Pinacol boronate

Although boronates are quite susceptible to hydrolysis, they have been useful for the protection of carbohydrates. Note that as the steric demands of the diol increase, the rate of hydrolysis decreases. For example, pinacol boronates are rather difficult to hydrolyze in fact, they can be isolated from aqueous systems with no hydrolysis. The section on the protection of boronic acids should be consulted. 

The reaction of hydrazonoester 6 with allenyl pinacol boronate 7 was set as a model, and several metal hydroxides (20 mol%) were screened as catalysts in H20-DMF (1 3) at room temperature [104]. It was found that allenyl adduct 8 was produced with high selectivity in the presence of bismuth(III) hydroxide, Bi(OH)3 (Scheme 3). Interestingly, copper(II) hydroxide, Cu(OH)2, preferentially gave propargyl adduct 9. On the basis of these promising results, we further optimized the reaction conditions using Bi(OH)3 and Cu(OH)2 (Table 5). 

To elucidate the reaction pathway, deuterium-labeled allenyl pinacol boronate 10 was prepared, and the addition reaction with hydrazonoester 6 was conducted in the presence of Bi(OH)3 and Cu(OH)2 (Scheme 4). In both Bi- and Cu-catalyzed cases, the reactions proceeded smoothly (in quantitative yields in both cases). In the Bi(OH)3-catalyzed reaction, a major product was allenyl compound 11, in which the internal position was deuterized. It was assumed that a propargyl bismuth was formed via transmetalation from boron to bismuth, followed by addition to hydrazonoester via y-addition to afford allenyl compound 11. Thus, two y-additions could selectively provide a-addition products [75, 76, 105, 106]. It was confirmed that isomerization of 10 did not occur. Recently, we reported Ag20-catalyzed anti-selective a-addition of a-substituted allyltributyltin with aldehydes in aqueous media [107], On the other hand, in the Cu(OH)2-catalyzed reaction, a major product was propargyl compound 12, in which the terminal position was deuterized. A possible mechanism is that Cu(OH)2 worked as a Lewis acid catalyst to activate hydrazonoester 6 and that allenyl boronate 10 [83-85] reacted with activated 6 via y-addition to afford 12. 

Thus, it was found that selective propargylation or allenylation reactions of hydrazonoester with allenyl pinacol boronate proceeded smoothly in the presence of a catalytic amount of bismuth(III) or copper(II) hydroxide in aqueous media. The use of metal hydroxide as a catalyst in organic synthesis is rare, and it is noteworthy that efficient catalysis occurred in aqueous media. In addition, the allenyl adduct was produced with high selectivity in the presence of Bi(OH)3, whereas the propargyl adduct was obtained with high selectivity in the presence of Cu(OH)2 as a catalyst. 

A reactor containing an ice-cooled solution of the step 2 product (19.76 mmol) dissolved in 150 ml THF was treated dropwise with -butyl lithium (2.5M in hexanes 19.76 mmol) and after 2 hours treated with pinacol boronate (21.72 mmol). The ice bath was then removed and the mixture stirred overnight at ambient temperature. The reaction was quenched with aqueous NH4CI and the mixture extracted three times with 70 ml of ethyl acetate. Combined extracts were then washed with brine, dried over MgSC>4, and concentrated. The residue was purified by column chromatography on silica eluting with petroleum ether/ethyl acetate, 9 1, respectively, and 9.52 g of product isolated as a blue oil. 

In a similar way, Guiles and co-workers immobilized an aryl pinacol boronate on resin via an ester linkage, and then a small number of aryl halides were coupled to this (Scheme 31). The products were cleaved and immediately transformed into their methyl esters, presumably for ease of analysis and separation from unreacted boronate. The reaction was found to be slower than that of the opposite polarity (i.e., with the resin-bound iodide), and only moderate yields were obtained after as much as 48 h. Yields could be considerably improved upon a second round of coupling, but only one example was given of this. The aryl bromides were found to react only upon heating. 

Z)- and (E)-Terminal 1,3-dienes The pinacol boronate (1) derived from trimethylsilylallyllithium provides a stereoselective route to (Z)- and (E)-terminal 1,3-dienes. Deoxysilylation of 2 can be effected to give either 3 or 4 with less than 3% of the other isomer. 

Pinacolborane 49 is a highly stable hydroborating agent. It can be easily prepared and stored without decomposition. Pinacolborane 49 reacts with alkenes and alkynes under relatively milder conditions unlike catecholborane 38. Alkenes 50 react slower than alkynes and usually undergo hydroboration in 2-3 days at 50 °C furnishing the terminal pinacol boronates 51 as the major regioisomer (>98%). Hydroboration of terminal alkynes 52 with pinacolborane proceeds at room temperature with an excellent level of regioselectivity to yield the terminal vinyl boronates 53 (Scheme 7). 

The reaction of pinacolborane with styrenes 127 in the presence of bis(chloro-l,5-cyclooctadienylrhodium) at room temperature provides styrenyl pinacol boronate 128 <1999TL2585, 2002BCJ825>. While hydroboration of alkenes is the predominant reaction with phosphine-containing rhodium catalysts such as Wilkinson s catalyst and Rh(PPh3)2COCl, dehydrogenative borylation dominates over hydroboration in the presence of phosphine-free... 

To determine the diastereoselectivity of the above bora-ene reaction, boronate 193 derived from a-pinene was synthesized. Reaction of a-pinene 192 with Schlosser s base (BunLi + KOBu ) furnishes the allyl carbanion, which upon treatment with triisopropyl borate and subsequent transesterification with pinacol yields a-pinanyl pinacol boronate 193. Bora-ene reaction with this allyl boronate and S02 at — 78 °C in CH2CI2 yields the mixed anhydride 194 as a 2.3 1 mixture of diastereomers upon removal of excess S02. Treatment of this mixture of anhydrides with aryl Grignard led to the formation of two diastereomers of aryl sulfoxides 195 in 3.2 1 ratio (Scheme 33) <2006TL2783>. 

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]. 

Figure 2.5. Boron derived inhibitors (5a) boronic acid (5b) difluoroborane (5c) pinacol boronate ester.

Figure 22.6 Boron-based monomers 14, 15, and 19-22 and reagents 16-18 for the incorporation of the pinacol-boron group into monomers.

Ligands 5 and 6 are particularly efficacious for the borylation of aryl chlorides to pinacol boronate esters, thus allowing the direct one-pof synthesis of unsymmetrical biaryls from two aryl chlorides (Equation 2.23) [41]. Due to the wide breadth and scope that this family of biaryldialkylphosphine Hgands offers for palladium-catalyzed couplings of aryl chlorides, many are commercially available and aU are highly crystalline, air-stable solids, and hence easy to use. 

Fandrick et al. used the same strategy to form a catalyst in situ for the preparation of zinc ethoxide from diethyl zinc and ethanol, to catalyze allylation of a wide range of ketones by allyl pinacol boronate, 122 (reaction 7.26) with over 90% yield [76]. 

This monomer, also named 9,9-dihexylfluorene-2,7-diboronic acid bis(l,3-propanediol) ester, is commercially available. The propanediol or pinacol boronate esters of dialkylfluorenes with different alkyl chain lengths are also commercially available products, and these compounds can be used directly in the following Suzuki polymerization. However, the given synthetic procedures for boronate ester monomers will be useful for preparing new fluorene monomers, which are not commercially available. 

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