New Chiral Hydroxyoxazolines Based on Ketopinic Acid and Their Use in the Asymmetric Diels-Alder Reaction

Santiago Barroso; Gonzalo Blay; Luz Cardona; José R. Pedro

doi:10.1055/s-2007-991052

LETTER

New Chiral Hydroxyoxazolines Based on Ketopinic Acid and Their Use in the Asymmetric Diels-Alder Reaction

Santiago Barroso, Gonzalo Blay, Luz Cardona, José R. Pedro*
Departament de Química Orgànica, Facultat de Química, Universitat de València, 46100 Burjassot (València), Spain
Fax: +34(96)3544328; e-Mail: jose.r.pedro@uv.es;

Abstract

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Abstract

Several chiral hydroxyoxazolines have been prepared starting from (1S)-(+)-ketopinic acid and enantiopure β-amino alcohols by short synthetic routes. They have been employed in the catalytic asymmetric Diels-Alder reaction, resulting in ee values of up to 90%.

Key words

asymmetric catalysis - Diels-Alder reactions - copper - alkenes - ligands

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References

References and Notes

<A NAME="RD03807ST-1A">1a</A> Transition Metals for Organic Synthesis Beller M. Bolm C. Wiley-VCH; Weinheim: 1998.

<A NAME="RD03807ST-1B">1b</A> Comprehensive Asymmetric Catalysis Jacobsen EN. Pfaltz M. Yamamoto H. Springer; Berlin: 1999.

<A NAME="RD03807ST-1C">1c</A> Catalytic Asymmetric Synthesis 2nd ed.: Ojima I. Wiley-VCH; Weinheim: 2000.

For discussions on C ₂-symmetric ligands, see:

<A NAME="RD03807ST-2A">2a</A> Whitesell J. Chem. Rev. 1989, 89: 1581

<A NAME="RD03807ST-2B">2b</A> Halm C. Kurth MJ. Angew. Chem. Int. Ed. 1998, 37: 510

<A NAME="RD03807ST-3">3</A> For a discussion on C ₁-symmetric ligands, see: Humphries AC. Pfaltz A. In Stimulating Concepts in Chemistry Vögtle F. Stoddart JF. Shibashaki M. Wiley-VCH; Weinheim: 2000. p.89

<A NAME="RD03807ST-4">4</A> For a review on BOX-catalyzed reactions see: Desimoni G. Faita G. Jørgensen KA. Chem. Rev. 2006, 106: 3561

<A NAME="RD03807ST-5A">5a</A> Angell RM. Barrett AGM. Braddock DC. Swallow S. Vickery BD. Chem. Commun. 1997, 919

<A NAME="RD03807ST-5B">5b</A> Sagasser I. Helmchen G. Tetrahedron Lett. 1998, 39: 261

<A NAME="RD03807ST-5C">5c</A> Davenport AJ. Davies DL. Fawcett J. Garratt SA. Russell DR. J. Chem. Soc., Dalton Trans. 2000, 4432

<A NAME="RD03807ST-5D">5d</A> Chelucci G. Sanna MG. Gladiali S. Tetrahedron 2000, 56: 2889

<A NAME="RD03807ST-5E">5e</A> Wu X.-Y. Xu H.-D. Tang F.-Y. Zhou Q.-L. Tetrahedron: Asymmetry 2001, 12: 2565

<A NAME="RD03807ST-5F">5f</A> Brunner H. Kagan H. Kreutzer G. Tetrahedron: Asymmetry 2003, 14: 2177

<A NAME="RD03807ST-5G">5g</A> Västila P. Pastor IM. Adolfsson H. J. Org. Chem. 2005, 70: 2921

<A NAME="RD03807ST-5H">5h</A> Lee J.-Y. Miller JJ. Hamilton SS. Sigman MS. Org. Lett. 2005, 7: 1837

<A NAME="RD03807ST-6">6</A> Bolm C. Zani L. Rudolph J. Schiffers I. Synthesis 2004, 2173

