A sequential Pummerer-Diels-Alder route for the generation and trapping of furo[3,4-c]pyridines: synthesis of heterocyclic analogues of 1-arylnaphthalene lignans.
The Pummerer reaction of an o-benzoyl-substituted pyridylmethyl sulfoxide generates an alpha-thiocarbocation, the interception of which by a neighboring keto functionality produces an alpha-thio-substituted furo[3,4-c]pyridine as transient intermediate; the latter undergoes a Diels-Alder cycloaddition with an added dienophile. Base-induced ring opening of the cycloadduct followed by aromatization gives an isoquinoline derivative that may be looked upon as a heterocyclic analogue of 1-arylnaphthalene lignans. This procedure occurs readily with electron-poor dienophiles and the entire sequence can be run in one pot. The facility of the sequential Pummerer-Diels-Alder reaction hinges on the experimental conditions, the best results being obtained with heptafluorobutyric anhydride as the triggering agent in toluene containing a catalytic amount of p-toluenesulfonic acid. In the absence of a dienophile it is possible to isolate and characterize a rather unstable furo[3,4-c]pyridine derivative. An intramolecular variant of this protocol is also feasible with use of unactivated alkenyl tethers of variable length; however, the bridged cycloadducts are unisolable in these cases as they undergo spontaneous ring opening and aromatization to yield cycloalka[h]isoquinolines. The usefulness of the sequential Pummerer-Diels-Alder reaction is further demonstrated through the synthesis of a heterolignan with a built-in lactone ring via oxidation of the initial [4+2]-cycloadduct followed by extrusion of phenyl sulfinate and elaboration of the resulting hydoxylated isoquinoline derivative.
Sarkar
Tarun K
TK
Department of Chemistry, Indian Institute of Technology, Kharagpur-721302, India. tksr@chem.ittkgp.ernet.in
Panda
Niranjan
N
Basak
Sankar
S
D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D017705:Lignans / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D009281:Naphthalenes / Q000138:chemical synthesis*; D011725:Pyridines / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D006571:Heterocyclic Compounds; D007202:Indicators and Reagents; D017705:Lignans; D009281:Naphthalenes; D011725:Pyridines