Regioselective reductions of β,β-disubstituted enones catalyzed by nonracemically ligated copper hydride

CuH-catalyzed 1,2-additions to β,β-disubstituted α,β-unsaturated ketones have been further explored. Asymmetric reductions of enones lacking an α-substituent can be achieved with CuH complexed by DTBM-SEGPHOS in Et₂O at ?25 °C leading to the generation of highly valuable nonracemic allylic alcohols. The corresponding 1,4-reductions can also be achieved using the same reaction conditions by switching the ligand to a JOSIPHOS analog affording nonracemic β,β-disubstituted ketones. DFT calculations of the enone conformations and transition-state energies for model 1,2- and 1,4-additions were carried out to clarify the factors affecting the product ratios.     

The first example of hydrozirconation of alkynes in room temperature ionic liquids

Hydrozirconation of terminal alkynes in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF₆]) at 30 °C gave highly regio- and stereoselectively (E)-vinylzirconium complexes, which underwent a cross-coupling reaction with aryl halides in the presence of Pd(PPh₃)₄ to afford (E)-1,2-disubstituted ethenes in good to high yields. Our system not only avoids the use of easily volatile THF or CH₂Cl₂ as solvent but also solves the basic problem of palladium catalyst reuse.     

Rhodium-Catalyzed Asymmetric Synthesis of 1,2-Disubstituted Allylic Fluorides

Although there are many methods for the asymmetric synthesis of monosubstituted allylic fluorides, construction of enantioenriched 1,2-disubstituted allylic fluorides has not been reported. To address this gap, we report an enantioselective synthesis of 1,2-disubstituted allylic fluorides using chiral diene-ligated rhodium catalyst, Et₃N ⋅ 3HF as a source of fluoride, and Morita Baylis Hillman (MBH) trichloroacetimidates. Kinetic studies show that one enantiomer of racemic MBH substrate reacts faster than the other. Computational studies reveal that both syn and anti π-allyl complexes are formed upon ionization of allylic substrate, and the syn complexes are slightly energetically favorable. This is in contrast to our previous observation for formation of monosubstituted π-allyl intermediates, in which the syn π-allyl conformation is strongly preferred. In addition, the presence of an electron-withdrawing group at C2 position of racemic MBH substrate renders 1,2-disubstituted π-allyl intermediate formation endergonic and reversible. To compare, formation of monosubstituted π-allyl intermediates was exergonic and irreversible. DFT calculations and kinetic studies support a dynamic kinetic asymmetric transformation process wherein the rate of isomerization of the 1,2-disubstituted π-allylrhodium complexes is faster than that of fluoride addition onto the more reactive intermediate. The 1,2-disubstituted allylic fluorides were obtained in good yields, enantioselectivity, and branched selectivity.     

KF/Al2O3: an efficient solid heterogeneous base catalyst in one-pot synthesis of benzimidazoles and bis-benzimidazoles at room temperature

Abstract  

KF/Al₂O₃ is an efficient solid heterogeneous base catalyst in the one-pot synthesis of 2-substituted benzimidazoles and 2,2′-disubstituted bis-benzimidazoles from 1,2-phenylenediamines or 3,3′-diaminobenzidines and acid chlorides, anhydrides, and esters at room temperature.     

Synthesis of 1,2-disubstituted acetylenes via copper-catalyzed Suzuki coupling of organoboronic acids with 1,1-dibromo-1-alkenes

An efficient synthesis of 1,2-disubstituted acetylenes has been described. Reactions of organoboronic acids with 1,1-dibromo-1-alkenes in the presence of a catalytic amount of CuI (10 mol %), 8-hydroxyquinoline (10 mol %), and using potassium phosphate as base in C₂H₅OH afforded the desired 1,2-disubstituted acetylenes in good to excellent yields. It is important to note that the formation of 1,3-diynes, which are derived from the homocoupling of 1,1-dibromo-1-alkenes, can be almost completely suppressed under these optimized conditions.     

Synthesis of 1,4-disubstituted 1,2,3-triazoles based on cobalt bis(1,2-dicarbollide)

An approach to the synthesis of new 1,4-disubstituted 1,2,3-triazoles, in which one or both substituents contain the cobalt bis(1,2-dicarbollide) fragment, was suggested based on the 1,3-dipolar cycloaddition of azides to alkynes catalyzed by copper(I) compounds. The reaction of cobalt bis(1,2-dicarbollide) azido derivatives with different terminal acetylenes led to 1,2,3-triazoles with the [((CH₂)₂X(CH₂)₂O-C₂B₉H₁₀)Co(C₂B₉H₁₁)] (X = O or CH₂) substituent at position 1 and the organic substituent at position 4. The [3+2] cycloaddition reaction of cobalt bis(1,2-dicarbollide) alkynyl derivatives with methyl azidoacetate furnished isomeric 1,4-disubstituted 1,2,3-triazoles with the metallacarborane fragment at position 4. 1,2,3-Triazole with metallacarborane substituents at positions 1 and 4 containing 36 boron atoms was also synthesized.     

