a-Cyclopropylcyclopropanemethanol

[14300-33-5]  · C7H12O  · (MW 112.17)

(reagent for carboxylic acid protection1)

Alternate Name: dicyclopropylmethanol, dicyclopropylcarbinol, Dcpm-OH.

Physical Data: bp 66-68 °C (12 mmHg),2 48 °C (3 mmHg).3

Solubility: soluble in all common organic solvents.

Analysis of Reagent Purity: 1H NMR, elemental analysis.

Preparative Methods: the title reagent can be prepared by the reduction of dicyclopropyl ketone by means of LiAlH42,3 or NaBH4.4

Handling, Storage, and Precautions: stable under normal conditions but suffers ring opening in the presence of acids.5 Some Fmoc amino acid Dcpm esters suffer deblocking to the free acid on TLC or column chromatography over silica gel.1

Carboxylic Acid Protection

The Dcpm group was recommended for protection of the carboxyl function in cases where selectivity in deblocking relative to O-tert-butyl or N-trityl protection was needed.1 An example involves the rapid solution assembly of 1 and its conversion to 2 by treatment with 1% trifluoroacetic acid in methylene chloride.

A general method has been given for the synthesis of amino acid Dcpm esters via the acid chloride or acid fluoride in the presence of pyridine.1

Homoallylic Rearrangement of Dcpm-OH

As is the case for most secondary and tertiary cyclopropylmethyl alcohols, Dcpm-OH undergoes ring opening with conversion to the homoallyl alcohol on treatment with an acidic reagent (1).5-8 The trans product is favored. Ring opening is avoided in the presence of a good nucleophile such as a mercaptan or azide ion.

Conversion to Ring-Retained Sulfides

Dcpm protection of mercaptans is possible via reaction of the alkoxide of Dcpm-OH in the presence of N,N-methylphenylaminotriphenylphosphonium iodide (2).9

Conversion to Dcpm-NH2

Dcpm-OH is a convenient source of the corresponding amine, Dcpm-NH2, useful as a less-sensitive amide protectant than the Dmcp analog.1 Reaction with NaN3/CCl3CO2H to give the azide is followed by reduction to the amine (3).1


1. Carpino, L. A.; Chao, H.-G.; Ghassemi, S.; Mansour, E. M. E.; Riemer, C.; Warrass, R.; Sadat-Aalaee, D.; Truran, G. A.; Imazumi, H.; El-Faham, A.; Ionescu, D.; Ismail, M.; Kowaleski, T. L.; Han, C.-H.; Wenschuh, H.; Beyermann, M.; Bienert, M.; Shroff, H.; Albericio, F.; Triolo, S. A.; Sole, N.; Kates, S. A., J. Org. Chem. 1995, 60, 7718.
2. Hanack, M.; Eggensperger, H., Liebigs Ann. Chem. 1963, 663, 31.
3. Hart, H.; Curtis, O. E., Jr., J. Am. Chem. Soc. 1956, 78, 112.
4. Neckers, D. C.; Schaap, A. P., J. Org. Chem. 1967, 32, 22.
5. Sarel, S.; Yovell, J.; Sarel-Imber, M., Angew. Chem., Int. Ed. Engl. 1968, 7, 577.
6. McCormick, J. P.; Barton, D. L., J. Chem. Soc., Chem. Commun. 1975, 303.
7. Argenti, L.; Bellina, F.; Carpita, A.; Dell'Amico, N.; Rossi, R., Synth. Commun. 1994, 24, 3167.
8. Matveeva, E. D.; Kvasha, M. P.; Kurts, A. L., Russ. J. Org. Chem. 1996, 32, 17.
9. Tanigawa, Y.; Kanamaru, H.; Murahashi, S.-I., Tetrahedron Lett., 1975, 16, 4655.

Louis A. Carpino

University of Massachusetts, Amherst, Massachusetts, USA



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