Synthesis of optically active 3-alkoxy-6-hydroxymethyl-6-methyl-2-cyclohexenone

Optically active 3-alkoxy-6-hydroxymethyl-6-methyl-2-cyclohexenone and 6-acetoxymethyl-3-alkoxy-6-methyl-2-cyclohexenone were efficiently obtained by lipase-catalyzed kinetic resolution. (R)-6-Acetoxymethyl-3-(methoxymethoxy)-6-methyl-2-cyclohexenone was converted to the synthetic intermediate of cassiol.     

Circular dichroism, optical rotation and absolute configuration of 2-cyclohexenone-cis-diol type phenol metabolites: redefining the role of substituents and 2-cyclohexenone conformation in electronic circular dichroism spectra

The absolute configurations of 2-cyclohexenone cis-diol metabolites resulting from the biotransformation of the corresponding phenols have been determined by comparison of their experimental and calculated circular dichroism spectra (TDDFT at the PCM/B2LYP/Aug-cc-pVTZ level), optical rotations (calculated at the PCM/B3LYP/Aug-cc-pVTZ level) and by stereochemical correlation. It is found that circular dichroism spectra and optical rotations of 2-cyclohexenone derivatives are strongly dependent on the ring conformation (M or P sofa S(5) or half-chair), enone non-planarity and the nature and positions of the hydroxy and alkyl substituents. The effect of non-planarity of the enone chromophore, including the distortion of the C=C bond, is determined for the model structures by TDDFT calculations at the PCM/B2LYP/6-311++G(2d,2p) level. Non-planarity of the C=C bond in the enone chromophore is commonly encountered in 2-cyclohexenone derivatives and it is a source of significant rotatory strength contribution to the electronic circular dichroism spectra. It is shown that the two lowest-energy transitions in acrolein and 2-cyclohexenone and its derivatives are n(C=O)-π(C=O)* and π(C=C)-π(C=O)*, as expected, while the shorter-wavelength (below 200 nm) transitions are of more complex nature. In 2-cyclohexenone and its alkyl derivatives it is predominantly a mixture of π(C=C)-π(C=C)* and π(C=C)-σ* transitions, whereas the presence of hydroxy substituent results in a dominant contribution due to the n(OH)-π(C=O)* transition. A generalized model for correlation of the CD spectra of 2-cyclohexenones with their structures is presented.     

Theoretical study of the photochemical [2 + 2]-cycloadditions of cyclic and acyclic alpha,beta-unsaturated carbonyl compounds to ethylene

The ground and first triplet excited-state potential energy surfaces of the [2 + 2]-cycloadditions of 2-cyclohexenone, methyl acrylate, and methyl crotonate to ethylene have been studied by means of CASSCF and DFT-B3LYP calculations. The attack of ethylene to the (3)(pi-pi) alpha,beta-unsaturated carbonyl compound leads to the formation of a triplet 1,4-biradical intermediate that evolves to the ground-state potential energy surface. The outcome of the reaction is governed by the competition between the deactivation of the (3)(pi-pi) alpha,beta-unsaturated carbonyl compound itself and its reaction with ethylene to form the triplet 1,4-biradical. For 2-cyclohexenone, the potential energy barrier corresponding to the formation of the biradical intermediate is lower than for the acyclic systems. On the other hand, the energy necessary to reach the crossing point between the (3)(pi-pi) and the ground-state potential energy surfaces is lower for the acyclic systems than for 2-cyclohexenone. For methyl acrylate and methyl crotonate, the decay of the (3)(pi-pi) state of the isolated molecule is therefore expected to be faster than the formation of the 1,4-biradical, so that the [2 + 2]-cycloaddition will not take place. However, for 2-cyclohexenone the formation of the triplet 1,4-biradical is favorable, and the process will lead to the formation of the corresponding cyclobutane derivative.     

Glutathionyl transferase catalyzed addition of glutathione to COMC: a new hypothesis for antitumor activity

[reaction: see text] Data are presented indicating that the potent antitumor activity of 2-crotonyloxymethyl-(4R,5R,6R)-4,5,6-trihydroxy-2-cyclohexenone (COTC) and 2-crotonyloxymethyl-2-cyclohexenone (COMC) is not likely the result of glyoxalase I inhibition, as has long been assumed. An alternative hypothesis is presented, based on the finding that COMC is a substrate for human glutathionyl transferase, which produces a transient, highly electrophilic glutathionylated 2-exomethylenecyclohexanone that can covalently modify proteins and nucleic acids.     

