Organosulphur compounds : XLVII Alkylation of sulphinic acids by o-alkylisoureas: o-versus s-reactivity and asymmetric synthesis of alkyl sulphinates

The reaction of 0-alkylisoureas with sulphinic acids was found to produce the corresponding sulphones and sulphinates, the latter being predominantly formed. The sulphinate to sulphone ratio is strongly influenced by the kind of alkyl groups in the 0-alkylisourea and appeared to be also dependent on the solvent used. A few optically active sulphinates (e.e. up to 8.1%.) were prepared in the reaction between benzenesulphinic acid and a series of 0-alkylisoureas bearing optically active substituents at the nitrogen atom. A possible reaction mechanism is discussed.     

N-BROMOSUCCINIMIDE-CATALYSED TRANSESTERIFICATION AND RACEMIZATION OF SULPHINATES

Abstract

Both aliphatic and aromatic sulphinates undergo transesterification reaction in the presence of N-bromosuccinimide. Isopropanolysis of optically active alkyl arenesulphinates was found to give racemic isopropyl arenesulphinates. The rate of racemization of optically active isopropyl p-toluenesulphinate was found to be first order with respect to both N-bromosuccinimide and isopropyl alcohol, suggesting that the reaction is a bimolecular nucleophilic substitution at the sulphur atom. The para electrodonating substituents in the aromatic ring accelerate slightly the rate of racemization. At the same time the rate of racemization was found to be retarded by the increase of steric requirements of the substituent at the sulphinyl sulphur atom suggesting that the initial formation of bromoxonium salt is the rate-determining step. Completely nonstereospecific isopropanolysis of optically active alkyl p-toluenesulphinates suggests that a sulphurane is formed as an intermediate in the exchange step of the reaction.     

New aromatic azo compounds: syntheses and liquid-crystalline properties

The chemical syntheses of 12 new azo dyes are reported. The optically active compounds were prepared by the Mitsunobu reaction, amide formation, and esterification with optically active alcohols or acids. Several new compounds showed liquid-crystalline properties, and their phase transition behavior was investigated.     

A convenient method for synthesis of enantiomerically enriched methylphenidate from N-methoxycarbonylpiperidine

[formula: see text] This report describes a new method to prepare optically active methylphenidate starting from piperidine. The method consists of a transformation of N-methoxycarbonylpiperidine to the corresponding alpha-methoxylated carbamate I by utilizing electrochemical oxidation followed by the coupling reaction with optically active Evans imides II to produce optically active methylphenidate derivatives III with high stereoselectivities, threo-(2R,2'R)-Methylphenidate (IV; Ar = Ph; Ritalin) was easily prepared from III in three steps.     

Syntheses of stereoregular and optically active polyamides from active 4-chloro-1-benzotriazolyl diesters and diamines

A new route to prepare optically active polyamides was established, based on the polycondensation of two new active diesters: the active diesters of 4-chloro-1 hydroxybenzotriazole, such as 1,1'-(terephthaloyldioxy)bis(4-chloro-benzotriazole), and 1,1'-(isophthaloyldioxy)bis(4-chlorobenzotriazole), with optically active isomers of 2,4-diaminopentane. Dipolar aprotic solvents such as N,N-dimethylformamide and dimethyl sulfoxide were used as reaction solvents. The solution polycondensation carried out in solution at room temperature afforded optically active polyamides. The aminolysis of the two active diesters was carried out as a model reaction study.     

General route to racemic and enantiomeric carbo- and heterocyclic vinyl sulfoxides via tandem Michael addition/Horner olefination of alpha-phosphorylvinyl sulfoxides

A new one-pot synthesis of heterocyclic and carbocyclic vinyl sulfoxides has been developed which involves reaction of alpha-phosphorylvinyl sulfoxides with carbonyl compounds bearing oxygen, nitrogen, and carbon nucleophilic centers. Use of optically active alpha-phosphorylvinyl p-tolyl sulfoxides in this tandem Michael addition/Horner olefination reaction leads to the corresponding optically active cyclic sulfoxides. In this way, a variety of optically active chromene, pyrrolizine, chinoline, and cyclopentene sulfoxides have been efficiently prepared.     

