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

[A0014] 

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Received: 15 July 2000 / Uploaded: 30 July 2000

Organoselenium reagents are largely used in organic synthesis to introduce new functional groups into organic substrates under very mild experimental conditions.[1] In recent years, several research groups have described the synthesis of a number of chiral non racemic diselenides which can be transformed in situ into electrophilic selenenylating agents to effect efficient asymmetric syntheses.[2][3][4][5][6][7] Diselenides containing a nitrogen atom in the chiral moiety have also been employed as useful ligands in various transformations such as diethilzinc additions to aldehydes,[8] asymmetric hydrosilylation[9] and transfer hydrogenation reactions.[10] Moreover these diselenides can also be employed in the sequential catalytic stereoselective oxyselenenylation-elimination reactions using ammonium persulfate to generate the electrophilic selenenylating species and to promote the elimination process.[11]

Herein we report the synthesis of two new chiral nitrogen containing diselenides and the use of these compounds as precursors of electrophilic species in asymmetric additions of organoselenium reagents to olefins.

The condensation of the commercially available compounds 1 and 2 readily afforded the intermediate 3 which was reduced with sodium triacetoxyborohydride in acetic acid at �78�C to give a 91:9 mixture of the diastereomeric chiral secondary amines 4. The mixture of 4 was refluxed with formic acid and formaldehyde and was thus quantitatively converted into the amines 5 and 6. The two compounds were separated by flash chromatography and independently transformed into the corresponding diselenides 7 and 8 by treatment with t-BuLi and elemental selenium. The absolute configuration of the chiral carbon atom generated during the reduction was assigned on the basis of the observation that the debromination of 6 (t-BuLi, water) afforded the corresponding meso derivative.

Diselenides 7 and 8 were employed to effect asymmetric addition reactions to olefins. Preliminary experiments were carried out in the methoxyselenenylation and hydroxyselenenylation of styrene. As indicated in the following scheme the two sets of experiments gave the addition products 9a-10a and 11a-12a, respectively. From the data collected in Table 1 it can be seen that, using ammonium persulfate as oxidizing agent and working at room temperature, the diselenide 7 (entries 1 and 4) gave higher diastereomeric ratios than 8 (entries 2 and 5). No substantial differences were observed when the reactions were run at �78�C and using the triflate as the counter ion (entries 3 and 6).

Table 1: Methoxyselenenylation and Hydroxyselenenylation of Styrene Promoted by the Diselenides 7 and 8

The absolute configuration of compounds 9a and 11a was established by reductive deselenenylation with triphenyltin hydride and AIBN in refluxing benzene. As indicated in the following scheme compound 9a gave the chiral ether (+)-(R)-methoxyphenylethane 13 and compound 11a gave the (-)-(S)-methoxyphenylethane 14. As expected, the enantiomeric excess of 13 and 14 corresponded to diastereomeric ratio in 9a and 11a, respectively.

On the basis of the results of the preliminary experiments described above the selenomethoxylation and selenohydroxylation reactions of several alkenes were carried out using the diselenide 7 under the experimental conditions described in Table 1 (entries 1 and 4) .The results obtained from these experiments are collected in Table 2. In a tipical experiment ammonium persulfate and trifluoromethanesulfonic acid were added to a stirred solution of the diselenide 7 in diethyl ether. The mixture was stirred at room temperature for 15 minutes and then a solution of the alkene in methanol (entries 1,3,4,5) or in a 1:1 mixture of acetonitrile and water(entry 2) was added. Stirring was continued for 60 h. The results reported in Table 2 indicate that satisfactory to good chemical yields were obtained in every case. Good facial selectivities were observed in the case of the methoxyselenenylation reactions with the exception of the reaction carried out with cyclohexene. As observed in previous cases [12] the hydroxyselenenylation reactions gave poorer results.

Table 2: Selenoaddition Reactions Using the Diselenide 7

The efficiency of diselenide 7 was also tested in the case of ciclofunctionalization processes, For this purpose the E-3-alkenols 15 and 16 were treated with a stoichiometric amount of selenenylating agent prepared from 7 as described above in a 3:1 mixture of diethyl ether and methanol. The nucleophilic solvent did not compete with the intramolecular process and only the tetrahydrofurans 17 and 18 were isolated as the reaction products. In both cases good chemical yields and facial selectivities were observed.

