Zearalenone Tsuji synthesis

Intramolecular alkylations of nitrile-stabilized carbanions have been used to synthesize large rings such as those with 10 and 14 members. Tsuji and coworkers carried out a synthesis of the macrocy-clic antibiotic zearalenone by this route. As shown in Scheme 70, conversion of either of the protected cyanohydrins (144) or (145) to the corresponding dianions, resulting from deprotonation at the benzylic positions and a to the nitrile groups, gave the same cyclization product (146) in excellent yields. Dianion formation (i) provided control of the conformation of the side chain (ii) protected the ester from nucleophilic attack and (iii) appeared to increase the rate of the intramolecular cyclization. 

Acylation of 145 with acid chloride 95 afforded ester 146 in 90% yield. Ester 146, containing all the necessary carbons at easily adjustable oxidation states, required only cyclization and minor functional group manipulations to afford the zearalenone system. As in Tsuji s previous synthesis of di-O-methyl lasiodi-plodin, macrocyclization was effected via deprotonation at the benzylic position and intramolecular alkylation to give 147 in 85% yield. Oxidative elimination of the thiophenyl group and removal of the ketal with acid afforded 127 (67%). the Merck group had previously demonstrated the ready conversion of 127 to zearalenone (119). 

Takahashi T, Kasuga K, Takahashi M, Tsuji J (1979) A Simple Total Synthesis of ( )-Zearalenone by Intramolecular Alkylation Using a Butadiene Telomer as Building Block. J Am Chem Soc 101 5072... 

There is an impressive number of publications on the application of transition metal-catalyzed carbonylation reactions in total synthesis. In 1980 Tsuji and colleagues applied palladium-catalyzed alkoxycarbonylation in the synthesis of Zearalenone [22] and Curvularin [23]. Starting from the corresponding aryl iodides or benzyl chlorides and alcohols, the parent molecules for Zearalenone and Curvularin were prepared in good yields and finally transferred to the target products by a few more steps (Scheme 10.1). 

Tsuji reported a total synthesis of zearalenone using Pd-catalyzed carbonylation. In this total synthesis, they synthesized the key compound by Pd-catalyzed carbonylation. The reacion of l-iodo-2-phenylthiomethyl-4,6-dimethoxybenzene 3 (Scheme 7) with 10-iodo-6,2 -[l,3]dioxolane-2-decanol 4 was carried out under carbon monoxide (12 atm) to afford the corresponding m-iodoalkyl ester of 2-phenylthiomethy 1-4,6-dimethoxybenzene 5. 

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