Malonate, dimethyl phenyl

A series of diaryl-2-pyrrolidinemethanols have been tested as catalysts for the enan-tioselective Michael addition of malonate esters to nitroalkenes.30 Bis-(3,5-dimethyl-phenyl)[(S)-pyrrolidin-2-yl]methanol (6), easily prepared from L-proline, has been found the most efficient bifunctional organocatalyst, providing up to 56% ee. 

Asymmetric palladium(0)-catalysed substitution of racemic allylic substrates with malonate and benzylamine as nucleophiles were performed using new enantiopure cyclic (3-iminophosphine ligands namely (2,6-dimethyl-phenyl)-( 1 -phenyl-2, 3,3a, 8a-tetrahydro- 1H-1 -phospha-cyclopenta[-a]inden-8-ylidene)-amines 1 (RP)... 

Successful results have been obtained (Renfrew and Chaney, 1946) with ethyl formate methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec.-butyl and iso-amyl acetat ethyleneglycol diacetate ethyl monochloro- and trichloro-acetates methyl, n-propyl, n-octyl and n-dodecyl propionates ethyl butyrate n-butyl and n-amyl valerates ethyl laurate ethyl lactate ethyl acetoacetate diethyl carbonate dimethyl and diethyl oxalates diethyl malonate diethyl adipate di-n-butyl tartrate ethyl phenylacetate methyl and ethyl benzoates methyl and ethyl salicylates diethyl and di-n-butyl phthalates. The method fails for vinyl acetate, ieri.-butyl acetate, n-octadecyl propionate, ethyl and >i-butyl stearate, phenyl, benzyl- and guaicol-acetate, methyl and ethyl cinnamate, diethyl sulphate and ethyl p-aminobenzoate. 

Other examples of CN/CC replacement are observed in reactions of l-phenyl-pyrimidin-2(l//)-one with active methylene compounds, such as diethyl malonate and benzoylacetate, giving in good yield 2-oxo-l,2-dihydro-3-pyridinecarboxylate and 3-benzoylpyridin-2(l H)-one, respectively (84CPB2942, 87H2223) (Scheme 8). In a similar way 4,6-dimethyl-1-phenylpyrimidin-2( 1 //)-one, 4,6-dimethyl-1 -phenylpyrimidine-2( 1 //)-thione and 4,6-dimethyl-1 -phenyl-2-phenylimino-1,2-dihydropyrimidine yield with malonitrile 2-amino-4,6-dimethyl-3-pyridinecarbonitrile. In a similar way 2,3-diarylpyrimidin-4(3//)-thiones give with malonitrile CN/CC replacement (84H763) (Scheme 8). The reaction takes a similar course as described in Scheme 7. 

The diastereoselectivity and the stereochemical outcome of the addition of 2,3,4,6-tetrahydro-3, 4-dimethyl-2-phenyl-1,4-oxazepine-5,7-dione, derived from ephedrine and methyl hydrogen malonate, to 1 -nitrocyclohexene was found to be dependent on the nature of the base and the solvent. The highest diastereoselectivity was obtained when potassium /tr/-butoxide in the presence of dicyclohcxyl-18-crown-6 was employed. In the absence of crown ether the diastereoselection was poor and the sense of the stereochemical outcome was reversed26. 

R1 = C(CH3)3 R2 = CN (2,2-Dimethyl-l-phenyl-propyl)-malons(iure-dinitrilb —80% d.Th. R1 = ChH, R2 = COOC2H5 Diphenylmethyl-malonsdure-dthylester-nitril6 —80% d.Th. 

Tetramethoxypropadiene 88 or l-methoxy-l-(trimethylsilyl)-3-phenyl-l,2-pentadiene 89 may be easily protonated and then leads to dimethyl malonate or 1-tri-methylsilyl-3-phenyl-2-penten-l -one [42]. 

Dimethyl malonate was first treated dropwise with phenyl isothiocyanate in the presence of sodium hydride in N,7V-dimethylacetamide at 0°C. The reaction mixture was stirred at ambient temperature for 1.5 hr and then cooled to 0°C, and methyl iodide was added dropwise. After stirring for 4 hr at room temperature, (methylthio)(phenylamino)methy-lenemalonate (341) was obtained in 79% yields (69T4649). 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Chiral nonracemic bidentate 2-[o-(diphenylphosphino)phenyl]-5,6-dihydro-4//-l,3-oxazine derivatives proved to be effective P,N-ligands in Pd-catalyzed asymmetric transformations. When used in the Pd-catalyzed allylic alkylations of 1,3-diphenylallyl acetate with dimethyl malonate, phosphino-oxazines 147 and 148 and the... 

