Abstract
SummaryIn transition metal-catalyzed asymmetric synthesis, enantioselectivity strongly depends on the structures of chiral ligands, so the development of new chiral ligands is crucial. Here, an efficient and highly enantioselective palladium-catalyzed intramolecular hydroarylation has been developed, and a new kind of N-heterocycles, 1H-pyrazolo[5,1-a]isoindol-2(8H)-ones containing a quaternary stereocenter, was prepared in high yields and excellent enantiomeric excess values. The reaction was effectively catalyzed by palladium-diphosphine complexes with numerous functional group tolerance, in which the newly developed axially chiral cyclic diphosphine ligands played key roles in the reactivity and enantioselectivity of the substrates. We believe that the cyclic diphosphine ligands with adjustable dihedral angles will find wide application in asymmetric synthesis.
Highlights
Nitrogen-containing compounds widely occur in biologically active molecules including natural products (Ruiz-Sanchis et al, 2011), agrochemicals, and pharmaceuticals (Leeson and Springthorpe, 2007)
We have developed a kind of novel axially chiral cyclo[1,10-biphenyl]-2,20-diols (CYCNOL) with adjustable dihedral angles (Zhang et al, 2016), and the chiral cyclic phosphoramidite ligands derived from CYCNOL have been successfully applied in iridium-catalyzed enantioselective arylation of unactivated racemic secondary allylic alcohols (Tian et al, 2017) and synthesis of dihydroimidazoquinazolinones (Peng et al, 2017)
Crystal Structures of Ligands Single crystals of the axially chiral cyclic diphosphine ligands (S)-CYC-8-BIPHP ((S)-E), (S)-CYC-9-BIPHP ((S)-F), and (S)-CYC-10-BIPHP ((S)-G) from mixed hexane and dichloromethane solvent were prepared, and their structures were unambiguously confirmed by X-ray diffraction analysis
Summary
Nitrogen-containing compounds widely occur in biologically active molecules including natural products (Ruiz-Sanchis et al, 2011), agrochemicals, and pharmaceuticals (Leeson and Springthorpe, 2007). Over 90% of pharmaceuticals contain at least one nitrogen atom in their structures, so the development of efficient approaches to N-heterocycles is of paramount importance (Carey et al, 2006; Duggers et al, 2005). Compounds containing a l,8-diazabicyclo[3.3.0]octane skeleton exhibit diverse biological activities. They are used as the androgen receptor modulator (Ullrich et al, 2014), angiotensin II receptor antagonist (Levin et al, 1994), and DNA topoisomerase inhibitor (Figure 1) (Katayama et al, 1999). To the best of our knowledge, enantioselective synthesis of this kind of compounds containing a quaternary stereocenter has not been reported far
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
