Synthesis of highly rigid phosphine–oxazoline ligands for palladium-catalyzed asymmetric allylic alkylation

Abstract

Rigid phosphine–oxazoline ligands with a spirocarbon stereogenic center were developed, which exhibited excellent catalytic performance for Pd-catalyzed allylic alkylation reactions.

Spiro Indane-Based Phosphine-Oxazolines as Highly Efficient P,N Ligands for Enantioselective Pd-Catalyzed Allylic Alkylation of Indoles and Allylic Etherification

“…The chiral phosphine-oxazoline ligands L1 – L4 were synthesized according to the literature [36]. We investigated the ability of four representative spiro phosphine-oxazoline ligands L1 – L4 for palladium-catalyzed asymmetric allylic alkylation of indole.…”

“…HPLC was performed on a Shimadzu LC-20 Liquid Chromatograph ( Shimadzu, Kyoto, Japan) using chiralcel OD-H, AD-H and OJ-H columns. Ligands L1 – L4 were prepared according to the reported procedure [36].…”

“…So far, there are four kinds of spiro phosphine-oxazoline ligands reported, including SIPHOX (spirobiindane-based phosphine-oxzoline ligands) by Zhou [25,26,27,28,29,30], SpinPHOX (spiro[4.4]-1,6-nonadiene-based phosphine-oxazoline ligands) by Ding [31,32,33,34], HMSI-PHOX (hexamethyl-1,1’-spirobiindane phosphine-oxazoline ligands) by Lin [35] and SMI-PHOX (an abbreviation for spiro mono-indane-based phosphine-oxazoline ligands L1 – L4 in Scheme 1) by us [36,37]. Compared with the other three ligands, SMI-PHOX ligands possess potentially distinct features: (i) first spiro indane-based phosphine-oxazoline ligand with non- C 2 -symmetric skeleton in asymmetric metal catalysis; (ii) better stability and higher rigidity; (iii) only one chiral center avoiding the complex stereochemistry; (iv) modularity by changing easily accessible carboxylic acid and ClPR 2 2 [36]. Because of the aforementioned properties, SMI-PHOX ligands have demonstrated excellent catalytic performance in several asymmetic reactions [36,37].…”

“…Compared with the other three ligands, SMI-PHOX ligands possess potentially distinct features: (i) first spiro indane-based phosphine-oxazoline ligand with non- C 2 -symmetric skeleton in asymmetric metal catalysis; (ii) better stability and higher rigidity; (iii) only one chiral center avoiding the complex stereochemistry; (iv) modularity by changing easily accessible carboxylic acid and ClPR 2 2 [36]. Because of the aforementioned properties, SMI-PHOX ligands have demonstrated excellent catalytic performance in several asymmetic reactions [36,37]. Therefore, we envisaged that they would be efficient chiral ligands for an indole C3-allylic alkylation reaction.…”

New Rigid Polycyclic Bis(phosphane) for Asymmetric Catalysis

“…Since the formation of the Heck reaction product is rather non-typical for norbornene substrates, we supposed that the observed minor by-product could have the structure of a tetracyclic compound ( 4 ). Interestingly, the best chiral ligands used in the transition-metal-mediated asymmetric synthesis display chirality in the backbones of the ligand and a rigid structure weakly influenced by random conformational changes [14]. This phenomenon has its roots in the fact that the catalysts with restricted freedom of conformational movements more significantly differentiate the competitive transition states leading to enantiomeric reaction products.…”