Level 3 – Case 36
242
A An ns sw we er r t to o Q Qu ue es st ti io on n 2 2
Following the VNS mechanism, the first step of the reaction is the nucleophilic
addition of the enolate of ethyl 2-cloropropionate to the nitrobenzene ring (the ester forms the enolate in the reaction medium in the presence of NaH). As stated
above, the ortho/para selectivity in VNS reactions is controlled by steric factors.
Hence, a tertiary carbanion like 8 would attack exclusively in the para-position
leading to V-adduct 9. The next step will be the base-induced elimination of HCl
in 9 to yield anion intermediate 10, which is trapped by the electrophile (benzyl
bromide) giving the reaction product 11 (Scheme 36.6).
NO 2
CO 2 Et
Me
Cl
N
O
O
H
CO 2 Et
Cl
Me
NaH
HCl
N
O
O
CO 2 Et
Me
N
O
O
CO 2 Et
Me
BnBr
NO 2
CO 2 Et
Me
Bn
8
9
10
11
Scheme 36.6
A Ad dd di it ti io on na al l C Co om mm me en nt ts s
This problem is based on the work by Makosza M, Lemek T, Kwast A, Terrier F
(2002) J. Org. Chem. 67:394-400 and by Lawrence NJ, Liddle J, Bushell SM,
Jackson DA (2002) J. Org. Chem. 67:457-464.
S Su ub bj je ec ct ts s o
of f R Re ev vi is si io on n
Nucleophilic aromatic substitutions. Primary and secondary KIEs.