Controllable Pd-Catalyzed Allylation of Indoles with Skipped Enynes: Divergent Synthesis of Indolenines and N-Allylindoles

Abstract

An unprecedented acid- and ligand-controlled divergent allylation of indoles with unactivated skipped enynes via Pd hydride catalysis has been disclosed. This redox-neutral transformation went through multiple hydropalladation insertion, β-hydrogen elimination, π–σ–π isomerization, and allylic substitution steps. This method not only provides a platform for synthesizing indolenines and N-allylindoles but also allows facile access to functional 1,3-dienes with high atom and step economy.

Rhodium‐Catalyzed Chemodivergent Regio‐ and Enantioselective Allylic Alkylation of Indoles

“…[13] No catalystc ould realize the chemoswitchable asymmetric C3 and N1 allylation process due to the innate nature of the p-allyl-metal intermediates. [14] We have developed an ew catalysts ystem based on Rh I /bisoxazolinephosphanet oa chieve regio-and enantioselective allylation of aliphatic allylic substrates with different nitrogen, carbon,o xygen, and sulfur pronucleophiles. [15,16] The easy modification of the counteranions and ligands as well as the broad range of reactiont emperature and utilization of the released base enables flexible adjustment of the electrophilicity of the p-allylrhodium intermediate.…”

Ligand-Controlled, Palladium-Catalyzed Asymmetric [4+4] and [2+4] Cycloadditions

“…Although the transition metal- or organocatalyst-mediated asymmetric divergent synthesis reactions have been well established, it is still difficult to implement the chemoselective, regioselective, enantioselective, and product-selective reactions via simply modifying the chiral ligands . As a continuation of our research interests in catalytic divergent synthesis, we herein describe ligand-controlled, palladium-catalyzed asymmetric [4+4] and [2+4] cycloaddition reactions of benzofuran-derived azadienes with tert -butyl [2-(hydroxymethyl)­allyl] carbonate for the synthesis of chiral benzofuro­[2,3- c ]­[1,5] oxazocines and tetrahydropyran-fused spirocyclic scaffolds for the first time (Scheme b). In this work, the inherent steric and electronic effects of two different chiral ligands led to the allyl palladium species with distinct reactivities after the initial oxo-Michael addition.…”

Rhodium(III)‐Catalyzed Synthesis of Skipped Enynes via C(sp3)–H Alkynylation of Terminal Alkenes

“…Here, we report on a directing group-free transformation for the direct construction of C(sp 3 )-C(sp) bonds from simple terminal alkenes under [Cp*Rh]-catalyzed conditions. [13] This new protocol is suitable for the synthesis of 1,4-enynes from terminal alkenes without prior functionalization, which are valuable synthons [14] traditionally prepared by cross cou-pling, [15] allylic alkynylation, [16] allylic alkylation, [17] and nucleophilic substitution. [18] Grounding from our recent work on C(sp 2 /sp 3 )-C(sp) bond formation, [19] we first investigated the reactivity of hex-5-en-1-ol (1 a) and bromoalkyne 2 a with [Cp*RhCl 2 ] 2 (5 mol %), AgSbF 6 (20 mol %), Ag 2 CO 3 (50 mol %) and LiOAc (40 mol %) in 1,2-dichloroethane (DCE) at 23 8C.…”