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

SILYLATION OF NITRO COMPOUNDS AS A PROCESS 699
Table 3.35 Rearrangement of cyclic six-membered N -siloxynitroso acetals 507a–g.
Product Yield,
Entry (508)(507) R 1 R 2 R 3 R 4 R 5 Si Conditions (508) %
1 a H Ph H Me Me TMS TMSOTf, Py,
−78 ◦ C, 1 h
2 b H An –(CH2)4 – H TMS TMSOTf, Py,
−78 ◦ C, 1 h
3 c Me An H OMe Me TMS CHCl3, 20 ◦ C,
24 h
4 d Me An H OEt H TBS CHCl3, 20 ◦ C,
24 h
5 e Me Ph H OMe Me TMS CHCl3, 20 ◦ C,
24 h
6 f 4-Cl-Ph An H OMe Me TBS TBSOTf, Et3N,
−78 ◦ C, 1 h
7 g An An H OMe Me TMS TMSOTf, Et3N,
−78 ◦ C, 24 h
8 h CO2Me An H OMe Me TMS No reaction
TMS–SiMe3, TBS–SiMe2Bu t , An–4-MeO-C6H4; a de > 95%
contrast, internal nitroso acetals 507c–e most readily undergo rearrangements at
ambient temperature in the absence of Lewis acids after storage in chloroform to
give a new stereocenter with very high diastereoselectivity (Table 3.35, entries
3–5). Interestingly, other solvents (hexane or ethyl acetate) do not facilitate the
rearrangement under these conditions. If R 1 is an electron-donating aryl fragment
(see e.g., in product (507 g)), the rearrangement (507→508) can also occur in
the absence of LA. However, to increase the chemoselectivity of the reaction, it
is worthwhile to perform this reaction at lower temperature (see entry 7, Table
3.35).
Entry 8 (Table 3.35) indicates that nitroso acetals (507) containing electronwithdrawing
substituents at the end of the double bond, that is, those having no
considerable π→σ* effect and destabilizing the cationic intermediate A (Scheme
3.260), do not undergo rearrangements into respective α-hydroxy oxime derivatives
at all. It should be noted that the reaction of nitroso acetal (507a) inthe
presence of trißuoroacetic anhydride produces 5,6-dimethyl-4-phenyl-3-trißuoroacetoxymethylene-5,6-dihydro-4H
-oxazine in 85% yield (535).
The reactions of six-membered cyclic nitroso acetals containing an alkoxy
group at C-6 with nucleophiles leads to a very interesting rearrangement (237b)
(Scheme 3.264). Initially, the SiMe3 group is eliminated from nitroso acetal (507i)
to give the anion A, which is stabilized to form nitrosoalkene A ′ by elimination
of the methoxy anion. The A ′ immediately adds MeO − to give anion B which is
silylated by the next nitroso acetal molecule (507i) to give rearrangement product
(508i).
92
66
95 a
74 a
92 a
88 a
88 a