Transmetalation three-component reaction

A new three-component reaction has been made possible by treating an alkenylzir-conium reagent of type 66 with an alkyne 67 and an aldehyde 68 in the presence of catalytic amounts of Ni(cod)2 (10 mol%) and ZnC.F (20 mol%). The resulting penta-dienyl alcohols like 69 are obtained in satisfactory yield. The transmetalation of the... 

A three-component reaction based on the umpolung of re-allylpalladium (II) complexes indium metal was reported by Grigg and co-workers (Scheme 8.31) [74]. In this reaction, the electrophilic nature of the n-allyl palladium species generated from aryl halides and allenes is reversed by transmetallation with indium metal. The resultant nucleophilic allylindium reagent subsequently adds to the third component - aldehyde [75] or imine [76] - to give the corresponding homo-allylic alcohol 64 or amine 65 respectively. 

Aryl-rhodium species readily undergo the 1,4-addition to enones under mild conditions, although elevated temperatures are required in the case of alkynes. However, in 2006, Shinokubo et al. [176] observed that an emulsion of phenyl-boronic acid, 5-decyne, and methyl acrylate, in the presence of [Rh(OH)(cod)]2 (4mol%), afforded the three-component reaction product 4-butyl-5-phenylnona-2,4-dienoic acid methyl ester in 81% yield. The reaction, which only takes place as an emulsion in H O, can be explained by coordination of alkyne and acrylate to the aryl-Rh species 163 obtained after transmetalation of arylboronic acid, followed by addition of the aryl fragment to the carbon-carbon triple bond of alkyne and the double bond of acrylate in either a concerted or stepwise step. The obtained alkyl rhodium species 164 can undergo a p-hydride elimination to afford the observed product 167 (Scheme 3.68, Eq. 1). This methodology can be extended to other boronic acids 165 and... 

Recently, Larock and coworkers used a domino Heck/Suzuki process for the synthesis of a multitude of tamoxifen analogues [48] (Scheme 6/1.20). In their approach, these authors used a three-component coupling reaction of readily available aryl iodides, internal alkynes and aryl boronic acids to give the expected tetrasubsti-tuted olefins in good yields. As an example, treatment of a mixture of phenyliodide, the alkyne 6/1-78 and phenylboronic acid with catalytic amounts of PdCl2(PhCN)2 gave 6/1-79 in 90% yield. In this process, substituted aryl iodides and heteroaromatic boronic acids may also be employed. It can be assumed that, after Pd°-cata-lyzed oxidative addition of the aryl iodide, a ds-carbopalladation of the internal alkyne takes place to form a vinylic palladium intermediate. This then reacts with the ate complex of the aryl boronic acid in a transmetalation, followed by a reductive elimination. 

Hi. Carbon-silicon bonds. Following the earlier reports mentioning the palladium-catalysed addition of organosilylstannanes to alkynes or isonitriles , Mori and coworkers realized tandem transmetallation-cyclization reactions with bifunctional halogeno triflates and Bu3SnSiMe3 18. The reactivity of 18 under palladium catalysis was used for the silylstannylation of alkenes or the synthesis of allylic silanes via a three-component (aryl iodide - - diene - - 18) coupling reaction. Recently, a similar... 

Based on a transformation described by Catellani and coworkers [80], Lautens s group [81] developed a series of syntheses of carbocycles and heterocycles from aryl iodide, alkyl halides and Mizoroki-Heck acceptors. In an early example, the authors described a three-component domino reaction catalysed by palladium for the synthesis of benzo-annulated oxacycles 144 (Scheme 8.37). To do so, they used an m-iodoaryl iodoalkyl ether 143, an alkene substimted with an electron-withdrawing group, such as t-butyl acrylate and an iodoalkane such as -BuI in the presence of norbomene. It is proposed that, after the oxidative addition of the aryliodide, a Mizoroki-Heck-type reaction with nor-bornene and a C—H activation first takes place to form a palladacycle PdCl, which is then alkylated with the iodoalkane (Scheme 8.37). A second C—H activation occurs and then, via the formation of the oxacycle OCl, norbomene is eliminated. Finally, the aryl-palladium species obtained reacts with the acrylate. The alkylation step of palladacycles of the type PdCl and PdCl was studied in more detail by Echavarren and coworkers [82] using computational methods. They concluded that, after a C—H activation, the formation of a C(sp )—C(sp ) bond between the palladacycle PdCl and an iodoalkane presumably proceeds by oxidative addition to form a palladium(IV) species to give PdC2. This stays, in contrast with the reaction between a C(sp )—X electrophile (vinyl or aromatic halide) and PdCl, to form a new C(sp )—C(sp ) bond which takes place through a transmetallation. 

Transition-metal-mediated cycloaddition of aUcenes and alkynes meets a major challenge to achieve both high reactivity and predictable selectivity between different unsaturated substrates in the formation of complex molecules. The employment of zirconacyclopentanes incorporating a carboranyl unit to reaction with alkynes after transmetalation to nickel can realize the three-component [2 + 2 + 2] cycloaddition of carboryne, unactivated alkenes, and alkynes. 

Three-component Petasis reactions among salicylaldehydes, amines, and organo-boronic acids have been catalysed with a chiral thiourea BINOL catalyst to prepare alkylaminophenols with yields and ee values of up to 92% and 95%, respectively. Formation of amino esters Et02CCH(Ar)NR2 by Petasis combination of Et02CH0, R2NH, and ArB(OH)2, catalysed by Cu(I), is believed to involve transmetallation from boron to copper from which Ar is delivered intramolecularly to the iminium group of the coordinated intermediate. ... 

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