An Expeditious and Atom‐Economical Synthesis of a New Generation of Substituted [4.6.4.6]Fenestradienes

Abstract

only one or two bonds are formed at a time, but by triggering a cascade of reactions many bonds can be formed in one operation and thus simple starting materials can be efficiently converted into highly sophisticated complex structures. Achieving complexity with such brevity is indeed a key characteristic of the ideal and green synthesis. [2] Toward these ends, we have focused our attention on developing facile routes to unusual scaffolds to prepare structurally diverse materials of potential theoretical and biological value. [3] Fenestranes have been examined by different research groups from both a theoretical and a synthetic perspective because of their unique structure and occurrence in nature, and their unexplored potential as molecular scaffolds, probes, and materials. [4] Several syntheses of fenestranes have been reported and since the appearance of the earliest contributions in this field, access to these compounds has improved in terms of the number of steps required and overall yield. [5] Intramolecular arene–olefin photo-cycloadditions, [6] photoinduced [2+2] cycloadditions, [7] transition-metal-induced cyclizations, [8] and cascade cyclizations [9] are some of the powerful methods that have been used to generate this class of compounds. A new approach to the fenestranes was recently demonstrated by our group. [10] Although, fenestradienes 4 were obtained in excellent yields, the method required the use of tin compounds, a sensitive nickel(0) catalyst, and hydrogen, and the intermediate trienyne species 3 was prone to polymerization if not handled with special care (Scheme 1). We herein report a one-step procedure that overcomes these problems and provides facile access to substituted fenestradienes 2 directly from alkenyl bromides 1 (Scheme 1). Our approach was inspired by a method developed by Trost et al. [11] for the selective synthesis of head-to-tail enynes in the presence of Pd(OAc)2 and tris(2,6-dimethoxyphenyl)phosphine (TDMPP), and a similar method developed by Gevorgyan and Rubina for the palladium-catalyzed headto-head dimerization of aryl acetylenes (Scheme 2). [12] The high regio- and stereoselectivities of these reactions were attributed to the strong steric influence of the ester group R 2 and specific agostic interactions between the ortho proton of the aromatic ring and the palladium center, respectively.