Asymmetric synthesis of 3-substituted 8-hydroxy-3,4-dihydroisocoumarins from (S)-4-isopropyl-2-(2-methoxy-6-methylphenyl)oxazoline

Reaction of the laterally lithiated (S)-4-isopropyl-2-(2-methoxy-6-methylphenyl)oxazoline with p-tolualdehyde gave an inseparable mixture of the addition products in low diastereoselectivity. However, the (S,S)-product cyclized to the corresponding 3,4-dihydroisocoumarin faster than the (S,R)-product on silica gel, which allowed to be produced both enantiomers of 8-methoxy-3-(p-tolyl)-3,4-dihydroisocoumarin in moderate to good optical purity [S-enantiomer: 75% ee; R-enantiomer: 96% ee]. This procedure was applied to the short-step synthesis of optically active 3,4-dihydroisocoumarin natural products such as (R)-8-hydroxy-3-(1-tridecyl)-3,4-dihydroisocoumarin and (R)-phyllodulcin.     

Asymmetric synthesis of 3-substituted 3,4-dihydroisocoumarins via stereoselective addition of laterally lithiated chiral 2-(o-tolyl)oxazolines to aldehydes followed by diastereomer-selective lactonization

Lateral lithiation of (S)-4-isopropyl-2-(o-tolyl)oxazoline in diethyl ether followed by the reaction with aldehydes in the presence of TMEDA produced the addition products with stereoselectivities up to 84% de. Utilization of TMEDA as a ligand is essential for the good selectivity. Rationale for the stereoselectivity is proposed based on ab initio calculation of the lateral lithio species. The major (S,S)-products lactonized faster than the minor (S,R)-products to the corresponding 3,4-dihydroisocoumarins under acidic conditions. Thus, (3S)-3,4-dihydroisocoumarins were obtained in good optical purities up to 97% ee by sequential application of these matched stereoselective reactions.     

Synthesis, structure, and properties of piperidinium 3-(4-chlorophenyl)-2-cyano-3-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)thiopropionimidate

Condensation of 4-chlorobenzaldehyde with cyanothioacetamide and dimedone in the presence of piperidine afforded piperidinium 3-(4-chlorophenyl)-2-cyano-3-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)thiopropionimidate. This salt was studied by X-ray diffraction analysis and used in the synthesis of the previously unknown partially hydrogenated 2-alkylthioquinolin-2-ones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 733–737, April, 2000.     

2,5-二甲基-4-羟基-3(2H)呋喃酮的合成

以乙酰丙酮(1)为原料，经电解氧化偶联，Paal-Knorr闭环，Baeyer-Villiger氧化，水解等步骤，合成了一种重要的杂环香料，2,5-二甲基-4-羟基-3(2H)呋喃酮(6)。     

Reactions of Ru(Cp) complexes with P(o-tolyl)3

Reaction of [Ru(Cp^∗)(CH₃CN)₃](PF₆) with P(o-tolyl)₃ affords [Ru(Cp^∗){(η⁶-o-tolyl)P(o-tolyl)₂}](PF₆) (4) in which the P-atom is not coordinated to the metal. The solid-state structure of 4 has been determined. A related reaction with P(p-tolyl)₃ reveals a small quantity [Ru(Cp^∗){(η⁶-p-tolyl)P(o-tolyl)₂}](PF₆), in solution, but mostly the expected bis-phosphine complex. Reaction of the Ru(IV) dication, [Ru(Cp^∗)(η³-PhCHCHCH₂)(DMF)₂](PF₆)₂, with P(o-tolyl)₃ gives a mixture of the phosphonium salt, C₆H₅CHCHCH₂P(o-tolyl)₃ (9) and the dication [Ru(Cp^∗) (η⁶-C₆H₅CHCHCH₂P(o-tolyl)₃)](PF₆)₂ (10). Salt 9 forms via attack of the P-atom on the allyl ligand. The latter product results from complexation of 9 via the phenyl group of the former allyl ligand. It would seem that the sterically demanding P(o-tolyl)₃ ligand is not readily compatible with the Ru(Cp^∗) fragment, in either the +2 or +4 oxidation state. Detailed NMR studies are reported.     

