Second-Generation Total Synthesis of the Pigment Aurantricholone

Our first total synthesis of aurantricholone established its benzotropolone core by the ring-enlargement of a tetralone. Here we describe another total synthesis of aurantricholone. It reaches the benzotropolone core from a known olefin metathesis product via an equally known dibromide, both of which contain a ketoketal moiety. The next transformation - step 9 overall - engaged this motif in a beta-elimination of ROH rather than in a hydrolysis under the forcing acidic conditions indispensable in all prior benzotropolone preparations from such an intermediate. In step 10, the Csp2-Br bonds of the elimination product underwent two doubly Z-selective Suzuki couplings with a boronylated O-methyl 4-methylidenetetronate. This gave penta(O-methyl)aurantricholone. Its NMR shifts matched essentially those of a derivative of natural aurantricholone by Steglich et al. Three O-Me bonds were cleaved with BBr3/CH2Cl2 (step 11) and two O-Me bonds with LiBr/DMF (step 12). A 1 : 3 co-crystal of aurantricholone and DMSO allowed for an X-ray structure analysis. Previously, 6,6-dimethoxy-6,7-dihydrobenzocyclohepten-5-ones (ketoketals) gained by ring-closing metatheses (RCMs) gave 6-hydroxybenzocyclohepten-5-ones (benzotropolones) by hydrolyses with 10 equiv. of hot TsOH. Now, an RCM-based ketoketal allowed to reach the benzotropolone aurantricholone by total synthesis for the second time and to avoid a forcing hydrolysis. Another key to success was establishing the pulvinone(-like) motifs by our recently developed Suzuki strategy.image

Automated summary

This study describes another total synthesis of aurantricholone, reaching its core structure through known olefin metathesis products and dibromide compounds. By optimizing the reaction conditions, the study successfully avoids the forcing hydrolysis required in traditional synthesis methods and analyzes the structure of the product in detail.