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

252 NITRONES: NOVEL STRATEGIES IN SYNTHESIS
2.6.6.1.2. Addition of Heterocyclic Compounds Stereocontrolled nucleophilic
addition of heterocyclic compounds to chiral nitrones is of great synthetic importance
in the synthesis of natural and biologically active compounds. In these
reactions, the nitrone group serves as an amino group precursor and the heterocycle
furnishes the formyl group (from thiazole) (192, 195, 214, 215, 579) or the
carboxyl group (from furan) (194–196, 580–584) (Scheme 2.149).
In most cases, the stereochemical course of heterocyclic addition can be altered
by pre-complexation of nitrones with Lewis acids. In the absence of complexation
agents (Et2AlCl, TiCl4), addition of lithio-hetaryl derivatives to chiral β-alkoxy
nitrones (292a–d) gives β-alkoxy-α-hydroxylamino-2-alkylhetaryls (346a–d) in
good yields with syn-selectivity. In the presence of diethylaluminum chloride
the reaction leads to the same adducts, but with anti-selectivity (Scheme 2.150)
(Table 2.12) (581).
O
+ −
Sugar CH = N(O)R
O
R
292 a−d
O
N
+
Bn
N
S Li
O Li
Scheme 2.149
O Li
see Table 6.4
R = a: H; b: CH2OBn; c: CH2OSiMe2Bu O
t ; d:
−
Scheme 2.150
O
Sugar CH CHO
NH 2
Sugar CH CO2H
O
NH2
O
R
O
O
N(OH)Bn
R
syn-346 a−d
O
+
O
N(OH)Bn
anti-346 a−d