Catalytic Asymmetric Syntheses of 2‐Aryl Chromenes

Abstract

Chiral chromene motifs are important heterocycles in numerous natural products and bioactive molecules. Among them, flavenes, flavanes, and flavanones, which consist of the 2-aryl-chromene skeleton are observed most frequently. As subgroups of flavonoids, they often occur in various plants and show many biological activities, such as antitumor, antioxidant, antibacterial, anti-inflammatory, and anticoagulant properties. This Minireview summarizes recent reports on catalytic asymmetric synthesis of flavenes, flavanes, and flavanones. derivatives 1, giving the adduct 6. The subsequent intramolecular adol reaction and dehydration providing the desired product 3 (Scheme 2).Almost the same time, professor Córdova and coworkers presented the same domino reaction between 1 a and 2 catalyzed by 4 a, providing a series of 2H-flavenes in high yields and with 83-98% ees (Scheme 3). [5] Notably, by using 2nitrobenzoic acid as an additive, product 3 a could be obtained with 37% yield and 88% ee, comparing to 10% yield and 9% ee when adding no additives. More significantly, another additive, 4 Å molecular sieves, promoted the reaction significantly, increasing the product yield from 37% to 81% with no enantioselectivity erosion. The authors believed that the addition of an organic acid accelerated the adol condensation by activating the benzaldehyde. Also, the organic acid could stabilized the iminium intermediate, facilitating the oxa-Michael addition. The product 7 could be observed by NMR analysis, which gave an obvious evidence to the proposed reaction pathway (Scheme 2).By applying the similar approach, Wang and coworkers developed the asymmetric reaction of 1 and 2 catalyzed by organocatalyst 4 b. [6] Different from Córdova's condition, Wang found that Cl(CH 2 ) 2 Cl was the best solvent to provide the highest enantioselectivity. Lowering the reaction temperature improved ee with prolonged time for completion. The reaction had a broad scope and the functionalized 2H-flavenes were synthesized respectively high yields (53-98%) and with good to excellent levels of enantioselectivities (75-99% ee). However, the electronic nature of the α,β-unsaturated aldehydes 2 had a remarkable effect on the reactivities and ees that 2 bearing electron-withdrawing groups, such as nitro group, generally Scheme 2. Proposed mechanism of the organocatalytic asymmetric oxa-Michael addition/intramolecular adol reaction/dehydration cascade. Scheme 3. Direct organocatalytic asymmetric domino oxa-Michael/aldol condensations between 1 a and α, β-unsaturated aldehydes 2.

Recyclable catalysts for the synthesis of heterocyclic compounds using carbon materials

“…Chiral 2‐arylbenzopyranones (flavanones) are important biologically active moiety and in pharmaceuticals, which can also be obtained by the oxa ‐Michael reaction of 2′‐hydroxychalcone or 1‐(2‐hydroxyaryl) α,β‐unsaturated aromatic ketones. [52] The isomerization of 2′‐hydroxychalcones to flavanones belongs to the oxa ‐Michael addition reaction, which produces a chromane core that is characteristic of many flavonoids. [53] In 2017, Ranganath and co‐workers introduced a heterogeneous catalyst based on carbon nanotubes, which acted as nano reaction vessels for asymmetric synthesis of flavanones.…”

Asymmetric hydrogenation and transfer hydrogenation in the enantioselective synthesis of flavonoids

“…22 More recently, organocatalytic and chiral acid-promoted variations of these transformations have also been developed. 22,23 With advances in asymmetric transition-metal catalysis during the late 1990s and 2000s, enantioselective arylation reactions rapidly became one of the most efficient methods for the asymmetric synthesis of flavonoids. 23–25 Lastly, the enantioselective synthesis of homoisoflavonoids has been recently reviewed by Seo's group.…”

Synthesis of 2-trifluoromethyl chromenes via double carbonyl–ene reaction

“…Consequently, numerous methods have been developed to access these scaffolds. [3][4][5] On the other hand, the development of new methodologies for the construction of fluorine-containing heterocycles is a subject of intensive research in medicinal chemistry [6][7][8][9][10] and agrochemical science. [11][12][13] The introduction of trifluoromethyl (-CF 3 ) substituent into the structure of organic compounds can provide potentials to improve their polarity, lipophilicity, and metabolic stability.…”