Synthesis of new optically active propargylic fluorides and application to the enantioselective synthesis of monofluorinated analogues of fatty acid metabolites

A new approach to obtain optically active unsaturated or polyunsaturated systems with a single fluorine atom in an allylic or propargylic position is reported. Central to this strategy is the high regio- and stereocontrol observed during the fluorination of propargylic alcohols allowing a short and efficient synthesis of 1. Further, simple functional group transformations gave the enals 2 and 3. These three key intermediates were used for the preparation of optically active monofluorinated analogues of fatty acid metabolites.     

Palladium-catalyzed synthesis of novel optically active tryptophan analogues

[reaction: see text] Both unsaturated proline derivatives and optically active tryptophan analogues have been obtained via Pd-catalyzed cyclization of aniline-containing acetylenic amino acids. The side chain length of the cyclization precursor determines which one of the two possible products will be formed.     

A new synthesis of optically active α-alanine

Summary Optically active -alanine has been synthesized from pyruvic acid using N-aminoanabasine as the asymmetrizing agent.     

A new strategy for the synthesis of benzylic sulfonamides: palladium-catalyzed arylation and sulfonamide metathesis

An efficient two-step strategy has been developed to access diversely functionalized benzylic sulfonamides. Execution of this strategy required the development of two reaction methods: the palladium-catalyzed cross-coupling of aryl halides with CH-acidic methanesulfonamides and a metathesis reaction between the resulting alpha-arylated sulfonamides and diverse amines. The broad scope of the cross-coupling process combined with a versatile sulfonamide metathesis constitutes an efficient strategy for the synthesis of various benzylic sulfonamides.     

A new convenient route to enantiopure 2-coumarinyloxypropanals: application to the synthesis of optically active geiparvarin analogues

A new convenient route to enantiopure 2-coumarinyloxypropanals is described: Rosenmund reduction of (R)- or (S)-2-coumarinyloxypropanoyl chlorides afforded in good yields the corresponding 2-coumarinyloxypropanals. Their subsequent aldolic condensation with 3(2H)-furanones, followed by dehydration, led to enantiopure geiparvarin analogues now being investigated as promising antitumoral compounds.     

A new and efficient strategy for the synthesis of podophyllotoxin and its analogues

[structure: see text]. An efficient and stereoselective strategy for the total synthesis of podophyllotoxin was developed. This route leads to podophyllotoxin 1 in only 12 steps with 29% overall yield. A notable feature of this synthetic strategy is the use of the cascade addition-alkylation to ensure the key C1-C2 stereochemistry that is pivotal for the synthesis of podophyllotoxin.     

Reaction of oxophosphoranesulphenyl chlorides with phosphorus trichloride : A new synthesis of dialkyl phosphorochloridothionates and their optically active analogues

The reaction of acyclic oxophosphoranesulphenyl chlorides, with phosphorus trichloride has been found to give thiophosphoryl chlorides, and phosphoryl oxychloride—the products of the exclusive deoxygenation of sulphenyl chloride. Optically active phosphonochloridothionates and phosphorochloridothionates in a high state of optical purity have been obtained with inversion of configuration from optically active sulphenyl chlorides and phosphorus trichloride. It has been shown, however, that cyclic oxophosphoranesulphenyl chlorides undergo simultaneous desulphurisation and deoxygenation when treated with phosphorus trichloride. Using cis- and trans-isomers of 2-chlorothio-4-methyl-1,3,2-dioxaphosphorinan-2-one it has been demonstrated that deoxygenation is accompanied by inversion, whereas desulphurisation occurs with retention at phosphorus. The mechanism of the title reaction is discussed.     

A new method for the synthesis of glycosyl fluorides

Neat (diethylamino)sulfur trifluoride (DAST) has been found to react with the free anomeric hydroxyl of suitably protected aldoses and ketoses to afford glycosyl fluorides.     

A new synthesis of alkyl fluorides

Reduction of -fluorosulfides with sodium in alcohol results in the formation of fluoroalkanes.     

Development of a chemoenzymatic strategy for the synthesis of optically active and orthogonally protected polyamines

The chemical preparation and stereoselective enzymatic desymmetrization of a series of prochiral 2-substituted-1,3-propanediamines have been carried out using Pseudomonas cepacia lipase as biocatalyst. Syntheses of novel optically active orthogonally protected di- or triamines have been achieved for the first time with different grade of enantiodiscrimination depending on the C-2 substitution of the propane-1,3-diamine fragment. Final monoselective deprotection reactions of (S)-3-allyl-2-tert-butyl-1-(9-fluorenylmethyl)propane-1,2,3-triyltriscarbamate have allowed us to obtain a panel of novel enantiomerically enriched disubstituted triamines, compounds of difficult access by conventional synthetic methods.     

