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

NITRONE REACTIONS 237
Nucleophilic addition of organometalic reagents occurs when the nitrone form
is in equilibrium with the hydroxylamine form, for instance, in the case of
N -benzyl-N -glycosyl hydroxylamines (Scheme 2.130) (213).
Addition of organometalic compounds to nitrones is known as an efÞcient
method of enantioselective synthesis of primary amines that can be easily obtained
by the reduction of hydroxylamines which are the products of nucleophilic
addition.
2.6.6.1.1. Addition of Alkyl and Aryl Derivatives To illustrate stereoselective
syntheses in nucleophilic reactions of nitrones, the synthesis of ( + )-lentiginosine
(313) is presented in Scheme 2.131. One of the important steps is the addition
of benzyloxybutylmagnesium bromide to pyrroline-N -oxide (312) (555).
Diastereoselective addition of a wide range of Grignard reagents to C -alkyl
and C -aryl-N -[α-phenyl- or α-methyl-β-(benzyloxy)ethyl]nitrones is determined
by the presence of a stereogenic N -substituent (136, 137). High diastereoselectivity
in the addition of organometalic compounds to N -(β-methoxyalkyl) nitrones
can be explained by a simple chelation model (Scheme 2.132) (136).
Addition of (4-methoxybenzyl)magnesium chloride to the pyrroline derivative
(312) is a key step in the stereoselective synthesis of antibiotics (−)-anisomicine
(314) (52) and (−)-deacetylanisomicine (315) (Scheme 2.133) (200).
R
H Ph
R
H
H
H
Ph
Me
O
L
O Mg
L
O Mg
O
Me
L
L
R
R′MgX H
major
minor
Scheme 2.132
R H
H R
H R
R′ H
O Mg
N
Ph
L
L
H
O Mg
N
Ph
L
L
N
H
R′
R′
Ph
N
R′
O
H
L
OMe
Mg L
OMe
Ph
O
L
OMe
Mg L
OMe