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

SILYLATION OF NITRO COMPOUNDS AS A PROCESS 681
which are silylated with SiN< to form a mixture of silylated and free α-amino
oximes. The latter can be subjected to desilylation with methanol or analogous
agents. This process is accompanied by the side reaction of nitroso intermediate
B with silanol, which yields oximes (455) or its bis-silyl derivatives (456)
corresponding to the rearrangement product of BENA (see Section 3.5.1.2).
According to these concepts, the reaction shown in Scheme 3.243 could be
characterized by the presence of an induction period. Silyl derivatives of amines
( > N-Si) are not involved in this reaction. The sterically hindered triorganosilyl
substituents in BENAs (434) also should inhibit the process.
German researchers, who were the Þrst to discover BENAs (464), demonstrated
that BENAs (434) (both terminal and internal) readily react with secondary
amines to give, after aqueous treatment, the corresponding amino oximes (457)
in yields from moderate to high (Scheme 3.244).
The presence of sterically hindered substituents in amines leads to a decrease
in the yield of target products.
The reactions of primary amines with BENAs proceed in a more complex fashion
(499, 521). In the absence of steric hindrance in the amine, terminal BENAs
are readily and rapidly involved in double β-oximino-alkylation with primary
amines (Scheme 3.245, product A ′ ). To stop the process at the mono-alkylation
step (intermediate A), a large excess of amine should be used.
Intermediates A and A ′ can be separated by two procedures: complete silylation
of these derivatives followed by fractionation of silylated amino oximes (458)
or by complete desilylation of these intermediates followed by chromatographic
puriÞcation of the amino oximes (459).
The N,C -coupling reactions of primary amines with BENAs are very sensitive
to steric factors in BENAs. For example, the reactions with terminal BENAs are
difÞcult to stop at the mono-alkylation step, whereas in internal BENAs, it is very
difÞcult to isolate the bis-coupling product. A special procedure, based on this
fact, enables one to synthesize bis-oximes (460) containing various oximinoalkyl
substituents at the nitrogen atom. It should be emphasized that diastereoselectivity
of N,C -coupling reactions of amines with terminal BENA is very low.
R 3
R 3
For R1 = R2 = H : R3 and R4 –(CH2) 4 –(64%), –(CH2) 5 –(79%), –(CH2) 2–O–(CH2) 2–(68%),
R3 = R4 = Pri (33%).
For R1 = H; R2 = Me : R3 and R4 –(CH2)5– (58%).
For R1 = Me; R2 = H : R3 and R4 R
–(CH2)5– (81%).
1 R
N(OSiMe3)2
434
2
R2 N R1 N H
R
N
4
R4 OX
R2 N R1 R
N
457
4
H2O
X = H or Me3Si
OH
Scheme 3.244
R 3