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Synlett 2005(7): 1090-1094  
DOI: 10.1055/s-2005-865212
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Rearrangement of β-Hydroxy-N-acyloxazolidin-2-ones to Afford N-2-Hydroxyethyl-1,3-oxazinane-2,4-diones

Fred J. P. Feuillet, D. Gangani Niyadurupola, Rachel Green, Matt Cheeseman, Steven D. Bull*
Department of Chemistry, University of Bath, BA2 7AY, UK
Fax: +44(1225)386231; e-Mail: s.d.bull@bath.ac.uk;
Further Information

Publication History

Received 8 February 2005
Publication Date:
14 April 2005 (online)

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Abstract

Zinc alkoxides of syn- or anti-β-hydroxy-N-acyloxazol­idin-2-ones undergo stereoselective rearrangement to afford their corresponding syn- or anti-N-2-hydroxyethyl-1,3-oxazinane-2,4-diones in good yield.

Key words

aldol reaction - diastereoselective - intramolecular rearrangement - 1,3-oxazinane-2,4-dione - zinc alkoxide

    References

  • 1a Tubulin polymerisation inhibitors, see: Mu F. Lee DJ. Pryor DE. Hamel E. Cushman M. J. Med. Chem.  2002,  45:  4774 
    CrossrefPubMedGoogle Scholar
  • 1b Antibacterial: Heinisch L. Wittmann S. Stoiber T. Berg A. Ankel-Fuchs D. Möllmann U. J. Med. Chem.  2002,  45:  3032 
    CrossrefPubMedGoogle Scholar
  • 1c Matrix metalloproteinase inhibitors: Chollet A.-M. Le Diguarher T. Kucharczyk N. Loynel A. Bertrand M. Tucker G. Guilbaud N. Burbridge M. Pastoureau P. Fradin A. Sabatini M. Fauchère J.-L. Casara P. Bioorg. Med. Chem. Lett.  2002,  10:  531 
    CrossrefPubMedGoogle Scholar
  • 1d Peptidoleukotriene antagonist: Brown FJ. Bernstein PR. Cronk LA. Dosset DL. Hebbel KC. Maduskuie TP. Shapiro HS. Vacek EP. Yee YK. Willard AK. Krell RD. Snyder DW. J. Med. Chem.  1989,  32:  807 
    CrossrefPubMedGoogle Scholar
  • 1e Cestodicidal agents: Dubey SK. Singh AK. Singh H. Sharma S. Iyer RN. Katiyar JC. Goel P. Sen AB. J. Med. Chem.  1978,  21:  1178 
    CrossrefPubMedGoogle Scholar
  • 2a Larksarp C. Alper H. J. Org. Chem.  1999,  64:  9194 
    CrossrefGoogle Scholar
  • 2b Boontheung P. Perlmutter P. Tetrahedron Lett.  1998,  39:  2629 
    CrossrefGoogle Scholar
  • 2c Kamal A. Rao AB. Sattur PB. Tetrahedron Lett.  1987,  28:  2425 
    CrossrefGoogle Scholar
  • 2d Kemp DS. Duclos JM. Bernstein Z. Welch WM. J. Org. Chem.  1971,  36:  157 
    CrossrefGoogle Scholar
  • 2e May EL. J. Med. Chem.  1967,  10:  505 
    CrossrefGoogle Scholar
  • 2f Miyano M. J. Am. Chem. Soc.  1965,  87:  3958 
    CrossrefGoogle Scholar
  • 2g Stenseth RE. Baker JW. Roman DP. J. Med. Chem.  1963,  6:  212 
    CrossrefGoogle Scholar
  • 3a Barton DHR. Liu W. Chem. Commun.  1997,  571 
    CrossrefGoogle Scholar
  • 3b Pintye J. Fülöp F. Bernáth G. Sohár P. Monatsh. Chem.  1985,  116:  857 
    CrossrefGoogle Scholar
  • 3c Sainsbury M. In Comprehensive Heterocyclic Chemistry   Vol. 3:  Katritzky AR. Rees CW. Pergamon Press; New York: 1984.  p.995-1038  ; and references contained therein.
    CrossrefGoogle Scholar
  • 4 For a demonstration of the synthetic potential of N-2-hydroxyethyl-1,3-oxazinane-2,4-diones see: Kamino T. Murata Y. Kawai N. Hosokawa S. Kobayashi S. Tetrahedron Lett.  2001,  42:  5249 
    CrossrefGoogle Scholar
  • 5 Ozaki S, and Koto K. inventors; Jpn. Tokkyo Koho, JP  19660502. For a patent on their usage as sedatives, hypnotics, anticonvulsants and depressants see: ; Chem. Abstr. 1969, 72, 43701
