PROXIMALLY FUNCTIONALIZED CAVITANDS AND SYNTHESIS OF A FLEXIBLE HEMICARCERAND

A general study on the synthesis of partly bridged octols 3a-d and 4c- d is described. Tri-bridged diol 3c can be prepared in 54% yield in DM SO at 70 degrees C with excess CH2BrCl or in 52% yield in DMF at 70 de grees C with only 4 equiv, of CH2BrCl. 1,3-Di-bridged tetrol 4a, one o f the two possible di-bridged isomers formed in preference to the othe r, was obtained in 30% yield. Tri-bridged diols 3c and d can be select ively debrominated in one step by treatment with 5 equiv. of n-BuLi in THF to afford the corresponding dibromo derivatives 8a and b in 77% a nd 76% yields, respectively. After incorporation of the fourth bridge, the remaining two bromines can be replaced by C(O)OMe to give 9c (60% ), by OH to give 9d (62%) or by CN to give 9f (> 95%). When the lithia ted derivatives of 3c and d are quenched with electrophiles other than H+, a selectively functionalized tri-bridged diol with hydroxyl (8c, 47%) and selectively functionalized cavitands with thiomethyl (9g, 25% ) or iodo (9h, 20%) groups can be synthesized. Two molecules of 9d wer e coupled with CH2BrCl in DMSO/THF under high dilution conditions to g ive the flexible hemicarcerand 10 in 71% yield.