The asymmetric synthesis of terminal aziridines by methylene transfer from sulfonium ylides to imines.

A new ylide-based protocol for the asymmetric aziridination of imines via methylene transfer has been developed involving the use of a simple chiral sulfonium salt and an organic strong base. A systematic study identified triisopropylphenyl sulfonylimines as optimal substrates for the process. Unexpectedly, hindered C2-symmetric sulfonyl salts incorporating bulky ethers at C-2 and C-5--which had previously been useful in the corresponding epoxidation chemistry--decomposed in these aziridination reactions via competing elimination pathways. Under optimised conditions it was found that a simple salt derived from (2R,5R)-2,5-diisopropyl thiolane could mediate asymmetric methylene transfer to a range of imines with uniformly excellent yields with 19-30% ee. Since this is a similar level of enantiomeric excess to that obtained using these same salts in epoxidation chemistry, it was concluded that if more bulky sulfonium salts could be devised which were resistant to decomposition under the reaction conditions, that highly enantioselective aziridine formation by methylene transfer would be possible.

Highly enantioselective ylide-mediated synthesis of terminal epoxides.

The highly efficient asymmetric epoxidation of aldehydes by methylene transfer is now possible using new sulfonium salts.

Catalytic (asymmetric) methylene transfer to aldehydes.

An investigation into the poor activity of sulfides as catalysts for sulfonium-ylide-mediated methylene transfer to aldehydes has indicated that ylide formation is the problematic catalytic cycle step. Alkylation with traditional electrophiles does not proceed with sufficient efficiency to allow the sulfide to be used catalytically. Methyl triflate rapidly alkylates cyclic thiolanes under mild conditions, allowing their use in efficient aldehyde epoxidation reactions (in conjunction with phosphazene bases) at loadings as low as 10 mol %.

Urea derivatives are highly active catalysts for the base-mediated generation of terminal epoxides from aldehydes and trimethylsulfonium iodide.

N,N'-Diarylureas have been shown to efficiently catalyse sulfonium ylide-mediated aldehyde epoxidation reactions for the first time. These processes are of broad scope and can be coupled with a subsequent Cu(II) ion-catalysed Meinwald rearrangement to give an efficient and convenient protocol for aldehyde homologation without intermediate purification.