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

SILYLATION OF NITRO COMPOUNDS AS A PROCESS 623
In recent years, silylation of six-membered cyclic nitronates has been comprehensively
studied by Russian researchers in collaboration with Prof. Denmark
(264, 472). This process is mechanistically shown in Scheme 3.202.
As in the case of double silylation of AN, the formation of target enamines
(343) is accompanied by side processes, which should be minimized when
developing convenient procedures for the synthesis of nitroso acetals (343).
First, it should be noted that the starting nitronates (342) or target nitroso
acetals (343) can undergo stereoisomerization under the action of electrophiles,
which can be accompanied by reversible cleavage of the endocyclic N–O bond
reactions (342⇆342’)or(343⇆343’). To suppress these processes, it is necessary
to perform the transformation (342→343) under conditions as mild as possible
and to use a silylating agent containing a small excess of a base.
Second, one should take into account the stability of nitroso acetals (343)
associated with the possibility of their rearrangement to give oxazines (344). In
addition, it should be taken into account that cyclic nitroso acetals (343) can
be transformed into halo derivatives of dihydrooxazines (345). (These transformations
of nitroso acetals (343) will be considered in more detail in Section
3.5.4.3.3.)
Taking into account all the aforesaid, simple procedures were developed for
preparation of most six-membered cyclic nitronates. These procedures allow
one to stereo- and regioselectively synthesize the corresponding cyclic nitroso
acetals (343), which retain the conÞgurations of the stereocenters of the starting
nitronates (342) (see Table 3.19) (264, 472–474). It should be emphasized that,
in the presence of the substituent R 1 , the internal C,C double bond in the resulting
nitroso acetals (343) always is of trans conÞguration.
For silylation of six-membered cyclic nitronates (342), the inßuence of the
nature of base on the regioselectivity of the synthesis of nitrosals (343) was
studied in sufÞcient detail. Intermediate cations A can be deprotonated at the
α-C atom of the substituent at C-3 as well as the C-4 atom (see Scheme 3.202
and Table 3.20) (264, 474).
It appeared that triethylamine is the base of choice for generating nitrosals
(343). However, sterically less hindered amines deprotonate the C-4 atom to
give, after retro-[4 + 2]-cycloaddition of the intermediate enamines (346), the
corresponding conjugated enoximes (347).
Interestingly, nitrogen bases containing the strongly shielded nitrogen atom
give not nitroso acetals but instead the corresponding enamines, which substantially
decreases the rate of this reaction (see entries 3 and 4 in Table 3.20). For
unknown reasons, silylation of nitronates (342t,u) with Me3SiBr/Et3N also leads
to deprotonation at the C-4 atom.
Silylation of 3-alkyl-substituted Þve-membered cyclic nitronates remains virtually
unknown, although one example of the successful synthesis of the corresponding
nitroso acetal was documented (Scheme 3.203) 475.
Recall that, unlike six-membered analogs, N-oxyisoxazolines-3 are quite stable
(see Scheme 3.111 and Reference 82).