Boronic carbopalladation

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. 

However, studies on the scope of this sequence revealed that the substrate has to be an N-tosyl sulfonamide and that certain boronic acids are not trans-metallated but rather give rise to the formation of the pyrrole 21 or a pyridine derivative 22 (Scheme 7). The peculiar outcome as a carbopalladation-Suzuki sequence is rationalized by co or dinative stabilization of the insertion intermediate 18 by the sulfonyl oxygen atom, as represented in structure 19, now suppressing the usual /3-hydride elimination. If the transmetallation is rapid the Suzuki pathway is entered leading to product 17. However, if the transmetallation is slow, as for furyl or ferrocenyl boronic acid, either /i-hydride elimination or a subsequent cyclic carbopalladation occurs. The former leads to the formation of the diene 20 that is isomerized to the pyrrole 21. The latter furnishes the cyclopropylmethyl Pd species 23, which rearranges with concomitant ring expansion to furnish piperidyl-Pd intermediate 24 that suffers a -hydride elimination to give the methylene tetrahydro pyridine 22. 

The formation of homoallylpalladium intermediates of type 77 from the initial car-bopalladation products 76 can essentially be described as an intramolecular carbopallada-tion of one of the proximal cyclopropyl bonds by the adjacent cyclopropylpalladium moiety. Thus, the analogous silyl-substituted homoallylpalladium intermediates 85 also arise via intramolecular carbopalladation, and this is not followed by /3-dehydropalladation, but by reductive elimination to give the homoaUylsilanes, -boronates, -stannanes, and so on 86—X (Scheme 21). This type of overall transformation of bicyclopropylidene (50) is particularly versatile with trimethylsilyl cyanide, as it yields the trimethylsilyl-substi-tuted 4-cyclopropylidenebutyronitrile 86—CN that can readily be converted to a number... 

Palladium-catalyzed annulation reactions of conjugate acceptors and allenyl boronic ester provide substituted cyclopentenes in high yields and diastereose-lectivities (Scheme 6.24). These reactions are hypothesized to commence by the conjugate addition of a nucleophilic propargyl-palladium complex. Transmetalation of allenylboronic acid pinacol ester with a Pd(II) catalyst proceeds via an SE2 mechanism to provide the propargyl-palladium complex, which on conjugate attack on the electrophile furnishes an allene intermediate. Finally, endo carbopalladation of the pendant allene and protodepalladation generates the cyclopentene [28]. 

The aryl (or alkyl) palladium species needed for a Heck reaction can be generated fi om boronic acids and their derivatives if the overall reaction is conducted under oxidative conditions. In contrast to haloarenes, transmetalation is leaving the metal oxidation state unchanged. Therefore, an additional oxidant is needed to gain back Pd(ll) after a completed catalytic circle. So-called oxidative Heck reactions have been reported for the first time by Cho and Uemura and Karami et al The group of Park has shown that enamides are suitable substrates for this carbopalladation mode (Scheme 5-40). ... 

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