Exploration of chiral diastereomeric spiroketal (SPIROL)-based phosphinite ligands in asymmetric hydrogenation of heterocycles

Abstract

New and readily available chiral SPIROL-based diphosphinite ligands (SPIRAPO) have been prepared and employed for iridium catalyzed asymmetric hydrogenations of quinolines, quinoxalines and 2H-1,4-bezoxazin-2-ones.

Synthesis and Evaluation of C2-Symmetric SPIROL-Based bis-Oxazoline Ligands

“…The general information about reagents and equipment and the copies of 1 H and 13 C NMR spectra for compounds 2-8 and HPLC traces for chiral product 4 are provided in Supplementary Materials. Enantiopure (R,R,R)-SPIROL (2) [15,16] (500.0 mg, 1.60 mmol, 1.0 equiv.) and pyridine (2.85 mL, 37.8 mmol, 23.6 equiv.)…”

“…Our studies commenced with the (R,R,R)-SPIROL (2) (Scheme 2), which was obtained in an enantiopure form after recrystallization using the protocol previously described by our group [15,16]. Using 2 as the starting material, the bistriflate (R,R,R)-5 was synthesized in 97% yield by reacting it with triflic anhydride and pyridine.…”

“…Thus, for example, (S,S,S)-SPIRAP was found to be an excellent ligand for the asymmetric Ir-catalyzed hydroarylation reaction (cf. Scheme 1B), while the same reaction with its diastereomer (R,S,S)-SPIRAP as the ligand did not produce any product [15]. Similarly, (R,S,S)-SPIRAPO was found to be a superior ligand for the Ir-catalyzed dearomatizative hydrogenation of heterocyclic compounds that was used to accomplish gram-scale synthesis of (-)-(R)-angustureine (cf.…”

“…In particular, the developments in the design of C2-symmetric spirocyclic ligands has greatly impacted the field of asymmetric catalysis, and thousands of recent studies are focused on exploring such ligands in asymmetric synthesis and catalysis [5][6][7][8]. Powered by our long-term interests in chiral phosphoric acid catalysis [9][10][11][12][13][14], our group has been engaged in the development and exploration of new spiroketal-based C2-symmetric spirocyclic ligands (SPIROLs) [15,16]. Thus, in 2018 we described the one-step asymmetric synthesis of diastereomeric (S,S,S)-and (R,S,S)-SPIROL (2) cores from the readily available chiral alcohols (S)-1 (Scheme 1A).…”

Catalytic asymmetric synthesis of N-substituted tetrahydroquinoxalines via regioselective Heyns rearrangement and stereoselective transfer hydrogenation in one pot

“…Therefore, extensive efforts have been devoted to the enantioselective synthesis of this class of heterocycles. Among the different strategies, asymmetric hydrogenation 5 or transfer hydrogenation 6 of quinoxalines represents one of the most straightforward choices ( Scheme 1a ). Many elegant catalytic systems have been reported using transition-metal catalysis or organocatalysis.…”