The synthesis of diacetal trioxa-cage compounds via a sequential cyclization reaction of norbornene derivatives induced by electrophiles in a short sequence is reported. Treatment of the norbornene derivatives 2a-d and 10b with I 2 in aqueous THF in the presence of KI at 25 °C regioselectively gave the iodo-cage compounds 3a-d and 11 in 80-90% yields, respectively, via a iodine-induced sequential cyclization reaction. No detectable amount of other regioisomers or monocyclization products was obtained. The synthesis of trioxa-cages 14a-e was accomplished from 3a-d and 11 in a two-step sequence. Treatment of diacylnorbornenes 15a-f with I 2 in aqueous THF at 25 °C regioselectively and stereoselectively gave the sequential cyclization products 16a-f, respectively, which were converted in one step to the diacetal trioxa-cages 24a-f in high yields. The structure of these trioxa-cages was proven by X-ray analysis of the crystalline compound 14e. Other electrophiles, such as bromine, m-CPBA, and Hg(OAc) 2 , were also found to be effective for the sequential cyclization reaction. Oxymercuration of 15a-f and 2a-c with Hg(OAc) 2 in aqueous THF followed by reduction with NaBH 4 at 25 °C gave compounds 28a-f and 30b,d,c in high yields, respectively.

No abstract

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 regioselective and stereoselective hydride rearrangement of tetraoxa-cages are reported. Reaction of the tetraacetal tetraoxa-cages 1 with 3 equiv of triethylsilane (at -78 degrees C), cyanotrimethylsilane (at 25 degrees C), and allyltrimethylsilane (at -78 degrees C) in dichloromethane in the presence of TiCl(4) gave the double nucleophilic substitution products 2, 6, and 7 in 85-90% yields, respectively. No detectable amount of other regioisomers was obtained. Reaction of 1a with (methylthio)trimethylsilane and (phenylthio)trimethylsilane in dichloromethane in the presence of TiCl(4) at -78 degrees C gave the symmetric products 10a,b and the unsymmetric products 11a,b in 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 TiCl(4) or MeSO(3)H in dichloromethane at 25 degrees C for 3 h regioselectively and stereoselectively gave the novel hydride rearrangement products 16a,b and 23a-c respectively. No detectable amount of other regioisomers was observed. The stereochemistry of the hydride rearrangement was proven by DIBAL-H reduction of 16 and 23 and X-ray analysis of the reduction product 24a. We attribute the high regioselectivity of the double nucleophilic substitution and the hydride rearrangement of the tetraoxa-cages 1 to the bond angle strain of the unusually large bond angle of C(3)-O(4)-C(5) of the tetraoxa-cages.

No abstract

No abstract