Synthetic Uses of Tosylmethyl Isocyanide (TosMIC)

Abstract

TosMIC is the acronym for 4‐tolylsulfonylmethyl isocyanide or tosylmethyl isocyanide. It is the best‐known member of a series of about 25 sulfonyl‐substituted methyl isocyanides RSO 2 CH 2 NC collected in Chart 1 (p. 426). TosMIC is a multipurpose synthetic reagent. It is by far the most versatile synthon derived from methyl isocyanide. This chapter provides a complete account of the synthetic uses of TosMIC based on a literature search closed in January 1996, and supplemented with further data available to the authors. Also included are applications of some of the more important TosMIC homologs (TosCHRNC). TosMIC is the only commercially available sulfonylmethyl isocyanide. It is a stable, colorless, practically odorless solid, which can be stored at room temperature without decomposition. Four brief review papers on the chemistry of TosMIC have appeared, in 1980, 1987, 1993, and 1995. Several reviews on the chemistry of isocyanides in general are available. An effort has been made to make this chapter as complete as possible, in coverage both by tables and by references, with respect to the immediate objective: a survey of the “Synthetic Uses of TosMIC.” Emphasis is on the primary products derived from reactions of TosMIC and related isocyanides, with limited reference to the further utilization of these products. Thus, the next section gives a complete account of reductive cyanation, the conversion of aldehydes or ketones into cyanides with the use of TosMIC, but for obvious reasons synthetic applications of the product cyanides are not treated in this chapter. One of the subsequent sections describes the application of TosMIC to the synthesis of pyrroles, including 2,3‐divinylpyrroles, which are important precursors in a new synthesis of indoles. This latter transformation, made possible by the easy availability of the precursors through TosMIC chemistry, is afforded brief coverage. As a rule, reference to preliminary papers has been omitted when the same information is available from the corresponding full papers. The patent literature is covered highly selectively and is cited only when providing new and relevant information. Negative results of reactions are reported in the text or tables only when at least some relevant information is available with respect to the conditions of such unsuccessful attempts.

Chemistry and Biology Of Multicomponent Reactions

“…80 TOSMICs display a high functional group density. Thus TOSMIC chemistry is determined by three distinct properties: the isocyanide reactivity, the strong α-acidity of the adjacent methylene group embedded between the two electron withdrawing sulfone and isocyanide group ( N , S -acetal) and the leaving group ability of the sulfone group (Figure 18).…”

A Van Leusen deprotection-cyclization strategy as a fast entry into two imidazoquinoxaline families

“…In addition to the isonitrile functional group, a well-known multi-purpose synthetic tool, TOSMICs also display two more reactive features: 1 namely, these molecules are endowed with a tosyl residue that can easily act as a leaving group, 2 and with an activated methylene they are prone to attack electrophiles upon deprotonation. Thanks to their peculiar nature, TOSMICs have been fruitfully employed in the preparation of several families of heterocycles, such as oxazoles, 3 pyrroles, 4 imidazoles, 5 benzofuranes, 6 quinoxalines, 7 and pyrrolopyrimidines.…”

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

“…The utility and importance of MCRs have been recognized by chemists [20–23]. Several MCRs are now well-established reactions, such as Ugi [24], Passerini [25], Van Leusen [26], Strecker [27], Hantzsch [28], and Biginelli [29–31]. …”