Asymmetric Nucleophilic Catalysis with an Octahedral Chiral-at-Metal Iridium(III) Complex

Abstract

Herein, we report about the design, synthesis, and application of a nucleophilic octahedral chiral-only-at-metal iridium­(III) complex. We demonstrate that the enantiopure form of this complex serves as an efficient catalyst for the asymmetric Steglich rearrangement of O-acylated azlactones (up to 96% ee and 99% yield) and the related asymmetric Black rearrangement of O-acylated benzofuranones (up to 94% ee and 99% yield). We provide insight into the mechanisms of these two acyl migration reactions and the catalyst’s manner of chiral recognition with crystal structures of the active catalyst and a catalysis intermediate analog, as well as with quantum chemical calculations based on them. Furthermore, we demonstrate that the presented catalyst also efficiently catalyzes the asymmetric reaction between aryl alkyl ketenes and 2-cyanopyrrole to give the corresponding α-chiral N-acyl pyrroles (up to 95% ee and 99% yield).

The Selective N‐Functionalization of Indoles via aza‐Michael Addition in the Ligand Sphere of a Chiral Nickel(II) Complex: Asymmetric Synthesis of (S)‐1H‐Indole‐Alanine Derivatives

“…Top‐side attack is clearly preferred for both N1‐ and C3‐alkylations. The lowest‐energy N1‐alkylation TS is favored over the lowest‐energy C3‐alkylation TS by 0.4 kcal/mol, which results in 66:34 product ratio under assumption of the first step irreversibility (according to Curtin–Hammett principle). However, the first step is not irreversible, not even at room temperature, at least, when the addition proceeds via carbon: the activation energies of breaking the newly‐formed bonds in this reaction are ≈ 20 kcal/mol for C–N bonds, but only ≈ 13 kcal/mol for C–C bonds.…”

Synthesis and Biological Evaluation of Nipecotic Acid and Guvacine Derived 1,3‐Disubstituted Allenes as Inhibitors of Murine GABA Transporter mGAT1

“…Analytical and spectroscopic data are consistent with those reported earlier. [34] 2'-Isopropyl-[1,1'-biphenyl]-2-carbaldehyde (17 r): GP2 was followed using 2-bromobenzaldehyde (0.24 mL, 2.0 mmol), (2-isopropylphenyl)boronic acid (328 mg, 2.00 mmol) and Pd(PPH 3 ) 4 (116 mg, 0.100 mmol) in 30 mL of the solvent mixture for 2.25 h. Purification afforded the desired aldehyde 17 r as colorless viscous oil (384 mg, 86 %). Analytical and spectroscopic data are consistent with those reported earlier.…”

Enantioselective Acyl Migration Reactions of Furanyl Carbonates with Chiral DMAP Derivatives

“…Enantioselective constructions of all‐carbon quaternary stereogenic centers are some of the most important transformations in organic synthesis . Among them, enantioselective Steglich‐type (Black) rearrangements (azlactones, oxindoles,, furanones,, benzofuranones,,, pyrazoles) with a nucleophilic catalyst are well‐established methods for the enantioselective construction of an all‐carbon quaternary stereogenic center at its 3‐position (Figure a). Particularly, a 3,3′‐disubstituted 2‐benzofuranone skeleton has been found in numerous natural products .…”

“…In 2003, Fu and co‐workers reported the first enantioselective Steglich‐type (Black) rearrangement of furanyl carbonates with a ferrocene‐based nucleophilic catalyst . Their study inspired the development of various methods using a nucleophilic catalyst ,,. Several reports showed high enantioselectivity, but required high catalyst loading (typically 10–20 mol %) and a long reaction time (>24 h), and the ability of the reactions to tolerate functional groups was not fully studied (only simple alkyl and aryl groups were tested).…”