A Facile Enantioselective Alkynylation of Chromones

Abstract

The first catalytic enantioselective alkynylation of chromones is reported. In this process, chromones are silylated to form silyloxybenzopyrylium ions that lead to silyl enol ethers after Cu‐catalyzed alkyne addition using StackPhos as a ligand. The outcome of the reaction is impacted by distal ligand substituents with differing electronic character and it was found that successful reactions could be achieved with different ligand congeners by using different solvents. This sequence enables access to different products by protonation or further functionalization, thus increasing complexity in a divergent manner. The transformation is high yielding over a broad scope to provide a variety of useful chromanones in high enantioselectivity.

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

“…This reasoning was inspired by Watson's work demonstrating that copper acetylides undergo addition to in situ‐generated oxocarbenium ions with high levels of enantiomeric excess when a bis(oxazoline) ligand was present . While this manuscript was under preparation, Aponick and co‐workers recently reported enantioselective alkynylation of chromones with their StackPhos ligands (Scheme C) . Herein, we describe our findings of copper bis(oxazoline) catalysis as an excellent platform for the reaction of terminal alkynes and unhindered benzopyrylium triflates (R=H) to generate desirable products with excellent levels of enantiocontrol.…”

“…[10] While this manuscript was under preparation,A ponick and co-workers recently reported enantioselective alkynylation of chromones with their StackPhos ligands (Scheme 1C). [11] Herein, we describe our findings of copper bis(oxazoline)c atalysis as an excellent platform for the reaction of terminal alkynes and unhindered benzopyrylium triflates (R = H) to generate desirable products with excellent levels of enantiocontrol. This method represents a more practical approachb ecause it requires readily accessible bis(oxazoline)l igands.…”

“…The yield of the reaction was improved from 69 to 72 %b y conducting the reactioni nasingle flask, the enantiomeric excess remained excellent at 97 %( Ta ble 1, entry 10). The reductiono ft he catalyst loading from1 0t o5 mol %a nd 1mol %r esulted in small losses in enantiomeric excess (entries [11][12].…”

Configuration Sampling With Five‐Membered AtropisomericP,N‐Ligands

“… [10] Ligands L1 , [8e,h] L2 , [8a] and L3 [8e] (Scheme 1 d) should systematically change the position of the phenyl groups in the chiral pocket while holding the identity of the groups, and thus the inherent steric demand of these groups, constant. In this reaction, our StackPhos ligand L2 proved optimal and afforded 3 in 89 % yield and 94 % ee [10] . With StackPhim L1 , which would be predicted to be the most hindered of these ligands, the product was obtained in 96 % yield but the selectivity was reduced to 74 % ee .…”

Enantioselective Synthesis of Chromanones through Organocatalytic Tandem Reactions

“…[3] Generally, the asymmetric reactions using the reagents containing a chromone motif are efficient ways to construct enantiomerically enriched chromanones. [4][5][6][7] In this context, various types of enantioselective transformations have been established via organic catalysis or metal catalysis, including asymmetric 1,4-addition with organometallics, [4] asymmetric alkylation, [5] hydrogenation, [6] cascade reactions, [7] and other transformations. [8] In contrast, the enantioselective ring construction of chromanone skeleton remains limited.…”