Organoboronic acids transmetallation

Scheme 1 Synthesis of organoboronic acids, esters, and amides via transmetallation with Li or Mg compounds.

Addition reactions of organoboronic acids to electron-deficient alkenes were found to be catalyzed by rhodium(i)931 or dicationic palladium(n) complexes.932,933 The reaction proceeding through the transmetallation to a transition metal has been proved to be a general technique for a wide range of selective carbon-carbon bond formation via 1,4-addition to a,/ -unsaturated ketones, aldehydes, esters, and amides, and the 1,2-addition to aldehydes and imines (Equation (217)).934... 

The metal-catalyzed addition reaction of organoboron compounds have not yet been well developed, but die reaction of NaBPh4 or arylboronic acids with enones in the presence of Pd(OAc)2 and NaOAc or SbCL, was recently reported by Uemura and his coworkers.2 The reaction was proposed to proceed through the oxidative addition of the C-B bond to the Pd(0) species however, another probable process, the transmetalation to transition metals, may allow a similar catalytic transformation by the use of organoboronic acids. We report here the 1,4-addition reaction of organoboronic acids to oc, J-unsaturated ketones or esters and 1,2-addition to aldehydes or imines catalyzed by a (acac)Rh(CHj=CH2)2/phosphine complex, which may involve the B-Rh transmetalation as the key step. 

Although there is no direct evidence that the boronate anions, such as RB(OH)3, are capable of effecting the transmetafl tiQQjit is quite reasonable to assume a similar effect of the base for the transmetallation of organoboronic acids. The cross-coupling reaction of arylboronic acids with aryl halides at pH 7-8.5 is retarded relative to the reaction at pH 9.5-11 [51]. The of phenylboronic acid is 8.8, thus suggesting the formation of the hydroxyboronate anion [RB((OH)3 at pH > pA and its transmetallation to the palladium(II) halides. The formation of ArB(OH)3 at pH 11-12 has been reported [52]. 

The main limitations of using organoboronic acids in cross-coupling chemistry are threefold. These compounds are quite reactive towards many nucleophiles and oxidants, which prohibits installation of the boronic acid functional group early in a synthetic sequence. Moreover, purification of boronic acids is often problematic. Finally, since the C—B bond is relatively nonpolar, transmetalation of an organoboron reagent to Pd(ll) will not occur without coordination of an anionic base or a fluoride ion to the boron atom to afford a four-coordinate ate -complex (e.g. 20 shown below). This requirement poses some limitations with respect to transformations of base- or fluoride-sensitive substrates, although these... 

Mechanism of the palladium-catalyzed ketone synthesis, comprising oxidative addition of carboxylic anhydride, transmetallation with organoboronic acid, and reductive ehmination, is shown in Scheme 1.12. 

The B-C bonds of tetraorganohorate, BRJ, and organoboronic acid, RB(OH)2, are more reactive toward transmetalation than that of triorganoborane, BR3. Phenyl group transfer from BPhJ to transition metals takes place under mild conditions. The reaction of PdCl2 with NaBPh4 in the presence of norbornadiene produces a Pd complex with a phenylnorbornenyl ligand (Eq. 5.16) [53]. 

Scheme 5.5 Proposed mechanism for the transmetallation of organoboronic acids. [Rh] = Rh(l)/L [9b, 14].

The role of the base was unraveled through DFT-B3LYP studies by Maseras, Ujaque and co-workers [70] concluding that the role of the base was to react with the organoboronic acid to generate the anionic species [RB(OH)3] this is the reactive species taking part in the transmetalation process by substituting the halide and the subsequent transmetalation step. 

The overall mechanism is closely related to that of the other cross-coupling methods. The aryl halide or triflate reacts with the Pd(0) catalyst by oxidative addition. The organoboron compound serves as the source of the second organic group by transmetala-tion. The disubstituted Pd(II) intermediate then undergoes reductive elimination. It appears that either the oxidative addition or the transmetalation can be rate-determining, depending on reaction conditions.134 With boronic acids as reactants, base catalysis is normally required and is believed to involve the formation of the more reactive boronate anion.135... 

The covalent B-G bond of organoboron compounds shows little reactivity toward representative electrophiles, but the presence of an empty low-lying orbital facilitates transmetallation to other metals. The transmetallation to zinc709 and other metal reagents has been extensively studied for carbon-carbon bond formation via addition and coupling reactions of trialkylboranes and alkylboronic acids. 

The mechanistic aspects of this Lewis acid promoted reaction have been examined by low temperature NMR studies, and reaction of the lithium alkynides with the Lewis acid activated epoxides is indicated. The order of the addition of the reagents does not affect the product yields provided that the reaction is carried out at -78 C addition of BF3-OEt2 to a mixture of an epoxide and an alkynide or addition of an epoxide to a mixture of an alkynide and BF3-OEt2 are both possible. The transmetalation between RLi and BF3 which produces unreactive organoboron compounds is shown to be very slow at this temperature. - ... 

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