Photocycloaddition of Arenes and Allenes

• Published in: Journal of organic chemistry 2013-07, Vol.78 (14), p.6890-6910
• Main Authors: Streit, Ursula, Birbaum, Frédéric, Quattropani, Anna, Bochet, Christian G
• Format: Article
• Language: English
• Subjects: Alkadienes - chemistry; Benzene Derivatives - chemistry; Benzoxepins - chemical synthesis; Benzoxepins - chemistry; Bridged Bicyclo Compounds - chemical synthesis; Bridged Bicyclo Compounds - chemistry; Cyclization; Molecular Structure; Photochemical Processes; Stereoisomerism
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo4002307

In this work, we report on a new intramolecular para cycloaddition of arenes with allenes, yielding attractive rigid scaffolds bearing several reactive functionalities to build in further diversity. Bicyclo[2.2.2]octadiene-type products and benzoxepine acetals are formed in this reaction, in ratios and yields depending on the substitution pattern on the aromatic ring, the nature of the chromophore, and the tether. This unprecedented reaction has remarkable features that distinguish it from many other photochemical transformations: it is particularly robust with respect to substituents, it can be scaled up without a notable loss of efficiency, and it can lead to structures with a high degree of complexity in low to good yields. All photochemical precursors could be synthesized readily in three steps. We confirmed the compatibility of the nitrogen atom in the photocycloaddition step, which gives access to a bicyclo[2.2.2]octadiene scaffold with two points that allow further diversification. This reaction was scaled up to multigram quantities without erosion of the typically high yields in photocycloadducts. Sequential deprotection of the N- or C-terminus of bicyclic amino acids gave access to two conformationally constrained unnatural amino acids with different dispositions of the two anchor points.