Bis(pinacolato)diboron-Enabled Ni-Catalyzed Reductive Arylation/Vinylation of Alkyl Electrophiles.

Herein, the use of economically and environmentally friendly bis(pinacolato)diboron (BPin) is described as a non-metallic reductant in mediating Ni-catalyzed C(sp)-C(sp) reductive cross-coupling of alkyl electrophiles with aryl/vinyl halides. This method exhibits excellent suitability for heteroaryl halides and alkyl halides/Katritzky salts. The present study is compatible with an in situ halogenation of alcohol method, allowing for selective mono-functionalization of diols and bio-relevant alcohols (e.

Insights into Recent Nickel-Catalyzed Reductive and Redox C-C Coupling of Electrophiles, C(sp)-H Bonds and Alkenes.

ConspectusTransition metal-catalyzed reductive cross-coupling of two carbon electrophiles, also known as cross-electrophile coupling (XEC), has transformed the landscape of C-C coupling chemistry. Nickel catalysts, in particular, have demonstrated exceptional performance in facilitating XEC reactions, allowing for diverse elegant transformations by employing various electrophiles to forge C-C bonds. Nevertheless, several crucial challenges remain to be addressed.

Retraction: Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides.

Retraction of 'Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides' by Yingying Pan , , 2019, , 4230-4233, https://doi.org/10.1039/C9OB00628A.

Expeditious preparation of β--alkyl vicinal amino alcohols used for chiral ligand synthesis.

An economical route providing quick access to chiral β-amino alcohols bearing one β--alkyl group was developed. This protocol starts with commercially available and cheap chiral sources such as derivatives of L-serine and L-threonine. A series of vicinal amino alcohols with high optical purity were prepared in good yields through 4 or 6 operationally simple steps.

Ni-Catalyzed Reductive Coupling of Heteroaryl Bromides with Tertiary Alkyl Halides.

We disclose here a nickel-catalyzed reductive coupling of bromopyridines with tertiary alkyl bromides for the synthesis of alkylated pyridines bearing an all-carbon quaternary center. This strategy features mild conditions, broad substrate scope, and high functional group tolerance. The method reported here offers an alternative solution to the challenging task of forging sterically congested alkylpyridines, which we believe will significantly benefit the synthetic community and pharmaceutical industry.

Nickel-Catalyzed Thermal Redox Functionalization of C(sp )-H Bonds with Carbon Electrophiles.

C(sp )-H bond coupling with carbon electrophiles remains rarely explored under thermo-driven hydrogen atom transfer (HAT) conditions due to the challenge of integrating oxidation and reduction in a single operation. We report here a Ni-catalyzed arylation and alkylation of C(sp )-H bonds with organohalides to forge C(sp )-C bonds by merging economical Zn and tBuOOtBu (DTBP) as the external reductant and oxidant. The mild and easy-to-operate protocol enables facile carbofunctionalization of N-/O-α- and cyclohexane C-H bonds, and preparation of a few intermediates of bioactive compounds and drug derivatives.

Alkenylation and Arylation of Peptides via Ni-Catalyzed Reductive Coupling of α--Tosyl Peptides with Csp Triflates/Halides.

A Ni-catalyzed reductive cross-coupling between α-C-tosyl peptides and Csp triflates/halides has been developed. This protocol enables the formation of various unnatural di- and tripeptides containing vinyl and aryl side chains, and it expands the applications of Ni-catalyzed reductive cross-coupling in late-stage diversification of peptides.

Nickel-catalyzed asymmetric reductive arylation of α-chlorosulfones with aryl halides.

We report an asymmetric Ni-catalyzed reductive cross-coupling of aryl/heteroaryl halides with racemic α-chlorosulfones to afford enantioenriched sulfones. The reaction tolerates a variety of functional groups under mild reaction conditions, which complements the current methods. The utility of this work was demonstrated by facile late-stage functionalization of commercial drugs.

Preparation of α-amino acids Ni-catalyzed reductive vinylation and arylation of α-pivaloyloxy glycine.

