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

SILYLATION OF NITRO COMPOUNDS AS A PROCESS 691
monitoring. Methanolysis of these intermediates affords oximes (480) containing
the carbonyl group or their respective cyclic ethers 481. The tautomeric equilibria
(477)⇄(478) and (480)⇄(481) were observed by NMR. If NuH is n-BuNH2,
oximes (480) can be cyclized into derivatives of tetrahydropyridine (482).
If the alkoxy group at the C-6 atom in nitroso acetals (475) is absent, silyl
derivatives (476) are generated instead of nitroso ketones A ′ , and methanolysis
of compounds (476) gives rise to γ-hydroxy oximes (479).
Generally, the N,C-coupling reactions of compounds (475) with nucleophiles
are performed at 20 ◦ C in dichloromethane in the presence of 5% triethylamine
or N-methylimidazole.
Hence, oximes (476) to(482) are the major products of this reaction sequence
(Table 3.34).
In many cases, the yields of these products are high. However, the use of
N-silylated triazoles as nucleophiles or the use of cyclic nitroso acetals (475) substituted
at the C-3 atom leads to a noticeable decrease in the yield of the oximes.
Therefore, steric hindrance in nitroso acetals and a decrease in nucleophilicity of
N -centered nucleophiles result in an increase in the contribution of side reactions.
It should be emphasized that C -nucleophiles, such as anions of nitro compounds,
are not involved in coupling reactions with cyclic nitroso acetals (475). However,
the products, which formally correspond to the C,C-coupling mechanism, can be
prepared by the nucleophilic substitution of chlorine in compound (476 d) bya
SN2 mechanism (Scheme 3.254, product (483c), the yield was 79%).
The nucleophilic substitution of halogen by the CN − or N3 − anions in product
(476 d) provides an alternative route to bis-silyl derivatives of oximes (476a)
and (477a) (cf. entries 7 and 10, Table 3.34). Interestingly, desilylation of these
products can be performed in steps by removing silyl protecting groups from the
oximino and hydroxyl groups successively.
An efÞcient procedure for the synthesis of 5-aminoisoxazoles starting from
BENAs (Scheme 3.242) was described in Section 3.5.4.2.2.1. An analogous
approach to the synthesis of aminooxazoles can be successfully used in the case
of silyl derivatives of α-cyano-substituted oximes (476a,b) (Scheme 3.255).
It should be noted that one of the N,C-coupling reactions, involving cyclic
nitroso acetals, cannot be explained by a traditional explanation involving inter-
mediate conjugated nitrosoalkenes (Scheme 3.256).
It cannot be ruled out that this reaction occurs by an SN2 ′ mechanism, which
has been proposed many times earlier for the interpretating the reactions of nucleophiles
with BENA (see, e.g., Scheme 3.236). The removal of the Me3Si group
from nitroso acetals is facilitated by the contribution of the π→σ* interaction.
The reaction shown in Scheme 3.256 is highly diastereoselective.
3.5.4.2.4. Behavior of BENA in Radical Reactions Until recently, data on the
behavior of BENAs in radical reactions have been lacking in the literature. However,
several successive approaches to radical alkylation of BENA at the β-C
atom have been recently developed by Korean researchers (527).