N-Vinyl-2-Oxazolidinone: New Preparation Methods and First Uses as a Dienophile

Abstract

N-Vinyloxazolidinone was conveniently prepared in 73% overall yield by an easy two-step procedure based on the dehydroalkoxylation of an intermediate hemiaminal using trimethylsilyl trifluoromethanesulfonate and triethylamine. The good dienophilicity of this enecarbamate was demonstrated in several [4+2] stereocontrolled processes involving activated 1-oxabutadienes under appropriate Lewis-acid catalyzed conditions. In addition, an unexpected amido-alkylation of the title compound is described under mild conditions.

N-vinyl oxazolidinone - N,O-acetal - lanthanide - dienophile - heterocycloaddition

References and Notes

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4e Also see: Koseki Y. Kusano S. Ichi D. Yoshida K. Nagasaka T. Tetrahedron  2000,  56:  8855 

The first examples of inverse-electron demand [4+2] heterocycloadditions of allenamides and allenimides (including chiral ones) were recently described:

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13 Preparation of N-vinyl-2-oxazolidinone 1: A mixture of oxazolidinone (2.05 g, 23.4 mmol), acetaldehyde diethyl acetal (33 mL, 0.23 mol) and d,l-camphorsulfonic acid (0.27 g, 1.17 mmol) was heated for 15 h at 55 °C. After cooling, aq. NaHCO₃ (15 mL) was added and the reaction mixture extracted with Et₂O (3 × 8 mL). The organic layer was washed with brine and dried over MgSO₄. Removal of solvent yielded crude N,O-acetal 2 (3.72 g, quantitative) used without further purification. To a cooled solution (0 °C) of crude N,O-acetal 2 (3.72 g, 23.4 mmol) in anhydrous CH₂Cl₂ under nitrogen (22 mL) were dropwise added distilled NEt₃ (4.9 mL, 37.7 mmol) and, trimethylsilyl triflate (5.5 mL, 30.4 mmol). After slow return to r.t. and stirring for 16 h, the mixture was filtered on basic alumina. Removal of solvent and purification by filtration (silica gel 4/1; ether) yielded 1 (1.95 g, 73%) as a pale yellow oil;R_f = 0.37 (Cyclohexane-AcOEt, 1:1); IR(film): 1753 (C=O), 1633 (C=C), 1248, 1080 (C-O) cm^-1; ¹H NMR (400 MHz, CDCl₃), δ 3.72 (t, 2 H, J _{4 ′ -5 ′} = 8.2 Hz, H-4′), 4.30 (dd, 1 H, J _2B-1 = 15.8 Hz, J _AB = 1.0 Hz, H-2_B), 4.44 (dd, 1 H, J _2A-1 = 8.9 Hz, J _AB = 1.0 Hz, H-2_A), 4.47 (t, 2 H, J _{5 ′ -4 ′} = 8.2 Hz, H-5′), 6.89 (dd, 1 H, J _1-2B = 15.8 Hz, J _1-2A = 8.9 Hz, H-1); ¹³C NMR(100 MHz, CDCl₃), δ 41.7 (C-4′), 62.0 (C-5′), 93.3 (C-2), 129.7 (C-1), 155.2 (C-2′).

14

General preparation of hetero-adduct 4a-f with Eu(fod) ₃ : A solution of heterodiene 3 (0.5 mmol), N-vinyl-2-oxazol-idinone 1 (0.5 mmol) and Eu(fod)₃ (0.025 mmol) in cyclo-hexane (5 mL) was refluxed under nitrogen for the time referred to Table [2] . After removal of solvent the crude product was chromatographed (silica gel 40/1) using cyclohexane-AcOEt, 70:30 to 50:50. Compounds 4a-f obtained with yields referred to Table [2] are new and analytical data of one representative example is included in ref. 15.

15

Analytical data of hetero-adduct 4a cis: white crystal, mp 59-61 °C(ether); R_f = 0.23 (cyclohexane-AcOEt, 1:1); ¹H NMR (400 MHz, CDCl₃), δ 1.94 (dt, 1 H, J _AB = 12.8 Hz,
J _2ax-3 = J _2ax-1 = 11.3 Hz, H-2_ax), 2.26 (ddt, 1 H, J _AB = 12.8 Hz, J _2eq-3 = 6.4 Hz, J _2eq-1 = J _2eq-4 = 2 Hz, H-2_eq), 3.57 (dt, 1 H, J_AB = J _{4 ′ B-5 ′ B} = 8.9 Hz, J _{4 ′ B-5 ′ A} = 6.2 Hz, H-4′_B), 3.81 (s, 3 H, OCH₃), 3.84 (m, 1 H, H-4′_A), 3.89 (ddd, 1 H, J _3-2ax = 11.3 Hz, J _3-2eq = 6.4 Hz, J _3-4 = 2.5 Hz, H-3), 4.38 (dt, 1 H, J _AB = J _{5 ′ B-4 ′ B} = 8.9 Hz, J _{5 ′ B-4 ′ A} = 6.9 Hz, H-5′_B), 4.46 (dt, 1 H, J_AB = J _{5 ′ A-4 ′ A} = 8.9 Hz, J _{5 ′ A-4 ′ B} = 6.2 Hz, H-5′_A), 5.76 (dd, 1 H, J _1-2ax = 11.3 Hz, J _1-2eq = 2 Hz, H-1), 6.17 (t, 1 H, J _4-3 = J _4-2eq = 2 Hz, H-4), 7.22 (d, 2 H, J = 6.9 Hz, H _o ), 7.29 (t, 1 H, J = 7.4 Hz, H _p ), 7.35 (t, 2 H, J = 7.4 Hz, H _m ); ¹³C NMR (100 MHz, CDCl₃), δ 35.5 (C-2), 39.5 (C-3), 40.1 (C-4′), 52.7 (OCH₃), 62.9 (C-5′), 81.3 (C-1), 114.6 (C-4), 127.5 (C _o ), 127.7 (C _p ), 129.3 (C _m ), 142.5 (C _n ), 144.4 (C-5), 157.8 (C-2′), 163.0 (CO₂). IR(film): 1758 (C=O), 1643 (C=C), 1134, 1248, 1288 (C-O) cm^-1; SM C₁₆H₁₇NO₅ [M]^+· 303 (1.8%); HRMS (EI) calcd for C₁₆H₁₅NO₄ [M-H₂O]⁺ 285.1001, found 285.1008.

