A general and nonempirical approach to the determination of the absolute configuration of 1-aryl-1,2-diols

We describe herein a simple, general, and reliable nonempirical approach, based on the exciton coupling method, to assign the absolute configuration of the benzylic stereogenic center of 1-aryl-1,2-diols. According to this method, it is only necessary to prepare the 4-biphenylboronic esters of the diols and to record their CD spectra in the 230-300 nm range, i.e., in the range corresponding to the long-axis (1)L(a) transition of the biphenyl chromophore. From the sign of the CD couplet or Cotton effect at 260 nm it is possible to know the chirality defined by the aryl and biphenyl chromophore transitions and then to determine the absolute configuration of the benzylic carbon. By this approach, simple rules have been formulated which allow us to establish the absolute configuration of many classes of 1-aryl-1,2-diols.     

Asymmetric hydrolytic kinetic resolution with recyclable macrocyclic Co(III)-salen complexes: a practical strategy in the preparation of (R)-mexiletine and (S)-propranolol

A chiral cobalt(III) complex (1e) was synthesized by the interaction of cobalt(II) acetate and ferrocenium hexafluorophosphate with a chiral dinuclear macrocyclic salen ligand that was derived from 1R,2R-(-)-1,2-diaminocyclohexane with trigol bis-aldehyde. A variety of epoxides and glycidyl ethers were suitable substrates for the reaction with water in the presence of chiral macrocyclic salen complex 1e at room temperature to afford chiral epoxides and diols by hydrolytic kinetic resolution (HKR). Excellent yields (47% with respect to the epoxides, 53% with respect to the diols) and high enantioselectivity (ee>99% for the epoxides, up to 96% for the diols) were achieved in 2.5-16 h. The Co(III) macrocyclic salen complex (1e) maintained its performance on a multigram scale and was expediently recycled a number of times. We further extended our study of chiral epoxides that were synthesized by using HKR to the synthesis of chiral drug molecules (R)-mexiletine and (S)-propranolol.     

Application of the okahara cyclization to the preparation of crown ethers with aromatic units

A series of crown ethers with single benzene, naphthalene, biphenyl and binaphthyl units are prepared by the intramolecular Okahara cyclization of appropriate symmetrical diols. The method is used to synthesize new crown ether compounds and to prepare previously-reported crown ethers in improved yields.     

Asymmetric electrochemical lactonization of diols on a chiral 1-azaspiro[5.5]undecane N-oxyl radical mediator-modified graphite felt electrode

A graphite felt electrode modified with (6S,7R,10R)-4-amino-2,2,7-trimethyl-10-isopropyl-1-azaspiro[5.5]undecane N-oxyl was prepared for electrocatalytic oxidation of diols; electrolysis of diols on the modified electrode yielded optically active lactones (92.0-96.4%), with an enantiopurity of 82-99% ee.     

Straight and versatile synthesis of substituted perhydrofuro[2,3-b]pyrans from 2-chloromethyl-3-(2-methoxyethoxy)propene

The reaction of 2-chloromethyl-3-(2-methoxyethoxy)propene with an excess of lithium powder and a catalytic amount of naphthalene (2.5%) in the presence of a carbonyl compound (E¹=R¹R²CO) in THF at −78 to 0°C, followed by the addition of an epoxide [E²=R³R⁴C(O)CHR⁵] at 0 to 20°C leads, after hydrolysis, to the expected methylidenic diols. These diols when subjected to successive hydroboration-oxidation and further oxidation, spontaneous cyclization occurs to furnish a series of differently substituted perhydrofuro[2,3-b]pyrans.     

Straightforward synthesis of 1,7-dioxaspiro[4.4]nonanes

The reaction of 2-chloromethyl-3-(2-methoxyethoxy)prop-1-ene with an excess of lithium powder and a catalytic amount of naphthalene (2.5%) in the presence of a carbonyl compound (E¹=R¹R²CO) in THF at −78 to 0 °C, followed by the addition of an epoxide [E²=R³R⁴C(O)CHR⁵] at 0 to 20 °C leads, after hydrolysis, to the expected methylidenic diols. These diols, in the presence of iodine and silver(I) oxide in dioxane-water, undergo double intramolecular iodoetherification to give the corresponding 1,7-dioxaspiro[4.4]nonanes, which in addition can be easily oxidised to a variety of 1,7-dioxaspiro[4.4]nonan-6-ones.     

