Synthesis of Naphthalene Natural Products Dehydrocacalohastine and Musizin

Abstract

Natural methylated naphthalene compounds, possessing diverse biological activities, remain to be studied because of low content in plants and lacking synthetic methods. Herein, we have disclosed new approaches to methylated naphthalene natural products represented by dehydrocacalohastine and musizin from simple and commercially available naphthalene molecules with the assistance of our reported regioselective C−H methylation. The dehydrocacalohastine has been firstly synthesized from 1‐bromonaphthalen‐2‐ol in overall 8.9% yield with 8 steps. Additionally, the solution to musizin saved 2 steps with comparative yields to previous reported route.

C−H Functionalization of Aldehydes and Ketones with Transient Directing Groups: Recent Developments

“…[19] Mechanistic studies as well as DFT calculations were performed to explain the regioselectivity and this methodology was successfully applied to the synthesis of natural products such as musizin or dehydrocacalohastine. [20] As shown previously with iridium, transition metals other than palladium could be used for TDG CÀ H activations. For instance, Sundararaju's group developed a cobalt(III)-catalyzed amidation reaction with aniline to form the TDG (Scheme 9.a).…”

“…After having developed an oxygenation reaction (Scheme 2.b), a regioselective C2‐ or C8‐methylation was reported involving a palladium catalysis with glycine to form the TDG to achieve a C8‐selectivity and a combination of iridium catalyst with metanilic acid for the C2‐functionalization (Scheme 8). [19] Mechanistic studies as well as DFT calculations were performed to explain the regioselectivity and this methodology was successfully applied to the synthesis of natural products such as musizin or dehydrocacalohastine [20] …”