Pd(II)-Catalyzed Hydroxyl-Directed C−H Olefination Enabled by Monoprotected Amino Acid Ligands

Abstract

A novel Pd(II)-catalyzed ortho-C-H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote the reaction, and an array of olefin coupling partners could be used. When electron-deficient alkenes were used, the resulting olefinated intermediates underwent subsequent Pd(II)-catalyzed oxidative intramolecular cyclization to give the corresponding pyran products, which could be converted into ortho-alkylated alcohols under hydrogenolysis conditions. The mechanistic details of the oxidative cyclization step are discussed and situated in the context of the overall catalytic cycle.

Alcohols or Masked Alcohols as Directing Groups for C–H Bond Functionalization

“…In 2010, Yu and co-workers disclosed a Pd(II)-catalyzed aromatic ortho-CH olefination using spatially remote unprotected alcohols as the directing groups. 7 Their initial attempts to perform CH palladation with a fully depronated alcohol (via a [Pd II OR] species) turned out to be unfruitful. However, they then envisioned that a different coordination mode with a neutral alcohol could be more effective (Scheme 1).…”

Palladium‐Catalyzed Oxidative CC Bond Cleavage Cyclization of Biaryl‐2‐amines with Alkenes Involving CH Olefination and Carboamination

“…[4][5][6][7] Complexation of Pd(II) and then C À H functionalization forms [12] In summary, we have described a novel palladiumcatalyzed oxidative cleavage cyclization of biaryl-2-amines with alkenes involving C À H oxidative olefination and carboamination. This method displayed high substrate compatibility: it tolerates a wide range of biaryl-2-amines and alkenes for the C À C bond oxidative cleavage cyclization through a tandem process.…”

“…To overcome these drawbacks, a strategy including C À H olefination, initially studied by Fujiwara and Moritani, is an attractive alternative. [2][3][4][5][6][7] Among the C À H olefination methods, considerable efforts were devoted to the directing group strategy using Pd(II)/[O] catalytic system recently because it could improve the reactivity, extend substrate compatibility and control selectivity. [3][4][5][6][7] However, examples of the C À H olefination, followed by cyclization with directing groups are much less abundant.…”

“…[2][3][4][5][6][7] Among the C À H olefination methods, considerable efforts were devoted to the directing group strategy using Pd(II)/[O] catalytic system recently because it could improve the reactivity, extend substrate compatibility and control selectivity. [3][4][5][6][7] However, examples of the C À H olefination, followed by cyclization with directing groups are much less abundant. [4][5][6][7] Actually, this C À H olefination and cyclization strategy is useful for the synthesis of complicated heterocycles, which makes the directed C À H olefination more fascinating.…”

“…[3][4][5][6][7] However, examples of the C À H olefination, followed by cyclization with directing groups are much less abundant. [4][5][6][7] Actually, this C À H olefination and cyclization strategy is useful for the synthesis of complicated heterocycles, which makes the directed C À H olefination more fascinating. [5][6][7] Diamond and co-workers have first reported the formation of both 2-methylquinoline and N-ethylaniline from the reaction of aniline with ethylene and PdCl 2 at 200 8C.…”