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Synlett 2006(3): 0364-0368  
DOI: 10.1055/s-2006-926240
LETTER
© Georg Thieme Verlag Stuttgart · New York

The Nicholas-Type Activation of Cyclopropanes toward Reactions with ­Nitrones in the Homo-[3+2]-Dipolar Cycloaddition

Terry P. Lebold, Cheryl A. Carson, Michael A. Kerr*
Department of Chemistry, The University of Western Ontario, London, Ontario, N6A 5B7, Canada
Fax: +1(510)6613022; e-Mail: makerr@uwo.ca;
Further Information

Publication History

Received 22 September 2005
Publication Date:
06 February 2006 (online)

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Abstract

2-Ethynyl-1,1-carboethoxyclopropane, when treated with Co2(CO)8, results in the formation of the Co2(CO)6 adduct which in turn undergoes smooth cycloaddition in the presence of Sc(OTf)3 to form the corresponding tetrahdyro-1,2-oxazines. The adducts can either be decomplexed to yield the parent acetylenes or made to undergo Pauson-Khand reactions to form 6-cyclo­pentenyltetrahydro-1,2-oxazines.

Key words

tetrahydro-1,2-oxazine - cycloaddition - cyclopropanes - Pauson-Khand

9

Typical Experimental Procedure for the Cycloaddition of Cobalt-Complexed Cyclopropanediesters. Preparation of Compound 14.
A flame-dried round-bottom flask was charged with cyclopropane 9 (100 mg, 0.202 mmol) in 5 mL of dry CH2Cl2 under an argon atmosphere. Nitrone 10 (44 mg, 0.222 mmol) and Sc(OTf)3 (10 mg, 0.020 mmol) were added and the mixture was stirred until the reaction appeared complete by TLC (3 h). The solvent was evaporated and the residue was purified by flash column chromatography on silica gel (5% EtOAc-hexanes). Tetrahydro-1,2-oxazine 14 (126 mg, 0.182 mmol, 90%) was obtained as a red crystalline solid; mp 158-159 °C; R f = 0.57 (25% EtOAc-hexanes). 1H NMR (600 MHz, CDCl3): δ = 7.54-7.53 (m, 2 H), 7.18-7.14 (m, 5 H), 7.12-7.10 (m, 2 H), 6.84 (t, J = 7.2 Hz, 1 H), 6.19 (s, 1 H), 5.73 (s, 1 H), 5.10 (dd, J = 11.9, 2.9 Hz, 1 H), 4.43-4.37 (m, 2 H), 3.94-3.84 (m, 2 H), 2.81 (dd, J = 14.1, 2.9 Hz, 1 H), 2.72 (dd, J = 14.1,11.9 Hz, 1 H), 1.36 (t, J = 7.2 Hz, 3 H), 0.99 (t, J = 7.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 199.2, 169.4, 167.5, 148.6, 134.5, 130.6, 128.5, 128.1, 127.7, 121.9, 116.2, 91.5, 77.6, 71.3, 66.8, 62.5, 61.8, 59.4, 33.6, 14.1, 13.5. IR (thin film): νmax = 2986, 2098, 2026, 1740, 1598, 1493, 1454, 1368, 1298, 1256, 1183, 1075, 1020, 877, 755, 700 cm-1. HRMS (CI, isobutane): m/z calcd for C30H25Co2NO11: 694.0170; found: 694.0078.
Characterization data for compound 17, prepared as above: mp 164-165 °C; R f = 0.57 (25% EtOAc-hexanes). 1H NMR (600 MHz, CDCl3): δ = 7.20-7.17 (m, 3 H), 7.14-7.13 (m, 2 H), 6.91-6.87 (m, 2 H) 6.80 (dd, J = 5.1, 3.3 Hz, 1 H), 6.18 (s, 1 H), 6.05 (s, 1 H), 5.09 (dd, J = 12.2, 2.4 Hz, 1 H), 4.40 (m, 2 H), 4.00 (m, 1 H), 3.96 (m, 1 H), 2.83 (dd, J = 14.0, 2.4 Hz, 1 H), 2.734 (dd, J = 14.0, 12.2 Hz, 1 H), 1.37 (t, J = 7.2 Hz, 3 H), 1.07 (t, J = 7.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 199.3, 168.9, 167.1, 148.4, 133.5, 129.4, 128.4, 127.0, 125.2, 122.5, 116.5, 90.8, 78.3, 71.4, 65.0, 62.5, 62.0, 59.6, 33.7, 14.1, 13.7. IR (thin film): νmax = 2985, 2098, 2029, 1749, 1597, 1454, 1369, 1295, 1267, 1246, 1202, 1074, 1023, 958, 860, 760, 704 cm-1. HRMS (CI, isobutane): m/z calcd for C28H23Co2NO11S: 699.9734; found: 699.9707.
Characterization data for compound 22, prepared as above: mp 128-129 °C; R f = 0.43 (25% EtOAc-hexanes. 1H NMR (600 MHz, CDCl3): δ = 8.19 (d, J = 8.1 Hz, 2 H), 7.83 (d, J = 8.1 Hz, 2 H), 7.28-7.23 (m, 3 H), 7.17 (d, J = 7.2 Hz), 6.06 (s, 1 H), 5.02 (s, 1 H), 4.98 (dd, J = 12.0, 2.4 Hz, 1 H), 4.43-4.31 (m, 2 H), 3.90-3.80 (m, 2 H), 3.82 (d, J = 12.6 Hz, 1 H), 3.61 (d, J = 12.6 Hz, 1 H), 2.74 (dd, J = 14.4, 2.4 Hz, 1 H), 2.42 (dd, J = 14.4, 12.0 Hz, 1 H), 1.33 (t, J = 7.2 Hz, 3 H), 0.98 (t, J = 7.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 199.0, 168.7, 167.3, 147.8, 142.5, 136.2, 132.2, 128.5, 128.2, 127.3, 122.8, 91.8, 76.6, 70.9, 65.3, 62.5, 62.0, 59.4, 59.3, 33.2, 14.1, 13.6. IR (thin film): νmax = 2988, 2097, 2057, 2030, 1740, 1606, 1526, 1349, 1254, 1184, 1089, 1017, 859, 699 cm-1. HRMS (CI, isobutane): m/z calcd for C31H26Co2N2O13: 753.0177; found: 753.0140.

