Asymmetric oxidation of 1,2-diols using N-bromosuccinimide in the presence of chiral copper catalyst

Asymmetric oxidation of 1,2-diols using N-bromosuccinimide (NBS) in the presence of copper(II) triflate and (R,R)-Ph-BOX has been exploited. This oxidation was applicable to asymmetric desymmetrization of meso-hydrobenzoin and kinetic resolution of dl-hydrobenzoin and racemic-cycloalkane-cis-1,2-diols to afford optically active α-ketoalcohols with good to high enantiomeric excess.     

Aerobic oxidative desymmetrization of meso-diols with bifunctional amidoiridium catalysts bearing chiral N-sulfonyldiamine ligands

Asymmetric aerobic oxidation of a range of meso- and prochiral diols with chiral bifunctional Ir catalysts is described. A high level of chiral discrimination ability of Cp^∗Ir complexes derived from (S,S)-1,2-diphenylethylenediamine was successfully demonstrated by desymmetrization of secondary benzylic diols such as cis-indan-1,3-diol and cis-1,4-diphenylbutane-1,4-diol, providing the corresponding (R)-hydroxyl ketones with excellent chemo- and enantioselectivities. Enantiotopic group discrimination in oxidation of symmetrical primary 1,4- and 1,5-diols gave rise to chiral lactones with moderate ees under similar aerobic conditions.     

Enantiomerically Pure Cyclic trans-1,2-Diols,Diamines, and Amino Alcohols by Intramolecular Pinacol Coupling of Planar Chiral Mono-Cr(CO)3 Complexes of Biaryls

Without any formation of stereoisomers , the intramolecular pinacol cyclization of 1 —planar chiral mono-Cr(CO)₃ complexes of 1,1′-biphenyls with carbonyl functionalities at the 2- and 2′-positions—with samarium diiodide gives cyclic trans-1,2-diols 2 . Upon exposure to sunlight, the chromium-complexed diols 2 produce optically pure chromium-free trans-diols 3 . Similarly, the corresponding enantiomerically pure trans-1,2-diamines and amino alcohols are obtained from the planar chiral chromium complexes of biphenyls with diimino or keto-imino functionalities. R¹=H, OMe; R²=H, Me; R³=H, Me.     

Mechanistic investigation of the Candida albicans CCT 0776 stereoinversion system and application to obtain enantiopure secondary alcohols

Phenylethanol deracemization with Candida albicans CCT 0776 whole cells yields the (R)-enantiomer in over 99% enantiomeric excess and 98% yield. The deracemization process involves, in the first step, a fast, highly (S)-selective oxidation (NADP and O₂ dependent) and, in the second step, a slower partially (S)-selective reduction (NADH dependent) of the intermediate ketone. The process was extended to other 2-alkanols, 1,2-diols and 1,3-diols and, with the exception of 1,3-diol (unreactive), the enantiomeric excess and yield of the deracemization were about 99% and 62–98%, respectively.     

Kinetic resolution of vic-diols by Bacillus stearothermophilus diacetyl reductase

The kinetic resolution of several racemic syn- and anti-1,2-diols by enzymatic oxidation with Bacillus stearothermophilus diacetyl reductase is described. The enantiomerically pure (R,R)- and (R,S)-diols are recovered in almost quantitative yield.     

Sequential use of regio- and stereoselective lipases for the efficient kinetic resolution of racemic 1-(5-phenylfuran-2-yl)ethane-1,2-diols

Possible routes for the enzymatic transformation of various substituted 1-(5-phenylfuran-2-yl)ethane-1,2-diols and their mono- and diacetylated counterparts were studied. Combining the regioselectivity of LPS mediated acylation of the starting racemic diols, the stereoselectivity of LAK shown in the enantiomer selective transformation of the previously formed racemic primary acetates and the LPS mediated mild hydrolysis-alcoholysis of the resolution products, an efficient preparative scale procedure for the synthesis of various highly enantiomerically enriched (R)- and (S)-phenylfuran-2-yl-ethane-1,2-diols has been developed.     

