Metal-Free Assembly of Polysubstituted Pyridines from Oximes and Acroleins

Abstract

Transition-metal-catalyzed synthesis of N-heterocycles from oximes has been previously well established. In this paper, for the first time a metal-free protocol with the combinational employment of iodine and triethylamine has been demonstrated to be effective to trigger the oxime-based synthesis of pyridines with high chemo-selectivity and wide functional group tolerance. A broad range of functional pyridines were prepared in moderate to excellent yields. While neither iodine nor triethylamine could trigger this transformation, mechanistic experiments indicated a radical pathway for the reaction. The resultant 2-aryl-substituted pyridines have been proved to be versatile building blocks in a range of transition-metal-catalyzed C-H functionalization reactions.

Iodine‐Promoted Semmler–Wolff Reactions: Step‐Economic Access to meta‐Substituted Primary Anilines via Aromatization

“…Therefore, our observations are preliminarily in agreement with a radical mechanism (Scheme c). The I 2 ‐mediated homolysis of N−O bond in oxime A gives imine radical B , which may quickly isomerize to α‐carbon radical C via 1,3‐H shift . Radical C undergoes two possible paths.…”

Tri‐Functional Elemental Sulfur Enabling Bis‐Heteroannulation of Methyl Ketoximes with Methyl N‐Heteroarenes

“…In recent studies on the transformation of methyl ketoxime acetates, transition-metal-catalysts such as copper, [11] iron, [12] ruthenium, [13] and others [14] were generally employed to activate NÀO bond of oximes, while few examples used iodine reagents. [15] Very recently, we discovered a copper-catalyzed system for the bis-annulation of ketoximes with elemental sulfur and benzaldehydes, in which the utilized copper catalyst played a key role to activate ketoxime acetates since only trace amounts of products were observed in the absence of a copper salt [16] (Figure 2, top). Interestingly, when we replaced benzaldehyde with 4-methylpyridine, the target bis-annulation was equally effective with or without the addition of a copper catalyst.…”

A Metal‐Free Based New Approach to 2,4‐Disubstituted Pyridines via One‐Pot Sequential Reaction of Cyclic Sulfamidate Imines with β‐Substituted Acroleins

“…It was witnessed that cyclic imine 1a efficiently participated in the Michael reaction with a range of α,β‐unsaturated aldehydes ( 2m‐2s ) bearing electron‐donating (OMe, OBn) and electron‐withdrawing (Cl, F, CF 3 , NO 2 ) substituents on the benzene rings catalyzed by L‐proline. As a consequence, all of the reactions led to the satisfactory to high yields (68‐83%) of the corresponding 2‐phenyl‐4‐arylpyridines ( 3am‐3as ) as these frameworks are widely used in the transition‐metal catalyzed C‐H functionalization reactions as well as preparation of a highly photoluminescent transition‐metal complexes . Similarly, not only aryl‐substituted cyclic imines ( 1c and 1g ) with MeO and Br groups on the aryl rings but also hetero‐substituted cyclic imine 1h underwent spotless reaction with a number of aryl‐substituted acroleins by this procedure to produce the corresponding 2‐aryl/heteroaryl‐4‐arylpyridines ( 3cm‐3hs ) in 65‐82% yields.…”