Molecular scaffolds with remote directing groups for selective palladium-catalyzed C–H bond functionalizations

Abstract

Materials and Methods. All reactions were performed under an argon atmosphere unless otherwise noted. Tetrahydrofuran, N,N-dimethylformamide, dichloromethane, hexanes, and toluene were purified by passing through activated alumina columns. Diisopropylamine was distilled over CaH 2. 2-Fluoropyridine was freshly distilled before use. All other reagents were used as received unless otherwise noted. Commercially available chemicals were purchased from Alfa Aesar (Ward Hill, MA), Sigma-Aldrich (St. Louis, MO), Gelest (Morrisville, PA), Oakwood Products (West Columbia, SC), Strem (Newburport, MA), Mallinckrodt Chemicals (Phillipsburg, NJ), Spectrum (Gardena, CA) Fischer Scientific (Fair Lawn) and TCI America (Portland, OR). Qualitative TLC analysis was performed on 250 mm thick, 60 Å, glass backed, F254 silica (Silicycle, Quebec City, Canada). Visualization was accomplished with UV light and exposure to either p-anisaldehyde or KMnO 4 solution followed by heating. Flash chromatography was performed using Silicycle silica gel (230-400 mesh). 1 H NMR spectra were acquired on either a Varian Mercury 300 (at 300 MHz), a Varian Inova 400 (at 400 MHz), or a Varian 400 MR (at 400 MHz) and are reported relative to SiMe 4 (δ 0.00). 13 C NMR spectra were acquired on either a Varian Inova 400 (at 100 MHz), a Varian Mercury 300 (at 75 MHz), or a Varian 400 MR (at 100 MHz) and are reported relative to SiMe 4 (δ 0.0). All IR spectra were obtained on NaCl plates (film) with either a Nicolet Magna FTIR 760, a Nicolet 380 FTIR, or a Bruker Tensor 27. High resolution mass spectrometry data were acquired by the Colorado State University Central Instrument Facility on an Agilent 6210 TOF LC/MS. Optical rotations were obtained with an Autopol-III automatic polarimeter.

An analysis of the complementary stereoselective alkylations of imidazolidinone derivatives toward α-quaternary proline-based amino amides

“…Included in these electrophiles is 2-fluoropyridine, representing a straightforward strategy for synthesizing our aforementioned targeted molecular scaffolds. 2 Lithium chloride as an additive was notably helpful for this specific electrophile. The benefits of LiCl as an additive in anionic additions to glycine methyl ester have been noted; 13 a similar Lewis acid coordination of the pyridyl electrophile may be operative here.…”

“…As part of an overarching strategy for novel catalytic directed C-H functionalizations based on temporary molecular scaffolds, 2 we had discovered compounds reminiscent of the structural classes that are synthesized via SRS chemistry (e.g., amide 1 , Fig. 2).…”

“…2). These compounds were designed to covalently attach to carbonyl substrates, and when attached (as imidazolidinones), could induce site-specific Pd-catalyzed acetoxylations and olefinations on both sp 2 - and sp 3 -hybridized bonds. Given the observed ability of these molecules to impart this reactivity, we desired a simple and direct approach to this class of scaffolds, ideally with sufficient modularity to accommodate variations in both amide and ligating group.…”

Asymmetric C–H functionalization of cyclopropanes using an isoleucine-NH2 bidentate directing group

“…Elegant examples of the diastereoselective functionalization of unactivated C(sp 3 )–H in chiral substrates were revealed by the Corey, 3 b Daugulis 3 q and Chen groups. 3d , 3m Moreover, remarkable achievements in catalytic asymmetric C–H activation have been demonstrated using a chiral auxiliary 8 and a chiral ligand. 9 We hypothesized that an appropriate chiral bidentate directing group embedded in the substrate could induce high levels of stereocontrol during C–H functionalization via a steric repulsion model.…”

Diastereoselective Substrate-Controlled Transition-Metal-Catalyzed C–H Activation: An Old Solution to a Modern Synthetic Challenge

“…In 2012, Ferreira proposed a complementary strategy to achieve regio-and stereoselective C-H activation. 16 Contrary to the standard directing-group strategy, in which a DG is directly embedded within the substrate, this approach involved the use of a specific chiral molecular framework bearing an additional nonstereogenic coordinating moiety. This molecular framework should be easy to install on a C-H activation substrate and might be readily removable after the functionalization step.…”