Reaction Steps
A solution of chlorosulfonylisocyanate (4.36 ml, 0.05 mol) in benzene (15 mL) was placed into a three necked flask, equipped with a thermometer, a droping funnel and a reflux condenser under a nitrogen atmosphere. The flask was immersed in a water bath. A solution of methanol (2.02 mL, 0.05 mmol) in 3 ml of benzene was added dropwise such that the temperature was maintained in a range of 25-30° C. After complete addition, the mixture was stirred for an additional 30 minutes and allowed to cool to 0-5° C. Hexane (15 mL) was added to the reaction mixture with cooling in an ice bath for 5 minutes. The fine white precepitate was collected by filtration, washed with hexane and dried to afford 8.00 g (92.2%) of the chlorosulfane derivative. A solution of ascomycin (791 mg, 1 methanol (Bundy, G. L. and Peterson. D. C. Tetrahedron Lett., 1978, 41), acetic acid: water (3:1) (Corey, E. J. and Varma. R. K. J. Am. Chem. Soc., 1971, 93, 7319), Dowex 50W-X8 in methanol (Corey, E. I., Ponder, J. W. and Ulrich, P. Tetrahedron Lett., 1980, 21, 137), boron trifluoride etherate in chloroform (Kelly, D. R., Roberts, M. S. and Newton, R. F. Synth. Commun. 1979, 9, 295), methanolic hydrogen fluoride (Hanessian, S. and Lavallee, P. Can. J. Chem., 1975, 53, 2975; ibid., 1977, 5, 562), and pyridinuim fluoride in tetrahydrofuran (Nicolaou, K. C.. Seitz, S. P., Pavia, M. R. and Petasis, N. A. J: Org. Chem., 1979, 44. 4011); pyridinium p-toluenesulfonate in ethanol (Prakash, C., Salch, S. and Blair, I. A. Tetrahedron Lett., 1989, 30, 19); N-bromosuccinimide in dimethylsulfoxide (Batten, R. J., Dixon, A. J., Taylor, R. J. K. and Newton, R. F. Synthesis, 1980, 234 ); or Tetraethyldiboroxane in the presence of catalytic amounts of trimethylsilyl triflate (Dahlhoff, W. V. and Taba, K. M. Synthesis, 1986, 561) and the like.
