合成路线1

Chiral cyclopropanesulfonyl chloride intermediate (VIII) can be prepared as follows. Lithiation of (trimethylsilyl)acetylene (XVII) with t-BuLi in THF at –78 °C, and subsequent coupling with TBDMS-protected (S)-glycidol (XVIII) in the presence of BF3·Et2O at –78 °C affords the (S)-pentynol derivative (XIX). Then, the TMS-protecting group of intermediate (XIX) is selectively removed by means of K2CO3 in MeOH to give alkyne (XX). Iodoboration of alkyne (XX) with B-I-9-BBN in CH2Cl2 at 0 °C followed by deborination with AcOH yields 4-iodo-4-pentene-1,2(S)-diol (XXI). O-Protection of diol (XXI) with TBDMSOTf and pyridine in THF provides the bis-silyl ether (XXII), which is then submitted to Simmons-Smith cyclopropanation with CH2I2 in the presence of Et2Zn and TFA in DCE to produce 1,2-O-bis-TBDMS-3-(1-iodocyclopropyl)propane-1,2(S)-diol (XXIII). Desilylation of compound (XXIII) using HCl in THF gives 3-(1-iodocyclopropyl)propane-1,2(S)-diol (XXIV), which by trans-ketalization with 2,2-dimethoxypropane (XXV) by means of PPTS in CH2Cl2 gives 4(S)-(1-iodocyclopropylmethyl)-2,2-dimethyl-1,3-dioxolane (XXVI). Finally, alkyl iodide (XXVI) is treated with t-BuLi in Et2O at –78 °C, followed by chlorosulfonation with SO2Cl2 in Et2O (3).
Alternatively, deprotonation of dicyclopropyl disulfide (XXVII) with BuLi in THF, followed by alkylation with 4(R)-(bromomethyl)-2,2-dimethyl-1,3-dioxolane (XXVIII) at –78 °C affords the dimeric bis-acetonide (XXIX), which is reductively cleaved to the corresponding thiol monomer (XXX) by treatment with PPh3 and HCl in dioxane/H2O. Air oxidation of cyclopropanethiol derivative (XXX) in the presence of NaOH in DMF gives sodium cyclopropanesulfonate derivative (XXXI), which can also be obtained by direct oxidation of disulfide (XXIX) with H2O2 and NaOAc in AcOH at 80 °C. Finally, sulfonate (XXXI) is chlorinated using POCl3 at 80 °C. Alternatively, sulfonyl chloride (VIII) can be directly obtained from disulfide (XXIX) by oxidative cleavage with NCS in the presence of HCl in MeCN .