Synthesis and Evaluation of Enantiopure HMPA Analogs in Samarium-Diiodide-Promoted Dearomatizations of N-Acylated Indole Derivatives

Abstract

A series of (S)-proline-based enantiopure phosphorus triamide derivatives were prepared and evaluated as HMPA alternative in samarium diiodide cyclization reactions of N-acylated indole derivatives. The expected tricyclic indoline derivatives were generally obtained in good to excellent yields, however, the induced enantioselectivities were at best moderate. In our model reaction, the phosphorus triamide derivative with a (dimethyl)hydroxymethyl group at the stereogenic center provided the cyclization product in almost quantitative yield and with an enantiomeric excess of approximately 24 %. No separate proton source is required by applying this chiral Lewis base which was recovered in 93 % yield. Bulkier substituents at the stereogenic center did not furnish improved results. Although in our preliminary study only low to moderate enantioselectivities could be achieved, the observed fast conversions and the high yields demonstrate the basic suitability of chiral pyrrolidine-based phosphoramide Lewis bases in samarium(II)-induced reactions.