 (hexane–Et₂O = 1:2). IR (neat): 3592, 2979, 2934, 1681, 1369, 1172, 992, 714 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 1.37 (d, J = 6.6 Hz, 3 H), 1.51 (s, 9 H), 3.24 (br s, 3 H), 3.84 (s, 3 H), 4.45–4.47 (m, 1 H), 5.53 (br s, 1 H), 5.86 (br s, 1 H), 5.99 (ddd, J = 10.5, 5.1, 2.4 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 17.9, 28.4, 32.4, 50.7, 62.2, 74.3, 81.7, 122.3, 130.0, 154.2. N-tert-Butoxycarbonyl-3-[(tert-butyldimethylsilyloxy)-methyl]-6-methoxycarbonyl-3,6-dihydro-2H-1,2-oxazine (2m) TLC: R_f  = 0.66 (hexane–EtOAc = 1:1). IR (neat): 2954, 2930, 2857, 1766, 1741, 1710, 1253, 1106, 834, 777 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 0.07 (s, 6 H), 0.89 (s, 9 H), 1.49 (s, 9 H), 3.73 (dd, J = 9.9, 7.2 Hz, 1 H), 3.81 (s, 3 H), 3.88 (dd, J = 10.2, 7.2 Hz, 1 H), 4.46 (br s, 1 H), 5.16–5.19 (m, 1 H), 6.01 (td, J = 1.5, 10.2 Hz, 1 H), 6.11 (ddd, J = 10.5, 4.2, 2.7 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = –5.3, –5.3, 18.2, 25.6, 25.8, 28.3, 52.6, 55.8, 63.6, 74.7, 82.1, 123.5, 127.0, 154.2, 167.8.
• 15 Adamo MF. A, Bruschi S. J. Org. Chem. 2007; 72: 2666
• 16 Zhang D, Süling C, Miller MJ. J. Org. Chem. 1998; 63: 885
• 17 Bollans L, Bacsa J, Iggo JA, Morris GA, Stachulski AV. Org. Biomol. Chem. 2009; 7: 4531