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The synthesis and crystallographic structure of a bora-oxazino-oxazolidine derivative of resorcinarene obtained from (−)-(1R,2R)-norpseudoephedrine
Inorganic Chemistry Communications 8 (2005) 603–605 www.elsevier.com/locate/inoche
The synthesis and crystallographic structure of a bora-oxazino-oxazolidine derivative of resorcinarene obtained from ()-(1R,2R)-norpseudoephedrine Waldemar Iwanek b
a,*
, Roland Fro¨hlich b, Alicja Wzorek
a
a Pedagogical University, Institute of Chemistry, Che˛cin˜ska 5, 25020 Kielce, Poland University of Mu¨nster, Institute of Organic Chemistry, Corrensstrasse 40, 48149 Mu¨nster, Germany
Received 4 January 2005; accepted 22 February 2005 Available online 23 May 2005
Abstract The paper presents the highly diastereoselective synthesis (>99%) of a novel chiral bora-oxazino-oxazolidine derivative of resorcinarene obtained from ()-(1R,2R)-norpseudoephedrine and its crystallographic structure. 2005 Elsevier B.V. All rights reserved. Keywords: Resorcinarene; Aminoalcohols; Boron; Diastereoselectivity; Crystal structure
Resorcinarenes are cavity-shaped macrocycles which can be easily synthesized from resorcinol and aldehydes [1]. Their known derivatives comprise both oxazine [2] and oxazolidine [3] derivatives, including also chiral ones. Our previous paper employed L-prolinol [4] and (+)ephedrine [5], demonstrating that these two types of derivatives can be combined in a single compound, using phenylboronic acid to link the hydroxy groups and a lone electron pair of the nitrogen atom. This communication describes the molecular structure of a bora-oxazino-oxazolidine derivative of resorcinarene and its synthesis from primary amines ()-(1R,2R)-norpseudoephedrine. The Mannich reaction afforded the chiral aminomethyl derivatives of resorcinarene, where the free hydroxy groups and the nitrogen electron pair are linked to boron via phenylboronic acid. The diastereoselective synthesis of novel bora-oxazino-oxazolidine derivatives of resorcinarene 3 is shown in Scheme 1. Interestingly, this reaction is *
Corresponding author. Fax: +48 41 361 4942. E-mail address: [email protected] (W. Iwanek).
1387-7003/$ - see front matter 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.inoche.2005.02.016
characterized by an unusually high diastereoselectivity, d.e. > 99% [6]. In principle, when viewed from the calixarene cavity, the oxazine ring can be closed clockwise (P) or anticlockwise (M). Moreover, regarding the H–N–B–Ph bond, cis and trans isomers can be formed. Furthermore, the hydrogen atom on nitrogen and the phenyl groups on boron can be oriented inwards (endo) or outwards (exo) the resorcinarene cavity. The crystallographic structure of the single diastereoisomer is shown in Fig. 1 [7]. The chirality of ()-(1R,2R)-norpseudoephedrine and the rigid structure of bora-oxazino-oxazolidine determine the formation of the diastereoisomer itself, wherein all the resorcinol units in the resorcinarene molecule undergo synchronous anticlockwise closure (M) of the oxazine rings when viewed from inside the cavity. Besides, the hydrogen atom on nitrogen and phenyl group of boron atoms are cis-oriented and they are directed towards the resorcinarene cavity. Taking into account all these structural elements, this diastereoisomer can be classified as M–cis–endo. During the reaction
604
W. Iwanek et al. / Inorganic Chemistry Communications 8 (2005) 603–605 Ph
HO HO
Ph
CH3
CH3 H
O
HN
OH
N B
1)
HO
2)
OH
Ph O
OH
4 4
1
2
4
3, d.e. > 99 %
1) (-)-(1R,2R)-norpseudoephedrine, CH2O, MeOH, RT; 2) PhB(OH)2, toluene, 140 oC
Scheme 1.