Borane-Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio- and Diastereoselective Construction of trans-2,3-Disubstituted-1,2,3,4-Tetrahydroquinoxalines

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4-tetrahydroquinoxalines. However, enantio- and diastereoselective access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair-based catalyst generated via in situ hydroboration of 2-vinylnaphthalene with HB(C₆F₅)₂ allows for the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones with commercially available PhSiH₃ to exclusively afford trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst derived from HB(C₆F₅)₂ and a binaphthyl-based chiral diene to give rise to enantioenriched trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines in high yields with almost complete diastereo- and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20-gram scale production are demonstrated. The enantio- and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations.     

Reaction of ketenes with N,N-disubstituted α-aminomethyleneketones. XVIII. Synthesis of N,N-disubstituted 4-amino-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones

1,4-Cycloaddition of phenylchloroketene to N,N-disubstituted 2-aminomethylene-3,4-dihydro-1(2H)naphthalenones gave the corresponding adducts, namely N,N-disubstituted 4-amino-3-chloro-3,4,5,6-tetrahydro-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones II, in the case of aliphatic N,N-disubstitution or aromatic N-monosubstitution. Apart from IIf (NR₂ = NMePh), adducts II were unstable and were dehydrochlorinated in situ with DBN to give N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-naphtho[1,2-b]pyran-2-ones III in fair overall yields. Compounds III were dehydrogenated with Pd/C in boiling p-cymene to afford the title compounds generally in high yields.     

Remote stereocontrol by the sulfinyl group. Diels–Alder reaction of cyclopentadiene with substituted (S)-[2-(p-tolylsulfinyl)styrenes and (S)-[2-(p-tolylsulfinyl)phenyl] vinyl ketones

The ability of a homochiral sulfinyl group at the dienophile to act as a remote stereocontrol inductor in the Diels–Alder reaction with cyclopentadiene has been evaluated. High pressure conditions were required for the reactions of (S)-2-(p-tolylsulfinyl)styrenes 3–5 (E-1,2-disubstituted double bond) and 6–8 (1,1-disubstituted double bond). A good facial selectivity and total endo selectivity were attained with 1,1-disubstitued dienophiles, though the 1,2-disubstituted ones afforded poorer results. In contrast, (S)-[2-(p-tolylsulfinyl)phenyl] vinyl ketones 9–11 reacted readily at low temperature (?40 °C) with complete endo selectivity and high facial selectivity in the presence of Yb(OTf)₃ as a chelating reagent of sulfinyl and carbonyl oxygen atoms. Concerning furan reactions, β-trifluoromethyl enone 14 afforded Diels–Alder adducts with high facial selectivity in the presence of the Lewis acid, but β-non-substituted enones 9 and 12 yielded products of furan conjugate addition to the double bond.     

Asymmetric construction of pyrido[1,2-a]-1H-indole derivatives via a gold-catalyzed cycloisomerization

Pyrido[1,2-a]-1H-indoles are important scaffolds found in many biologically active compounds. Herein, we first developed an IPrAuCl/AgSbF₆-catalyzed cycloisomerization of N-1,3-disubstituted allenyl indoles affording pyrido[1,2-a]-1H-indoles. Then the axial-to-central chirality transfer starting from enantio-enriched N-1,3-disubstituted allenylindoles affording optically active pyrido[1,2-a]-1H-indoles has been realized in excellent yields and enantioselectivities. A mechanism has been proposed based on mechanistic studies. Synthetic applications have also been demonstrated.

We reported an IPrAuCl/AgSbF₆-catalyzed cycloisomerization of enantio-enriched N-1,3-disubstituted allenylindoles affording optically active pyrido[1,2-a]-1H-indoles in excellent yields and enantioselectivities.     

Synthesis of hexopyranosyl acetates and 2,3-disubstituted tetrahydropyrans via chemoselective hydrogenation of hex-2-enopyranosyl acetates

A simple and easy method for chemoselective synthesis of hexopyranosyl acetates and 2,3-disubstituted tetrahydropyrans from hex-2-enopyranosyl acetates was demonstrated. The former was achieved by hydrogenation catalyzed by Rh/Al₂O₃ in EtOAc/toluene solvent at 0 °C, while the latter was carried out using Pd/C in EtOH/AcOH at 25 °C.     

Synthesis of 3,3-disubstituted oxindoles through Pd-catalyzed intramolecular cyanoamidation

The cyanoamidation of olefins was achieved. When N-(2-vinylphenyl)cyanoformamides were treated with palladium catalyst, intramolecular cyanoamidation took place to give corresponding 3,3-disubstituted oxindoles. P(t-Bu)₃ showed a remarkable effect on this reaction. When it was used with Pd(dba)₂, the reaction was completed in 15 min at 100 °C for many substrates. Furthermore, the enantioselective cyanoamidation was accomplished with Pd(dba)₂ and an optically active phosphoramidite to provide optically active 3,3-disubstituted oxindoles. Manipulation of the resulting oxindoles has been studied.     

