SC-1997-701-酯交换制备环亚硫酸酯.pdfVIP

SYNTHETIC COMMUNICATIONS, 27(4), 701-707 (1997) PREPARATION OF CYCLIC SULFITES BY TRANSESTERIFICATION OF DIOLS AND DIISOPROPYL SULFITE Steven A. King,* Brenda Pipik,* David A. Conlon and M. Bhupathy Department of Process Resear, Merck Research Laboratories R80Y-355, P.O.Box 2000, Rahway, NJ 07065-0900,USA Abstract: Cyclic Sulfites of 1.2-, 1,3- and 14-diols canbe prepared in high yield by acid or base catalyzed transesterificationwith diisopropyl sulfite. Cyclic sulfites of 1.2- and 1.3- diols have seen increasing use in organic chemistry.* This moiety, together with the derived cyclic sulfate, allows selective monofunctionalization by a nucleophile. Recently, we encountered the diol 1 which we wanted to convert to the cyclic sulfite 2 en route to the thiol-acid side chain 3 of the LTD4 antagonist MK-476.2 Typical procedures employing thionyl chloride and base led to production of a complicated mixture of 2 and the byproducts 4 and 5. Although, it was clear that the dimer was thermodynamically disfavored, all attempts to eliminate 4 at high dilution failed. We conjectured that the highly reactive3 sulfonyl chloride intermediate 6 must be responsible for the kinetic dimerization. We thought that it should be possible to prepare 2 by acid or base catalyzed transesterification of diol 1with a simple sulfite diester (eq. I ) . ~ In this approach, 5would not be formed due to the absence of chloride; the highly reactive 6 would also be avoided. Copyright O 1997 by Marcel Dekker, Inc. 702 KING ETAL. Nal x DMF Our initial work using 1mol% methanesulfonic acid as catalyst in toluene showed that the reaction (eq. 1) was viable and