Diversity-Oriented One-Pot Synthesis to Construct Functionalized Chroman-2-one Derivatives and Other Heterocyclic Compounds

Abstract

The asymmetric organocatalyzed diversity-oriented one-pot synthesis has been developed to construct chroman-2-one derivatives and other heterocyclic compounds with excellent efficiency and stereoselectivity. The reactions represent a challenging issue, since it altered the inherent selectivity profiles exhibited by the substrates of 2-hydroxycinnamaldehyde 1 and trans-β-nitrostyrene 2, which was previously reported as the asymmetric oxa-Michael-Michael cascade to generate chiral chromans. It should be noted that polycyclic O,O-acetal-containing compounds, which are found in numerous natural products and biologically interesting molecules, could also be achieved in good yields with excellent enantioselectivity as a single diastereoisomer with five continuous stereogenic centers.

C5‐Disubstituted Meldrum's Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

“…To the best of our knowledge, the group of Scheidt has reported the single one‐step asymmetric construction of 3‐substituted dihydrocoumarins upon NHC organocatalysis eliciting a (4+2) cycloaddition reaction with er ranging from 75:25 to 93:7 . Beside the elegant but two steps enamine‐based approaches developed by Xie and Liu,– requiring the final oxidation of a lactol intermediate, List and co‐workers have pioneered the challenging enantioselective delivery of a small proton atom to ketene dithioacetals . One of the obtained product was hydrolyzed into an α‐phenyl dihydrocoumarin with high enantiomeric excess.…”

Recent Advances in Organocatalyzed Asymmetric Synthesis of Benzopyran and Benzodihydropyran (Chromane) Nuclei

“…An example of acidic conditions is the reaction with trans-β-nitrostyrenes. This reaction was already envisaged as a formal cycloaddition [18], but, recently, the reaction was further investigated and a diversity-oriented synthesis made it possible to prepare some different compounds (Scheme 10) [19]. o-Hydroxycinnamaldehydes are another valuable substrate for the asymmetric synthesis of chromane derivatives.…”

Diversified Synthesis of Chiral Chromane-Containing Polyheterocyclic Compounds via Asymmetric Organocatalytic Cascade Reactions

“…7 Although 2-hydroxy cinnamaldehyde could serve as the valuable precursor of chroman-2-ol under iminium-catalyzed reduction conditions, this feature opens the possibility of discovering the new application of 2-hydroxy cinnamaldehyde for the preparation of structurally diverse polyheterocyclic molecules via sequential cascade procedures. 8 Indeed, there are other two reported examples of iminium-catalyzed enantioselective oxa-Michael-initiated cascade reactions, where the 2-hydroxy cinnamaldehyde was used to react with electron-deficient olefins, 9 such as nitroolefins and methyleneindolinones, for the preparation of polysubstituted chromane derivatives with good results. However, despite the wide applicability of 1-aza-1,3-butadienes in the sequential cascade synthesis of chiral polycyclic compounds, to the best of our knowledge, there is no report of asymmetric synthesis of highly functionalized chromane derivatives via [4 + 2] cycloaddition of 2-hydroxy cinnamaldehydes with 1-aza-1,3-butadienes as a two-carbon unit, leading to the products with the remaining ketimine moiety of 1-aza-1,3-butadienes, which offers ample opportunity for further transformations to provide diversified polyheterocyclic frameworks with high molecular and stereogenic complexity.…”

“…We recently found that chroman-2-ol could be directly used in the asymmetric enamine catalysis to access chiral polyheterocyclic compounds bearing a chromane fragment, which is the main core of a wide variety of biologically active compounds . Although 2-hydroxy cinnamaldehyde could serve as the valuable precursor of chroman-2-ol under iminium-catalyzed reduction conditions, this feature opens the possibility of discovering the new application of 2-hydroxy cinnamaldehyde for the preparation of structurally diverse polyheterocyclic molecules via sequential cascade procedures . Indeed, there are other two reported examples of iminium-catalyzed enantioselective oxa-Michael-initiated cascade reactions, where the 2-hydroxy cinnamaldehyde was used to react with electron-deficient olefins, such as nitroolefins and methyleneindolinones, for the preparation of polysubstituted chromane derivatives with good results.…”