STRATEGIES AND TACTICS IN ORGANIC SYNTHESIS, VOL. 7 © 2007 Elsevier Ltd. All rights reserved. Chapter XX Seduced by a Siren’s Call: Expanding Applications for Aromatic Compounds and the Synthesis of (+)-Rishirilide B Thomas Pettus and Todd Wenderski Department of Chemistry and Biochemistry University of California at Santa Barbara Santa Barbara, California 93106-9510 I. A burgeoning interest in aromatic compounds .........................................................1 II. Why choose a particular phenol skeleton for oxidation? .......................................5 III. Developing easy access to various resorcinol systems ............................................7 IV. Total synthesis of (±)-epoxysorbicillinol ................................................................ 11 V. Plans for chiral auxiliaries disintergrate................................................................ 12 VI. Stereochemistry describes an unexpected transition state ................................. 12 VII. Beating the clock, tuning the reaction and improving yields ............................. 13 VIII. Controlling β -dione tautomerization and protection .......................................... 15 IX. A lactic acid derived protecting-directing group ................................................. 16 X. New methods for cleavage of the directing-protecting group ............................. 19 XI. The total synthesis of (+)-rishirilide B ................................................................... 20 XII. New horizons for this method and oxidative dearomatization .......................... 22 XIII. Acknowledgment of mentors, colleagues and other supporters ........................ 24 XIV. References .................................................................................................................. 24 I. A burgeoning interest in aromatic compounds It’s often tough to tell when a story truly begins. I’ll start at Virginia Tech, where I was working in the laboratories of Professor Tomás Hudlicky, (T’Hud). My organic college professor, Dr. Maurice Maxwell (Max), was visiting VPI for a summer research program and had brought me along. I was assigned to the bench of Gustavo Seoane, who served as my immediate mentor and handler for the summer of 1988. Gustavo’s mission, which no doubt doubled his work-load, was to prevent me from hurting myself, others, and taking out a wall while carrying out an experiment. T’Hud had recently recognized the importance of a Gibson paper reporting the formation of (+)-cis-2,3- dihydroxy-1-methyl-cyclohexadiene from toluene by a mutant strain (39D) of the soil microbe Pseudomonas putida, and he and his group were just beginning to finish enantioselective syntheses of terpenes and prostanoids from arene diols (Scheme 1). 1 T’Hud