Addition of Hydroxylamines to DE-Unsaturated Esters 51
If the reaction between cinnamate 1 and hydroxylamines occurred through a
concerted mechanism, the process should take place through a cyclic (five-memd
bered ring) transition state, similar to the ones proposed for [3+2] dipolar cycloadditions or retro-Cope eliminations. The cyclic transition state for the concerted addition of deuterated N-methylhydroxylamine N N
to ethyl cinnamate 1 is represented in
Scheme 8.7 (atoms involved in the cyclization colored blue). As the nitrogen atom
and the deuterium approach the C=C bond from the same side, the addition is syn,
leading to intermediate 12. A rapid proton shift would give compound 3 which can
be either isolated or cyclized in the presence of a Lewis acid to the isoxazolidinone 4 by intramolecular transesterification. The stereochemistry of the products 3
and 4 is determined during the concerted addition step.
N
O
D
Ph
H
H
C O O E t
Me
D
COOEt
H
H
Ph h
N
O
D
Me
D
D
N
O
Ph
Me
H
H
D
O
D
N
Ph
H
COOEt
H
OD
Me
D
N
Ph
H
COOEt
H
O O
Me
D
G
G
1
12
3
4
Scheme 8.7
A similar process would explain the trans-stereochemistry of 6, the product obtained in the reaction between hydroxylamine and deuterated cinnamate 5
(Scheme 8.8, labeled atom in red). The nitrogen atom and the proton are incorporated to the C=C bond from the same side, leading to intermediate 13 that after a
rapid proton shift and cyclization would give isoxazolidinone 6. The addition of
the reagent is also syn, but in this case leading to the cyclic trans-isomer.
As we have commented before, the transition state of a concerted process is little influenced by a change in solvent polarity. This fact could fit with the insensitivity of the reaction with the change of the solvent from THF to the more polar
EtOH.