  • 6 For a review on the use of oxazolidin-2-ones as chiral auxiliaries for asymmetric synthesis see: Ager DJ. Prakash I. Schaad DR. Aldrichimica Acta  1997,  30:  3 
    Google Scholar
  • 7a Evans DA. Bartroli J. Shih TL. J. Am. Chem. Soc.  1981,  103:  2127 
    CrossrefGoogle Scholar
  • 7b Evans DA. Nelson JV. Taber T. Top. Stereochem.  1982,  13:  1 
    CrossrefGoogle Scholar
  • 7c Davies SG. Nicholson RL. Smith AD. Org. Biomol. Chem.  2004,  2:  3385 
    CrossrefGoogle Scholar
  • 8a Nerz-Stormes M. Thornton ER. J. Org. Chem.  1991,  56:  2489 
    Article in Thieme ConnectGoogle Scholar
  • 8b Evans DA. Rieger DL. Bilodeau MT. Urpi F. J. Am. Chem. Soc.  1991,  113:  1047 
    Article in Thieme ConnectGoogle Scholar
  • 8c Yan TH. Tan CH. Lee HC. Lo HC. Huang TY. J. Am. Chem. Soc.  1993,  115:  2613 
    Article in Thieme ConnectGoogle Scholar
  • 8d Crimmins MT. She J. Synlett  2004,  1371 
    Article in Thieme ConnectGoogle Scholar
  • 9 Kagoshima H. Hashimoto Y. Ogura D. Saigo K. J. Org. Chem.  1998,  63:  691 
    CrossrefGoogle Scholar
  • 10 Walker MA. Heathcock CH. J. Org. Chem.  1991,  56:  5747 
    CrossrefGoogle Scholar
  • 11 Gabriel T. Wessjohann L. Tetrahedron Lett.  1997,  38:  4387 
    CrossrefGoogle Scholar
  • 12 Evans DA. Tedrow JS. Shaw JT. Downey CW. J. Am. Chem. Soc.  2002,  124:  392 
    CrossrefGoogle Scholar
  • For previous reports where these type of 1,3-oxazinane-2,4-diones were formed as unwanted products of other types of synthetic transformation see:
  • 13a Mickel SJ. Sedelmeier GH. Niederer D. Schuerch F. Koch G. Kuesters E. Daeffler R. Osmani A. Seeger-Weibel M. Schmid E. Hirni A. Schaer K. Gamboni R. Bach A. Chen S. Chen W. Geng P. Jagoe CT. Kinder FR. Lee GT. McKenna J. Ramsey TM. Repiè O. Rogers L. Shieh W.-C. Wang R.-M. Waykole L. Org. Proc. Res. Dev.  2004,  8:  107 
    CrossrefGoogle Scholar
  • 13b Keck GE. Lundquist GD. J. Org. Chem.  1999,  64:  4482 
    CrossrefGoogle Scholar
  • 13c Narasaka K. Yamamoto I. Tetrahedron  1992,  48:  5743 
    CrossrefGoogle Scholar
  • 14 For a report where reaction of the boron enolate of a related N-propionyl-1,3-oxazinan-2-one with benzaldehyde in the presence of excess Bu2BOTf resulted in a rearranged 1,3-oxazinane-2,4-dione product see: Abbas TR. Cadogan JIG. Doyle AA. Gosney I. Hodgson PKG. Howells GE. Hulme AN. Parsons S. Sadler IH. Tetrahedron Lett.  1997,  38:  4917 
    CrossrefGoogle Scholar
  • 15 Kende AS. Kawamura K. DeVita RJ. J. Am. Chem. Soc.  1990,  112:  4070 
    CrossrefGoogle Scholar
  • 16 Ito Y. Terashima S. Tetrahedron  1991,  47:  2821 
    CrossrefGoogle Scholar
  • 18 These conditions have been employed previously for asymmetric syn-aldol reactions using imidazolidin-2-one derived glycine enolates, see: Caddick S. Parr NJ. Pritchard MC. Tetrahedron Lett.  2000,  41:  5963 
    CrossrefGoogle Scholar
  • 19 We have reported previously on a single example of this rearrangement see: Feuillet FJP. Robinson DEJE. Bull SD. Chem. Commun.  2003,  2184 
    CrossrefGoogle Scholar
  • 24 A similar reversible retro-aldol/aldol mechanism has been proposed to explain the diastereoselectivity observed for reaction of metal enolates of N-acyl-oxazolidin-2-ones with ketones, see: Bartroli J. Turmo E. Belloc J. Forn J. J. Org. Chem.  1995,  60:  3000 
    Google Scholar
17

