Alkenyl halides cross-coupling

KUMADA NEGISHI Cross coupling Stsreospecific alkenyl aluminum-alkenyl halide cross coupling catalyzed by Pd or Ni... 

The cross-coupling of boron compounds with aryl or alkenyl halides (Suzuki coupling) was used for the preparation of polycyclic aromatic compounds in a biphasic reaction medium. For example, 2-bromobenzonitrile and 4-methylphenylboronic acid gave 4-methyl-2"-cyanobiphenyl in good jdeld with Pd/TPPTS catalyst at 80°C in a toluene-ethanol-aqueous Na2C03 solvent mixture (Scheme 37). The product, isolated by phase separation, was free of metal or ligand impurities and the catalyst could be recycled in the aqueous phase (208). 

Synthetic applications of the alkenyl-alkenyl Negishi cross-coupling are intimately related to the preparation method of the alkenylzinc nucleophile. Reagents obtained by Zn(0) insertion from the corresponding halide, or by a halogen-hthium or a tin-lithium exchange/transmetallation sequence, are weU suited, as illustrated with the preparation of compounds 202 [170] and 205 (Scheme 4.46) [46]. Further evidence for the applicability of this method is its use in recent total syntheses of natural products, such as xerulinic acid [171], 6,7-dehydrostipiamide [172], epolactaene [173], and the side chains of mycolactones A and B [174]. 

In 1979 Wenkert reported the cross-coupling reaction of alkenyl methyl ethers with phenyl and methyl magnesium halides via the activation of C(sp )-OMe bonds by using NiCl2(PPh3)2 as a catalyst precursor [Eq. (2)] [12, 13]. This alkenyl ether cross-coupling was further extended to silyl enol ethers [14] and cyclic ethers, such as dUiydrofurans [15-23], which offer a unique method for the stereoselective construction of alkenes (see Sect. 4). 

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

Polymerization using the Stille coupling, the cross-coupling of aryl-alkenyl halides with organotins in the presence of palladium catalysts (Scheme 9.10),13 appeared in 1989 (Scheme 9.11).14 The low nucleophilicity of organotins makes it possible to use functionalized monomers for the polymerization.15... 

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. 

Aryl-alkenyl cross-coupling is straightforward. Simple alkylmagnesium reagents (Me, Et, CH2SiMe3, etc.) can be easily involved in Ni-catalyzed cross-coupling (27),139,140 while more complex alkyl halides—particularly branched ones prone to /3-hydride elimination—require Pd catalysts with bidentate phosphines, such as dppf, to achieve good selectivity (Section 9.6.3.4.7). 

Cross-coupling of terminal acetylenes used as nucleophiles with aryl or alkenyl halides (referred to as the Sonogashira-Hagihara, or SH, reaction) is a versatile method of synthesis for acetylenic compounds, which are rapidly gaining importance as advanced new materials and building blocks for implementing unusual molecular architectures. 

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