Fig. 1. The crystallographic structure of the bora-oxazino-oxazolidine of resorcinarene 3 synthesized from ()-(1R,2R)-norpseudoephedrine. Hydrogen atoms are omitted for clarity.
two new stereocenters are created per unit at the N- and B-atoms. Since the reaction employed enantiomerically pure (1R,2R)-norpseudoephedrine, in the M–cis–endo diastereomer nitrogen and boron atoms both adopt the S configuration. The calixarene, when crystallized from methanol, contains a methanol molecule in its cavity. In the solid state, it has C4 symmetry which is stabilized by hydro-
gen bonds between the phenolic hydroxy groups; the ˚ distances between the oxygen atoms are: 2,753 A ˚ ˚ (O19A–O13D), 2.688 A (O19B–O13A), 2.711 A ˚ (O19C–O13B), and 2.815 A (O19D–O13A). In turn, the lengths of nitrogen–boron bonds are as follows: ˚ (N5A–B1A), 1.634 A ˚ (N5B–B1B), 1.599 A ˚ 1.619 A ˚ (N5C–B1C), 1.628 A (N5D–B1D); these lengths are similar to that of other derivatives of this type [4,5,8]. The
W. Iwanek et al. / Inorganic Chemistry Communications 8 (2005) 603–605 Table 1 ˚ ) for Crystallographic data and selected O–O and N–B bond length (A derivate 3 3 Formula M ˚ a/A ˚ b/A ˚ c/A b/deg ˚3 V/A Dcalc/g cm3 Z Cyst. syst. Space group R O19A–O13D O19B–O13A O19C–O13B O19D–O13A N5A–B1A N5B–B1B N5C–B1C N5D–B1D
C108H120B4N4O12 * 8 CH3OH 1983.67 12.239(1) 33.578(1) 15.217(1) 110.22(1) 5868.2(6) 0.953 2 Monoclinic P21 0.105 2.753 2.688 2.711 2.815 1.619 1.634 1.599 1.628
1
H NMR spectrum confirms that this compound adopts the C4 symmetry in DMSO solution; the proton signals are well resolved [9]. The selected crystallographic data, the distances between the oxygen atoms and the bond lengths between nitrogen and boron atoms are listed in Table 1. Data sets were collected with a Nonius Kappa CCD diffractometer, equipped with a rotating anode generator Nonius FR591. Programs used: data collection COLLECT (Nonius B.V., 1998), data reduction Denzo-SMN [10], absorption correction SORTAV [11], structure solution SHELXS-97 [12], structure refinement SHELXL-97 [13], graphics SCHAKAL (E. Keller, Universita¨t Freiburg, 1997). In conclusion, we present here the first example of a highly diastereoselective synthesis (d.e. > 99%) of a novel chiral bora-oxazino-oxazolidine of resorcinarene 3 obtained from primary chiral amines ()-(1R,2R)-norpseudoephedrine, and its crystallographic structure.
Supplementary material Crystallographic data for the structure analysis have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC 183054. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: int. code +44(1223)336-033, e-mail: [email protected]].
