Asymmetric catalytic epoxide ring -opening reactions: Synthesis of highly enantiomerically enriched terminal aziridines, O-(2-hydroxyalkyl)oxime ethers, 1,2-aminooxy alcohols

I. General catalytic synthesis of highly enantiomerically enriched terminal aziridines. Asymmetric synthesis of N-Ns- and N-SES-protected terminal aziridines was achieved by an indirect kinetic resolution process. Low selectivity in the [(salen)Co]-catalyzed kinetic resolution of terminal epoxides with N-Boc sulfonamides was parlayed into an efficient one-pot synthesis of enantiopure amino alcohol derivatives by hydrolytic kinetic resolution (HKR) followed by ring-opening of the "mismatched", unreacted enantiomer of the epoxide by a sulfonamide derivative promoted by the same catalyst. The resulting amino alcohols were converted to terminal aziridines by Boc-deprotection/mesylation/cyclization. A variety of terminal aziridines were thus synthesized in 58--86% overall yield and 98.8->99% ee (13 examples). Enantiopure N-Ns- and N-SES-chloromethylaziridine were synthesized for the first time and were used in the synthesis of other enantiopure terminal aziridines and in a three step route to 3-aminotetrahydroquinoline. The mechanism of the reaction between terminal epoxides and N-Boc sulfonamide catalyzed by [(salen)Co] was investigated using a range of kinetic techniques. A distinctive mechanism involving nucleophile activation by catalyst and epoxide activation by the nucleophile is proposed.;II. Asymmetric catalytic synthesis of O-(2-Hydroxyalkyl)oxime ethers and 1,2-aminooxy alcohols. A highly enantioselective route to O-(2-hydroxyalkyl)oxime ethers and 1,2-aminooxy alcohols was developed using an oligomeric [(salen)Co] catalyst. Kinetic resolution of terminal racemic epoxides was achieved with arylaldoximes, ketoximes, and hydroxylamine derivatives as nucleophilic partners. The desired oxime ethers and 1,2-aminooxy alcohols were synthesized in 90--100% yield and 98--99.8% ee (12 examples). Alkylaldoxime ether derivatives were not accessible by this route, but they could be prepared efficiently from the corresponding N-Boc-protected aminooxy alcohols.