p -Toluenesulfonylmethyl Isocyanide: a Versatile Synthon in Organic Chemistry

Abstract

TosMIC, a versatile synthon in organic chemistry, has been extensively used for the synthesis of a wide variety of small, medium and large ring heterocycles. It has immense implications in the synthesis of nitriles, aldehydes, ketones, alkanes, cyclophanes and large number of natural products. Several drug intermediates and pharmacologically active compounds have been synthesized from TosMIC. In addition, chiral TosMIC analogs have been synthesized and employed for synthesis of optically active compounds.

Synthesis of Multi-Substituted Pyrrole Derivatives Through [3+2] Cycloaddition with Tosylmethyl Isocyanides (TosMICs) and Electron-Deficient Compounds

“…TosMIC is a colorless, odorless, stable solid that can be stored at room temperature. It is an important organic synthesis intermediate, and widely used in the synthesis of five-membered nitrogen-containing heterocycles [ 23 ]. Under the Van Leusen pyrrole synthesis reaction conditions, TosMIC loses a proton to form a carbanion under the action of a base because of the electron-withdrawing effect of the sulfone and isocyanide.…”

Synthesis of Imidazole-Based Medicinal Molecules Utilizing the van Leusen Imidazole Synthesis

“…Since it was introduced and applied in organic synthesis by the Dutch professor van Leusen in 1972, this reagent is also known as van Leusen's reagent. Up to now, TosMIC and its derivatives have been recognized as one of the most significant building blocks in nitrogen heterocyclic synthesis, which have been fruitfully employed especially in the preparation of imidazole-based heterocycles [25][26][27][28][29].…”

[3+2] Cycloaddition of Tosylmethyl Isocyanide with Styrylisoxazoles: Facile Access to Polysubstituted 3-(Isoxazol-5-yl)pyrroles

“…In the past decades, a variety of elegant methods for the synthesis of pyrroles or oligofunctional pyrroles have been reported, including the classical Hantzsch reaction [ 10 ], the Paal-Knorr cyclization reaction [ 10 ], the van Leusen cyclization [ 11 ], and other cyclizations [ 11 ]. Among them, the [3+2] cycloaddition of tosylmethyl isocyanide with electron-deficient olefins, developed by van Leusen et al, is one of the most promising methods [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. A wide range of electron-deficient olefins, such as α,β-unsaturated esters, ketones or nitriles, nitroolefins and styrenes, etc., are well tolerated in this reaction [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”