Stereoselective Coupling of N-tert-Butanesulfinyl Aldimines and β-Keto Acids: Access to β-Amino Ketones

Abstract

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.

Enantioselective Synthesis, DFT Calculations, and Preliminary Antineoplastic Activity of Dibenzo 1-Azaspiro[4.5]decanes on Drug-Resistant Leukemias

“…NMR Spectra were recorded at 300 or 400 MHz for 1 H NMR and or 100 MHz for 13 C NMR, using CDCl 3 and CD 3 OD as the solvents, and TMS as internal standard (0.00 ppm). 19 Found 438.0563. 1R)-1-(2-Bromobenzyl)-N-(tert-butanesulfinyl)-1,2,3,4-tetrahydronaphthalen-1…”

“…Supporting Information. Copies of 1 H, 13 C NMR and DEPT spectra for all the reported compounds, 19 F NMR for compound R S )-6g, X-ray structure of compound (R S )-6h ( Figure S1), as well as computational methods, transitions structures, energy values, energy profiles, NCI calculations and cartesian coordinates. Just Accepted "Just Accepted" manuscripts have been peer-reviewed and accepted for publication.…”

Applications oftert-butanesulfinamide in the synthesis of N-heterocyclesviasulfinimines

“…In 2018, the utility of N-tert-butanesulnyl aldimines as chiral imines in decarboxylative Mannich reactions was investigated to synthesise b-amino ketones with good diastereocontrol and yields. 27 Importantly, they proposed an 8-membered cyclic transition state to explain the observed stereoselection. Further, the methodology was applied in synthesising the piperidine based alkaloid (À)-pelletierine.…”

Enantiodivergent Approach to the Synthesis of Cis-2,6-Disubstituted Piperidin-4-ones

“…Due to that, new general, simple and efficient methods to prepare cis-2,6-disubstituted piperidin-4-ones in an enantioselective fashion are highly desirable. For that reason, we envisaged a new strategy in which a sequential decarboxylative Mannich reaction of a chiral N-tert-butanesulfinyl imine and a β-keto acid, 7 followed by an organocatalyzed intramolecular Mannich reaction involving an aldehyde 8 would produce the substituted piperidines in a straightforward manner, comprising this methodology three synthetic operations (imine formation and two consecutive Mannich reactions) from readily available starting materials (Scheme 1C).…”