Two Regiocomplementary Approaches to Angular Furanocoumarins with Chromium Carbene Complexes: Synthesis of Sphondin, Thiosphondin, Heratomin, and Angelicin

Article abstract of DOI:10.1021/ja00230a023

Two regiocomplementary syntheses of the angular furanocoumarin sphondin are described utilizing the benzannulation reaction of furylcarbene complexes of chromium.The high regioselectivity of an intermolecular synthesis employing the reaction of <(2-furyl)(methoxy)methylene>pentacarbonylchromium (8) and methyl 4-pentynoate is thought to be controlled by the preferred conformation of an alkyne-carbene complex intermediate.By utilizing the same acetylene, heratomin and an unnatural derivative of sphondin, 6-methoxy-2-oxo(2H)-thiofuro(2,3-h)benzopyran were prepared from <(2-furyl)(3-methyl-2-butenoxy)carbene>pentacarbonylchromium (37) and <(2-thiofuryl)(methoxy)carbene>pentacarbonylchromium (31), respectively.An intramolecular synthesis of sphondin from <(3-furyl)<<2-(phenylthio-5-(trimethylsilyl)-4-pentynyl>oxy>carbene>pentacarbonylchromium (10e) incorporates the acetylene with reversed regiochemistry due to the geometrical constraints of the intramolecular annulation.Control over the formation of the regiochemistry correct for the carbon skeleton of sphondin is possible due to the regioselectivity in the annulation of unsymmetrical aromatic substituents (3-furyl) on the carbene carbon.The intramolecular synthesis is thus related to the intermolecular synthesis by a double reversal in the regiochemistry.A convergent synthesis of sphondin and angelicin is described which has the phenol 72 produced from the intramolecular benzannulation of complex 10e as a branch point and is differentiated by whether the phenol functionality is retained or reduced.