Pyridines from Azabicyclo[3.2.0]hept-2-en-4-ones through a Proposed Azacyclopentadienone

Abstract

Pyridines have been formed by heating azabicyclo[3.2.0]hept-2-en-4-ones in toluene. The generation of a 3-azacyclopentadienone intermediate via a [2 þ 2]-cycloreversion is proposed as the key step. A DielsÀAlder reaction of a styrene, extrusion of carbon monoxide, and loss of hydrogen then gives the pyridine. The process parallels the well-known synthesis of benzenes from cyclopentadienones. The azabicyclo[3.2.0]hept-2-en-4-ones were synthesized from the reaction between readily available cyclopropenones and 1-azetines, in which the cyclopropenones behave as all-carbon 1,3-dipolar equivalents.The pyridine ring occupies a position of great importance to the synthetic chemist due to its relevance in the pharmaceutical industry, in the agrochemical industry, in natural product chemistry, and in materials science. 1À3 It is thus the case that the synthesis of the pyridine ring by the use of new cycloaddition 1 and other 2 methodologies continues to be of current value, and such recent contributions ensure that this most studied 3 of areas remains a rich source for significant discoveries. Among the more recent

2-Methylsulfanylbenzo[f]isoquinoline

“…2-Methylthio-4-(naphth-2-yl)-1-azetine 5 (Scheme 1) has been synthesized by us before [9,10] and used in cycloaddition reactions. Previously, the 1-azetine was obtained by alkylation of the readily available [9,10] thiolactam 7, as shown in Scheme 1.…”

“…Previously, the 1-azetine was obtained by alkylation of the readily available [9,10] thiolactam 7, as shown in Scheme 1. When this reaction mixture is worked up and purified immediately, the 1-azetine is the major product, as already reported [9,10].…”

“…Previously, the 1-azetine was obtained by alkylation of the readily available [9,10] thiolactam 7, as shown in Scheme 1. When this reaction mixture is worked up and purified immediately, the 1-azetine is the major product, as already reported [9,10]. However, we have now found that when the crude 1-azetine reaction mixture from the reaction of thiolactam 7 with trimethyloxonium tetrafluoroborate is left overnight rather than used immediately, the 1-azetine is not the isolated product, but rearranges to give 2-methylthiobenzo[f]isoquinoline 4 (35% from 7) instead.…”

“…To 4-naphthylazetidin-2-thione 7 [9,10] (300 mg, 1.42 mmol) in dry dichloromethane (10 mL) in a 50 mL round-bottomed flask was added Meerwein's salt (312 mg, 2.11 mmol) under an atmosphere of dry nitrogen. The mixture was stirred at room temperature for 1 h and then at reflux for 1 h. The solution was cooled to room temperature and added drop-wise to a 50% aqueous solution of potassium carbonate (10 mL) at −10 °C and left to warm to room temperature overnight.…”

Synthesis, conformation and antiproliferative activity of isothiazoloisoxazole 1,1-dioxides

“…25 Nonetheless, we have shown that 1-azetines are able to act as precursors for the synthesis of benzoisoquinolines, 21 homotropane related heterocycles 22 and pyridines 23 via a formal [3+2]-cycloaddition reaction with cyclopropenones (which act as all-carbon 1,3-dipole equivalents) as well as acting as dipolarophiles for the synthesis of 1,2,4-oxadiazoles 24 via reaction with nitrile oxides. As a result of these successes, and given our interest in the β-sultam nucleus, we wished to explore the chemistry of the unsaturated β-sultam system, the thiazete 1,1-dioxide (4).…”