Iron‐Catalyzed Reactions of 2‐Pyridone Derivatives: 1,6‐Addition and Formal Ring Opening/Cross Coupling

Abstract

In the presence of simple iron salts, 2‐pyridone derivatives react with Grignard reagents under mild conditions to give the corresponding 1,6‐addition products; if the reaction medium is supplemented with an aprotic dipolar cosolvent after the actual addition step, the intermediates primarily formed succumb to ring opening, giving rise to non‐thermodynamic Z,E‐configured dienoic acid amide derivatives which are difficult to make otherwise. Control experiments as well as the isolation and crystallographic characterization of a (tricarbonyl)iron pyridone complex suggest that the active iron catalyst generated in situ exhibits high affinity to the polarized diene system embedded into the heterocyclic ring system of the substrates, which likely serves as the actual recognition element.

Pd-Catalyzed Asymmetric Allylic Substitution Cascade of Substituted 4-Hydroxy-2H-pyrones with meso-Allyl Dicarbonates

“…Interestingly, when 3a was treated with CH 3 MgBr and acetylacetone iron(III), the pyrone rings opened with carboxylic acid 5 being obtained in 82% yield but with only 47% ee, mainly due to use of the Grignard reagent CH 3 MgBr, which is strongly basic, and the somewhat stronger acidity of the allyl hydrogen at the cis-chiral centers of 5. 14 The carbonyl can be transformed into a methylene group in the presence of DIBAL-H, and the desired product 6 was obtained in 75% yield and 99% ee. 15 In conclusion, we have successfully achieved the selective synthesis of chiral tetrahydro-1H-pyrano [4,3-b]benzofuran-1ones that are kinetic products in ≤87% yield and ≤99% ee, via a temperature-controlled RuPHOX/Pd-catalyzed asymmetric allylic substitution cascade of substituted 4-hydroxy-2Hpyrones with meso-allyl dicarbonates.…”

“…Then, two transformations of product 3a were carried out (Scheme , bottom). Interestingly, when 3a was treated with CH 3 MgBr and acetylacetone iron­(III), the pyrone rings opened with carboxylic acid 5 being obtained in 82% yield but with only 47% ee, mainly due to use of the Grignard reagent CH 3 MgBr, which is strongly basic, and the somewhat stronger acidity of the allyl hydrogen at the cis -chiral centers of 5 . The carbonyl can be transformed into a methylene group in the presence of DIBAL-H, and the desired product 6 was obtained in 75% yield and 99% ee …”

Iodine-promoted insertion of the oxygen atom from water in η4-vinylketene[Fe(CO)3] complexes

“…Similar iron tricarbonyl complexes have been isolated from 2-pyrone and 2-pyridone in the presence of Fe(CO) 5 . 19…”

“…Similar iron tricarbonyl complexes have been isolated from 2-pyrone and 2-pyridone in the presence of Fe(CO) 5 . 19 Once the 2(5H)-furanone is formed, the decoordination of the Fe complex is not very favorable as the ether molecules that we use to fill the coordination vacancies do not sufficiently stabilize the complex. Therefore, it is necessary for the subsequent oxidation of the complex (as observed in the experiments) to favor the decoordination of the lactone.…”

A General Iridium-Catalyzed Reductive Dienamine Synthesis Allows a Five-Step Synthesis of Catharanthine via the Elusive Dehydrosecodine

“…Encouraged by these preliminary data, we began investigating the scope of this reaction by varying the substituents and substitution patterns on the lactam substrate (Scheme ). These substrates were accessible via α-functionalization of the parent lactam ( 15b , 15d ), already known in the literature ( 15c , 15e ), or synthesized using a recently developed three-component reaction ( 15f , 15g ) . We were pleased to find that, when used in conjunction with N -phenyl­maleimide (1.05 equiv) as the dienophile, the corresponding cycloadducts of increasing complexity 19a – 19g could be isolated in good to excellent yields and with essentially complete diastereoselectivity.…”