Cobalt-catalyzed Hydroboration Research Articles

Regio- and Stereoselective Cobalt-Catalyzed Hydroboration of Vinylcyclopropanes to Access Homoallylic Boronates

Herein, a cobalt-catalyzed hydroboration of vinylcyclopropanes was reported to access the corresponding homoallylic boronates with excellent regio- and stereoselectivity. This reaction features a broad substrate scope and could be carried out on a gram scale. The possible mechanism and models for selectivity have been proposed.

Enantioselective Cobalt-Catalyzed Hydroboration of Fluoroalkyl-Substituted Alkenes to Access Chiral Fluoroalkylboronates.

Selective defluoroborylation and asymmetric hydroboration reactions of fluoroalkyl-substituted terminal alkenes with pinacolborane (HBpin) have been developed with cobalt catalysts generated from Co(acac)2 and bisphosphine ligands. A variety of fluoroalkyl-substituted terminal alkenes undergo this enantioselective hydroboration, affording the corresponding chiral alkylboronates containing fluoroalkyl-substituted stereogenic carbon centers with high enantioselectivity (up to 98% ee). This asymmetric hydroboration provides a versatile foundation for the synthesis of a variety of chiral organofluorine compounds containing fluoroalkyl-substituted stereogenic carbon centers.

Highly Regioselective Cobalt-Catalyzed Hydroboration of Internal Alkynes.

Herein, we report the development of new Co complexes that have cyclopropane-based diphosphine ligands and can catalyze highly chemo-, regio-, and stereoselective hydroboration reactions of unsymmetrical internal alkynes. These reactions exhibited unusual regioselectivity: specifically, reactions of aryl alkyl internal alkynes showed excellent cis-β-addition selectivity, and reactions of dialkyl internal alkynes gave excellent cis-α-addition selectivity. Highly regioselective hydroboration of unsymmetrical dialkyl internal alkynes cannot be achieved by other known methods. The reactions described herein are highly synthetically useful, particularly for the stereoselective synthesis of trisubstituted alkenylborates and alkenes. Mechanistic studies indicate that a CoI -H species is a plausible active catalyst and the rigid structure of the cyclopropane skeleton of the ligands and the crowded reaction pocket were responsible for the unprecedented regioselectivity.

Enantioselective Cobalt-Catalyzed Hydroboration of Ketone-Derived Silyl Enol Ethers

Enantioselective Cobalt-Catalyzed Hydroboration of Ketone-Derived Silyl Enol Ethers

Cobalt-Catalyzed Hydroboration of Terminal and Internal Alkynes.

A novel methodology to access synthetically versatile vinylboronic esters through a ligand-controlled cobalt-catalyzed hydroboration of terminal and internal alkynes is reported. The approach relies on the in situ reduction of Co(II) by H-BPin in the presence of bisphosphine ligands generating catalytically active Co(I) hydride complexes. This procedure avoids the use of stoichiometric amounts of base, and no boron-containing byproducts are generated which is translated into high functional group tolerance and atom economy.

Regioselective Markovnikov Cobalt-Catalyzed Hydroboration of Alkynes

Regioselective Markovnikov Cobalt-Catalyzed Hydroboration of Alkynes

Highly Enantioselective Cobalt-Catalyzed Hydroboration of Diaryl Ketones.

A highly enantioselective cobalt-catalyzed hydroboration of diaryl ketones with pinacolborane was developed using chiral imidazole iminopyridine as a ligand to access chiral benzhydrols in good to excellent yields and ee. This protocol could be carried out in a gram scale under mild reaction conditions with good functional group tolerance. Chiral biologically active 3-substituted phthalide and (S)-neobenodine could be easily constructed through asymmetric hydroboration as a key step.

Cobalt-Catalyzed Regio- and Stereoselective Hydroboration of Allenes.

An efficient pincer-ligand-based cobalt-complex-catalyzed allene hydroboration affording Z-allylic boronates is described. The reaction demonstrates an excellent regio- as well as Z-stereoselectivity and a wide substrate scope that tolerates many functional groups. Based on solvent-assisted electrospray ionization mass spectrometry (SAESI-MS) studies, a rationale for the cobalt-catalyzed hydroboration involving the highly selective insertion of an allene into the Co-H bond to form Z-allylic cobalt intermediates is proposed.

Cobalt-Catalyzed Hydroboration of Alkenes, Aldehydes, and Ketones.

An operationally convenient and general method for hydroboration of alkenes, aldehydes, and ketones employing Co(acac)3 as a precatalyst is reported. The hydroboration of alkenes in the presence of HBpin, PPh3, and NaO tBu affords good to excellent yields with high Markovnikov selectivity with up to 97:3 branched/linear selectivity. Moreover, Co(acac)3 could be used effectively to hydroborate aldehydes and ketones in the absence of additives under mild reaction conditions. Inter- and intramolecular chemoselective reduction of the aldehyde group took place over the ketone functional group.

