Stéphane Perrio

Organocatalytic asymmetric synthesis of sulfoxides from sulfenic acid anions mediated by a Cinchona-derived phase-transfer reagent.

Preliminary results concerning a conceptually novel route to chiral sulfoxides based on the asymmetric alkylation of sulfenate salts with alkyl halides mediated by a chiral phase-transfer catalyst are described. As a representative example, o-anisyl methyl sulfoxide was produced in 96% yield and with an enantiomeric excess of 58% using commercial cinchonidinium derivative 2a.

Formation stéréocontroˆlée de deux centres chiraux contigus par thio-rearrangement de claisen d'α-hydroxydithioacétals de cétène s-allylés.

Abstract β-hydroxydithioesters 8–14 were easily doubly deprotonated to afford one single dianion whose cis geometry results from chelation control. These dianions were transformed by S-allylation into ( Z )-α-hydroxy ketene dithioacetals 20Z-29Z . Thio-Claisen rearrangement of these dienic compounds occured even at room temperature. It gave the corresponding α-allylic β-hydroxydithioesters 32–41 with a uniformly high level of syn stereoselectivity in excess of 90/10 independently of the ketene geometry as illustrated by the rearrangement of the ( E ) ketene dithioacetal 20E issued from the S-allyl β-hydroxydithioester 15 with a syn/anti ratio 93/7. Syn and anti configurations were assigned after transformation of a syn-anti mixture of 32 or 39 into the corresponding esters 44 and 45 and comparison with a rich anti mixture of the same esters prepared according to Fraters alkylation. These assignments were confirmed by a syn selective aldol reaction of 4-pentenedithioates with the appropriate aldehydes. A few 13 C NMR generalization rules allowing syn and anti configuration determination were also put forth. A transition state model is proposed to explain the observed asymmetric induction by the external hydroxy group as a result of both steric and stereoelectronic control.

Asymmetric induction in the thio-claisen rearrangement. Creation of three contiguous stereogenic centres from α-hydroxy ketene dithioacetals

Abstract Syn β-hydroxy γ-methyl dithioesters were deprotonated with two equivalents of LDA. A subsequent S-alkylation of the resulting dianions yielded α-hydroxy S-allyl ketene dithioacetals. A single isomer was observed, arising from a selective cis deprotonation. These dithioacetals underwent a rapid and highly diastereoselective thio-Claisen rearrangement at an ambient temperature. Syn-syn α-allyl β-hydroxy γ-methyl dithioesters were mainly formed. The syn-syn/anti-syn ratios ranged from 85 : 15 to 99 : 1. The selectivity observed originated from asymmetric induction with a noteworthy stereoelectronic effect of the hydroxyl group. Configurations were assigned by a spectroscopic method using previously reported 13 C NMR rules and then confirmed by a syn-syn diastereoselective aldol reaction. This novel and efficient method for the creation of frameworks with three contiguous stereogenic centres, involves two diastereoselective steps : an aldol reaction follwed by a thio-Claisen rearrangement.

Stereospecific thio-claisen rearrangement of S-crotylic α-hydroxy ketene dithioacetals. Creation of three contiguous stereogenic centres

Abstract All four diastereoisomeric S-crotylic α-hydroxy ketene dithioacetals (ZE′, ZZ′, EE′ and EZ′) were prepared uniquivocally from S-methyl or S-crotyl (Z or E) β-hydroxy dithioesters by a tandem cis-deprotonation with LDA and S-alkylation. These dithioacetals underwent, in a refluxing cyclohexane solution, an easy thio-Claisen rearrangement into dithioesters, containing three contiguous chiral centres. The rearrangement is stereospecific. Furthermore each of the four system led to the formation of a different major diastereoisomer, thus making all of the four possible isomers (anti-anti, syn-syn, anti-syn and syn-anti) accessible. A relationship between the main component configuration and the starting dithioacetal geometry has been ruled out. The observed stereospecificity originates from two independent stereocontrols, an internal and an external one. The former is an aggreement with the classical internal control obtained with a [3.3] sigmatropic shift. The latter is a result of an asymmetric induction but surprisingly, is dependent on the S-crotylic double bond geometry. All the results were rationalised by transition state models and the configurations proven by chemical correlations: transformation into known esters and Swern oxidation.