<A NAME="RD03807ST-7">7</A> Bolm C. Schmidt F. Zani L. Tetrahedron: Asymmetry 2005, 16: 1367

<A NAME="RD03807ST-8A">8a</A> Chang J.-W. Jang D.-P. Uang B.-J. Liao F.-L. Wang S.-L. Org. Lett. 1999, 1: 2061

<A NAME="RD03807ST-8B">8b</A> Li X. Yeung C.-H. Chan ASC. Yang T.-K. Tetrahedron: Asymmetry 1999, 10: 759

<A NAME="RD03807ST-8C">8c</A> Chen C.-J. Chu Y.-Y. Liao Y.-Y. Tsai Z.-H. Wang C.-C. Chen K. Tetrahedron Lett. 1999, 40: 1141

<A NAME="RD03807ST-8D">8d</A> Yang K.-S. Chen K. Org. Lett. 2000, 2: 729

<A NAME="RD03807ST-8E">8e</A> Jang D.-P. Chang J.-W. Uang B.-J. Org. Lett. 2001, 3: 983

<A NAME="RD03807ST-8F">8f</A> Gilbertson SR. Fu C. Org. Lett. 2001, 3: 161

<A NAME="RD03807ST-8G">8g</A> Palomo C. Aizpurua JM. Oiarbide M. García JM. González A. Odriozola I. Linden A. Tetrahedron Lett. 2001, 42: 4829

<A NAME="RD03807ST-8H">8h</A> Chang C.-W. Yang C.-T. Hwang C.-D. Uang B.-J. Chem. Commun. 2002, 54

<A NAME="RD03807ST-8I">8i</A> Yang K.-S. Chen K. Org. Lett. 2002, 4: 1107

<A NAME="RD03807ST-8J">8j</A> Yang K.-S. Lee W.-D. Pan J.-F. Kwmin C. J. Org. Chem. 2003, 68: 915

<A NAME="RD03807ST-8K">8k</A> Bunlaksananusorn T. Knochel P. J. Org. Chem. 2004, 69: 4595

<A NAME="RD03807ST-8L">8l</A> Hari Y. Aoyama T. Synthesis 2005, 583

<A NAME="RD03807ST-8M">8m</A> Chen J.-H. Venkatesham U. Lee L.-C. Chen K. Tetrahedron 2006, 62: 887

<A NAME="RD03807ST-9">9</A> (S)-(+)-Ketopinic acid is commercially available, although it can be readily prepared by oxidation of (1S)-(+)-10-camphorsulfonyl chloride with KMnO₄: Bartlett PD. Knox LH. Org. Synth., Coll. Vol. V Wiley; New York: 1973. p.689

<A NAME="RD03807ST-10">10</A> Sakakura A. Kondo R. Ishihara K. Org. Lett. 2005, 7: 1971

<A NAME="RD03807ST-11A">11a</A> Evans DA. Johnson JS. In Comprehensive Asymmetric Catalysis Vol. 3: Jacobsen EN. Pfaltz A. Yamamoto H. Springer; Berlin: 1999. p.1177

<A NAME="RD03807ST-11B">11b</A> Cycloaddition Reactions in Organic Synthesis Kobayashi S. Jørgensen KA. Wiley; New York: 2002.

<A NAME="RD03807ST-11C">11c</A> Lewis Acids in Organic Synthesis Vol. 1: Yamamoto H. Wiley; New York: 2000.

<A NAME="RD03807ST-11D">11d</A> Lewis Acids in Organic Synthesis Vol. 2: Yamamoto H. Wiley; New York: 2000.

