Pierre Beslin

Stereochimie de la deprotonation et de la reaction d'aldolisation des dithioesters

Abstract Cis lithium thioenolates are preferentially formed by deprotonation of dithiopropanoates with lithium diisopropylamide in tetrahydro-furan at -78°C. The cis selectivity observed, is unproved by increasing the alkylthio group size or by the ability of this group to chelate the lithium cation. When more bulkier bases such as lithium 2,2,6,6-tetramethylpiperi-dide or lithium hexamethyldisilazane are used, the selectivity is lowered. This lowering of selectivity is suppressed when the deprotonation is performed in presence of 12-crown-4. Addition of hexamethyl phosphoramide to the base does not invert the selectivity as it uas reported for the deprotonation of esters ; a rather better cis selectivity is reached in the case of methoxymethyl dithiopropanoate. These original results are well understood in terms of an open transition state model. Preformed lithium thioenolates are reacted uith a variety of aldehydes and afford stereo-specifically syn aldols. The influence of hexamethylphosphoramide and reaction time is also examined.

Préparation de thiocétones acycliques α-insaturées. dimérisation régiosélective en 4h-dithiine-1,3

Abstract α-Unsaturated acyclic thioketones 6 a–d were prepared by a retro-Diels-Alder reaction using flash thermolysis technique. They were detected at low temperature (blue coloured pyrolysate) but dimerize in solution as soon as the temperature rose to −60° (case 6 a–c) and −20° (case 6 d). The structure of 6 d was established by UV and NMR spectra taken at −60°. Dimeric products were proved to be 4H - 1,3 dithiin by spectral data and by univocal synthesis of 7 c and 7 d from the corresponding monomeric ketone. 1–3 Dithiin 7 d was isomerized at 190° into the thermodynamic isomer ( 8 ). This observed orientation of dimerisation agrees with theorical results obtained from molecular frontier orbital calculations.

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.

Mono S-trimethylsilyl ketene dithioacetals as versatile tools for the synthesis of α-hydrazinodithioesters. A novel access to endothiopeptides.

Abstract Mono-S-trimethylsilylketene dithioacetals have been prepared from dithioesters by the action of trimethylsilyl iodide formed in situ. They were reacted easily with dialkylazodicarboxylates to give good yields of α-hydrazinodithioesters. The latter were transformed into thioamides or endothiodipeptides by aminolysis either with an amine or an amino acid.

Thioacrolein S-oxide

Abstract Thioacrolein S -oxide was synthesized for the first time and characterized by low temperature NMR spectroscopy. Theoretical calculations about this unsaturated sulfine and two of its possible cyclic isomers were performed.

Stereocontrolled thio-Claisen rearrangement of S-allylic ketene aminothioacetals by an hydroxysubstituted adjacent stereogenic centre

Abstract (Z)-S-allylic ketene aminothioacetals were prepared from N,N-Dimethyl β-hydroxythioamides 2–8 by deprotonation with LDA (2 eq.) at −78°C followed by S-alkylation with allylic bromide. Rearrangement of these compounds occured easily at room temperature affording major syn N,N-dimethyl β-hydroxy α-allylic thioamides 9–21 with a syn/anti ratio of 80 20 to 98 2 . The syn configuration of the major diastereoisomer was confirmed by an univocal synthesis of syn thioamides 9 and 11. The structure assignments were confirmed by empirical 13C NMR rules. The observed induction is well supported by a proposed transition state model.

Reactivity of a novel ambident dianion formed by double deprotonation of β-thiosubstituted dithiopropanoates: a lithio-acrylate equivalent

Abstract A novel lithium allyl dianion has been generated by double deprotonation of β-alkyl (aryl) thio-dithioester. Reactions of this dianion with alkyl iodide, trimethylsilyl chloride and epoxyde occur at the γ-site. The regiochemistry of its addition to carbonyl compounds depends on the carbonyl compounds, e.g., for aldehydes ketones, α -and γ-regioselectivity respectively, were observed. The reactivity with cyclopentenone was also examined. γ-Selectivity with alkyl halides and epoxydes; γ and α-prefered selectively with respectively ketones and aldehydes.

Preparation et dimerisation de la butene-3 thione-3 et de la methyl-4 pentene-3 thione-2 (1)

Abstract 3-buten-2-thione and 4-methyl-3-penten-2 thione are prepared by a retro- Diels reaction using flahs thermolysis technique. Their particular mode of dimerisation is elucidated.