Stereoselective Synthesis of Piperidines

Abstract

This review presents the recent progress in the stereoselective formation of piperidines focussing on synthetic key steps. Both chiral pool-derived routes, auxiliary controlled methods and catalytic asymmetric reactions are described.

Catalytic Enantioselective Addition of Dialkylzinc Reagents to N‐Acylpyridinium Salts

“…A solution of the catalyst, freshly prepared at room temperature from Cu(OTf) 2 (0.0125 mmol, 5 mol %) and (S)-L3 (0.025 mmol, 10 mol %) in THF (1 mL), was cooled down to À78 8C and the corresponding dialkylzinc reagent (2.5 equiv) was added. Subsequently, solution A was added dropwise to the reagent mixture (to collect all the salt 1 a in the syringe, the flask was washed twice with 2 portions of THF (0.5 mL) each).…”

“…[2] An important strategy for their construction is the direct asymmetric addition of nucleophiles to N-acylpyridinium salts. Although significant progress has been achieved in this area, [3] most studies have focused on the use of chiral pyridine substrates.…”

N‐Sulfinyl Amines as a Nitrogen Source in the Asymmetric Intramolecular Aza‐Michael Reaction: Total Synthesis of (−)‐Pinidinol

“…Flash column chromatography was performed with the indicated solvents on silica gel 60 (particle size: 0.040-0.063 mm). 1 H, 13 C, and 19 F NMR spectra were recorded on a 300 MHz spectrometer. Chemical shifts are given in ppm (d), referenced to the residual proton resonances of the solvents or fluorotrichloromethane in 19 F NMR spectroscopic experiments.…”

“…[1] Among them, pyrrolidine and piperidine substructures are worth mentioning due to their ubiquitous presence in the skeleton of several naturally occurring alkaloids [2] and their utility as chiral auxiliaries and chiral ligands in asymmetric catalysis. [3] Among the traditional methodologies for generating chiral b-amino carbonyl compounds, asymmetric Mannichand aza-Michael-type reactions are the most powerful strategies for the synthesis of these moieties.…”

Studies toward the First Stereoselective Total Synthesis of (±)-Quinolizidine 195C and Other Transformations

“…The piperidine ring is one of the most abundant molecular fragments in both natural and synthetic compounds displaying various biological activities [1][2][3][4]. Among the piperidine natural products are the bicyclic indolizidines and quinolizidines [5][6][7][8][9][10][11][12][13][14][15][16].…”