A convenient domino access to substituted alkyl 1,2-dihydropyridine- 3carboxylates from propargyl enol ethers and primary amines

A convenient domino access to substituted alkyl 1,2-dihydropyridine-3- carboxylates from propargyl enol ethers and primary amines was reported. A solution of propargyl sinyl ether 1a and p-anisidine in toluene was placed in a microwave-special closed vial and the solution was irradiated for 30 minutes in a single-mode microwave oven. The reaction mixture was dried over anhydrous sodium sulfate and filtrated using dichloromethane as solvent. After removing the solvent at reduced pressure the products were purified by flash column chromatography. Accordingly, the microwave irradiation of an ethanolic mixture of propargyl enol ether 1 a and MeONH2.HCl in the presence of NaOAc yielded the methyl 2-phenyl-4-pyridinecarboxylate in a convenient 54% yield. These results seem to point out to a new reaction pathway involving different thermally-driven rearrangements of the 2,4-dienal 3 intermediate.This research was supported by the Spanish Ministerio de Ciencia e Innovación, the European Regional Development Fund (CTQ2005-09074-C02-02 and CTQ2008-06806-C02-02) and the Spanish MSC ISCIII (RETICS, RD06/0020/1046, and RD06/0020/0041), CSIC (Proyecto Intramural Especial 200719), FUNCIS (REDESFAC PI01/06 and 35/06) and the Fundación Instituto Canario de Investigación del Cancer (FICI-G.I.N808/2007). G.M.-A. thanks Spanish MEC for a FPU grant.Peer Reviewe

Sodium borohydride-amberlyst-15 (H+): An effective reductor for hindered and unreactive ketones in aprotic solvent

The combination of sodium borohydride and amberlyst-15 (H+) in tetrahydrofurane is a powerful reductor for unreactive ketones. The reduction is fast, high-yielding and the work-up is extremely simple. Ketals, silyl ethers and other organic functions are not disturbed during the reduction.This work was supported by the Spanish DGICYT (PB94-0028). JRC thanks the ICI for a predoctoral fellowship.Peer Reviewe

Coupled domino processes: Synthesis of 3,5,8-trisubstituted coumarins from propargyl vinyl ethers

The generation of a small and representative library of 3,5,8-trisubstituted coumarins (21 compounds, 7 families, 3 groups) is described. The library was built from the corresponding propargyl vinyl ethers and three different 1,3-dicarbonyl derivatives using a one-pot coupled domino strategy. These coumarins constitute a novel chemotype defined by the presence of a chemical handle in the pyranone ring and a varied substitution pattern adorning the aromatic ring, which includes fluorine- or oxygen-containing functionalities. © 2013 American Chemical Society.This research was supported by the Spanish Ministerio de Economía y Competitividad (MICINN) and the European Regional Development Fund (CTQ2011- 28417-C02-02). L.C. thanks the Spanish MEC for an FPI grant.Peer Reviewe

Synthesis of Fully Substituted Pyrimidines

A novel approach to the synthesis of fully substituted pyrimidine derivatives armed with an oxy-functionalized acetate chain at the ring is described. The manifold uses amidines as the nitrogen source and activated skipped diynes as the electrophilic reactive partners in a coupled domino strategy. In the first domino reaction, two consecutive aza-Michael additions assemble the six-membered ring heterocycle, while in the second domino process, a [H]-shift and a [3,3]-sigmatropic rearrangement lead to the aromatization of the product.This research was supported by the Spanish Ministerio de Economía y Competitividad (MICINN) and the European Regional Development Fund (CTQ2011- 28417-C02-02). S.L.T. thanks the Spanish MEC for an FPU grant.Peer Reviewe

General synthesis of substituted 1,2-dihydropyridines

A general and practical metal-free protocol for the synthesis of 1,2-dihydropyridines with wide structural/functional diversity at the ring and featuring mono, double, or spiro substitution at the sp3 position is described. The protocol entails a microwave-assisted domino reaction of a propargyl vinyl ether (secondary or tertiary) and a primary amine (aliphatic or aromatic) in toluene or methanol. © 2014 American Chemical Society.This research was supported by the Spanish Ministerio de Economı́a y Competitividad (MICINN) and the European Regional Development Fund (CTQ2011-28417-C02-02). L.C. and G.M.-A. thank the Spanish MEC for FPI and FPU grants, respectively.Peer Reviewe