Metal catalyzed, arylation alkenes

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Most electrophilic carbene complexes with hydrogen at Cjj will undergo fast 1,2-proton migration with subsequent elimination of the metal and formation of an alkene. For this reason, transition metal-catalyzed cyclopropanations with non-acceptor-substituted diazoalkanes have mainly been limited to the use of diazomethane, aryl-, and diaryldiazomethanes (Tables 3.4 and 3.5). 

Furthermore, Pd-catalyzed aminations can be sequentially coupled with alkene insertion and amination. Wolfe and Lira [102] have established a transformation involving two different sequential metal-catalyzed reactions that lead to AT-aryl-2-benzylindolines 125 in moderate to excellent yields upon formation of two C - N bonds and one C - C bond in a one-pot process (Scheme 45). Interestingly, the selective installation of two different aryl groups in this sequence can be accomplished by in situ modification of the Pd catalyst system Pd-126 upon addition of the chelating ligand dpephos prior to addition of the second aryl bromide (Scheme 46). The selectively substituted indoline derivatives 127 were isolated in good to excellent yields. 

The Pd )-catalyzed reaction of aryl diazonium salts with mono-substituted alkenes [1] was found to be an interesting alternative to the well-known Pd - catalyzed arylhalide alkene coupling (Heck type reaction) or the copper mediated reaction of aryl diazonium salts with alkenes (Meerwein arylation) [2], The reaction can be run without isolation of the diazonium salt in presence of only 0.5 to 1 mol% of the Palladium catalyst in a one pot procedure, in high yield and under nuld conditions. The resulting styrene is reduced in a subsequent hydrogenation step with an in situ generated heterogeneous Pd-catalyst. The combination of three reaction steps without isolation of intermediates and the virtually complete recovery of the Pd-metal at the end of the reaction sequence makes this process [4] extremely efficient. 

Direct (instead of stepwise) transition metal catalyzed dicarboration is achieved by a modification of the palladium-catalyzed Heck reaction 2 4-85,86 116 if the final dehydropal-ladation step is suppressed. This step usually occurs after alkene insertion into an aryl - or a vinyl-palladium bond formed from the corresponding halide or triflate. 

Over the past two decades, Pd- or Ni-catalyzed cross-coupling, especially Pd-catalyzed version, has become one of the most common methods (possibly the most common method) for highly selective synthesis of arylated alkenes, conjugated dienes, conjugated enynes (Sect, in.2.8), and other related aUcene derivatives, hi addition to Mg, Zn, Al, and Zr used since the 1970s, several other metals including Sn,[2 ] [27] and Cu[2 ] [ i have been extensively employed since around 1980. 

As with other transition metal-catalyzed reactions (Ziegler-Natta polymerization of alkenes, olefin metathesis), the mechanism of the Heck reaction is complicated. In brief, the species that reacts with the aryl halide is I Pd, where L is a ligand such as tiiphenylphosphine. By a process known as oxidative addition, palladium inserts into the carbon-halogen bond of the aryl halide. 

Several independent protocols using a combination of transition metal-catalyzed stereoselective hydrosilylation, such as palladium-catalyzed crosscoupling sequence leading to stereodefined r-conjugated alkene derivatives, have been successfully developed in the last decade (4). Alkenylsilanes or siloxanes, prepared via platinum or rhodium complex-catalyzed intermolecular hydrosilylation of terminal alkynes have been highly stereospecifically cross-coupled with aryl and alkenyl halides to give unsymmetrical stilbenes, alkenylbenzenes, and conjugated dienes (Scheme 24) (4). 

Balme has reported a one-pot threecomponent alkene carboamination between propargylic amines, alkylidene malonates, and aryl halides [43]. For example, treatment of N-methyl propargylamine (2 equiv), dimethyl benzylidene malonate (2 equiv) and 1,4-diiodobenzene (1 equiv) with n-BuLi and a palladium catalyst provided 43 as a single diastereomer (Eq. (1.20)) [43a]. The formation of the C—N bond in this process does not appear to be metal catalyzed. Instead, initial conjugate addition of the nitrogen nucleophile to the activated alkene affords a malonate anion, which undergoes carbopalladation followed by reductive elimination to afford the pyrrolidine product. 

Transition Metal-catalyzed Reactions. Chlorodimethylvinyl-silane has been used in the synthesis of silyl-containing Heck reaction precursors.24 Heck reaction of aryl or alkenyl iodides with dimethylvinylsilylpyridine (36) using Pd2(dba)3 and tri-2-furylphosphine (TFP) produced the coupled alkene products 37 (R = Ph, 2-py, 2-thiophene, and others) in high yields and with exclusive E selectivity due to the pyridine directing group (eq 17). The pyridine moiety was also employed as a phase tag, which enabled easy purification via acid-base extraction. The silicon linker was subsequently cleaved by H2O2 oxidation. ... 

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