An Aminocatalyzed Michael Addition/Iron-Mediated Decarboxylative Cyclization Sequence for the Preparation of 2,3,4,6-Tetrasubstituted Pyridines: Scope and Mechanistic Insights

Abstract

A novel, scalable strategy for the preparation of 2,3,4,6-tetrasubstituted pyridines is described. This protocol has two steps: an aminocatalyzed addition of ketones to alkylidene isoxazol-5-ones, followed by an iron-mediated decarboxylative cyclization event. Mechanistic insights for both steps are provided based on HRMS-ESI(+) studies.

Isoxazole Strategy for the Synthesis of α-Aminopyrrole Derivatives

“…Physical and spectral data of 4-(4-chlorobenzylidene)-3-phenyl-5­(4 H )-one ( 1a ), 4-(4-bromobenzylidene)-3-phenyl-5­(4 H )-one ( 1b ), 4-(4-methoxybenzylidene)-3-phenyl-5­(4 H )-one ( 1d ), and 4-(3,4-dimethoxybenzylidene)-3-phenyl-5­(4 H )-one ( 1f ), prepared according to the reported procedures, were in agreement with previously reported values.…”

“…For all new compounds, 13 C{ 1 H} and 13 C DEPT-135 spectra were recorded and calibrated according to the peak of CDCl 3 (77.00 ppm) or DMSO-d 6 (39.51 ppm). 19 F NMR spectra were calibrated according to a CFCl 3 external standard (δ = 0 ppm). Electrospray ionization (ESI) mass spectra were recorded on a mass spectrometer, HRMS-ESI-QTOF, electrospray ionization.…”

Visible-Light-Mediated Strategies to Assemble Alkyl 2-Carboxylate-2,3,3-Trisubstituted β-Lactams and 5-Alkoxy-2,2,4-Trisubstituted Furan-3(2H)-ones Using Aryldiazoacetates and Aryldiazoketones

“…Imines 4 and sulfoxonium ylides 6 can be employed in a variety of chemical transformations affording densely functionalized molecules (see the Supporting Information for examples of such applications, 11a – 11d , 12a , and 12b ). On the basis of our interest in the chemistry of heterocycles, we decided to explore the possibility of accessing β-lactams 9 starting from imines 4 and furan-3­(2H)-ones 10 starting from sulfoxonium ylides 6 , also using visible-light-mediated transformations.…”

RuCl3/ PPh3‐ Catalyzed Direct Conversion of Isoxazol‐5‐ones to 2,3‐Disubstituted Pyridines

“…Peters and co‐workers have described the conversion of isoxazol‐5‐ones 4 and vinylketones 5 to 2,3,6‐trisubstituted pyridines 6 via a reaction sequence starting with a Pd(OAc) 2 ‐catalyzed Michael addition, followed by a hydrogenation step using Pd(PPh 3 ) 4 as catalyst (Scheme b) . Finally, Jurberg and co‐workers have also reported a two‐step procedure involving an aminocatalyzed addition of ketones 8 to 4‐alkylideneisoxazol‐5‐ones 7 , followed by a Fe‐mediated decarboxylative cyclization event to afford the corresponding 2,3,4,6‐tetrasubstituted pyridines 9 (Scheme c) …”