Alkylboronic esters

The rhodium-catalyzed borylation of methyl C-H bonds is compatible with several moieties containing oxygen, nitrogen, and fluorine.154 For example, the reaction of pinacol acetal of 2-hexanone with bis(pinacolato)diborane (B2pin2) in the presence of Cp Rh(774-C6Me6) catalyst gives the alkylboronate ester in 74% yield (Equation (111)). The rhodium-catalyzed C-H activation and borylation occur at the least hindered and least electron-rich methyl group. 

The catalytic hydroboration of vinylarenes has also been well studied and, depending on the rhodium or iridium catalytic system used, the product distribution can be tuned. [lrCl2(T -C5Me5)]2 catalyzed the hydroboration of 4-vinylanisole in the presence of HBcat with the exclusive formation of the terminal hydroboration product, in contrast to the analogue rhodium complexes which mainly afford the branched alkylboronate ester (Scheme 7.13) [14]. 

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... 

Scheme 5.13 Rhodium-catalyzed carboxylation of alkylboronic esters under mild conditions...

Scheme 5.14 Optimized copper-catalyzed carboxylation of alkylboronic esters [52].

Alkylboronic esters, as catalysts, 9, 223 Alkyl-bridged compounds, transition metal-Group 13 alkyl combinations, 3, 271... 

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. 

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)). 

The alkylboronic ester of chiral diol was used as the most efficient chiral ligand for the enantioselective Simmons-Smith cyclopropanation of substituted allylic alcohols (Equation (252)).1056-1059... 

Renaud and coworkers have also recently found that related TBDMS-protected B-alkylboronate esters are suitable radical (see Radicals) precursors for conjugate addition to activated olefins such as methyl acrylate (equation 12). Catalyzed hydroborations gave the 1,3-addition products with regioselectivity opposite to those obtained in uncatalyzed reactions. 

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. ... 

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. 

Table 3. Optically Active Secondary Amines From Alkenes via Alkylboronic Esters 1 and Alkyldichlorobo-ranes 2...

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. ... 

Brown and coworkers have described an alternative synthesis of chiral alkylboronic esters. In this synthesis prochiral alkenes are hydroborated with monoisopinocamphenylborane to yield isopinocam-phenylalkylboranes which are then readily transformed to chiral alkyllraronic esters (Scheme 39). Homologation with dichloromethyllithium, followed by reduction with potassium triisopropoxyborohy-dride (KIPBH) and oxidation, finely yields B-chiral alcohols (Scheme 40). These alcohols are not easily prepared by other methods. Aldehydes can be prepared by homologation from chiral alkylboronic esters with LiCH(OMe)SPh and oxidation (Scheme 41). ... 

Although lithium alkyls, owing to higher reactivity, show a tendency to form dialkylated products , they can also be used to prepare certain alkylboronic esters ... 

Alkylborinic esters, obtained from alkylboronic esters and an organometallic reagent, are converted into the corresponding ketones by the reaction with dichloromethyl methyl ether in the presence of a hindered base, followed by oxidation with hydrogen peroxide in pH 8 buffer or with anhydrous trimethylamine Ar-oxide18. 

These chiral alkylboronic esters are exceptionally promising intermediates for C-C bond formation reaction in the synthesis [8, 9] of a-chiral aldehydes, P Chiral alcohols, a-chiral acids, and a-chiral amines. Brown et al [10], in a real breakthrough, discovered that LiAlH readily converts these relatively inert boronic esters to a very high reactive lithium monoalkylborohydrides R BHjLi (5) of very high optical purity. The optically active monoalkylborane (R BH2) is generated, when required, by a convenient reaction with trimethylsilyl chloride [6]. Consequently, the desired B-R -9-BBN is prepared conveniently by hydroboration of 1,5-cyclooctadiene with RBHj (prepared in situ), and the desired stable 1,5-isomer is obtained by thermal isomerization. The whole sequence is illustrated in Scheme 9.1. 

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