C-N crosscoupling reactions

In contrast to PPhs, P(c -Tol)3 cannot reduce Pd (OAc)2 to a Pd(0) complex, but a P,C-palladacycle, rran5-di(/r-acetato)-bis[o-(di-o-tolylphosphino)benzyl]dipaIladium (5) is formed via a cyclometallation [27, 55]. The palladacycle 5 is an efficient catalyst for Mizoroki-Heck reactions involving aryl bromides and activated aryl chlorides (i.e. substituted by EWGs) [lj,l,o,s-v, 27, 55]. When 5 is used as catalyst in C—N crosscoupling reactions, Louie and Hart wig [56] have established that the true catalyst is aPd(0) complex, Pd P(o-Tol)3 2 formed by reduction of the palladacycle by the nucleophile (a secondary amine as a hydride donor in the presence of a strong base). 

This section addresses typical problems encountered in Pd-catalyzed C-N crosscoupling reactions. By-products of the attempted C-N cross-coupling are often symptomatic and help identify the problematic steps in the catalytic reaction. Thus, even if the catalytic transformation does not proceed with the expected efficiency, an analysis of the reaction products is highly recommended. 

Scheme 17.5 Benzyne-mediated mechanism, operative for C-N crosscoupling reactions.

Liebeskind reported a copper-catalyzed Chan-Lam C-N crosscoupling methodology for JV-imination of boronic acids by using oxime O-carboxylates 291 as iminating agents and either Cu(I)-thiophene-2-carboxylate (CuTC) or Cu(OAc)2 as the catalyst under nonbasic and nonoxidizing conditions.Subsequently, the A-alkenylated a,3-unsaturated ketoxime 0-pentafluorobenzoates 293, were preeursors in a cascade reaction for the one-pot synthesis of tri-, tetra-, and penta-substituted pyridines 295 in moderate to excellent isolated yields. 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

In contrast to the synthetic approaches described in Sects. 3.2.1 and 3.2.2, the N-arylation and C-C coupling steps can also be reversed. Suzuki-Miyaura coupling of N-substituted 2-haloarylamines 189 with arylboronic acids 190 provides N-substituted 2-aminobiaryls 191 (Scheme 43). A palladium(II)-catalyzed oxidative cyclization of the latter forms the tricyclic carbazole framework. Different from the first reaction step in Scheme 24, this is an oxidative C-N coupling which requires N-H and C-H activation, whereas the C-C bond is formed in a crosscoupling process. 

Pyridine N-oxides were shown to undergo C-H activation and crosscoupling reaction with unaaivated secondary and tertiary alkyl bromides, despite the steric bulk of these halides (Scheme 33) (13JA616). While... 

TRANSITION METAL-MEDIATED CARBON-HETEROATOM CROSSCOUPLING (C-N, C-O, C-S, C-Se, C-Te, C-P, C-As, C-Sb, AND C-B BOND FORMING REACTIONS) ... 

In the past decades Pd-catalyzed C-C and C-X (X O, N, S, Si, heteroatom, etc.) crosscoupling reactions have become one of the most powerful processes in the toolbox of organic synthesis due to the high yields achieved, mild conditions, wide scope, and compatibility with a large variety of functional groups. Scheme 2.15 shows some of the possible coupling reactions promoted by Pd catalyst. 

Hypervalent iodine(m) reagents can be applied to aryl-aryl C-H crosscouplings. Recently, Antonchick achieved CDC between various N-hetero-cycles and aldehydes (Scheme 8.18). The use of PIFA and TMSN3 is effective at promoting this reaction to give a variety of acyl iV-heterocyclic compounds... 

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