1,3-Dicyclohexylcarbodiimide-Copper(I) Chloride1

(DCC)

[538-75-0]  · C13H22N2  · 1,3-Dicyclohexylcarbodiimide-Copper(I) Chloride  · (MW 206.33) (CuCl)

[7758-89-6]  · ClCu  · 1,3-Dicyclohexylcarbodiimide-Copper(I) Chloride  · (MW 99.00)

(dehydrating reagent used for preparation of a,b-enones,2,3 enimines,4 and nitroalkenes;5 used for esterification of secondary alcohols with inversion of configuration6)

Physical Data: for details see individual entries for 1,3-Dicyclohexylcarbodiimide and Copper(I) Chloride.

Dehydration.

DCC in the presence of a catalytic amount of CuCl efficiently dehydrates alcohols with a b-substituted acceptor group. Reaction of b-hydroxy ketones, 2-hydroxyimines, and nitroaldols with DCC/CuCl affords a,b-unsaturated ketones (60-80% yield) (eq 1),2,3 enimines (31-75% yield) (eq 2),4 and nitroalkenes (60-99% yield) (eq 3),5 respectively.

The mild reaction conditions provide an alternative to methods utilizing acidic conditions that promote polymerization and interfere with other functional groups. Yields for the DCC/CuCl method are comparable to the acidic conditions.2-5

a-Cyclopropyl ketones (eq 4) can be prepared by DCC/CuCl dehydration of g-hydroxy ketones7 which compares to other methods, e.g. alkylation of g-chloro ketones or Simmons-Smith cyclopropanation of a,b-unsaturated ketones. A drawback to this method is the formation of dihydrofurans in the event of ketone enolization (eq 5). This phenomenon offers insight into the reaction mechanism, suggesting a syn elimination of H2O.3,8

Esterification.

DCC/CuCl reacts with secondary alcohols (eq 6), affording an isourea ether or carbamidate adduct (1). Treatment of (1) with a carboxylic acid gives an ester with inverted configuration9 in good yield (50-83%) with high enantioselectivity (>99% ee)6 and compares to the Mitsunobu procedure.10 Saponification of the resulting ester produces an alcohol with inversion of configuration, which is a viable alternative to existing methods.11


1. Mathias, L. J. S 1979, 561.
2. Schmidt, E.; Moosmüller, F. LA 1955, 597, 235.
3. Alexandre, C.; Rouessac, F. BSF(2) 1971, 1837.
4. Schuster, E.; Hesse, C.; Schumann, D. SL 1991, 916.
5. Knochel, P.; Seebach, D. S 1982, 1017.
6. Kaulen, J. AG(E) 1987, 26, 773.
7. Alexandre, C.; Rouessac, F. TL 1970, 1011.
8. Corey, E. J.; Andersen, N. H.; Carlson, R. M.; Paust, J.; Vedejs, E.; Vlattas, I.; Winter, R. E. K. JACS 1968, 90, 3245.
9. Däbritz, E. AG(E) 1966, 5, 470.
10. Mitsunobu, O. S 1981, 1.
11. (a) Cainelli, G.; Manescalchi, F.; Martelli, G.; Panunzio, M.; Plessi, L. TL 1985, 26, 3369. (b) Kruizinga, W. H.; Strijtveen, B.; Kellogg, R. M. JOC 1981, 46, 4321. (c) Torisawa, Y.; Okabe, H.; Ikegami, S. CL 1984, 1555.

Elisabeth R. Johnston & Christopher W. Alexander

Emory University, Atlanta, GA, USA



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