Pd-catalyzed access to mono- and di-fluoroallylic amines from primary anilines

Abstract

The Pd-catalyzed highly selective synthesis of mono- and di-2-fluoroallylic amines is herein described from gem-difluorocyclopropanes and ubiquitous unprotected primary anilines. Initial kinetic investigations suggest a first order in the gem-difluorocyclopropane...

CO2 and palladium enabled highly chemoselective hydroxylation of gem-difluorocyclopropanes

“…From these experiments, it can be deduced that CO 2 prevents the formation of double C-O coupling product 3a, presumably through transient carbonate ester protection, in contrast to N 2 . Increasing the temperature further to 110 °C under N 2 atmosphere, along conditions previously reported by us for amines, 70 afforded the double C-O coupling product 3a in 25% yield (Fig. 6, eqn (3)).…”

“…Increasing the temperature further to 110 °C under N 2 atmosphere, along conditions previously reported by us for amines, 70 afforded the double C-O coupling product 3a in 25% yield (Fig. 6, eqn (3)).…”

“…We therefore initially selected 4-methyl- gem -difluoro-cyclopropane ( 1a ) as a model substrate. Based on a previous report from our group, 70 we serendipitously realized that 1a produces fluoroallyl alcohol product 2a in high isolated yield (93%) when exposed to Pd(dba) 2 (10 mol%), Xphos (20 mol%), water (10 equiv. ), and K 3 PO 4 (3 equiv.)…”

“…Based on literature precedents, [70][71][72] we conceived that the Pd(0) active species would first perform the oxidative addition into the strained C-C bond of substrate 1 leading to strained palladacycle intermediate Int-I (Fig. 2).…”

Pd-IHept-Catalyzed Ring-Opening of gem-Difluorocyclopropanes with Malonates Via Selective C–C Bond Cleavage: Synthesis of Monofluoroalkenes

“…We first investigated the common Pd-NHC catalysts 15 such as Pd-IMes (IMes = N, N′-bis(2,4,6trimethylphenyl)imidazol-2-ylidene) and Pd-IPr (IPr = N,N′bis(2,6-di(2-propyl)phenyl)imidazol-2-ylidene), and the desired product 3a was obtained in 5 and 16% yields, respectively (entries 1 and 2). We then tested the bulky IPr* ligand that was developed by Markóand co-workers, 16 with which 3a was achieved in 40% yield, along with an 8% yield of the double fluoroallylation 17 product 4a (entry 3). Given the limited flexibility of the IPr* ligand, we next investigated the Pd-PEPPSI-ITent (PEPPSI = pyridine-enhanced precatalyst preparation stabilization and initiation; Tent = tentacular) catalysts (entries 4−6), which are more σ-donating with flexible steric bulk.…”