A domino Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines and application to the synthesis of the ceramide transport inhibitor (±)-HPA-12

A Kornblum-DeLaMare/aza-Michael reaction of 3,6-dihydro-1,2-dioxines with primary and secondary amines has been developed which affords 4-hydroxy-3-aminoketones. The aza-Michael products were reduced using non-selective NaBH₄/MeOH or diastereoselective (up to 92:8) SnCl₄/NaBH₄ conditions yielding (1R¹,3S¹)-3-amino-1,4-diols in up to 97% and 70% yield respectively. The major reduction product was converted in two steps to (±)-HPA-12, which is an inhibitor of the cytosolic ceramide transporting protein.     

Preparation of chiral trans-5-substituted-acenaphthene-1,2-diols by baker’s yeast-mediated reduction of 5-substituted-acenaphthylene-1,2-diones

A series of trans-5-substituted-acenaphthene-1,2-diols were obtained in 21–72% yield with 97–100% ee by baker’s yeast-mediated reduction of the corresponding acenaphthylene-1,2-diones, in the presence of DMSO as a co-solvent and under vigorous agitation. The absolute configuration of (?)-trans-5-methoxy-acenaphthene-1,2-diol trans-3b and (?)-trans-5-bromo-acenaphthene-1,2-diol trans-3c was assigned as (S,S) and (?)-trans-5-thiomorpholin-acenaphthene-1,2-diol trans-3d was established as (R,R) by exciton-coupled circular dichroism.     

A new synthetic approach to enantiomerically enriched dihydrobenzofurans: use of a hydrolytic kinetic resolution and an intramolecular epoxide ring opening protocol using 1-benzyloxy-2-oxiranylmethylbenzenes

A novel approach towards the preparation of racemic 1-benzyloxy-2-oxiranylmethylbenzenes using dimethyldioxirane and their hydrolytic kinetic resolution using (R,R)(Salen)Co(III)(OAc) (Jacobsen’s catalyst) to afford the (R)-epoxides and (S)-1,2-diols, enantioselectively, is described. The (R)-1-benzyloxy-2-oxiranylmethylbenzenes were then cyclized via an intramolecular epoxide opening reaction to give (S)-2-hydroxymethyl-2,3-dihydrobenzofurans.     

Synthesis,resolution, and applications of 3-amino-2,2-dimethyl-1,3-diphenylpropan-1-ol,a conformationally restricted 1,3-aminoalcohol

Efficient synthetic routes to both syn and anti diastereomers of a conformationally restricted 1,3-aminoalcohol were devised. Resolution of the aminoalcohols was accomplished through diastereomeric salt with R-(?)-O-acetyl mandelic acid. These aminoalcohols were examined as ligands for two standard reactions, namely, enantioselective addition of Et₂Zn to aldehydes and reduction of prochiral ketones with BH₃.     

Investigation of the ceriumIV oxidation of poly(vinyl alcohol)

Initiation of ceric ion-induced grafting from poly(vinyl alcohol) (PVOH) was studied by examining the formation and lifetime of colored complexes between cerium^IV and (1) a commercial PVOH, (2) a diol-free PVOH, and (3) several model 1,2-diols. UV/visible spectroscopy was employed using a wavelength of 520 nm. Results showed that the 1,2-diols, which are an inherent defect in PVOH, are the sites most reactive toward ceric ion. The observed rate constant for the reaction was found to increase with decreasing [Ce^IV] until the maximum rate was reached at which time reaction took place exclusively with 1,2-diols. The activation energy for oxidation of commercial PVOH at the maximum rate was 15.4 kcal/mol while that for diol-free PVOH was 22.4 kcal/mol. The 1,2-diols of PVOH displayed a high equilibrium constant for complexation with ceric ion, compared to the model 2,3-butanediol. It was suggested that the PVOH chain segments bring about crowding of the diol group, and this leads to a higher equilibrium constant for complexation. The lowest energy conformation of a PVOH chain segment containing a 1,2-diol linkage was calculated using the CHEMLAB-II molecular design program, and the 1,2-diol was predicted to be at the center of a sharp bend in the chain brought about by its presence.     