605
References [1] P. Timmerman, W. Verboom, D.N. Reinhoudt, Tetrahedron 52 (1996) 2663. [2] (a) W. Iwanek, J. Mattay, Liebigs Ann. (1995) 1463; (b) M.T. El Gihani, H. Heaney, A.M. Slavin, Tetrahedron Lett. 36 (1995) 4905; (c) R. Arnecke, V. Bo¨hmer, S. Friebe, S. Gebauer, G. Krauss, I. Thondorf, W. Vogt, Tetrahedron Lett. 36 (1995) 6221; (d) K. Airola, V. Bo¨hmer, E. Paulus, K. Rissanen, Ch. Schmidt, I. Thondorf, W. Vogt, Tetrahedron 53 (1997) 10709; (e) Ch. Schmidt, E.F. Paulus, V. Bo¨hmer, W. Vogt, New J. Chem. 25 (2001) 374; (f) W. Iwanek, Tetrahedron Asymm. 9 (1998) 3171. [3] (a) W. Iwanek, Ch. Wolff, J. Mattay, Tetrahedron Lett. 36 (1995) 8969; (b) Ch. Schmidt, T. Straub, D. Fala`bu, E.F. Paulus, E. Wegelius, E. Kolehmainen, V. Bo¨hmer, K. Rissanen, W. Vogt, Eur. J. Org. Chem. (2000) 3937. [4] W. Iwanek, R. Froehlich, P. Schwab, V. Schurig, Chem. Commun. (2002) 2516. [5] W. Iwanek, R. Froehlich, V. Schurig, J. Inclus. Phen. Macroc. Chem. 49 (2004) 75. [6] Procedure for preparation of compound 3: The reaction was conducted without isolation of the aminomethylene derivative of resorcinarene (2), using four equivalents of formaldehyde and four equivalents of the chiral ()-(1R,2R)-norpseudoephedrine. The reaction was carried out in methanol. The solvent was evaporated after 24 h. Toluene and five equivalents of PhB(OH)2 were added to the residue, followed by azeotropic removal of water for 4 h. The thus obtained product was crystallised from methanol. Total yield 55%.. [7] X-ray crystal structure analysis of 3: formula C108H120B4N4O12 Æ 8CH3OH Æ H2O, M = 1983.67, light yellow crystal 0.30 · 0.10 · ˚, b= 0.10 mm, a = 12.239(1), b = 33.578(1), c = 15.217(1) A ˚ 3, qcalc = 1.123 g cm3, l = 0.76 cm1, 110.22(1), V = 5868.2(6) A empirical absorption correction via SORTAV (0.978 6 T 6 0.993), Z = 2, monoclinic, Space group P21 (No. 4), ˚ , T = 198 K, x and u scans, 41027 reflections k = 0.71073 A ˚ 1, 17488 independent collected (±h, ±k, ±l), [(sin)/k] = 0.59 A (Rint = 0.089) and 9863 observed reflections [I P 2r(I)], 1235 refined parameters, R = 0.105, wR2 = 0.231. [8] (a) P.D. Woodgate, G.M. Horner, N.P. Maynard, C.E. Rickard, J. Organometall. Chem. 592 (1999) 180; (b) H.I. Beltram, S.J. Alas, R. Santillan, N. Farfan, Can. J. Chem. 80 (2002) 801. [9] Spectral data for compound 3: M.p. > 300 C; ½a20 D ¼ 138.25 (c = 0.515, acetone); 1H NMR (400 MHz, DMSO) d: 0.955 (dd, JJ = 6.57 Hz, 24H, CH3), 1.147(d, J = 6.32 Hz, 12H, CH3), 1.688 (m, 4H, CH), 2.324 (m, 8H, CH2), 2.215(m, 4H, CH), 3.552 (dd, J = 14.40 Hz, J = 2.27 Hz, 4H, CH), 4.010 (d, J = 14.40 Hz, 4H, CH), 4.522 (d, J = 9.34 Hz, 4H, CH), 4.732 (t, 4H, CH), 5.952 (d, J = 9.85 Hz, 4H, NH), 7.110–7.320 (m, 32H, ArH), 7.450–7.525 (m, 8H, ArH), 7.773 (s, 4H, OH). 13C NMR (100 MHz, DMSO) d: 12.767, 23.400, 23.676, 27.044, 32.498, 39.800, 43.276, 62.382, 83.407, 107.087, 124.593, 125.858, 127.051, 127.669, 127.880, 127.933, 128.448, 128.775, 133.517, 143.262, 150.811, 151.313. HR-MS (ESI) m/z: 877.4662 (M–Na2)+2, (calc. 877.4535). [10] Z. Otwinowski, W. Minor, Method. Enzymol. 276 (1997) 307. [11] (a) R.H. Blessing, Acta Cryst. A 51 (1995) 33; (b) R.H. Blessing, J. Appl. Cryst. 30 (1997) 421. [12] G.M. Sheldrick, Acta Cryst. A 46 (1990) 467. [13] G.M. Sheldrick, Universita¨t Go¨ttingen, 1997.
