Development of a New Chiral Spiro Oxazolinylpyridine Ligand (Spymox) for Asymmetric Catalysis

Abstract

A novel optically active 2-(oxazolinyl)pyridine ligand (Spymox) having a spiro binaphthyl backbone was synthesized from an α,α-disubstituted α-amino acid (H-Bin-OH), and successfully used in palladium-catalyzed asymmetric allylic alkylations to afford the corresponding alkylated products with 99% ee.

ligand design - α-amino acid - spiro compounds - asymmetric catalysis - allylic substitution

References and Notes

1 A recent review for chiral phosphine ligands on a spiro scaffold: Xie J.-H. Zhou Q.-L. Acc. Chem. Res.  2008,  41:  581 

Most of the reported efficient spiro chiral ligands have a 1,1′-spirobiindane backbone. For examples, see:

2a Birman VB. Rheingold AL. Lam K.-C. Tetrahedron: Asymmetry  1999,  10:  125 

2b Hu A.-G. Fu Y. Xie J.-H. Zhou H. Wang L.-X. Zhou Q.-L. Angew. Chem. Int. Ed.  2002,  41:  2348 

2c Xie J.-H. Wang L.-X. Fu Y. Zhu S.-F. Fan B.-M. Duan H.-F. Zhou Q.-L. J. Am. Chem. Soc.  2003,  125:  4404 

2d Xie J.-H. Duan H.-F. Fan B.-M. Cheng X. Wang L.-X. Zhou Q.-L. Adv. Synth. Catal.  2004,  346:  625 

2e Zhu S.-F. Yang Y. Wang L.-X. Liu B. Zhou Q.-L. Org. Lett.  2005,  7:  2333 

2f Cheng X. Zhang Q. Xie J.-H. Wang L.-X. Zhou Q.-L. Angew. Chem. Int. Ed.  2005,  44:  1118 

2g Zhu S.-F. Xie J.-B. Zhang Y.-Z. Li S. Zhou Q.-L. J. Am. Chem. Soc.  2006,  128:  12886 

2h Chen C. Zhu S.-F. Liu B. Wang L.-X. Zhou Q.-L. J. Am. Chem. Soc.  2007,  129:  12616 

Examples of spiro chiral ligands other than those listed in ref. 2:

3a Jiang Y. Mi A. Yan M. Sun J. Lou R. Deng J. J. Am. Chem. Soc.  1997,  119:  9570 

3b Arai MA. Arai T. Sasai H. Org. Lett.  1999,  1:  1795 

3c Arai MA. Kuraishi M. Arai T. Sasai H. J. Am. Chem. Soc.  2001,  123:  2907 

3d Wu S.-L. Zhang W.-C. Zhang Z.-G. Zhang X.-M. Org. Lett.  2004,  6:  3565 

3e Lin CW. Lin C.-C. Lam LF.-L. Au-Yeung TT.-L. Chan ASC. Tetrahedron Lett.  2004,  45:  7379 

3f Lait SM. Parvez M. Keay BA. Tetrahedron: Asymmetry  2004,  15:  155 

3g Guo Z. Guan X. Chen Z. Tetrahedron: Asymmetry  2006,  17:  468 

3h Koranne PS. Tsujihara T. Arai MA. Bajracharya GB. Suzuki T. Onitsuka K. Sasai H. Tetrahedron: Asymmetry  2007,  18:  919 

Recent reviews on nitrogen-containing chiral ligands:

4a Fache F. Schulz E. Tommasino ML. Lemaire M. Chem. Rev.  2000,  100:  2159 

4b McManus HA. Guiry PJ. Chem. Rev.  2004,  104:  4151 

Synthesis of H-Bin-OR and their application to peptide chemistry:

5a Mazaleyrat J.-P. Gaucher A. Wakselman M. Tchertanov L. Guilhem J. Tetrahedron Lett.  1996,  37:  2971 

5b Mazaleyrat J.-P. avrda J. Wakselman M. Tetrahedron: Asymmetry  1997,  8:  619 

5c Mazaleyrat J.-P. Boutboul A. Lebars Y. Gaucher A. Wakselman M. Tetrahedron: Asymmetry  1998,  9:  2701 

5d Mazaleyrat J.-P. Wright K. Gaucher A. Wakselman M. Oancea S. Formaggio F. Toniolo C. Setnika V. Kapitán J. Keiderling TA. Tetrahedron: Asymmetry  2003,  14:  1879 

6a Catalytic Asymmetric Synthesis   2nd ed.:  Ojima I. Wiley-VCH; New York: 2000. 

