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

(R 1 O)m
O
47
( )n
OH
+ RNHOH
(R 1 O) m
(R 1 O) m
OH
O
48
( )n
( )n
Scheme 2.18
O −
N +
SYNTHESIS OF NITRONES 145
OH
R
N
R
R = Alk
R = H
Ox
R 2 CHO
(R 1 O)m
Oxidation with MnO2 of N-glycosylhydroxylamines (48), obtained in the
reaction of sugars (47), with N-methyl- and N -benzylhydroxylamines, leads selectively
to the corresponding C -unsubstituted and C -phenyl-N -glycosyl nitrones
(49) (Scheme 2.18) (118, 119).
The use of sodium hypochlorite (bleach) as an oxidant was suggested due to
its efÞciency and environmental safety (120). This method can be easily applied
in a large scale production. To catalyze enantioselective oxidation of hydroxylamines
with hydrogen peroxide, sodium hypochlorite, m-CPBA, UHP and PhIO,
Jacobsen’s catalyst (Salen)Mn(III)Complex (Salen ligand: N,N’-bis(salicylidene)
ethylenediamine) was used (121). Using the system, N -tert-butylbenzenesulÞneimidoyl
chloride/diazabicycloundecene (DBU) in CH2Cl2, under mild conditions
(−78 ◦ C), both cyclic and acyclic nitrones have been isolated in high yields
(122). Tetra-n-propylammonium perruthenate (TPAP) is used as a catalyst in
the oxidation of secondary hydroxylamines with NMO (123). In the oxidation
of hydroxylamines into nitrones, polymer supported perruthenate (PSP) was utilized
(124).
Oxidative ring opening of isoxazolidines leads to nitrones. Thus, bicyclic isoxazolidines
(50) and (51), treated with m-CPBA, afford nitrones (52), (53), (54),
and (55) (Scheme 2.19). Conformational analysis has conÞrmed the key role of
the nitrogen lone pair with respect to regioselectivity of the reaction and of the
intramolecular kinetic deprotonation of the intermediate oxoammonium derivative
(125).
Similar oxidative ring opening occurs in other bi- and tricyclic isoxazolidines
upon treatment with m-CPBA (126, 127).
Oxidation with m-CPBA of monocyclic isoxazolidines (56) without H at α-C
gives a tautomeric mixture of acyclic nitrones (57) and six-membered cyclic
hydroxylamines (58), with their proportion depending on the substituents
O
( )n
49
O −
N +
R 2