One Reacts as Two: Applications of N-Isocyaniminotriphenylphosphorane in Diversity-Oriented Synthesis

Abstract

N-Isocyaniminotriphenylphosphorane (NIITP) is a functionalized isonitrile that has been extensively applied in a variety of organic reactions during the last two decades. This Review summarizes the most important applications in organic synthesis of this versatile reactant, with the focus posed on mechanistic and methodological aspects allowing the generation of molecular diversity. NIITP combines the reactivity of isonitriles with that of phosphoranes to enable chemical transformations employed in the construction of compound libraries. Here, we cover from the initial applications of NIITP in the Nef isocyanide reaction to further derivations that render a variety of heterocyclic scaffolds. The presence of the isonitrile moiety in this singular compound makes possible the double addition of nucleophiles and electrophiles, which followed by inter­(intra)­molecular aza-Wittig type transformations enable several multicomponent and tandem processes. In particular, we stress the impact of NIITP in oxadiazole chemistry, from the early two-component transformations to recent examples of multicomponent reactions that take place in the presence of suitable electrophiles. In addition, we briefly describe the role of NIITP chemistry in generating skeletal and conformational diversity in cyclic peptides. The reaction of NIITP with alkynes is thoroughly revised, with particular emphasis on silver-catalyzed processes that have been developed in the last years. Biomedicinal applications of some reaction products are also mentioned along with a perspective of future applications of this reactant.

Synthesis and characterization of novel hercynite@sulfuric acid and its catalytic applications in the synthesis of polyhydroquinolines and 2,3-dihydroquinazolin-4(1H)-ones

“…[1][2][3][4] This synthetic method has been utilized to prepare a variety of N-containing heterocycles, which are interesting drugs and useful organic intermediates in synthetic organic chemistry. [5][6][7][8][9] In this regard, dihydropyridines and 2,3dihydroquinazolin-4(1H)-ones are important classes of heterocycles having high nitrogen content. 6,10,11 Moreover, they are frequently used as bioisosteres of pyridines exhibiting a plethora of applications in pharmaceuticals and drug designing as explosives and also in material science as important precursors in synthetic chemistry for the synthesis of other nitrogenous heterocycles.…”

Switchable construction of oxa-heterocycles with diverse ring sizes via chemoselective cyclization controlled by dibrominated compounds

“…On the other hand, diversity-oriented synthesis is of great importance and, could provide quick access to structurally diverse scaffolds with minor adjustments. 4 Hence, developing reactions for convenient and controllable construction of oxa-heterocycles with diverse ring sizes, including relatively inaccessible medium-sized oxa-heterocycles, from readily available building blocks is highly desirable.…”

Isocyanide 2.0

“…18,19 Similarly, N-isocyanoiminotriphenylphosphorane also called Fehlhammer isocyanide 12 after its inventor is a highly versatile example. [20][21][22] Ramazani, for example, introduced 12 in the elegant oxadiazole synthesis (13), which was also probed in complex head-to-tail cyclic peptide syntheses. 23,24 Another example is Boc protected o-aminophenyl isocyanide 14, which has been used in the elegant work of Hulme to form hybrid pyridinone-3-yl-benzimidazol-2-ones 15 in just one synthetic step.…”