Base Metal Catalyzed Isocyanide Insertions

Abstract

Isocyanides are diverse C1 building blocks considering their potential to react with nucleophiles, electrophiles, and radicals. Therefore, perhaps not surprisingly, isocyanides are highly valuable as inputs for multicomponent reactions (MCRs) and other one‐pot cascade processes. In the field of organometallic chemistry, isocyanides typically serve as ligands for transition metals. The coordination of isocyanides to metal centers alters the electronic distribution of the isocyano moiety, and reaction pathways can therefore be accessed that are not possible in the absence of the metal. The tunable reactivity of the isocyanide functional group by transition metals has evolved into numerous useful applications. Especially palladium‐catalyzed isocyanide insertion processes have emerged as powerful reactions in the past decade. However, reports on the use of earth‐abundant and cheap base metals in these types of transformations are scarce and have received far less attention. In this Minireview, we focus on these emerging base metal catalyzed reactions and highlight their potential in synthetic organic chemistry. Although mechanistic studies are still scarce, we discuss distinct proposed catalytic cycles and categorize the literature according to 1) the (hetero)atom bound to and 2) the type of bonding with the transition metal in which the (formal) insertion occurs.

Chemo‐Enzymatic One‐Pot Two‐Step Functionalization of 1,2,3,4‐Tetrahydroisoquinolines by Monoamine Oxidase‐Ugi‐Joullié Reaction Sequence

“…THIQs with chloro-substituent(s) (1 i-k), as well as 1 l and 1 o gave only moderate conversions (45-63 %) in the MAO oxidations even at 10 mM concentration and/or at higher as well as some further unwanted compounds presumably resulting from the versatile reactivity of isonitriles. [48][49][50][51][52] We tested then a range of carboxylic acids and isonitriles using 1 m as amine and 4 a for carboxylic acid and N-Boc-l-phenylalanine (3 e; giving product 6 d) and cinnamic acid (3 h, giving product 6 g) had a negative effect on the MAOoxidation (65 % and 60 % conversion in 22 h, respectively). In the latter case, strong precipitation of 6 g could drive the Ugi-Joullié-reaction to completion in only 6 h. It must be mentioned that α-oxo-carboxylic acids such as pyruvic acid and phenylpyruvic acid led to complex reaction mixtures which were not We used then aliphatic (4 a-c), aromatic (4 d-f) and heteroaromatic (4 g) isonitriles to diversify the amino amide sidechain.…”

“…5 a – 5 o were isolated with low to moderate yields (10–53 %). It has to be mentioned that formation of side‐products analogous to 10 were identified in LC–MS analysis to varying extent in each case as well as some further unwanted compounds presumably resulting from the versatile reactivity of isonitriles [48–52] …”

Selective sulfonylation and isonitrilation of para-quinone methides employing TosMIC as a source of sulfonyl group or isonitrile group

“…Isocyanide is an important C1 synthon. Its special reactivity, such as the ability to react with electrophilic, nucleophilic, and radical reagents [25][26][27][28], determines that it can participate in many types of reactions such as multicomponent reactions [29][30][31][32], tandem reactions [33,34], and insertion reactions [35][36][37][38][39], etc. In this context, the electron-rich aryl(phenol)methane isonitrile may be a new active unit, which can be seen from the previous case of p-QMs type reaction [40][41][42][43][44][45][46][47][48][49][50][51] and the abovementioned properties of isocyanide.…”

Catalytic Benzolactamization Through Isonitrile Insertion Enabled 1,4-Palladium Shift

“…Ever since the discovery of Passerini and Ugi reactions, 45 isonitriles have been widely employed as ambivalent reagents to prepare nitrogen-containing products. [46][47][48][49][50][51] Inspired by our recent achievements on carbene bridging C-H activation (CBA), [17][18][19][20][21][22] we envisioned that a palladium-catalyed formal [2+3] annulation of isonitriles with ortho-bromobenzaldehydes would give 3unsubstituted isoindolinones in a rapid manner (Fig. 2d).…”