Synthesis of 2,2-dimethyl-5-hydroxy-3-(3-oxobutyl)-7-pentyl-4-chromone

Alkylation and deformylation of 2,2-dimethyl-3-hydroxymethylene-5-hydroxy-7-pentyl-4-chromone occurs in the same step to give the title compound.     

Synthesis and biological activity of 1-(aryloxy)-3-(6-chloro-4,4-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-yl)propan-2-ols

Treatment of 1-(4-chlorobenzylamino)-2-methylpropan-2-ol with concentrated sulfuric acid at 0°C gave 6-chloro-4,4-dimethyl-1,2,3,4-tetrahydroisoquinoline which reacted with (aryloxymethyl)oxiranes to afford new propan-2-ol derivatives of the tetrahydroisoquinoline series, 1-(aryloxy)-3-(6-chloro-4,4-dimethyl-1,2,3,4-tetrahydroisoquinolin-2-yl)propan-2-ols. Some of the synthesized compounds or their hydrochlorides showed moderate adrenergic blocking and sympatholytic activities.     

Ring-chain isomerization of 2-substituted 3-hydroxy-3-(4-dimethyl-aminophenyl)isoindolinones

N-Unsubstituted and N-monosubstituted amides of 2-(4-dimethylaminobenzoyl)benzole acid exist in the chain form of 3-hydroxyisoindolinones in the crystalline state and in solutions in dioxane, whereas the tautomeric amide hydroxyisoindolinone equilibrium occurs (except for the methyl derivative) in more polar solvents. The analogous N-(1-adamantanyl)amide exists in the open form and does not undergo cyclization under alkaline catalysis conditions; protonation of the dimethylamino group is accompanied in all cases by splitting out of water to give compounds with a quinoid structure; an equilibrium between the protonated and quinoid forms, which is shifted markedly to favor the latter, is observed for some compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 780–785, June, 1979.     

5-叔丁基-5-(1'-羟基-2'-甲基丙基)-2,2-二甲基-1,3-二氧六环的合成研究

为得到3,4-二取代双环硫化磷酸酯的中间体5-叔丁基-5-(1'-羟基-2'-甲基丙基)-2,2-二甲基-1,3-二氧六环, 通过5-叔丁基-5-甲酰基-2,2-二甲基-1,3-二氧六环与异丙基溴化镁反应没有得到目标化合物, 而得到了还原产物, 改用异丙基锂代替异丙基溴化镁反应后得到目标化合物, 通过超声波辅助反应, 大幅度提高了反应收率.     

芳亚甲基双(3-羟基-5,5-二甲基-2-环己烯-1-酮)类化合物的合成

在水溶剂中,酸性离子液体[bmim][HSO4]可以有效地催化芳香醛与5,5-二甲基-1,3-环己二酮反应3～5h,得到产率为76%～86%的芳亚甲基双(3-羟基-5,5-二甲基-2-环己烯-1-酮)类化合物.该反应产物后处理简单,催化剂可以回收利用.催化剂在循环使用五次时对产物的收率影响不大,是一种环境友好的绿色合成方法.     

Determination of absolute configuration of 2-methyl-1-(o-tolyl)naphthalene and the related axially chiral biaryls

An enantiomerically enriched sample (84.3% ee) of (aS)-2-methyl-1-[(((o-triisopropylsilyl)oxy)methyl)phenyl]naphthalene was produced via catalytic asymmetric Suzuki-Miyaura cross-coupling using an atropisomeric naphthamide-derived phosphine (A²phos) as the chiral ligand. After one recrystallization, enantiopurity of the biaryl product was improved to 98.9% ee and its absolute configuration was determined by X-ray crystal structural analysis. Through chemical transformations, the (aS)-enantiomers of 1-[(o-hydroxymethyl)phenyl]-2-methylnaphthalene, 1-[(o-chloromethyl)phenyl]-2-methylnaphthalene, and 2-methyl-1-(o-tolyl)naphthalene were obtained. Several other chiral biaryls were synthesized and stereochemically assigned.     