Sequential Birch reduction-allylation and Cope rearrangement of o-anisic acid derivatives

A new method for the construction of quaternary centers on cycloalkane rings is reported. The Cope rearrangement of 4-methyl-2-allyl-2-(N-pyrrolidinyl)-carboxamide-3-cyclohexenone yields 4-methyl-4-allyl-2-(N-pyrrolidinyl)-carboxamide-2-cyclohexenone in high yield. The rearrangement substrates are easily generated from Birch reduction-allylation of o-anisic acid derivatives.     

(R)- and (S)-5-trimethylsilyl-2-cyclohexenone: a versatile chiral source for the synthesis of optically active cyclohexanone derivatives

5-Trimethylsilyl-2-cyclohexenone was synthesized from anisole and was successfully resolved to the optically pure form utilizing kinetic resolution method of the reaction with thiol in the presence of cinchonidine. (+)-α-curcumene was synthesized from (R)-((3)-5-trimethylsilyl-2-cyclohexenone.     

The Mukaiyama-Michael addition of a β,β-dimethyl substituted silyl ketene acetal to α,β-unsaturated ketones using tetra-n-butylammonium bibenzoate as a nucleophilic catalyst

The Michael addition of a β,β-dimethyl substituted silyl ketene acetal [Me₂CC(OMe)OSiMe₃] to α,β-unsaturated ketones, namely, 2-cyclopentenone, 2-cyclohexenone, 3-methyl-2-cyclohexenone, isophorone, methyl vinyl ketone and mesityl oxide occurs smoothly in the presence of the nucleophilic catalyst, tetra-n-butyl ammonium bibenzoate (TBABB) in THF giving the corresponding 1,4-adducts in excellent yields.     

Manganese(III) acetate based oxidation of substituted α′-position on cyclic α,β-unsaturated ketones

Selective oxidation of the tertiary α′-position on various 2-cyclopentenone, 2-cyclohexenone and aromatic ketone derivatives with manganese(III) acetate is described.     

A method for the catalytic enantioselective synthesis of 6-silylated 2-cyclohexenones

6-Silylated-2-cyclohexenones can be synthesized enantioselectively by hydrosilylation of the corresponding diazo-2-cyclohexenone in the presence of a chiral Rh(II) catalyst.     

Catalyzed Diels-Alder reaction of alkylidene- or arylideneacetoacetates and Danishefsky's dienes with lanthanide salts aimed at selective synthesis of cis-4,5-dimethyl-2-cyclohexenone derivatives.

The first successful example of the catalyzed Diels-Alder reaction of 1-methoxy-3-trimethylsiloxy-1,3-diene (Danishefsky's diene, 2a), giving the corresponding carbocyclic adducts, is described. The reaction of (Z)-ethylideneacetoacetate 1a with 2a is catalyzed with lanthanide salts such as Yb(OTf)(3) at 0 degrees C, affording the corresponding 2-cyclohexenone 3a in good yield with complete integrity of the starting geometry of 1a. The thermal version of the same cycloaddition results in a decrease in the cis arrangement of the 5-methyl and the 4-alkoxycarbonyl groups on 2-cyclohexenone. The catalyzed reaction of (E)-1a unexpectedly affords the cis-arranged 3a. The reaction path for the catalyzed Diels-Alder reaction is postulated on the basis of these results.     

Opening the 'black box': oscillations in organocuprate conjugate addition reactions

Under the conditions of a rapid injection experiment, the conjugate addition reactions of butyl Gilman reagents with 2-cyclohexenone undergo oscillations of a complex nature.     

Stereoselective synthesis of some cis 2,3- disubstituted cyclanones : Ring size influence on the stereoselectivity of 2-substituted endocyclic enolates protonation

Conjugate addition of carbanionic reagents formed from aryl-or phenyl-thioacetonitriles 1a–1c and 2 to 2-methyl and 2-phenyl 2-cyclohexenone or 2-methyl 2-cyclopentenone, followed by acidic quench, under kinetic control, leads to different ratios of cis and trans 2,3-disubstituted cyclanones according to ring size. From 2-methyl and 2-phenyl 2-cyclohexenone, the cis isomer is highly predominant (85 to 98%). From 2-methyl 2-cyclopentenone a cis/trans mixture is obtained: the cis isomer only predominates when a bulky reagent (1c) is used (80%); in the other cases a mixture of nearly 1:1 is obtained.     

