Asymmetric synthesis of 2-substituted chroman-4-ones using lipase-catalyzed kinetic resolutions

Minimizing Aryloxy Elimination in RhI‐Catalyzed Asymmetric Hydrogenation of β‐Aryloxyacrylic Acids using a Mixed‐Ligand Strategy

“…Treatment of product ( R )‐ 2 a with trifluoroacetic acid and trifluoroacetic acid anhydride afforded flavanone ( R )‐ 5 through Friedel‐Crafts acylation in 84 % yield with 98 % ee , which upon reduction with NaBH 4 gave the flavanol (2 R ,4 R )‐ 6 in 87 % yield and 95:5 d.r. without loss of optical purity (Scheme ) 1c. Intramolecular Friedel–Crafts acylation of ( R )‐ 2 k under similar conditions furnished 5,7‐dimethoxyflavanone ( R )‐ 7 (97 % ee ), which, on selective demethylation using a literature procedure, would give ( R )‐Pinostrobin (Scheme ) 14.…”

“…Excellente nantioselectivities (92-> 99 % ee)w ere achievedf or aw ide variety of chiral b-aryloxypropionicacids with minora ryloxy elimination in most cases. The resultantp roductsw ere readily transformed into biologically activec ompounds through simple synthetic manipulations.Asymmetric hydrogenation (AH) of b-aryloxy acrylic acids to directly afford optically active b-aryloxypropionic acids, one type of key structurale lement in ab road range of pharmaceuticals, bioactive compounds, and natural products (Scheme 1), [1][2][3][4][5] remains largely unexplored probably due to the difficulty associated with easy aryloxy elimination in the hydrogenation to give undesired achiral 3-aryl propionic acid derivatives, [6] despite the fact that an umber of chiral catalysts have been successfully developed for AH of variouss ubstituted acrylic acids [7] including b-alkoxyacrylic amide or esters. [6,8] Herein, we com-municate our resultso nt he first example of highly efficient AH of b-aryloxyacrylic acids, using aR h I catalyst based on the heterocombination of ar eadily availablec hiralm onodentate secondary phosphine oxide (SPO) and an achiral monodentate phosphine ligand.E xcellent enantioselectivities( 92-> 99 % ee) were attainedf or av ariety of chiral b-aryloxypropionic acids with minor aryloxy elimination in most cases, some of which were transformed into biologicallya ctive compoundst hrough simple synthetic manipulations.Secondary phosphine oxide (SPO) has been widely used as ap religand in an umber of transition metal-catalyzed reactions, [9] and recently our group reported the successful applications of chiralS PO preligandsi nR h I -catalyzedA Ho fu nsaturated phosphonic acids andc arboxylic acids.…”

Asymmetric Methods for the Synthesis of Flavanones, Chromanones, and Azaflavanones

“…[28] Mitsunobu inversion of homoallylic alcohol 12 with phenol generated the alkyl phenyl ether 13 , which was then oxidized to the carboxylic acid and subjected to enzymatic transesterification to generate a mixture of butyl ester 14 and acid 15 . Enzymatic hydrolysis of butyl ester 14 and subsequent Friedel–Crafts acylation generated (2 S )-chromanone 16 , whereas acylation of 15 allowed for generation of the enantiomeric chromanone 16 .…”

“…[28] Similarly to the steps detailed above, the first step of their synthesis involved enzymatic transesterification of the arylhomoallylic alcohol and a subsequent Mitsunobu reaction, which unfortunately involved minor racemization. Oxidation of the terminal alkene to the carboxylic acid, followed by Friedel–Crafts acylation, produced enantio-enriched flavanone.…”

Copper Bis(oxazoline)‐Catalyzed Enantioselective Alkynylation of Benzopyrylium Ions

“…Given the frequency with which the 2-stereocentere merges in several families of bioactive chromenones and tetrahydroxanthones, there has been significanti nterest in learningh ow to create this bond with high levelsofe nantiocontrol. [2] In the context of naturalp roduct synthesis, there are only a limited number of strategies with demonstrated success. Porco has shownaracemic siloxyfuran addition to benzopyrylium triflates followed by asequence that includes aBirman resolution can be ap roductive approacht os ynthesizingt etrahydroxanthonesw ith excellent levels of enantiomeric excess (Scheme 1A).…”