Figure 8.9 Results of palladium-catalyzed asymmetric allylic alkylation of 1,3-di phenyl al lyl acetate and dimethyl malonate upon applying a ligand library of self-assembled bidentate ligands. The ligands a-i on the x-axis are defined in Figure 8.8. 

Heating of a mixture of 2-phenyl-1,4-naphthoquinone (1 eq.) with dimethyl malonate (4 eq.) and manganese(III) acetate (6 eq.) in acetic acid at 80°C for 16 hours gives 1 in 76% yield, and this has been shown to be a general type of reaction for a variety of 2-aryl-l,4-naphthoquinones. 

Michael addition-alkylation pathway has to be considered because simple methylene active compounds such as dimethyl malonate or methylcyanoac-etate were found to be good Michael donors with /1-substituted unsaturated esters such as 5-phenyl-2-pentenoate in the reaction conditions. However, when the reaction was quenched before completion, a substantial amount of product resulting from attack onto the zr-allylPd complex was isolated, bringing an evidence for the alkylation/Michael addition pathway. 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

Transition Metal-Cataijrzed Reactions. Application of this ligand to the Pd-catalyzed ally lie alkylation of l,3-diphenyl-2-propenyl acetate with dimethyl malonate provides an alkylated product in >99.5% enantiomeric excess (eq 1). The enantiose-lectivity of the process is dependent on the ligand Pd ratio, the palladium precursor, and the nature of the nucleophile. Optimal conditions employed Pd(dba)s as the Pd precursor and 2 equiv of phosphine ligand, suggesting that two phosphines coordinate to the active Pd catalyst. Replacement of l,3-diphenyl-2-propenyl acetate with pent-3-en-2-yl acetate decreased the ee to 34% due to the reduced sterics of methyl relative to phenyl substituents. It is noteworthy that in contrast to this ligand, most monodentate ligands provide low enantioselectivity in this reaction. ... 

The reaction between dimethyl 2-bromo-l-phenylpropylidenemalonate and sodium methoxide in methanol affords a complex reaction mixture consisting of dimethyl 2-methyl-3-phenyl-2-cyclopropene-l,l-dicarboxylate (303,19%), dimethyl (2,2-dimethoxy-l-methyl-2-phenylethyl)malonate (304, 4%), dimethyl 2-methoxy-l-phenylpropyl-idenemalonate (305, 11%), dimethyl 2-bromo-l-phenyl-1-propenylmalonate (306 -isomer, 10% Z-isomer, 13%) and dimethyl (l,2-dimethoxy-l-phenylpropyl)malonate... 

Scheme 4.24 Cinchona alkaloid derived phenyl selenides in Pd-catalyzed alkylation of dimethyl malonate with l,3-diphenyl-2-propenyl acetate.

Obtained from active methylene compounds, such as malonic esters, -0x0 esters and jS-oxo sulfones, iodonium ylides serve as precursors of the corresponding carbenes. Their decomposition by a catalytic amount of a copper salt in the presence of a C-C double bond has been used for inter- and intramolecular cyclopropanation reactions. Thus, reaction of cyclohexene with bis(methoxycarbonyl)methylene(phenyl)iodine(III) under the catalytic action of bis(acetylacetonato)copper(II) yielded dimethyl bicyclo[4.1.0]heptane-7,7-dicarboxylate (1) (38%, mp 91-93°C) in addition to tetrakis(methoxycarbonyl)ethene (41%). ... 

E and Z isomers of esters can display significantly different properties such as acidity, as observed in the case of methyl acetate the E isomer has been calculated to be more acidic than the Z form [6], and this theoretical result has been related to the unusually low pKa of Meldrum s acid (pKa = 7.3 to be compared to dimethyl malonate pKa = 15.9) [7,8], In contrast, the Z E ratio of methyl thio-noformate (HCOSMe) is 97 3 in acetone (AG° = 1.29 kcal mol-1) in the 177-192 K range, whereas the ratio is 77 29 for cyclopropyl thionoformate in the same conditions (AG° = 0.31 kcal mol-1). The energy difference is even dose to zero (AG° = 0.13 kcal mol-1) in the particular case of phenyl thioformate [9]. 

---