Absolute configuration and conformational stability of (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane

Enantiopure (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane were prepared using literature procedures and investigated using vibrational circular dichroism (VCD). Experimental absorption and VCD spectra of (+)-2,5-dimethylthiolane and (-)-2,5-dimethylsulfolane in CCl(4) solution in the 2000-900 cm(-)(1) region were compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6-311G(2d, 2p) basis set for different conformers of (2R,5R)-2,5-dimethylthiolane and (2R,5R)-2,5-dimethylsulfolane. This comparison indicates that (+)-2,5-dimethylthiolane is of the (2R,5R)-configuration and has two predominant conformations in CCl(4) solution. In addition, (-)-2,5-dimethylsulfolane is of (2R,5R)-configuration and has only one predominant conformation. The stereochemical assignment is in agreement with literature.     

Asymmetric addition of dimethylzinc to N-tosylarylimines catalyzed by a rhodium-diene complex toward the synthesis of chiral 1-arylethylamines

[STRUCTURE: SEE TEXT] A rhodium complex coordinated with a chiral diene, (R,R)-2,5-diphenylbicyclo[2.2.2]octa-2,5-diene (Ph-bod), catalyzed the asymmetric addition of dimethylzinc to N-tosylarylimines to give high yields of chiral 1-aryl-1-ethylamines with high enantioselectivity (94-98% ee).     

Synthesis and auration of primary and di-primary heteroaryl-phosphines

Convenient high-yield syntheses of the primary and di-primary heteroaryl-phosphines R-PH2 and H2P-R'-PH2(with R = 2-thienyl, 2-furyl, and R'= 2,5-thiophenediyl, 2,5-furandiyl, respectively) are presented. The products and a set of precursor molecules have been characterized by analytical and spectral data, and the crystal structures of selected molecules have been determined: 2-C4H3O-PCl2, 2,5-(Cl2P)2C4H2O, 2,5-[(Et2N)2P]2C4H2E (with E = O, S). In the crystals, the two molecules with -PCl2 substituents adopt trans conformations, while the other two have the -P(NEt2)2 groups rotated into a twist conformation. The reaction of the thienyl compounds with tris[(tert-phosphine)gold]oxonium tetrafluoroborates gave almost quantitative yields of the tri- and hexanuclear gold complexes, respectively: {2-C4H3S-P[Au(PR3)]3}+BF4- and [2,5-{[(R3P)Au]3P}2C4H2S]2+(BF4(-)2, (R =tBu, Ph). The structures of the compounds with R3P =tBu3P ligands have been determined. In both cases the [2-C4H3/2S-P] units cap triangles of gold atoms in an array that can be described as three [Au(PR3)]+ cations bridged by a phosphido dianion (RP)2-.     

Revision of the absolute configuration of the tricyclic sesquiterpene (+)-kelsoene by chemical correlation and enantiospecific total synthesis of its enantiomer

The absolute configuration of the recently identified sesquiterpene (+)-kelsoene was revised by chemical correlation with (R)-(+)-pulegone; the correct structure is (1R,2S,5R,6R,7R,8S)-2,8-dimethyl-6-(1-methylethenyl)tricyclo[5.3.0.0 (2,5)]decane.     

Enantioselective biotransformations of racemic and meso pyrrolidine-2,5-dicarboxamides and their application in organic synthesis

In this paper, we report the amidase-catalyzed hydrolysis of pyrrolidine-2,5-dicarboxamides and their application in organic synthesis. Catalyzed by Rhodococcus erythropolis AJ270, an amidase containing microbial whole cell catalyst, racemic trans-pyrrolidine-2,5-carboxamide was kinetically resolved into (2S,5S)-pyrrolidine-2,5-dicarboxamide and (2R,5R)-5-carbamoylpyrrolidine-2-carboxylic acid in high yields and excellent enantioselectivity. Biocatalytic desymmetrization of meso cis-pyrrolidinedicarboxamide afforded enantiomerically pure (2R,5S)-5-carbamoylpyrrolidine-2-carboxylic acid in an almost quantitative yield. In both kinetic resolution and desymmetrization, the amidase always exhibited excellent 2R-enantioselectivity, although its catalytic efficiency was influenced dramatically by the steric effect of the substituent on the nitrogen atom of pyrrolidine ring. The synthetic potential of biotransformation was demonstrated by the scalable preparation of (2R,5R)- and (2R,5S)-5-carbamoylpyrrolidine-2-carboxylic acids and their conversions to aza-nucleoside analogues and druglike pyrroline-fused diazepin-11(5H)-one compounds.     

Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-D-glucitol

1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6-dideoxy-D-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Likewise, using aqueous base at pH 12, ring closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9b). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only the corresponding six-membered ring 1,5-iminuronic acid mimetics, namely (2R,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-galactonic acid, 16) and (2S,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-talonic acid, 17), were obtained. The corresponding enantiomers, L-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic acids (2,6-dideoxy-2,6-imino-L-talonic acid, ent-17), respectively.     

A chiral chelating diene as a new type of chiral ligand for transition metal catalysts: its preparation and use for the rhodium-catalyzed asymmetric 1,4-addition

As a new type of chiral ligand, a C2-symmetric norbornadiene derivative (1R,4R)-2,5-dibenzylbicyclo[2.2.1]hepta-2,5-diene (1) was prepared and used for the rhodium-catalyzed asymmetric addition of organoboron and -tin reagents to alpha,beta-unsaturated ketones, which gave high yields of the 1,4-addition products with up to 99% enantioselectivity.     

Chemistry of Unsymmetrical Quarternary Carbon Compounds III. Synthesis of (-)-Dimethyl 2-Cyano-2-Methylsuccinate and Determination of Its Absolute Configuration

(?)-Dimethyl 2-cyano-2-methylsuccinate ((?)-IIIa) was synthesized from menthyl cyanoacetate ((?)-I), and the absolute configuration of which was elucidated as (S)-configuration by chemical correlation to the known (R)(+)-β-methylterbic acid ((R)(+)-VII). (?)-Dimethyl 2-carbamoyl-2-methylsuccinate ((?)-IV) and (?)-methyl 3-methyl-2,5-dioxo-3-pyrrolidinecarboxylate ((?)-V) are also confirmed as belonging to (S)-configuration and (+)-3-(1-hydroxy-1-methylethyl)-3-methyl-2,5-pyrrolidinedione ((+)-VI) is belonging to (R)-configuration. Preliminary experiments on racemic compounds are also described.     

Preparation of ferrocene-containing phosphinamine ligands possessing central and planar chirality and their application in palladium-catalyzed asymmetric allylic alkylation

The preparation of [2-(S(p))-[(trans-(2R,5R)-2,5-dialkylpyrrolidinyl)methyl]]ferrocenyldiphenyl phosphines, new ferrocenylphosphinamine ligands possessing one site of planar and two stereogenic centers, is described. trans-(2R,5R)-2,5-Dialkyl-1-(ferrocenylmethyl)pyrrolidines were diastereoselectively lithiated and quenched with chlorodiphenylphosphine. For the dimethyl ligand, chemical yields of up to 65% and des of up to 90% were obtained whereas the diethyl ligand afforded lower chemical yields (10%) and des of 78%. Diastereomerically pure material was obtained in both cases after a single recrystallization from ethanol. (S)-Planar chirality was confirmed by X-ray crystallographic analysis of the dimethyl ligand. The palladium complexes of the new ligands were applied in the allylic alkylation of 1,3-diphenylprop-2-enyl acetate with reasonable chemical yields and moderate ees of up to 36% and 38% when dimethyl malonate and dimethyl methyl malonate were employed as nucleophiles, respectively. Importantly, it was found that the new ligands possessing the combination of planar and central chirality gave the opposite enantiomeric alkylation products compared to ligands which possess only the central chirality of the trans-2,5-dimethylpyrrolidinyl moiety. Solution NMR studies of the 1,3-diphenylallyl palladium complex of the dimethyl ligand revealed the presence of only the exo-configured allyl diastereomer.     

2,5-Dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene: first member of the hetero-DuPHOS family

[reaction: see text] The 2,5-dimethyl-3,4-bis[(2R,5R)-2,5-dimethylphospholano]thiophene (UlluPHOS), a new thiophene-based analogue of (R,R)-1,2-bis(phospholano)benzene (Me-DuPHOS), was synthesized, geometrically and electronically characterized, and employed as ligand of Rh and Ru in some standard hydrogenation reactions of prostereogenic functionalized carbon-carbon and carbon-oxygen double bonds. The synthesis of UlluPHOS is much easier than that provided for Me-DuPHOS. UlluPHOS and Me-DuPHOS display very similar geometries, while the electronic availability of the former is higher than that exhibited by the latter. The Rh and Ru complexes of UlluPHOS produced excellent enantiomeric excesses (98.9-99.5%) in the hydrogenation of N-acetyl-alpha-enamino acids and reaction rates higher than those found when employing the analogous complexes of Me-DuPHOS.     

