Catalytic Enantioselective Double Carbopalladation/C−H Functionalization with Statistical Amplification of Product Enantiopurity: A Convertible Linker Approach

Abstract

Combining acatalytic enantioselective reaction with dimerization in as ingle operation is an efficient way to upgrade the enantiomeric excesses (ee) of the product. Palladium-catalyzed reaction of N-(2-iodophenyl)-N-methyl methacrylamide derivatives with oxadiazole afforded, by adouble enantioselective carbopalladation/intermolecular heteroarene C À Halkylation sequence,homodimers in good yields with excellent ee values.T he dimer was subsequently elaborated to the monomer in which the linker (oxadiazole) was incorporated into the target product. Scheme 1. The Horeau Duplication Principle:C oncept and reaction design. FG = functional group.[*] Dr.

Stereoselective 1,2-Dicarbofunctionalization of Trisubstituted Alkenes by Palladium-Catalyzed Heck/Suzuki or Heck/Sonogashira Domino Sequence

“…In 2007, Zhu's group 32 developed a palladiumcatalyzed asymmetric aryl-cyanation of acrylamides through an intramolecular carbopalladation/anionic 41 examples up to 94% ee > 19:1 dr capture sequence, affording 3-cyanomethyl-2-oxindoles bearing quaternary stereocenters in moderate enantioselectivities (Figure 1a). Subsequently, by applying isonitriles and azoles as terminating agents, Zhu's group [33][34][35][36] achieved functional oxindoles in high enantioselectivities and applied them as key materials for the synthesis of (+)esermethole and (+)-physostigmine. By using the carbonylation reaction to interrupt the Heck process, Correia's group, 37 Zhu's group, 38 and Guan's group 39 were able to independently construct 3,3′-disubstituted dihydrobenzofurans, 2-oxindole-based spiro-lactones/lactams, and 3,3′-disubstituted oxindoles in excellent enantioselectivities.…”

Palladium-Catalyzed Asymmetric Domino Heck/Carbocyclization/Suzuki Reaction: A Dearomatization of Nonactivated Naphthalenes

“…Palladium (Pd)-catalyzed asymmetric domino Heck reaction is one of the most powerful methods for the construction of quaternary stereocenters. 26,27 Through trapping of the in situ generated alkyl-PdX intermediate, various enantioselective domino reactions, including Heck tandem coupling with azoles, 28,29…”

Enantioselective Three‐Component Coupling of Heteroarenes, Cycloalkenes and Propargylic Acetates

“…[11] Additionally, Zhu et al reported that oxadiazoles and other heteroarenes containing acidified C À H bonds were in situ deprotonated by bases and intercepted alkyl palladium species, which were produced from asymmetric Heck-type cyclization. [12] Previously, we reported Pd-catalyzed enantioselective Wacker-type coupling of propargylic acetates, cycloalkenes and weak O-and N-nucleophiles, such as alcohols, water and (hetero)arylamines. [13] Herein, we extend the Wacker reactivity to nucleophilic heteroarenes including indoles, pyrroles and some activated furans and thiophenes, as well as some anilines.…”