Palladium(0)-catalyzed highly regio- and stereoselective addition of organoboronic acids with 1,2-allenylphosphonates forming tri- or tetrasubstituted 1(E)-alkenylphosphonates

A highly regio- and stereoselective palladium(0)-catalyzed addition of organoboronic acids with 1,2-allenylphosphonates in the presence of HOAc forming tri- or tetrasubstituted 1(E)-alkenylphosphonates is reported in this paper. The stereoselectivity is much higher than the reported cases. The effects of different R(1), R(2), and R(3) were studied. A mechanism of this reaction is proposed on the basis of our previous study.     

Regio- and stereoselective synthesis of alkyl allylic ethers via gold(I)-catalyzed intermolecular hydroalkoxylation of allenes with alcohols

Reaction of 1-phenyl-1,2-butadiene with 2-phenyl-1-ethanol catalyzed by a 1:1 mixture of a gold(I) N-heterocyclic carbene complex and AgOTf at room temperature for 1 h led to isolation of (E)-(3-phenethoxy-1-butenyl)benzene in 96% yield as a single regio- and stereoisomer. Gold(I)-catalyzed intermolecular allene hydroalkoxylation was effective for monosubsituted, 1,1- and 1,3-disubstituted, trisubstituted, and tetrasubstituted allenes and for a range of primary and secondary alcohols, methanol, phenol, and propionic acid.     

Catalytic Enantioselective Addition of Thioacids to Trisubstituted Nitroalkenes

The first example of a catalytic enantioselective addition to and nitronate protonation of trisubstituted nitroalkenes to produce highly enantioenriched products with a tetrasubstituted carbon is reported. Thioacids added in excellent yields and with high enantioselectivities to both activated and unactivated nitroalkenes. The 1,2‐nitrothioacetate products can be readily converted in two steps to biomedically relevant 1,2‐aminosulfonic acids without loss of enantiopurity.     

Microwave assisted,sequential two-step,one-pot synthesis of novel imidazo[1,2-a]pyrimidine containing tri/tetrasubstituted imidazole derivatives

A series of novel imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives (1-10) has been synthesized via sequential two-step, one-pot, multicomponent reaction using imidazo[1,2- a ]pyrimidine-2-carbaldehyde, benzil, primary amines, and ammonium acetate catalyzed by p -toluenesulfonic acid under microwave-assisted conditions. The results showed that target compounds can be obtained from a wide range of primary amines bearing different functional groups with moderate to good yields (46%-80%) under optimum reaction conditions. This method provides a green protocol for imidazo[1,2- a ]pyrimidine containing tri/tetrasubstituted imidazole derivatives due to ethyl alcohol as a green solvent, microwave irradiation as a greener heating method and one-pot multicomponent reaction as a green technique. The synthesized compounds have been elucidated using various spectroscopic tools such as FT-IR, ¹H NMR, ¹³ C NMR, and MS.     

1-(Organosulfonyloxy)-3(1H)-1,2-benziodoxoles: Preparation and Reactions with Alkynyltrimethylsilanes

Organosulfonyloxy derivatives of 1,2-benziodoxol-3(1H)-one (3a-c) and 3,3-bis(trifluoromethyl)-3(1H)-1,2-benziodoxole (5a-c) can be prepared in high yield by the reaction of 1-hydroxybenziodoxoles 1 or 4 and the corresponding sulfonic acids or Me(3)SiOTf in the form of stable, but moderately hygroscopic, microcrystalline solids. Reaction of the triflate derivatives 3a and 5a with alkynyltrimethylsilanes affords either alkynyliodonium triflates 6, or (E)-beta-(trifluoromethanesulfonyloxy)alkenyliodonium triflates 7, while the same reaction in the presence of pyridine selectively gives the respective 1-alkynylbenziodoxoles 8 and 9 in 82-90% yield.     

Synthesis of enantiomerically pure 1,4-dioxanes from alkenes promoted by organoselenium reagents

An alkene can be converted into two enantiomerically pure diastereomeric selenoethers through a regio- and stereospecific anti addition reaction mediated by N-(phenylseleno)phthalimide in the presence of an enantiomerically pure 1,2-diol. This alkoxyselenylation reaction can be employed as the key step to allow the synthesis of several isomeric tetrasubstituted 1,4-dioxanes in enantiomerically pure form.     