<A NAME="RD03807ST-12">12</A> Evans DA. Barnes DM. Johnson JS. Lectka T. von Matt P. Miller SJ. Murry JA. Norcross RD. Shaughnessy EA. Campos KR. J. Am. Chem. Soc. 1999, 121: 7582

Experimental Procedure for the Synthesis of Compound 2d: A solution of (S)-(+)-ketopinic acid (1, 1.0 g, 5.5 mmol) in SOCl₂ (4.5 mL) was refluxed for 2 h and the excess SOCl₂ was removed under reduced pressure. The residue dissolved in CH₂Cl₂ (3.8 mL) was added dropwise to a solution of (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol (3d, 0.82 g, 5.5 mmol) and Et₃N (0.75 mL, 5.5 mmol) in CH₂Cl₂ (3 mL) at 0 °C under nitrogen. After 1 h, the mixture was diluted with EtOAc (150 mL), washed with 2 M HCl (2 × 30 mL), sat. aq NaHCO₃ (2 × 30 mL) and brine (30 mL), dried over MgSO₄ and concentrated. The crude product was crystallized from hexane-CH₂Cl₂ to give 4d; yield: 2.0 g (80%); mp 163-165 °C; [α]_D ²⁵ +28.5 (c = 0.69, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.85 (d, J = 7.6 Hz, 1 H), 7.25 (m, 4 H), 5.47 (dd, J = 5.0, 8.1 Hz, 1 H), 4.70 (ddd, J = 2.1, 5.1, 5.1 Hz, 1 H), 3.19 (dd, J = 5.2, 16.6 Hz, 1 H), 3.00 (dd, J = 2.0, 16.6 Hz, 1 H), 2.63 (m, 1 H), 2.53 (m, 1 H), 2.13-2.23 (m, 3 H), 2.00 (d, J = 18.7 Hz, 1 H), 1.67 (m, 1 H), 1.46 (m, 1 H), 1.30 (s, 3 H), 1.10 (s, 3 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 216.6 (s), 169.7 (s), 140.6 (s), 140.1 (s), 128.0(d), 127.0(d), 125.3 (d), 124.2 (d), 73.5 (d), 65.4 (s), 57.5 (d), 50.1 (s), 43.7 (t), 43.4 (d), 39.6 (t), 27.9 (t), 27.5 (t), 20.8 (q), 20.7 (q). MS (FAB): m/z (%) = 314 (100) [M⁺ + 1], 282 (45), 154 (40). HRMS: m/z [M + H] calcd for C₁₉H₂₃NO₃: 313.1751; found: 314.1749.
A solution of 4d (2.49 g, 7.9 mmol) and (NH₄)₆Mo₇O₂₄·4H₂O (988 mg, 0.8 mmol) in toluene (160 mL) was refluxed with a Dean-Stark trap for 4 h. The reaction mixture was filtered through a short pad of silica gel (2 cm), concentrated and the residue was chromatographed on silica gel using hexane-EtOAc mixtures to give 5d; yield: 1.60 g (64%); mp 118-121 °C; [α]_D ²⁵ +228.3 (c = 0.69, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.47 (m, 1 H), 7.21 (m, 3 H), 5.53 (d, J = 7.9 Hz, 1 H), 5.39 (ddd, J = 1.8, 6.8, 8.5 Hz, 1 H), 3.41 (dd, J = 6.8, 17.8 Hz, 1 H), 3.18 (dd, J = 1.5, 17.8 Hz, 1 H), 2.39-2.54 (m, 2 H), 2.06 (dd, J = 4.4, 4.4 Hz, 1 H), 1.96 (m, 1 H), 1.91 (d, J = 18.3 Hz, 1 H), 1.74 (ddd, J = 4.8, 9.3, 14.0 Hz, 1 H), 1.36 (ddd, J = 4.1, 9.2, 12.8 Hz, 1 H), 1.02 (s, 3 H), 0.73 (s, 3 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 211.8 (s), 164.4 (s), 142.2 (s), 139.1 (s), 128.1 (d), 127.2 (d), 125.3 (d), 125.0 (d), 83.2 (d), 75.8 (d), 62.5 (s), 49.6 (s), 44.3 (d), 43.7 (t), 39.8 (t), 27.1 (t), 26.5 (t), 21.5 (q), 19.3 (q). MS (EI): m/z (%) = 295 (50) [M⁺], 280 (10), 267 (29), 252 (39), 226 (15), 165 (16), 130 (62), 115 (100), 104 (52), 77 (39), 67 (31). HRMS: m/z [M] calcd for C₁₉H₂₁NO₂: 295.1572; found: 295.1551.