6b Comprehensive Asymmetric Catalysis   Vol. 1-3:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; New York: 1999. 

7a Dalko PI. Moisan L. Angew. Chem. Int. Ed.  2004,  43:  5138 

7b Berkessel A. Gröger H. Asymmetric Organocatalysis   Wiley-VCH; Weinheim: 2005. 

7c Enantioselective Organocatalysis: Reactions and Experimental Procedures   Dalko PI. Wiley-VCH; Weinheim: 2007. 

Reviews on the asymmetric allylic alkylation reaction:

8a Paquin J.-F. Lautens M. In Comprehensive Asymmetric Catalysis   Suppl. 2:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 2004.  p.73-95  ; and references therein

8b Pfaltz A. Lautens M. In Comprehensive Asymmetric Catalysis   Vol. 2:  Jacobsen EN. Pfaltz A. Yamamoto H. Springer; New York: 1999.  p.833-884  ; and references therein

9

Palladium-catalyzed asymmetric allylic alkylation using a spiro chiral ligand having a 1,1′-spirobiindane backbone (SDP) has been reported, see ref. [²d] .

10

A previous report on asymmetric allylic alkylation using pymox-Pd complex also shows moderate enantioselectivity (50% ee): Nordström K., Macedo E., Moberg C.; J. Org. Chem.; 1997, 62: 1604

Palladium-catalyzed asymmetric allylic alkylations with fluorinated carbanion:

11a Fukuzumi T. Shibata N. Sugiura M. Yasui H. Nakamura S. Toru T. Angew. Chem. Int. Ed.  2006,  45:  4973 

11b Jiang B. Huang Z.-G. Cheng K.-J. Tetrahedron: Asymmetry  2006,  17:  942 

11c Zhang F. Song ZJ. Tschaen D. Volante RP. Org. Lett.  2004,  6:  3775 

11d Komatsu Y. Sakamoto T. Kitazume T. J. Org. Chem.  1999,  64:  8369 

12 For compounds 6a, 8c, see: Imamoto T. Nishimura M. Koide A. Yoshida K. J. Org. Chem.  2007,  72:  7413 

13 For compounds 6b-d, 8b, see: Kinoshita N. Kawabata T. Tsubaki K. Bando M. Fuji K. Tetrahedron  2006,  62:  1756 

14 For compound 8a, see: Braga AL. Vargas F. Sehnem JA. Braga RC. J. Org. Chem.  2005,  70:  9021 

15 For compound 8d, see: Jiang B. Huang Z.-G. Cheng K.-J. Tetrahedron: Asymmetry  2006,  17:  942 

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Compound 1: ^¹H NMR (300 MHz, CDCl₃): δ = 8.71 (m, 1 H), 8.08 (m, 1 H), 7.95 (m, 4 H), 7.77 (m, 1 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.46-7.38 (m, 4 H), 7.33 (d, J = 8.8 Hz, 1 H), 7.27-7.20 (m, 2 H), 4.65 (d, J = 8.8 Hz, 1 H), 3.95 (d, J = 8.8 Hz, 1 H), 2.94 (d, J = 13.1 Hz, 1 H), 2.88 (d, J = 13.3 Hz, 1 H), 2.72 (d, J = 13.3 Hz, 1 H), 2.65 (d, J = 13.1 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 162.1, 149.8, 147.0, 136.7, 135.4, 134.7, 134.5, 133.7, 133.1, 133.0, 132.1, 131.9, 128.7, 128.5, 128.4, 128.4, 128.3, 127.5, 127.4, 127.2, 126.0, 125.7, 125.4, 125.1, 124.4, 82.5, 77.3, 44.4, 43.5. IR (neat): 3847, 3741, 3475, 3053, 2938, 1635, 1577, 1469, 1361, 1302, 1092, 968, 813, 751, 696, 615 cm^-¹. Anal. Calcd (%) for C₃₀H₂₂N₂O: C, 84.48; H, 5.20; N, 6.57. Found: C, 84.67; H, 5.15; N, 6.36. [α]_D -72.4 (c 1.25, CHCl₃).