Reactions of N- and C-alkenylanilines: IX. Synthesis, oxidation, and nitration of some 7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles

Heating of 4-acyl-3-iodo-7-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in piperidine gave 4-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles which were oxidized with KMnO4 to obtain the corresponding 4-acyl-7-methyl-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indole-1,2-diols. Oxidation of 4-acyl-7-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles at the olefinic double bond with hydrogen peroxide in acetonitrile in the presence of formic acid afforded stereoisomeric epoxides with cis and trans orientation of the nitrogen-containing and oxirane rings. Nitration with a mixture of ammonium nitrate and trifluoroacetic anhydride produced 5-nitro derivatives. The structure of 1-{(1aR*,1bR*,6bS*,7aS*)-5-methyl-1a,1b,2,6b,7,7ahexahydrooxireno[4,5]cyclopenta[1,2-b]indol-2-yl}ethanone was determined by X-ray analysis.     

Syntheses of new C2-symmetric,optically active 1,2-diols bearing tertiary alkyl groups

New C₂-symmetric chiral 1,2-diols, 1,2-bis(1-adamantyl)-1,2-ethanediol and 3,3,6,6-tetramethyl-1,2-cyclohexanediol, were synthesized by the use of a new resolution method.     

Two chiral mononuclear and one-dimensional cadmium(II) complexes constructed by (1R,2R)-N1,N2-bis(pyridinylmethyl)cyclohexane-1,2-diamine derivatives: Effect of positional isomerism

Reactions of (1R,2R)-N¹,N²-bis(pyridinylmethyl)cyclohexane-1,2-diamine derivatives, (1R,2R)-2-bpcd and (1R,2R)-3-bpcd [(1R,2R)-2-bpcd = (1R,2R)-N¹,N²-bis(pyridin-2-ylmethyl)cyclohexane-1,2-diamine, (1R,2R)-3-bpcd = (1R,2R)-N¹,N²-bis(pyridin-3-ylmethyl)cyclohexane-1,2-diamine], with CdI₂ in an analogous way led to the formation of a chiral discrete mononuclear complex and a chiral one-dimensional polymeric chain, respectively, which may be attributed to the positional isomerism of the ligands. The chiral organic ligands and complexes display luminescent properties indicating that they may have a potential application as optical materials. Powder second-harmonic generation (SHG) efficiency measurement shows that the SHG efficiency of the complexes is approximately 0.3 and 0.45 times that of KDP, respectively.     

Peroxidative bromination and oxygenation of organic compounds: Synthesis, X-ray crystal structure and catalytic implications of mononuclear and binuclear oxovanadium(V) complexes containing Schiffbase ligands

Treatment of of (R,R)-N,N-salicylidene cyclohexane 1,2-diamine(H₂L¹) in methanol with aqueous NH₄VO₃ solution in perchloric acid medium affords the mononuclear oxovanadium(V) complex [VOL¹(MeOH)]·ClO₄ (1) as deep blue solid while the treatment of same solution of (R,R)-N,N-salicylidene cyclohexane 1,2-diamine(H₂L¹) with aqueous solution of VOSO₄ leads to the formation of di-(μ-oxo) bridged vanadium(V) complex [VO₂L²]₂ (2) as green solid where HL² = (R,R)-N-salicylidene cyclohexane 1,2-diamine. The ligand HL² is generated in situ by the hydrolysis of one of the imine bonds of HL¹ ligand during the course of formation of complex [VO₂L²]₂ (2). Both the compounds have been characterized by single crystal X-ray diffraction as well as spectroscopic methods. Compounds 1 and 2 are to act as catalyst for the catalytic bromide oxidation and C-H bond oxidation in presence of hydrogen peroxide. The representative substrates 2,4-dimethoxy benzoic acid and para-hydroxy benzoic acids are brominated in presence of H₂O₂ and KBr in acid medium using the above compounds as catalyst. The complexes are also used as catalyst for C-H bond activation of the representative hydrocarbons toluene, ethylbenzene and cyclohexane where hydrogen peroxide acts as terminal oxidant. The yield percentage and turnover number are also quite good for the above catalytic reaction. The oxidized products of hydrocarbons have been characterized by GC Analysis while the brominated products have been characterized by ¹H NMR spectroscopic studies.     

