Dehydrogenative coupling heteroarenes

Scheme 56 Rh- (a) and Cu-catalyzed (b) cross-dehydrogenative coupling of IH-indoles and 1 H-pyrroles with heteroarenes.

Ruthenium- and rhodium-catalytic systems for the direct cross-dehydrogenative coupling (CDC) of acrylamides with electron-deficient alkenes forming (Z, )-dienamides using copper(II) acetate as the oxidant has been developed. Both methods exhibit wide functional group compatibility and substrate flexibility. It is proposed that the reaction is initiated by cyclometalation of acrylamide by amide-directing C-H bond activation. Coordination of the alkene to the metal centre, followed by insertion of the carbon-carbon double bond, forms a seven-membered ruthacycle or rhodacycle species. Subsequent -elimination occurs to afford the desired (Z, )-dienamide. A CDC between two heteroarenes is effected with copper(II) acetate in the absence... 

Falck has recently reported dehydrogenative silylation of heteroarenes with triethylsilane (18) [97]. Coupling with the Si-H bond of triethylsilane, rather than the disilane Si-Si bond, in conjunction with the use of norbomene that presumably acts as a hydrogen acceptor, gives good yields with indoles, thiophenes, and furans, under relatively mild condition (80°C). Unlike the reaction shown in Scheme 7, silylation of indole did not require protection of the N-H group. 

The first cross-dehydrogenative intermolecular arylation of a heteroarene with an arene was reported by Fagnou in 2007. N-acetyl-lH-indoles were coupled with simple arenes and selective C3-arylation was obtained (88 89) in the presence of Pd(TFA)2 as catalyst in combination with superstoichiometric Cu(OAc)2 as terminal oxidant (Scheme 40) (2007SCI1172). The N-acetyl group proved to be crucial as no reaction product was achieved with IH-indoles, furthermore N-methyl-lH-indoles gave only self-dimerized products. 

The oxazoline-based double coordination strategy allows the otherwise difficult dehydrogenative C-N coupling of various heteroarenes and heteroarylamines to afford heteroatom-rich diarylamines of pharmaceutical importance (Eq. 32)... 

Oxidative and Dehydrogenative C-H Cross-couplings. 2-Formylthiophene was used as a coupling partner with NMI in a Pd(II)-catalyzed, Cu-mediated oxidative C-H cross-coupling, forming the heteroarene in modest yield with some diarylated product (eq 71). ... 

Dehydrogenative Cross-coupling of Heteroarenes. Phenan-throline derivatives can be directly arylated via an oxidative C-H/C-H cross-coupling process (eq 40)... 

A dehydrogenative cross-coupling between pyridines or five-membered heteroarenes with secondary phosphites has recently been developed (Schemes 4.251 and 4.252) [406]. The approach used silver nitrate as the promoter and K S Og as an oxidant. When the... 

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