E. R. De Waard

Chlorination of α-sulfonyl carbanions with hexachloroethane: A novel preparation of α-halosulfones

Abstract The cyclic sulfones 1 , 2 , and 3 are lithiated in benzene with n-butyllithium. Lithiation is demonstrated to lead to α-mono, α,α′-di and/or α,α-di and α,α,α′ trimetallation. The lithiated sulfones are chlorinated with hexachloroethane (HCE). Some mechanistic aspects of the reaction of the lithiosulfones with vicinal dihalides are discussed.

The michael induced ramberg-bäcklund homologation to conjugated isoprenoids

Abstract Treatment of the sulfones 1 or 2 with sodium phenylsulfinate in DMSO affords the head-to-tail coupled conjugated monoterpenoids 5–8 in comparable amounts. The corresponding reaction of 3 gives the isomers 16 and 17 . The tail-to-tail homologation of 4 furnishes chiefly a 2 E ,4 E/Z -mixture of the conjugated isoprenoids 18 and 19 . The various isoprenoid mixtures are separated into their components and the configuration of the isomers is established by 1 H NMR double resonance and the NMR/NOE technique. The head-to-tail and tail-to-tail coupled isoprenoid mixtures 5–8 and 18–21 , respectively, are isomerized to 2 E/Z , 4 E -mixtures in a 2:1 ratio. The C 15 -sulfones 11 and 13 are obtained by treatment of 1 with the head-functionalized isoprene synthon 10 . Some speculations on the stereochemical course of the MIRB-homologation are presented.

Isoprenoid homologation: A synthesis of isoprenoid alcohols using terpene building blocks

Abstract This paper describes the synthesis of linalool and nerolidol by means of a regioselective coupling of the hydroxy-sulfoxide 6a with prenyl-and geranylbromide, followed by reductive desulfurization.

Configurational inversion and hexachloroethane chlorination of α-sulfonylcarbanions☆

Abstract The cis fused bicyclic sulfones 1a, 1c and 3a are lithiated in benzene with n-butyllithium under concomitant cis/trans isomerization of the ring fusion, involving intramolecular proton transfer. H/D exchange of the three α-hydrogens in protic solvents proceeds with retention of configuration. The lithiated sulfones are chlorinated with hexachloroethane (HCE) and show a strong preference for introduction of halogen at an equatorial α-position.

Isoprene functionalization : Hydroxy sulfone terpene building blocks by ring opening of cyclic alkoxy oxosulfonium intermediates

Abstract Hydroxy sulfoxide 1 reacts with SO 2 Cl 2 to give the (Z)-C 5 terpene building block 3b via cyclic alkoxy oxosulfonium salt 2 . The conversion of 1 via the corresponding sulfone 4 leads to the (E) isomer 6b . An explanation is offered for the stereoselective course of the reactions.

A saturated asymmetric isoprene synthon : Synthesis, resolution and absolute configuration

Abstract The unknown racemic 3-methyl-4-phenylsulfonylbutanoic acid (4) is synthesized by standard procedures. The acid is resolved into its enantiomers by alternating treatment with l- and d-ephedrine. The S-(+)-acid 4 is converted into R-(+)-dihydrocitronellol (7) in order to determine the absolute configuration and to illustrate its use as a saturated isoprene building block in isoprenoid homologation.

Base induced rearrangements of α-halosulfones α-sulfonyl carbanions with bridgehead electrofugal centre☆

Abstract The KOtBu-induced Ramberg-Backlund reaction of the trans bicyclic halosulfones 1 and 2 is studied in DME and DMSO. Strong indications are obtained that the reaction proceeds via the intermediate Z-episulfone with retention-inversion (involving exo-S-geometry). 1 Base induced epimerization at the nucleofugal centre (from axial to equatorial halogen) is demonstrated in DMSO.

An effective [1,4]-charge affinity inversion of sulfur functionalized isoprenes

Consecutive [1,2]- and [1,3]-migrations of the sulfur functionality convert the hydroxysulfoxide terpene building block 1a into the charge affinity inverted synthon 6 or the desulfurized chloro aldehyde 9a.

Model Studies of the Thymidylate Synthase Reaction. Design of Mechanism-Based Potential Inhibitors of DNA Biosynthesis

The enzyme thymidylate synthase (TS) mediates the conversion of dUMP to dTMP which is utilized in the biosynthesis of DNA. The methyl group transferred to the dUMP substrate in this reaction is provided by the cofactor 5,10-methylenetetrahydrofolate (5,10-CH2-H4-folate) in a multi-step process. The proposed mechanism of the transformation is outlined in scheme I 1.