Cyclohexyl Isocyanide1

[931-53-3]  · C7H11N  · Cyclohexyl Isocyanide  · (MW 109.17)

(reagent for phosphorylation of phosphomonoesters;2 formylation of secondary anilines4)

Physical Data: bp 173-176 °C; d 0.878 g cm-3.

Form Supplied in: colorless liquid; widely available.

Handling, Storage, and Precautions: toxic. Use in a fume hood.

Phosphorylation.

Cyclohexyl isocyanide has been utilized2 in the activation of phosphates, in a mode similar to 1,3-Dicyclohexylcarbodiimide.3 The method enables the generation of phosphodiesters from phosphomonoesters by selective use of the alcoholic medium (eq 1). An extension of this procedure permits the preparation of 2,3-cyclic phosphates of nucleosides from nucleoside 2 (or 3) phosphates (eq 2).

Formylation.

Employment of cyclohexyl isocyanide in the ortho formylation of secondary anilines, which are synthetically versatile in heteroannulation reactions, has been demonstrated.4 In a typical sequence, the secondary aniline is treated with Boron Trichloride to generate an anilinoborane which may be isolated. Further reaction of the borane with cyclohexyl isocyanide, in the presence of Triethylamine, yields the o-alkylaminobenzaldehyde upon acid hydrolysis (eq 3).

In this investigation, cyclohexyl isocyanide offered the highest yield and shortest reaction time for the isocyanides and secondary anilines studied. Although the method claims a practical advantage over a previous o-formylation approach,5 it was found to be unsuitable for primary anilines.

Copper-Isocyanide Complexes.

The availability of a nonbonding pair of electrons in an sp-hybridized orbital on the terminal carbon atom enables isocyanides to behave as strong carbon ligands for transition metals, for which many complexes have been synthesized. Within the chemical literature, the synthetic value of copper-isocyanide complexes has been amply demonstrated. Cyclopentane- and cyclohexanecarboxylates have been prepared6 from the stepwise cycloaddition of 1,o-diiodopropanes and -butanes, respectively, with dialkyl fumarate and maleate in the presence of cyclohexyl isocyanide and metallic Copper (eq 4).

The reported yields are greater for cyclopentane formation (90% trans, 89% cis), than for the cyclohexane cycloadduct (37% trans, 55% cis), where the occurrence of a single stereoisomer for each homolog is a consequence of maleate isomerization by the isocyanide complex prior to cyclization.

Other synthetic uses of copper (or Copper(I) Oxide)-cyclohexyl isocyanide complexes include conjugate additions7 of activated methylene species, cyclopropanations,8 allene synthesis9 from gem-dibromocyclopropanes (eq 5), dimerization of alkyl halides,10 and hydrosilylations of acrylonitriles.11


1. For general isocyanide reviews, see (a) Isonitrile Chemistry; Ugi, I., Ed.; Academic: New York, 1971. (b) Periasamy, M. P.; Walborsky, H. M. OPP 1979, 11, 295.
2. Mizuno, Y.; Kobayashi, J. CC 1974, 997.
3. Weimann, G.; Khorana, H. G. JACS 1962, 84, 4329.
4. Sugasawa, T.; Hamana, H.; Toyoda, T.; Adachi, M. S 1979, 99.
5. Gassman, P. G.; Drewes, H. R. JACS 1974, 96, 3002.
6. Ito, Y.; Nakayama, K.; Yonezawa, K.; Saegusa, T. JOC 1974, 39, 3273.
7. Saegusa, T.; Ito, Y.; Tomita, S.; Kinoshita, H. BCJ 1972, 45, 496.
8. (a) Saegusa, T.; Yonezawa, K.; Ito, Y. SC 1972, 2, 431. (b) Saegusa, T.; Yonezawa, K.; Murase, I.; Konoike, T.; Tomita, S.; Ito, Y. JOC 1973, 38, 2319.
9. Crozet, M. P.; Surzur, J.-M. TL 1979, 20, 3077.
10. Ballatore, A.; Crozet, M. P.; Surzur, J.-M. TL 1979, 20, 3073.
11. Svoboda, P.; Hetflejv, J. CCC 1973, 38, 3834.

Richard Wisedale

University of Bristol, UK



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