Michael addition to a chiral non-racemic 2-phosphono-2,3-didehydrothiolane S-oxide

The Michael addition of selected sulfur and nitrogen nucleophiles to a chiral non-racemic 2-phosphono-2,3-didehydrothiolane S-oxide is fully diastereoselective. The enantiomeric excesses of the adducts obtained could be determined by 31P NMR spectroscopy using (R)-(+)-tert-butyl(phenyl)phosphinothioic acid as a chiral solvating agent. The addition of thiophenol was monitored by 31P NMR spectroscopy which made it possible to observe the formation and evolution of the kinetic and thermodynamic adducts in the reaction mixture. The structures of both enantiomeric thiophenol adducts have been determined by X-ray analysis.

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(+)-2-[2′-(5,5-Dimethyl-1,3,2-dioxaphosphorinano]-2,3-didehydrothiolane 1-oxideC9H15O4PSEe >90%[α]D = +77.0 (c 0.55, acetone)Source of chirality: asymmetric oxidation with (+)-(2S, 8aR)-8,8-dichloro-camphorsulfonyloxaziridineAbsolute configuration: (S)

3-Phenylsulfanyl-2-[2′-(5,5-dimethyl-1,3,2dioxaphosphorinanyl)]thiolane 1-oxideC15H21PO4S2Ee = 68%[α]D = +13.2 (c 0.25, acetone)Source of chirality: diastereoselective addition to a non-racemic substrateAbsolute configuration: (1SS,2R,3R)

3-Phenylsulfanyl-2-[2′-(5,5-dimethyl-1,3,2dioxaphosphorinanyl)]thiolane 1-oxideC15H21PO4S2Ee >90%[α]D = +19.5 (c 1.0, acetone)Source of chirality: diastereoselective addition to an enantiopure substrateAbsolute configuration: (1SS,2R,3R)

3-Phenylsulfanyl-2-[2′-(5,5-dimethyl-1,3,2dioxaphosphorinanyl)]thiolane 1-oxideC15H21PO4S2Ee >90%[α]D = −19.1 (c 1.1, acetone)Source of chirality: diastereoselective addition to an enantiopure substrateAbsolute configuration: (1RS,2S,3S)

3-p-Tolylsulfanyl-2-[2′-(5,5-dimethyl-1,3,2 dioxaphosphorinanyl)]thiolane 1-oxideC16H24PO4S2Ee = 70%[α]D = +16.5 (c 1.0, acetone)Source of chirality: diastereoselective addition to a non-racemic substrateAbsolute configuration: (1SS,2R,3R)

3-tert-Butylsulfanyl-2-[2′-(5,5-dimethyl-1,3,2-dioxaphosphorinanyl)]thiolane 1-oxideC13H26PO4S2Ee = 60%[α]D = +8.5 (c 1.4, acetone)Source of chirality: diastereoselective addition to a non-racemic substrateAbsolute configuration: (1SS,2R,3R)

Phenylamino-2-[2′-(5,5-dimethyl-1,3,2-dioxaphosphorinanyl)]thiolane 1-oxideC15H23PO4NSEe = 70%[α]D = +30.0 (c 0.5, CHCl3)Source of chirality: diastereoselective addition to a non-racemic substrateAbsolute configuration: (1SS,2R,3R)