A multicomponent approach to substituted benzenes involving sequential nickel-catalyzed reactions

Two sequential nickel-catalyzed reactions allow the preparation of highly functionalized alkylidene cyclohexenols. Dehydration of the resulting cycloadducts allows the preparation of densely functionalized aromatic ring systems, whereas a simple sequence involving oxidation followed by carbonyl addition or enolization allows additional diversity incorporation.     

A radical mediated approach to the core structure of huperzine A

The synthesis of the core structure of huperzine A by cyclisation of 2-pyridylmethyl radicals is described. (2-Methylpyridin-3-yl)cyclohexenols are directly selenated at the benzylic position by deprotonation/selenation and the products undergo either 5-exo-trig or 6-exo-trig radical cyclisations giving access to hexahydroindenopyridines and the bicyclo[3.3.1]nonane core of huperzine A, respectively.     

Enantioselective Ring Opening of Aza and Oxabicyclic Alkenes with Dimethylzinc

A system for efficient, asymmetric alkylative ring opening of azabenzonorbornadienes and [2.2.1] and [3.2.1] oxabicyclic alkenes was developed. The use of Pd(CH(3)CN)(2)Cl(2) and chiral phosphinooxazoline ligands gives the dihydronaphthalenes, cyclohexenols, and cycloheptenols in excellent yields and enantiomeric excesses.     

A new asymmetric synthesis of trans-hydroisoquinolones

[reaction: see text]. A convenient enantioselective synthesis of trans-hydroisoquinolones is described. This synthesis capitalizes on the ready availability of enantioenriched 2-substituted cyclohexenols by exploiting the asymmetry of an allylic carbon-oxygen sigma bond to control carbon-carbon bond formation in pinacol-terminated cyclizations of N-acyliminium cations.     

Highly-functionalised difluorinated (hydroxymethyl)conduritol analogues via the Diels-Alder reactions of a difluorinated dienophile

A difluorodienophile, synthesised using a Stille coupling reaction underwent tin(iv)-catalysed cycloaddition with three furans to afford oxa[2.2.1]bicycloheptenes in good yield. Reduction of ester and carbamate carbonyl groups and diol protection as the acetonide set the stage for palladium-catalysed hydrostannylation in two cases. Treatment of the stannanes with methyllithium triggered ring-opening to afford highly-functionalised difluorinated cyclohexenols which could be deprotected to afford (hydroxymethyl)conduritol analogues.     

Nickel-catalyzed C-P coupling of aryl mesylates and tosylates with H(O)PR1R2

A method was developed for the nickel-catalyzed phosphonylation of aryl mesylates and tosylates with H(O)PR(1)R(2). To the best of our knowledge, this is the first example of nickel-catalyzed C-P coupling of aryl mesylates and tosylates. Most of the substrates gave moderate to good yields under our catalytic system.     

Nickel-catalyzed reductive carboxylation of styrenes using CO2

A nickel-catalyzed reductive carboxylation of styrenes using CO2 has been developed. The reaction proceeds under mild conditions using diethylzinc as the reductant. Preliminary data suggests the mechanism involves two discrete nickel-mediated catalytic cycles, the first involving a catalyzed hydrozincation of the alkene followed by a second, slower nickel-catalyzed carboxylation of the in situ formed organozinc reagent. Importantly, the catalyst system is very robust and will fixate CO2 in good yield even if exposed to only an equimolar amount introduced into the headspace above the reaction.     

Stereoselective formation of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem‑difluoroalkenes with lithium organoborates

A method for stereoselective construction of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem?difluoroalkenes in mild conditions was described. The combination of lithium organoborate and ZnBr₂ generated in situ lithium aryl zincates, which facilitates the transmetalation step of the nickel-catalyzed cross coupling reaction.     

Diastereoselective nickel-catalyzed reductive couplings of aminoaldehydes and alkynylsilanes: application to the synthesis of d-erythro-sphingosine

A strategy for the nickel-catalyzed reductive coupling of α-aminoaldehydes with silyl alkynes has been developed. The process proceeds with exceptional regiocontrol and diastereoselectivity. A variety of protected serinal derivatives were examined, and Garner aldehyde afforded the highest chemical yields of an easily deprotected coupling product. Use of a C-15 alkyne allowed a direct and efficient synthesis of d-erythro-sphingosine. With this silyl alkyne of interest, coupling reactions were most efficient when trace water was employed with THF as solvent. Using this procedure, d-erythro-sphingosine was prepared by a short sequence, wherein the alkene stereochemistry, C-3 stereocenter, and the C-3-C-4 carbon-carbon bond were all efficiently installed by the key nickel-catalyzed coupling process.     

Formal synthesis of salinosporamide A using a nickel-catalyzed reductive aldol cyclization-lactonization as a key step

Application of a sequential nickel-catalyzed reductive aldol cyclization-lactonization reaction in a short formal synthesis of salinsporamide A, a potent 20S proteasome inhibitor and anti-cancer compound, is described.     