Finally the following scheme illustrates a further use of the diselenide 7. Ammonium persulfate and the diselenide 7 were employed to effect the catalytic one-pot conversion of the b,g-unsatured ester 19 into the allylic ether 20 according to our recently described selenenylation-elimination procedure.[13] The results of these experiments are reported in Table 3. The reaction was first carried out in diethyl ether and methanol (2:1) in the presence of trifluoromethanesulfonic acid using stoichiometric (entry 1) and catalytic (entry 2) amounts of 7 and an excess of ammonium persulfate. Under these conditions conversion rates were very low. However, in both cases excellent facial selectivities were observed (94% ee). The reaction was repeated using a stoichiometric amount of nickel(II) nitrate as additive (entry 3). In this case the conversion rate was considerably increased but the enantioselectivity was very poor (45% ee). Further investigations are presently under way to improve the results of this one-pot selenenylation-elimination sequence.

Table 3: One pot Conversion of the b,g-Unsatured Ester 19 into the Allylic Ether 20.

Acknowledgements. Financial support from MURST, National Project "Stereoselezione in Sintesi Organica. Metodologie e Applicazioni", the University of Perugia, Progetti di Ateneo, and CNR, Rome is gratefully acknowledged.

[1] M. Tiecco. In Topics in Current Chemistry: Organoselenium Chemistry: Modern Developments in Organic Synthesis; Wirth, T., Ed. Electrophilic Selenium, Selenocyclizations. Springer-Verlag: Heidelberg, 2000; pp 7-54.

[2] T. Wirth, Tetrahedron 1999, 55, 1-28.

[3] ^[3a] K.Fujita, K. Murata, M. Iwaoka, S. Tomoda, Tetrahedron 1997, 53, 2029-2048.-^[3b] K. Fujita, K. Murata, M. Iwaoka, S. Tomoda, Tetrahedron Lett. 1995, 36, 5219-5222.- ^[3c] K. Fujita, K. Murata, M. Iwaoka, S. Tomoda, J. Chem Soc., Chem. Commun. 1995, 1641-1642.

[4] ^[4a] T. Wirth, Liebigs Ann. 1997, 2189-2196 and references cited therein.- ^[4b] T. Wirth, G. Fragale, Chem. Eur. J. 1997, 3, 1894-1902. ^[4c] T. Wirth, S. Humptli, M. Leuenberger, Tetrahedron Asymmetry 1998, 547-550.- ^[4d] T. Wirth, G. Fragale, M. Spichty J. Am. Chem. Soc. 1998, 120, 3376-3381. ^[4e] C.Santi, G. Fragale, T. Wirth, Tetrahedron Asymmetry 1998, 3625-3628

[5] ^[5a] S. Fukuzawa, K. Takahashi, H. Kato, H. Yamazaki, J. Org. Chem. 1997, 62, 7711-7716.- ^[5b] Y. Nishibayashi, S. K. Srivastava, H. Takada, S. Fukuzawa, S. Uemura, J. Chem. Soc., Chem. Commun. 1995, 2321-2322.- ^[5c] S. Fukuzawa, Y. Kasugahara, S. Uemura, Tetrahedron Lett. 1994, 35, 9403-9406.

[6] R. Deziel, E. Malenfant, C. Thilbault, S. Frèchette, M. Gravel, Tetrahedron Lett. 1997, 38, 4753-4756 and references cited therein.

[7] T. G. Back, B.P. Dyck, M. Parvez, J. Org. Chem. 1995, 60, 703-710.

[8] C. Santi, T. Wirth, , Tetrahedron Asymmetry 1999, 1019-1023.

[9] ^[9a]Y. Nishibayashi, J.D. Singh, K. Segawa; S.-I. Fukuzawa, S. Uemura J. Chem Soc., Chem. Commun. 1994, 1375-1376. ^[9b] Y. Nishibayashi, K. Segawa, J.D. Singh; S.I. Fukuzawa, K. Ohe; S. Uemura Organometallics 1996, 15, 370-379.

[10] Y. Nishibayashi, J.D. Singh; Y. Arikawa, S. Uemura, M. Hidai Organomet. Chem. 1997, 531, 13-18.

[11] T. Wirth, S. Humptli, M. Leuenberger Tetrahedron Asymmetry 1998, 547-550\.

[12] M. Tiecco, L. Testaferri, C. Santi, F. Marini, L. Bagnoli, A. Temperini, C. Tomassini, Eur. J. Org. Chem. 1998, 2275-2277.

[13] M. Tiecco, L. Testaferri, M. Tingoli, L. Bagnoli, C. Santi J. Chem Soc., Chem. Commun. 1993, 637-639.

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