Borates/boronates, nucleophilic

All examples mentioned so far correspond to reactions between two aromatic groups, however, couplings in which one or both partners are alkyl groups can be achieved using electron-rich boron-based nucleophiles. Fiirstner has reported the use of B-alkyl or 5-allyl methoxy-9-BBN anions for the efficient coupling with some aryl chlorides using an in situ prepared IPr HCl/Pd(OAc)j system [118], Some of the results obtained with these easy-to-handle borate-based nucleophiles are shown below (Scheme 6.34). 

C-nucleophile (X = active H-borate, boronate) N-nucleophile (amine, NaN3, tosyl amide, amide, lactam, imine, carbamate, urea) O-nucleophile (alcohol, acid, carbonate) S-nucleophile (PhS02Na)... 

Some boronic acid-based enzyme inhibitors undergo strong yet reversible covalent attachment to a nucleophile at the enzyme s active site, while others simply act as competitive inhibitors in their borate conjugate base form. Boronic acid-based inhibition of thrombin has been achieved <93MI109>, and that of P-lactamases has been particularly effective <95TL8399, 96M1688>. When compared to other covalent transition-state analog inhibitors of P-lactamases like phos-... 

The mechanism is very similar to that of the Stille coupling. Oxidative addition of the vinylic or aromatic halide to the palladium(O) complex generates a palladium(II) intermediate. This then undergoes a transmetallation with the alkenyl boronate, from which the product is expelled by reductive elimination, regenerating the palladium(O) catalyst. The important difference is the transmetallation step, which explains the need for an additional base, usually sodium or potassium ethoxide or hydroxide, in the Suzuki coupling. The base accelerates the transmetallation step leading to the borate directly presumably via a more nucleophilic ate complex,... 

The synthetic value of the reaction lies in the modification of these organoboranes. The commonest reaction involves the decomposition of the borane by alkaline hydrogen peroxide. The highly nucleophilic hydroperoxide anion attacks the electron-deficient boron with the formation of an ate complex. Rearrangement of this leads to the formation of a borate ester which then undergoes hydrolysis to an alcohol in which an oxygen atom has replaced the boron (Scheme 3.15). The overall outcome of this reaction is the anti-Markownikoff hydration of the double bond. The regiochemistry is the reverse of the acid-catalysed hydration of an alkene. The overall addition of water takes place in a cis manner on the less-hindered face of the double bond. 

The thermal reactions of the pyridinium borate salts are likely to follow the same electron-transfer path. Experimental evidence for this conclusion is the fact that the 5cc-butyl transfer is substantially faster than methyl transfer although a nucleophilic substitution mechanism would predict the less hindered group to be transferred preferentially. The fast rates of 5cc-butyl transfer can be readily explained on the basis of the electron-transfer mechanism (Eqs. 69-71) by considering the different boron-carbon bond strength [189, 190] for the various alkylborates. The boron-carbon bond cleavage (Eq. 70) is apparently the critical step, and its relative rate [191] as compared to that of the back electron transfer determines the overall rate for thermal alkyl transfers in pyridinium tetraalkylborate salts. 

Tetracoordinated borate complexes are usually formed as intermediates, which are not always isolated. Convenient methods for the synthesis of aryl borates consist of the reaction of boron halides with an appropriate organometallic compound or the complexation of boranes with a nucleophile (76JOM281 78JCS(P2)1225 79MI2). Application of the former... 

Alternatively, a similar borate intermediate can be obtained by the reaction of organoborate with chloromethyl- or (dichloromethyl)lithiums (eq (22) and (23)). When a chiral diol ester reacts w ith (dichloromethyl)lithium, an optically active a-chloroalkylboronate is produced with an excellent enantiomeric excess [34] (eq (23)). The C-Cl bond is then displaced readily w ith alkyl, aryl, or 1-alkenyl nucleophiles with inversion of configuration. The procedure has been extensively used for the preparation of chiral boronates, which have been used in organic syntheses [30]. 

The 5 y -opening of epoxides is a challenging reaction pathway to access. The use of arylborates, 122, may provide a general non-catalyzed route to such a reaction manifold <05CC1426>. Treatment of epoxide 121 with borate 122 provides 123 in 63% yield. The reaction occurs through an initial activation of the epoxide with the boron followed by syn-nucleophilic attack of the phenolic oxygen. This reaction occurs with some A-Boc aziridines as well although both syn and anfi-opened products are obtained. 

In addition to ketone substrates, the 4-o-hydroperoxyflavin can also react by nucleophilic attack on other molecules. Thus, boronic acid substrates were transformed into the corresponding alcohols via the intermediate borate esters as hydrolytically labile initial enzyme productsl90> 91). 

In studies concerned with optimization of the Suzuki cross-coupling of 2-pyridyl nucleophiles, lithium triisopropyl 2-pyridylborates are shown to be the most suitable boron coupling partners (eq 60). The borates are isolated and subjected to coupling with various aryl and hetaryl halides (X = Cl, Br) to give the corresponding azabiaryls. ... 

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