Palladium-Catalyzed Chemoselective Negishi Cross-Coupling of Bis[(pinacolato)boryl]methylzinc Halides with Aryl (Pseudo)Halides

We describe a palladium-catalyzed chemo-pharmaceutical selective Negishi cross-coupling of a bis[(pinacolato)boryl]-methylzinc halide with aryl (pseudo)halides. This reaction affords an array of benzylic 1,1-diboronate esters, which can serve as useful synthetic handles for further transformations. The developed coupling reaction is compatible with various functional groups and can be easily scaled up. The coupling of bis[(pinacolato)boryl]methylzinc halides with pharmaceuticals and the subsequent late-stage manipulations demonstrate the power of the developed protocol.11Nsciescopu

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.11Nsciescopu

Generation and Application of (Diborylmethyl)zinc(II) Species: Access to Enantioenriched gem-Diborylalkanes by an Asymmetric Allylic Substitution

We report the successful generation of (diborylmethyl)zinc(II) species by transmetallation beteween isolable (diborylmethyl)lithium and zinc(II) halide (X=Br, Cl) and their application in the synthesis of enantioenriched gem‐diborylalkanes bearing a stereogenic center at the β‐position of the diboryl groups by an asymmetric allylic substitution reaction. The reaction has a broad substrate scope, and various enantioenriched gem‐diborylalkanes can be obtained in good yields with excellent enantioselectivity. Further elaboration of the enantioenriched gem‐diborylalkanes provides access to a diverse set of valuable chiral building blocks.11Nscopu

Copper-Catalyzed Diastereoselective Addition of Diborylmethane to N-tert-Butanesulfinyl Aldimines: Synthesis of β-Aminoboronates

We have developed a highly chemo- and diastereoselective alkylation of N-tert-butanesulfinyl aldimines with diborylmethane. Whereas the addition of diborylmethane under metal-free conditions shows poor diastereoselectivity, the use of a copper catalyst and a bidentate phosphine ligand significantly enhances the diastereoselectivity, providing chiral beta-aminoboronates in good yields. On the basis of the stereochemical outcome, we propose that the reaction likely proceeds via a boron-chelating six-membered chairlike transition state.112816sciescopu

Stereoselective Access to Tetra‐ and Tri‐Substituted Fluoro‐ and Chloro‐borylalkenes via Boron‐Wittig Reaction

Reported herein is the efficient synthesis of tetra- and tri-substituted ( Z )-fluoro- and ( Z )-chloro-borylalkenes by the Boron–Wittig reaction of ketones and aldehydes with bench-top stable halo-diborylmethanes. The substrate scope is broad and the Boron–Wittig reaction proceeds from a diverse range of ketones and aldehydes including biologically relevant molecules with fluoro- or chloro-diborylmethanes, providing tetra- and tri-substituted ( Z )-fluoro- and ( Z )-chloro-borylalkenes in good yields with high stereoselectivity. The utilities of the obtained ( Z )-fluoro- and ( Z )-chloro-borylalkenes are highlighted by further modifications to afford fluoroalkene derivatives or all-carbon substituted alkene.11Nsciescopu

Chemo- and stereoselective crotylation of aldehydes and cyclic aldimines with allylic gem-​diboronate ester

11114Nsciescopu

Diborylmethyl Group as a Transformable Building Block for the Diversification of Nitrogen-Containing Molecules

© 2022 Wiley-VCH GmbH.The development of new approaches to installing diverse carbon fragments to a nitrogen atom has attracted considerable attention in chemical science. While numerous strategies have been devised to forge C(sp3)−N bonds, one conceptually powerful and straightforward approach is to insert a transformable sp3-carbon unit onto a nitrogen atom for modular diversification. Here we describe the successful synthesis of halo-diborylmethanes and their applications to the preparation of nitrogen-substituted diborylmethanes through their homologative coupling with a variety of nitrogen nucleophiles including biologically relevant molecules. This process exhibits a remarkably broad substrate scope, and the usefulness of the obtained compounds is demonstrated by the modular diversification of the diborylmethyl group to access various nitrogen-containing molecules.11Nsciescopu

Copper-Catalyzed Diastereoselective Addition of Diborylmethane to <i>N</i>-<i>tert</i>-Butanesulfinyl Aldimines: Synthesis of β‑Aminoboronates

We have developed a highly chemo- and diastereoselective alkylation of <i>N</i>-<i>tert</i>-butanesulfinyl aldimines with diborylmethane. Whereas the addition of diborylmethane under metal-free conditions shows poor diastereoselectivity, the use of a copper catalyst and a bidentate phosphine ligand significantly enhances the diastereoselectivity, providing chiral β-aminoboronates in good yields. On the basis of the stereochemical outcome, we propose that the reaction likely proceeds via a boron-chelating six-membered chairlike transition state

Chemo- and Stereoselective Crotylation of Aldehydes and Cyclic Aldimines with Allylic <i>gem</i>-Diboronate Ester

We report a highly chemo- and stereoselective crotylation of aldehydes and cyclic aldimines with allylic-<i>gem</i>-diboronate ester as a new type of organoboron reagent. The allylic-<i>gem</i>-diboronate ester undergoes the crotylation with aldehydes and cyclic aldimines in excellent stereoselectivity, forming <i>anti</i>-5,6-disubstituted oxaborinin-2-ols or (<i>E</i>)-δ-boryl-<i>anti</i>-homoallylic amines in high efficiency. The reaction shows a wide range of substrate scope and excellent functional group tolerance. The synthetic applications of the obtained products, including stereospecific C–C, C–O, and C–Cl bond formation, are also demonstrated

Chemoselective Coupling of 1,​1-​Bis[(pinacolato)​boryl]​alkanes for the Transition-​Metal-​Free Borylation of Aryl and Vinyl Halides: A Combined Experimental and Theoretical Investigation

1121Nsciescopu