172
5.2.1.3 C(sp
2
)-C(sp
2
) Cross-Coupling Reactions
In a further demonstration of the utility of CCHE reactions, Wu and co-workers
extended this strategy to direct coupling of C(sp
2
)-H bonds. They developed a
visible- light-driven indole synthesis via the CCHE process. Using Ir(ppy) 3 and
Co(dmgH) 2 (4-CO 2 Mepy)Cl as a photocatalytic system, various N-aryl enamines
were smoothly converted to the corresponding indoles under oxidant-free conditions [14] (Scheme 5.24).
To probe the reaction mechanism, 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) was included as a radical scavenger. Adding two equivalents of TEMPO
decreased the yields of the indole and H 2 . This result suggested that some radical
intermediates might be involved in this transformation (Scheme 5.25).
Based on the above results, the following mechanism for the reaction was proposed. Under visible-light irradiation, photosensitizer Ir(ppy) 3 was activated to its
excited state Ir(ppy) 3 *. Subsequent electron transfer from Ir(ppy) 3 * to the cobaloxime species afforded Ir(IV) and Co(II). Next, N-aryl enamine 55a was oxidized by
the generated Ir(IV) species to form the cation radical 56a and ground-state Ir(III).
With the release of a proton, cation radical 56a produced radical 57a, which was in
resonance with 58a. The desired product indole 60a was formed from intermediate
58a through consecutive intramolecular radical addition, oxidation, and deprotonation processes. The electron and proton eliminated from substrate 55a were transformed to H 2 promoted by the cobaloxime HEC (Scheme 5.26).
O +
Acr
+
-Mes
Co(dmgH) 2 pyCl
Cu(OTf) 2 , CH 3 CN
blue LED, 24 h
O
+
D 2
[D 2 ]-50
[ D 2 ]-51
[ D 2 ]-52, 75 %
O
OEt
O
OEt
O
O
D D
D D
D
D
O +
Acr
+
-Mes
Co(dmgH) 2 pyCl
Cu(OTf) 2 , CD 3 CN
blue LED, 24 h
O
+
H 2
50
51
52, 72 %
O
OEt
O
OEt
O
O
79 %
O +
Acr
+
-Mes
Co(dmgH) 2 pyCl
Cu(OTf) 2 , CH 3 CN
blue LED, 1 h
O
+ H 2 /HD/D 2
50
51
52/[D]-52
O
OEt
O
OEt
O
O
K H /K D = 2.3
O
[D 2 ]-50
D D
+
H/D
0.2 mmol
0.2 mmol
Scheme 5.23 Deuterium experiment for the photocatalytic CCHE reaction of isochromans with
β-keto esters
W. Ai et al.
5.2.1.3 C(sp
2
)-C(sp
2
) Cross-Coupling Reactions
In a further demonstration of the utility of CCHE reactions, Wu and co-workers
extended this strategy to direct coupling of C(sp
2
)-H bonds. They developed a
visible- light-driven indole synthesis via the CCHE process. Using Ir(ppy) 3 and
Co(dmgH) 2 (4-CO 2 Mepy)Cl as a photocatalytic system, various N-aryl enamines
were smoothly converted to the corresponding indoles under oxidant-free conditions [14] (Scheme 5.24).
To probe the reaction mechanism, 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) was included as a radical scavenger. Adding two equivalents of TEMPO
decreased the yields of the indole and H 2 . This result suggested that some radical
intermediates might be involved in this transformation (Scheme 5.25).
Based on the above results, the following mechanism for the reaction was proposed. Under visible-light irradiation, photosensitizer Ir(ppy) 3 was activated to its
excited state Ir(ppy) 3 *. Subsequent electron transfer from Ir(ppy) 3 * to the cobaloxime species afforded Ir(IV) and Co(II). Next, N-aryl enamine 55a was oxidized by
the generated Ir(IV) species to form the cation radical 56a and ground-state Ir(III).
With the release of a proton, cation radical 56a produced radical 57a, which was in
resonance with 58a. The desired product indole 60a was formed from intermediate
58a through consecutive intramolecular radical addition, oxidation, and deprotonation processes. The electron and proton eliminated from substrate 55a were transformed to H 2 promoted by the cobaloxime HEC (Scheme 5.26).
O +
Acr
+
-Mes
Co(dmgH) 2 pyCl
Cu(OTf) 2 , CH 3 CN
blue LED, 24 h
O
+
D 2
[D 2 ]-50
[ D 2 ]-51
[ D 2 ]-52, 75 %
O
OEt
O
OEt
O
O
D D
D D
D
D
O +
Acr
+
-Mes
Co(dmgH) 2 pyCl
Cu(OTf) 2 , CD 3 CN
blue LED, 24 h
O
+
H 2
50
51
52, 72 %
O
OEt
O
OEt
O
O
79 %
O +
Acr
+
-Mes
Co(dmgH) 2 pyCl
Cu(OTf) 2 , CH 3 CN
blue LED, 1 h
O
+ H 2 /HD/D 2
50
51
52/[D]-52
O
OEt
O
OEt
O
O
K H /K D = 2.3
O
[D 2 ]-50
D D
+
H/D
0.2 mmol
0.2 mmol
Scheme 5.23 Deuterium experiment for the photocatalytic CCHE reaction of isochromans with
β-keto esters
W. Ai et al.