Transmetalation active species

In the direct coupling reaction (Scheme 30), it is presumed that a coordinatively unsaturated 14-electron palladium(o) complex such as bis(triphenylphosphine)palladium(o) serves as the catalytically active species. An oxidative addition of the organic electrophile, RX, to the palladium catalyst generates a 16-electron palladium(n) complex A, which then participates in a transmetalation with the organotin reagent (see A—>B). After facile trans- cis isomerization (see B— C), a reductive elimination releases the primary organic product D and regenerates the catalytically active palladium ) complex. 

Besides rhodium catalysts, palladium complex also can catalyze the addition of aryltrialkoxysilanes to a,(3-unsaturated carbonyl compounds (ketones, aldehydes) and nitroalkenes (Scheme 60).146 The addition of equimolar amounts of SbCl3 and tetrabutylammonium fluoride (TBAF) was necessary for this reaction to proceed smoothly. The arylpalladium complex, generated by the transmetallation from a putative hypercoordinate silicon compound, was considered to be the catalytically active species. 

The starting material bis(pinacolato)diboron is a poor Lewis acid and 1 B-NMR of KOAc and B2bin2 in DMSO-d6 shows no evidence of the coordination of the acetoxy anion to a boron atom leading to a tetrahedral activated species. However, the formation of an (acetato)palladium(II) complex after the oxidative addition of the halide influences the reaction rate of the transmetalation step. The Pd-O bond, which consists of a hard Lewis base with a soft Lewis acid, is more reactive than a Pd-X (X=Br, I) bond. In addition, the high oxophilicity of boron has to be considered as a driving force for the transmetalation step, which involves an acetato ligand. 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

Mechanism The Pd complex such as Pd(PPh3)4 activates the organic halides by oxidative addition into the carbon-halogen bond. The copper(I) halides react with the terminal alkyne and produce copper acetylide, which acts as an activated species for the coupling reactions. The oxidative addition step is followed by the transmetallation step. The proposed catalytic cycle is shown in Scheme 5.21. 

The mechanism of the Sonogashira cross-coupling follows the expected oxidative addition-reductive elimination pathway. However, the structure of the catalytically active species and the precise role of the Cul catalyst is unknown. The reaction commences with the generation of a coordinatively unsaturated Pd species from a Pd " complex by reduction with the alkyne substrate or with an added phosphine ligand. The Pd " then undergoes oxidative addition with the aryl or vinyl halide followed by transmetallation by the copper(l)-acetylide. Reductive elimination affords the coupled product and the regeneration of the catalyst completes the catalytic cycle. 

According to investigations by Hartwig et al. [6a] the actual catalytically active species in the amination reaction seems to be a pal-Iadium(0)-bis(tri-o-tolylphosphine) complex. The catalytic cycle starts with an oxidative addition of the palladium(O) complex into the aryl-halogen bond. Then the resulting arylpal-ladium(II) complex reacts with the tin amide under transmetalation this step is postulated... 

A proposed reaction mechanism includes the formation of a silver alkyl complex 285 at the initial stage of the catalytic cycle, followed by the reaction with the terminal alkyne to produce an alkenyl silver complex 286. The latter species then leads to the formation of the corresponding alkenyl Grignard reagent and regeneration of the catalytically active species on transmetallation (Scheme 10.96) [76]. 

The transmetallation with organoboron reagent precedes the carbometallative addition of the arylrhodium intermediates 394 to the unsaturated substrate, and the intermediate alkenylrhodium species 395 then undergo hydrolysis to close the catalytic cycle with regeneration of the catalytically active species 393 and formation of the observed enamide products. An intermolecular carborhodation event was proposed to occur in a three-component coupling of arylboronic acids with disubstituted alkynes in the presence of methyl acrylate (Scheme 10.135) [113]. 

For the Stille reaction, on-line ESI( + )-MS(/MS) monitoring allowed interception and characterization of (a) the actual catalytically active species Pd(Ph3)2, (b) the oxidative addition product 60a as the corresponding ionic species 60b, and (c) the transmetalation intermediate 62a and two products of this process 63a and 64. Gas phase reductive elimination (for 65 ) was observed. Therefore, for the first time, most of the major intermediates of a Stille reaction were intercepted, isolated, and characterized. Using ESI(-)-MS, the counteranion I was the single species detected. 

This reaction is far-reaching, because a wide variety of air- and thermally stable organoboron reagents are commercially available or easily synthesized, and it has indeed found extensive use in natural product synthesis. The Suzuki reaction allows the introduction of alkenes, alkynes and arenes in C-C coupling processes, the hydroboration of alkenes and alkynes being very well known. It is the addition of a base in the medium of the Suzuki reaction that leads to the transformation of a borane BR3 into a boronate BR3(OH) that is the active species for transmetallation towards Pd ... 

If using a palladium(Il) catalyst, the catalytic active species palladium(O) 9 is generated in situ from reduction of the palladium(II) precursor with the organostannane present in the medium. Oxidative addition of the organic electrophile then generates a 16-electron palladium(Il) complex intermediate 10, which then undergoes a transmetalation step to... 

Kobayashi and coworkers reported catalytic asymmetric Simmons-Smith type reaction of allylic alcohols (Scheme 6.98). In this reaction, Lewis acid (R,R)-(112) prepared by premixing of (1R,2R)-cyclohexane bis-sulfonamide and i-Bu2AlH was found to realize good enantioselectivity. Since, in the similar reaction catalyzed by chiral Zn complex derived from (1R,2R)-cyclohexane bis-sulfonamide and Et2Zn instead of chiral aluminum complex, the same enantioselectivity was observed, chiral Zn carbenoid species formed from (R,R)-(112) and Et2Zn via Al-Zn transmetallation was proposed as an active species [117]. 

The catalytic process is also achieved in the Pd(0)/Cr(II)-mediated coupling of organic halides with aldehydes (Scheme 33) [74], Oxidative addition of a vinyl or aryl halide to a Pd(0) species, followed by transmetallation with a chromium salt and subsequent addition of the resulting organo chromate to an aldehyde, leads to the alcohol 54. The presence of an oxophile [Li(I) salts or MesSiCl] allows the cleavage of the Cr(III) - 0 bond to liberate Cr(III), which is reduced to active Cr(II) on the electrode surface. 

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