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Compound 4: ^¹H NMR (300 MHz, CDCl₃): δ = 8.45 (m, 1 H), 8.23 (m, 2 H), 7.96-7.86 (m, 5 H), 7.55 (m, 1 H), 7.48-7.37 (m, 6 H), 7.29-7.23 (m, 2 H), 5.19 (dd, J = 5.2, 8.0 Hz, 1 H), 4.01 (dd, J = 8.0, 11.5 Hz, 1 H), 3.83 (dd, J = 5.2, 11.5 Hz, 1 H), 3.23 (d, J = 13.7 Hz, 1 H), 3.11 (d, J = 12.4 Hz, 1 H), 2.54 (d, J = 13.7 Hz, 1 H), 2.45 (d, J = 12.4 Hz, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 165.0, 149.6, 148.2, 137.8, 135.4, 135.4, 134.8, 134.6, 134.4, 133.2, 133.2, 133.1, 132.0, 132.0, 128.6, 128.4, 128.4, 128.1, 128.1, 127.4, 126.6, 126.1, 126.0, 125.6, 125.4, 122.3, 70.2, 66.9, 41.0, 38.9. IR (neat): 3846, 3343, 3053, 2928, 1667, 1525, 1457, 1324, 1245, 1058, 817, 752, 697, 621, 436 cm^-¹. Anal. Calcd (%) for C₃₀H₂₄N₂O₂: C, 80.06; H, 5.44; N, 6.30. Found: C, 81.34; H, 5.74; N, 6.03. [α]_D -90.5 (c 1.0, CHCl₃).

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Compound 5e: ^¹H NMR (300 MHz, CDCl₃): δ = 7.29-7.05 (m, 8 H), 6.60 (d, J = 15.3 Hz, 1 H), 6.41-6.28 (m, 2 H), 2.36 (s, 3 H), 2.32 (s, 3 H), 2.13 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 170.2, 139.3, 138.4, 138.2, 136.2, 132.6, 129.0, 128.9, 128.63, 128.57, 127.8, 127.5, 124.2, 124.0, 76.4, 21.6, 21.49, 21.45. Anal. Calcd (%) for C₁₉H₂₀O₂: C, 81.40; H, 7.19; O, 11.41. Found: C, 81.06; H, 6.62.

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Compound 6e: ^¹H NMR (300 MHz, CDCl₃): δ = 7.26-7.00 (m, 8 H), 6.44 (d, J = 15.6 Hz, 1 H), 6.29 (dd, J = 15.6 Hz, 1 H), 4.21 (dd, J = 10.8, 8.4 Hz, 1 H), 3.94 (d, J = 10.8 Hz, 1 H), 3.70 (s, 3 H), 3.53 (s, 3 H), 2.33 (s, 3 H), 2.31 (s, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 168.4, 168.0, 140.3, 138.4, 138.1, 136.9, 131.9, 129.1, 128.7, 128.5, 128.0, 127.2, 124.8, 123.7, 57.7, 52.76, 52.74, 52.60, 52.57, 49.3. Anal. Calcd (%) for C₂₂H₂₄O₄: C, 74.98; H, 6.86; O, 18.16. Found: C, 74.69; H, 6.86. [α]_D +24.1 (c 0.63, CHCl₃). The er was determined by HPLC [hexane-2-PrOH (96:4), 0.5 mL/min] using a CHIRALPAK AD column (0.46 cm × 25 cm): t _R (major isomer) = 23.0 min; t _R (minor isomer) = 26.5 min.