Gilles Hanquet

ASYMMETRIC SYNTHESIS OF SYN AND ANTI 1,2-DIOLS FROM DIETHYL OXALATE USING THE STEREOSELECTIVE SULFOXIDE DIRECTED REDUCTION OF 1,2-DIKETONE DERIVATIVES

Abstract A new chiral Wittig reagent, a β-keto-γ-( S )-hydroxy-δ-( R )- p -tolylsulfinyl phosphonate, readily made from ethyl oxalate and stereoselective sulfoxide mediated reduction of the resulting β-ketosulfoxide, was used to prepare enantiomerically pure syn and anti 1,2-diols. This method was applied to the enantioselective synthesis of two acetogenin derivatives, (−)-( R,R )-muricatacin and its epimer (−)-( R,S )-epi-muricatacin.

Stereoselective synthesis towards the C8–C18 subunit of pamamycin-607 induced by a chiral sulfoxide group

Abstract A close precursor of the C8–C18 subunit of pamamycin-607 was prepared by asymmetric synthesis from ethyl butyryl acetate via a chiral β,δ-diketosulfoxide.

Wang p-alkoxyphenylsulfoxide as a new linker and Pummerer cleavage strategy in solid-phase preparation of 1,2-diols

Abstract para -Hydroxyphenyl-β-ketosulfide was attached to a Wang resin and oxidised to the corresponding sulfoxide with a N -protonated oxaziridinium trifluoroacetate. Reduction of the β-ketosulfoxides to the corresponding β-hydroxysulfoxides with Dibal-H was shown to be as stereoselective as in solution. Finally it was shown that the Pummerer reaction could be carried out on solid-phase and was a very efficient way to obtain diols that validates the sulfoxide group as a versatile linker for solid-phase chemistry.

Stereoselective sulfoxide directed reduction of 1,2-diketo-derivatives to enantiomerically pure syn and anti 1,2-diols. Correction of the relative configuration by X-ray and chemical correlation to goniobutenolides A and B

Abstract In our recent report on the enantioselective synthesis of syn and anti 1,2-diols from oxalyl-di-(N-methyl-N-methoxyamide), an unfortunate sample inversion for 13 C NMR analysis led us to an incorrect attribution of their relative configurations. We report now the correction of the configurations of these diols by X-ray analysis and chemical correlation to two known natural products, goniobutenolides A and B.

Stereoselective sulfoxide directed reduction of 1,2-diketo-derivatives to enantiomerically pure syn and anti 1,2-diols

Abstract A new route to enantiopure syn and anti 1,2-diols is described from oxalyl-di-(N-methyl-N-methoxyamide) via the corresponding β-ketosulfoxide. This is the first report of the stereoselective reduction of a γ-keto-β-hydroxysulfoxide.

Diastereodivergent synthesis of the C8–C18 precursor and C1′–C11′ subunit of pamamycin 607 induced by a chiral sulfoxide group

A key step in obtaining the C8–C18 and C1′–C11′ fragments of pamamycin 607, which differ by the syn- and anti-configuration of one chiral center α to the tetrahydrofuran ring, was the chelation controlled E–Z-isomerization of the substituted vinyl tetrahydrofuran intermediate 3a which has so far been obtained only in the more stable E-configuration.

Hemisynthesis of two marine cheilanthane sesterterpenes from (−)-sclareol: First enantioselective synthesis of petrosaspongiolide R

The synthesis of two marine sponge metabolites 5 and 8 from naturally occurring (−)-sclareol is described here. The sesterterpenolide (5) is synthetised for the first time, establishing the absolute configuration of this compound. The key intermediate, aldehyde (10), was obtained from (−)-sclareol in good overall yields. The use of Katsumuras Wittig reagent and subsequent photochemical oxidation delivered the sesterterpenolide (8), which was chemoselectively epoxidized on exocyclic terminal olefin using the oxaziridinium salt (14) and transformed in four steps to carboxylic acid (5).

New insights into the reduction of β,δ-diketo-sulfoxides

Abstract New developments in the reduction of β,δ-diketo-sulfoxides, a reaction that affords important key intermediates for total synthesis, are described. We showed without ambiguity using NMR experiments, that the β-carbonyl group is totally enolised. This result is inconsistent with the previous hypothesis, which supposed the other tautomer (enolisation at the δ-position) as the major one. We propose a rationale to explain the side reactions occurring during the reduction of unprotected β,δ-diketo-sulfoxides and showed that judicious protection of the δ-carbonyl group gave all diastereoisomers of β-hydroxy-δ-ketosulfoxides.

Hemisynthesis of new labdane derivatives from (−)-sclareol

A straightforward and very simple access to different analogues of (+)-subersic acid 7, the unnatural enantiomer (compounds 12) from naturally occurring (−)-sclareol 1 is described. We also report new conditions for the preparation of keto-intermediate 8 using maleic acid and describe hemiketal 11 as the new intermediate of degradative oxidation of 1.

Regio- and diastereoselection in the oxaziridinium salt oxidation of acyclic allylic acetates

Abstract Oxaziridinium salt 1 is a versatile oxygen transfer agent towards olefins. An important threo selectivity is observed with acyclic allylic acetates due to 1,3-allylic strain (A 1,3 ). The π-facial selectivity in the epoxide formation is interpretated as a consequence of an interaction between the residual positive charge on nitrogen and the neighbouring acetate in the transition state. Such an interaction is not strong enough to balance the lowered nucleophilicity of the 2,3 double bond in the geraniol acetate 3a .