10

Typical Experimental Procedure for the Decomplexation of the Cycloadducts. Preparation of Compound 27. A solution of tetrahydro-1,2-oxazine 14 (179 mg, 0.259 mmol) in 5 mL of dry THF was cooled to 0 °C in a 50-mL round-bottom flask. A solution of I2 (979 mg, 3.89 mmol) in 20 mL of THF was added via cannula and the mixture was stirred for 2 h. The reaction mixture was then poured into a solution of sat. NaHCO3 and Na2SO3 (1:1 v/v, 100 mL). The aqueous mixture was extracted with Et2O (3 × 100 mL), the organic layers were combined, washed with brine and dried over anhyd MgSO4. The solvent was then evaporated to yield tetrahydro-1,2-oxazine 27 (102 mg, 0.250 mmol, 97%) as a colorless oil. R f = 0.40 (40% EtOAc-hexanes). 1H NMR (600 MHz, CDCl3): δ = 7.54-7.53 (m, 2 H), 7.19-7.14 (m, 5 H), 7.07-7.05 (d, J = 8.4 Hz, 2 H), 6.84 (t, J = 7.8 Hz, 1 H), 5.64 (s, 1 H), 4.75 (d, J = 12.6, 2.4 Hz, 1 H), 4.40-4.32 (m, 2 H), 3.93-3.83 (m, 2 H), 2.90 (dd, J = 14.4, 12.6 Hz, 1 H), 2.77 (dd, J = 14.4, 2.4 Hz, 1 H), 1.34 (t, J = 7.2 Hz, 3 H), 1.00 (t, J = 7.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 169.1, 167.3, 148.2, 130.6, 128.5, 128.5, 128.2, 127.9, 122.1, 116.2, 74.9, 67.7, 66.6, 62.5, 61.9, 58.7, 31.6, 14.1, 13.6 (one sp carbon not visible). IR (thin film): νmax = 3285, 2983, 1739, 1597, 1494, 1454, 1390, 1368, 1229, 1186, 1152, 1075, 1020, 942, 875, 755, 700 cm-1. HRMS (EI): m/z calcd for C24H25NO5: 407.1733; found: 407.1738.

12

Typical Experimental Procedure for the Pauson-Khand Reactions of the Cobalt-Complexed Cycloadducts. Preparation of Compound 31.
Tetrahydro-1,2-oxazine 14 (102 mg, 0.147 mmol) was dissolved in 4 mL of CH2Cl2 and ethene gas was bubbled through the solution for 5 min. 4-Methylmorpholine N-oxide (103 mg, 0.882 mmol) was then added and the reaction mixture was stirred under a balloon of ethene until the reaction appeared to subside by TLC. The solvent was then evaporated and the crude reaction mixture was purified by chromatography on silica gel (5% EtOAc-hexane). Tetrahydro-1,2-oxazine 31 was obtained as a white solid (42 mg, 0.091 mmol). Alternatively, tetrahydro-1,2-oxazine 14 could be prepared according to the typical procedure for the homo-[3+2]-dipolar cycloaddition and the reagents for the Pauson-Khand reaction could be added to the reaction mixture once the cycloaddition was complete. Tetrahydro-1,2-oxazine 31 was obtained in an overall yield of 68% using this one-pot procedure. Mp 47-49 °C; R f = 0.20 (25% EtOAc-hexane). 1H NMR (400 MHz, CDCl3): δ = 7.81 (s, 1 H), 7.56-7.54 (m, 2 H), 7.18-7.12 (m, 5 H) 7.06 (d, J = 8.0 Hz, 2 H), 6.80 (t, J = 7.2 Hz, 1 H), 5.73 (s, 1 H), 4.82 (d, J = 8.0 Hz, 1 H), 4.43-4.30 (m, 2 H), 3.97-3.80 (m, 2 H), 2.80 (dd, J = 14.2, 1.8 Hz, 1 H), 2.72-2.62 (m, 3 H), 2.50-2.48 (m, 2 H), 1.35 (t, J = 7.2 Hz, 3 H), 1.01 (t, J = 7.2 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 206.9, 169.2, 167.8, 159.0, 148.0, 144.6, 134.9, 130.6, 128.4, 128.0, 127.8, 121.5, 115.7, 72.5, 65.9, 62.3, 61.7, 58.7, 34.9, 29.9, 26.9, 14.0, 13.6. IR (thin film): νmax = 3095, 3062, 3029, 2984, 2932, 1738, 1706, 1600, 1493, 1453, 1367, 1344, 1246, 1186, 1089, 1030, 961, 919, 876, 789, 756, 734, 702, 622 cm-1. HRMS (EI): m/z calcd for C27H29NO6: 463.1995; found: 463.1998.

13

In the case of ethylene, a balloon of the gas was placed over the reaction mixture and NMO was added.

14

It is notable that the one-pot cycloaddition/Pauson-Khand yield for adduct 31 is higher than the combined yield for the two individual processes. The reasons for this are not clear although the reaction time allowed for the Pauson-Khand in the latter case was significantly longer and was done in the presence of a Lewis acid. This is under investigation.