Enantioselective Cu-catalyzed double hydroboration of alkynes to access chiral gem-diborylalkanes

Abstract

Chiral organoborons are of great value in asymmetric synthesis, functional materials, and medicinal chemistry. The development of chiral bis(boryl) alkanes, especially optically enriched 1,1-diboron compounds, has been greatly inhibited by the lack of direct synthetic protocols. Therefore, it is very challenging to develop a simple and effective strategy to obtain chiral 1,1-diborylalkanes. Herein, we develop an enantioselective copper-catalyzed cascade double hydroboration of terminal alkynes and highly enantioenriched gem-diborylalkanes were readily obtained. Our strategy uses simple terminal alkynes and two different boranes to construct valuable chiral gem-bis(boryl) alkanes with one catalytic and one ligand pattern, which represents the simplest and most straightforward strategy for constructing such chiral gem-diborons.

Enantioselective copper-catalysed cascade hydroboration and hydroallylation of alkynes to access chiral homoallylic boronates

“…6d). Based on these control experiments and the present related literature, [51][52][53][57][58][59][60][61][62][63][65][66][67][68] a proposed mechanistic picture for this cascade asymmetric hydroboration and hydroallylation of alkynes was shown in Fig. 6e.…”

“…63 Despite these impressive advances, the asymmetric geminal difunctionalizations of alkynes remain scarce and are confined to deliver 1,1heterodifunctionalized molecules to date. [57][58][59][60][61][62][63] The exploration of an asymmetric version involving at least one C-C bond formation has been met no success. This is possibly due to the extra competitive, inevitable reduction reaction of metal hydride with carbon-based electrophile.…”

“…[59][60][61][62] Quite recently, another advance on double hydroboration of alkynes as a facile manner to prepare chiral gem-diborylalkanes has also been made by the groups of Song and Yu. 63 Despite these impressive advances, the asymmetric geminal difunctionalizations of alkynes remain scarce and are confined to deliver 1,1heterodifunctionalized molecules to date. [57][58][59][60][61][62][63] The exploration of an asymmetric version involving at least one C-C bond formation has been met no success.…”

Ir-Catalyzed Regioselective Dihydroboration of Thioalkynes toward Gem-Diboryl Thioethers

“…Hydroboration of alkynes represents one of the most straightforward, practical, and atom-economic methods for the synthesis of organoboron compounds. − Recently, various catalytic systems have also been developed to achieve alkyne dihydroboration, providing efficient access to diverse gem -diboryl alkanes. − However, so far, these reactions have been mainly limited to terminal alkynes and some activated electron-poor alkynes. − The resulting products are essentially those gem -diboryl compounds bearing an α-carbon substitution but never a heteroatom-based substituent (other than boryl). Indeed, to achieve the latter goal, a hetero-substituted alkyne has to be used, and hydroboration has to take place twice with both α-regioselectivity, which unfortunately remains unknown.…”

Copper-Catalyzed Protoboration of 1,3-Diynes as a Platform for Iterative Functionalization

“…Additionally, -Bdan derivatives impart aggregation-induced emission (AIE) and other interesting optical properties as a pendant linkage . The pioneering work of Zweifel on the dihydroboration of 1,3-diynes with borane providing 1,4-diboryl-1,3-dienes highlighted the importance of a route to boryldienes. − Metal-catalyzed hydro/protoboration of 1,3-enynes are also prominent. − However, there are no reports on the metal-catalyzed diprotoboration of 1,3-diynes providing isolable diboryl-1,3-dienes.…”