Representative Synthetic Protocol for syn -Aldol Reactions.
A 0.5 M solution of 9-BBN·OTf in hexanes (1.2 equiv) was added to a stirred solution of N-acyloxazolidin-2-one (1 equiv) in CH2Cl2 at 0 °C and allowed to stir for 5 min. N,N-Diisopropylethylamine (1.4 equiv) was added, the reaction stirred for 25 min at 0 °C and cooled to -78 °C. An aldehyde (1.1 equiv) was then added, the reaction was stirred for 2 h and the reaction then allowed to warm to 0 °C for 30 min. Then, pH 7.0 phosphate buffer was added, followed by a 2:1 solution of MeOH-H2O2. The reaction was extracted with CH2Cl2 (3 ×) and the combined organic extracts washed with aq NaHCO3, brine, dried (MgSO4) and concentrated in vacuo to afford the appropriate syn-aldol which was then purified by chromatography.

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Representative Synthetic Protocol for Rearrangement Reaction.
A 1.0 M solution of Et2Zn in toluene (0.1 equiv) was added dropwise to a stirred solution of the syn-aldol (1 equiv) in CH2Cl2 at r.t. The reaction was stirred for 2 h. Then, sat. aq NH4Cl was added and the reaction extracted with CH2Cl2 (3 ×). The combined organic extracts were washed with brine, dried (MgSO4), and concentrated in vacuo to afford the desired syn-1,3-oxazinane-2,4-dione which was then purified by chromatography.