Enantioselective hydrogenation of alkenes and imines by a gold catalyst

A new neutral dimeric gold(I) complex bearing the 1,2-bis[(2R,5R)-2,5-dimethylphospholanebenzene] [(R,R)-Me-Duphos] ligand has been synthesized which catalyzes the asymmetric hydrogenation of alkenes and imines under mild reaction conditions.     

A new unusual natural pigment from Selaginella sinensis and its noticeable physicochemical properties

A new unusual pigment with a novel carbon framework named selaginellin (1) was isolated from the acetone extract of Selaginella sinensis, and its methoxy derivative (1a) was synthesized. Both selaginellin 1 and 1a are racemic compounds. The structure of selaginellin 1 was established as (R,S)-4-[(4'-hydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one and 1a as (R,S)-4-[(4'-methoxy-4-(methoxymethyl)-3-((4-methoxyphenyl)ethynyl)biphenyl-2-yl)(4-methoxyphenyl)methylene]-2,5-cyclohexadien-1-one by the analysis of one- and two-dimensional NMR data, HR-ESIMS, EI-MS, IR, UV, CD, and single-crystal X-ray experiments, and the mechanism of their color change according to different pH values and fluorescent properties was studied.     

X-Ray structural investigation of 1,3,6-trichloro-3,6-dimethylcycloheptanecarbonitrile and 2,5-dimethyl-2,5-dichlorohexane — Products of the reaction of 2,5-dimethyl-1,5-hexadiene with trichloroacetonitrile

Addition of trichloroacetonitrile to 2,5-dimethyl-1,5-hexadiene in the presence of cuprous amine complexes is studied. Single crystal X-ray diffraction unambiguously proves that the main product is a racemic mixture of the cyclic symmetric nitrile: (1r,3R,6S)-and (1r,3S,6R)-1,3,6-trichloro-3,6-dimethylcycloheptanecarbonitrile. Established relative configuration of the product confirms the ring closure mechanism suggested before. Also, a side product 2,5-dimethyl-2,5-dichlorohexane is isolated (the product of hydrochlorination of the starting alkadiene). Low-temperature (190 K) structural examination of this centrosymmetrical molecule indicates that the unit cell comprises one molecule.     

Efficient asymmetric hydrogenation with rhodium complexes of C(1)-symmetric 2,5-dimethylphospholane-diphenylphosphines

The unsymmetrical, optically active ligands 1,2-C(6)H(4)(PPh(2))((R,R)-2,5-dimethylphospholanyl) and the new 1,1'-Fe(C(5)H(4))(2)(PPh(2))((R,R)-2,5-dimethylphospholanyl) form complexes of the type [PtCl(2)(diphos)] and [Rh(diphos)(diene)][BF(4)]. The crystal structure of reveals that only one quadrant is blocked. Asymmetric hydrogenation of acrylic esters and enamides using and as catalysts show that the phenylene-backboned diphosphine gives a more efficient catalyst in terms of asymmetric induction than the more flexible ferrocene-backboned diphosphine. The best results, which were obtained with and enamide substrates, exceeded those obtained with Duphos catalysts. The rate of hydrogenation of the enamides with was 10 times faster than with [Rh(Duphos)(diene)][BF(4)]. A quadrant diagram can be used to predict the configuration of the major product, provided it is assumed to be derived from the less sterically congested intermediate.     

Synthese und chemie von 4R-silacyclohexa-2,5-dienen und 4R-silacyclohexa-2,4-dienen

The 1(Z),4(Z)-1,5-dilithium-3R-3-methoxypenta-1,4-dienes, available by cleavage of 1,1-di-n-butyl-4R-4-methoxy-1-stannacyclohexane-2,5-dienes with n-BuLi in ether, react with dichlorosilanes (R′R″ SiCl₂; R′, R″ = H, alkyl, aryl, alkoxy) to give 1R′,1R″,4R-4-methoxy-1-silacyclohexa-2,5-dienes.Claevage of the ether group with BBr₃, BCl₃ or PCl₃ gives 6-chloro(bromo)-1-silacyclohexa-2,4-dienes or 1,5-dichloro-1-silacyclohexane-2,4-dienes, respectively.Ether cleavage of 4R-4-methoxy-1-silacyclohexa-2,5-dienes with sodium results in the formation of 4R-1-silacyclohexadienyl anions, which can be hydrolyzed to give 1-silacyclohexa-2,4-dienes which reach further with trichloromethylsilane to give 6-trimethylsilyl-1-silacyclohexa-2,4-dienes.Phase transfer-catalyzed conversion of 1-chlorosilacyclohexadienes into the fluoro derivatives as well as further substitution reactions of 1-chlorosilacyclohexadienes are described.The ¹H NMR, ¹³C NMR, IR and mass spectra of the silacyclohexadienes are discussed.     

