Palladium‐ and Ruthenium‐Catalyzed Intramolecular Carbene C_Ar−H Functionalization of γ‐Amino‐α‐diazoesters for the Synthesis of Tetrahydroquinolines

Abstract

A synthetic method to prepare tetrahydroquinoline‐4‐carboxylic acid esters has been developed through the transition‐metal‐catalyzed intramolecular aromatic C−H functionalization of α‐diazoesters. Both [{Pd(IMes)(NQ)}2] (IMes=1,3‐dimesitylimidazol‐2‐ylidene, NQ=1,4‐naphthoquinone) and the first‐generation Grubbs catalyst proved effective for this purpose. The ruthenium catalyst was found to be the most versatile, although in a few cases the palladium complex afforded better yields or selectivities. According to DFT calculations, Pd0‐ and RuII‐catalyzed sp2‐CAr−H functionalization proceeds through different reaction mechanisms. Thus, the Pd0‐catalyzed reaction involves a Pd‐mediated 1,6‐H migration from the sp2‐CAr−H bond to the carbene carbon atom, followed by a reductive elimination process. In contrast, electrophilic addition of the ruthenacarbene intermediate to the aromatic ring and subsequent 1,2‐proton migration are operative in the Grubbs catalyst promoted reaction.

Palladium-Catalyzed Trans-Selective Synthesis of Spirocyclic Cyclobutanes Using α,α-Dialkylcrotyl- and Allylhydrazones

“…The structure of 13 was confirmed by an X-ray crystallographic analysis. Assuming C–H insertion products arise from a square planar palladium­(II) carbene intermediate, we tentatively attribute the selectivity for compound 3b to the poor migratory aptitude of the enone group into the carbene carbon . Thus, the enone may serve as an ancillary ligand on palladium that increases the electrophilicity of the carbene intermediate.…”

Ruthenium Catalyzed Intramolecular C−X (X=C, N, O, S) Bond Formation via C−H Functionalization: An Overview

“…A methodology for the preparation of tetrahydroquinoline‐4‐carboxylic acid esters was reported by the groups of Solé and Fernández with transition‐metal catalyzed intramolecular C−H functionalization of α‐diazoesters (Scheme 27). [37] The reaction works well with both the first‐generation Grubbs catalyst and the palladium catalyst ([{Pd(IMes)(NQ)} 2 ] (IMes=1,3‐dimesitylimidazol‐2‐ylidene, NQ=1,4‐naphthoquinone)). The ruthenium catalyst (Grubbs catalyst) was found to be quite versatile and operates in relatively mild condition.…”

Recent advances in transition-metal-catalyzed carbene insertion to C–H bonds

“…Notably, palladium catalysts have also been documented to enable intramolecular aryl C(sp 2 )-H functionalization by carbene insertion. 310,311 To suppress cyclopropanation as the side reaction the strategy is to diminish coordination of the CQC bond of an arene or alkene substrate to the catalytically active metal center. 4,216,293 Scheme 84 Ru(II)-catalyzed aryl C(sp 2 )-H functionalization by carbene insertion with diazo compounds.…”