Chiral-auxiliary-controlled diastereoselectivity in the epoxidation of enecarbamates with DMD and mCPBA

[structure: see text] Chiral oxazolidinone-substituted enecarbamates 1 are epoxidized in a diastereoselectivity up to 93:7 for both DMD and mCPBA. The diastereofacial differentiation depends on the steric interaction between the R(1) substituent on the oxazolidinone ring and the incoming electrophile. The stereochemical course of epoxidation was assessed by chemical correlation with the known optically active diols.     

Synthesis and complexation of a ‘mixed’-pyridine-naphthalene homooxacalixarene

A deep-cavity ‘mixed’ octahomotetraoxacalix[2]naphthalene[2]pyridine macrocycle has been synthesised and its single-crystal X-ray structure has been determined. Molecular modeling studies suggested that this macrocycle could be an effective host for guest aromatic diol(s) similar to Wang's methylazacalixpyridines. Binding constants were determined using ¹H NMR chemical shifts changes and comparisons were made between the diols which were tested.     

Studies on thermotropic liquid crystalline polymers. XVI. Synthesis and properties of fully aromatic poly(amide-ester)s with naphthalene structures

A series of novel, fully aromatic high-molecular-weight poly(amide-ester)s was prepared by the direct polycondensation from terephthalic acid (TPA) and 2,6-naphthalene dicarboxlic acid (NDC) with various aromatic diols and diamines in the presence of diphenyl chlorophosphate (DPCP), LiCl, and pyridine. The structures and thermal properties of these synthesized poly(amide-ester)s were examined by FTIR, wide-angle x-ray diffraction (WAXD), differential scanning calorimetry (DSC), thermal polarized optical microscope, thermogravimetric analysis (TGA), and dynamic mechanical analysis (DMA). The effects of the kinds of the aromatic diols and diamines (bisphenyl units, naphthalene, and (un)substituted phenylene structures) on the thermal properties of the synthesized poly(amide-ester)s were investigated in this study. Strong interchain interactions were induced by using a 50:50 molar ratio of the amide groups to the ester groups, and, thus, no LC properties but good thermal stabilities were found in all of the synthesized poly(amide-ester)s containing naphthalene, substituted hydroquinone, or bisphenol segments in this study. However, another series of poly(amide-ester)s with a molar ratio of diamine to diol of 20:80 exhibited excellent mesophase stabilities, with various molar ratio of terephthalic acid (TPA) to 2,6-naphthalene dicarboxlic acid (NDC). © 1996 John Wiley & Sons, Inc.     

Production of epoxydammaranes by the enzymatic reactions of (3R)- and (3S)-2,3-squalene diols and those of 2,3:22,23-dioxidosqualenes with recombinant squalene cyclase and the mechanistic insight into the polycyclization reactions

The enzymatic cyclizations of (3R)- and (3S)-2,3-squalene diols by squalene cyclase afforded bicyclic compounds and epoxydamamranes in a ca. 3 : 2 ratio. Formation of the epoxydammarane scaffold indicates that a 6/6/6/5-fused tetracyclic cation is involved as the intermediate in the polycyclization reaction. 2,3:22,23-Dioxidosqualenes also afforded an epoxydammarane skeleton, i.e., 3alpha- or 3beta-hydroxyepoxydammaranes, but the amount of bicyclic compounds produced was markedly lower than that of the squalene diols, indicating that the larger steric bulk of the diols had a more significant influence on the polycyclization pathway than the smaller bulk of the expoxide. All the epoxydammaranes had 17R,20R stereochemistry except for one product, demonstrating that these analogs were folded into an all-chair conformation in the reaction cavity. The mechanistic insight into the observed stereochemical specificities indicated that the organized all-chair conformation is rigidly constricted by squalene cyclase and, thus, free conformational change is not allowed inside the reaction cavity; a small rotation of the hydroxyl group or the epoxide toward the intermediary cation gave a high yield of the enzymatic products, while a large rotation led to a low yield of the product. The stereochemistries of the generated epoxydammaranes are opposite to those from natural sources, and thus almost all of the enzymatic products described here are novel.     

