Substrate Plasticity Enables Group-Selective Transmetalation: Catalytic Stereospecific Cross-Couplings of Tertiary Boronic Esters.

Activation of enantiomerically enriched tertiary alkylboronic esters with adamantyllithium generated in situ enables stereoretentive boron-to-copper transmetalation. The resulting alkylcopper species can undergo cross-coupling reactions with an array of electrophiles to furnish synthetically useful compounds bearing quaternary stereocenters. DFT calculations of the transmetalation process provide insights for reactivity and selectivity.

Enantioselective Construction of Carbocyclic and Heterocyclic Tertiary Boronic Esters by Conjunctive Cross-Coupling Reaction.

Synthesis of stereodefined carbocyclic and heterocyclic tertiary boronic esters is accomplished by performing a conjunctive cross-coupling reaction on preformed cyclic boron ate complexes. Boronates bearing spirocyclic and aryl bicyclic skeletons can be synthesized enantioselectively using a chiral PHOX-ligated Pd catalyst with achiral starting material, while substrates bearing continuous stereogenic centers can be generated diastereoselectively. A variety of aryl and alkenyl electrophiles are incorporated.

Stereospecific Transformations of Alkylboronic Esters Enabled by Direct Boron-to-Zinc Transmetalation.

Chiral secondary organoboronic esters, when activated with t-butyllithium, are shown to undergo efficient stereoretentive transmetalation with either zinc acetate or zinc chloride. This reaction provides chiral secondary alkylzinc reagents that are configurationally stable under practical experimental conditions. The organozinc compounds were found to engage in stereospecific reactions with difluorocarbene, catalytic cross-couplings with palladium-based catalysts, and trifluoromethylation with a copper(III) complex. Mechanistic and computational studies shed light on the inner workings of the transmetalation event.

Desymmetrization of Vicinal Bis(boronic) Esters by Enantioselective Suzuki-Miyaura Cross-Coupling Reaction.

The development of an enantioselective catalytic Suzuki-Miyaura reaction that applies to meso 1,2-diborylcycloalkanes is described. This reaction provides a modular route to enantiomerically enriched substituted carbocycles and heterocycles that retain a synthetically versatile boronic ester. With appropriately constructed substrates, compounds bearing additional stereogenic centers and fully substituted carbon atoms can be generated in a straightforward fashion. Preliminary mechanistic experiments suggest that substrate activation arises from the cooperative effect of vicinal boronic esters during the transmetalation step.

Palladium-Catalyzed Conjunctive Cross-Coupling with Electronically Asymmetric Ligands.

Palladium-catalyzed conjunctive cross-coupling can be accomplished with the use of chiral phosphine-oxazoline based ligand structures. Of note, the reaction can be conducted on Grignard-based boron ate complexes and operates without the use of halide-scavenging additives, which are required for other catalyst systems.

1,2-Diborylsilanes: Catalytic Enantioselective Synthesis and Site-Selective Cross-Coupling.

A Pt-catalyzed enantioselective hydrosilylation of (Z)-1,2-diborylethylene provides a 1,2-diboryl-1-silylalkane that can be used in catalytic cross-coupling reactions. Depending on the catalyst employed and the cross-coupling reaction conditions, the coupling can occur at either α or ß relative to the silane center.

Copper-Catalyzed Coupling of Alkyl Vicinal Bis(boronic Esters) to an Array of Electrophiles.

A neighboring boronate group in the substrate provides a dramatic rate acceleration in transmetalation to copper and thereby enables organoboronic esters to participate in unprecedented site-selective cross-couplings. This cross-coupling operates under practical experimental conditions and allows for coupling between vicinal bis(boronic esters) and allyl, alkynyl, and propargyl electrophiles as well as a simple proton. Because the reactive substrates are vicinal bis(boronic esters), the cross-coupling described herein provides an expedient new method for the construction of boron-containing reaction products from alkenes. Mechanistic experiments suggest that chelated cyclic ate complexes may play a role in the transmetalation.

Copper-Catalyzed Stereospecific Transformations of Alkylboronic Esters.

Copper-catalyzed stereospecific cross-couplings of boronic esters are reported. Boron "ate" complexes derived from pinacol boronic esters and tert-butyl lithium undergo stereospecific transmetalation to copper cyanide, followed by coupling with alkynyl bromides, allyl halides, propargylic halides, ß-haloenones, hydroxylamine esters, and acyl chlorides. Through this simple transformation, commercially available inexpensive compounds can be employed to convert primary and secondary alkylboronic esters to a wide array of synthetically useful compounds.

Stereocontrolled Pericyclic and Radical Cycloaddition Reactions of Readily Accessible Chiral Alkenyl Diazaborolidines.

In this paper is described an easily synthesized chiral diazaborolidine that is inexpensive, stable, and provides excellent stereoselection across a number of reaction classes. These versatile compounds possess utility in four different classes of cycloaddition reactions, offering good yield and stereoselectivity. X-ray structure analysis provides insight about the origin of stereocontrol.

Enantioselective Synthesis of Tertiary ß-Boryl Amides by Conjunctive Cross-Coupling of Alkenyl Boronates and Carbamoyl Chlorides.

Synthesis of versatile ß tert-boryl amides is accomplished by conjunctive cross-coupling of α-substituted alkenyl boron "ate" complexes and carbamoyl chloride electrophiles. This reaction can be accomplished in an enantioselective fashion using a palladium catalyst in combination with MandyPhos. The addition of water results in enhanced chemoselectivity for the conjunctive coupling product relative to the Suzuki-Miyaura cross-coupling product. Transformations of the reaction products were examined as well as application to the synthesis of (+)-adalinine.

Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters.

In this paper is described a synthesis of enantiomerically enriched, configurationally stable organozinc reagents by catalytic enantioselective carbozincation of a vinylboronic ester. This process furnishes enantiomerically enriched α-borylzinc intermediates that are shown to undergo stereospecific reactions, producing enantioenriched secondary boronic ester products. The properties of the intermediate α-borylzinc reagent are probed and the synthetic utility of the products is demonstrated by application to the synthesis of (-)-aphanorphine and (-)-enterolactone.

Diastereoselective Diboration of Cyclic Alkenes: Application to the Synthesis of Aristeromycin.

The Pt-catalyzed diboration of cyclic alkenes is extended to unsaturated heterocycles and bicyclic compounds and can be accomplished in a diastereoselective fashion. The optimal procedures, substrate scope, and diastereoselectivity were investigated, and examples employing both homogeneous and heterogeneous catalysis were examined. Lastly, application to the construction of the nucleoside analog (±)-aristeromycin was conducted.

Construction of Azacycles by Intramolecular Amination of Organoboronates and Organobis(boronates).

Intramolecular amination of organoboronates occurs with a 1,2-metalate shift of an aminoboron "ate" complex to form azetidines, pyrrolidines, and piperidines. Bis(boronates) undergo site-selective amination to form boronate-containing azacycles. Enantiomerically enriched azacycles are formed with high stereospecificity.

α-Boryl Organometallic Reagents in Catalytic Asymmetric Synthesis.

Recent years have witnessed an increase in the popularity of α-boryl organometallic reagents as versatile nucleophiles in asymmetric synthesis. These compounds have been adopted in chemo- and stereoselective coupling reactions with a number of different electrophiles. The resulting enantioenriched boronic esters can be applied in stereospecific carbon-carbon or carbon-heteroatom bond construction reactions, enabling a two-step strategy for the construction of complex structures with high efficiency and functional group compatibility. Due to these reasons, tremendous effort has been devoted to the preparation of enantiomerically enriched α-boryl organometallic reagents and to the development of stereoselective reactions of related racemic or prochiral materials. In this review, we describe the enantio- or diastereoselective reactions that involve α-boryl organometallic reagents as starting materials or products and we showcase their synthetic utility.

Studies toward the Synthesis of Amphidinolide C1: Stereoselective Construction of the C(1)-C(15) Segment.

An enantioselective synthesis of the C(1)-C(15) segment of the marine natural product amphidinolide C has been accomplished by a route that includes a stereoselective boron-Wittig reaction to furnish a trisubstituted alkenylboronate. In addition, the route employs enantioselective alkene diboration to install the C(6) hydroxyl group which undergoes intramolecular conjugate addition to establish a tetrahydrofuran ring. Lastly, a catalytic Suzuki-Miyaura cross-coupling is accomplished to construct the C(9)-C(10) bond.

Recent Advances in Radical Addition to Alkenylboron Compounds.

The addition of carbon-centered radicals to alkenylboron compounds provides a useful method for the construction of organoboron reagents which are versatile reagents in chemical synthesis. While the first examples of this type or process appeared 70 years ago, until recently, attention to this type of reaction has been limited. A number of examples of this reactivity have been demonstrated recently, and strategies are emerging that allow for tuning the reagent structure in order to modulate reactivity. This review surveys recent advances in this class of reaction.

Diastereo- and Enantioselective 1,4-Difunctionalization of Borylenynes by Catalytic Conjunctive Cross-Coupling.

Enantioselective conjunctive cross-coupling of enyne-derived boronate complexes occurs with 1,4 addition of the electrophile and migrating group across the π system. This reaction pathway furnishes α-boryl allenes as the reaction product. In the presence of a chiral catalyst, both the central and axial chirality of the product can be controlled during product formation.

Catalytic Enantioselective Synthesis of anti-Vicinal Silylboronates by Conjunctive Cross-Coupling.

Chiral 1,2-bimetallic reagents are useful motifs in synthetic chemistry. Although syn-1,2-bimetallic compounds can be prepared by alkene dimetallation, anti-1,2-bimetallics are still rare. The stereospecific 1,2-metallate shift that occurs during conjunctive cross-coupling is shown to enable a practical and modular approach to the catalytic synthesis of enantioenriched anti-1,2-borosilanes. In addition to reaction development, the synthetic utility of anti-1,2-borosilanes was investigated, including applications to the synthesis of anti-1,2-diols and anti-1,2-amino alcohols.

Alkyl Group Migration in Ni-Catalyzed Conjunctive Coupling with C(sp3) Electrophiles: Reaction Development and Application to Targets of Interest.

A catalytic conjunctive cross-coupling reaction is developed that allows the construction of chiral organoboronic esters from alkylboron ate complexes and alkyl iodide electrophiles. The process occurs most efficiently with a Ni/Pybox-comprised catalyst and with an acenapthoquinone-derived boron ligand. Because of the broad functional group tolerance of this reaction, it can be a versatile tool for organic synthesis. Applications to the construction of (R)-coniine and (-)-indolizidine 209D are described.

Enantioselective Radical Addition/Cross-Coupling of Organozinc Reagents, Alkyl Iodides, and Alkenyl Boron Reagents.

A hybrid transition-metal/radical process is described that results in the addition of organozinc reagents and alkyl halides across alkenyl boron reagents in an enantioselective catalytic fashion. The reaction can be accomplished both intermolecularly and intramolecularly, providing useful product yields and high enantioselectivities in both manifolds.