‐Aminonitriles: From Sustainable Preparation to Applications in Natural Product Synthesis

Abstract

Due to their numerous reactivity modes, α‐aminonitriles represent versatile and valuable building blocks in organic total synthesis. Since their discovery by Adolph Strecker in 1850, this compound class has seen a wide dissemination in synthetic applications from laboratory to million‐ton industrial scale and was extensively used in the syntheses of various classes of natural products. As these compounds provide a multitude of reactivity options, we feel that a broad overview of their multiple reaction modes may reveal less familiar opportunities for successful total synthesis planning. This personal account article will thus focus on α‐aminonitriles used as key intermediates in selected natural product synthesis sequences which have been reported in the two decades since Enders’ and Shilvock's seminal review. Natural α‐aminonitriles will also briefly be treated.

Applications of Oxone® in Organic Synthesis: An Emerging Green Reagent of Modern Era

“…α ‐Iminonitriles, also known as imidoyl cyanides, are the key precursors to acquire the diverse functional groups for example cyanoenamides, amides, keto‐acids, amidines, and N ‐keteneimines. Nonetheless, only few methods are reported involving the multistep sequences to form the α ‐iminonitriles but in low yields with severe limitation of substrates scope [414–418] . In this context, Zhu's group has reported one‐pot synthesis of α ‐iminonitriles 576 a – p using aldehydes, amines, and trimethylsilyl cyanide (TMSCN) in a biphasic solvent system (toluene/H 2 O) with the usage of oxone, tetrabutylammonium bromide (TBAB) and NaHCO 3 (Scheme 183).…”

Cyanide Anions as Nucleophilic Catalysts in Organic Synthesis

“…Considering the triethylsilyl group to behave as a 'big proton', 61 the mechanism of the silyl benzoin reaction is very similar to the benzoin condensation: cyanation of acylsilane 45 gives intermediate 48, which undergoes [1,2]-Brook rearrangement furnishing the carbon nucleophile 50. The latter adds to the aldehyde 46 to give species 51.…”

“…The imino-version of the latter reaction leads to -amino acids after acidic hydrolysis of the intermediate aminonitriles. 2 Known as the Strecker reaction, 3 it defines an important industrial process. These examples point out that the cyanide anion is an exceptionally good nucleophile with its sp-hybridized lone pair at the carbon atom.…”

Nanostructured silicate catalysts for environmentally benign Strecker-type reactions:status quoandquo vadis

“…Based on MCRs, chemical processes in the preparation of diverse highly complex, functionalized molecules, such as ne chemicals, pharmaceuticals, agrochemicals or advanced materials, are a topic of signicant interest in academia and industry. [1][2][3][4] Possessing many apparent advantages over multistep processes, such as high efficiency, atom economy, reduced waste generation, and time and energy economy, almost all MCRs comply with the majority of Anastas and Warner's principles of green chemistry, making the use of MCRs an ideal synthetic strategy. 5 However, to be a practical synthetic tool, MCRs need to be completed with alternative energy input systems, safe reaction media, and effective catalysts.…”