Synthesis of Euchrestifoline Using Iron‐ and Palladium‐Catalyzed C–H Bond Activations

Abstract

We describe a short and efficient synthetic route to euchrestifoline. Key steps of our approach are the iron(III)‐catalyzed Wacker‐type oxidation of a chromene derivative with hexadecafluorophthalocyanine‐iron (FePcF16) as catalyst, a palladium(0)‐catalyzed Buchwald–Hartwig amination, and the final palladium(II)‐catalyzed oxidative cyclization of the resulting diarylamine to the natural product.

Mechanistic Studies on the Hexadecafluorophthalocyanine–Iron‐Catalyzed Wacker‐Type Oxidation of Olefins to Ketones**

“…The formation of minor amounts of silanol R' 3 SiOH ( 6) is explained by reaction of hydrosilane with the hydroxy-iron(III) complex which provides an alternative pathway to the hydrido-iron(III) complex. This mechanism for the formation of the silanol R' 3 SiOH ( 6) derives support from the fact that in contrast to the oxygen atom of the ethoxysilane 5, the oxygen atom of 6 originates from the oxygen atmosphere (see the 18 O-labeling experiment in Scheme 7, below). The hydrido-iron(III) complex opens up two different mechanistic pathways generating either an alkyl radical by hydrogen atom transfer (HAT) [2e,29,31] to the olefin (Scheme 3, path D1) [32] or a (1-methylalkyl)-iron(III) complex by hydrometalation (path D2).…”

“…a Et Et Et 6 72 9 --3 [c] b iPr iPr iPr 24 0 0 --4 [d] c TMS TMS TMS 6 0 0 --5 pyrano[3,2-a]carbazole alkaloid euchrestifoline. [18] When triphenylsilane (2 k) was applied, triphenylethoxysilane (5 k) and small amounts of triphenylsilanol (6 k) were isolated as by-products.…”

Iron‐Catalyzed Wacker‐type Oxidation of Olefins at Room Temperature with 1,3‐Diketones or Neocuproine as Ligands**

“…[24] Finally,w ed emonstrated the applicability of the present method for the synthesis of natural products. Oxidation of the pyrano [3,2-a]carbazole alkaloid girinimbine (1q) [25] using Fe(dbm) 3 as catalyst (method A) provided the naturally occurring euchrestifoline (2q) [26] in 54 %yield along with 43 %o ft he corresponding alcohol 3q,w hereas methods Ba nd Cfailed in this case.…”

The 15th Frank Warren Organic Chemistry Conference

“…In a continuation of the theme of developing environmentally benign methodologies in his third visit to the conference, Prof. Dr. Hans‐Joachim Knölker walked us through his progress in regioselective iron(III)‐catalyzed intermolecular oxidative coupling of diaryl amines, as well the iron(III)‐catalyzed Wacker type oxidations . Prof. Dr. Hans‐Günther Schmalz gave an account of his group's work in the development of modular chiral P , P ‐ligands, for the enantioselective synthesis of structurally complex marine natural products .…”

“…In ac ontinuation of the themeo fd eveloping environmentally benignm ethodologies in his third visit to the conference, Prof. Dr.H ans-Joachim Knçlker walked us through his progress in regioselective iron(III)-catalyzed intermolecular oxidative couplingo fd iaryl amines, [11] as well the iron(III)-catalyzed Wacker type oxidations. [12] Prof. Dr.H ans-Günther Schmalz gave an account of his group'sw ork in the development of modular chiral P,P-ligands, for the enantioselective synthesis of structurally complex marine natural products. [13,14] Prof. Henok Kinfe used his keynote lecture to exhibit the utility of glycals in synthetic organic chemistryf or the construction of complex bioactive heterocycles, [15] while Prof. GarethA rnott detailed the potentialo fi nherently chiral calixarenes and his journey toward selectived erivatization of these molecules.…”