The synthesis and crystallographic structure of a bora-oxazino-oxazolidine derivative of resorcinarene obtained from ()-(1R,2R)-norpseudoephedrine Waldemar Iwanek b
a,*
, Roland Fro¨hlich b, Alicja Wzorek
a
a Pedagogical University, Institute of Chemistry, Che˛cin˜ska 5, 25020 Kielce, Poland University of Mu¨nster, Institute of Organic Chemistry, Corrensstrasse 40, 48149 Mu¨nster, Germany
Received 4 January 2005; accepted 22 February 2005 Available online 23 May 2005
Abstract The paper presents the highly diastereoselective synthesis (>99%) of a novel chiral bora-oxazino-oxazolidine derivative of resorcinarene obtained from ()-(1R,2R)-norpseudoephedrine and its crystallographic structure. 2005 Elsevier B.V. All rights reserved. Keywords: Resorcinarene; Aminoalcohols; Boron; Diastereoselectivity; Crystal structure
Resorcinarenes are cavity-shaped macrocycles which can be easily synthesized from resorcinol and aldehydes [1]. Their known derivatives comprise both oxazine [2] and oxazolidine [3] derivatives, including also chiral ones. Our previous paper employed L-prolinol [4] and (+)ephedrine [5], demonstrating that these two types of derivatives can be combined in a single compound, using phenylboronic acid to link the hydroxy groups and a lone electron pair of the nitrogen atom. This communication describes the molecular structure of a bora-oxazino-oxazolidine derivative of resorcinarene and its synthesis from primary amines ()-(1R,2R)-norpseudoephedrine. The Mannich reaction afforded the chiral aminomethyl derivatives of resorcinarene, where the free hydroxy groups and the nitrogen electron pair are linked to boron via phenylboronic acid. The diastereoselective synthesis of novel bora-oxazino-oxazolidine derivatives of resorcinarene 3 is shown in Scheme 1. Interestingly, this reaction is *
Corresponding author. Fax: +48 41 361 4942. E-mail address: [email protected] (W. Iwanek).
1387-7003/$ - see front matter 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.inoche.2005.02.016
characterized by an unusually high diastereoselectivity, d.e. > 99% [6]. In principle, when viewed from the calixarene cavity, the oxazine ring can be closed clockwise (P) or anticlockwise (M). Moreover, regarding the H–N–B–Ph bond, cis and trans isomers can be formed. Furthermore, the hydrogen atom on nitrogen and the phenyl groups on boron can be oriented inwards (endo) or outwards (exo) the resorcinarene cavity. The crystallographic structure of the single diastereoisomer is shown in Fig. 1 [7]. The chirality of ()-(1R,2R)-norpseudoephedrine and the rigid structure of bora-oxazino-oxazolidine determine the formation of the diastereoisomer itself, wherein all the resorcinol units in the resorcinarene molecule undergo synchronous anticlockwise closure (M) of the oxazine rings when viewed from inside the cavity. Besides, the hydrogen atom on nitrogen and phenyl group of boron atoms are cis-oriented and they are directed towards the resorcinarene cavity. Taking into account all these structural elements, this diastereoisomer can be classified as M–cis–endo. During the reaction
604
W. Iwanek et al. / Inorganic Chemistry Communications 8 (2005) 603–605 Ph
HO HO
Ph
CH3
CH3 H
O
HN
OH
N B
1)
HO
2)
OH
Ph O
OH
4 4
1
2
4
3, d.e. > 99 %
1) (-)-(1R,2R)-norpseudoephedrine, CH2O, MeOH, RT; 2) PhB(OH)2, toluene, 140 oC
Scheme 1.
