A REMARKABLE EFFECT OF C-O-C BOND-ANGLE STRAIN ON THE REGIOSELECTIVE DOUBLE NUCLEOPHILIC-SUBSTITUTION OF THE ACETAL GROUP OF TETRAACETAL TETRAOXA-CAGES AND A NOVEL HYDRIDE REARRANGEMENT OF TETRAOXA-CAGES

A remarkable effect of C-O-C bond angle strain on the regioselective d ouble nucleophilic substitution of the acetal group of tetraacetal tet raoxa-cages and a novel regioselective and stereoselective hydride rea rrangement of tetraoxa-cages are reported. Reaction of the tetraacetal tetraoxa-cages 1 with 3 equiv of triethylsilane (at -78 degrees C), c yanotrimethylsilane (at 25 degrees C), and allyltrimethylsilane (at -7 8 degrees C) in dichloromethane in the presence of TiCl4 gave the doub le nucleophilic substitution products 2, 6, and 7 in 85-90% yields, re spectively. No detectable amount of other regioisomers was obtained. R eaction of 1a with (methylthio)trimethylsilane and (phenylthio)trimeth ylsilane in dichloromethane in the presence of TiCl4 at -78 degrees C gave the symmetric products 10a,b and the unsymmetric products 11a,b i n ratios of 8-10:1. The stereochemistry of the symmetric substitution products was proven by X-ray analysis of the crystalline compound 10a. The mechanism of the double nucleophilic substitution of the tetraoxa -cages 1 are discussed. Treatment of the tetraoxa-cages 1a,c and 22a-c with 2 equiv of TiCl4 or MeSO3H in dichloromethane at 25 degrees C fo r 3 h regioselectively and stereoselectively gave the novel hydride re arrangement products 16a,b and 23a-c respectively. No detectable amoun t of other regioisomers was observed. The stereochemistry of the hydri de rearrangement was proven by DIBAL-H reduction of 16 and 23 and X-ra y analysis of the reduction product 24a. We attribute the high regiose lectivity of the double nucleophilic substitution and the hydride rear rangement of the tetraoxa-cages 1 to the bond angle strain of the unus ually large bond angle of C(3)-O(4)-C(5) of the tetraoxa-cages.