1,2-silyl-migrative cyclization of vinylsilanes bearing a hydroxy group: stereoselective synthesis of multisubstituted tetrahydropyrans and tetrahydrofurans(1)

Acid-catalyzed intramolecular addition of a hydroxy group to alpha-alkylated vinylsilanes has been studied. Treatment of (Z)-5-alkyl-5-silyl-4-penten-1-ols 1 (R = alkyl) with 5 mol % TiCl(4) in CHCl(3) gave trans-2-alkyl-3-silyltetrahydropyrans 2 exclusively (trans/cis = >99/1 to 97/3). The cyclization efficiency and rate strongly depended on the geometry of the C-C double bond and the silyl group. The use of (E)-vinylsilanes resulted in lower yields with poor cis-selectivity. In the cyclization of (Z)-1 (R = Bu), the silyl group used, the reaction time, and the yield of 2 were as follows: SiMe(2)Ph, 9.5 h, 75%; SiMe(3), 7.5 h, 66%; SiMePh(2), 24 h, 58%; SiMe(2)-t-Bu, 0.75 h, 85%; SiMe(2)Bn, 1.5 h, 78%. This 1,2-silyl-migrative cyclization could be applied to stereoselective synthesis of trisubstituted tetrahydropyrans. The acid-catalyzed reaction of 1-, 2-, or 3-substituted (Z)-5-silyl-4-nonen-1-ols 8 gave r-2,t-3,c-6-, r-2,t-3,t-5-, or r-2,t-3,c-4-trisubstituted tetrahydropyrans with high diastereoselectivity, respectively. (Z)-4-Alkyl-4-silyl-3-buten-1-ols 5 as well as 1 underwent the 1,2-silyl-migrative cyclization to give 2-alkyl-3-silyltetrahydrofurans 6 with high trans-selectivity. This silicon-directed cyclization was also available for the stereoselective synthesis of tri- and tetrasubstituted tetrahydrofurans.     

Addition of TMS-substituted oxiranyl anions to acylsilanes. A highly stereoselective approach to tetrasubstituted (Z)-β-hydroxy-α-TMS silyl enol ethers

A highly stereoselective approach to novel tetrasubstituted (Z)-β-hydroxy-α-TMS silyl enol ethers is described. The reaction proceeds via a sequential addition/[1,2]-Brook rearrangement/epoxide-opening process of TMS-substituted oxiranyl anions with acylsilanes.     

A highly stereoselective approach to tetrasubstituted (E)-β-hydroxy silyl enol ethers by addition of aryl-substituted oxiranyl anions to acylsilanes

A highly stereoselective approach to tetrasubstituted (E)-β-hydroxy silyl enol ethers is described. The reaction proceeds via a sequential addition/[1,2]-Brook rearrangement/epoxide-opening process of aryl-substituted oxiranyl anions with acylsilanes.     

Intramolecularly sensitized precipitons: a model system for application to metal sequestration

We have investigated light-triggered or catalytically activated precipitation agents and have proposed the name "precipiton" for such molecules or molecular fragments. A phase separation is induced when the precipiton isomerizes to a low-solubility form. In this paper we describe the first intramolecularly activated precipitons. The isomerization process is induced by intramolecular triplet energy transfer from a covalently attached metal complex. As expected, intramolecular sensitization leads to a more rapid isomerization than can be achieved by intermolecular sensitization at accessible concentrations. Two isomeric bichromophoric precipiton species, each containing [Ru(bpy)(3)](2+) and 1,2-bis(biphenyl)ethene units covalently linked together by an ether tether, have been synthesized and characterized, and their photochemical properties have been investigated. The rates of photoisomerization of these complexes, [((Z)-1,2-bis(biphenyl)ethene-bpy)Ru(bpy)(2)](PF(6))(2) (2Z) and [((E)-1,2-bis(biphenyl)ethene-bpy)Ru(bpy)(2)](PF(6))(2) (2E), were compared to those of their untethered analogues, (Z)-1,2-bis(biphenyl)ethene-OTBS (1Z) and (E)-1,2-bis(biphenyl)ethene-OTBS (1E), where ruthenium sensitization occurred through an intermolecular pathway. Upon irradiation with visible light (lambda > or = 400 nm) in degassed solution, 2Z/E and 1Z/E obeyed reversible first-order rate kinetics. The intramolecularly sensitized precipiton 2Z isomerized 250 times faster (k(2Z-->2E) = 1.0 x 10(-3) s(-1) with a 51% neutral density filter) than the intermolecular case 1Z (k(1Z-->1E) = 0.80 x 10(-5) s(-1)). For 1E and 2E, the isomerization rates were k(1E-->1Z) = 11.0 x 10(-5) s(-1) and k(2E-->2Z) = 1.6 x 10(-3) s(-1), respectively. The average Z/E mole ratio at the photostationary state was 62/38 for 2Z/E and 93/7 for 1Z/E. The impetus for this study was our desire to evaluate the possibility of using metal-binding precipitons that would precipitate only upon metal-to-precipiton binding and would be inert to visible light in the absence of metals.     

