The preparation of substituted indoles: Towards the synthesis of indole alkaloids

N-Arylsulfonyl quinone monoimines were prepared using literature procedures and underwent smooth cycloadditions in a [4+2] sense with a variety of 1,3-butadienes to yield the expected cycloadducts. Treatment of these crude adducts with catalytic amounts of base yielded the corresponding dihydronaphthalenes. Subjection of these highly substituted dihydronaphthalenes to a short series of simple transformations produced synthetically useful quantities of 5-hydroxyindole derivatives in excellent yields (39-68 % over the six steps). The 5-triflyloxyindoles were then subjected to a variety of cross-coupling reactions illustrating their versatility in the construction of more sophisticated indole motifs.;The first synthesis of the western hemisphere of lolicine A and B was achieved utilizing our indole forming methodology. The synthesis was accomplished in 23 linear steps with an overall yield of 2.1%. Following the preparation of the highly substituted indole via the Diels-Alder/Plieninger indolization strategy, the key step in the sequence is the tandem conjugate addition/aldol cyclization. This one step sets the relative stereochemistry of the tetrahydrofuran ring as well as produces the benzofused tricyclic system containing all of the suitable functional groups for conversion into the natural product. Subsequent functional group manipulations and deprotections completed the synthesis of the target molecule.;Key words. Indole, Diels-Alder, Plieninger indolization, cross-coupling reactions, hapalindole, enyne metathesis, lolicines, lolitrems, organocuprate, phenylseleno-etherification, total synthesis, alkaloids.;The synthesis of the tetracyclic skeleton of the hapalindole alkaloids was accomplished through the use of the enyne metathesis/Diels-Alder approach. Utilizing the Plieninger indolization procedure, construction of a suitable enyne metathesis precursor that contained the required geminal dimethyl quaternary center was achieved. Enyne metathesis of this molecule followed by a Diels-Alder cycloaddition yielded the tetracyclic skeleton found in the hapalindole alkaloids in 13 steps with an overall yield of 6.9%. This research has laid the groundwork for the total synthesis of one, or several hapalindoles using this approach. The remainder of the synthesis has been outlined and is expected to be accomplished in due course.