Osmium catalyzed dihydroxylation of 1,2-dioxines: a new entry for stereoselective sugar synthesis

A series of 3,6-substituted 3,6-dihydro-1,2-dioxines were dihydroxylated with osmium tetroxide to furnish 1,2-dioxane-4,5-diols (peroxy diols) in yields ranging from 33% to 98% and with de values not less than 90%. The peroxy diols were then reduced to generate a stereospecific tetraol core with R,R,S,S or "allitol" stereochemistry. The peroxy diols and their acetonide derivatives were also ring-opened with Co(II) salen complexes to give novel hydroxy ketones in 77-100% yield, including the natural sugar psicose. Importantly, preliminary work on the catalytic asymmetric ring-opening of meso-peroxy diols using the Co(II) Jacobsens's catalyst indicates that asymmetric sugar synthesis from 1,2-dioxines is possible.     

Ab initio conformational studies on diols and binary diol-water systems using DFT methods. Intramolecular hydrogen bonding and 1:1 complex formation with water

Studies on the conformational equilibrium for the following diols, ethane-1,2-diol (12EG, CAS 107-21-1), 2R-D-(-)-propane-1,2-diol (12PG, CAS 4254-14-2), (2S,3S)-L-(+)-butane-2,3-diol (L23BD, CAS 19132-06-0), and (2S,3R)-meso-butane-2,3-diol (m23BD, CAS 5341-95-7), are described using Gaussian ab initio calculations involving density functional theory (DFT) methods. We also report in this article results on the stability and conformation for the 1:1 water-diol complex formed by ethane-1,2-diol, propane-1,2-diol, and L- and meso-butane-2,3-diol. The relative stability of the intramolecular (internal) hydrogen bond in a range of diols (n = 2 to 6), based on ab initio geometry optimization and determination of the -O...H- distance, dOH, and -O-H...O- angle, theta, increases through the sequence 1,2 approximately equals 2,3 < 1,3 < 1,4 approximately equals 1,5 approximately equals 1,6, as judged from the bond linearity and -O...H- separation. Quantum mechanical and topological analysis of possible intramolecular hydrogen bonding in this complete series of diols provides convincing evidence for this in diols in which the hydroxyl groups are separated by three or more carbon atoms, that is, in (n, n+m) diols for m > or = 2, but not for ethane-1,2-diol or other vicinal diols, which do not satisfy Popelier's topological and electron density criteria based on the AIM theory of Bader. Based on these criteria it is unlikely that vicinal diols are in fact capable of forming an intramolecular hydrogen bond, in spite of geometric and spectroscopic data in the literature suggesting otherwise.     

Structural analysis of diols by electrospray mass spectrometry on boric acid complexes

A method is presented to characterize diols using negative ion electrospray (ES) mass spectrometry in combination with collision-induced dissociation tandem mass spectrometry (MS/MS). The analyte diol is added to a solution containing an ethylene glycol/boric acid [2:1] complex and then subjected to infusion ES. The following boric acid complexes are formed: (i) a complex with two ethylene glycol molecules, (ii) a mixed ethylene glycol/analyte complex, and (iii) a complex with two analyte molecules. The first complex serves as a reference for the assessment of the extent of complex formation with the analyte. The ES mass spectra of acyclic vicinal diols all feature intense mixed complex signals, indicative of efficient complex formation. Chemical fine tuning is achieved by MS/MS experiments. Thus, although the (2R,3R)-(-)-2,3-butanediol and meso-2,3-butanediol stereo-isomers show the same complexation efficiency, MS/MS experiments reveal pronounced structure characteristic differences. By contrast, 1,3- and 1,4-diols are less prone to complex formation as they give only weak signals relative to the reference. For cyclic vicinal diols only the cis isomer produces an intense mixed complex, whose MS/MS spectrum is characteristically different from that of the trans form. The above procedure does not permit an unambiguous differentiation of acyclic polyhydroxy compounds like mannitol and sorbitol. However, structurally related methyl glycosides show characteristic MS/MS spectra. Our findings indicate that the above simple procedure may be useful to probe the presence and structure of diols and other polyols in aqueous solutions. Copyright 1999 John Wiley & Sons, Ltd.     

