Concise Synthesis of Fagaridine and Decarine, Phenolic Benzo[c]-phenanthridine Alkaloids, Using the Palladium-assisted Biaryl Coupling Reaction

Abs tract-Total synthesis of fagaridine ( 5) and decarine (6), phenolic benzo[c]phenanthridine alkaloids, was accomplished via the aryl-aryl coupling reaction of bromo amides protected by an isopropyl group with palladium, followed by reduction with LiAlH 4 and treatment with conc.HCl Palladium-assisted aryl-aryl coupling reactions have been used to synthesize many condensed aromatic compounds. 1 Recently, we reported that intramolecular coupling reactions between aromatic halides and arenes using palladium reagents were a very versatile way to synthesize polycyclic heteroaromatic compounds 2-5 and a novel palladium reagent prepared from Pd(OAc) 2 , DPPP (1,3bis(diphenylphosphino)propane), and Bu 3 P was very effective for coupling reactions, not only between aryl triflates and arenes, but also between aryl halides and arenes. 6 Moreover, we succeeded in synthesizing the benzo[c]phenanthridine alkaloids chelerythrine (1), 2,7 nitidine (2), 4,7 norchelerythrine (3), 3,7,12methoxydihydrochelerythrine (4), 2a, 7 and others, 3,6 by taking advantage of the palladium-assisted aryl-aryl coupling reaction.Subsequently, in order to examine the generality of these methods, we designed a plan to synthesize fagaridine (5) and decarine (6), phenolic benzo[c]phenanthridine alkaloids, as shown in Scheme 1.This is the subject of this paper.In 1973, Torto et al. identified a quaternary phenolic alkaloid, fagaridine, from Fagara xanthoxyloides, and proposed its structure. 8However, Nakanishi and Suzuki revised the structure of fagaridine as 5 after synthesizing it in 1998. 9A tertiary phenolic alkaloid, decarine (6), was isolated from Zanthoxylum decaryi by Cave et al. 10 and synthesized via the benzyne route by Kesser et al. 1 1 We designed a common retorosynthetic plan for these phenolic alkaloids, as shown in Scheme 1.We postulated that isopropyl or TBDMS group could be used to protect the phenol, because they are stable in the hydride reduction and can be deprotected with hydrochloric acid, two steps that are very useful for † Dedicated to Professor Yuichi Kanaoka for the celebration of his 75th birthday.