NaBH₄ (22.6 mg, 0.6 mmol) was added to a solution of 5d (178 mg, 0.6 mmol) and CeCl₃·7H₂O (223 mg, 0.6 mmol) in MeOH (4 mL) at -10 °C. After 10 min, sat. aq NH₄Cl (5 mL) was added, the mixture was diluted with EtOAc (100 mL) and washed with brine (2 × 10 mL), dried and concentrated under reduced pressure. Column chromatography (hexane-EtOAc, 8:2) gave 2d (88 mg, 50%) and epi-2d (18 mg). Compound 2d: mp 98-101 °C; [α]_D ²⁵ +214.2 (c = 0.80, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.47 (m, 1 H), 7.27 (m, 3 H), 5.79 (br s, 1 H), 5.58 (d, J = 8.1 Hz, 1 H), 5.29 (ddd, J = 1.8, 7.2, 8.1 Hz, 1 H), 3.90 (dd, J = 3.5, 7.8 Hz, 1 H), 3.47 (dd, J = 7.0, 18.0 Hz, 1 H), 3.23 (dd, J = 1.6, 18.0 Hz, 1 H), 2.07 (m, 1 H), 1.91 (m, 1 H), 1.81 (m, 2 H), 1.71 (dd, J = 7.8, 12.9 Hz, 1 H), 1.24 (s, 3 H), 1.10 (m, 2 H), 1.07 (s, 3 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 169.2 (s), 141.7 (s), 139.4 (s), 128.3 (d), 127.3 (d), 125.5 (d), 125.1 (d), 81.5 (d), 77.3 (d), 75.4 (d), 52.7 (s), 50.0 (s), 45.6 (d), 39.6 (t), 39.4 (t), 29.9 (t), 27.5 (t), 21.9 (q), 20.6 (q). MS (EI): m/z (%) = 297 (13) [M⁺], 282 (50), 269 (69), 254 (61), 228 (17), 214 (42), 186 (13), 151 (14), 132 (20), 115 (100), 104 (23), 77 (24). HRMS: m/z [M] calcd for C₁₉H₂₃NO₂: 295.1729; found: 297.1723.
Experimental Procedure for the Enantioselective Diels-Alder Reaction: Copper triflate (9.0 mg, 0.025 mmol) in a Schlenk tube was dried at 90 °C under vacuum for 1 h. The tube was filled in with nitrogen and 2d (7.5 mg, 0.025 mmol) was added followed by CH₂Cl₂ (1.5 mL). The mixture was stirred for 1 h and the dienophile 7 (35 mg, 0.25 mmol) was added. After stirring for 30 min cyclopentadiene (6; 115 mg, 1.75 mmol) was added at -78 °C. After 1 h, the solvent was removed under reduced pressure and the product was purified by column chromatography to give compound 8; yield: 50.5 mg (98%); [α]_D ²⁵ -149.0 (c = 1.0, CHCl₃; for a 90% ee and 98:2 endo/exo mixture). ¹H NMR (300 MHz, CDCl₃): δ = 6.23 (dd, J = 3.1, 5.6 Hz, 1 H), 5.86 (dd, J = 2.8, 5.6 Hz, 1 H), 4.40 (m, 2 H), 3.95 (m, 3 H), 3.30 (br s, 1 H), 2.93 (br s, 1 H), 1.94 (ddd, J = 3.7, 9.2, 12.1 Hz, 1 H), 1.50-1.38 (m, 3 H). Chiral HPLC: Chiralpak AD-H, hexane-i-PrOH (93:7), flow rate: 1 mL/min, exo _minor t _R = 16.5 min, endo(S)_major t _R = 17.6 min, exo _major t_R = 21.5 min, endo(R)_minor t _R = 22.5 min.