Synthesis of 2-substituted 3,4-bis(diethoxyphosphorylmethyl)furans

Bromination of ethyl 4-(diethoxyphosphorylmethyl)-5-methylfuran-2-carboxylate and 4-(diethoxyphosphorylmethyl)-5-methylfuran-2-carbonitrile with N-bromosuccinimide followed by phosphorylation via the Arbuzov reaction have yielded the corresponding 2-substituted 4,5-bis(diethoxyphosphorylmethyl)furans. Synthesis and transformations of bisphosphorylated 2-furoic acid and its derivatives are described.

     

Synthesis of some cyclopentenones and crystal structure of 4-hydroxy-3,4-bis(4-methoxyphenyl)-5,5-dimethyl-2-cyclopenten-1-one

Abstract  

Sodium-hydroxide-catalyzed condensation of di-p-methyl- and di-p-methoxybenzil with acetone derivatives was investigated in methanol. Di- and trisubstituted products were obtained as cyclopentenones, while tetraaryl-substituted systems were isolated as cyclopentadienones. The structures of the products were identified by elemental analysis, infrared (IR), nuclear magnetic resonance (¹H NMR), and mass spectroscopy. The solid-state structure of 4-hydroxy-3,4-bis(4-methoxyphenyl)-5,5-dimethyl-2-cyclopenten-1-one was further studied by single-crystal X-ray diffraction analysis. The title compound crystallizes in an orthorhombic space group and intermolecular O–H···O and C–H···O hydrogen bonds stabilize the crystal lattice.     

Effect of ortho-substituents on the stereochemistry of 2-(o-substituted phenyl)-1H-imidazoline-palladium complexes

Palladium complexes composed of [Pd(Ln)₂Cl₂] (n = 1, 2, 3, 4, 6), [L5a]₂[PdCl₄] and [Pd(L5b)₂], where L1 = 4,5-dihydro-2-phenyl-1H-imidazole (=2-phenyl-1H-imidazoline), L2 = 2-(o-fluorophenyl)-1H-imidazoline, L3 = 2-(o-methylphenyl)-1H-imidazoline, L4 = 2-(o-tert-butylphenyl)-1H-imidazoline, L5a = 2-(o-hydroxyphenyl)-1H-imidazolinium, L5b = 2-(1H-imidazolin-2-yl)phenolate, and L6 = 2-(o-methylphenyl)-1H-imidazole, were synthesized. Molecular structures of the isolated palladium complexes were characterized by single crystal X-ray diffraction analysis. The effect of ortho-substituents on the phenyl ring on trans-chlorine geometry was noted for complexes [Pd(L1)₂Cl₂] 1a and 1b, [Pd(L2)₂Cl₂] 2 and [Pd(L6)₂Cl₂] 6, whereas cis-chlorine geometry was observed for [Pd(L3)₂Cl₂] 3 and [Pd(L4)₂Cl₂] 4. PdCl₂ reacts with 2-(o-hydroxyphenyl)-1H-imidazoline in DMF to give [L5a]⁺ and [L5b]^- so that [L5a]₂[PdCl₄] 5a and [Pd(L5b)₂] 5b were obtained. In complex 5b, as an N,O-bidentate ligand, two ligands L5b coordinated with the central Pd(II) ion in the trans-form. The coordination of PdCl₂ with 2-(o-hydroxyphenyl)-1H-imidazolines in solution was investigated by NMR spectroscopy.     

Synthesis of ethyl 3-(3-hydroxy-2-thienyl)-3-oxopropanoates

An approach to the synthesis of substituted ethyl 3-(3-hydroxy-2-thienyl)-3-oxopropanoates was developed based on the reaction of ethyl cyanoacetate, carbon disulfide, and ethyl 4-chloroacetoacetate. The reaction regioselectively involved the ester group, rather than the nitrile one like in the case when malononitrile or cyanacetamide were used.