Transmetalation cross-coupling reactions

These are called cross-coupling reactions and usually involve three basic steps oxidative addition, transmetallation, and reductive elimination. In the transmetallation step an organic group is transferred from the organometallic reagent to palladium. 

In contrast to the transition metals, where there is often a change in oxidation level at the metal during the reaction, there is usually no change in oxidation level for boron, silicon, and tin compounds. The synthetically important reactions of these three groups of compounds involve transfer of a carbon substituent with one (radical equivalent) or two (carbanion equivalent) electrons to a reactive carbon center. Here we focus on the nonradical reactions and deal with radical reactions in Chapter 10. We have already introduced one important aspect of boron and tin chemistry in the transmetallation reactions involved in Pd-catalyzed cross-coupling reactions, discussed... 

The involvement of organocopper intermediates in various cross-coupling reactions carried out in the presence of Cu1 is often suggested, although in the majority of cases no experimental proof is provided, and the actual role of Cu1 may be different (Section 9.6.3.2.1). The potential of copper-mediated cross-coupling can be shown by the stereospecific reaction of 3-trimethylsilylallylic alcohols, which takes place via a prior transmetalation of Si to Cu (37).157... 

The palladium-catalyzed cross-coupling reaction featured in this procedure occurs under neutral conditions in the presence of many synthetically useful functional groups (e.g. alcohol, ester, nitro, acetal, ketone, and aldehyde). The reaction works best in N,N-dimethylformamide with bis(triphenylphosphine)palladium(ll) chloride, PdCI2(PPh3)2, as the catalyst. Lithium chloride is added to prevent decomposition of the catalyst.143 13 It is presumed that conversion of the intermediate aryl palladium triflate to an aryl palladium chloride is required for the transmetallation step to proceed.9... 

Scheme 1.23. Pd- or Ni-catalyzed cross-coupling reactions of alkenylzirconium derivatives by Zr-to-Pd (or Ni) transmetallation.

It is well known that alkenylzirconocenes are transmetalated to zinc and conveniently undergo further palladium-catalyzed cross-coupling reactions [7k,8a,32]. Although the transmetalation of zirconacyclopentadienes to zinc is not yet well developed, some interesting reactions that take place in the presence of ZnCl2 have already been described (Eq. 2.30) [9]. 

It proceeds by the standard mechanism for cross-coupling reactions oxidative addition of Pd(0) to the C-I bond, transmetallation to give the C-Pd(II)-C compound, and reductive elimination. 

Transmetalation of this type has also been used to assist palladium(0)-catalyzed cross-coupling reactions in sterically congested substrates. Transmetalation of stan-nanes into alkenylcopper intermediates considerably accelerates subsequent palladium(0)-catalyzed cross-coupling with arylsulfonates (Scheme 2.50) [103]. 

As well as alkenylstannanes [106-108], other classes such as a-heteroatom-substituted alkyltributylstannanes [109] and, more importantly, allylic stannanes [110, 111] also undergo these Sn-Cu transmetalations. Otherwise difficult to prepare, allylic copper reagents may, however, be obtained by treatment of allylic stannanes (produced in turn from organolithium, magnesium, or zinc organometallics) with Me2CuLi LiCN. They enter into cross-coupling reactions with alkyl bromides [110] or vinyl triflates (Scheme 2.52) [111]. 

Palladium-catalyzed cross-coupling reaction of organoboranes with organic halides, triflates, etc. in the presence of a base (transmetalation is reluctant to occur without the activating effect of a base). For the catalytic cycle, see Kumada coupling on page 345. 

When the metallic additive to the intermediate 374 was zinc dihalide (or another Lewis acid, such as aluminum trichloride, iron trichloride or boron trifluoride), a conjugate addition to electrophilic olefins affords 381 . In the case of the lithium-zinc transmetallation, a palladium-catalyzed Negishi cross-coupling reaction with aryl bromides or iodides allowed the preparation of arylated componnds 384 ° in 26-77% yield. In addition, a Sn2 allylation of the mentioned zinc intermediates with reagents of type R CH=CHCH(R )X (X = chlorine, bromine) gave the corresponding compounds 385 in 52-68% yield. ... 

---