Investigation of Differently Substituted Allylboronic Esters in Allylation Reactions

One of the most attractive reactions in the field of asymmetric synthesis is the aldehydeallylation by using allylic boronates as reagents. Due to their efficiency, non-toxicity as well as their high predictability concerning the stereochemical outcome, they have been the focus of the research of many groups, including Hoffmann et al.,[2,3] Roush et al.,[4] Corey et al.,[5] and Brown et al.[6] The reaction was explained to proceed via a closed six-membered chair-like transition state,[7-9] resulting in chiral homoallylic alcohols, which are valuable building blocks for the synthesis of many natural products. Moreover, it has been shown that reagents presenting a stereogenic centre at the $\alpha$-position with respect to the boronic ester provide increased chirality transfer. The resulting absolute configuration has been demonstrated to be dependenton two principle factors: the steric bulk of the boronic esters protecting group and the presence of a substituent exercising an electronic effect in the molecule.[10] In the past years Pietruszkaet al. have developed a tartrate derived chiral auxiliary[11] diol 1, which was used as a protective group for boronic acids, and allowed the formation of stable $\alpha$-substituted alkenyl boronic esters. Their addition to aldehydes led to the formation of enantiomerically pure Z-homoallylicalcohols, as the reagents possessed an important factor improving the Z selectivity: a sterically demanding diol covering the boronic acid.[12] Differently substituted diastereomerically pure allylboronic esters were synthesized in this work, and their addition to aldehydes was investigated in detail. The resulting enantio-enriched homoallylic alcohols were then applied in the attempt towards the synthesis of a natural product. Highly substituted allylboronic esters 2 and 4 were synthesized by two different methods (Scheme 1). Starting from the protected alkyne 3c, a one-pot hydroboration, oxidation, and transesterification sequence, followed by deprotection of the silyl group furnished 2 in a good yield. On the other hand, the haloboration reaction of protected propargyl alcohol 5 and subsequent esterification with diol 1 proceeded via an intermediate haloalkenyl boronate. Next, a Negishi coupling reaction took place in the presence of palladium catalyst and dimethyl zinc. Subsequent deprotection of the alcohol group yielded 4 in 29% over 4 step

Synthesis of Alkenylboronic Esters: An Alternative Route to Trisubstituted Homoallylic Alcohols

New alkenylboronic esters were synthesised from halo-substituted alkenylboronic esters through cross-coupling reactions. Upon Johnson rearrangement, enantiomerically pure allylboronates bearing a stereogenic centre in the position α to the boron moiety were obtained in moderate yield (53 %; 29 % over six steps from the protected propargylic alcohols). The products of these reactions were separable by medium-pressure liquid chromatography, and could be used in highly stereoselective allylation reactions to synthesise enantiomerically enriched homoallylic alcohols containing a 1,1,2-trisubstituted (Z)-configured double bond

Synthesis of Highly-Substituted Enantiomerically Pure Allylboronic Esters and Investigation of Their Stereoselective Addition to Aldehydes

Diastereomerically pure allylboronates bearing the readily available tartrate derivative were obtained via sigmatropic rearrangement. Allyl additions were performed, and the influence of γ-disubstituted allylboronates was studied. Highly γ-substituted boronic esters were found to lead to the corresponding enantiomerically enriched homoallyl alcohols with exclusively <i>E</i> configuration; their synthesis and the mechanism of the reaction is proposed here

Synthesis of Highly-Substituted Enantiomerically Pure Allylboronic Esters and Investigation of Their Stereoselective Addition to Aldehydes

Diastereomerically pure allylboronates bearing the readily available tartrate derivative were obtained via sigmatropic rearrangement. Allyl additions were performed, and the influence of γ-disubstituted allylboronates was studied. Highly γ-substituted boronic esters were found to lead to the corresponding enantiomerically enriched homoallyl alcohols with exclusively <i>E</i> configuration; their synthesis and the mechanism of the reaction is proposed here

Synthesis of Highly-Substituted Enantiomerically Pure Allylboronic Esters and Investigation of Their Stereoselective Addition to Aldehydes

Diastereomerically pure allylboronates bearing the readily available tartrate derivative were obtained via sigmatropic rearrangement. Allyl additions were performed, and the influence of γ-disubstituted allylboronates was studied. Highly γ-substituted boronic esters were found to lead to the corresponding enantiomerically enriched homoallyl alcohols with exclusively <i>E</i> configuration; their synthesis and the mechanism of the reaction is proposed here

Synthesis of Highly-Substituted Enantiomerically Pure Allylboronic Esters and Investigation of Their Stereoselective Addition to Aldehydes

Diastereomerically pure allylboronates bearing the readily available tartrate derivative were obtained via sigmatropic rearrangement. Allyl additions were performed, and the influence of γ-disubstituted allylboronates was studied. Highly γ-substituted boronic esters were found to lead to the corresponding enantiomerically enriched homoallyl alcohols with exclusively <i>E</i> configuration; their synthesis and the mechanism of the reaction is proposed here

Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors

Boronic acid transition-state inhibitors (BATSIs) represent one of the most promising classes of β-lactamase inhibitors. Here we describe a new class of BATSIs, namely, 1-amido-2-triazolylethaneboronic acids, which were synthesized by combining the asymmetric homologation of boronates with copper-catalyzed azide-alkyne cycloaddition for the stereoselective insertion of the amido group and the regioselective formation of the 1,4-disubstituted triazole, respectively. This synthetic pathway, which avoids intermediate purifications, proved to be flexible and efficient, affording in good yields a panel of 14 BATSIs bearing three different R1 amide side chains (acetamido, benzylamido, and 2-thienylacetamido) and several R substituents on the triazole. This small library was tested against two clinically relevant class C β-lactamases from Enterobacter spp. and Pseudomonas aeruginosa. The Ki value of the best compound (13a) was as low as 4 nM with significant reduction of bacterial resistance to the combination of cefotaxime/13a