3.2 Rh-Catalyzed C–H Bond Alkylation
47
4 mol % [Cp*RhCl 2 ] 2
16 mol % AgSbF 6
20 mol % PivOH
1,2-DCE, 25 C, 12h
+
96 % yield
N
O
N 2
COOMe
MeOOC
N
O
CH(COOMe) 2
Scheme 3.30 Rh(III)-catalyzed C–H bond activation and alkylation of quinoline N-oxides at C-8
position
efficiently at room temperature with excellent regioselectivity and functional group
tolerance.
Lin and co-workers [59] carry out DFT calculations to investigate the mechanism of this reaction. As shown in Fig. 3.31, the catalytic cycle starts from a
cationic Cp*Rh(III) complex 3-144. An outer-sphere electrophilic deprotonation by
extra quinoline N-oxide takes place via transition state 3-145ts with an activation
barrier of 25.3 kcal/mol to generate five-membered rhodacycle intermediate 3-146.
The coordination of diazo compound onto Rh(III) leads to carbenation via transition state 3-148ts with an overall energy barrier of 28.0 kcal/mol. Consequently, it
was considered to be rate-determining step. The subsequent migratory insertion of
carbene into the C(aryl)–Rh bond occurs via transition state 3-150ts with a barrier
of only 1.7 kcal/mol to generate the six-membered rhodacycle intermediate 3-151.
3-144
0.0
G(M06, dichloroethane)
(kcal/mol)
3-145ts
25.3
3-146
8.1
C-H bond cleavage
3-148ts
28.0
formation of carbene
3-149
4.4
3-150ts
6.1
-33.1
3-152ts
-14.3
3-152
-32.6
3-144
-41.4
carbene insertion
protonation
3-144
3-145ts
H QNO
3-146
QNO
3-147
3-147
3-148ts
N 2
N 2
COOMe
MeOOC
3-149
3-150ts
3-151
H QNO
3-152ts
QNO
3-153
3QNO
3-154
N
O
CH(COOMe) 2
3-154
Rh
ONQ
QNO
ONQ
2+
Rh
N
O
+
QNO
Rh
N
O
2+
QNO
H QNO
Rh
N
O
+
COOMe
COOMe
Rh
N
O
+
COOMe
COOMe
Rh
N
O
+
COOMe
COOMe
Rh
N
O
+
COOMe
COOMe
N 2
N
O
O
OMe
MeO O
2+
3-151
Rh
N
O
O
OMe
MeO O
2+
Rh
H
ONQ
Fig. 3.31 Free energy profiles for the Rh(III)-catalyzed C–H bond activation and alkylation of
quinoline N-oxides at C-8 position. The values are the relative free energies given in kcal/mol
calculated at the M06/6-311++G(d,p)/LANL2DZ//B3-LYP/6-31G(d)/LANL2DZ level of theory in
dichloroethane
47
4 mol % [Cp*RhCl 2 ] 2
16 mol % AgSbF 6
20 mol % PivOH
1,2-DCE, 25 C, 12h
+
96 % yield
N
O
N 2
COOMe
MeOOC
N
O
CH(COOMe) 2
Scheme 3.30 Rh(III)-catalyzed C–H bond activation and alkylation of quinoline N-oxides at C-8
position
efficiently at room temperature with excellent regioselectivity and functional group
tolerance.
Lin and co-workers [59] carry out DFT calculations to investigate the mechanism of this reaction. As shown in Fig. 3.31, the catalytic cycle starts from a
cationic Cp*Rh(III) complex 3-144. An outer-sphere electrophilic deprotonation by
extra quinoline N-oxide takes place via transition state 3-145ts with an activation
barrier of 25.3 kcal/mol to generate five-membered rhodacycle intermediate 3-146.
The coordination of diazo compound onto Rh(III) leads to carbenation via transition state 3-148ts with an overall energy barrier of 28.0 kcal/mol. Consequently, it
was considered to be rate-determining step. The subsequent migratory insertion of
carbene into the C(aryl)–Rh bond occurs via transition state 3-150ts with a barrier
of only 1.7 kcal/mol to generate the six-membered rhodacycle intermediate 3-151.
3-144
0.0
G(M06, dichloroethane)
(kcal/mol)
3-145ts
25.3
3-146
8.1
C-H bond cleavage
3-148ts
28.0
formation of carbene
3-149
4.4
3-150ts
6.1
-33.1
3-152ts
-14.3
3-152
-32.6
3-144
-41.4
carbene insertion
protonation
3-144
3-145ts
H QNO
3-146
QNO
3-147
3-147
3-148ts
N 2
N 2
COOMe
MeOOC
3-149
3-150ts
3-151
H QNO
3-152ts
QNO
3-153
3QNO
3-154
N
O
CH(COOMe) 2
3-154
Rh
ONQ
QNO
ONQ
2+
Rh
N
O
+
QNO
Rh
N
O
2+
QNO
H QNO
Rh
N
O
+
COOMe
COOMe
Rh
N
O
+
COOMe
COOMe
Rh
N
O
+
COOMe
COOMe
Rh
N
O
+
COOMe
COOMe
N 2
N
O
O
OMe
MeO O
2+
3-151
Rh
N
O
O
OMe
MeO O
2+
Rh
H
ONQ
Fig. 3.31 Free energy profiles for the Rh(III)-catalyzed C–H bond activation and alkylation of
quinoline N-oxides at C-8 position. The values are the relative free energies given in kcal/mol
calculated at the M06/6-311++G(d,p)/LANL2DZ//B3-LYP/6-31G(d)/LANL2DZ level of theory in
dichloroethane