Stability of boronic esters - Structural effects on the relative rates of transesterification of 2-(phenyl)-1,3,2-dioxaborolane

Relative rates of reaction of the achiral cyclic phenylboronic ester 2-(phenyl)-1,3,2-dioxaborolane with a wide variety of structurally modified diols, have been studied to understand the factors influencing the relative stabilities of boronic esters. It is found that the alkyl substituents on the α-carbons of diols slow down the transesterification, but produce thermodynamically more stable boronic ester. Six-membered boronic esters are thermodynamically more stable than their corresponding five-membered analogs. Amongst cyclic 1,2-diols, cis-1,2-cyclopentanediol displaces ethylene glycol instantaneously whereas trans-1,2-cyclopentanediol is totally unreactive, which suggests that the cis-stereochemistry of the 1,2-diol is a prerequisite for transesterification. Among the 1,5-diols, diethanolamine displaces ethylene glycol quite rapidly forming a more stable bicyclic chelate in which nitrogen is attached to boron by a coordinating bond (as evident by ¹¹B NMR spectroscopy). The oxygen atom of di(ethylene glycol) and the sulfur atom of 2,2′-thiodiethanol do not assist in displacing the ethylene glycol from their boronic esters.     

Copper complex catalyzed asymmetric monosulfonylation of meso-vic-diols

Asymmetric desymmetrization of meso-vic-diols was performed by tosylation in the presence of copper(II) triflate and (R,R)-Ph-BOX as a catalyst. The method was successfully applied to asymmetric desymmetrization of cyclic and acyclic meso-vic-diols in high enantioselectivity with up to >99% ee.     

Electrochemically driven stereoselective approach to syn-1,2-diol derivatives from vinylarenes and DMF

We have developed an electrochemically driven strategy for the stereoselective synthesis of protected syn-1,2-diols from vinylarenes with N,N-dimethylformamide (DMF). The newly developed system obviates the need for transition metal catalysts or external oxidizing agents, thus providing an operationally simple and efficient route to an array of protected syn-1,2-diols in a single step. This reaction proceeds via an electrooxidation of olefin, followed by a nucleophilic attack of DMF. Subsequent oxidation and nucleophilic capture of the generated carbocation with a trifluoroacetate ion is proposed, which gives rise predominantly to a syn-diastereoselectivity upon the second nucleophilic attack of DMF.

An electrochemical method that provides an operationally simple synthesis of masked syn-1,2-diols from styrenes and DMF has reported. The TFA ion is engaged in the formation of a key intermediate, which gives rise predominantly to syn-selectivity.     

Assignment of the relative and absolute configurations of acyclic secondary 1,2-diols

The NMR profiles (¹³C-δ, ¹H-δ, ¹H(OH)-δ, and ³J_H,H) of syn- and anti-diols—3a,b in achiral solvents were found to be very similar to each other. Contrarily, their Δδ (Δδ=δ_(R,R)-2−δ_(S,S)-2) behaviors in chiral bidentate NMR solvent (R,R)- and (S,S)-BMBA-p-Me (2) were found to be significantly different. On the basis of this NMR characteristic, a method has been developed to predict both the relative and absolute configurations of acyclic secondary 1,2-diols.     

Selective oxidation of benzylic or allylic hydroxyl group of sec-1,2-diols

A mild and efficient method to selectively oxidize chiral sec-1,2-diols has been developed, which demonstrates that 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) can selectively oxidize benzylic or allylic hydroxyl group of sec-1,2-diols under ultrasound wave promotion. The configuration of the adjacent chiral center is retained.