Development of Chemo‐ and Enantioselective Palladium‐Catalyzed Decarboxylative Asymmetric Allylic Alkylation of α‐Nitroesters

Abstract

We describe the development of aP d-catalyzed decarboxylative asymmetric allylic alkylation of a-nitro allyl esters to afforda cyclic tetrasubstituted nitroalkanes.O ptimization of the reaction parameters revealed unique ligand and solvent combinations crucial for achieving chemo-and enantioselective C-alkylation of electronically challenging benzylic nitronates and sterically encumbered 2-allyl esters.S ubstrates were efficiently accessed in acombinatorial fashion by across-Claisen/ a-arylation sequence.The method provides functional group orthogonality that complements nucleophilic imine allylation strategies for a-tertiary amine synthesis.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…More promising results were recently published by Trost and co-workers. After an initial study of the intermolecular Pd-catalyzed allylic alkylation of α-secondary benzylic nitroalkanes with allyl methyl carbonate, which afforded the desired C-allylated products, but only in moderate ee values, 632 they turned their attention to the corresponding decarboxylative variant. 633 They found that both the chiral ligand and the solvent had a significant effect on the ratio of C - versus O -allylation.…”

“…A range of aromatic groups with differing electronic properties were tolerated, as were α-ethyl nitroesters and bulky β-siloxymethallyl esters, forming α-allylated benzylic nitro compounds in up to 99% yield and up to 98% ee . 632 …”

“…A range of aromatic groups with differing electronic properties were tolerated, as were α-ethyl nitroesters and bulky β-siloxymethallyl esters, forming α-allylated benzylic nitro compounds in up to 99% yield and up to 98% ee. 632 On the basis of the findings of Lloyd-Jones and Norrby, the authors proposed a transition state in which hydrogen-bonding between one of the ligand NH groups and the nitronate accelerates the reaction and controls the approach of the nucleophile such that C-allylation becomes favored over Oallylation (Figure 27).…”

Recent Advances in the Construction of Quaternary Stereocenters via Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation

“…Scheme 3 Pd-catalyzed DAAA of 1,4-diazepan-5-ones A Pd-catalyzed DAAA pathway of allyl nitroesters have been developed by Trost group, furnishing acyclic asymmetric tetrasubstituted nitroalkanes via alkylation of sterically hindered π-allyl substrates (Scheme 4). 33 The reaction proceeded with L1 and Pd2dba3 as the catalyst in ethyl acetate to generate the alkylation products in up to 99% yield and 98% ee. Due to the competitive O-alkylation pathway during Pd-catalyzed DAAA reaction, combination of L1 and the solvent ethyl acetate is crucial for the C-alkylation pathway to give the desired products.…”

Rhodium-Catalyzed Tandem Isomerization–Allylation: From Diallyl Carbonates to α-Quaternary Aldehydes

“…The palladium-catalyzed rearrangement of allyl enol carbonates is an efficient and versatile method to access stereochemically enriched α-allylated carbonyl containing compounds (see Scheme a) . In contrast to classical enolate alkylation chemistry, these reactions avoid the requirement of stoichiometric strong base, allowing for better functional group tolerance and high chemoselectivity and regioselectivity …”