Pharmacokinetic effects of ginsenoside Rg1 on aconitine,benzoylaconine and aconine by UHPLC–MS/MS

Ginseng and aconite are well-known couplet medicinals. Ginsenoside Rg1 is the main active ingredient in ginseng, and aconitine (AC), benzoylaconine (BAC) and aconine (ACN) are three representative alkaloids in aconite, which belong to the diester alkaloids, monoester alkaloids and alkanolamine alkaloids respectively. The aim of this study was to investigate the pharmacokinetic effects of ginsenoside Rg1 on the three types of alkaloids and to provide evidences for their compatibility mechanism. In this study, the ginsenoside Rg1 was simultaneously intragastrically administered to rats with AC, BAC and ACN, respectively, and the rat plasma was collected at different time points. The plasma drug concentrations of the three types of alkaloids were determined by UHPLC–MS/MS, and the pharmacokinetic parameters were calculated. The results indicated that the peak concentration and area under the concentration–time curve of BAC were significantly increased (P < 0.05), those for AC were decreased (P < 0.05), and the values for ACN did not change after pretreatment with ginsenoside Rg1. It was inferred that ginsenoside Rg1 may affect the absorption and metabolism of AC and BAC and then change their pharmacokinetic parameters. Subsequently, their absorption and metabolism were further investigated using the Caco-2 cell monolayer and rat liver microsomes in vitro. The Caco-2 cell monolayer absorption assay indicated that ginsenoside Rg1 could promote the absorption of AC and BAC, and the rat liver microsomes metabolism assay indicated that ginsenoside Rg1 accelerated the metabolism of AC and did not affect the other two alkaloids. All of the results indicated that ginsenoside Rg1 may reduce the toxicity of aconite and improve its efficacy by promoting the absorption of BAC and accelerating the metabolism of AC. These results could provide evidence for the compatibility mechanism of the traditional Chinese herbal formula Shenfu Decoction.     

Highly stereoselective approach to alk-2-yne-1,4-diols by oxazaborolidine-mediated reduction of alk-2-yne-1,4-diones

We performed the borane-mediated reduction of a series of symmetrical alk-2-yne-1,4-diones (5) in the presence of the oxazaborolidine (R)-6 to afford (R,R)-alk-2-yne-1,4-diols ((R,R)-1) in good yields and high stereoselectivities (up to 99.9% ee). In some cases, the stereochemical purity of 1 was improved by a two-step process: (i) temporary transformation of 1 into its vic-dibromo derivatives 9, which allowed us to remove the minor meso isomer by chromatography, and (ii) regeneration of the enantioenriched diols 1 with SmI2. Reduction of the hexacarbonyldicobalt complexes 8 derived from 5 was also successful.     

The Williamson Reaction: A New and Efficient Method for the Alternate Resolution of 2,2'-Bis(bromomethyl)-1,1'-binaphthyl and 1,1'-Binaphthalene-2,2'-diol

Treatment of 2,2'-bis(bromomethyl)-1,1'-binaphthyl [(R,S)-2] with 1,1'-binaphthalene-2,2'-diol (+)-(R)-1 and cesium or potassium carbonate in refluxing acetone, gave the diastereoisomeric dioxacyclophanes (-)-(R,S)-3a and (+)-(R,R)-3b, both obtained in high yield, and the cyclic tetraether (+)-(R,R,R,S)-4 as isolated side product. Boron tribomide-promoted ether cleavage of 3a and 3b gave optically pure (-)-(S)-2 and (+)-(R)-2, respectively, and the recovered diol (+)-(R)-1. Alternatively, the same reaction sequence furnished the resolved diols (-)-(S)-1 and (+)-(R)-1 from (R,S)-1 and (+)-(R)-2, as well as optically pure 2,2'-bis(chloromethyl)-1,1'-binaphthyl (+)-(R)-5 from the racemic dibromide (R,S)-2 by using boron trichloride for ether cleavage.     

