A Useful Modification of the Evans Auxiliary: 4-Isopropyl-5,5-diphenyloxazolidin-2-one

The 4-isopropyl-5,5-diphenyloxazolidinone ( 1 ) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250°, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus, the soluble N-acyl-oxazolidinones ( 7 – 16 ) can be prepared from 1 with BuLi at temperatures around 0° instead of −78° (Scheme 3), their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12), with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4+2) cycloaddition (Scheme 11). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TiCl₄ complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.     

环状碳酸酯5,5-二甲基-1,3-二噁烷-2-酮的合成

在三乙胺存在下,2,2-二甲基-1,3-丙二醇和氯甲酸乙酯反应合成了环状碳酸酯5,5-二甲基-1,3-二噁烷-2-酮,其结构经1H NMR和IR表征。提出了可能的反应机理。     

Reaction of 5,5-dimethyl-4-cyanomethylene-1,3-oxathiolan-2-one with amines and ammonia

A simple method for the synthesis of 5,5-dimethyl-4-cyanomethylene-2-cyanomethyl-2-[1-methyl-1-(carbamoyloxy)ethyl]-1,3-dithiolanes was developed on the basis of the reaction of 5,5-dimethyl-4-cyanomethylene-1,3-oxathiolan-2-one with amines (primary and secondary) and ammonia.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 335–338, March, 1992.     

Dynamic NMR and computational study of 5,5-dimethyl-3,4-di-p-tolyl-2-cylopenten-1-one

The restricted rotation of p-tolyl moiety in 5,5-dimethyl-3,4-di-p-tolyl-2-cyclopenten-1-one was studied by variable temperature NMR spectroscopy at a temperature range of 218-368 K. A free rotation, in NMR time scale, was observed at temperatures higher than 368 K; while, the rotation froze below 248 K. From dynamic NMR analysis, the Arrhenius energy of activation ΔG? was calculated as 56.37 kJ mol(-1). The experimental results were confirmed by theoretical calculation using the density functional theory method B3LYP with basis sets, 6-31G and 6-31+G.     

Novel heterocyclization of 3-(2-aminophenylamino)- 5,5-dimethyl-2-cyclohexen-1-one

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5,5-dimethyl-1,3-dioxan-4-ol as orthogonally protected equivalent of 2,2-dimethyl-3-hydroxypropanal

Condensation of isobutyraldehyde with aqueous formaldehyde in the presence of Ba(OH)2 gave a new gem-dimethyl-substituted building block.     

Reactions of 2-cyano-3-ethoxy-5,5-dimethyl-2-cyclohexen-1-one with 2-amino- and 2-hydrazionobenzimidazoles

The reactions of 2-cyano-3-ethoxy-5,5-dimethyl-2-cyclohexen-1-one with 2-amino- and 2-hydrazinobenzimidazoles gave 1-oxo-3,3-dimethyl-11-amino-1,2,3,4-tetrahydroquinazolino[3,2-a]benzimidazole and 2-(2-benzimidazolyl)-3-amino-4-oxo-6,6-dimethyl-4,5,6,7-tetrahydroindazole, respectively.Riga Technical University, Riga LV-1658. Latvian Institute of Organic Synthesis, Riga LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 235–240, Feburary, 1997.     

Synthesis and reactions of 2-hydroxy-5,5-dimethyl- and 2-hydroxy-5,5-pentamethylene-2-trifluoromethyltetrahydro-4-pyranones withN-nucleophiles

Condensation of 4-hydroxy-3,3-dimethyl- and 4-hydroxy-3,3-pentamethylenebutan-2-ones with ethyl trifluoroacetate in the presence of LiH in hexane afforded 2-hydroxy-5,5-dimethyl-and 2-hydroxy-5,5-pentamethylene-2-trifluoromethyltetrahydro-4-pyranones, whose behavior in reactions withN-nucleophiles is analogous to that of unsymmetrical polyfluorinated β-diketones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1201–1205, June, 1998.     

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.     

2,2’-(4-氯苯基)亚甲基双(3-羟基-5,5-二甲基-2-环己烯-1酮)的晶体结构

标题化合物C23H27O4Cl是由邻氯苯甲醛与5，5-二甲基-1，3-环己二酮在N，N-二甲基甲酰胺中反应而得。结构通过单晶X-射线衍射法测定，其晶体属于单斜晶系，空间群晶体结构用直接法解出，使用全矩阵最小二乘法对原子参数进行修正，最后的偏离因子为在晶体结构中，存在两个共轭的烯醇式结构。四个C－O健长分别为1．283（2），1．285（2），1．287（3）和1．298（2）     

Hydrazones and hydrazides of 4, 6-dimethyl-5-carboxypyrid-2-one and 4-methyl-6-carboxymethylpyrid-2-one

With a view to elucidating antitubercular activity, from the hydrazides of 4, 6-dimethyl-5-carboxypyrid-2-one and 4-methyl-6-carboxymethylpyrid-2-one, are synthesized the hydrazones of acetone, methyl ethyl ketone, acetophenone, benzaldehyde, p-hydroxypropiophenone, p-dimethylaminobenzaldehyde and tetrahydrothiopyi-4-one.     

Synthesis and Crystal Structure of 5,5-Dimethyl-2-(4-chlorophenyl)(3-hydroxy-5,5-dimethyl-2-cyclohexen-1-one-2-yl)methyl-3-(4-methoxyphenylamino)-2-cyclohexene-1-one

The title compound 5,5-dimethyl-2-(4-chlorophenyl)(3-hydroxy-5,5-dimethyl-2-cyclohexen-1-one-2-yl)methyl-3-(4-methoxyphenylamino)-2-cyclohexen-1-one has been synthesized,and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to monoclinic,space group P21/c with a=9.4193(13),b=26.915(4),c=21.188(3),β =101.906(3)°,V =5256.2(13)3,Z =4,C60H68Cl2N2O8,Mr=1016.06,Dc=1.284 g/cm3,F(000)=2160,λ(MoKα)=0.71073,μ=0.182 mm–1,R=0.0530 and wR=0.1131 for 4128 observed reflections (I>2σ(I)). X-ray analysis reveals that there are two independent molecules in the unit and the cyclohexenone rings adopt different conformations. In addition,there are four intramolecular hydrogen bonds in the title molecule.     

Asymmetric synthesis of 2-alkyl- and 2-aryl-3-aminopropionic acids (beta2-amino acids) from (S)-N-acryloyl-5,5-dimethyloxazolidin-2-one SuperQuat derivatives

Conjugate addition of lithium amides to (S)-N-acryloyl- or (S)-N-2'-alkylacryloyloxazolidinones and alkylation or protonation of the resulting enolates with 2-pyridone respectively provides a highly stereoselective and product complementary route to a range of (R)- and (S)-2-alkyl-3-aminopropionic acids in good yield and in high ee.