Proximally functionalized cavitands and synthesis of a flexible hemicarcerand

A general study on the synthesis of partly bridged octols3a-d and4c-d is described. Tri-bridged diol3c can be prepared in 54% yield in DMSO at 70°C with excess CH₂BrCl or in 52% yield in DMF at 70°C with only 4 equiv. of CH₂BrCl. 1,3-Di-bridged tetrol4a, one of the two possible di-bridged isomers formed in preference to the other, was obtained in 30% yield. Tri-bridged diols3c andd can be selectively debrominated in one step by treatment with 5 equiv. ofn-BuLi in THF to afford the corresponding dibromo derivatives8a andb in 77% and 76% yields, respectively. After incorporation of the fourth bridge, the remaining two bromines can be replaced by C(O)OMe to give9c (60%), by OH to give9d (62%) or by CN to give9f (>95%). When the lithiated derivatives of3c andd are quenched with electrophiles other thanH⁺, 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 of9d were coupled with CH₂BrCl in DMSO/THF under high dilution conditions to give the flexible hemicarcerand10 in 71% yield.Supplementary Data. A list of observed and calculated structure factors have been deposited with the British Document Supply Centre as Supplementary Publication No. SUP 82170 (50 pages)This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.