Fig. 1. The crystallographic structure of the bora-oxazino-oxazolidine of resorcinarene 3 synthesized from ()-(1R,2R)-norpseudoephedrine. Hydrogen atoms are omitted for clarity.
two new stereocenters are created per unit at the N- and B-atoms. Since the reaction employed enantiomerically pure (1R,2R)-norpseudoephedrine, in the M–cis–endo diastereomer nitrogen and boron atoms both adopt the S configuration. The calixarene, when crystallized from methanol, contains a methanol molecule in its cavity. In the solid state, it has C4 symmetry which is stabilized by hydro-
gen bonds between the phenolic hydroxy groups; the ˚ distances between the oxygen atoms are: 2,753 A ˚ ˚ (O19A–O13D), 2.688 A (O19B–O13A), 2.711 A ˚ (O19C–O13B), and 2.815 A (O19D–O13A). In turn, the lengths of nitrogen–boron bonds are as follows: ˚ (N5A–B1A), 1.634 A ˚ (N5B–B1B), 1.599 A ˚ 1.619 A ˚ (N5C–B1C), 1.628 A (N5D–B1D); these lengths are similar to that of other derivatives of this type [4,5,8]. The
W. Iwanek et al. / Inorganic Chemistry Communications 8 (2005) 603–605 Table 1 ˚ ) for Crystallographic data and selected O–O and N–B bond length (A derivate 3 3 Formula M ˚ a/A ˚ b/A ˚ c/A b/deg ˚3 V/A Dcalc/g cm3 Z Cyst. syst. Space group R O19A–O13D O19B–O13A O19C–O13B O19D–O13A N5A–B1A N5B–B1B N5C–B1C N5D–B1D
C108H120B4N4O12 * 8 CH3OH 1983.67 12.239(1) 33.578(1) 15.217(1) 110.22(1) 5868.2(6) 0.953 2 Monoclinic P21 0.105 2.753 2.688 2.711 2.815 1.619 1.634 1.599 1.628
1
H NMR spectrum confirms that this compound adopts the C4 symmetry in DMSO solution; the proton signals are well resolved [9]. The selected crystallographic data, the distances between the oxygen atoms and the bond lengths between nitrogen and boron atoms are listed in Table 1. Data sets were collected with a Nonius Kappa CCD diffractometer, equipped with a rotating anode generator Nonius FR591. Programs used: data collection COLLECT (Nonius B.V., 1998), data reduction Denzo-SMN [10], absorption correction SORTAV [11], structure solution SHELXS-97 [12], structure refinement SHELXL-97 [13], graphics SCHAKAL (E. Keller, Universita¨t Freiburg, 1997). In conclusion, we present here the first example of a highly diastereoselective synthesis (d.e. > 99%) of a novel chiral bora-oxazino-oxazolidine of resorcinarene 3 obtained from primary chiral amines ()-(1R,2R)-norpseudoephedrine, and its crystallographic structure.
Supplementary material Crystallographic data for the structure analysis have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication CCDC 183054. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax: int. code +44(1223)336-033, e-mail: [email protected]].
