IBX mediated reaction of β-enamino esters with allylic alcohols: a one pot metal free domino approach to functionalized pyridines

Abstract

IBX facilitated the reaction of β-enamino esters with allylic alcohols affording a direct, one-pot and metal free synthesis of functionalized pyridines including 2-substituted nicotinic acids, densely substituted pyridines and precursors of azafluorenones. The methodology also afforded the racemic pyridine core of cyclothiazomycin.

Enaminone, Enaminoesters, and Related Compounds in the Metal‐Free Synthesis of Pyridines and Fused Pyridines

“…A direct, one‐pot metal‐free synthesis of functionalized pyridines 105 has been developed via the IBX mediated reaction of readily available β‐enamino esters 103 and allylic alcohols 104 . This reaction afforded 2‐substituted nicotinic acids, tetrasubstituted unsymmetrical pyridines and precursors of azafluorenones . (Scheme ).…”

Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

“…Figure depicts several drug molecules that contain a nicotinate scaffold, including dexamethasone isonicotinate (an anti‐inflammatory, anti‐allergic glucocorticoid), morniflumate (an analgesic, antipyretic and anti‐inflammatory agent), flunixin meglumin (a cyclooxygenase inhibitor), vitamin E nicotinate (an antioxidants), nicorandil (a vasodilatory drug), and hepronicate (a hypolipidemic drug) . To date, many of approaches have been successfully developed to produce nicotinate skeletons by employing electron‐deficient β ‐enamino esters ( β ‐EAEs) as the readily accessible C,N ‐dinucleophilic synthons combined with the condensation of 1,3‐dicarbonyl compounds, α,β ‐unsaturated ketones, alkynones, Mannich base hydrochlorides, and IBX‐mediated oxidative annulation of allylic alcohols (Scheme ) . However, most of these methods have been compromised by harsh reaction conditions, stoichiometric halogenated reagents, functionalized starting materials, which could not fulfill the requirements of reagent efficiency.…”

Synthesis of new chiral lactam-fused pyridine derivatives

“…Meanwhile, 5a was obtained in 54% yield by treatment with an excess amount of ammonium acetate at room temperature in MeOH. 14 With these building blocks in hand, we attempted the reaction of 5a with 1.5 equivalents of 4a by stirring in MeOH, which led to complete consumption of 5a within 2 hours. Subsequent addition of 1.5 equivalents of pyridinium p-toluenesulfonate (PPTS) followed by stirring at room temperature for 9 days gave 3c in low yield.…”