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

NITRONE REACTIONS 245
Addition of various organometalic reagents to chiral nitrones, derived from
L-erythrulose, proceeds with variable diastereoselectivity, depending on Lewis
acids as additives. ZnBr2 facilitates the attack at the Si face of the C=N bond,
whereas Et2AlCl makes the attack at the Re face more preferable. The obtained
adducts can be transformed into derivatives of N -hydroxy-α,α-disubstitutedα-amino
acids, with their further conversion into α,α-disubstituted α-amino acids
(193, 202).
C -Phenyl-N -erythrosyl nitrone (336), as a C1,C’1-bis-electrophile, when subjected
to the double addition of Grignard reagents (in a domino style), leads to
acyclic hydroxylamine (338) via the formation of open-chain nitrone (337 ′ ). The
reaction proceeds at 0 ◦ C with variable diastereoselectivity ranging from medium
to good, depending on the organometalic reagent used (Scheme 2.140) (564).
As in all cases already mentioned, diastereoselective addition of Grignard
reagents to β-amino nitrones (α-aminoalkyl nitrones) is a key step in the stereocontrolled
syntheses of α,β-diamino acids (Scheme 2.141) (565, 566), of unsymmetrical
α-amino hydroxylamines and 1,2-diamines (Scheme 2.142) (209, 567).
Recently, semiempirical PM3 computational analysis (568) and Þrst ab initio
study (569) of the nucleophilic addition to chiral nitrones of Grignard reagents
have been carried out. The data revealed that all reactions are exothermic and
proceed through pre-complexation of nitrones with the organometalic reagent.
HO R
OH
N
O O
338
R
Ph
O -
O
N
Ph
O
O N
O O O O
RMgX
+
−
+
O
O N
336
excess
RMgX
MgX
Ph
Ph
Ph
XMg
O
−
O +
N
R
O O O O
Scheme 2.140
337 337′
+
−
R