This work emphasizes easy access to α-vinyl and aryl amino acids Ni-catalyzed cross-electrophile coupling of bench-stable -carbonyl-protected α-pivaloyloxy glycine with vinyl/aryl halides and triflates. The protocol permits the synthesis of α-amino acids bearing hindered branched vinyl groups, which remains a challenge using the current methods. On the basis of experimental and DFT studies, simultaneous addition of glycine α-carbon (Gly) radicals to Ni(0) and Ar-Ni(ii) may occur, with the former being more favored where oxidative addition of a C(sp) electrophile to the resultant Gly-Ni(i) intermediate gives a key Gly-Ni(iii)-Ar intermediate.

Nickel-catalyzed reductive 1,3-diene formation from the cross-coupling of vinyl bromides.

Facile construction of 1,3-dienes building upon cross-electrophile coupling of two open-chain vinyl halides is disclosed in this work, showing moderate chemoselectivities between the terminal bromoalkenes and internal vinyl bromides. The present method is mild and tolerates a range of functional groups and can be applied to the total synthesis of a tobacco fragrance solanone.

Nickel-Catalyzed Reductive Vinylation of Chloro-hexahydropyrroloindoline Derivatives with Vinyl Triflates.

This work emphasizes facile construction of C-3a vinyl substituted hexahydropyrrolidinoindolines based upon Ni-catalyzed reductive coupling of chloro-hexahydropyrroloindoline derivatives with a wide range of alkyl-decorated vinyl triflates. The remarkable compatibility of sterically hindered branched vinyl groups is highlighted.

Ni-Catalyzed Cross-Electrophile Coupling of Aryl Triflates with Thiocarbonates via C-O/C-O Bond Cleavage.

A nickel-catalyzed reductive coupling of aryl triflates with thiocarbonates is reported here. Both electron-rich and -deficient aryl C(sp)-O electrophiles as well as a class of -Bu -alkyl thiocarbonates are compatible with the optimized reaction conditions, as evidenced by 49 examples. The reaction also proceeds with good chemoselective cleavage of the C-O bond with regard to thioesters.

Diverse Synthesis of Chiral Trifluoromethylated Alkanes via Nickel-Catalyzed Asymmetric Reductive Cross-Coupling Fluoroalkylation.

The trifluoromethyl group represents one of the most functional and widely used fluoroalkyl groups in drug design and screening, while the drug candidates containing chiral trifluoromethyl-bearing carbons are still few due to the lack of efficient methods for the asymmetric introduction of trifluoromethyl group into organic molecules. Herein, we described a nickel-catalyzed asymmetric trifluoroalkylation of aryl iodides, for the first time, by utilizing reductive cross-coupling in enantioselective fluoroalkylation. This novel method has demonstrated high efficiency, mild conditions, and excellent functional group tolerance, especially for substrates containing diverse pharmaceutical and bioactive molecules moieties.

Zn- and Cu-Catalyzed Coupling of Tertiary Alkyl Bromides and Oxalates to Forge Challenging C-O, C-S, and C-N Bonds.

We describe here the facile construction of sterically hindered tertiary alkyl ethers and thioethers via the Zn(OTf)-catalyzed coupling of alcohols/phenols with unactivated tertiary alkyl bromides and the Cu(OTf)-catalyzed thiolation of unactivated tertiary alkyl oxalates with thiols. The present protocol represents one of the most effective unactivated tertiary C(sp)-heteroatom bond-forming conditions via readily accessible Lewis acid catalysis that is surprisingly less developed.

Nickel-Catalyzed, Regio- and Enantioselective Benzylic Alkenylation of Olefins with Alkenyl Bromide.

A NiH-catalyzed migratory hydroalkenylation reaction of olefins with alkenyl bromides has been developed, affording benzylic alkenylation products with high yields and excellent chemoselectivity. The mild conditions of the reaction preclude olefinic products from undergoing further isomerization or subsequent alkenylation. Catalytic enantioselective hydroalkenylation of styrenes was achieved by using a chiral bisoxazoline ligand.

Cross-Electrophile Couplings of Activated and Sterically Hindered Halides and Alcohol Derivatives.

