The reaction of chiral N-tert-butanesulfinyl aldimines with β-keto acids under basic conditions at room temperature proceeds with high levels of diastereocontrol, leading to β-amino ketones in high yields. Based on DFT calculations, an eight-membered cyclic transition state involving coordination of the lithium atom to the oxygens of carboxylate and sulfinyl units was proposed, being in agreement with the observed experimental diastereomeric ratios. The synthesis of the piperidine alkaloid (-)-pelletierine was successfully undertaken in order to demonstrate the utility of this methodology.
Enantiopure β-amino ketone derivatives were synthesized by decarboxylative Mannich reaction of chiral N-tert-butanesulfinyl imines with β-keto acids, and were subsequently transformed into cis-2,6-disubstituted piperidin-4-ones through an organocatalyzed condensation with aldehydes. Both enantiomers were accessible from the same precursors by inverting the order in the reaction sequence of the aldehydes involved in the imine formation and the intramolecular Mannich condensation. The synthesis of the piperidine alkaloids (+)-241D, (−)-epimyrtine and (−)lasubine II demonstrated the utility of this methodology.
The total synthesis of (+)-C(9a)-epiepiquinamide has been achieved starting from ethyl 5-bromopentanoate, (R S)-tert-butanesulfinamide, nitromethane, ethyl acrylate and acetic anhydride. The diastereoselective coupling of ethyl 4-nitrobutanoate and a chiral N-tert-butanesulfinyl imine, along with a double cyclization involving a primary amine through an intramolecular N-alkylation and lactam formation, are key steps of this synthesis.
The reaction of epoxides with tert‐butanesulfinamide in the presence of a Lewis acid, such as erbium triflate or boron trifluoride–diethyl ether, in THF as solvent, under microwave or thermal activation, produces N‐tert‐butylsulfinylimines in reasonable yields. Aromatic and gem‐disubstituted and trisubstituted alkyl epoxides performed better than mono‐alkyl‐substituted compounds. After imine formation, a subsequent indium‐promoted allylation can be carried out in the same reaction flask in a single synthetic operation leading to homoallylamine derivatives with generally high yields.
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