16

Preparation of hetero-adduct 4a trans with SnCl ₄ : To a cooled solution (-78 °C) of heterodiene 3a (95 mg, 0.5 mmol) and N-vinyl-2-oxazolidinone 1 (57 mg, 0.5 mmol) in anhydrous CH₂Cl₂ (5 mL) under nitrogen was added dropwise SnCl₄ 1 M in CH₂Cl₂ (0.25 mL, 0.25 mmol). After stirring (5 min) the mixture was quenched with sat. aq. NaHCO₃ (5 mL). After returning to r.t. and extraction with CH₂Cl₂ (2 × 5 mL), the resulting organic layer was dried (MgSO₄). Removal of solvent and purification by chromatography (silica gel 40/1; cyclohexane-AcOEt, 70:30 to 50:50) yielded 4a (143 mg, 94%) as a mixture cis/trans, 68:32. 4a trans was thus isolated as a white solid; R_f = 0.16 (cyclohexane-AcOEt, 1:1); ¹H NMR (400 MHz, CDCl₃), δ 2.03 (dq, 1 H, J _AB = 13.3 Hz, J_2eq-1 = J_2eq-3 =
J _2eq-4 = 2 Hz, H-2_eq), 2.33 (ddd, 1 H, J _AB = 13.3 Hz, J _2ax-1 = 11.3 Hz, J _2ax-3 = 6.6 Hz, H-2_ax), 3.61 (dt, 1 H, J _AB = J _{4 ′ B-5 ′ B} = 8.6 Hz, J _{4 ′ B-5 ′ A} = 5.9 Hz, H-4′_B), 3.81 (m, 2 H, H-3 + H-4′_A), 3.83 (s, 3 H, OCH₃), 4.34 (q, 1 H, J_AB = J _{5 ′ B-4 ′ B} = J _{5 ′ B-4 ′ A} = 8.5 Hz, H-5′_B), 4.42 (dt, 1 H, J_AB = J _{5 ′ A-4 ′ A} = 8.9 Hz, J _{5 ′ A-4 ′ B} = 5.9 Hz, H-5′_A), 5.43 (dd, 1 H, J _1-2ax = 11.3 Hz, J _1-2eq = 2.2 Hz,
H-1), 6.25 (dd, 1 H, J _4-3 = 5.3 Hz, J _4-2eq = 1.5 Hz, H-4), 7.23 (d, 2 H, J = 6.9 Hz, H _o ), 7.27 (t, 1 H, J = 5.9 Hz, H _p ), 7.35 (t, 2 H, J = 7.4 Hz, H _m ); ¹³C NMR (100 MHz, CDCl₃), δ 33.8 (C-2), 37.1 (C-3), 40.5 (C-4′), 52.7 (OCH₃), 62.8 (C-5′), 77.7 (C-1), 111.9 (C-4), 127.6 (C _p ), 128.4 C _o ), 129.3 (C _m ), 143.2 (C _n ), 144.7 (C-5), 157.8 (C-2′), 163.1 (CO₂).

17 A similar gap of reactivity was previously observed between 4a and 4d-e towards ketone enol ethers as the dienophiles: Martel A. Leconte S. Dujardin G. Brown E. Maisonneuve V. Retoux R. Eur. J. Org. Chem.  2002,  3:  514 

18a Ichikawa Y. Nishiyama T. Isobe M. Synlett  2000,  1253 

18b Wolfe S. Whangbo M. Mitchell DJ. Carbohydr. Res.  1979,  69:  1 

19a Gizecki P. Dhal R. Toupet L. Dujardin G. Org. Lett.  2000,  2:  585 

19b Gizecki P. Ph.D. Thesis   CNRS-Université du Maine; Le Mans: 2001. 

19c

Gizecki, P.; Dhal, R.; Dujardin, G.; submitted.

20

Selected data of 9: ¹H NMR (400 MHz, CDCl₃), δ 6.87 (1 H, dd, J = 14.3 and 1.2 Hz), 5.13 (1 H, dd, J = 14.3 and 6.4 Hz).IR(film): 3309 (NH); 1747 (C=O), 1670 (C=C), 1637 (C=O) cm^-1.