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

Abstract

The stereocontrolled construction of biologically relevantc hromanones and tetrahydroxanthones has been achieved through the additiono fa lkynes to benzopyrylium trilfates under the influence of copperb is(oxazoline) catalysis. Excellent levelso fe nantiocontrol (63-98% ee) are achieved in the addition of av ariety of alkynes to an array of chromenones with ah ydrogen in the 2-position. Promising levels of enantiocontrol (54-67 % ee)a re achieved in the alkynylation of chromenones with esters in the 2-position,g enerating tertiary ether stereocentersr esembling those frequently found in naturallyo ccurring metabolites.

Catalytic Enantioselective Reactions with (Benzo)Pyrylium Salts

“…In 2020, Mattson presented a highly stereoselective Cu-catalyzed alkyne addition to an array of chromones using in this case TBSOTf as silylating reagent and (S,S)-BnBox as chiral bis(oxazoline) ligand (Scheme 6, right). [12] Excellent levels of enantiocontrol were achieved, affording desirable 2-ethynyl chromanones in good yields and up to 98% ee.…”

“…Alternatively, the enantioselective alkynylation of 4-chromones was investigated independently by Aponick [11] and Mattson. [12] Embracing the same approach, a first treatment with a silane tri- In 2010, Suga expanded his study of Rh and chiral Lewis acid co-catalyzed asymmetric cycloadditions of cyclic carbonyl ylides with olefinic substrates (Scheme 9). [16d] This time, other lanthanoids such as Eu(OTf) 3 , Ho(OTf) 3 , Gd(OTf) 3 or Lu(OTf) 3 (10 mol %) were used as Lewis acids in combination with the (4S,5S)-PyBox-Ph 2 chiral ligand, which allowed the cycloaddition reaction with electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, butyl-tert-butyldimethylsilylketene acetal and vinyl ethers, affording the adducts in moderate and good yield and moderate to high enantioselectivities depending on the addition sequence, the dipolarophile and the Lewis acid used (up to 96% ee).…”

Enantioselective Dearomative Alkynylation of Chromanones: Opportunities and Obstacles

“…The scope of the alkynylation reaction proved broad with respect to both the chromone and alkyne, giving rise to useful, nearly enantiopure chromanones in high yield. 14a…”

Robust, Enantioselective Construction of Challenging, Biologically Relevant Tertiary Ether Stereocenters

“…As shown in Scheme , the enantioselective construction of the 10a tertiary ether stereocenter in 7 was inspired by our earlier discoveries: alkyl and aryl copper acetylides under the influence of bis (oxazoline) ligation add to benzopyrylium triflates (R = H) with excellent levels of enantiocontrol (>90% ee, Scheme D) . While in the midst of our own reaction development, Aponick separately advanced the addition of copper acetylides to benzopyrylium triflates in the presence of StackPhos ligands (Scheme C) .…”