Novel rearrangement of an isocaryolane sesquiterpenoid under mitsunobu conditions

Under modified Mitsunobu reaction conditions, a novel skeleton rearrangement of terpenes has been obtained. The reactivity of 8, 9-dioxygenated isocaryolane derivatives has been investigated. When either (8R,9R)-8-methoxyisocaryolane-9-ol (7) or (8R, 9R)-isocaryolane-8,9-diol (10) are treated under acidic conditions, isocaryolan-9-one (9) and the rearrangement compound (1S,2S,5R,8S)-1, 4,4-trimethyltricyclo[6.2.1.0(2,5)]undecane-8-carbaldehyde (11) are obtained. Otherwise treatment of compounds 7 and 10 under modified Mitsunobu conditions leads to the novel sesquiterpene derivative (1S, 2S,5R,9R)-1,4,4-trimethyltricyclo[7.2.1.0(2,5)]dodecan-8-one (8). This is the first example, to our knowledge, of a Mitsunobu-induced pinacol rearrangement. The influences of the substrate and reaction conditions on the evolution of the reaction are both explored. This modification of the Mitsunobu reaction conditions introduces a new, one-pot, procedure for preparing this class of rearrangement product.     

Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists

The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.     

Selaginellin A and B, two novel natural pigments isolated from Selaginella tamariscina

Two new unusual natural pigments were first isolated from the whole herbs of Selaginella tamariscina. The structure of selaginellin A (1) was established as (R,S)-4-[(4'-hydroxy-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one and selaginellin B (2) as (R,S)-4-[(4'-methoxy-4-(methyl)-3-((4-methoxyphenyl)ethynyl)biphenyl-2-yl)(4-methoxyphenyl)methylene]-2,5-cyclohexadien-1-one, along with four known biflavonoids, amentoflavone (3), hinokiflavone (4), heveaflavone (5), and 7'-O-methylamentoflavone (6). Their chemical structures were elucidated by spectral analysis of electrospray ionization mass spectroscopy (ESI-MS), one-dimensional nuclear magnetic resonance spectroscopy (1D-NMR) and two-dimensional-nuclear magnetic resonance spectroscopy (2D-NMR) including (1)H-NMR, (13)C-NMR, distortionless enhancement by polarization transfer (DEPT) and heteronuclear multiple bond coherence (HMBC), and single-crystal X-ray diffraction techniques.     

5-Demethoxyfumagillol, a potent angiogenesis inhibitor isolated from Aspergillus fumigatus

A novel angiogenesis inhibitor, 5-demethoxyfumagillol (1), was obtained by isolation, purification and saponification of cultured broth of Aspergillus fumigatus. The structure was assigned as (3R,4R,6R)-4-[(2R,3R)-2-methyl-3-(3-methyl-but-2-enyl)-oxiranyl]-1-oxa-spiro[2,5]octan-6-ol (1) by spectroscopic analysis and confirmed by independent synthesis from fumagillol (3). In addition, 6-O-(chloroacetylcarbamoyl)-5-demethoxyfumagillol (7) showed a potential anti-angiogenic activity in CAPE cells in vitro.     

On the mechanism of the unexpected facile formation of meso-diacetate products in enzymatic acetylation of alkanediols

The mechanism of the unexpected facile formation of meso-diacetate previously observed in the enzymatic resolution of dl/meso mixtures of 2,4-pentanediol and 2,5-hexanediol with Candida antarctica lipase B has been elucidated. It was found that the formation of meso-diacetate proceeds via different mechanisms for the two diols. Enzyme-catalyzed acylation of AcO-d(3) labeled (R)-monoacetates of meso-2,4-pentanediol and meso-2,5-hexanediol and analysis of the meso-diacetates obtained show that the former reaction proceeds via intramolecular acyl migration while the latter occurs via direct S-acylation of the alcohol. For the (R)-monoacetate of (R,S)-2,4-pentanediol the intramolecular acyl migration was fast and therefore direct S-acylation by the external acyl donor is suppressed. For the hexanediol monoacetate the rate ratio (pseudo E value) between (5R,2R)- and (5R,2S)-5-acetoxy-2-hexanol was experimentally determined to be k(R,R)/k(R,S) = 25, which is about 10-20 times lower than the E value for 2-pentanol and 2-octanol. In a preliminary experiment it was demonstrated that facile acyl migration in the 1,3-diol derivative can be utilized to prepare syn-1,3-diacetoxynonane (>90% syn) in high enantioselectivity (>99% ee) via a chemoenzymatic dynamic kinetic asymmetric transformation of a meso/dl mixture of 1,3-nonanediol.