Dithianes, unsymmetrical bisalkylation

Tietze and coworkers found a symmetrical bisalkylation of a silyl dithiane with 2 equivalents of an epoxide involving 1,4-silyl migrations369. Smith and Boldi applied the method to the unsymmetrical bisalkylation of silyldithiane 233 (equation 150)368. 

The syntheses of the C1-C12 AB and C13-C28 CD segments, 528 and 535, are summarized in Scheme 75. The syntheses of the two segments are based on a one-pot unsymmetric bisalkylation of 2-TBS-l,3-dithiane (525) with Brook rearrangement. Epoxides 521, 522, 523, and 524 were synthesized as coupling partners. 

The unsymmetric bisalkylation of the dithiane 525 with epoxides 522 and 521 was efficiently carried out in one pot to give 526. Deprotection of TES and ace-tonide followed by tosylation gave triol 527, which was subjected to acetoniza-tion, dethioacetalization, intramolecular hemiketalization, and iodination to give B ring 528. 

The synthesis of the CD segment 532 also started with dithiane 525. One-pot unsymmetric bisalkylation of 525 with 523 and 524 also effectively afforded coupling product 529, after methylation. Deprotection of TBS and acetonide followed by dethioketalization afforded a 2 1 mixture of 530 and 531. Treatment of 530 with HCIO4 effected epimerization to 531. Functional group manipulation converted 531 to iodide 532, which was coupled with thioacetal 533, prepared by Roush asymmetric crotylboration, to give adduct 534. The thioketal 534 was converted into 535 via reduction of ketone (dr = 1 3.5) and introduction of a phenyl-sulfone group. 

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