XX-th ARS SEPARATORIA Szklarska Poręba, Poland 2005

Transcription

1 XX-th A EPAATIA zklarska Poręba, Poland 2005 TABLE AND DYNAMIC, in situ FMED, DIATEEME A INTEMEDIATE IN ELUTIN F HETEATM CNTAINING ACEMATE AND MEAUEMENT F ENANTIMEIC EXCE VALUE J.DABWICZ, a,b P.ŁYŻWA, a J.ŁUCZAK, a B.DUDZIŃKI, a M.MIKŁAJCZYK, a.cllna, c N.GAGGE, c Y.YAMAMT, d K.- Y.AKIBA, e T.GIEK, b L.M.YAGUPLKII, f Y.L.YAGUPLKII, f A.V.MATNEV f a Center of Molecular and Macromolecular tudies, Polish Academy of ciences, Department of Heteroorganic Chemistry, Łódź, ienkiewicza 112, Poland b Jan Długosz University of Częstochowa, Department of Chemistry and Environmental Protection, Częstochowa, Armii Krajowej Ave 13/15, Poland c Centro CN and Istituto di Chimica rganica della Facolta di Farmacia, Univesita degli tudi di Milano, via Venenzian 21, Milano, Italy d Department of Chemistry, Graduate chool of cience, Hiroshima University, Kogamiyama, Higashi-Hiroshima , Japan e Advance esearch Center for cience and Engineering, Waseda University, hkubo, hinjuku, Tokyo , Japan f Institute of rganic Chemistry, National Academy of ciences of Ukraine, Kiev, Murmanskaya tr. 5, Ukraine A variety of optically active heteroorganic compounds, particularly those having a stereogenic sulfur [1], phosphorus [2] and selenium [3] atom are commonly applied both as models and chiral auxiliaries in mechanistic studies and spectroscopically based determination of absolute configurations and enantiomeric excess values [4] as well as stoichiometric reagents and catalysts in asymmetric synthesis [5]. Very often preparations of such optically active heteroatom-containing compounds are based on resolutions of stable diastereomers or on the generation of dynamic diastereomers as reaction intermediates. imultaneously in structural studies such dynamic diastereomers are also used as key structures. In this lecture we would like to present our own results and the literature reports dealing with these topics. ur own results will focus on: a) preparation of diastereo- and enantiomeric sulfinic derivatives by the aminemediated condensation of sulfinyl chlorides with chiral and achiral alcohols and thiols; b) bovine serum albumin catalyzed asymmetric oxidation of tertiary amines to the corresponding N-oxides; c) chromatographic resolutions of racemic trifluoromethyl aryl sulfoxides and spiroselenurane oxide; 2

2 XX-th A EPAATIA zklarska Poręba, Poland 2005 d) enantiomeric excess value determinations with the use of 2,2 -dihydroxy- 1,1 -binaphtol and t-butylphenylthiophosphinic acid as chiral solvating agents. PEPAATIN F CHIAL ULFINYL DEIVATIVE Chiral sulfinyl derivatives ()X 1 (X=,,N), are important intermediates that are widely applied in the synthesis of chiral organosulfur compounds and in their configurational correlations [1]. The most general approach to such structures is based on the asymmetric condensation of racemic sulfinyl chlorides 1 with chiral alcohols, thiols or amines in the presence of achiral bases or with achiral alcohols, thiols or amines in the presence of optically active base as asymmetric reagents. In the first case, the stable diastereomeric derivatives 2 are isolated as final reaction products and in the second one the in situ generated dynamic diastereomers 3 of a sulfinyl chloride and an optically active amine afforded upon reaction with an achiral nucleophile the final enantiomeric sulfinyl derivatives 4 (cheme 1). 1 XH B 2 X 1 + BHCl 1 Cl B [()Cl B] 3 1 XH 4 X 1 + B HCl cheme 1. The bovine serum albumin catalyzed asymmetric oxidation of tertiary amines to the corresponding N-oxides In a sharp contrast to chiral sulfoxides [1] and phosphine oxides [2], the nitrogen analogues i.e. chiral tertiary amine N-oxides 5 are much less known and without practical use in asymmetric synthesis [6]. This results mainly from the fact that an 3

