[1001-56-5]  · C4H3N  · 2,3-Butadienenitrile  · (MW 65.07)

(reactive in transformations involving nucleophilic conjugate addition,1 radical addition,2 and dipolar addition, especially with nitrones3)

Alternate Names: allenecarbonitrile; cyanoallene; cyanopropadiene.

Physical Data: bp 50-51.5 °C/50 mmHg.

Solubility: sol EtOH, THF, toluene, chloroform, benzene.

Analysis of Reagent Purity: IR 1970, 2230 cm-1.

Preparative Methods: this reagent is not commercially available, but at least two preparative methods have been reported. One proceeds through a Wittig reaction between cyanomethylidenetriphenylphosphorane and ketene.4 However, the procedure to be recommended involves the formation of 3-butynenitrile and its isomerization in situ to 2,3-butadienenitrile (eq 1).5 The indicated product mixture can be produced on a scale near 100 g, and its fractional distillation affords pure 2,3-butadienenitrile.

Purification: vacuum distillation.

Handling, Storage, and Precautions: this reagent has been reported6 to cause severe allergic reactions in some individuals. Handling with double, heavy-duty rubber gloves is recommended. This reagent should only be handled in a fume hood.

Procedures Involving Nucleophilic Conjugate Addition to 2,3-Butadienenitrile.

Transformations in which this reagent behaves as a conjugate addition electrophile are well known. For example, eq 21 shows an unsaturated amino acid synthesis based on this concept.

A similar process underlies the [2 + 2] cycloaddition between 2,3-butadienenitrile and cyclohexanone morpholine enamine (eq 3).7

A more sophisticated exploitation of this chemistry is incorporated in the procedure8 for alkylation ortho to aromatic amino nitrogen (eq 4). This protocol delivers an intermediate cyano ketone through nucleophilic addition of the hydroxamate anion to 2,3-butadienenitrile and subsequent [3,3]-sigmatropic rearrangement and tautomerization. Formic Acid treatment of the cyano ketone then produces the 2-substituted indole. Likewise, a mechanistically related sequence carried out on a substrate incapable of tautomerization and rearomatization delivers carbocyclic products (eq 5).9

2,3-Butadienenitrile can also function in a formal sense as the nucleophilic component in the conjugate addition to Methyl Vinyl Ketone depicted in eq 6.10 However, this transformation also occurs by way of conjugate addition of methoxide to this reagent, followed by reaction of the derived allylic nitrile anion with methyl vinyl ketone and base-induced ejection of methoxide to deliver the observed product.

Transformations Involving Radical Addition to 2,3-Butadienenitrile.

Several transformations in which radicals add to 2,3-butadienenitrile have been reported. For example, 1-adamantyl engages the central carbon in the reagent to provide a modest yield of the corresponding 2-substituted 2-butenenitrile (eq 7).2 Related reactions are shown in eqs 811 and eq 9.6

Dipolar Additions of Nitrones to 2,3-Butadienenitrile.

Eq 3 formally constitutes a cycloadditive process involving this reagent. However, among cycloadditions involving 2,3-butadienenitrile, dipolar additions of nitrones are the most commonly encountered (eqs 10 and 11).3 When the nitrone carries a sterically demanding group on the nitrogen, cis stereoselectivity is eroded (eq 11).

A transformation reminiscent of eq 4 is illustrated in eq 12.12 Formation of the nitrone occurs in situ, and initiates a sequence involving dipolar addition, [3,3]-sigmatropic rearrangement, and further transformation into the 2-vinylindole indicated through a one-pot procedure.

Related Reagents.

Allene; Propynenitrile.

1. Paik, Y. H.; Dowd, P. JOC 1986, 51, 2910.
2. Ohno, M.; Ishizaki, K.; Eguchi, S. JOC 1988, 53, 1285.
3. Padwa, A.; Kline, D. N.; Koehler, K. F.; Matzinger, M.; Venkatramanan, M. K. JOC 1987, 52, 3909.
4. Hamlet, Z.; Barker, W. D. S 1970, 543.
5. Kurtz, P.; Gold, H.; Disselnkötter, H. LA 1959, 624, 1.
6. Pasto, D. J.; L'Hermine, G. JOC 1990, 55, 685.
7. (a) Baldwin, J. E.; Fleming, R. H.; Simmons, D. M. JOC 1972, 37, 3963. (b) For an experimental procedure but an incorrect assignment of the product structure, see: Reid, W.; Käppeler, W. LA 1965, 687, 183.
8. Blechert, S. HCA 1985, 68, 1835.
9. Bosum, A.; Blechert, S. AG(E) 1988, 27, 558.
10. Padwa, A.; Yeske, P. E. JOC 1991, 56, 6386.
11. Mitchell, T. N.; Belt, H.-J. JOM 1990, 386, 167.
12. Wilkens, J.; Kühling, A.; Blechert, S. T 1987, 43, 3237.

Charles S. Swindell

Bryn Mawr College, PA, USA

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