Redox Condensations of o-Nitrobenzaldehydes with Amines under Mild Conditions: Total Synthesis of the Vasicinone Family

Abstract

A total synthesis of the vasicinone family of natural products from bulk chemicals was developed. Reductive condensation of o-nitrobenzaldehydes with amines utilizing iron pentacarbonyl as a reducing agent followed by subsequent oxidation leads to a great variety of polycyclic nitrogen-containing heterocycles under mild conditions. Enantiomerically pure vasicinone, rutaecarpine, isaindigotone, and luotonin were synthesized from readily available starting materials like hydroxy­proline, nitrobenzaldehyde, pyrrolidine, and piperidine in two to four operational steps without chromatography. The antifungal activity of all products was tested.

Direct Reductive Amination of Camphor Using Iron Pentacarbonyl as Stoichiometric Reducing Agent: Features and Limitations

“…Its price is comparable to the price of some HPLC solvents, and it is readily available all over the world. The applicability of iron pentacarbonyl for the reductive modifications of carbonyl compounds was earlier demonstrated by our group . In particular, it was found that iron pentacarbonyl is a very efficient reducing agent in the reductive amination of highly inert ketones like benzophenone .…”

“…The applicability of iron pentacarbonyl for the reductive modifications of carbonyl compounds was earlier demonstrated by our group. [27][28][29] In particular, it was found that iron pentacarbonyl is a very efficient reducing agent in the reductive amination of highly inert ketones like benzophenone. [29] In addition, there are a lot of iron-based catalysts applicable in reductive amination using different reducing agents e.g.…”

Condensation-Based Methods for the C–H Bond Functionalization of Amines

“…109 An interesting, alternative pathway to aminals and the corresponding amidines was recently reported by Chusov and coworkers. 110 Ortho-nitrobenzaldehydes serve as starting materials in place of ortho-aminobenzaldehydes. Reactions are promoted by iron pentacarbonyl, enabling the formation of ring-fused aminals and amidines under mild conditions.…”

Synthesis of a 3,4-Dihydro-1,3-oxazin-2-ones Skeleton via an Intermolecular [4 + 2] Process of N-Acyliminium Ions with Ynamides/Terminal Alkynes

“…The discovery of an efficient methodology to access privileged azacycles and corresponding benzo heterocycles is one of the most important areas in current organic syntheses due to their existence as unique scaffold in a large number of biologically active compounds and clinic drugs, as well as important auxiliaries and building blocks in organic synthesis. As a prime instance (Figure ), 1 H -benzo­[d]­[1,3]­oxazin-2­(4 H )-one 1 and 4 H -benzo­[d]­[1,3]­oxazin-4-one 2 , which are pharmacologically interesting molecules and the key framework of Efavirenz (a prescription medicine for the treatment of HIV), have received intensive attention in recent years .…”