Regio‐ and Stereoselective 1,2‐Dihydropyridine Alkylation/Addition Sequence for the Synthesis of Piperidines with Quaternary Centers

Abstract

The first example of C-alkylation of 1,2-dihydropyridines with alkyl triflates and Michael acceptors was developed to introduce quaternary carbon centers with high regio- and diastereoselectivity. Hydride or carbon nucleophile addition to the resultant iminium ion also proceeded with high diastereoselectivity. Carbon nucleophile addition results in an unprecedented level of substitution to provide piperidine rings with adjacent tetrasubstituted carbons.

Regio- and Diastereoselective Synthesis of Highly Substituted, Oxygenated Piperidines from Tetrahydropyridines

“…In this model, the depicted structure of protonated 3a corresponds to that observed in the x-ray crystal structure of the 2,4,6-trinitrobenzenesulfonate salt of 3a . 7a …”

“…[RhCl(coe) 2 ] 2 was stored inside an N 2 -filled inert atmosphere glovebox at −25 °C. The ligand, Me 2 N-C 6 H 4 -PEt 2 , was synthesized according to a previously published procedure 7a and stored inside an N 2 -filled inert atmosphere glovebox at −25 °C. Stock solutions of the rhodium catalyst were made by dissolving [RhCl(coe) 2 ] 2 (50.0 mg, 69.7 μmol) and Me 2 N-C 6 H 4 -PEt 2 (30.0 mg, 143 μmol) in anhydrous PhMe until a total volume of 3.0 mL is reached.…”

“…17 All imines except ( E )-1-cyclohexyl- N -(( E )-3-methylpent-3-en-2-ylidene)methanamine were prepared according to literature procedures. 6,7a With the exception of the tetrahydropyridines for which the preparations are described below, all tetrahydropyridines were prepared according to literature procedures. 6,7b …”

“…These tetrahydropyridines, which have different alkene regiochemistries and stereochemical displays, are obtained by a Rh(I)-catalyzed C–H alkenylation/electrocyclization cascade to give a common 1,2-dihydropyridine intermediate 1 followed by divergent kinetic or thermodynamic protonation and reduction sequences. 6–7 …”

Lanthanides and actinides: Annual survey of their organometallic chemistry covering the year 2014

“…2.10. ORGANOLANTHANIDES IN ORGANIC SYNTHESIS Allyl cerium reagents have been employed in a regio-and stereoselective 1,2-dihydropyridine alkylation/addition sequence for the synthesis of piperidines with quaternary centers [121]. The reaction of thioiminium iodides with organocerium reagents derived by transmetalation of the corresponding lithium reagents with anhydrous cerium(III) chloride has been investigated.…”