Pd-Catalyzed Regio- and Enantioselective Aminoarylation of Allenols with Aryl Iodides and 2-Pyridones

Abstract

A new asymmetric catalytic protocol for the synthesis of enantioenriched N-allyl 2-pyrodones has been developed via the first Pd-catalyzed regio- and enantioselective aminoarylation of allenols with aryl iodides and 2-pyridones. By using a palladium complex generated in situ from Pd2(dba)3·CHCl3 and (S,S,S)-SKP as a catalyst, the three-component aminoarylation proceeded smoothly to afford a variety of functionalized N-allylic 2-pyridones in high yields with good regioselectivities and excellent enantioselectivities.

Asymmetric Synthesis of Homoallylic Alcohols Featuring Vicinal Tetrasubstituted Carbon Centers via Dual Pd/Photoredox Catalysis

“…With these optimized conditions in hand, we then examined the generality of similar substrate combinations providing homoallylic alcohols with quaternary carbon stereocenters (Scheme , 3aa – 3ja ) . Variation of the aryl substituents on the VCC in the presence of Hantzsch ester 2a generally provided the homoallylic alcohols with remarkable branch-selectivity (b:l > 95:5) and in appreciable isolated yields of up to 78% ( 3ga ) . Good enantioinduction levels of up to 89:11 er for the majority of the products were achieved except for 3fa , 3ha , and 3ja .…”

Pd-Catalyzed regio- and stereoselective allylic substitution of vinylethylene carbonates with 1,2,4-triazoles

“…13 Branched-selective asymmetric allylic substitutions of VECs have also been developed to construct tetrasubstituted stereocenters with high efficiency. 14,15 Although the allylic amination of VECs was reported by Kleij and co-workers using various amine nucleophiles, 15 a , b the protocol with 1,2,4-triazoles as nucleophiles has not been realized. Based on our continuous efforts for the preparation of useful building blocks using VEC chemistry, we are interested to develop a process of Pd-catalyzed allylic substitution of VECs with 1,2,4-triazoles, providing a useful and practical N 1 -selective alkylation products.…”

“…As shown in Scheme 1c, we hypothesized that VECs react with the palladium complex to produce zwitterionic π-allylpalladium intermediate A , which might tautomerize to afford palladacyclic six-membered species B . 10–15 The intermediates could be intercepted by 1,2,4-triazoles as nucleophiles to deliver the desired product 3a . We herein report the first effective and practical method for the synthesis of N 1 -alkylated 1,2,4-triazoles via Pd-catalyzed allylic substitution of VECs with 1,2,4-triazoles.…”

“…However, Feringa's phosphoramidite ligand L1 was ineffective for the reaction (entry 9), even though it was an effective ligand in our previous studies on the allylic substitution of VECs. 9,14 With the best ligand of DPPE in hand, the solvent effect was next investigated (entries 10–15). As a result, THF was found to be a best solvent for the reaction.…”

Bifunctional Lewis Base Catalyzed Asymmetric N-Allylic Alkylation of 2-Hydroxypyridines

“…The Batey group disclosed a palladium-catalyzed asymmetric allylic [3,3]-rearrangement of 2-allyloxypyridines . Recently, the You group and Zhang group independently documented an elegant intermolecular asymmetric N -allylic alkylation of 2-hydroxypyridines using precious metal Rh, Ir, and Pd as catalysts (Scheme A). − Despite these impressive advances, there are still limitations including precious metals as catalysts, unavoidable O -alkylated products and linear products, , and stoichiometric amount of additional base. , Therefore, the development of a new and efficient strategy for enantioselective N -alkylation of 2-hydroxypyridines still remains a large need and is very valuable.…”