A study of asymmetric hydrocyanation of heteroaryl carboxaldehydes catalyzed by (R)-oxynitrilase under micro-aqueous conditions

A number of new optically active heteroaryl cyanohydrins have been prepared by hydrocyanation under micro-aqueous conditions catalyzed by almond meal (containing (R)-oxynitrilase). Substituent effects on the reaction are discussed. This micro-aqueous method provides an efficient, convenient and economical approach to optically active cyanohydrins.     

Optically active seleninate esters: isolation, absolute configuration, racemization mechanism, and transformation into chiral selenoxide

Optically active seleninate esters were obtained for the first time by chromatographic resolution on an optically active column. The absolute configurations of the optically active seleninate esters were determined by comparing their chiroptical properties with those of two analogous sulfinate esters, the absolute configuration of one of which is known and that of the other was determined by X-ray crystallographic analysis. The optically active seleninate esters were found to racemize in solution. Kinetic studies of the racemization, the oxygen exchange reaction with H(2)(18)O, and theoretical studies clarified that the racemization of the optically active seleninate esters in solution proceeded via an achiral hypervalent selenurane intermediate that was formed by the reaction with water. The reaction of the optically active seleninate ester and the sulfinate ester having bulky substituents with Grignard reagents was found to proceed with the retention of stereochemistry to give an optically active selenoxide and sulfoxides, respectively.     

Enantioselective organocatalytic allylic amination

A new strategy for catalytic enantioselective allylic amination based on organocatalysis has been developed. Using a commercially available organocatalyst we demonstrate a direct highly enantioselective allylic electrophilic functionalization of alkylidene cyanoacetates and malononitriles with azodicarboxylates. The reaction is broad in scope and proceeds in high yields and with enantioselectivities up to 99%. Furthermore, we demonstrate the synthetic utility of the optically active products formed: highly diastereoselective Diels-Alder reaction, reduction, and formation of optically active building blocks, which are found in various important bioactive compounds such as quinacrine, chloroquine, and analogues thereof.     

New route to optically active amine derivatives: ruthenium-catalyzed enantioselective hydrogenation of ene carbamates

The reaction of cyclic ketones with tert-butyl or benzyl carbamate under acidic conditions directly affords prochiral ene carbamates. Their enantioselective hydrogenation in the presence of a chiral ruthenium catalyst provides a new access to optically active carbamates easy to deprotect to the corresponding optically active amines.     

Microbial deracemization of alpha-substituted carboxylic acids: substrate specificity and mechanistic investigation

A new enzymatic method for the preparation of optically active alpha-substituted carboxylic acids is reported. This technique is called deracemization reaction, which provides us with a route to obtain the enantiomerically pure compounds, theoretically in 100% yield starting from the racemic mixture. This means that the synthesis of a racemate is almost equal to the synthesis of the optically active compound, and this concept is entirely different from the commonly accepted one in the asymmetric synthesis. Using the growing cell system of Nocardia diaphanozonaria JCM3208, racemates of 2-aryl- and 2-aryloxypropanoic acid are deracemized smoothly and (R)-form-enriched products are recovered in high chemical yield (>50%). In addition, using optically active starting compounds and deuterated derivatives as well as inhibitors, we have disclosed the fact that a new type of enzyme takes part in this biotransformation, and that the reaction proceeds probably via the same mechanism as that in rat liver.     

Oxiranyl anion-mediated synthesis of highly enantiomerically enriched styrene oxide derivatives

[reaction: see text] The stereospecific alpha-lithiation of optically active styrene oxides and the trapping reaction of the corresponding highly reactive intermediates with electrophiles to produce optically active styrene oxide derivatives are described. This methodology has been applied to the synthesis of an optically active oral antifungal agent of industrial interest.     

Asymmetric multicomponent copper catalyzed synthesis of chiral propargylamines

A three-component stereoselective reaction between an aldehyde, an amine and phenylacetylene to afford optically active propargyl amines in good yields was developed. The reaction is catalysed by copper complexes of enantiomerically pure bis-imines. The best results were obtained with imines readily prepared in very high yields from the commercially available binaphtyl diamine.

A very simple experimental procedure at room temperature allowed to obtain optically active propargyl amines in very good yields and enantioselectivity up to 75%. The extremely simple methodology and the mild reaction conditions, as well as the possibility of a modular approach for developing new and more efficient bis-imine-based chiral ligands make the present methodology very attractive.     

