Boronates alkylboronates

Diastereoselective homologation of chiral alkylboronates (cf. 12, 80-81). Investigations of this reaction have been carried out mainly on boronic esters (1)... 

A mild one-pot procedure based on a platinum-catalyzed diborylation of 1,3-butadienes (see Eq. 30) gives doubly allylic boronate 144, which adds to an aldehyde to form a quaternary carbon center in the intermediate 145 (Eq. 105). The use of a tartrate auxiliary in this process leads to good levels of enantiose-lectivity in the final diol product, which is obtained after oxidation of the primary alkylboronate intermediate. Although examples of aliphatic, aromatic, and unsaturated aldehydes have been described, enantioselectivities vary widely (33 to 74% ee), and are good only for aliphatic aldehydes. An intramolecular variant of this interesting tandem reaction is also known. ... 

Yet another use for bis(oxazoline) ligands is in the synthesis of (a-chloroalkyl) boronates. " " As shown in Figure 9.71, the alkylboronate 240 was converted to the a-chloro derivative 241 in 86% ee through the use of ytterbium(lll) triflate-complexed phe-box 6. 

A)-Pinanediol ethylboronate with (l,l-dichloroelhyl)lithium yields the (S)-a-chloro boronic ester (89 11 d.r.), which is converted by phenylmagnesium bromide to the (S)-tert-alkylboronate, the same isomer obtained from (S )-pinanediol phenylboronate. The enantiomeric excess of the derived (R)-2-phenyl-2-butanol is 70%. 

Homologation of boronic esters. The reagent 1 can be formed in situ by reaction of CH2C12 with lithium 2,2, 6,6 -tetramethylpiperidide (LiTMP) or even LDA. The product obtained on reaction of 1 with alkylboronic esters, an a-chlo-roboronic ester, is reduced by potassium triisopropoxyborohydride (KIPBH) to the homologated boronic ester.1... 

Alkylboronates can be obtained by the hydroboration of alkenes. This reaction is frequently applicable when the addition of an anion to a trialkyl boronate is not feasible. Cat-echolborane is an effective hydroboronating agent. 12 In addition to reacting with unsubstituted alkenes, it is effective in the hydroboronation of 1-haloalkenes at elevated temperatures 21 and at room temperature in the presence of Wilkinsons catalyst. 22 For example, 1,3-dibromopropene reacts with catecholborane to give 1,3-dibromopropylboronate... 

Alkylboron boron compounds, cross-coupling reactions,... 

Cross-coupling reactions 5-alkenylboron boron compounds, 9, 208 with alkenylpalladium(II) complexes, 8, 280 5-alkylboron boron, 9, 206 in alkyne C-H activations, 10, 157 5-alkynylboron compounds, 9, 212 5-allylboron compounds, 9, 212 allystannanes, 3, 840 for aryl and alkenyl ethers via copper catalysts, 10, 650 via palladium catalysts, 10, 654 5-arylboron boron compounds, 9, 208 with bis(alkoxide)titanium alkyne complexes, 4, 276 carbonyls and imines, 11, 66 in catalytic C-F activation, 1, 737, 1, 748 for C-C bond formation Cadiot-Chodkiewicz reaction, 11, 19 Hiyama reaction, 11, 23 Kumada-Tamao-Corriu reaction, 11, 20 via Migita-Kosugi-Stille reaction, 11, 12 Negishi coupling, 11, 27 overview, 11, 1-37 via Suzuki-Miyaura reaction, 11, 2 terminal alkyne reactions, 11, 15 for C-H activation, 10, 116-117 for C-N bonds via amination, 10, 706 diborons, 9, 167... 

One of the prominent synthetic protocols for the preparation of diazaborolines 323 involves the reaction of lithiated diamides 324 with boron halides and subsequent elimination of lithium halide salt. Another protocol involves synthesis via cyclocondensation of 1,2-diimines 325 with alkylboron halides to yield the diazaborolium salts 326 that undergo reduction with sodium amalgam yielding the diazaborolines 323 in high yield (Scheme 53) <2005EJI4715>. 

