Tosylmethyl isocyanide , pyrrole synthesis

Isonitrile cyclization provides a useful alternative method of the Knorr type cyclization for pyrrole synthesis. In 1972, Leusen and coworkers reported pyrrole synthesis based on the reaction of tosylmethyl isocyanide (TosMIC) with electron-deficient alkenes (Eq. 10.12).15... 

The [3 + 2] addition of type llbd is a significant method for synthesis of both simple and complex pyrrole derivatives. One manifestation of this pattern is seen in the base-catalyzed condensation of tosylmethyl isocyanide with alkenes having strong electron-accepting substituents. The aromatization by elimination of the arenesulfinic add occurs under the reaction conditions (equation 117) (72TL5337). This reaction can be applied to the synthesis of 2,3,4-trisubstituted pyrroles by using C-alkylated tosylmethyl isocyanides or AT-tosyl-methyl-S- methylthioimidates <77H(7)77, 81JHC1127). 

Tosylmethyl isocyanide (TosMIC) was employed in a key step for the synthesis of bicyclic heterocycles from L-glutamic acid <01H(55)2099>, while benzyl isocyanoacetate was utilized for reaction with a-acetoxynitro compound 41 to yield the pyrrole 42, an intermediate in the synthesis of (+)-deoxypyrro oline, a putative cross-link of bone collagen <01JOC11>. 

Gribble and Pelkey adapted the Barton-Zard pyrrole synthesis [84] to 3-nitroindoles and ethyl isocyanoacetate (and tosylmethyl isocyanide) to give 2,4-dihydropyrrolo [3,4-T [indoles (Scheme 15, equation 1) [85, 86], In complementary work, Gribble and cowoikers synthesized pyrrolo[3,4-fc]indoles from the 1,3-dipolar cycloaddition of 2- and 3-nitroindoles with miinchnones (1,3-oxazo-lium-5 elates) (eqnations 2, 3) [87, 88]. The mesoionic miinchnones were generated in situ from the appropriate Af-benzyl-Af-acylamino acids. Gribble and Kishbaugh... 

Alditol-l-yl substituted pyrroles or pyrazoles (e.g. 88 and 89) were obtained by addition to per-<7-acetylated 1,2-dideoxy-l-nitro-D- a/acm- and D-manno-l-hep-tenitols of the sodium salt of tosylmethyl isocyanide or the zwitterionic diaryl nitrile imines (e.g. PhC=N -N Ph), respectively. A general one-pot synthesis of alditol-l-yl substituted imidazoles (e.g. 90) involved reaction of aldoses with... 

---