Practical synthesis of optically active styrene oxides via reductive transformation of 2-chloroacetophenones with chiral rhodium catalysts

[reaction: see text] A practical method for the synthesis of optically active styrene oxides has been developed via formation of optically active 2-chloro-1-phenylethanols generated by reductive transformation of ring-substituted 2-chloroacetophenones. The optically active alcohols with up to 98% ee are obtainable from the asymmetric reduction of acetophenones with an S/C = 1000-5000 with a formic acid triethylamine mixture containing a well-defined chiral Rh complex, CpRhCl[(R,R)-Tsdpen].     

Organomentallic compounds : LXIII. Synthesis,optical stability,stereo-selective and -specific reactions of chiral triorganotin hydrides

Optically active triorganotin hydrides have been synthesized by asymmetric reduction of the corresponding halides. These optically stable compounds undergo stereoselective conversions into other optically stable compounds such as tetraorganotin compounds (by reaction with diazomethane or with bifluorenylidene) or hexaorganoditin compounds (by reaction in the presence of palladium) or into optically unstable compounds such as methylneophylphenyltin chloride (by reaction with CCl₄). The HD exchange between optically active methylneophylphenyltin hydride (deuteride) and triphenyltin deuteride (hydride) occurs with retention of configuration at the metal atom.     

Organocatalytic Asymmetric Formation of Steroids

A novel and simple one‐step approach for the construction of optically active steroids in a highly stereoselective manner by using organocatalysis is presented. The reaction of (di)enals with cyclic dienophiles in the presence of a TMS‐protected prolinol catalyst leads to the construction of important 14 β‐steroids. This new reaction allows an easy access to optically active steroids with a variety of substituents in the A ring in high yields and up to greater than 99 % ee. The reaction has been extended to include the construction of B‐ and D ‐homosteroids as well as steroids containing heteroatoms in the B ring. The angular substituent at C13 can be varied and alkyl, ester, and sulfone functionalities are introduced with excellent stereoselectivities. Simple synthetic procedures provide access to a range of naturally occurring steroids such as estrone and related analogues.     

Optically active seleninamides: isolation, absolute configuration, and racemization mechanism

Optically active seleninamides were obtained for the first time by chromatographic resolution on an optically active column. The absolute configurations of the optically active seleninamides were determined by comparing their chiroptical properties with those of analogous sulfinamides, the stereochemistry of which was determined by transformation into chiral sulfoxides of known configurations. The optically active seleninamides were found to racemize in solution. Kinetic studies of the racemization and theoretical studies clarified that the racemization of the optically active seleninamides in solution proceeds via hypervalent hydrates formed by the reaction with water.     

Synthesis and properties of novel diisocyanate based optically active polyimides

A new optically active diisocyanate was prepared from the reaction of l-leucine and pyromellitic dianhydride (PMDA) and subsequent transformation of intermediate imide-containing diacid to diisocyanate via Weinstock modification of Curtius rearrangement. Solution polycondensation reaction of the prepared diisocyanate with PMDA, 3,3,4,4-benzophenonetetracarboxylic dianhydride, and hexafluoroisopropylidene 2,2-bis(phthalic anhydride) resulted in the preparation of novel optically active polyimides. The optimal conditions for polyimidations (reaction duration and temperature programming) were obtained via study of the model compound. The monomer, model compound and polymers were characterized by FTIR, ¹HNMR, mass spectroscopy and elemental analysis and their optical and physical properties were studied as well.     

Palladium-catalyzed intra-molecular olefin insertion reaction of α-alkenyl-α-acyloxytrialkylsilane. Synthesis of optically active carbocycle

Pd-catalyzed intra-molecular olefin insertion/carbonylation reaction of optically active α-alkenyl-α-acyloxysilanes is described. The reactions proceeded in a stereoselective manner to give five- and six-membered optically active carbocycles having (E)-vinylsilane in their side chains. Under CO condition, optically active carbocycles containing one-carbon homologated side chain were produced by Pd-catalyzed tandem olefin insertion-carbonylation reaction.     

Asymmetric Allylation Polymerization of Bis(allylsilane) and Dialdehyde

The enantioselective addition of an allylsilane to an aldehyde is an excellent method to give optically active homoallyl alcohols. Applying this reaction to the asymmetric polymerization of bis(allylsilane) and dialdehyde, the synthesis of a new optically active polymer having chirality on the main chain was possible. Chiral acyloxyborane (CAB) was effective as a catalyst in this asymmetric allylation polymerization.