An efficient method for 4β-anilino-4′-demethylepipodophyllotoxins: Synthesis of NPF and W-68

Asymmetric Ring Opening of Benzo‐7‐oxabicyclo[2.2.1]heptadienes with Cationic Rhodium Complexes

“…The time to complete conversion is, for example, 45 min in the case of N-methylaniline as nucleophile with the THF solvate complex at 50 8C, whereas in the original work with 2 ](I)}" using the same substrate to nucleophile ratio a reaction time of 120 min at 80 8C was described. With o-bromophenol a reduc-…”

“…[1g] By using this hitherto applied in situ technique, 2 ] with the ligand}, however, the catalytically active species and its concentration remained unidentified. Furthermore, the ratio of nucleophile to oxabicycle of usually 5 is higher than the stoichiometric reaction would require; and the reaction temperature is at least 80 8C.…”

“…[8] Here we describe to what extent cationic rhodi-A C H T U N G T R E N N U N G um(I) solvate complexes are suitable instead of the hitherto applied m 2 -chloro bridged rhodium complexes using the example of the known asymmetric ring opening of benzo-7-oxabicyclo-[2.2.1]heptadiene. [9] The cationic solvate complexes 2 ]anion can easily be generated by hydrogenation of diolefins COD (1,5-cyclooctadiene) or NBD (2,5-norbornadiene) from the respective precatalysts…”

“…This fact points to the formation of a complex with the reaction product, in which the coordination to the rhodium takes place with a part of the product that all products share, i.e., the original oxabicycle: the double bond, and/or the OH group, or the arene [19] could be coordinated. By addition of reaction 2 }BF 4 the formation of very stable catalyst-product complexes Figure 3. X-ray structure of a) (1R,2R)-2-(ortho-bromophenoxy)-1-hydroxy-1,2-dihydronaphthalene and b) (1R,2R)-1-hydroxy-5-iodo-2-methoxy-1,2-dihydro-naphthalene [9] (ORTEP, 30% probability ellipsoids; the OH and OR moieties are arranged in trans configuration).…”

“…Pioneering work in this field using rhodium catalysts has been conducted by Lautens and co-workers. [1] From the desymmetrization of benzo-7-oxabicycloA C H T U N G T R E N N U N G [2.2.1]hepta-A C H T U N G T R E N N U N G diene, precursors of pharmaceutically relevant hydronaphthalenes [2] result as anti addition products by asymmetric ring opening with neutral dimeric complexes of rhodium (Scheme 1). [3,4] In contrast, asymmetric ring opening with Pd and Ni complexes, [5] and the rhodium-catalyzed ring opening with organoboronic acids [6] give the respective syn products.…”