Boronic pinacol derived

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. 

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>. 

The Suzuki-Miyaura tactic carried out on solid support (Scheme 28) [52] provides routes to small libraries of condensed heterocycles. Thus, Merrifield resin with the LeznofF-linked bromobenzene derivative 78 undergoes cross-coupling under normal solution-phase conditions with boron pinacolate 79 or boronic acid 80, prepared by DoM, to afford phenan-thridines 81 or, via 82 and some manipulation, dibenzopyranones 83 in good yields and with high purities. The Stille solid-support reaction has also been successfully executed [53]. 

The conversion of boronic acids into phenols has been achieved using visible light catalysis (Scheme 2.32) [42]. hi addition to light, the catalyst components consisted of a ruthenium bipyridine species, an amine, and DMF. All the components were needed for a successful reaction since low conversions were observed if any of the components were absent. The ability to use air as the oxidant was one of the practical aspects of this chemistry. While a wide range of arylboronic acids were successfully transformed into phenols, a pinacol-derived arylboronate also served as a substrate in these reactions (up to 94% conversion). In addition to the ruthenium-catalyzed reaction, a metal-free version of die chemistry was also developed using an organic dye. 

The convenient synthesis of the a-chloro-substituted pinacol-derived boro-nate 46 commences with the hydroboration of propargyl alcohol 57 (Scheme 5.10) [57]. Following protection of the secondary alcohol, hydroboration of the alkyne and transesterification furnishes boronate 59. Treatment of 59 with thionyl chloride stereospecifically installs the a-chloro substituent of 46. 

The Pd-catalyzed reaction of such polyfunctional boronic esters like 21b with various aryl halides provides the desired cross-coupling products like 22 in high yields [10,11]. Interestingly, a one-pot reaction allowing the selective reaction with two electrophiles is possible. Thus, the treatment of the meta-iodophenyl boronic pinacol ester 18 with i-PrMgCl LiCl followed by a transmetallation to the copper derivative and subsequent reaction with 2-methyl-3-iodocyclohexenone provides the intermediate boronic ester 23 that after a Suzuki-Miyaura cross-coupling, furnishes the heterocyclic product 24 in 52% yield (Scheme 3.6) [11]. 

Boronic esters are easily prepared from a diol and the boronic acid with removal of water, either chemically or azeotropically. (See Chapter 2 on the protection of diols.) Sterically hindered boronic esters, such as those of pinacol, can be prepared in the presence of water. Boronic esters of simple unhindered diols are quite sensitive to water and hydrolyze readily. On the other hand, very hindered esters, such as the pinacol and pinanediol derivatives, are exceedingly difficult to hydrolyze and often require rather harsh conditions to achieve cleavage. 

Allylboronates prepared from simple diols display appreciable reactivity, but eyelie boronate derivatives prepared from 1,2- or 1,3-diols display considerably less. The commonly employed pinacol esters are among the least reactive members of this class. 2-Allyl-3-methyl-l,3,2-oxaza-... 

Addition of a boron-boron bond across a carbon-carbon triple bond is known for some 40 years since the finding that diboron tetrahalides add to alkenes and alkynes in the absence of catalysts.36 Although the reaction seemed to be potentially attractive, the instability of diboron tetrahalides was the critical drawback for the practical use in synthesis. In 1993, much more stable pinacol ester derivative of diboron was found to add to alkynes in the presence of platinum catalysts such as Pt(PPh3)4, Pt(CH2=CH2)(PPh3)2, and Pt(CO)2(PPh3)2 (Figure 1, Scheme 2).37,38 Other... 

Pinacols (61) derived from a variety of aromatic aldehydes have been employed in enantio- and diastereo-selective allylations of aliphatic aldehydes.174 Their allyl-boronate derivatives react under Lewis acid conditions (SnCU) with a variety of aldehyde types, in good yield and ee. Even better results are obtained by addition of (61) as a I irons led acid (auto)catalyst, via coordination/activation of the tin catalyst. 

Since boronates derived from pinacol are air stable, we decided to prepare olefins of type (4) according to the following sequence ... 

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.

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

Then, the scaffold 9 was reacted with 12 boronic acid pinacol ester derivatives (10a-101), yielding the corresponding 6-arylcoumarins, lla-111. Although the compounds with an electron-withdrawing group, such as nitro (lie), cyano (Hi), or methoxycarbonyl (llj), were obtained in relatively low yield (28%, 45%, and 46%, respectively), most of the reactions proceeded in moderate yield. Some functional groups on the phenyl group were rather easily transformed, as observed in the syntheses of 11m, lln, and llo. 

A standard way to make vinyl boronic acids 237 is to hydroborate an alkyne with catechol borane38 235 and again hydrolyse the ester products 236. The empty orbital of the boron atom attacks the electron-rich terminus of the alkyne where is the larger HOMO of the Jt-bond. One detailed example39 includes Suzuki coupling to Z-styryl bromide. Another diester group commonly used in the Suzuki coupling is derived from pinacol - examples appear later. 

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