Batch and Flow Photochemical Benzannulations Based on the Reaction of Ynamides and Diazo Ketones. Application to the Synthesis of Polycyclic Aromatic and Heteroaromatic Compounds

available in PMC 2014 November 1Highly substituted polycyclic aromatic and heteroaromatic compounds are produced via a two-stage tandem benzannulation/cyclization strategy. The initial benzannulation step proceeds via a pericyclic cascade mechanism triggered by thermal or photochemical Wolff rearrangement of a diazo ketone. The photochemical process can be performed using a continuous flow reactor which facilitates carrying out reactions on a large scale and minimizes the time required for photolysis. Carbomethoxy ynamides as well as more ketenophilic bis-silyl ynamines and N-sulfonyl and N-phosphoryl ynamides serve as the reaction partner in the benzannulation step. In the second stage of the strategy, RCM generates benzofused nitrogen heterocycles, and various heterocyclization processes furnish highly substituted and polycyclic indoles of types that were not available by using the previous cyclobutenone-based version of the tandem strategy.National Institutes of Health (U.S.) (GM 28273)National Science Foundation (U.S.) (CHE-1111567)Boehringer Ingelheim PharmaceuticalsAstraZeneca (Firm) (Graduate Fellowship)Massachusetts Institute of Technology (George Buchi Summer Fellowships)Massachusetts Institute of Technology (Merck Fellowship)Massachusetts Institute of Technology (David A. Johnson Fellowship)Massachusetts Institute of Technology (C. P. Chu and Y. Lai Fund)Merck Research Laboratorie