A new flexible strategy for the synthesis of gem-difluoro-bisarylic derivatives and heterocyclic analogues

A new strategy has been designed for the preparation of gem-difluoro-bisarylic derivatives. It starts from easily accessible and reactive gem-difluoro-propargylic intermediates and elaborates the aromatic rings by a Diels-Alder-aromatization sequence. Heterocyclic systems can be also obtained by 1,3 dipolar cycloadditions, affording mixed aromatic/heteroaromatic derivatives with CF₂ as a linker. Since this motif is a bioisostere of O and CO, corresponding bisarylic scaffolds could be of use to prepare chemical libraries of fluorinated analogues of bioactive natural products and/or drugs.     

Synthesis of optically active imidazopyridinium salts and the corresponding NHCs

A convergent synthesis of chiral imidazo-[1,5-a]-pyridinium salts is described by facile introduction of a stereogenic center via the N2 substituent. Conversion of these optically active salts to the corresponding N-heterocyclic carbenes (NHCs) and their trapping with sulfur followed by optical activity measurements are discussed.     

Theoretical designs for neutral five-membered carbene analogues of the group 13 elements: a new target for synthesis

Potential energy surfaces for the chemical reactions of neutral five-membered group 13 carbenoids have been studied using density functional theory (B3LYP/LANL2DZ). Five five-membered group 13 carbenoid species, HCMeP(PhN)2X, where X = B, Al, Ga, In, and Tl, have been chosen as model reactants in this work. Also, three kinds of chemical reaction, C-H bond insertion, alkene cycloaddition, and dimerization, have been used to study the chemical reactivities of these group 13 carbenoids. Our present theoretical work predicts that the larger the angleNXN bond angle in the neutral five-membered group 13 carbenoid, the smaller the singlet-triplet splitting, the lower the activation barrier, and, in turn, the more rapid are its various chemical reactions. Moreover, the theoretical investigations suggest that the relative carbenoidic reactivity decreases in the order B > Al > Ga > In > Tl. That is, the heavier the group 13 atom (X), the more stable is its carbenoid with respect to chemical reactions. As a result, we predict that the neutral five-membered group 13 carbenoids (X = Al, Ga, In, and Tl) should be stable, readily synthesized, and isolated at room temperature. Furthermore, the neutral five-membered group 13 carbenoid singlet-triplet energy splitting, as described in the configuration mixing model attributed to the work of Pross and Shaik, can be used as a diagnostic tool to predict their reactivities. The results obtained allow a number of predictions to be made.     

A new approach to the synthesis of optically active disparlures — Attractants ofPorthetria dispar

A fairly simple and original one-stage method of obtaining optically active attractants ofPorthetria dispar-(+)- and (-)-2-methyl-Z- and E-7,8-epoxyoctadecanes has been developed. The synthesis is based on the epoxidation of 2-methyloctadec-Z-and -E-7-enes by chiral peroxide complexes of molybdenum of the type of MoO₃-L* in an organic solvent at room temperature. Derivatives of tartaric, lactic, β-aminopropionic, and aspartic acids have been used as the chiral ligands (L*).     

Palladium-catalyzed substitution and cross-coupling of benzylic fluorides

Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for cross-coupling with phenylboronic acid. For the bifunctional substrate 4-chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the regioselective displacement of either the chlorine or fluorine substituent. The leaving group ability of fluoride vs other groups displaced in substitution is CF(3)CO(2) ≈ p-NO(2)C(6)H(4)CO(2) ≈ OCO(2)CH(3) > F > CH(3)CO(2), a ranking similar to allylic fluorides under Pd catalysis.     

A simple and efficient procedure for the synthesis of optically active s-triazolothiadiazole derivatives

A series of novel s-triazolothiadiazoles 3a-h were prepared by condensation reaction of substituted amino triazoles la-b with N-phethaloyl-L-amino acids 2a-d in the presence of the phosphoroxy chloride（POCl₃） as an anhydrous reagent.The structure of all synthesized compounds was confirmed by IR,¹H NMR,and ¹³C NMR spectroscopy.     

Esterase-mediated synthesis of optically active GABA analogues containing a stereogenic all-carbon quaternary carbon atom

Esterase from Horse Liver (HLAP) was able to hydrolyze a series of linear and cyclic β,β-dialkyl-γ-nitroesters, in spite of the well-known reluctance of hydrolytic enzymes to recognize and transform hindered substrates, such as those possessing a stereogenic quaternary carbon atom next to the reaction site. The resulting optically active γ-nitroesters gave access to optically active β,β-disubstituted γ-aminoacids as well as α,α-disubstituted succinic acids, both being biologically relevant compounds.