Molecular Formula
C16H18N2O2
Boiling Point
542.1±50.0 ℃
Relative Density
1.282±0.06
General Description
HMNPC is an effective chiral ligand that is optimized for copper-catalyzed sulfination of (hetero)aryl chlorides. This ligand allows the direct transformation of a variety of aryl chlorides to synthetically useful methylsulfones, using sodium methanesulfinate as the sulfur reagent. The unique structural features - including the essential 2-methylnaphthalene group and free 4-hydroxyl moiety - work synergistically to enhance ligand stability, solubility, and copper coordination efficiency.
Application
HMNPC offers an accessible and cost-effective means to the pharmaceutical important (hetero)aryl methylsulfones, which are utilized as the building blocks for some drugs. The ligand shows good substrate scope for para/meta-substituted arenes, dichloroarenes (allowing regioselective mono-coupling) and a range of heteroaryl chlorides such as quinoline, pyridine and thiophene derivatives.
HMNPC is the optimal ligand identified so far for the first Cu-catalyzed coupling of (hetero)aryl chlorides with cheaper sodium methanesulfinate. Under standard conditions (10 mol % CuI, 10 mol % HMNPC, 1.0 equiv K3PO4, DMSO, 120 ℃, 24-36 h) a wide variety of electron-rich, electron-poor and sterically hindered aryl chlorides are efficiently converted to pharmaceutically important (hetero)aryl methylsulfones at 70-96 % isolated yield.
Mechanistically, the deprotonated HMNPC is proposed to chelate Cu(I) through pyrrolidine nitrogen and amide oxygen, which primes the oxidative addition of the C-Cl bond and reductive elimination. The protocol is free of unpleasant thiols or additional oxidation steps and enables an economical and late-stage-ready method for synthetically valuable (hetero)aryl methylsulfones.
Fig. 1 CuI/HMNPC catalyzed coupling of (hetero)aryl chlorides with sodium methanesulfinate. (Ma D.; et al. 2017)
References
- Ma D, et al. A New Class of Amide Ligands Enable Cu‐Catalyzed Coupling of Sodium Methanesulfinate with (Hetero) aryl Chlorides. Chinese Journal of Chemistry, 2017, 35(11): 1661-1664.
What is the IUPAC name for HMNPC?
((2S,4R)-4-Hydroxy-N-(2-methylnaphthalen-1-yl)pyrrolidine-2-carboxamide.
What is the HMNPC ligand used for?
HMNPC allows for Cu-catalyzed sulfone synthesis from aryl chlorides.
What are the main benefits of HMNPC?
High yield, wide substrate scope, no thiols/oxidation steps required.
Is HMNPC ligand process chemistry friendly?
Yes, suitable for scale-up and late-stage functionalization.
What is the MOQ for HMNPC?
Please inquire about details on the MOQ.