Computational studies performed on model complexes in collaboration with Hall and coworkers suggest that alkane borylation may occur by a ej-bond metathesis pathway (Scheme 3) [48]. The proposed mechanism for the borylation of alkanes by 1 begins with elimination of HBpin to generate the 16-electron complex Cp Rh(Bpin)2. This complex then forms a <7-complex (3) with the alkane. The vacant p-orbital on boron then enables cr-bond metathesis to generate a o-borane complex (4). Reductive elimination of the alkylboronate ester product and oxidative addition of B2pin2 then regenerate 1. 

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. 

The catalyzed hydrogenation of alkenylboronic esters was used for the diastereoselective synthesis of alkylboronic esters 276446 (Equation (75)). The hydrogenation of a pyrrolboronic acid provided a prolineboronic acid, which was then resolved by HPLC to give an optically active boronic ester 277447 (Equation (76)). 

Important advances in the field of C-H bond activation have involved the photochemical reactions of boryl complexes such as Cp W(CO)3(Bcat) (98, cat = 1,2-02-3,5-Me2C6H2). Transient species derived from these complexes efficiently activate the C-H bonds of alkanes and arenes (see Alkane Carbon-Hydrogen Bond Activation), and they can convert hydrocarbon solvents into alkylboronate esters (equation 27). Experimental and theoretical studies have shown that these reactions proceed via a boron-assisted, a-bond metathesis see a-Bond Metathesis) pathway involving back donation of electron density from the tungsten atom to a formally unoccupied p orbital centered on the boryl ligand. ... 

At the root of the instability of fluoroaUcylboron compounds is the availability of a vacant orbital on boron it will be seen that when boron is co-ordinately saturated, as in four-covalent boron derivatives (10.26A), or partially saturated by tt bonding with attached oxygen- or nitrogen-containing groups (10.26B), then the stability of perfluoro-alkylboron compounds increases (Figure 10.26). 

When 18 is treated with acetone, boronic ester 20 with a cyclooctatriene structure is cleanly obtained indicating the valence tautomerism between 18 and 19. In fact, 19 appears to be the kinetic product in the borylation of lithium or potassium cyclononatetraenide with alkylboron dihalides which rearranges quickly to 18 due to the comparatively high thermodynamic stability of the latter.1819 Acetaldehyde,... 

Di- and trisubstituted alkenes were converted to optically active alkylboronic esters (1) with 99% ee according to the procedure described in Section 1.23.3. The boronic esters were then treated sequentially with lithium aluminum hydride and hydrochloric acid to afford the required optically active alkyldichloroboranes 2 (>99% ee). The reaction of the alkyldichloroboranes with organic azides was best performed in 1,2-dichloromethane as the solvent to yield the required amines 3. Representative secondary amines containing one or two stereogenic centers, C2-sym-metrical and mew-amines have been synthesized by this route with >99% ee (Table 3)22. 

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]. 

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]. 

The hydroboration-coupling approach for the construction of carbon skeletons affords several advantages [139]. The high stereoselectivity of the hydroboration reaction provides a stereodefined alkyl center on boron. For instance, in the reaction shown in Scheme 2-49, the hydroboration occurs chemoselectively at the less hindered C(19)-C(20) double bond. In addition, the alkylboron group thus constructed can be readily cross-coupled with alkenyl or aryl halides under mild conditions. 

Boronic esters (8) react with dichloromethyllithium to form intermediate borate complexes which then undergo rearrangement to form 2-haloboronic esters (9). When treated with a Grignard reagent, the 2-haloboronic esters (9) rearrange to secondary alkylboronic esters (10 Scheme 3). 

Boronic esters are not as reactive as triorganylboranes towards nucleophiles however, rearrangement does take place if the boronic ester is treated with an a-halocarbanion (equation 54). In this case, the I-chloroethylboronate (36) can be obtained in 95% de due to the diastereofacial influence of the chiral pinanediol. Similarly, chloro- or bromo-alkylboronic esters react with Grignards reagents, alkyllithiums and enolates leading to rearranged products. ... 

On heating, alkylborons may undergo isomerization by migration of the boron to a less sterically encumbered position by a series of reversible j8-hydride elimina-tion-hydroboration steps. Displacement of the isomerized olefin may be effected by addition of a second olefin, which forms a more stable alkylboron than the one displaced. This reaction has been used to effect the contrathermodynamic isomerization of olefins. 

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