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

[A0027] 

Base promoted isomerization of aziridinyl ethers: a new access to a- and b-aminoacids

Laura Sbaragli, Francesco Russo, Michela Valacchi, Gianna Reginato, Alessandro Mordini* Centro CNR Composti Eterociclici, Dipartimento di Chimica Organica “U. Schiff”, Via Gino Capponi 9, I-50121 Firenze, Italia E-mail: [email protected]

Received: 23 July 2000 / Uploaded: 29 July 2000

In the last few years we have extensively studied the base-promoted isomerization of oxiranyl ethers showing that they can be stereoselectively converted in a number of synthetically useful products by treatment with mixed metal reagents (superbases) [1,2]. Depending on the substrate and the base used oxiranyl ethers 1 can be transformed into hydroxy enethers 2 [3,4] (R’= H), di- and tri-substituted oxetanes 3 via a 4-endo process [5-7] (R’= H or alkyl), 1,4-diols 4 using an excess of base [8], tetrahydrooxepines 5 (R’’= CH=CH₂) [9] and terminal allylic alcohols 7 (R’’= SPh) when radical anions are used. The use of superbasic mixtures is essential in order to have processes with a highly regio- and stereoselective behaviour and high yields of converted products.

In order to further extend the scope of our studies, we have recently undertaken an investigation of the reactivity of aziridinyl ethers with superbasic reagents, aiming at the synthesis of hydroxy amines and a- or b-aminoacids. Enantiomerically enriched aziridinyl ethers 11 can be prepared in a number of ways [10] among which we have selected the sequences starting from epoxy ethers 9, through ring opening with sodium azide and ring closure to aziridine with triphenyl phospine [11]. The aziridinyl ethers 11 have then been protected with some different groups on nitrogen, namely as benzyl- (12), tert-butoxycarbonyl- (BOC, 13) and para-toluenesulfonyl- (Ts, 14) aziridines.

Compounds 12a, 13a and 14a have been submitted to treatment with the superbasic misture lithium diisopropylamide/ potassium tert-butoxide (LIDAKOR) in order to first test the influence of the group on nitrogen on the isomerization process. We have found that only the tosyl aziridine 14a can be isomerized to the corresponding amino vinyl ether 15, while the benzyl derivative 12a doesn’t react and the BOC-aziridine 13a is simply deprotected to the starting aziridine 11a under the same reaction conditions. The conversion aziridine-amino vinyl ether is highly regio- and stereoselective and compound 15 is a very useful building block for further transformations. As an example 15 has been cleanly deprotected to the amino aldehyde 16 and the latter oxidized [12] to the b-aminoacid 17.

The formation of vinyl ether 15 is obviously due to selective deprotonation of the methylene group adjacent to the OMOM group and the aziridinyl ring. When we have applied the same reaction conditions to the aziridine 14b, having an additional acidic position (the benzylic methylene group), we have found a different reaction pathway, leading this time to the cinnamyl amino alcohol 18 in a very selective manner. Compound 18 is the precursor of the b,g-unsaturated a-amino acid, phenyl glicine and the extension of this methodology to other similar substrates could lead to a new approach to a large variety of unsaturated a-aminoacids.

Both the reaction sequences illustrated above disclose new methods for the synthesis of unnatural a- and b-amino acids.

 Acknowledgment. This work was supported by the Consiglio Nazionale delle Ricerche.

References

[1] A. Mordini in Comprehensive Organometallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon: Oxford, 1995 Vol. 11, p 93.

[2] A. Mordini in Advances in Carbanion Chemistry; Snieckus, V., Ed.; JAI Press: Greenwich,CT, 1992; Vol. 1, p 1.

[3] A. Mordini, S. Pecchi, G. Capozzi, A. Capperucci, A. Degl'Innocenti, G. Reginato, A. Ricci, J. Org. Chem. 1994, 59, 4784.

[4] A. Mordini, M. Valacchi, S. Pecchi, A. Degl’Innocenti, G. Reginato Tetrahedron Lett. 1996, 37, 5209.

[5] A. Mordini, S. Bindi, S. Pecchi, A. Degl’Innocenti, G. Reginato, A. Serci J. Org. Chem. 1996, 61, 4374.

[6] A. Mordini, S. Bindi, S. Pecchi, A. Capperucci, A. Degl’Innocenti, G. Reginato J. Org. Chem. 1996, 61, 4466.

[7] A. Mordini, M. Valacchi, C. Nardi, S. Bindi, G. Poli, G. Reginato J. Org. Chem. 1997, 62, 8557.

[8] A. Thurner, F. Faigl, A. Mordini, A. Bigi, G. Reginato, L. Toke Tetrahedron 1998, 54, 11597.

[9] A. Mordini, S. Bindi, D. Nistri, G. Reginato, M. Valacchi J. Org. Chem. 2000, 65, 0000.

 [10] H. M. I. Osborn, J. Sweeney Tetrahedron: Asymmetry 1997, 8, 1693;  R. S. Atkinson Tetrahedron 1999, 55, 1519.

[11] D. Tanner, P. Somfai Tetrahedron Lett. 1987, 28, 1211-1214.

[12] M. Zhao, J. Li, Z. Song, R. Desmond, D. M. Tschaen, E. J. J. Grabowski, P. J. Reider Tetrahedron Lett. 1998, 39, 5323.

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