Brian Tarbit

Functionalized Heteroarylpyridazines and Pyridazin-3(2H)-one Derivatives via Palladium-Catalyzed Cross-Coupling Methodology

A general method for the synthesis of functionalized pyridazinylboronic acids/esters is described involving a directed ortho metalation (DoM)--boronation protocol (Schemes 1 and 2). A comprehensive study of the reactivity of the C-B bond in palladium-catalyzed cross-couplings with aryl/heteroaryl halides is presented. Aryl-/heteroarylpyridazines are thereby obtained in synthetically viable yields (typically 40-75%) although in some cases competing protodeboronation has been observed. A series of pyridazin-3(2H)-one derivatives, including 4,6-diaryl/heteroaryl derivatives, have been obtained from the corresponding 3-methoxypyridazines in straightforward procedures (Schemes 3 and 4). Several X-ray crystal structures of aryl-/heteroarylpyridazines and derived pyridazin-3(2H)-one derivatives are reported. These multi-ring systems are of considerable interest in contemporary N-heterocyclic chemistry.

Synthesis of pyridine derivatives using aza Diels–Alder methodology

Abstract Amidrazone 1 reacted with the unsymmetrical tricarbonyls 2a , 2c and 2d giving triazines 3a , 3c and 3d , respectively. These triazines were converted into their corresponding pyridine derivatives 6a , 6c and 6d in aza Diels–Alder reactions with 2,5-norbornadiene 5 . Triazines 3c and 3d gave the pyridolactones 9c and 9d with 2,3-dihydrofuran.

Desymmetrization of dichloroazaheterocycles

3,6-Dichloropyridizine 1a was converted in good yield into its mono-iodo derivative 1b when treated with a mixture of hydriodic acid and sodium iodide. Pure samples of the mono-iodo derivatives 2b, 3b and 4b could not be obtained from their corresponding dichlorinated precursors with these reagents. Compounds 1b and 4b underwent palladium catalysed Suzuki, Sonogashira and other coupling reactions.

Synthesis of 2,2′-bipyridyl derivatives using aza Diels-Alder methodology

Amidrazone 1 and the tricarbonyl derivatives 2a-c gave the triazines 3a-c, respectively, which reacted with 2,5-norbornadiene 4 in boiling ethanol yielding the corresponding novel 2,2′-bipyridines 5a-c in good yield. Triazine 6 gave the 2,2′-bipyridyl derivative 7 (65%) with compound 4 in 1,2-dichlorobenzene at 140°C.

A convenient synthesis of substituted 2,2':6',2 -terpyridines

The 2,2′:6′,2″-terpyridines 7a–c were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 3a–c with bis-amidrazone 4 and 2,5-norbornadiene 6 in ethanol at reflux. Compounds 3a and 3b gave the 2,2′:6′,2″-terpyridines 9a and 9b, respectively, in moderate yield when treated with compound 4 and enamine 8.

5-Formyl-2-furylboronic acid as a versatile bifunctional reagent for the synthesis of π-extended heteroarylfuran systems

5-Formyl-2-furylboronic acid reacts cleanly with a range of heteroaryl bromides under Suzuki-Miyaura cross-coupling conditions to produce 2-formyl-5-heteroarylfuran derivatives. Subsequent Wittig olefination reactions afford pi-conjugated alkene-pyridyl-furan derivatives.

Arylated pyridines: Suzuki reactions of O-substituted 2,6-dihalogenated-3-hydroxypyridines

2-Bromo-6-iodo-3-methoxypyridine 5b yielded mono-arylated derivatives 6b–9b and teraryls 10b–14b in selective Suzuki reactions.