Transition metal catalyzed cross-electrophile coupling of alkyl electrophiles has evolved into a privileged strategy that permits the facile construction of valuable C(sp)-C bonds. Numerous elegant Ni-catalyzed coupling methods, for example, arylation, allylation, acylation, and vinylation of primary and secondary alkyl halides have been developed. This prior work has provided important mechanistic insights into the selectivity and reactivity of the coupling partners, which are largely dictated by both the catalysts and the reactants.

Metal catalyst-free photo-induced alkyl C-O bond borylation.

Metal catalyst free, blue visible light-induced C-O bond borylation of unactivated tertiary alkyl methyl oxalates has been developed to furnish tertiary alkyl boronates. From the secondary alcohols activated with imidazolylthionyl, moderate yields of boronates were attained under standard photo-induced conditions. Preliminary mechanistic studies confirmed the involvement of a (DMF)2-B2cat2 adduct that weakly absorbs light at 437 nm so as to initiate a Bcat radical.

Iron-Catalyzed Reductive Vinylation of Tertiary Alkyl Oxalates with Activated Vinyl Halides.

We present herein a rare and efficient method for the creation of vinylated all carbon quaternary centers via Fe-catalyzed cross-electrophile coupling of vinyl halides with tertiary alkyl methyl oxalates. The reaction displays excellent functional group tolerance and broad substrate scope, which allows cascade radical cyclization and vinylation to afford complex bicyclic and spiral structural motifs. The reaction proceeds via tertiary alkyl radicals, and the putative vinyl-Br/Fe complexation appears to be crucial for activating the alkene and enabling a possibly concerted radical addition/C-Fe forming process.

Formation of allylated quaternary carbon centers via C-O/C-O bond fragmentation of oxalates and allyl carbonates.

Disclosed herein emphasizes Fe-promoted cross-electrophile allylation of tertiary alkyl oxalates with allyl carbonates that generates all C(sp3)-quaternary centers. The reaction involves fragmentation of tertiary alkyl oxalate C-O bonds to give tertiary alkyl radical intermediates, addition of the radicals to less hindered alkene terminals, and subsequent cleavage of the allyl C-O bonds. Allylation with 2-aryl substituted allyl carbonates was mediated by Zn/MgCl2, and Fe is used to promote the radical addition efficiency.

AAAA-DDDD Quadruple H-Bond-Assisted Ionic Interactions: Robust Bis(guanidinium)/Dicarboxylate Heteroduplexes in Water.

The use of geminal di(guanidinium) and acridin-9(10)-one-derived di(carboxylate) derivatives (- and -, respectively) allows stabilization of heterodimers characterized by high binding affinities in water (maximum Δ < -7 kcal mol, > 10 M) as inferred from UV-vis spectroscopic titrations and ITC measurements, therefore rivaling or surpassing the interaction energy between the strongest DNA or RNA triplet pairs. These duplexes are readily accessible and are structurally modifiable, rendering them attractive as building blocks for creating heteroduplex constructs. Incorporating poly(ethylene glycol)-decorated benzyl groups into the dicarboxylate, allows formation of hydrogels in the case of -.

Copper-Catalyzed and Indium-Mediated Methoxycarbonylation of Unactivated Alkyl Iodides with Balloon CO.

This work emphasizes the synthesis of alkyl esters via Cu-catalyzed and In-mediated alkoxycarbonylation of unactivated alkyl iodides in the presence of In or InI. The reactions were suitable for the preparation of primary, secondary, and even tertiary alkyl esters, representing an exceptionally rare example for the creation of quaternary carbon centers upon formation of esters. The preliminary mechanistic studies indicated that alkyl radicals were involved, and Cu/In/CO played a cooperative role in the carbonylation event.

Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides.

This work describes Ni-catalyzed cross-electrophile coupling of benzyl chloroformate derivatives with aryl iodides that generates a wide range of diaryl methane products. The mild reaction conditions merit the C-O bond radical fragmentation of benzyl chloroformates via halide abstraction or a single electron reduction by a Ni catalyst. This work offers a new substrate type for cross-electrophile couplings.