Organoboronic acids esters

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

Under oxygen and in the presence of Pd(OAc)2 organoboronic acids/esters couple with electron-deficient alkenes, no base is needed. 

Much attention has recently been focused on organoboronic acids and their esters because of their practical usefulness for synthetic organic reactions including asymmetric synthesis, combinatorial synthesis, and polymer synthesis [1, 3, 7-9], molecular recognition such as host-guest compounds [10], and neutron capture therapy in treatment of malignant melanoma and brain tumor ]11]. New synthetic procedures reviewed in this article wiU serve to find further appHcations of organoboron compounds. 

The rhodium-catalyzed asymmetric conjugate addition is applicable to a,yS-unsaturated esters (Scheme 3.8). Hayashi reported [20] that the reachon of 5,6-dihydro-2H-pyran-2-one 19a with phenylboronic acid gave a 94% yield of phenylated lactone (S)-20am with 98% enanhomeric excess. For the linear enoates, organoboronic acids did not give... 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

The covalent C-B bonds of organoboronic acids and esters are very inert to ionic and radical reactions, thus allowing functionalization of remote sites other than the B-G bond (Equations (94)-(97)). Bulky diols such as pinacol have been used as the protecting group of B(OH)2 because of their high stability to nucleophiles and water and silica gel in amination of 316,474 hydroboration-amination of 317,475 Wittig reaction of 3 18,476 and oxidation-alkylation of 319.477... 

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... 

Triflates (pseudohalides) instead of halides as well as boron esters instead of organoboronic acid may also be used. 

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. 

Potassium aryl- and 1-alkenyltrifluoroborates (ArBFsK and RBF3K) are easily prepared from organoboronic acids or esters. In general, the trifluoroborates have greater air stability and greater nucleophilicity " when compared to the... 

Organoboronic acids or their esters are generally stable to air and thermal treatment. Thus, the boronic esters can be isolated by distillation, and acids by crystallization. 

I) Mercurideboronations. Organoboronic acids, RB(OH)2 or their esters with mercury salts HgXj [X = Cl, Br or OAc (OAc is 0C(0)CH3)] provide RHgX ... 

Other boryl esters of dithiocarboxylic acids 69 are obtained by sulfurization of the corresponding carboxylic acids, esters or amides with organoboron sulfides such as (9-BBN)2S andbis(l,5-cyclooctanediylboryl) sulfide (Scheme 16) [124,125]. Methanolysis of the boryl esters 69 gives the corresponding dithiocarboxylic acids. 

Scheme 16 Formation of boryl esters of dithiocarboxylic acids by sulfurization of the corresponding carboxylic acids, esters or amides with an organoboron sulfide...

Copper-catalyzed conjugate addition of organoboronic acids and esters to electron-deficient alkynes, precursors of natural products analogs 13YGK296. 

A solution of CuCl (1.5 mg, 15 pmol), the NHC ligand precursor (8.7 mg, 17 pmol), and NaOMe (32.4 mg, 0.600 mmol) in THF (0.40 mL) was stirred for 15 min at RT. The organoboronic acid neopentylglycol ester (0.600 mmol) was added and the mixture stirred for 5 min at RT. The allylic phosphate (0.300 mmol) was then added with additional THF (0.20 mL), and the resulting mixture was stirred for 16 h at 30 °C. After dilution wifli EtOAc, the mixture was passed through a pad of silica gel with EtOAc, and the solvent was then removed under vacuiun. The residue was purified by silica gel preparative TLC using EtOAc/hexane to afford the desired product. For ee analysis, the product was converted into the corresponding primary alcohol via a hydroboration-oxidation sequence. 

Organoboron dihalides from boronic acid esters... 

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. 

The rhodium-catalyzed addition of aryl- and 1-alkenylboronic acids tooc, unsaiurated ketones, aldehydes, esters, and amides gave the conjugate 1,4-addition products in high yidds. The ifaodium(I) complexes also catalyzed the 1,2-addition of organoboronic acids to aldehydes or N-sulfonyl aldimines. The dficiency of protocol was demonstrated in the asymmetric addition reactions of organoboronic acids in the presoice of a rhodium(acacV BINAP complex. 

Asymmetric addition of 4-chlorophenylboronic acid (2u) to a,P-unsaturated y-amino ester (26a), followed by deprotection and ester hydrolysis gave optically active 4-amino-3-(4-chlorophenyl)butyric acid (Baclofen) hydrochloride (Scheme 4.10), which plays an important role in various nervous system functions. The best result was observed with a large excess of organoboronic acids (5.0 equiv to 26a) in a 10 1 dioxane-water mixture containing aqueous cesium carbonate [24]. 

Miyaura, N. Metal-Catalyzed Reactions of Organoboronic Acids and Esters. Bull. Chem. Soc. Jpn. 2008,81,1535-1553. 

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