Arylboronic add

The use of expensive and unstable ZnPli2 in the preparation of chiral di-arylmethanol derivatives, with electronically and sterically similar aryl rings, made this approach less attractive for the enantioselective synthesis. In order to avoid this inconvenience, other alternative preparations of arylzinc reagents were evaluated.As a first choice, Yus et al. proposed the use of arylboronic adds as a viable source of phenyl (Scheme 4.19). Thus, the reaction of various boronic acids with an excess of ZnEt2 at 70 °C gave the corresponding arylzinc intermediates (probably aryl(ethyl)zincs), which were trapped by reaction with dif-... 

The palladium-catalyzed coupling of boronic acids with aryl and alkenyl halides, the Suzuki reaction, is one of the most efficient C-C cross-coupling processes used in reactions on polymeric supports. These coupling reactions requires only gentle heating to 60-80 °C and the boronic acids used are nontoxic and stable towards air and water. The mild reaction conditions have made this reaction a powerful and widely used tool in the organic synthesis. When the Suzuki reaction is transferred to a solid support, the boronic add can be immobilized or used as a liquid reactant Carboni and Carreaux recently reported the preparation of the macroporous support that can be employed to efficiently immobilize and transform functionalized arylboronic adds (Scheme 3.12) [107, 246, 247]. 

Nishimura, M. Ueda, M. Miyaura, N. Palladium-catalyzed biaryl-coupling reaction of arylboronic adds in water using hydrophilic phosphine ligands. Tetrahedron 2002, 58, 5779-5787. 

Cho, C. S. Motoffisa, S.-I. Ohe, K. Uemura, S. Shim, S. C. A new catalytic activity of SbCl3 in Pd(0)-catalyzed conjugate addition of aromatics to a,/3-unsaturated ketones and aldehydes with NaBPh and arylboronic adds. 

Fig. 5.32. Electrophilic functionalization ortho to an O-bonded MDG preparation of an arylboronic add.

The reaction was rather sensitive to electronic effects both in aldehydes and arylboronic adds, suggesting the mechanism proceeds through the nucleophilic attack of the aryl group to the carbonyl (Table 4). Thus, the reaction was facilitated in the presence... 

The coupling of an arylboronic add with a phenyl group of a phosphine stabilizing ligand if present in fhe Pd catalyst used [76]... 

Various Suzuki reactions have been performed by using 5 x 10 " mol. equiv. of support-bound catalyst 41 (Scheme 9). The reaction of 46 with electron-rich (47) or electron-deficient (48) arylboronic adds catalyzed by 50 ppm (5 x 10 mol. equiv.) of 41 afforded the corresponding biaryl products 49 and 50 in almost quantitative yields. The reactions of electron-deficient aryl bromides 51 and 52 with 53 proceeded smoothly in the presence of 500 ppm (5 x lO"" mol. equiv.) of 41 to give the corresponding biaryls 54 and 55 in 97-98% yield. This catalyst also proved effective in reactions with alkenyl halides. Ethyl cis-3-iodomethylacrylate 56 was converted to the corresponding coupling product 57 in 96% yield. 

The catalytic asymmetric synthesis of diarylmethylamines by a rhodium/phos phoramidite catalyzed addition of arylboronic adds to N,N dimethylsulfamoyl pro tected aldimines has been reported by de Vries and Feringa [118], The reaction produces very high yields and high enantioselectivities of the protected amine. Deprotection of the amine is achieved without any racemization upon heating the product in the microwave with 1,3 diaminopropane (Scheme 1.35). 

The metal-catalyzed addition reaction of organoboron compounds have not yet been well developed, but the reaction of NaBPh or arylboronic adds with enones in the presence of Pd(OAc)2 and NaOAc or SbClj was recently reported by Uemura and his co-workCTS. 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 adds to a,P-unsaturated ketones or esters and 1,2-addition to aldehydes or imines catalyzed by a (acac)Rh(CH2=CH2)2/phosphine complex, which may involve the B-Rh transmetalation as the key step. 

