Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones

Abstract

The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee’s up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

Highly Enantioselective Formation of α‐Allyl‐α‐Arylcyclopentanones via Pd‐Catalysed Decarboxylative Asymmetric Allylic Alkylation

“…Cyclopentanones have also been shown to be challenging substrates to obtain high ee in the DAAA until a very recent report by Stoltz for the preparation of α‐alkyl/benzyl cyclopentanones in up to 94 % ee [Eq. (3), Scheme ] …”

Advances in Stereoconvergent Catalysis from 2005 to 2015: Transition-Metal-Mediated Stereoablative Reactions, Dynamic Kinetic Resolutions, and Dynamic Kinetic Asymmetric Transformations

“…Since their development of an enantioselective allylic alkylation, the Stoltz group has increased the scope of this transformation substantially to include, 1,3-dioxan-5-one- ( 9 ), 21 β-thiocyclohexenone-( 10 ), 22,23 3-ketal- ( 11 ), 24 β-alkoxy-cycloheptenone- ( 12 ), 25,26 5-alkyl- and 5-alkoxy- ( 13 ), β-aminocyclohexenone- ( 14 ), 1-alkoxypiperidine-2,6-dione- ( 15 ), dihydropyridin-4(1 H )-one- ( 16 ), 27 cyclobutanone- ( 17 ), 28 valerolactam and 2-piperazinone- ( 18 ), 29 2-aminomethylcyclohexanone- ( 19 ), 30 4-oxazolidinone- ( 20 ), morpholin-3-one- ( 21 ), 1,2-oxazepan-3-one- ( 22 ), 31 and cyclopentanone-based ( 23 ) 32 allyl β-ketoesters (Figure 2). Notably, the use of oxygen- and nitrogen-based heterocycles allows for the facile synthesis of quaternary stereocenter-bearing polyketide and pharmaceutical-type fragments in a straightforward manner.…”

The Allylic Alkylation of Ketone Enolates

“…Analogously, ligand L6b provided the best result for the decarboxylative allylic alkylation of cyclopentanones (Scheme ) . The α‐quaternary ketones could be obtained in excellent yields and enantiomeric excesses.…”