Synthesis alkylboronic esters

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)). 

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). ... 

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. 

The reactions of dialkyl- or diarylborinic acid esters and alkylboronic acid esters with organolithium, Mg or Al compounds may serve to prepare unsymmetrical BRjR and BArjAr organoboranes " Synthesis of such organoboranes usually proceeds without complications ... 

Alkenylboronic acids and esters are also very useful substrates (Equation 71, Figure 1.38) [405], in particular to access substituted olefins and dienyl moieties commonly encountered in several classes of bioactive natural products [282, 406]. To this end, Kishi and co-workers examined the influence of the base, and developed an optimal variant using thallium hydroxide [281]. Recently, allylic alcohols were found to couple directly with alkyl and alkenyl boronic acids without the aid of a base [407]. In rare cases, the Suzuki reaction has been applied to the use of alkylboronic acids [296, 408], including cyclopropylboronic acids [409]. Hitherto notorious for their tendency to undergo [3-hydride elimination, alkyl bromides are now suitable as electrophiles under carefully optimized conditions that even allow Csp -Csp couplings with alkylboronic acids (Equation 72) [410]. The Suzuki reaction has also been applied very successfully in solid-phase chemistry and combinatorial library synthesis [411]. It has been applied industrially [412], especially in medicinal chemistry, e.g. in the production of the antihypertensive drug losartan [195]. 

Chiral alkyldihaloboranes are one of the most powerful chiral Lewis acids. However, in general, since alkyldihaloboranes readily decompose into alkanes or alkenes by protonolysis or (3-hydride elimination, it is difficult to recover them as alkylboronic acids quantitatively. Aryldichloroboranes are relatively more stable and can be reused as the corresponding boronic acids. Ishihara and Yamamoto et al. have developed chiral aryldichloroboranes 21 bearing binaphthyl skeletons with axial chirality as asymmetric catalysts for the Diels-Alder reaction of dienes and a,(3-unsaturated esters (Equation 31) [29]. (J )-2-Dihydroxyboryl-l,T-binaphthyl (20) can be synthesized from (R)-binaphthol in several steps [25]. The synthesis of racemic 20a has also been reported by Kaufmann et al. [30]. Compound 20 has been converted into 21 by two dif-... 

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