Pd(II)-Catalyzed Enantioselective Alkynylation of Unbiased Methylene C(sp³)–H Bonds Using 3,3′-Fluorinated-BINOL as a Chiral Ligand

Abstract

The first Pd(II)-catalyzed enantioselective alkynylation of unbiased methylene β-C(sp 3 )−H bonds is reported. The readily accessible and tunable BINOL derivatives are used as chiral ligands in C−H activation for the first time. 3,3′-Fluorinated-BINOL proved crucial in determining both the reactivity and enantioselectivity. A wide range of carboxylic acid derivatives are well tolerated with high enantioselectivities (up to 96% ee). Mechanistic studies suggest that multiple ligands may participate in the stereodetermining C−H palladation step, and a chiral amplification effect is observed.

Copper-catalyzed enantioselective Sonogashira-type oxidative cross-coupling of unactivated C(sp3)−H bonds with alkynes

“…Thus, directed palladium-catalyzed C−H activation has been shown to be an effective strategy for C( sp 3 )−H alkynylation 17–19 . However, only a few enantioselective examples have been disclosed with the expensive alkynyl bromide/iodine as the alkynylation reagents 16,20–22 . In comparison, an enantioselective Sonogashira-type cross-dehydrogenative coupling (CDC) of C( sp 3 )−H bonds with low-cost terminal alkynes would be more ideal due to the ready availability of both coupling partners.…”

Synthesis of Axially Chiral Styrenes through Pd‐Catalyzed Asymmetric C−H Olefination Enabled by an Amino Amide Transient Directing Group

“…[4f,h, 10] Inspired by the pioneering work by Yu and co-workers on the construction of central chirality through transient chiral auxiliary (TCA)-enabled CÀH functionalization, [11] we recently reported the highly atroposelective construction of biaryl atropoisomers using tert-leucine (Tle) as a TCA. [12] As part of our ongoing efforts in asymmetric C À H functionalization, [12,13] we had great interest in constructing axially chiral styrenes through a TCA strategy. We assumed that the enantiocontrolled introduction of a large substituent at the ortho position of properly designed 2-arylacrylaledhydes to lock the preformed axis through TCA-enabled C À H activation would be an attractive synthetic approach.…”

Synthesis of Chiral β‐Lactams by Pd‐Catalyzed Enantioselective Amidation of Methylene C(sp3)–H Bonds Enabled by a 2‐Pyridylisopropyl Auxiliary†

“…Based on our previous research on PIP, we hypothesized that the steric communication between gem ‐dimethyl group in our PIP auxiliary and backbone of a monodentate chiral C 2 ‐symmetric ligand may limit the free rotation to create a rigid and stronger chiral environment around the substrate (Scheme c, int‐A ). Fortunately, our group successfully developed a Pd(II)‐catalyzed enantioselective arylation and alkynylation of unbiased methylene C—H bonds enabled by the combination of PIP auxiliary with chiral phosphoric acids (CPAs) (up to 90% ee) or chiral 3,3’‐F 2 ‐BINOL (up to 96% ee), respectively (Scheme c) …”