A Convenient Procedure for the Synthesis of Substituted 3-α-Haloalkyl-5,6-dihydro-4H-1,2-oxazines

Abstract

A general and convenient method for the synthesis of the scarcely known 3-α-haloalkyl-5,6-dihydro-4H-1,2-oxazines 2 via silylation of the corresponding six-membered cyclic nitronates 1 or the first obtained 2-silyloxy-1,2-oxazines 3 by Me₃SiX/Et₃N (X = Cl or Br) is elaborated.

Key words

aliphatic nitro compounds - 5,6-dihydro-4H-1,2-oxazine N-oxides - 2-silyloxy-1,2-oxazines - 3-α-haloalkyl-5,6-dihydro-4H-1,2-oxazines - silylation

References

• 1 Denmark SE. Thorarensen A. Chem. Rev.  1996,  96:  137 
• 3 Tishkov AA. Lesiv AV. Khomutova YA. Strelenko YA. Nesterov ID. Antipin MY. Ioffe SL. Denmark SE. J. Org. Chem.  2003,  68:  9477 
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• 6a It is of interest to note that N,N-bis(silyloxy)enamines investigated by us recently gave as a rule quaternary ammonium salts instead of corresponding halosubstituted oximes under conditions shown in Scheme 2 and Table 1. For example, see: Dilman AD. Tishkov AA. Lyapkalo IM. Ioffe SL. Strelenko YA. Tartakovsky VA. Synthesis  1998,  181 
• 6b There is only one case known of generation of corresponding α-chlorooxime after silylation of methyl β-nitrobutyrate with Me₃SiCl/Et₃N: Danilenko VM. Strelenko YA. Karpenko NF. Ioffe SL. Tartakovsky VA. Bull. Acad. Sci. Div. Chem. Sci.  1989,  38:  1105 ; Chem. Abstr. 1990, 112, 35956
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• 15 Interestingly, the known C,C-coupling of N,N-bis(silyloxy)enamines with stabilized carbanions (see Dilman AD. Lyapkalo IM. Ioffe SL. Strelenko YA. Tartakovsky VA. Synthesis  1999,  1767 ) cannot be transferred to analogous enamines 3. Therefore, the preparation of oxazine 8 via intermediate halooxazine 2k seems to be the only convenient procedure for the synthesis of 5,6-dihydro-4H-1,2-oxazines containing functionalized substituent at C-3
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2

Smirnov, V. O.; Ioffe, S. L.; Tishkov, A. A.; Khomutova, Y. A.; Nesterov, I. D.; Antipin, M. Y.; Smit, W. A.; Tartakovsky, V. A. Angew. Chem. submitted.

7

Although pyridine is more efficient than Et₃N (see Table [2] ) it is not recommended owing to possible C-4 deprotonation (see also ref. [3] ).

10

CCDC 230282 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by e-mail to [e-mail], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: [phone].

14

The interaction of enamines 3 with Me₃SiCN gives not oxazines 7, but leads to another product, which contains a fragment of 5-aminoizoxazole. This reaction will be discussed in our following publications.

19

NMR spectra of enamines 3d,e,i are broadened (at 300 K) due to dynamic process (for details, see Ref. [3] and our next publication).