Short enantioselective synthesis of sedridines, ethylnorlobelols and coniine via reagent-based differentiation

The preparation of collections of structurally diverse small molecules is a useful tool for studying biology and medicine with chemistry. Herein, we demonstrate the versatility of the pure enantiomers of 2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl ester to prepare the biological active alkaloids sedridine, allosedridine, methylsedridine, methylallosedridine, ethylnorlobelol, and coniine in two steps and in a stereoselective way via a reagent-based differentiation. The described syntheses are a demonstration of the versatility of 2-(2-oxo-ethyl)-piperidine-1-carboxylic acid tert-butyl esters as chiral building blocks.

Figure optionsDownload as PowerPoint slide

(−)-2-(2-Hydroxy-propyl)-piperidine-1-carboxylic acid tert-butyl esterC13H25NO3[α]D = −38.9 (c 1, CHCl3)Ee = 94%Absolute configuration: 2S,2′S

(−)-2-(2-Hydroxy-propyl)-piperidine-1-carboxylic acid tert-butyl esterC13H25NO3[α]D = +34.7 (c 1, CHCl3)Ee = 89%Absolute configuration: 2R,2′R

(−)-2-(2-Hydroxy-propyl)-piperidine-1-carboxylic acid tert-butyl esterC13H25NO3[α]D = −60.2 (c 1.03, CHCl3)Ee = 95%Absolute configuration: 2S,2′R

(+)-2-(2-Hydroxy-propyl)-piperidine-1-carboxylic acid tert-butyl esterC13H25NO3[α]D = +56 (c 1.15, CHCl3)Ee = 85%Absolute configuration: 2R,2′S

(+)-N-MethylsedridineC9H19NO[α]D = +34.5 (c 0.85, EtOH)Ee = 85%Absolute configuration: 2R,2′R

(+)-N-MethylallosedridineC9H19NO[α]D = +67.5 (c 0.65, EtOH)Ee = 85%Absolute configuration: 2R,2′S

(+)-SedridineC8H17NO[α]D = +26.2 (c 0.85, EtOH)Ee = 94%Absolute configuration: 2S,2′S

(−)-SedridineC8H17NO[α]D = −25.6 (c 0.95, EtOH)Ee = 89%Absolute configuration: 2R,2′R

(−)-AllosedridineC8H17NO[α]D = −16.4 (c 0.80, MeOH)Ee = 95%Absolute configuration: 2S,2′R

(+)-AllosedridineC8H17NO[α]D = +15.5 (c 0.95, MeOH)Ee = 89%Absolute configuration: 2R,2′S

(+)-2-(2-Hydroxy-butyl)-piperidine-1-carboxylic acid tert-butyl esterC14H27NO3[α]D = +37.7 (c 1, CHCl3)Ee = 94%Absolute configuration: 2S,2′S

(+)-2-(2-Hydroxy-butyl)-piperidine-1-carboxylic acid tert-butyl esterC14H27NO3[α]D = +53.3 (c 1, CHCl3)Ee = 94%Absolute configuration: 2S,2′R

(+)-2-(2-Hydroxy-butyl)-piperidine-1-carboxylic acid tert-butyl esterC14H27NO3[α]D = −48.7 (c 1, CHCl3)Ee = 89%Absolute configuration: 2R,2′S

(+)-EthylnorlobelolC9H29NO[α]D = +17.5 (c 0.80, EtOH)Ee = 94%Absolute configuration:2S,2′S

(−)-2′-epi-EthylnorlobelolC9H19NO[α]D = −6.6 (c 0.80, EtOH)Ee = 94%Absolute configuration: 2S,2′R

(−)-Allyl-piperidine-1-carboxylic acid tert-butyl esterC13H23NO2[α]D = −49.2 (c 0.90, CHCl3)Ee = 94%Absolute configuration: 2S

(−)-2-Propyl-piperidine-1-carboxylic acid tert-butyl esterC13H25NO2[α]D = −39.8 (c 0.60, CHCl3)Ee = 94%Absolute configuration: 2R

(−)-ConiineC13H25NO2[α]D = −9.7 (c 0.93, CHCl3)Ee = 94%Absolute configuration: 2R