Dissociation of positively charged aliphatic epoxides. II. [C5H10O]+˙ epoxides and α,β unsaturated ethers

The unimolecular dissociations of C₅ epoxides ions mono- or disubstituted at C₁ give exclusive loss of CH₃ and exclusive formation of methoxy vinyl carbenium ion, both in the source and in the 2nd field-free region. In the case of the 1,2-disubstituted ion in the 2nd field-free region the loss of ethene is the only pathway, while a competition occurs for the trisubstituted ion leading to [C₃H₆O]⁺˙ and [C₄H₇O]⁺˙ ions, the structure of which are demonstrated. The first step of the different mechanisms is the cleavage of the heterocyclic C? C bond.     

13C nuclear magnetic resonance studies of the adducts of bis-(π-crotyl-D7-nickel iodide) and 2-alkylbutadienes as related to mechanism of polymerization

By ¹³C NMR spectroscopy, the structures of (C₄D₇Nil)₂ adducts with isoprene, 2-ethyl-, 2-isopropyl- and 2-tert. butylbutadienes have been investigated. The nature of the 2-alkyl substituent in the anti- and syn-1,2-disubstituted π-allylic complexes influences the character of electron charge densities distribution on the carbon atoms of a π-allylic ligand. Mutual arrangement of substituents in the π-allylic active sites has been shown to remain in the double bonds of elementary units of a polymer chain.     

Regioselectivity and reactivity in the addition of trichloromethyl radicals to amides of unsaturated carboxylic acids

The AM1 method was used to analyze the factors that correlate with regioselectivity in the addition of radicals to 1,2-disubstituted unsaturated compounds. The rate constants of the addition of^.CCl₃ radicals to RCH=CHC(O)X (R = Ph, Me; X = N-pyrrolidyl) were determined by ESR. The analysis of the spin density distribution in mono- and 1,2-disubstituted alkenes and the experimental values for the rate constants of the addition of^.CCl₃ radicals to these alkenes allowed the authors to conclude that the efficiency of the addition of^.CC1₃ to unsaturated compounds depends only on steric effects.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 452–455, March, 1995.     

Synthesis of 1,2-disubstitued benzimidazoles using SiO2/ZnCl2

A general and easy method for the synthesis of several 1,2-disubstituted benzimidazoles using SiO₂/ZnCl₂ and solvent-free conditions is described. This efficient and improved method furnishes selectively and in good yields the corresponding 1,2-bis(organyl)-benzimidazoles starting from o-phenylenediamine and aromatic or aliphatic aldehydes. The catalytic system was re-used up three times and the use of focused microwaves accelerates the reaction.     

Syntheses of homochiral 1,2-ferrocene-functionalized Lewis acids and acid/base pairs

We report a facile approach for the synthesis of homochiral 1,2-disubstituted ferrocene-functionalized Lewis acids and acid/base pairs. The synthesis is based on chiral induction facilitated by the ortho sulfinyl subsitutent in S-Fc{S(O)p-tol}, S-1, to obtain the key intermediate S,S_p-1,2-fc{S(O)p-tol}(BMes₂), S,S_p-2a (p-tol = C₆H₄Me-4, Mes = C₆H₂Me₃-2,4,6). Subsequent substitution of the -S(O)p-tol substituent in S,S_p-2a gives access to a range of enantiomerically pure S_p-1,2-ferrocene-functionalized Lewis acids and acid/base pairs including the first homochiral 1-phosphino-2-borylferrocene. Enantiomeric excesses (e.e.s) of >95% have typically been achieved using this methodology.     

Intercalation of 1,2-Alkanediols into α-Zirconium Hydrogenphosphate

Intercalation compounds of α-Zr(HPO₄)₂ · H₂O with 1,2-alkanediols (from C3 to C16) have been prepared by replacing 1-propanol in α-Zr(HPO₄)₂ · 2C₃H₇OH with the desired 1,2-alkanediols by a treatment in a microwave field. It was found that the intercalates contain 1.5 molecules of diol per formula unit. The diol molecules are placed between the host layers in a bimolecular way with their aliphatic chains tilted at an angle of 51°. The diol molecules are anchored in the interlayer space by H-bonds. A mixed intercalate, containing 1,2-butanediol and 1,2-decanediol in a roughly equimolar ratio, is formed when the α-Zr(HPO₄)₂ · 2C₃H₇OH intercalate, suspended in a mixture of 1,2-butanediol and 1,2-decanediol, is exposed to microwave radiation. No new phase containing both types of the guest molecules was observed when the 1-propanol intercalate, suspended in a mixture of 1-propanol and 1,2-octanediol, is exposed to microwave radiation.