Tandem Allylation/1,2-Boronate Rearrangement for the Asymmetric Synthesis of Indolines with Adjacent Quaternary Stereocenters

Abstract

A three-component coupling using lithiated indoles, boronate esters and allylic acetates generates chiral indolines with adjacent quaternary stereocenters. Successful stereocontrol required the use of phosphoramidite ligands not previously described for organopalladium chemistry. Mechanistic studies indicate a monodentate PdL intermediate, and a stepwise allylation-aryl/alkyl migration. A protodeborylation strategy was used to install a C− H bond in place of the C−B bond. A photoredox coupling was used to replace C−B bond with a C−C bond in a highly diastereoselective manner. In the specific case of methyl-vinyl ketone, a novel radical-mediated annulation provides polycyclic products with high enantio-and diastereoselectivity.

Transition‐Metal‐Free Synthesis of Heterobiaryls through 1,2‐Migration of Boronate Complex

“…Thereh as been an immense interesti nt ransition-metal-free CÀCb ond formation using 1,2-migration of boronate complexes. Vinyl boronate complex can be activated by a transition metal which was demonstrated by Ishikura, [22] Murakami, [23] Morken, [24] Ready, [25] and others. [20] Not only migration to the sp 3 carbon but also 1,2-migrationt ot he sp 2 carbon is equally attractive.…”

“…[21] In this process migration of the alkyl group from boron to carbon generates an intermediate alkyl boronic ester species 7,w hich participated in an anti-boron-iodine elimination in the presence of ab ase to furnish Z-alkene (Scheme 2a). Vinyl boronate complex can be activated by a transition metal which was demonstrated by Ishikura, [22] Murakami, [23] Morken, [24] Ready, [25] and others. After Zweifel's initial discovery,s everal groups emerged to develop CÀCb ond formation through 1,2-migrationt ot he vinyl boronates.…”

Vinylidenation of Organoboronic Esters Enabled by a Pd‐Catalyzed Metallate Shift

“…19 Perhaps unsurprisingly, direct extension to allyl electrophiles has proved a challenge, likely because η 3 coordination of the allyl group occupies a coordination site necessary for binding and activation of the ‘ate’ complex. Indeed, recent reports by Ready 20 suggest that enantioselective Pd-catalyzed reaction of indole-derived ‘ate’ complexes with allyl electrophiles, and similar racemic processes established by Ishikura 21 and Murakami 22 , appear to occur by outer-sphere anti addition of electron-rich alkynyl- and indole-derived ‘ate’ complexes to the back side of the Pd(allyl). In this report, we show that catalyst features that allow Pd(allyl) complexes to bind an ‘ate’ complex and promote the metallate shift also allow β-hydrogen elimination of the intermediate and thus equation 3 to operate.…”

Functionalization of Heterocycles through 1,2‐Metallate Rearrangement of Boronate Complexes

“…In 2018, Ready′s group expanded the scope of this reaction for the enantio‐ and diastereoselective synthesis of indolines with contiguous quaternary centers (Scheme 14). [48] Enantio‐ and diastereoselective synthesis of quaternary stereocenters at the C2‐ and C3‐positions of indole was a challenging task. Reaction of C3‐substituted indole boronate complexes with palladium π‐allylic complexes using Carrera phosphoramidate ligands [49] afforded the desired indoline in high enantio‐ and diastereoselectivity.…”