Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis : Novel ...

704 NITRONATES
The possibility of using these salts (513) in organic synthesis was exempliÞed
by the synthesis of amino oxazole (515) through ammonium salt (513a) (Scheme
3.267).
3.5.4.3.3. Synthesis of 5,6-Dihydro-4H-Oxazines Containing Functionalized Substituents
at the C-3 Atom Unlike BENAs, six-membered cyclic nitroso acetals
do not form quaternary ammonium salts in the reactions with SiX/Nu. §
The reactions of enamines (516) with trialkylsilyl halides in the presence of
triethylamine (or other nitrogen bases) produce 3-halomethyl-substituted oxazines
(517) (or 517 ′ ) in good yields (Scheme 3.268) (472).
It is very likely, that this reaction occurs due to the equilibrium between
trimethylsilyl halide and a nitrogen-containing nucleophile, which increases the
electrophilicity of silyl Lewis acids. It should be noted that the conÞguration of
stereocenters at the carbon atoms of the oxazine ring is partially distorted. Hence,
it is assumed that the reaction proceeds through the intermediate cation B, which
is partially isomerized into the stereoisomeric cation B ′ through the “open chain”
cation B ′′ .
Oxazines (517) can be prepared in somewhat lower yields directly from
six-membered cyclic nitronates (518) without isolation of the corresponding
nitroso acetals (516) (see Table 3.36).
The reactions (518→517 + 517 ′ )or(518→516→517 + 517 ′ ) are complex processes
and require optimization and the use of special procedures in each particular
case. If the starting nitronates or nitroso acetals are unsubstituted at the
C-3 atom, the target 3-halomethyl-oxazines can be synthesized in satisfactory
yields, although diastereomers (517) and (517 ′ ) are unseparable in some cases.
In the presence of a substituent R ′ (see entry 14), the yield of the product is
substantially lower, whereas the reaction is diastereoselective.
Halomethyl-substituted oxazines (517) can be considered as the key intermediates
in many strategies for organic synthesis. However, the lack of a convenient
procedure for generating these compounds undoubtedly delayed studies on their
possible use. Actually, very unstable α-halomethylnitroso alkenes could serve
as the only source of such products (537). The approach developed by Russian
chemists (472, 473) enables the synthesis of these products from stable and
available AN.
The advantages of this approach were provided by nitroethane (473)
(Scheme 3.269). A series of stereoisomerically pure six-membered cyclic
nitronates (519) were synthesized from nitroethane and other available AN, and
§ The only salt of this type was prepared by reßuxing of N -methylimidazole with
3-bromomethyl-6,6-dimethyl-4-phenyl-5,6-dihydro-4H -oxazine in toluene for 5 h (473).
Ph
O N
Br
N
N
−
+
99%