Synthesis of benzoquinones and annulated derivatives from conjugated ketenes

Abstract

difficulties. To the contrary, it has been our experience over the last 6 years that these molecules can be readily synthesized and are easy to handle. And with the generality of the quinone synthesis described herein, it is anticipated that newer, even simpler methods of cyclobutenedione synthesis will be explored in the near future. By combining the chemistry described in this manuscript with the numerous procedures known for directed metalation of aryl and heterocyclic systems,15 a powerful procedure is at hand for the synthesis of quinone based biologically active molecules.Acknowledgment. This investigation was supported by PHS Grant CA 40157 awarded by the National Cancer Institute, DHHS. We are grateful to Professor Harold Moore of U.C. Irvine for communicating his results to us prior to publication and to Dr. Romanworq Ferede and Mr. Charles McSwain for their efforts on the project. Supplementary Material Available: Complete experimental details for the synthesis of the compounds described in this manuscript (13 pages). Ordering information is given on any current masthead page.

Recent advances in 1,4-benzoquinone chemistry

“…189 A convergent general synthesis of annelated quinones and highly substituted quinones (149-151) from conjugated ketenes (146-148) was reported by Moore and co-workers. 190 The reaction proceeds via a thermal rearrangement (Schemes [33][34][35] (153). Electrocyclic ring opening of 153 gives the dienyl ketene (154) which then undergoes sixelectron electrocyclization followed by enolization to yield a phenol (155).…”

“…Tsutui et al 218 performed theoretical calculations on silyl-substituted 1,4-benzoquinones (190)(191)(192)(193)(194)(195)(196)(197), to investigate the structure and properties. Geometry optimizations and vibrational frequency calculations were performed at B3LYP/6-31G* level while the SPE calculation is carried out at MP2/6-311+G(2d,p) level.…”

New Insights into Cyclobutenone Rearrangements: A Total Synthesis of the Natural ROS‐Generating Anti‐Cancer Agent Cribrostatin 6

“…[17,18] Scheme 3. A short total synthesis of cribrostatin 6 (19). EDC = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.…”

“…Although the related synthesis of quino [b]thiophene 13 from thiophene 11 required a higher temperature (150 8C) and an aerial oxidation, it too proceeded efficiently, to give a 98 % yield over the two steps (Scheme 2). [19] To demonstrate the value of the method, we chose to tackle the synthesis of the marine natural product cribrostatin 6 (19), a popular target since it was identified by Pettit et al in 2003, that exhibits useful anti-neoplastic and antimicrobial activity. [5,6] In 2010, cribrostatin 6 was reported to induce death in cancer cells by inducing oxidative stress and the build-up of ROS.…”

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

“…Our laboratory has developed two complementary benzannulation strategies based on the reaction of alkynes and vinylketenes 2,3,4 and we have applied these methods to the synthesis of a number of bioactive natural products. 5,6 Recently we extended the cyclobutenone-based version of this benzannulation strategy to include ynamine derivatives, demonstrating that the use of certain ynamides as alkyne reaction partners suppresses side reactions that are observed in reactions with simple ynamines.…”