Ir-Catalyzed Asymmetric Allylic Alkylation of Dialkyl Malonates Enabling the Construction of Enantioenriched All-Carbon Quaternary Centers

Abstract

An enantioselective iridium-catalyzed allylic alkylation of malonates with trisubstituted allylic electrophiles to form all-carbon quaternary stereocenters is reported. This cross-coupling reaction features unprecedented reactivity at ambient temperature, particularly for challenging fully alkyl-substituted allylic electrophiles, and enables the preparation of a wide range of enantioenriched products in up to 93% yield and 97% ee. The products of this transformation can be readily converted to a number of valuable building blocks including vicinal quaternary stereodiads and β-quaternary acids. This method was also used to prepare an enantioenriched intermediate facilitating the asymmetric formal synthesis of the sporochnol family of natural products.

Quaternary Stereocenters via Catalytic Enantioconvergent Allylation of Epoxides

“…Transition metal catalysis has played a dominant role in achieving a high level of enantiocontrol through π-allyl metal complexes derived from allylic substrates . Therein, a variety of soft and prochiral nucleophiles have been identified for the allylations, including enolates and enamines, as well as their precursors such as β-ketoesters, esters, amides, ketones, nitriles, and aldehydes that features acidic α-hydrogens. Aromatic rings, such as phenols and indoles, have also been utilized via asymmetric dearomative allylation processes .…”

Diastereo‐ and Enantioselective Construction of Vicinal All‐Carbon Quaternary Stereocenters via Iridium/Europium Bimetallic Catalysis

“…[9] In this context, electrophiles have long focused on the linear, disubstituted allylic motif that would generate products bearing a tertiary allylic stereocenter. By contrast, trisubstituted allylic electrophiles are rarely employed in the realm of enantioselective iridium-catalyzed allylic alkylation reaction, [10][11][12][13][14][15] owing to the slow oxidative addition process and increased steric hindrance in the key catalytic CÀ C bond-forming step. From the perspective of synthetic utility, this challenging iridium-catalyzed allylic alkylation provides a potentially useful approach for the catalytic asymmetric synthesis of quaternary stereocenters.…”

Pd-IHept-Catalyzed Ring-Opening of gem-Difluorocyclopropanes with Malonates Via Selective C–C Bond Cleavage: Synthesis of Monofluoroalkenes

“…In the case of ethyl 2-cyanoacetate, 3ab was obtained in 16% yield. However, 1,3-diketones and keto-esters failed to undergo this transformation 19 under standard reaction conditions. To demonstrate the potential application of this protocol, we have applied it to the modification of complex molecules (Scheme 2c).…”