Asymmetric Palladium-Catalyzed Aminochlorination of Unactivated Alkenes

Abstract

A novel Pd-catalyzed enantioselective aminochlorination of alkenes via a 6-endo cyclization is reported herein, which provides easy access to a wide array of structurally diverse 3chloropiperidines in good yields with excellent enantioselectivities. Notably, both an electrophilic chlorination reagent (NCS) and the sterically bulky chiral pyridinyl-oxazoline (Pyox) ligand are crucial to the successful reaction.

Synthesis of 3-chloropiperidines by iodide-mediated electrolysis

“…9 We therefore took great interest in finding efficient synthetic methods for the 3-chloropiperidine moiety so that a large variety of derivatives can be screened for their pharmacological properties. Conventional synthetic methods have already been developed in the past (Scheme 1), commonly utilizing oxidants in stoichiometric quantity to chlorinate an unsaturated amine followed by cyclization via a strong acid, 10 transition metal catalysis [11][12][13][14] or iodide catalysis. 15,16 The cyclization via free radicals has been reported as well.…”

Carbene-Catalyzed [4+2] Cycloaddition of Cyclobutenones and Isatins for Quick Access to Chiral Chlorine-Containing Spirocyclic δ-Lactones

“…Therefore, the development of a new and efficient approach for the quick introdution of a chiral chlorine atom into various functional molecules has attracted a considerable amount of attention and is greatly significant. Althrough a great number of impressive achievements have been realized in the preparation of chiral organochlorines, − the formation of stereoselective carbon–chlorine (C–Cl) bonds via enol or enolate intermediates by chiral Lewis acid catalysts and other organic catalysts (e.g., amine − , or phosphoric acid) has always been explored as a useful tool in these catalytic transformations (Scheme a). However, preparing enantiomerically enriched alkyl chlorides remains difficult.…”