Intramolecular (4+3) Cycloadditions of Thiophenes

Abstract

The (4+3) cycloaddition is a convergent strategy for the synthesis of carbocyclic seven-membered rings.1 Most of these cycloadditions proceeded with common dienes such as cyclopentadiene and furan. In the intramolecular context, the vast majority of the cycloadditions are with furan. This is because cycloaddition precursors bearing furans are more readily synthesized; moreover, furan is an excellent diene for cycloaddition. Our studies on epoxy and aziridinyl enolsilanes as dienophiles showed that their intramolecular (4+3) cycloadditions occurred not only with furans, but also with various pyrroles,2 based on which we designed and accomplished a synthesis of the BCDEF rings of the Type II galbulimima alkaloids.3 Our continuing studies found that thiophenes also undergo intramolecular (4+3) cycloadditions to generate sulfur-bridged, tricyclic scaffolds. The reaction occurs with up to 81% yield, and tends to be exo-selective. This is the only example of any (4+3) cycloaddition with thiophenes, except for a singular report in 1985 with an unspecified yield.4 The sulfur-bridged cycloadducts can be desulfurized to yield bicyclo[5.4.0] undecene frameworks which are found in many natural products.