Enantioselective Phase‐Transfer Catalyzed α‐Sulfanylation of Isoxazolidin‐5‐ones: An Entry to β2,2‐Amino Acid Derivatives

An unprecedented enantioselective α-functionalization of C4-substituted N-alkoxycarbonyl isoxazolidin-5-ones, readily available platforms from Meldrums acid derivatives, by N-sulfanylphthalimide (PhthSR) electrophiles was achieved upon an efficient phase-transfer catalytic approach, mediated by a commercial N-spiro quaternary ammonium catalyst. Two catalytic activities of the in situ formed R4 N+ Phth- species were highlighted, the phtalimidate being involved in the anion metathesis event and likely as a Brønsted base. This sequence offers a straightforward access to α,α-disubstituted isoxazolidinones, which turned out to be useful precursors of α-sulfanyl-β2,2 -amino acid derivatives.

Chiral non-racemic sulfoxides by asymmetric alkylation of alkanesulfenates in the presence of a chiral ammonium phase-transfer catalyst derived from Cinchona alkaloid

Based on a previous study involving arenesulfenates, the enantioselective S-alkylation of benzyl and alkyl sulfenates R1SO− with alkyl halides, mediated by a cinchonidinium phase-transfer catalyst, was evaluated as a conceptually different synthetic approach to chiral sulfoxides. Direct application of our standard organocatalytic protocol, with methyl iodide as the electrophile, was rather disappointing mainly as a result of a sluggish release of the sulfur nucleophiles. However, slight modifications of the reaction conditions allowed the isolation of (R)-benzyl methyl sulfoxide in a 60% yield and a 38% ee, whereas (R)-cyclohexyl methyl sulfoxide was produced in a 34% yield and a 47% ee. GRAPHICAL ABSTRACT

Mild and efficient access to lithium alkanesulfinates based on oxaziridine-promoted oxidation of thiolates

Lithium alkanethiolates do not react with N-sulfonyloxaziridine 1 to generate sulfenate species, as uniformly reported in other series. In the present case, a double oxidation reaction is exclusively observed. This unexpected outcome was then exploited for a general, mild and straightforward route to aliphatic sulfinate salts. Investigation of further transformation into sulfones is also described.

Oxidation of Thiolates with Oxaziridines: an Efficient Method to the Preparation of Sulfoxides, Sulfones and Sulfonic Acid Derivatives

Oxaziridine-mediated oxidation reactions of thiolates into sulfenates and sulfinates are reported.

Diastereoselective Thio-Claisen Rearrangement of S-Allylic α-Silyloxyketene Dithioacetals

Abstract In continuing with the development of the use of the thio-Claisen rearrangement1 for the diastereoselective formation of carbon-carbon bonds, we wish to report herein the rearrangement of S-allylic α-silyloxyketene dithioacetals (PG[dbnd]SiMe3).

Enantiomerically Pure [2.2]Paracyclophane-4-thiol: A Planar Chiral Sulfur-Based Building Block Readily Available by Resolution with an Amino Acid Chiral Auxiliary.

Acyl chloride of N-phthaloyl-(S)-isoleucine is an efficient chiral auxiliary for the resolution of (±)-[2.2]paracyclophane-4-thiol. A preparative protocol, based on the conversion into diastereoisomeric thiolesters and separation by two fractional crystallizations and column chromatography, was developed. Deprotection with LiAlH4 allowed isolation of the individual thiol enantiomers in good yield (∼40%) and high enantiomeric purity (ee >93%). The absolute configurations were determined by comparison of the optical rotation value of the products with literature data and were confirmed by X-ray crystallography.