The results obtained for the asymmetric 1,4-addition of arylboronic adds to crotonates or cinnamates in the presence of a Rh(acac)(C2H4)2-(S)-binap catalyst are summarized in Table 3. The ester group (R ) significantly affects the %ee. Thus, the i-propyl, cyclohexyl, r-butyl, benzyl esters achieved a high %ee whereas the methyl and ethyl esters (entries 1-4) resulted in low asymmetric induction. The absolute configuration of benzyl 3-phenylbutanoate ([al -14.5 (c 1.02, CHClj) obtained from (S)-bin2 was established to be (R) by the specific rotation reported for (R)-3-phenylbutanoic add ([a]u -45.8 (c 0.77, benzene). 

Addition of Arylboronic Adds to a,p,y,5-Unsaturated Carbonyl Compounds... 

Several intermediates in the Suzuki-Miyaura coupUng of bromopyridines with arylboronic adds have been identified by in situ analysis of the reaction by electrospray ionization mass spectrometry (ESI-MS) [268]. Interestingly, monitoring the coupling by ESI-MS demonstrates that, at the end of the reaction, there is an accumulation of binuclear Pd(0)-Pd(II) halide clusters, which are stiU catalytically active [269]. 

In 2012, Itami and Yamaguchi discovered the bisoxazoHne-Pd catalysts such as 173 and 174 that enable the synthesis of hindered heterobiaryls by direct C-H coupling. Moreover, they demonstrated the first enantioselective C-H biaryl cross-coupling (Scheme 17.49) [227]. For example, when an n-PrOH solution of thiophene 175 and arylboronic acid 176 was treated with a Pd(OAc)2/biox 174 catalyst and TEMPO at 70 °C under air, (S)-177 was obtained in 41% ee (63% yield). When a more hindered arylboronic add 178 was used, the enantiometric excess of product (S)-179 was increased to 72% at the expense of lower yield. 

The cross-coupling reactions of organoboronic acids and carbon monoxide with hyper-valent iodonium salts affords unsymmetrical ketones (Scheme 30). The reaction proceeds smoothly at room temperature and in most cases completes within 0.5 h. Aryl-, alkenyl-, and alkynyliodonium salts react with arylboronic adds in the presence of 0.5% of Pd(PPh3)4 and 1.2 equiv of K2CO3 in DME to provide unsymmetrical aromatic ketones in high yields (Scheme 30). Phenylboronic acid dimethyl ester can be utilized as efficiently as phenylboronic acid. In most cases, a small amount of the direct crosscoupling product (R—Ph, less than 7-8%) is produced. 

SCHEME 20.71 CoupUng of arylboronic add/iodonium salts with phosphorus nucleophiles. 

SCHEME 23.33 Ortho-C-H silylation of arylboronic adds with transfmnable PG/DGs. 

Figure 2.24 A cross-section of resuits for the Cu-catalyzed regioselective O-arylation of C-6-substituted pyridin-2-ones with arylboronic adds, as reported by Chen et al. [131].

Liao and coworkers [49], in 2011, reported the synthesis of a new family of benzene-based chiral hetero-disulfoxide ligands and applied them successfully in the Rh-catalyzed asymmetric 1,4-addition of arylboronic adds to chromenones. The application of the Hayashi-Miyaura reaction on these substrate types is without a doubt a milestone in the development of this process, as the synthesis of enantiopure flavanones is a significantly challenging undertaking. With this procedure, the authors achieved the desired addition products in up to 70% yield and up to 95% ee (Scheme 5.12). 

Scheme 7.36 [RuHCKCOjtPPhjjjJ-catalyzed coupling reaction of arylboronic adds with aryl aldehydes, as described by Fukuyama and coworkers [54],...

One of the first and, probably, still the cheapest and most common way of synthesizing arylboronic adds involves the reaction of a hard organometallic intermediate (i.e., Hthium or magnesium) with a borate ester at low temperature. The corresponding zinc and cadmium species are much less effective [173]. 

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