Electrophile-initiated cyclizations of enantiopure homoallylic amines is a straightforward strategy to synthesize nitrogen heterocycles. In this work, our approach relies on the substrate with stereogenic carbon adjacent to the amine to direct a newly formed stereogenic center proceeding through a half-chair transition state. The requisite homoallylic amines were readily prepared by an indium-mediated allylation of and Ellman N-tert-butanesulfinyl imine. The chiral, non-racemic homoallylic N-tert-butanesulfinamide is then acylated with BOC anhydride in order to synthesize tert-butylcarbamates. Upon a screening of solvents, it was found that tetrahydrofuran was the best solvent for halosuccinimides and derivatives such as saccharin and hydantoin. Dichloromethane performed better for the molecular halogen electrophiles. The reactions tended to produce a single diastereomer as confirmed by both NMR and TLC. J-coupling analysis indicated the diastereomer had the C2 aromatic group and the C4 electrophile methylene group were trans to one another, which was later confirmed by X-ray crystallography. In another set of experiments, a guanidine moiety was installed on the free base of the homoallylic amine. Again, tetrahydrofuran was the optimal solvent for both Cbz-protected and Boc-protected with halosuccinimides and derivatives. Without the sulfonyl group protecting the nitrogen, the spectroscopic and crystallographic data showed the C2 aromatic group and the C4 electrophile methylene group were now cis to one another. We are currently investigating chalcone substrates as a means to activate the double bond.

Asymmetric synthesis of heterocycles via electrophile initiated cyclization of enantioenriched homoallylic N-tert-butanesulfonyl carbamates and bis-boc guanidines

ACS Spring Meeting 2021

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