Nickel-catalyzed reductive cross-coupling of polyfluoroarenes with alkyl electrophiles by site-selective C–F bond activation

A nickel-catalyzed reductive cross-coupling reactions between polyfluoroarenes and alkyl electrophiles is reported to access substituted fluoroarenes through chelation-assisted C–F activation. Diverse primary and secondary alkyl (pseudo)halides can be employed to couple with polyfluoroarenes, showing excellent regioselectivity. Furthermore, the nickel-catalyzed asymmetric cross-coupling of polyfluoroarenes with racemic alkyl halides is preliminarily explored. In addition, the practicability of the title transformation is also demonstrated by total synthesis of losmapimod and an analog as key steps. The developed method exhibits many advantages, including economic catalytic systems, commercially available alkyl electrophiles, and lack of sensitive organometallic reagents.     

Preparation of unsymmetrical terphenyls via the nickel-catalyzed cross-coupling of alkyl biphenylsulfonates with aryl Grignard reagents

Unsymmetrical terphenyl derivatives were prepared by sequential transition metal-catalyzed cross-coupling reactions of neopentyl bromobenzenesulfonates with arylboronic acids and arylmagnesium bromides in good yields. Biphenylsulfonates undergo nickel-catalyzed coupling reactions more rapidly than the corresponding benzenesulfonates. The stepwise palladium- and nickel-catalyzed reaction of the bromobenzenesulfonates appears to be a promising and conceptually straightforward route for preparing unsymmetrical terphenyls.     

Organolithium-induced enantioselective alkylative double ring-opening of epoxides: synthesis of enantioenriched unsaturated amino alcohols

The use of (−)-sparteine as an external chiral ligand in enantioselective organolithium-induced alkylative double ring-opening of dihydropyrrole epoxides and 7-azanorbornene-type epoxides gives unsaturated acyclic amino alcohols, and amino cyclohexenols in up to 87% ee.     

Intramolecular Baylis-Hillman and morita reactions using unsaturated thiol ester substrates containing enolizable aldehydes

[reaction: see text] Previously unknown intramolecular Baylis-Hillman and Morita reactions involving cyclization of an unsaturated thiol ester onto a pendant aldehyde function are reported. These can be used successfully for the preparation of both cyclopentenols and cyclohexenols, but the results are very sensitive to substrate and precise reaction conditions.     

Methylenecyclopropanes in [4+1] cycloaddition with enones

A nickel-catalyzed [4+1] cycloaddition of enones with methylenecyclopropanes leading to dihydrofurans was developed. The reaction outcome is attributed to the transformation of methlenecyclopropane, which is incorporated into a five-membered ring as a one-carbon fragment.     

Straightforward stereoselective synthesis of polyfunctionalised cyclohexenols using a multicomponent approach

An intramolecular Ugi 5-centre-4-component reaction (U-5C-4CR) followed by a palladium-catalysed ring-opening has been employed to transform oxabicycloheptene-based β-amino acids into two families of regioisomeric polyfunctionalised cyclohexenols. The whole process is completely stereoselective and enantiomerically pure products are obtained in high overall yields.     

Visible-light-induced,autopromoted nickel-catalyzed three-component arylsulfonation of 1,3-enynes and mechanistic insights

Science China Chemistry - A light-induced, nickel-catalyzed three-component arylsulfonation of 1,3-enynes in the absence of photocatalyst is reported. This methodology exhibited mild conditions,...     

Alkaloid catalysed asymmetric synthesis. The addition of selenophenols to 2-cyclohexen-1-ones and conversion to optically active allylic alcohols

The cinchona alkaloid catalyzed 1,4-addition reaction of selenophenols to cyclohexenols has been shown to proceed with asymmetric induction. Optically active selenium adducts are formed in quantitative chemical and up to 43% enantiomeric yields. The transformation to an optically active chiral allyl alcohol is described.     

Enantioselective total synthesis of (+)-testudinariol a using a new nickel-catalyzed allenyl aldehyde cyclization

An enantioselective total synthesis of (+)-testudinariol A was completed. A new nickel-catalyzed allenyl aldehyde cyclization was developed in the approach. In addition, an asymmetric anti aldol reaction and a two-directional oxocarbenium ion/vinyl silane condensation were employed as key steps.     

Nickel-catalyzed highly regioselective multicomponent coupling of ynamides, aldehydes, and silane: a new access to functionalized enamides

A new method for preparation of functionalized enamides by a nickel-catalyzed multicomponent coupling of ynamides, aldehydes, and silane has been developed. The coupling reaction proceeded in the presence of a nickel-IMes catalyst to give the corresponding gamma-silyloxyenamide derivative, which has an allylic alcohol moiety in the molecule, in a highly stereoselective manner.