Pd-Catalyzed Spirocyclization via C–H Activation and Benzyne Insertion

Abstract

A palladium-catalyzed spirocyclization forming spirooxindoles and spirodihydrobenzofurans has been achieved. Mechanistic studies suggest that the transformation proceeds through sequential carbopalladation, C-H activation, and benzyne insertion. Both classes of spirocycles have been synthesized in good to excellent yields, and the procedure is readily scalable.

Palladium‐Catalyzed Spirocyclization through C−H Activation and Regioselective Alkyne Insertion

“…Unfortunately, diastereo‐ and regioselective migratory insertion into the palladacycle involving highly reactive intermediates has proven to be challenging. In 2014, Garg and Houk experimentally and computationally reported that unsymmetrical and electronically biased arynes show excellent regioselective addition reactions, whereas in our study, these arynes undergo the migratory insertion with poor regiocontrol (Scheme A). Following this work, the García‐López group reported spirocyclization involving α‐diazocarbonyl compounds, albeit in modest diastereoselectivity (Scheme B) .…”

Palladium‐Catalyzed Spirocyclization through C−H Activation and Regioselective Alkyne Insertion

“…Recently,o ur group and the García-López group have employed C À Hf unctionalization in ad omino process to generate spirocycles through carbopalladation, C À Ha ctivation, and migratory insertion or direct reductive elimination. [11][12][13][14] Unfortunately,diastereo-and regioselective migratory insertion into the palladacycle involving highly reactive intermediates has proven to be challenging. In 2014, Garg and Houk [15] experimentally and computationally reported that unsymmetrical and electronically biased arynes show excellent regioselective addition reactions,w hereas in our study, [12,13] these arynes undergo the migratory insertion with poor regiocontrol (Scheme 1A).…”

“…[11][12][13][14] Unfortunately,diastereo-and regioselective migratory insertion into the palladacycle involving highly reactive intermediates has proven to be challenging. In 2014, Garg and Houk [15] experimentally and computationally reported that unsymmetrical and electronically biased arynes show excellent regioselective addition reactions,w hereas in our study, [12,13] these arynes undergo the migratory insertion with poor regiocontrol (Scheme 1A). Following this work, the García-López group reported spirocyclization involving a-diazocarbonyl compounds,albeit in modest diastereoselectivity (Scheme 1B).…”

“…Palladacycle C,w hich was synthesized previously in our group, [12] reacted with ethyl phenylpropiolate to afford 3a in 75 %yield and > 20:1 rr (Scheme 9). This result suggests that this complex is alikely intermediate in the catalytic cycle and the consistent regioselectivity observed further supports the proposed mechanism.…”

Palladium‐Catalyzed Oxidative Cascade Carbonylative Spirolactonization of Enallenols

“…[9][10][11] Furthermore,dearomatization reactions of different aromatic rings [12,13] and alkene metathesis with Grubbs catalysts [14] provide feasible methods for the synthesis of spirocycles.I na ddition, palladium-catalyzed carbocyclization reactions have also been used to form spirocycles. [15][16][17] However,l ess attention has been devoted to the efficient synthesis of spirolactones bearing an allcarbon quaternary center. [18] There is therefore ademand for new synthetic methods that provide access to spirolactones with an all-carbon quaternary center from readily available starting materials.…”