Alkylboronic acid

Compared to aryl- and alkenylboronic adds, alkylboronic acids and esters have found limited use as synthetic intermediates aside for their oxidation into alcohols (Section 1.5.2.1). This is due in part to their inferior shelf-stability. In addition, their trans-metallation with transition metal catalysts such as palladium is presumed to be more difficult than that of the unsaturated and aromatic boronic acid derivatives [296]. For example, alkylboronic adds have long been known to be reluctant substrates in the Suzuki-cross-couphng reaction, and they have become eflfident in this apphcation only very recently with the use of special bases and the advent of new and highly active catalyst systems (Section 1.5.3.1). Perhaps the most synthetically useful class of alkylboronic adds are the a-haloalkyl derivatives popularized by Matteson (Section 1.3.8.4), and their elegant chemistry is described in Chapter 8. 

Figute1.23 Alkylboronic acids (esters) selected examples of enantioselective preparative methods. 

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While the introduction of aryl groups has been well documented, the use of alkylboronic acids to decorate the pyridazine core is hitherto not well explored. Wermuth and co-workers nicely showed that hydroboration of alkenes with 9-BBN followed by Suzuki coupling with 3-iodopyridazines 180 and 182 yielded the corresponding 3-alkylpyr-idazines 181 and 183 in good yield (Schemes 43 and 44) <2002SL1123>. 

Keywords iodobenzene, alkylboronic acid, Suzuki coupling, palladium-doped... 

In 2006, Yu et al. combined pyridinyl-directed C-H activation and C-C bond formation with alkylboronic acids (see Section 10.5.4.2).23 The success of this transformation relied on the combination of palladium acetate (10 mol%), benzoquinone (1 equiv), and silver oxide or carbonate (0.5 equiv) in a protic solvent, but an excess of boronic acid (3 equiv) was required (Scheme 10.9). Interestingly, in this reaction silver oxide played a dual role as promoter for the transmetallation step and as cooxidant with benzoquinone. 

Apart from trimethylborate, other trialkyl- and triarylborates, as well as alkylboron acids, are used. E.g., trialkylborates are good catalysts for the polymerisation of acrylonitrile, methylmethacrylate, styrene, vinylacetate, vinylchloride, vinylidenchloride, etc. The polymerisation of these monomers requires traces of oxygen. Oxygen seems to transform part of trial-kylborate into peroxide, which reacts with unoxidised trialkylborate and forms free radicals initiating polymerisation. 

Alkylboron acids and their ethers are used as additives to engine fuels. Some alkylboron acids (nonyl- and dodecylboron) are bactericides, fungicides, surface active agents. They can be used as additives to petrol, as reactants in the synthesis of polymers and as stabilisers of aromatic amides. 

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. 

Although the reaction of alkylboronic acids is significantly slower than that of trialkylboranes, methylboroxine (MeBO)3 or methylboronic acid exceptionally alkylates bromo- and chloroarenes [125, 126]. Methylation of electron-poor bromoarenes was efficient, whereas prolonged reaction time was required for more electron-rich substrates. The reaction times can be shortened by use of the polar solvent DMF at 115 °C. B-Methyl-9-BBN and its oxy-derivative (48) [127] undergo methylation of aryl and vinyl halides under more mild conditions (Scheme 22). 

Alkylboronic acid esters, RB(OR )2, can be prepared by addition of an excess of an alcohol to the reaction abovc. ... 

Chiral alkyldihaloboranes are among the most powerful chiral Lewis acids. In general, however, because alkyldihaloboranes readily decompose to alkanes or alkenes as a result of protonolysis or /3-hydride elimination, it is difficult to recover them quantitatively as alkylboronic acids. Aryldichloroborane is relatively more stable and can be reused as the corresponding boronic acid. We have developed chiral aryldichlorobor-anes 23 bearing binaphthyl skeletons with axial chirality as asymmetric catalysts for the Diels-Alder reaction of dienes and a,/3-unsaturated esters (see, e.g., Eq. 37) [36]. 

Attempts to isolate clathrochelate technetium (III) tris-dioxi-mates via template cross-linking three dioxime molecules with alkylboronic acid have not been successful. Only semiclathrochelate TcNx(HNx)2(BR2)Hal and TcDm(HDm)2(BR2)Hal complexes (where HaF is Cr, Br R is CH3 and A1-C4H9) were prepared [87, 88],... 

Alkylboronic acids and arylboronic acids, RB(OH)2, and ArB(OH)2, respectively, are increasingly important in organic chemistry. The palladium catalyzed coupling reaction of aryl halides and aryl triflates with arylboronic acids (the Suzuki-Miyaura... 

Alkylboronic acids are coupled to aryl halides using a palladium catalyst, " analogous to the Suzuki reaction in 13-12. Conversely, arylboronic acids can be coupled to aliphatic halides Arylboronic acids can be coupled to allylic alcohols as well. " Arylboronic acids (12-28) were shown to react directly with benzene in the presence of Mn(OAc)3. " Arylboronic acids also couple with alkyl halides in... 

Boronic acids (5a) were among the first examples of low-molecular-weight, reversible inhibitors of serine proteinases [151, 152]. Significant inhibition was initially demonstrated against a-chymotrypsin. Unlike the carbonyl-derived reversible inhibitors, which require a polypeptide or peptide-like chain, activity was found with simple alkylboronic acids (e.g. the value for PhCH2CH2B(OH)2 with a-chymotrypsin was = 40 //M) [153], Weak inhibition of elastase (PPE) was first reported for a series of arylboronic acids, for example, (10-1) [123]. Some of the boron-based inhibitors Figure 2.5) were tested as either the difluoroboranes (5b) or as the pinacol boronate esters (5c). These modifications were employed because they were more readily synthesized and/or purified than the boronic acids. For both of these derivatives inhibition was shown to be due to in situ hydrolysis to the parent boronic acid (5a) [154, 155]. 

Although alkylboronic acids or their esters are quite inert under the above conditions, the organoboronates are more convenient to use, since they are stable in air and are... 

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