Regio- and Enantioselective Pd-Catalyzed Allylic Alkylation of Ketones through Allyl Enol Carbonates

Abstract

The Pd-catalyzed reorganization of enol allyl carbonates to allylated ketones occurs asymmetrically in the presence of chiral ligands previously developed in this group. With 2-methylcyclohexanone, asymmetric regioselective alkylation occurs at the more substituted carbon without complications of polyalkylation. Alkylation to create quaternary centers in indanones and benzonabenone occurs in much higher ee than using tin or lithium enolates. The sense of enantioinduction in tetralones is opposite from the tin and lithium enolate examples. For the first time, asymmetric creation of tertiary centers occurs with high ee (78-99%). The different results between this reaction and the use of lithium or tin enolates suggest different mechanisms may be involved.

Palladiumkatalysierte Kreuzkupplungen in der Totalsynthese

“…[235] C-C-Kupplungen [237] Geht man davon aus, dass die Stereoselektivität bei der Bildung der verbleibenden beiden Chiralitätszentren in der Zielverbindung 290 durch das anfangs eingeführte quartäre Stereozentrum gesteuert wurde, dann sind alle chiralen Elemente des Endprodukts auf die asymmetrische allylische Alkylierung zurückzuführen. [238] Erst kürzlich haben die Arbeitsgruppen um Stoltz [239] und Trost [240] unabhängig voneinander über eine Erweiterung der palladiumkatalysierten enantioselektiven Allylierung berichtet. Durch die dort beschriebene asymmetrische decarboxylierende Alkylierung der entsprechenden Allyl(enol)carbonat-Vorstufen wird eine größere Vielfalt an Keton-Derivaten mit quartären Stereozentren zugänglich.…”

Direct and enantioselective α-allylation of ketones via singly occupied molecular orbital (SOMO) catalysis

“…Seminal work from Doyle and Jacobsen (5), Trost and co-workers (6)(7)(8), Stoltz and co-workers (9, 10), Braun and co-workers (11,12), and Hartwig and co-workers (13,14) has introduced valuable previously undescribed technologies for (i) the enantioselective alkylation of preformed or in situ generated metal enolates (5,6,(11)(12)(13)(14)(15)(16)(17) and (ii) the asymmetric and decarboxylative conversion of allyl keto carbonates to α-allylated ketones (7)(8)(9)(10). With these key advances in place, a goal now for asymmetric catalysis has become the direct α-allylation of simple ketone substrates (18,19), an elusive yet potentially powerful bond construction (Scheme 1).…”

Construction of Trifluoromethyl‐Bearing Quaternary Carbon Centers by Intramolecular Decarboxylative Allylation of α‐Trifluoromethyl β‐Keto Esters

“…The successes of Stoltz [16] and Trost [17] on asymmetric Tsuji decarboxylative allylations [18] prompted us to attempt the asymmetric version of the intramolecular decarboxylative allylation of a-trifluoromethyl b-keto esters by the use of chiral bisphosphine ligands like the Trost ligand, P,N ligands or the like. A racemic allyl 2-trifluoromethyl-1-indanonecarboxylate (1a) was tested to be converted into the corresponding optically active 2-allyl-2-trifluoromethyl-1-indanone (2a) by palladium-catalyzed extrusion of carbon dioxide (Scheme 6).…”