Cobalt-Catalyzed Hydroboration and Borylation of Alkenes and Alkynes

Incorporation of the boryl moiety across a carbon–carbon multiple bond is a powerful method for the synthesis of organoboron compounds. This kind of transformation could be realized with high chemo-, regio-, and stereoselectivity by using an appropriate transition-metal catalyst. This account summarizes the latest advances from our group in the area of cobalt-catalyzed hydroboration and borylation of alkenes and alkynes, which lead to the formation of a variety of organoboron compounds, including alkylboronates, 1,1,1-tris(boronates), 1,1-diborylalkenes, and 1,1-diboronates.1 Introduction2 Cobalt-Catalyzed Hydroboration of Alkenes3 Cobalt-Catalyzed Dehydrogenative Borylations-Hydroboration4 Cobalt-Catalyzed Double Dehydrogenative Borylations of 1-Alkenes5 Cobalt-Catalyzed Hydroboration of Terminal Alkynes6 Summary and Outlook

Cobalt-Catalyzed 1,1-Diboration of Terminal Alkynes: Scope, Mechanism, and Synthetic Applications

A cobalt-catalyzed method for the 1,1-diboration of terminal alkynes with bis(pinacolato)diboron (B2Pin2) is described. The reaction proceeds efficiently at 23 °C with excellent 1,1-selectivity and broad functional group tolerance. With the unsymmetrical diboron reagent PinB-BDan (Dan = naphthalene-1,8-diaminato), stereoselective 1,1-diboration provided products with two boron substituents that exhibit differential reactivity. One example prepared by diboration of 1-octyne was crystallized, and its stereochemistry established by X-ray crystallography. The utility and versatility of the 1,1-diborylalkene products was demonstrated in a number of synthetic applications, including a concise synthesis of the epilepsy medication tiagabine. In addition, a synthesis of 1,1,1-triborylalkanes was accomplished through cobalt-catalyzed hydroboration of 1,1-diborylalkenes with HBPin. Deuterium-labeling and stoichiometric experiments support a mechanism involving selective insertion of an alkynylboronate to a Co-B bond of a cobalt boryl complex to form a vinylcobalt intermediate. The latter was isolated and characterized by NMR spectroscopy and X-ray crystallography. A competition experiment established that the reaction involves formation of free alkynylboronate and the two boryl substituents are not necessarily derived from the same diboron source.

Dual-Stereocontrol Asymmetric Cobalt-Catalyzed Hydroboration of Sterically Hindered Styrenes

An oxazoline aminoisopropylpyridine (OAP) was designed and synthesized for cobalt-catalyzed asymmetric hydroboration of sterically hindered styrenes. A unique dual-stereocontrol phenomenon was observed using a rigid OIP·CoCl2 complex or a flexible OAP with CoCl2 as precatalysts, respectively. The reaction could be easily carried out on a gram scale to afford chiral alkylboronic esters which could be converted into diverse C–X (X = C, N, O) bond cross-coupling products. The mechanistically distinct pathways were proposed on the basis of deuterium experiments.

Cobalt-Catalyzed Hydroboration of Alkynes

Cobalt-Catalyzed Hydroboration of Alkynes

Cobalt catalyzed z-selective hydroboration of terminal alkynes and elucidation of the origin of selectivity.

A bis(imino)pyridine cobalt-catalyzed hydroboration of terminal alkynes with HBPin (Pin = pinacolate) with high yield and (Z)-selectivity for synthetically valuable vinylboronate esters is described. Deuterium labeling studies, stoichiometric experiments, and isolation of catalytically relevant intermediates support a mechanism involving selective insertion of an alkynylboronate ester into a Co-H bond, a pathway distinct from known precious metal catalysts where metal vinylidene intermediates have been proposed to account for the observed (Z) selectivity. The identity of the imine substituents dictates the relative rates of activation of the cobalt precatalyst with HBPin or the terminal alkyne and, as a consequence, is responsible for the stereochemical outcome of the catalytic reaction.

Cobalt-catalyzed asymmetric hydroboration of aryl ketones with pinacolborane.

The highly enantioselective cobalt-catalyzed hydroboration reaction of aryl ketones with HBpin was developed using iminopyridine oxazoline ligands. Halides, amines, ethers, sulfides, esters and amides are well tolerated under the mild reaction conditions, demonstrating its synthetic advantage. Substituted diaryl ketones could also be hydroborated with high enantioselectivity.

(N-phosphinoamidinate)cobalt-catalyzed hydroboration: alkene isomerization affords terminal selectivity.

Herein we establish the utility of a three-coordinate (N-phosphinoamidinate)cobalt(amido) pre-catalyst that is capable of effecting challenging alkene isomerization/hydroboration processes at room temperature, leading to the selective terminal addition of the boron group.