Catalytic Chemo- and Enantioselective Transformations of gem-Diborylalkanes and (Diborylmethyl)metallic Species

CONSPECTUS: Chemo- and stereoselective transformations of polyborylalkanes are powerful and efficient methods to access optically active molecules with greater complexity and diversity through programmed synthetic design. Among the various polyborylalkanes, gem-diborylalkanes have attracted much attention in organic chemistry as versatile synthetic handles. The notable advantage of gem-diborylalkanes lies in their ability to generate two key intermediates, a-borylalkyl anions and (gem-diborylalkyl) anions. These two different intermediates can be applied to various enantioselective reactions to rapidly access a diverse set of enantioenriched organoboron compounds, which can be further manipulated to generate various chiral molecule libraries via stereospecific C(sp(3))-B bond transformations. In this Account, we summarize our recent contributions to the development of catalytic chemo- and stereoselective reactions using gem-diborylalkanes as versatile nucleophiles, which can be categorized as follows: (1) copper-catalyzed enantioselective coupling of gem-diborylalkanes with electrophiles and (2) the design and synthesis of (diborylmethyl)metallic species and their applications to enantioselective reactions. Since Shibata and Endo reported the Pd-catalyzed chemoselective Suzuki-Miyaura cross-coupling of gem-diborylalkanes with organohalides in 2014, Morken and Hall subsequently developed the first enantioselective analogous reactions using TADDOL-derived chiral phosphoramidite as the supporting ligand of a palladium catalyst. This discovery sparked interest in the catalytic enantioselective coupling of gemdiborylalkanes with electrophiles. Our initial studies focused on generating chiral (alpha-borylmethyl)copper species by enantiotopicgroup-selective transmetalation of gem-diborylalkanes with chiral copper complexes and their reactions with various aldimines and ketimines to afford syn-beta-aminoboronate esters with excellent enantio- and diastereoselectivity. Moreover, we developed the enantioselective allylation of gem-diborylalkanes that proceeded by reaction of in situ-generated chiral (alpha-borylalkyl)copper and allyl bromides. Mechanistic investigations revealed that the enantiotopic-group-selective transmetalation between gem-diborylalkanes and the chiral copper complex occurred through the open transition state rather than the closed transition state, thereby effectively generating chiral (alpha-borylmethyl)copper species. We also utilized (diborylmethyl)metallic species such as (diborylmethyl)silanes and (diborylmethyl)zinc halides in catalytic enantioselective reactions. We succeeded in developing the enantiotopic-group-selective cross-coupling of (diborylmethyl)silanes with aryl iodides to afford enantioenriched benzylic 1,1-silylboronate esters, which could be used for further consecutive stereospecific transformations to afford various enantioenriched molecules. In addition, we synthesized (diborylmethyl)zinc halides for the first time by the transmetalation of isolated (diborylmethyl)lithium and zinc(II) halides and their utilization to the synthesis of enantioenriched gem-diborylalkanes bearing a chiral center at the beta-position via an iridium-catalyzed enantioselective allylic substitution process. In addition to our research efforts, we also include key contributions by other research groups. We hope that this Account will draw the attention of the synthetic community to gem-diboryl compounds and provide guiding principles for the future development of catalytic enantioselective reactions using gem-diboryl compounds.

Automated summary

Chemical and stereoselective transformations of polyborylalkanes are powerful methods to access optically active molecules efficiently. Gem-diborylalkanes, as versatile synthetic handles, can generate key intermediates for various enantioselective reactions. Catalytic reactions using gem-diborylalkanes can rapidly access diverse enantioenriched organoboron compounds for further transformations.