Isoprene Epoxide

[1838-94-4]  · C5H8O  · Isoprene Epoxide  · (MW 84.13)

(ambident electrophile)

Alternate Names: 2-methyl-2-vinyloxirane; 3,4-epoxy-3-methyl-1-butene.

Physical Data: bp 80 °C; d 0.8563 g cm-3 (22 °C).

Solubility: sol most organic solvents.

Form Supplied in: clear liquid.

Preparative Methods: often made by reacting Isoprene with N-Bromosuccinimide and converting the bromohydrin to the epoxide under basic conditions.1 Few attempts to epoxidize conjugated dienes have been reported. Recently, a manganese catalyst has been employed in a method developed to epoxidize isoprene selectively in one step (eq 1).2

Handling, Storage, and Precautions: flammable liquid, flash point -7 °C; irritant; use in a fume hood.

Nucleophilic Opening at C-4.

Isoprene epoxide is often used as a model substrate for SN2 reactions.3 Organocuprates deliver carbon nucleophiles to the vinyl terminus in this reaction.4 One drawback to this method of introducing a five-carbon synthon is usually the lack of control over the geometry of the resulting trisubstituted alkene. However, in a synthesis of vitamin K1, the CuI-catalyzed reaction of a Grignard reagent afforded the (E)-alkene with high selectivity; a &egt;99:1 (E):(Z) mixture could be isolated after recrystallization (eq 2).5

Palladium catalysts also have been used to facilitate the SN2 addition of nucleophiles to isoprene epoxide.6 The coupling reactions occur at mild temperatures in polar solvents. This method has been used for the large scale synthesis of an amino alcohol (eq 3).7 While control of the geometry of the resulting alkene is problematic, distillation of the (E):(Z) mixture through a Vigreux column affords the higher boiling (E) isomer in 35-55% yield.

Carbonylation with carbon monoxide (30 atm) at the alkene terminus of isoprene epoxide has been accomplished with a palladium catalyst to yield the homologated ethyl ester (eq 4).8 Other alkenyloxiranes afford b-lactones and dienes.

Nucleophilic Opening at C-1.

Cyanide has been used to open epoxides to provide b-hydroxy nitriles under phase-transfer conditions. These conditions are not very successful for isoprene epoxide because the product is water soluble. This problem has been overcome by the use of Acetone Cyanohydrin to selectively open isoprene epoxide at the C-1 terminus. The product is isolated without an aqueous workup (eq 5).9

Functionalization at C-2.

In synthesis, one goal that remains elusive is the stereoselective construction of quaternary centers in acyclic systems. Employing Chromium(II) Chloride, it is possible to functionalize the tertiary position of isoprene epoxide with reasonable diastereoselectivity (eq 6).10 The reaction rate is slower and the yield is lower when the same reaction is run with butadiene monoxide.

Related Reagents.

1,3-Butadiene Monoxide; Ethylene Oxide; Propylene Oxide.

1. Reist, E. J.; Junga, I. G.; Baker, B. R. JOC 1960, 25, 1673.
2. Thomsen, D. S.; Schiott, B.; Jorgensen, K. A. CC 1992, 1072.
3. Marshall, J. A. CRV 1989, 89, 1503.
4. (a) Blanchot-Courtois, V.; Hanna, I. TL 1992, 33, 8087. (b) Lee, E. R.; Lakomy, I.; Bigler, P.; Scheffold, R. HCA 1991, 74, 146. (c) Lipshutz, B. H.; Crow, R.; Dimock, S. H.; Ellsworth, E. L.; Smith, R. A. J.; Behling, J. R. JACS 1990, 112, 4063. (d) Bock, I.; Bornowski, H.; Ranft, A.; Theis, H. T 1990, 46, 1199. (e) Lipshutz, B. H.; Ellsworth, E. L.; Dimock, S. H.; Reuter, D. C. TL 1989, 30, 2065. (f) Ng, J. S.; Behling, J. R.; Campbell, A. L.; Nguyen, D.; Lipshutz, B. TL 1988, 29, 3045.
5. Schmid, R.; Antoulas, S.; Ruttimann, A.; Schmid, M.; Vecchi, M.; Weiser, H. HCA 1990, 73, 1276.
6. (a) Larock, R. C.; Ding, S. JOC 1993, 58, 804. (b) Tueting, D. R.; Echavarren, A. M.; Stille, J. K. T 1989, 45, 979.
7. Schmid, R.; Hansen, H.-J. HCA 1990, 73, 1258.
8. Shimizu, I; Maruyama, T.; Makuta, T.; Yamamoto, A. TL 1993, 34, 2135.
9. Mitchell, D.; Koenig, T. M. TL 1992, 33, 3281.
10. Fujimura, O.; Takai, K.; Utimoto, K. JOC 1990, 55, 1705.

Edward W. Thomas

The Upjohn Company, Kalamazoo, MI, USA

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