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All new compounds were fully characterised. Selected data for new compounds:
syn -6-Ethyl-3-(2-hydroxyethyl)-5-isopropyl-1,3-oxazinane-2,4-dione (10b): 1H NMR (300 MHz, CDCl3): δ = 0.97 [3 H, d, J = 7.0 Hz, CH(CH 3)2], 1.00 (3 H, t, J = 7.5 Hz, CH2CH 3), 1.02 [3 H, d, J = 7.0 Hz, CH(CH 3)2], 1.60 (1 H, dqd, J = 14.0, 7.5, 5.0 Hz, CH AHBCH3), 1.80 (1 H, ddq, J = 14.0, 9.0, 7.5 Hz, CHA H BCH3), 2.08-2.21 [1 H, m, J = 7.0, 5.0, CH(CH3)2], 2.25 (1 H, br s, OH), 2.52 (1 H, dd, J = 5.0, 4.0 Hz, CHi-Pr), 3.74 (2 H, app t, J = 5.5 Hz, CH 2OH), 3.89 (1 H, app dt, J = 14.0, 5.5 Hz, CH A HBN), 4.01 (1 H, app dt, J = 14.0, 5.5 Hz, CHA H B N), 4.39 (1 H, ddd, J = 9.0, 5.0, 4.0 Hz, CHO). 13C NMR (100 MHz, CDCl3): δ = 9.0, 18.8, 21.2, 22.3, 14.5, 43.1, 48.4, 59.8, 78.0, 151.6, 170.0. IR: 3436 (br, OH), 1749 (C=O), 1691 (C=O) cm-1.
syn -3-(2-Hydroxyethyl)-5-isopropyl-6-[( E )-1-propenyl]-1,3-oxazinane-2,4-dione (10d): 1H NMR (300 MHz, CDCl3): δ = 0.97 [3 H, d, J = 7.0, CH(CH 3)2], 1.03 [3 H, d, J = 7.0 Hz, CH(CH 3)2], 1.71 (3 H, d, J = 7.0 Hz, CH 3CH=CH), 1.97 (1 H, t, J = 5.5 Hz, OH), 2.10 [1 H, m, J = 7.0 Hz, CH(CH3)2], 2.55 (1 H, dd, J = 7.0, 4.5 Hz, CHi-Pr), 3.74 (2 H, app dt, J = 5.5, 5.5 Hz, CH 2OH), 3.94-3.98 (2 H, m, CH 2N), 4.92 (1 H, app t, J = 7.0 Hz, CHO), 5.47 (1 H, ddd, J = 15.0, 7.0, 1.5 Hz, CH3CH=CH), 5.91 (1 H, dq, J = 15.0, 7.0 Hz, CH3CH=CH). 13C NMR (75 MHz, CDCl3): δ = 17.0, 19.7, 20.3, 24.8, 43.2, 49.5, 60.1, 76.6, 122.1, 132.7, 151.3, 169.7. IR: 3430 (br, OH), 1755 (C=O), 1699 (C=O) cm-1. (5 S ,6 R )-3-[( S )-1-Benzyl-2-hydroxyethyl]-6-ethyl-5-methyl-1,3-oxazinane-2,4-dione (10e): [α]D 20 -6.4 (c 0.47, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 0.82 (3 H, t, J = 7.5 Hz, CH2CH 3), 0.99 (3 H, d, J = 7.5, CH 3CH), 1.33 (2 H, m, CH 2 CH3), 2.50 (1 H, qd, J = 7.5, 3.5 Hz, CHCH3), 2.99 (1 H, dd, J = 14.0, 7.0 Hz, PhCH ACHB), 3.16 (1 H dd, J = 14.0, 10.5 Hz, PhCHACH B), 3.68 (2 H, obscured m, CHO), 3.82 (1 H, dd, J = 12.0, 4.0 Hz, CH AHBOH), 4.01 (1 H, dd, J = 12.0, 7.0 Hz, CHA H BOH), 5.04 (1 H, app dtd, J = 10.5, 7.0, 4.0 Hz, CHN), 7.10-7.15 (5 H, m, Ph). 13C NMR (75 MHz, CDCl3): δ = 9.2, 9.5, 22.6, 33.7, 39.2, 56.5, 63.3, 78.4, 126.6, 128.5, 129.1, 137.4, 151.8, 173.1. IR: 3462 (br, OH), 1755 (C=O), 1700 (C=O) cm-1.
(5 S ,6 R )-3-[( S )-1-Benzyl-2-hydroxyethyl]-6-ethyl-5-isopropyl-1,3-oxazinane-2,4-dione (10h): [α]D 20 -6.8 (c 0.59, CH2Cl2). 1H NMR (300 MHz, CDCl3): δ = 0.84 (3 H, t, J = 7.5 Hz, CH2CH 3), 0.85 [3 H, d, J = 7.0 Hz, CH(CH 3)2], 0.92 [3 H, d, J = 7.0 Hz, CH(CH 3)2], 1.31-1.46 (1 H, dqd, J = 14.0, 7.5, 5.0 Hz, CH AHBCH3), 1.45-1.61 (1 H, m, CHA H BCH3), 1.94-2.05 [1 H, m, CH(CH3)2], 2.18 (1 H, app t, J = 4.5 Hz, CHi-Pr), 2.53 (1 H, br s, OH), 2.99 (1 H, dd, J = 14.0, 7.0 Hz, CH AHBPh), 3.13 (1 H, dd, J = 14.0, 10.5 Hz, CHA H BPh), 3.64 (1 H, obscured m, CHO), 3.82 (1 H, dd, J = 12.0, 4.0 Hz, CH AHBOH), 4.02 (1 H, dd, J = 12.0, 7.0 Hz, CHA H BOH), 5.04-5.14 (1 H, app dtd, J = 10.5, 7.0, 4.0 Hz, CHN), 7.08-7.22 (5 H, m, Ph). 13C NMR (75 MHz, CDCl3): δ = 10.4, 20.2, 22.6, 23.4, 25.5, 34.3, 50.2, 56.5, 63.7, 79.4, 127.0, 128.9, 129.5, 135.0, 152.5, 171.4. IR: 3423 (br, OH), 1754 (C=O), 1691 (C=O) cm-1.
syn -3-(2-Hydroxyethyl)-5-methyl-6-phenyl-1,3-oxazinane-2,4-dione (10i): 1H NMR (300 MHz, CDCl3): δ = 1.01 (3 H, d, J = 7.5 Hz, CH 3), 2.17 (1 H, s, OH), 2.99 (1 H, qd, J = 7.5, 3.5 Hz, CHCH3), 3.75-3.82 (2 H, m, CH 2OH), 3.97 (1 H, app dt, J = 14.0, 5.5 Hz, CH A HBN), 4.05 (1 H, app dt, J = 14.0, 5.5 Hz, CHA H B N), 5.62 (1 H, d, J = 3.5 Hz, CHO), 7.24-7.38 (5 H, m, Ph-H). 13C NMR (75 MHz, CDCl3): δ = 10.4, 41.5, 44.6, 61.2, 78.1, 126.0, 129.2, 129.4, 134.4, 152.4, 173.2. IR: 3447 (br, OH), 1755 (C=O), 1703 (C=O) cm-1.
syn -3-(2-Hydroxyethyl)-5-isopropyl-6-(4-methoxy-phenyl)-1,3-oxazinane-2,4-dione (10k): mp 79-81 °C. 1H NMR (300 MHz, CDCl3): δ = 0.87 [3 H, d, J = 7.0 Hz, CH(CH 3)2], 0.98 (3 H, d, J = 7.0 Hz, CH(CH 3)2], 1.96 [1 H, m, J = 7.0, 4.0 Hz, CH(CH3)2], 2.26 (1 H, br s, OH), 2.79 (1 H, t, J = 4.0 Hz, CHi-Pr), 3.83 (3 H, s, ArOCH 3), 3.81-3.87 (2 H, m, CH 2OH), 4.02 (1 H, app dt, J = 14.0, 5.5 Hz, CH A HBN), 4.16 (1 H, app dt, J = 14.0, 5.5 Hz, CHA H B N), 5.71 (1 H, d, J = 4.0 Hz, CHO), 6.94 (2 H, d, J = 8.5 Hz, Ar-H), 7.29 (2 H, d, J = 8.5 Hz, Ar-H). 13C NMR (75 MHz, CDCl3): δ = 19.8, 23.1, 26.0, 44.7, 52.0, 55.7, 61.3, 78.4, 114.6, 126.7, 127.1, 152.9, 160.1, 171.4. IR: 3353 (br, OH), 1740 (C=O), 1691 (C=O) cm-1.