Keteniminium-Driven Umpolung Difunctionalization of Ynamides

A three-component Pd-catalyzed coupling of ynamides, aryl diazonium salts, and aryl boronic acids for the synthesis of novel triaryl-substituted enamides is described. This transformation represents the first example of an umpolung regioselective unsymmetrical syn-1,2-diarylation/aryl-olefination of ynamides. The aryl moieties of the diazonium salt (electrophile) and boronic acid (nucleophile) are explicitly incorporated in the electrophilic α- and nucleophilic β-position, respectively, of the ynamide, resulting in a single isomer of the N-bearing tetrasubstituted olefin. The scope is broad (68 examples), showing excellent functional-group tolerance. DFT calculations substantiate the rationale of the mechanistic cycle and the regioselectivity. The chemoselectivity and synthetic potential of the enamide products were also studied.     

Reactivity of a sterically hindered Fe(II) thiolate dimer with amines and hydrazines

The sterically hindered Fe(II) thiolate dimer Fe(2)(mu-STriph)(2)(STriph)(2) (1; [STriph](-) = 2,4,6-triphenylbenzenethiolate) reacts with primary amines ((t)BuNH(2), aniline) and N(2)H(4) to form the structurally characterized addition complexes Fe(STriph)(2)(NH(2)(t)Bu)(2), Fe(2)(mu-STriph)(2)(STriph)(2)(NH(2)Ph)(2), and Fe(2)(mu-eta(1):eta(1)-N(2)H(4))(2)(N(2)H(4))(4)(STriph)(4) in high yield. Chemical and NMR spectroscopic evidence indicate that the binding of these nitrogen donors is labile in solution and multispecies equilibria are likely. With arylhydrazines, 1 catalytically disproportionates 1,2-diphenylhydrazine to aniline and azobenzene, and it rearranges 1-methyl-1,2-diarylhydrazines to give, after treatment with alumina, mononuclear, trigonal bipyramidal Fe(III) complexes of composition Fe(ISQ)(2)(STriph), where [ISQ](-) denotes an appropriately substituted bidentate o-diiminobenzosemiquinonate ligand. Complex 1 shows no reaction with hindered 1,2-dialkylhydrazines (isopropyl or tert-butyl) or tetrasubstituted 1,2-dimethyl-1,2-diphenylhydrazine.     

Direct allenol-based stereocontrolled access to substituted (E)-1,3-enynes

A stereoselective synthesis of 1-substituted (E)-2-aryl-but-1-en-3-ynes, including tetrasubstituted alkenes, has been developed from aryl-substituted α-allenols by treatment with the AcCl-NaOH (aqueous) system. This transformation might be explained through the elimination of acetic acid, made up of a δ-hydrogen and the acetate group in the initially formed α-allenic acetate.     

Macrocycles with 1,2-dicyano-1,2-dithioethene units

Abstract

The new unsaturated macrocyclic tetrathioethers (Z,Z)-4 (n = 0), (Z,Z)-5 (n = 1), (Z,Z)-6 (n = 2) and (Z,Z)-7 (n = 3) were synthesized by the cyclization of (Z)-disodium-1,2-dicyanoethene-1,2-dithiolate (Z)-3 with ω,ω'-dibromoalkanes BrCH₂CH₂(CH₂)nCH₂Br (n = 0;1;2;3) on refluxing in dioxane in yields up to 15%. By reaction of the dithiolate (Z)-3 with 1,3-dibromopropane the unsaturated hexathioether (Z,Z,Z)-6 was also obtained. By the cyclization of dithiolate (Z)-3 with 1,5-dibromopentane and 1,6-dibromohexane the (Z,E)- and (E,E)-isomers, respectively, were formed in addition to the (Z,Z)-isomers. The (E,E)- and (Z,E)-isomers are photochemically convertable to the corresponding themodynamically more stable (Z,Z)-isomers by irradiation with UV-light. The (E,E)-isomers can be synthesized in a straightforward manner using the (E)-disodium-1,2-dicyanoethene-1,2-dithiolate (E)-3. Crystal structures of (Z,Z)-5, (Z,Z)-6, (E,E)-6, (Z,E)-7 and (E,E)-7 are reported.     

An efficient synthesis of tetrasubstituted cyclohexyl-1,2-diamines

The synthesis of symmetrically tetrasubstituted diamines derived from the (R,R)-cyclohexyl-1,2-diamine is reported. We comment on the efficiency of this sequential substitution approach as a method for the synthesis of tetrasubstituted diamines and discuss the acceptable substitution pattern for this methodology.     