3 XX-th A EPAATIA zklarska Poręba, Poland 2005 access to optically active to tertiary N-oxides is very limited in comparison with the sulfur and phosphorus analogues. To fill this gap we have been working [7] on the protein-catalyzed asymmetric oxidation of unsymmetrical tertiary amines 6 to the corresponding optically active N-oxides 5 (equation 1). It should be noted here that this conversion fulfils at least one of the conditions which characterize an ideal dynamic kinetic resolution procedure [8], namely the starting material enantiomers (tertiary amines) are always in an equilibrium due to a very fast pyramidal inversion on the stereogenic nitrogen atom of the substrates. 1 N BA [] 1 N (1) CHMATGAPHIC ELUTIN N CHIAL CLUMN We have found [9] that the oxidative kinetic resolution procedure based on the partial oxidation of a starting sulfoxide to the corresponding sulfone does not work for the racemic mixtures of trifluoromethyl aryl sulfoxides 7a-d due to their complete intertness to the Davis oxaziridines [10]. imilarly, the non-classical optical resolution via complexation with chiral host molecules can not be applied for the sulfoxide 7a-d due to their inability to form supramolecular complexes with β- cyclodextrin or mandelic acid [11]. n the other hand we have [9] successed in the isolation of the enantiomers of these sulfoxide by enantioselective liquid chromatography on analytical Chiracel D or Chiraplak A columns with hexaneipr-h mixtures as a mobile phase [9]. CF 3 p-x-c 6 H 4 7a-d a, X=H; b, X=Cl; c, X=F; d, X=H 4

4 XX-th A EPAATIA zklarska Poręba, Poland 2005 imilarly, the enantiomers of the first optically active selenurane oxide ever reported, C 2 -symmetric 3,3,3,3 -tetramethyl-1,1 -spirobi[3h,2,1]-benzoxaselenole oxide 8 were isolated when a solution of the racemate was passed through an analytical chiral HPLC column. They were also obtained by spontaneous resolution that occurs during the slow evaporation of acetonitryle solution of the racemate or its slow crystallization from the same solvent [12]. e 8 ENANTIMEIC EXCE VALUE DETEMINATIN Dynamic association complexes that are diastereoemric should, in principle, have different NM spectral parameters [13]. This fact allows the use of this technique for determining enantiomeric excess values and absolute configurations. H H t-bu Ph P 10 H 9 ince the first report on this possibility [13], more than 50 chiral solvating agents have been reported to induce enantiomeric nonequivalence in the NM spectra of a 5

5 XX-th A EPAATIA zklarska Poręba, Poland 2005 variety of solutes [14]. Among them are enantiomers of 2,2-dihydroxy-1,1 - binaphthol 9 [15] and t-butylphenylphosphiniothioic acid 10 [16]. EFEENCE 1. M.Mikołajczyk, J.Drabowicz, P.Kiełbasiński, Chiral ulfur eagents: Applications in tereoselective and Asymmetric ynthesis, CC Boca aton, K.M.Pietrusiewicz, M.Zabłocka, Chem.ev., 94 (1994) Topics in Current Chemistry Vol. 208, rganoselenium Chemistry: Modern Developments in rganic ynthesis, Ed. T.Wirth, pringer, Berlin, E.L.Eliel,.H.Wilen, tereochemistry of rganic Compounds, Wiley, New York, 1994, p J.eyden-Penne, Chiral Auxiliaries and Ligands in Asymmetric ynthesis, Wiley, New York, F.A.Davis, J..H.Jenkins, in Asymmetric ynthesis, Ed. J.D.Morrison, Academic Press, New York, 1983, Vol. 4, pp Colonna, N.Gaggero, J.Drabowicz, P.Łyżwa, M.Mikołajczyk, Chem.Commun., 1999, M.M.Jones, J.M.J.Williams, Chem.Commun., 1998, J.Drabowicz, J.Łuczak, M.Mikołajczyk, L.M.Yugopolskii, N.Kondratenko, Phosphorus, ulfur and ilicon, 180, 1417 (2005). 10. F.A.Davis et al., J.Am.Chem.oc., 114, 1428 (1992). 11. J.Drabowicz, unpublished results. 12. J.Drabowicz, J.Łuczak, M.Mikołajczyk, Y.Yamamoto,.Matsukawa, K.- y.akiba, Chirality, 16, 1 (2004). 13. W.H.Pirkle, D.J.Hoover, Topics in tereochemistry, 13, ). 14. D.Parker, Chem.ev., 91, 1441 (1991). 15. J.Drabowicz, H.Duddeck, ulfur Letters, 10, 37 (1989). 16. a) J.Drabowicz, B.Dudziński, M.Mikołajczyk, Tetrahedron: Asymmetry, 3, 1231 (1992); b) J.Drabowicz, B.Dudziński, M.Mikołajczyk,.Colonna, N.Gaggero, Tetrahedron: Asymmetry, 8, 2267 (1997). 6