22

syn-1,3-Oxazinane-2,4-diones exhibit J ( 5,6) coupling constants of <4.5 Hz, whilst anti-1,3-oxazinane-2,4-diones exhibit J ( 5,6) coupling constants of >10.0 Hz; see ref. 13c, 14, 16.

23

An alternative mechanism involving zinc alkoxide-catalysed epimerisation of the α-stereocentres of syn-β-aryl-aldols 9i-l (or syn-β-aryl-1,3-oxazinane-2,4-diones 10i-l) was discounted because their acidities are similar to those of the α-stereocentres of syn-β-alkyl-aldols 9a-k that had been shown to rearrange with no loss of stereocontrol under these conditions.

25

N-Acyl-oxazolidin-2-one-anti-aldol 15 was prepared using Evans’ magnesium halide-catalysed protocol, see ref. 12.

26

anti -3-(2-Hydroxyethyl)-5-methyl-6-phenyl-1,3-oxazinane-2,4-dione (16). 1H NMR (300 MHz, CDCl3): δ = 1.02 (3 H, d, J = 7.0 Hz, CH 3), 2.21 (1 H, br s, OH), 2.89 (1 H, dq, J = 11.5, 7.0 Hz, CHCH3), 3.77-3.80 (2 H, app t, J = 5.5 Hz, CH 2OH), 3.94 (1 H, dt, J = 14.0, 5.5 Hz, CH A HBN), 4.06 (1 H, app dt, J = 14.0, 5.5 Hz, CHA H B N), 5.04 (1 H, d, J = 11.5 Hz, CHPh), 7.24-7.38 (5 H, m, Ph-H). 13C NMR (75 MHz, CDCl3): δ = 10.1, 40.4, 43.5, 59.6, 80.5, 126.1, 127.9, 128.7, 134.2, 151.1, 170.5. IR: 3435 (br, OH), 1755 (C=O), 1694 (C=O) cm-1.