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Synlett 2006(14): 2239-2240  
DOI: 10.1055/s-2006-949616
LETTER
© Georg Thieme Verlag Stuttgart · New York

Catalytic Carbonylation of 3-Bromomethyl-5,6-dihydro-4H-1,2-oxazines: General Approach to the Synthesis of 3-Methoxycarbonylmethyl-5,6-dihydro-4H-1,2-oxazines from Available Precursors

Oleg L. Eliseev*, Pavel E. Ivashkin, Aduard G. Ostapenko, Alexey V. Lesiv, Yulia A. Khomutova, Sema L. Ioffe*, Albert L. Lapidus
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 119991 Moscow, Russian Federation
Fax: +7(095)1355328; e-Mail: oleg@ioc.ac.ru;
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Publication History

Received 7 June 2006
Publication Date:
24 August 2006 (online)

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Abstract

A general approach to the stereoselective synthesis of previously unknown 5,6-dihydro-4H-1,2-oxazine-3-yl acetates by catalytic carbonylation of available 3-bromomethyl-5,6-dihydro-4H-1,2-oxazines is elaborated.

Key words

1,2-oxazines - carbonylations - palladium

    References and Notes

  • 1 Klenov MS. Lesiv AV. Khomutova YA. Nesterov ID. Ioffe SL. Synthesis  2004,  1159 
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  • 2 Cotel G. Denmark SE. Nitronates In The Chemistry of Heterocyclic Compounds   Vol. 59:  Pawda A. Pearson WH. J. Wiley & Sons Inc.; New York: 2002.  p.83-167  
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  • 3 Lapidus AL. Eliseev OL. Bondarenko TN. Sizan OE. Ostapenko AG. Beletskaya IP. Synthesis  2002,  317 
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  • 5 Hesse M. Meier H. Zeeh B. Spektroskopische Methoden in der Organischen Chemie   Thieme; Stuttgart: 1995.  p.108 
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  • 7 Juaristi E. Enantioselective Synthesis of β-Amino Acids   Wiley-VCH; New York: 1996. 
  • A few successful attempts to prepare α-amino acids from 3-methoxycarbonyl-5,6-dihydro-4H-1,2-oxazines and β-amino acids from 4-methoxycarbonyl-5,6-dihydro-4H-1,2-oxazines were reported previously, see:
  • 8a Chrystal EJT. Gilchrist TL. Stretch W. J. Chem. Res., Synop.  1987,  180 
    Thieme Connect
  • 8b Henning R. Lerch U. Urbach H. Synthesis  1989,  265 
    Thieme Connect
  • 8c Tishkov AA. Reissig H.-U. Ioffe SL. Synlett  2002,  863 
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Compounds 2; General Procedure
Bromide 1 (1.0 mmol), Et3N (1.5 mmol), Pd(PPh3)2Cl2 (0.01 mmol), and MeOH (10 mL) were placed in a stainless steel reactor equipped with a Hastelloy® liner and magnetic stirrer. The reactor was flushed with CO, pressurized (15 bar), and heated to 100 °C with stirring for 3 h. The resulting mixture was evaporated under reduced pressure, treated with an aq solution of NaHSO4 (2 mmol) and extracted with Et2O (3 × 15 mL). The combined extracts were washed with brine (10 mL), dried (Na2SO4), and evaporated under reduced pressure. The residue was subjected to column chromatography on silica gel (Table [1] ).
Methyl [4-(4-methoxyphenyl)-6,6-dimethyl-5,6-dihydro-4 H -1,2-oxazin-3-yl]acetate (2a)
Oil; R f 0.56 (silica gel; hexane-EtOAc, 1:1, UV). 1H NMR (300.13 MHz, CDCl3): δ = 1.36 (s, 6 H, 2 Me), 1.89 (dd, J = 11.8, 13.8 Hz, 1 H, CH2), 2.06 (dd, J = 7.9, 13.8 Hz, 1 H, CH2), 2.95 (d, J = 17.1 Hz, 1 H, CH 2CO2Me), 3.19 (d, J = 17.1 Hz, 1 H, CH 2 CO2Me), 3.64 (s, 3 H, CO2Me), 3.66 (dd, J = 7.9, 11.8 Hz, 1 H, CH), 3.80 (s, 3 H, OMe), 6.87 (d, J = 8.5 Hz, 2 H, Ph), 7.06 (d, J = 8.5 Hz, 2 H, Ph). 13C NMR (CDCl3): δ = 22.6 and 28.4 (2 × Me), 38.5 and 38.7 (2 × CH2), 40.5 (CH), 52.0 (CO2 CH3), 55.3 (OMe), 75.0 (CON), 114.6 (Ph-CH), 129.4 (Ph-CH), 131. 8 (Ph-C), 153.9 (C=NO), 158.9 (COMe), 170.6 (CO2Me). Anal. Calcd for C16H21NO4: C, 65.96; H, 7.27; N, 4.81. Found: C, 66.20; H, 7.35; N, 4.75.