Directed hydroarylation alkynes

Scheme 1. Conventional (top) and direct (bottom) hydroarylation of alkynes.

While this protocol relied on the in situ generation of the relevant phosphite for catalytic hydroarylation reactions, Murai and coworkers developed effective methodologies for the direct use of Lewis-basic substrates, such as acetophenone 20 (Scheme 9) [18, 59], Thereby, regioselective ruthenium-catalyzed anti-Markovnivkov alkylations and alkenylations were accomplished using alkenes or alkynes [60] as substrates, respectively. Recently, an extension of this protocol to terminal alkynes was reported, which involved a phosphine ligand-free catalytic system (see below), along with stoichiometric amounts of a peroxide [61]. 

Ruthenium(II)-Catalyzed Regio- and Stereoselective Hydroarylation of Alkynes via Directed C-H Functionalization... 

Phosphine oxide directing groups enable both redox-neutral and oxidative C-H olefinations (Scheme 23.17) [76, 77], In combination with [Ru(p-cymene)Clj]j, cw-selective hydroarylations of alkynes can be achieved. Furthermore, in the presence of [Cp RhCy/AgSbF, Cu(OAc)j, and AgjCOj, oxidative C-H olefinations are possible with electron-poor olefins as coupling partners. The latter reactions proceed with complete selectivity for the fran -product. 

To date, most research on NHCP transition-metal catalysis has been devoted to cross-couplings [13] or related reactions such as hydroarylation of alkenes [18], direct arylation of alkynes [17], or oxidative homocoupling of terminal alkynes [19]. All NHCP systems used in these studies feature one or two... 

Insertions of alkynes into palladium-hydride complexes have been reported to take place as part of catalytic cycles, resulting in circumstantial yet credible evidence for the occurrence of alkenylpalladium complexes. The first example of palladium-catalyzed hydroarylation of alkynes with organoboronic acids B(OH)2R has been given. The mechanistic interpretation based on labeling studies involves hydropalladation of the alkyne to give an intermediate alkenylpalladium(ii) species that reacts with the organoboronic acid (Scheme 11). Similar direct coupling reactions... 

Abstract The selective catalytic activation/functionalization of sp C-H bonds is expected to improve synthesis methods by better step number and atom economy. This chapter describes the recent achievements of ruthenium(II) catalysed transformations of sp C-H bonds for cross-coupled C-C bond formation. First arylation and heteroarylation with aromatic halides of a variety of (hetero)arenes, that are directed at ortho position by heterocycle or imine groups, are presented. The role of carboxylate partners is shown for Ru(II) catalysts that are able to operate profitably in water and to selectively produce diarylated or monoarylated products. The alkylation of (hetero)arenes with primary and secondary alkylhalides, and by hydroarylation of alkene C=C bonds is presented. The recent access to functional alkenes via oxidative dehydrogenative functionalization of C-H bonds with alkenes first, and then with alkynes, is shown to be catalysed by a Ru(ll) species associated with a silver salt in the presence of an oxidant such as Cu(OAc)2. Finally the catalytic oxidative annulations with alkynes to rapidly form a variety of heterocycles are described by initial activation of C-H followed by that of N-H or O-H bonds and by formation of a second C-C bond on reaction with C=0, C=N, and sp C-H bonds. Most catalytic cycles leading from C-H to C-C bond are discussed. 

The competitive experiments and KIE reactions show that C-H bmid cleavage is a rate-determining step and leads to a SeAr-like metallation. A five-membered ruthenacycle intermediate was proposed via an ortho C-H deprotonation directed by the carbonyl group with ruthenium catalyst by analogy to the alkenylation mechanism (Scheme 16). Then alkyne insertion into the resulting Ru-C bond gave a seven-membered intermediate, and the hydroarylated product was produced by protonolysis of the Ru-C bond (Scheme 17) [163, 164]. 

T. Kitamura, Transition-metal-catalyzed hydroarylation reactions of alkynes through direct functionaUzalion of C-H bonds a convenient tool for organic synthesis, Eur. J. Org. Chem. (2009) 1111-1125. 

Albrecht [133] and Sankararaman [174] have independently synthesized the cyclometallated phenyl-1,2,3-triazol-5-ylidenes complexes 77a-b (Scheme 11). Both groups have found that the cyclometallation is selective for aryl groups in the 1-position of the l,2,3-triazol-5-ylidenes units presumably because the direct attachment to the nitrogen atom increases the acidity of the 1-substituted aryl group, making the deprotonation more facile. It is noted that 77b is a catalyst for the stereoselective hydroarylation of alkynes [174]... 

The ruthenium-catalysed hydroarylation of alkynes (151) with benzamides (150) has been reported to proceed regio- and stereo-selectively and is believed to involve the amide-directed ort/to-metallation, carbometallation of the alkyne, and protonolysis. Phenylazoles exhibit similar reactivity and regioselectivity. ... 

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