Structure-Based Kinetic Control in a Domino Process: A Powerful Tool Toward Molecular Diversity in Chromone Series

Abstract

Two successive original routes leading to two novel families of polyheterocycles starting from the versatile chromone-based Michael acceptors platform are reported herein. The major aspect of this work is the selective access to these frameworks by changing the course of the domino process involved in their formation. First, enaminochromanones were selectively accessed under uncommon kinetic control. In this study, we showed that the tuning of the selectivity toward the kinetic product could be achieved by key structural modifications of the different reaction partners involved in the domino process. Once selectivity was efficiently controlled, enaminochromanones were ultimately transformed into a more complex family of polyheterocycles containing the pyrrolo-oxazinone framework. Here, the modulation of the domino sequence toward these particularly scarce structures was enabled by a pivotal switch in reactivity induced by aryl-λ-iodanes.

Crystal structures of (E)-3-(4-hydroxybenzylidene)chroman-4-one and (E)-3-(3-hydroxybenzylidene)-2-phenylchroman-4-one

“…A search of the Cambridge Structural Database (CSD version 5.40, last update November 2018;Groom et al, 2016) using the scheme presented in Fig. 5 found 41 chromanone (Ishikawa et al, 2013a,b;Zimmerman et al, 2015;Katrusiak et al, 1987;Brien et al, 2012;Suresh et al, 2007;Boonsri et al, 2005;Biruntha et al, 2018;Talhi et al, 2016;Marx et al, 2008;Cheng et al, 2011;Valkonen et al, 2012;Lepitre et al, 2017;Suresh et al, 2007;Marx et al, 2008;Hassaine et al, 2016;Chantrapromma et al, 2006;Zhang et al, 2012;Augustine et al, 2008;Zhang et al, 2013) and four flavanone structures (Zhong et al, 2013;Kupcewicz et al, 2013;Monserrat et al, 2013). In the flavanone structures, the phenyl substituent at the C2 position is always nearly perpendicular to the chroman moiety, with the (2) 103Symmetry codes: (i) x À 1; Ày þ 1 2 ; z À 1 2 ; (ii) x; Ày þ 1 2 ; z À 1 2 ; (iii) x þ 1; Ày þ 1 2 ; z þ 1 2 ; (iv) x À 1; y; z.…”

Tandem Ring‐Opening/Double Ring‐Closing Synthesis of 1,2,4‐Triazolo[1,5‐a]pyridines from Chromone‐Containing Acrylonitriles

“…A similar role of triethylamine in the closure of pyridine ring was noted by some researchers. [12] In the A* structure, the cyano group becomes available for a second nucleophilic attack by the amino group. As a result, the pyridine ring closes and intermediate 4 aa is formed.…”

Synthesis and Reactivity of Electron-Deficient 3-Vinylchromones

“…In 2017, Daïch's group, 40 based on the data of their previous work on the synthesis of compounds 31, 36 developed a method for the preparation of enaminochromanones 36 from 3-(chromon-3-yl)acrylates 2c and ethanolamines under kinetic control, which, through the intermediacy of chromeno[2,3-c]pyrroles 37, were transformed into a more complex heterocyclic system with a pyrrolooxazinone fragment 38. These authors were able to show that treatment of chromanones 36 with [bis(trifluoroacetoxy)iodine]benzene (PIFA) in THF leads to chromenopyrroles 37, which, upon treatment in refluxing toluene with p-toluenesulfonic acid (PTSA), undergo intramolecular esterification into tetracyclines 38.…”