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.

Key-words

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

References and Notes

• 1a Boger DL. Weinreb SN. Hetero Diels-Alder Methodology in Organic Synthesis   Academic Press; San Diego: 1987. 
• 1b Tietze LF. Kettschau G. Top. Curr. Chem.  1997,  189:  1 
• For reviews, see:
• 2a Rappoport Z. The Chemistry of Enamines in The Chemistry of Functional Groups   John Wiley and Sons; New York: 1994. 
• 2b Whitesell JK. Whitesell MA. Synthesis  1983,  517 
• 2c Hickmott PW. Tetrahedron  1982,  38:  1975 
• 2d Hickmott PW. Tetrahedron  1982,  38:  3363 
• 2e Lenz GR. Synthesis  1978,  489 
• 2f For reviews on cycloaddition using dienamides, see: Campbell AL. Lenz GR. Synthesis  1987,  421 
• For recent studies involving enamides, see:
• 3a Fuchs JR. Funk RL. Org. Lett.  2001,  3:  3349 
• 3b Maeng J.-H. Funk RL. Org. Lett.  2001,  3:  1125 
• 3c Abbiati G. Clerici F. Gelmi ML. Gambini A. Pilati T. J. Org. Chem.  2001,  66:  6299 
• 3d Bach T. Schröder J. Brandl T. Hecht J. Harms K. Tetrahedron  1998,  54:  4507 
• For recent examples of synthesis and cycloadditions of dienamides, see:
• 4a Gauvry N. Huet F. J. Org. Chem.  2001,  66:  583 
• 4b von Wangelin AJ. Neumann H. Gordes D. Spannenberg A. Beller M. Org. Lett.  2001,  3:  2895 
• 4c Ha JD. Kang CH. Belmore KA. Cha JK. J. Org. Chem.  1998,  63:  3810 ; and references 1-7 cited therein.
• 4d For epoxydation of enamides, see: Adam W. Reinhardt D. Reissig H.-U. Paulini K. Tetrahedron  1995,  51:  12257 ; and references cited therein
• 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:
• 5a Wei L.-L. Xiong H. Douglas CJ. Hsung RP. Tetrahedron Lett.  1999,  40:  6903 
• 5b Wei L.-L. Hsung RP. Xiong H. Mulder JA. Nkansah NT. Org. Lett.  1999,  1:  2145 
• 6 Vani PV. Chida AS. Srinivasan R. Chandrasekharam M. Singh AK. Synth. Commun.  2001,  31:  2043 
• 7 Walles WE, Tousignant WF, and Houtman T. inventors; US Patent Appl.  2891058. 
• 8 Tulshian DB. Tsang R. Fraser-Reid B. J. Org. Chem.  1984,  49:  2347 
• 9 Dujardin G. Rossignol S. Brown E. Tetrahedron Lett.  1995,  36:  1653 
• 10 Akiba T. Tamura O. Hashimoto M. Kobayashi Y. Katoh T. Nakatani K. Kamada M. Hayakawa I. Terashima S. Tetrahedron  1994,  50:  3905 
• 11 Gassman PG. Burns SJ. Pfister KB. J. Org. Chem.  1993,  58:  1449 
• 12 Bach T. Brummerhop H. J. Prakt. Chem.  1999,  341:  410 
• 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′).
• 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.

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).

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.