Asymmetric michael addition of aromatic thiols to 2-cyclohexenone and maleic acid esters via formation of crystalline cyclodextrin complexes

The asymmetric Michael addition of aromatic thiols to 2-cyclohexenone and maleic acid esters has been carried out by utilizing their crystalline cyclodextrin complexes suspended in water. The best chiral induction, 30% enantiomeric excess (ee), was achieved in combinations of 2-cyclohexenone and octyl maleate with the crystalline -cyclodextrin complex of benzenethiol (method A) to afford (S)-3-phenylthiocyclohexanone and (S)-octyl-2-phenylthiosuccinate, respectively, whereas the reaction of benzenethiol with 2-cyclohexenone included in -cyclodextrin (method B) inversely induced the chiral recognition to give the (R)-adduct with 4–9% ee.     

Three component condensation of 6-quinolylamine with aromatic aldehydes and cyclohexyl 1,3-diketones

A three component condensation of 6-quinolylamine with 4-bromo-or 4-methoxybenzaldehyde, and 1,3-cyclohexanedione or dimedone gave 12-(4-bromophenyl)-and 12-(4-methoxyphenyl)-9,9-dimethyl-8,9,10,12-tetrahydro-7H-benzo[b][4,7]phenanthrolin-11-ones. The reaction intermediates obtained were N-arylmethylene-6-quinolylamines, 2-arylmethylenebis(1,3-cyclohexanediones), 3-(6-quinolylamino)-2-cyclohexenone, and 5,5-dimethyl-3-(6-quinolylamino)-2-cyclohexenone. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 6, pp. 877–885, June, 2007.     

“Delocalized model” in CNDO/2 framework. Application to reduction of 2-cyclohexenone

An attempts is made to develop the “delocalized model” in the CNDO/2 framework. This treatment is able to reproduce the results concerning the study of the factors influencing the 2-cyclohexenone reduction by hydride ions.     

Sonochemical asymmetric hydrogenation of isophorone on proline modified Pd/Al2O3 catalysts

The sonochemical asymmetric hydrogenation of isophorone (3,3,5-trimethyl-2-cyclohexenone) by proline-modified Pd/Al2O3 catalysts is described; presonication of a commercial Pd/Al2O3-proline catalytic system resulted in highly enhanced enantioselectivities (up to 85% ee).     

Copper catalysed 1,4-addition of organozinc reagents to α,β-unsaturated carbonyl compounds: a mechanistic investigation

A mechanistic study of the 1,4-addition of diethylzinc to 2-cyclohexenone catalysed by copper complexes of the Schiff base ligand H₂L1 was performed. The kinetic law of this system was determined and the nature of the different copper complexes involved in the reaction was investigated. The experimental results indicate a first-order dependence of the reaction rate on 2-cyclohexenone concentration, a zero-order on diethylzinc concentration, and a first-order dependence with respect to the concentration of a 1:1.2 mixture of Cu(OTf)₂ and H₂L1. A sharp change in the kinetics of the reaction was observed at catalyst concentrations higher than 9 mM, indicating the possible formation of catalytically inactive species. An aggregate copper complex, with the molecular formula [(CuL1)₂ · Cu(OTf)₂](TfOH)_1/3 (1), is formed upon mixing Cu(OTf)₂ and ligand H₂L1 in toluene. Complex 1 is reduced in situ to a catalytically active copper(I) species by addition of 12 equivalents of Et₂Zn. This species is able to perform the conjugate addition to 2-cyclohexenone under stoichiometric conditions and resumes its catalytic activity in the presence of 2-cyclohexenone and Et₂Zn.     

A tandem enyne/ring closing metathesis approach to 4-methylene-2-cyclohexenols: an efficient entry to otteliones and loloanolides

A short and efficient approach to a 4-methylene-2-cyclohexenone substructure present in otteliones and loloanolides is described. This strategy involves a tandem enyne/ring closing metathesis as the key reaction to construct this labile core unit.     

Synthesis of cis-decalin via diels-alder and double michael cycloaddition with substituted nazarov reagent

The base-catalyzed cycloaddition of the methyl substituted Nazarov reagent 2 with 2-carbomethoxy-2-cyclohexenone (1) yielding cis-decalin products is reported.     

Novel efficient synthesis of an enantiomeric pair of tricycloillicinone

The title synthesis was achieved starting with 3-ethoxy-2-cyclohexenone by a method featuring Davis’ asymmetric hydroxylation and Pauson-Khand reaction as the key steps.