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

SILYLATION OF NITRO COMPOUNDS AS A PROCESS 641
R 1
O2N
372
R2 R4 H2 H 1
R
3 H3
Me 3SiX/Base
R2 R3 R1 R4 O
H
N
Me3SiO O
2
R2 S
R3 R
NO2 1
R4 R
OSiMe3
2
R3 R1 R4 OSiMe3 H
N
Me3SiO O
2
H2 or or
373a 373b 373c
−CH2NO2 pKa ~ 10; CH3COC pKa ~ 20; AlkOCOC pKa ~ 25;
H
Ref.489
Ac2CH2 pKa – 8,9; (EtOCO) 2CH2 pKa 12,9
H
Ref.490
RNO2H + pKa ~ −12; RR′C=OH + pKa ~ −7
Scheme 3.212
involve deprotonation of the nitro fragment to form SENA (373a) astheÞrst
step.IfR 3 is Ac or CO2Alk, the rate of deprotonation of the C-1 atom can be
similar to that of deprotonation of C-3, and it is difÞcult to predict the character
of the primary silylation product. An increase in the strength of the silylating
agent would facilitate the primary attack of a more nucleophilic functional group,
whereas the use of a stronger base can, on the contrary, shift the reaction toward
initial silylation of the nitro fragment.
Double silylation of the nitro fragment of substrate (372) would afford the
[ > C=N(OSi)2] + cation, which should be trapped. To hinder deprotonation of
this cation, the substrate contains a bulky substituent R 2 at the C-2 atom. A priori,
based on the data on intermolecular C,C-coupling of the above-mentioned cations,
it can be suggested that the introduction of substituents at the C-1 atom should
decrease the reactivity of the cation and can adversely affect the thermodynamics
of such cations. Consequently, these substituents would hinder the generation as
well as trapping of cationic intermediates.
In intramolecular trapping of bis-oxyiminium cations, Me3SiBr was used as
the silylating agent, which makes it possible to smoothly perform silylation of
primary AN (see Chart 3.20). A representative group of substrates (372) was
synthesized for intramolecular trapping of cations (488).
3.5.2.4.1. Intramolecular C,C-Coupling of Bis-N,N-(trimethylsiloxy)Iminium
Cations As can be seen from Scheme 3.213, intramolecular C,C-coupling of the
nitro fragment and the acetyl group occurs smoothly upon silylation of substrates
(374) containing the acetyl group at the C-3 atom (153, 292, 470, 489).
O