用(R)-(+)-缩水甘油的亲核开环反应制备手性连二醇

以D-甘露醇为原料合成(R)-(+)-缩水甘油1。该环氧化合物的亲核开环反应为高立体选择性地(93%-96%e.e.)制备各种手性连二醇提供了一条简便途径。     

Relative and absolute stereochemistry of secondary/secondary diols: low-temperature 1H NMR of their bis-MPA esters

Comparison of the room- and low-temperature 1H NMR spectra of the bis-(R)- or bis-(S)-MPA ester derivative of an open chain sec,sec-1,2-diol allows the easy determination of its relative stereochemistry and in some cases absolute configuration. If the diol is anti, its absolute configuration can be directly deduced from the signs of DeltadeltaT1T2 for substituents R1/R2, but if the relative stereochemistry of the diol is syn, the assignment of its absolute configuration requires the preparation of two derivatives (both the bis-(R)- and bis-(S)-MPA esters), comparison of their room-temperature 1H NMR spectra, and calculation of the DeltadeltaRS signs for the methines Halpha(R1) and Halpha(R2) and R1/R2 protons. The reliability of these correlations is validated with 17 diols of known absolute configuration used as model compounds.     

A new synthetic route to enantiomerically pure axially chiral 2,2'-bipyridine N,N'-dioxides. Highly efficient catalysts for asymmetric allylation of aldehydes with allyl(trichloro)silanes

New axially chiral 2,2'-bipyridine N,N'-dioxides 1 were obtained in an enantiomerically pure form by way of cyclic diesters 6 or 7 which were formed by the esterification of diols 2 with (R)-2,2'-bis(chlorocarbonyl)-1,1'-binaphthalene (5). Epimerization of the kinetic products at the ester formation (R(nap),S(pyr))-6 to the thermodynamically stable isomers (R(nap),R(pyr))-7 was observed in refluxing toluene or in the presence of trifluoroacetic acid. One of the N,N'-dioxides 1a which is substituted with phenyl groups at the 6 and 6' positions was found to be highly catalytically active and enantioselective for the asymmetric allylation of aldehydes with allyl(trichloro)silane giving homoallyl alcohols.     

Reaction of tin porphyrins with vicinal diols

Reactions of tin porphyrins with vicinal diols were investigated. Treatment of (TTP)Sn(CCPh)(2) or (TTP)Sn(NHtolyl)(2) with pinacol and 2,3-diphenylbutane-2,3-diol afforded diolato complexes (TTP)Sn[OC(Me)(2)C(Me)(2)O] (1) and (TTP)Sn[OC(Ph)(Me)C(Ph)(Me)O] (2), respectively. Both complexes underwent C-C cleavage reactions to give (TTP)Sn(II) and ketones. Reaction of (TTP)Sn(CCPh)(2) with 1 equivalent of o-catechol generated (TTP)Sn(CCPh)(OC(6)H(4)OH) (3), which subsequently transformed into (TTP)Sn(OC(6)H(4)O) (4). With excess catechol, disubstituted (TTP)Sn(OC(6)H(4)OH)(2) (5) was obtained. (TTP)Sn(CCPh)(OCHRCHROH) (R = H, 6; R = Ph, 8) and (TTP)Sn(OCHRCHROH)(2) (R = H, 7; R = Ph, 9) were obtained analogously by treatment of (TTP)Sn(CCPh)(2) with appropriate diols. In the presence of dioxygen, tin porphyrin complexes were found to promote the oxidative cleavage of vicinal diols and the oxidation of alpha-ketols to alpha-diketones. Possible reaction mechanisms involving diolato or enediolato intermediates are discussed. The molecular structure of (TTP)Sn(CCPh)(OC(6)H(4)OH) (3) was determined by X-ray crystallography.