605
References [1] P. Timmerman, W. Verboom, D.N. Reinhoudt, Tetrahedron 52 (1996) 2663. [2] (a) W. Iwanek, J. Mattay, Liebigs Ann. (1995) 1463; (b) M.T. El Gihani, H. Heaney, A.M. Slavin, Tetrahedron Lett. 36 (1995) 4905; (c) R. Arnecke, V. Bo¨hmer, S. Friebe, S. Gebauer, G. Krauss, I. Thondorf, W. Vogt, Tetrahedron Lett. 36 (1995) 6221; (d) K. Airola, V. Bo¨hmer, E. Paulus, K. Rissanen, Ch. Schmidt, I. Thondorf, W. Vogt, Tetrahedron 53 (1997) 10709; (e) Ch. Schmidt, E.F. Paulus, V. Bo¨hmer, W. Vogt, New J. Chem. 25 (2001) 374; (f) W. Iwanek, Tetrahedron Asymm. 9 (1998) 3171. [3] (a) W. Iwanek, Ch. Wolff, J. Mattay, Tetrahedron Lett. 36 (1995) 8969; (b) Ch. Schmidt, T. Straub, D. Fala`bu, E.F. Paulus, E. Wegelius, E. Kolehmainen, V. Bo¨hmer, K. Rissanen, W. Vogt, Eur. J. Org. Chem. (2000) 3937. [4] W. Iwanek, R. Froehlich, P. Schwab, V. Schurig, Chem. Commun. (2002) 2516. [5] W. Iwanek, R. Froehlich, V. Schurig, J. Inclus. Phen. Macroc. Chem. 49 (2004) 75. [6] Procedure for preparation of compound 3: The reaction was conducted without isolation of the aminomethylene derivative of resorcinarene (2), using four equivalents of formaldehyde and four equivalents of the chiral ()-(1R,2R)-norpseudoephedrine. The reaction was carried out in methanol. The solvent was evaporated after 24 h. Toluene and five equivalents of PhB(OH)2 were added to the residue, followed by azeotropic removal of water for 4 h. The thus obtained product was crystallised from methanol. Total yield 55%.. [7] X-ray crystal structure analysis of 3: formula C108H120B4N4O12 Æ 8CH3OH Æ H2O, M = 1983.67, light yellow crystal 0.30 · 0.10 · ˚, b= 0.10 mm, a = 12.239(1), b = 33.578(1), c = 15.217(1) A ˚ 3, qcalc = 1.123 g cm3, l = 0.76 cm1, 110.22(1), V = 5868.2(6) A empirical absorption correction via SORTAV (0.978 6 T 6 0.993), Z = 2, monoclinic, Space group P21 (No. 4), ˚ , T = 198 K, x and u scans, 41027 reflections k = 0.71073 A ˚ 1, 17488 independent collected (±h, ±k, ±l), [(sin)/k] = 0.59 A (Rint = 0.089) and 9863 observed reflections [I P 2r(I)], 1235 refined parameters, R = 0.105, wR2 = 0.231. [8] (a) P.D. Woodgate, G.M. Horner, N.P. Maynard, C.E. Rickard, J. Organometall. Chem. 592 (1999) 180; (b) H.I. Beltram, S.J. Alas, R. Santillan, N. Farfan, Can. J. Chem. 80 (2002) 801. [9] Spectral data for compound 3: M.p. > 300 C; ½a20 D ¼ 138.25 (c = 0.515, acetone); 1H NMR (400 MHz, DMSO) d: 0.955 (dd, JJ = 6.57 Hz, 24H, CH3), 1.147(d, J = 6.32 Hz, 12H, CH3), 1.688 (m, 4H, CH), 2.324 (m, 8H, CH2), 2.215(m, 4H, CH), 3.552 (dd, J = 14.40 Hz, J = 2.27 Hz, 4H, CH), 4.010 (d, J = 14.40 Hz, 4H, CH), 4.522 (d, J = 9.34 Hz, 4H, CH), 4.732 (t, 4H, CH), 5.952 (d, J = 9.85 Hz, 4H, NH), 7.110–7.320 (m, 32H, ArH), 7.450–7.525 (m, 8H, ArH), 7.773 (s, 4H, OH). 13C NMR (100 MHz, DMSO) d: 12.767, 23.400, 23.676, 27.044, 32.498, 39.800, 43.276, 62.382, 83.407, 107.087, 124.593, 125.858, 127.051, 127.669, 127.880, 127.933, 128.448, 128.775, 133.517, 143.262, 150.811, 151.313. HR-MS (ESI) m/z: 877.4662 (M–Na2)+2, (calc. 877.4535). [10] Z. Otwinowski, W. Minor, Method. Enzymol. 276 (1997) 307. [11] (a) R.H. Blessing, Acta Cryst. A 51 (1995) 33; (b) R.H. Blessing, J. Appl. Cryst. 30 (1997) 421. [12] G.M. Sheldrick, Acta Cryst. A 46 (1990) 467. [13] G.M. Sheldrick, Universita¨t Go¨ttingen, 1997.