Oxidative Cyclization Reaction of 2‐Aryl‐Substituted Cinnamates To Form Phenanthrene Carboxylates by Using MoCl₅

Abstract

The oxidative cyclization reaction of 2-aryl cinnamates and derivatives thereof can be easily performed with MoCl5 as the oxidant. This powerful reagent allows oxidative coupling reactions for which other reagents fail. The best results are obtained when the 2-phenyl substituent of the cinnamate is equipped with two methoxy groups. Even iodo moieties in the bay region of phenanthrene are tolerated under the reaction conditions. If naphthalene moieties are involved, a rearrangement of the skeleton occurs, providing an elegant route to highly functionalized angular arenes. The cyclization is demonstrated for 15 example substrates with isolated yields of up to 99 % for the phenanthrene derivative. The broad scope of the reaction underlines the usefulness of MoCl5 and MoCl5 /TiCl4 in the oxidative coupling reaction.

Überoxidation als Schlüsselschritt im Mechanismus der MoCl5‐ vermittelten dehydrierenden Arenkupplung

“…Diese Reaktivität kann zum Aufbau von fünf‐ bis achtgliedrigen Ringen eingesetzt werden . Dies umfasst auch Carbazole und Phenanthrene mit einer großen Bandbreite an labilen, aber präparativ nützlichen funktionellen Gruppen, wie Iodsubstituenten und Ketalen –. Die Verträglichkeit mit empfindlichen Molekülbereichen wird der hohen Reaktionsgeschwindigkeit der oxidativen Kupplung durch MoCl 5 zugeschrieben .…”

MoV Reagents in Organic Synthesis

“…The phenanthrene skeleton is a common structural motif in many natural products with valuable biological and pharmacological activities ranging from antitumor properties to anti‐inflammatory, antifungal, or antibacterial activities 48. The already established synthetic routes to phenanthrenes mostly suffer from limited scope 10c. Hence, a simple, modular but versatile method for the construction of phenanthrenes is highly desirable.…”

“…Hence, a simple, modular but versatile method for the construction of phenanthrenes is highly desirable. Recently, a synthetic route to phenanthrenes using a MoCl 5 ‐mediated oxidative coupling reaction in the key step was developed 10c. The required starting materials are easily accessible by a Horner–Wadsworth–Emmons olefination protocol in good to excellent yields 49…”

“…Most probably, precoordination of MoCl 5 to the 1,2‐dialkoxy‐decorated aryl fragment occurs, followed by single‐electron transfer from the substrate to the reagent, leading to an organic radical cation (Figure 2). 10c,35 Lundquist and co‐workers report that the predominantly E ‐configured 2‐arylcinnamates are not planar because of steric repulsion between the two aromatic ring systems 50. Because the 2‐aryl substituent is tilted almost perpendicular out of the plane it will not be affected by the electron‐withdrawing character of the carbonyl group.…”

“…Therefore, the oxidative cyclization process should start on that aryl fragment. The formed radical cation then can undergo the electrophilic cyclization step to produce the phenanthrene 10c. For a detailed discussion of the influence of the substitution pattern on the reactivity and the full scope of the method see ref 10c…”