Efficient and Chemoselective Reduction of Pyridines to Tetrahydropyridines and Piperidines via Rhodium‐Catalyzed Transfer Hydrogenation

Abstract

Promoted by iodide anion the rhodium complex dimer, [Cp*RhCl 2 ] 2 , catalyzes efficiently the transfer hydrogenation of various quaternary pyridinium salts under mild conditions, affording not only piperidines but also 1,2,3,6-tetrahydropyridines in a highly chemoselective fashion, depending on the substitution pattern at the pyridinium ring. The reduction is conducted in azeotropic formic acid/triA C H T U N G T R E N N U N G ethylamine (HCOOH-Et 3 N) mixture at 40 8C, with catalyst loadings as low as 0.005 mol% being feasible.

ChemInform Abstract: Asymmetric Hydrogenation of 3‐Substituted Pyridinium Salts.

“…Although there is no general agreement on the mechanism of the AH of N-heteroarenes, [7,8] the current data led us to speculate that the poor enantiomerice xcesses obtained with 3-substituted pyridines in comparison to their 2-substituted analogues were due to an on-enantioselective enaminium-iminium isomerization of ap artially hydrogenated intermediate (Scheme 1). [9] Based on this hypothesis, we surmised that the addition of ab ase in the AH of N-benzylatedp yridines [5] could retardt he tautomerization by scavengingH Br produced duringt he reaction.…”

Artificial metalloenzymes for the diastereoselective reduction of NAD+ to NAD2H

“…18 Furthermore, related prochiral structures can be envisaged, namely 3,4 substituted pyridinium ions, which would provide valuable building blocks upon asymmetric conversion.…”

Katalytische Desaromatisierung von N‐Heteroarenen mit Silicium‐ und Borverbindungen

“…[6] Die herkçmmliche Reduktion von N-Heteroarenen erfolgt mit einem Metallhydrid (z. [8] Diese Reaktionen laufen aber normalerweise unter hohen Drücken (H 2 )u nd/ oder bei erhçhten Te mperaturen ab und erfordern häufig Naktivierte Pyridiniumderivate als Ausgangsverbindungen, was eine chemoselektive sequenzielle Reduktion erschwert. [7] In diesem Zusammenhang wurde basierend auf der Hydrierung als einfachster und atomeffizientester Reduktionsmethode eine Reihe komplizierter (Transfer)Hydrierungsmethoden zur selektiven Herstellung von (partiell) gesättigten azacyclischen Verbindungen aus N-Heteroarenen entwickelt.…”