Fourth International ElectronicConference on Synthetic Organic Chemistry (ECSOC-4), www.mdpi.org/ecsoc-4.htm, September 1-30, 2000

	N,N-Diisopropylcarbamate of -hydroxystyrenes: A New Entry to -hydroxy-ß-phenylethylamines and ephedrines

Julio A. Seijas*, M. Pilar Vázquez-Tato* , Luis Barreiro-Castro
 

Departamento de Química Orgánica. Facultad de Ciencias de Lugo. Universidad de Santiago de Compostela. Aptdo. 280. 27080-LUGO. SPAIN
E-mail: [email protected] , [email protected]

Received: 4 August 2000 / Uploaded: 5 August 2000

    Our group has been investigating on the transformation of styrene derivatives into ß-phenylethylamines [1]. We had previously worked on the carbolithiation of styrenic compounds  and we achieved successfully the hydroxylation of the -position of styrene [2]. However this method proved to be unsuccessful when applied to addition of lithium amides [3].
    ß-hydroxy-ß-phenylethylamines are very interesting due to their wide variety of pharmacological properties [4]. To achieve their synthesis we had to change our strategy. Instead of leaving the introduction of the oxygen atom at C- for the end of the synthesis, we decided to start from -hydroxystyrene derivatives, where the oxygen atom was present previously to the nucleophillic addition stage. Previously it had been reported that enolcarbamates could support the addition of organolithium without reaction of the carbonyl group [5]. Thus we prepared the N,N-diisopropylcarbamate of  the enol of acetophenone 1. We treated it with the lithium amide of morpholine obtaining the addition compound 2 in a 77% yield, the cleavage of isopropylcarbamates is performed by reduction with lithium aluminum hydride [6], thus we obtained ß-hydroxyl-ß-phenylethylamine 3  in 67% yield.
 

    Another interesting analogs of ß-phenylethylamines are ephedrine like compounds. To carry out the synthesis of this skeleton, we prepared the N,N-diisopropylcarbamate of the enol of propiophenone 4, this was reacted with the lithium amide of morpholine affording addition product 5 in 72% yield, the cleavage of carbamate group presenting 5 with lithium aluminum  hydride gave amino alcohol 6 in 79% yield.
 

    We think our method for the synthesis of ß-phenylethylamine derivatives, constitutes a interesting approach with good yields. Actually we are checking the scope of this methodology for a wide variety of primary and secondary amines.
 

Acknowledgments: Financial support from DGES (project PB96-0932) is gratefully acknowledged.

References:
1.- Seijas, J.A., Vázquez-Tato, M.P.; Entenza, C.; Martínez, M.M.; Ónega, M. G.; Veiga, S., Tetrahedron Lett., 1998, 39, 5073-5076. ECSOC-3, 1999, [a0022] "Microwave Enhanced Hydroamination of Styrene", Julio A. Seijas, M. Pilar Vázquez Tato and M.Montserrat Martínez. ECSOC-3, 1999, communication [a0025]: "Hydroamination of Cinnamyl Alcohol",  Seijas, J. A.; Vázquez-Tato, M. P.; Barreiro-Castro, L and Romero-Van-der-Schoot, R.

2.- Martínez, M.M.; Ónega, M.G.; Tellado, M.F.; Seijas, J.A.; Vázquez-Tato, M.P., Tetrahedron, 1997, 53, 14127-14130.

3.- M. Montserrat Martínez, Ph. D. Thesis, unpublished results

4.- "The Merck Index", 12th. edition. Merck and Co., Inc. Whitehouse Station, 1996.

5.- Hoppe, D.; Hense, T., Angew. Chem. Int. Ed. Engl., 1997, 36, 282-2316.

6.- Guarnieri, W.; Sendzik, M., Fröhlich, R.; Hoppe, D., Synthesis, 1998, 1274-1297.
 

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