An Unusual Rearrangement of a Lithiated N-Acyl-tetrahydroisoquinoline to an Amino-indan Skeleton and Structural Comparison of 3-Amino-2-methylindan- and -tetrahydronaphthalene-2-carboxylic Acids as Possible Building Blocks for Peptide-Turn Mimics

Lithium 1-lithio-6,7-dimethoxy-3-methyl-2-pivaloyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate rearranges to the dilithio derivative of 5,6-dimethoxy-2-methyl-1-(pivaloylamino)indan-2-carboxylic acid ( 2 , [1,2]-sigmatropic shift with retention of configuration) by 1,2-migration resembling the Wittig rearrangement of deprotonated ethers (Scheme 2). The structure, including absolute configuration of the rearrangement product, was determined by X-ray diffraction. Structural conditions for the rearrangement to occur are tested by subjecting various other tetrahydroisoquinoline derivatives ( 6 , 7 , 10 , 15 ) to the metalating conditions. Only one other compound was found to undergo the same rearrangement ( 15 → 16 ). Possible mechanisms of the rearrangement are discussed ( B–G ). Due to the presence of a tetrasubstituted C-atom, the indan-type β-amino-acid derivative 2 has a conformationally locked structure (N? C? C? CO₂R dihedral angle 44°). For comparison, the corresponding tetralin-type β-aminoacid derivatives 19–22 were prepared, and it was shown by X-ray analysis (of the ester 21 ) that these have larger dihedral angles (ca. 60°). It is proposed that β-amino acids of the type described here could be incorporated into peptides, providing bents of known angles along the peptide backbone.     

Synthesis of stereoisomerically pube (E)-1,5-diyn-3-enes and (E)-1-bromo-3-yn-1-enes by diastereoselective palladium-catalyzed cross-coupling reaction of 1-alkynylzinc chlorides with a stereoisomeric mixture of 1,2-dibromoethylene.

In the stepeospecific palladium-catalyzed cross coupling reaction of 1-alkynylzinc chlorides, (E)-1,2-dibromoethylene reacts preferentially in the presence of (Z)-1,2-dibromoethylene.Products of di- or mono-substitution can be obtained according to the ratio of reagents.     

Synthesis and stereochemical stability of new atropisomeric 1-(substituted phenyl)pyrrole derivatives

Addition of organometallic reagents to optically active methyl 1-(2-methoxycarbonyl-6-trifluoromethylphenyl)pyrrole-2-carboxylate provided the corresponding tetrasubstituted diols and/or pyrrolo[1,2-a]benzoxazepines as pure enantiomers or racemates depending on the organometallic reagents used. Rotational energy barriers around the interconnecting C-N bonds were estimated by molecular modeling calculations and NMR measurements with the aim of clarifying the stereochemical stability order of the new atropisomeric compounds. NMR methods for the determination of the enantiomeric purity of the new compounds are proposed.     

Iron-mediated hydrazine reduction and the formation of iron-arylimide heterocubanes

The reaction of Fe(N{SiMe(3)}(2))(2) (1) with 1 equiv of arylthiol (ArSH) results in material of notional composition Fe(SAr)(N{SiMe(3)}(2)) (2), from which crystalline Fe(2)(μ-SAr)(2)(N{SiMe(3)}(2))(2)(THF)(2) (Ar = Mes) can be isolated from tetrahydrofuran (THF) solvent. Treatment of 2 with 0.5 equiv of 1,2-diarylhydrazine (Ar'NH-NHAr', Ar' = Ph, p-Tol) yields ferric-imide-thiolate cubanes Fe(4)(μ(3)-NAr')(4)(SAr)(4) (3). The site-differentiated, 1-electron reduced iron-imide cubane derivative [Fe(THF)(6)][Fe(4)(μ(3)-N-p-Tol)(4)(SDMP)(3)(N{SiMe(3)}(2))](2) ([Fe(THF)(6)][4](2); DMP = 2,6-dimethylphenyl) can be isolated by adjusting the reaction stoichiometry of 1/ArSH/Ar'NHNHAr' to 9:6:5. The isolated compounds were characterized by a combination of structural (X-ray diffraction), spectroscopic (NMR, UV-vis, Mo?ssbauer, EPR), and magnetochemical methods. Reactions with a range of hydrazines reveal complex chemical behavior that includes not only N-N bond reduction for 1,2-di- and trisubstituted arylhydrazines, but also catalytic disproportionation for 1,2-diarylhydrazines, N-C bond cleavage for 1,2-diisopropylhydrazine, and no reaction for hindered and tetrasubstituted hydrazines.     

Synthesis of N,N′-disubstituted cyclic 1,2-diamines derived from (1R,2R)-1,2-diaminocyclohexane

The synthesis of N,N′-unsymmetrically tetrasubstituted cyclic 1,2-diamines derived from (1R,2R)-diaminocyclohexane is reported. We comment on the structural nature of these cyclic 1,2-diamines and discuss their characteristic features.