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

NITRONE REACTIONS 227
This reaction is very important for the synthesis of natural products and for the
design of diversely substituted ligands. The use of SmI2 in radical additions of
nitrones to α,β-unsaturated amides and esters, constitutes a convenient synthesis
of various functionalized γ-amino acids with high enantiomeric excess (Schemes
2.114 and 2.115) (531–533).
Reductive coupling of the corresponding nitrones with alkyl acrylate is the key
step in the short synthetic route of the selective and irreversible GABA inhibitor
of amino transferase (S)-vigabatine (534) and of polyhydroxy pyrrolizidine alkaloid
( + )-hyacinthacine A2 (535).
Using N-tert-butanesulÞnilimines instead of carbonyl derivatives, constitutes
an efÞcient synthetic route to optically pure asymmetric vicinal diamines that are
widely used in asymmetric synthesis (Scheme 2.116) (536).
2.6.5. Electrophilic Reactions of Nitrones
2.6.5.1. Reactions of Electrophilic Substitution of α-Alkyl Nitrones
2.6.5.1.1. Reactions of Halogenation and Nitrosation Nitrones with protons in
the α-alkyl group can occur in tautomeric nitrone–hydroxylamine equilibrium
(Scheme 2.117) similar to keto-enol and imine-enamine tautomerisms.
Generation of the enhydroxyamine form takes place upon treatment with both
bases and acids; the reaction with α-alkyl nitrones in D2O shows a quick deutero
exchange (537).
The reaction of nitrones of the 3-imidazoline series (295) with bromine and
amyl nitrite, in the presence of base, gives α-tribromomethyl-(296) and αhydroxyaminomethyl
derivatives (297) (538). Bromination of nitrones (295) with
N -bromosuccinimide (NBS) in CCl4 or bromine in methanol leads to the formation
of α-bromoalkyl (298 a,b, Hal= Br) and α-dibromomethyl (299) nitrones
(539–541). The reaction with iodine in methanol gives the mono iodo derivative
(300) (541). The reaction with N -chlorosuccinimide (NCS) in CCl4 leads
to α-chloroethyl nitrones (298b, Hal= Cl) and α,α-dichloromethyl nitrones (301)
(Scheme 2.118) (225).
Nitrosation in acid medium of α-bromomethyl nitrone (298a) affords the
chloro anhydride of hydroxymic acid (302), which is a precursor of nitrile
N -oxide (541).
2.6.5.1.2. Reactions with Aldehydes and Ketones Crotone-type products have
been obtained in reactions of nitrones (295a, R 2 = OH) with p-ethynyl-,
p-bromo-, and p-iodobenzaldehydes (Scheme 2.119) (542, 543).
R
+
N
O −
R
H
R = Alk, Ar, Het
Scheme 2.117
N OH