60
3 Theoretical Study of Rh-Catalyzed …
(kcal/mol)
3-254
0.0
6.0
3-257ts
22.5
migratory insertion
18.0
277
-56.1
3-258
4.8
3-259ts
C-H bond cleavage
ligand
exchange
3-261
-42.7
G(M06, dichloroethane)
3-254
3-255
3-256
3-257ts
3-258
3-259ts
3-260
I
CO 2 H
3-260
3-261
3-253
3-262
N
O
Me
TIPS
3-262
3-255
N
O
Me
Rh
O
I
O
TIPS
Rh SbF 6
SbF 6
2+
O
I
O
TIPS
N
O
Me
SbF 6
Rh
2+
O
I
O
TIPS
N
O
Me
SbF 6
SbF 6
H
SbF 6
Rh
2+
O
I
OH
TIPS
N
O
Me
SbF 6
SbF 6
Rh
2+
O
I
OH
TIPS
N
O
Me
SbF 6
SbF 6
Rh SbF 6
SbF 6
N
O
Me
TIPS
3-256
Fig. 3.50 Free energy profiles for Rh(III)-catalyzed C-8 alkynylation reaction of isoquinolones
with TIPS-EBX. The values are the relative free energies given in kcal/mol calculated at the M06/6311++G(d,p)/SDD//B3-LYP/6-31G(d,p)/LANL2DZ level of theory in dichloroethane
base to activate the C8–H bond in 3-255 with a barrier of 22.5 kcal/mol to give the fivemembered rhodacycle 3-258. In this step, the cleavage of I-O bond occurs simultaneously. The subsequent Rh-mediated nucleophilic substitution of ethynyliodonium
with aryl takes place via transition state 3-259ts forming C(acetyl)-C(aryl) bond by
the release of iodobenzene 3-260. Active species 3-254 can be regenerated by the
coordination of TIPS-EBX 3-253 and the release of alkynylation product 3-262.
3.5 Rh-Catalyzed C–H Bond Carbonylation
In Rh-catalyzed C–H functionalization reactions, the C–H bond cleavage leads to
the formation of a C-Rh bond, which can undergo a following migratory insertion
of CO to realize carbonylation [122–127]. In 2016, Huang and Lan [128] reported
a combination of experimental and theoretical studies of Rh(III)-catalyzed oxidative cyclocarbonylation of ketimines (Scheme 3.51). This transformation provided a
powerful method for the synthesis of methyleneisoindolinone. The KIE experiment
indicated that the C–H bond cleavage at the ortho position of the ketimine might be
involved in the rate-limiting step.
The calculated free energy profile for the dominant reaction pathway of cyclocarbonylation is shown in Fig. 3.52, which starts with the active Rh(III) catalyst 3-263.
3 Theoretical Study of Rh-Catalyzed …
(kcal/mol)
3-254
0.0
6.0
3-257ts
22.5
migratory insertion
18.0
277
-56.1
3-258
4.8
3-259ts
C-H bond cleavage
ligand
exchange
3-261
-42.7
G(M06, dichloroethane)
3-254
3-255
3-256
3-257ts
3-258
3-259ts
3-260
I
CO 2 H
3-260
3-261
3-253
3-262
N
O
Me
TIPS
3-262
3-255
N
O
Me
Rh
O
I
O
TIPS
Rh SbF 6
SbF 6
2+
O
I
O
TIPS
N
O
Me
SbF 6
Rh
2+
O
I
O
TIPS
N
O
Me
SbF 6
SbF 6
H
SbF 6
Rh
2+
O
I
OH
TIPS
N
O
Me
SbF 6
SbF 6
Rh
2+
O
I
OH
TIPS
N
O
Me
SbF 6
SbF 6
Rh SbF 6
SbF 6
N
O
Me
TIPS
3-256
Fig. 3.50 Free energy profiles for Rh(III)-catalyzed C-8 alkynylation reaction of isoquinolones
with TIPS-EBX. The values are the relative free energies given in kcal/mol calculated at the M06/6311++G(d,p)/SDD//B3-LYP/6-31G(d,p)/LANL2DZ level of theory in dichloroethane
base to activate the C8–H bond in 3-255 with a barrier of 22.5 kcal/mol to give the fivemembered rhodacycle 3-258. In this step, the cleavage of I-O bond occurs simultaneously. The subsequent Rh-mediated nucleophilic substitution of ethynyliodonium
with aryl takes place via transition state 3-259ts forming C(acetyl)-C(aryl) bond by
the release of iodobenzene 3-260. Active species 3-254 can be regenerated by the
coordination of TIPS-EBX 3-253 and the release of alkynylation product 3-262.
3.5 Rh-Catalyzed C–H Bond Carbonylation
In Rh-catalyzed C–H functionalization reactions, the C–H bond cleavage leads to
the formation of a C-Rh bond, which can undergo a following migratory insertion
of CO to realize carbonylation [122–127]. In 2016, Huang and Lan [128] reported
a combination of experimental and theoretical studies of Rh(III)-catalyzed oxidative cyclocarbonylation of ketimines (Scheme 3.51). This transformation provided a
powerful method for the synthesis of methyleneisoindolinone. The KIE experiment
indicated that the C–H bond cleavage at the ortho position of the ketimine might be
involved in the rate-limiting step.
The calculated free energy profile for the dominant reaction pathway of cyclocarbonylation is shown in Fig. 3.52, which starts with the active Rh(III) catalyst 3-263.