Synthesis of Enantioenriched N-Aryl-2-pyridones with Chiral C-N Axes by Rhodium-Catalyzed [2+2+2] Cycloaddition of Alkynes with Isocyanates

Ken Tanaka; Yoshihiro Takahashi; Takeshi Suda; Masao Hirano

doi:10.1055/s-2008-1078488

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2008(11): 1724-1728
DOI: 10.1055/s-2008-1078488

LETTER

Synthesis of Enantioenriched N-Aryl-2-pyridones with Chiral C-N Axes by Rhodium-Catalyzed [2+2+2] Cycloaddition of Alkynes with Isocyanates

Ken Tanaka*, Yoshihiro Takahashi, Takeshi Suda, Masao Hirano
Department of Applied Chemistry, Graduate School of Engineering, Tokyo University of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
Fax: +81(42)3887037; e-Mail: tanaka-k@cc.tuat.ac.jp;

Further Information

Publication History

Received 24 March 2008
Publication Date:
11 June 2008 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

Enantioenriched N-aryl-2-pyridones with axially chiral C-N bonds were prepared by a cationic rhodium(I)-BINAP or tol-BINAP-catalyzed enantioselective [2+2+2] cycloaddition of alkynes with ortho-substituted phenyl isocyanates.

Key words

alkynes - cycloaddition - isocyanates - pyridones - rhodium

References and Notes

1 Curran DP. Qi H. Geib SJ. DeMello NC. J. Am. Chem. Soc. 1994, 116: 3131

Crossref Google Scholar
2a Kitagawa O. Izawa H. Sato K. Dobashi A. Taguchi T. Shiro M. J. Org. Chem. 1998, 63: 2634

Crossref Google Scholar
2b Hughes AD. Price DA. Simpkins NS. J. Chem. Soc., Perkin Trans. 1 1999, 1295

Crossref Google Scholar
2c Kondo K. Fujita H. Suzuki T. Murakami Y. Tetrahedron Lett. 1999, 40: 5577

Crossref Google Scholar
2d Ates A. Curran DP. J. Am. Chem. Soc. 2001, 123: 5130

Crossref Google Scholar
3a Kitagawa O. Kohriyama M. Taguchi T. J. Org. Chem. 2002, 67: 8682

Crossref Google Scholar
3b Terauchi J. Curran DP. Tetrahedron: Asymmetry 2003, 14: 587

Crossref Google Scholar
4a Kitagawa O. Takahashi M. Yoshikawa M. Taguchi T. J. Am. Chem. Soc. 2005, 127: 3676

Crossref PubMed Google Scholar
4b Kitagawa O. Yoshikawa M. Tanabe H. Morita T. Takahashi M. Dobashi Y. Taguchi T. J. Am. Chem. Soc. 2006, 128: 12923

Crossref PubMed Google Scholar
5 Bennett DJ. Pickering PL. Simpkins NS. Chem. Commun. 2004, 1392

Crossref Google Scholar
6a Hata T. Koide H. Taniguchi N. Uemura M. Org. Lett. 2000, 2: 1907

Crossref Google Scholar
6b Koide H. Hata T. Yoshihara K. Kamikawa K. Uemura M. Tetrahedron 2004, 60: 4527

Crossref Google Scholar
Synthesis of axially chiral N-aryl indoles by stereoselective nucleophilic aromatic substitution reactions of planar-chiral tricarbonyl(2,6-disubstituted-1-fluorobenzene)chromium complexes, see:
7a Kamikawa K. Kinoshita S. Matsuzaka H. Uemura S. Org. Lett. 2006, 8: 1097

Crossref PubMed Google Scholar
7b Kamikawa K. Kinoshita S. Furusyo M. Takemoto S. Matsuzaka H. Uemura S. J. Org. Chem. 2007, 72: 3394

Crossref PubMed Google Scholar
8 Duan W.-L. Imazaki Y. Shintani R. Hayashi T. Tetrahedron: Asymmetry 2007, 63: 8529

Crossref Google Scholar
9 Brandes S. Bella M. Kjærsgaard A. Jørgensen KA. Angew. Chem. Int. Ed. 2006, 45: 1147

Crossref Google Scholar
10a Tanaka K. Takeishi K. Noguchi K. J. Am. Chem. Soc. 2006, 128: 4586

Article in Thieme Connect Google Scholar
10b Tanaka K. Takeishi K. Synthesis 2007, 2920

Article in Thieme Connect Google Scholar
11 For Rh(I)⁺-xyl-BINAP-catalyzed concurrent construction of both C-C and C-N axial chiralities, see: Oppenheimer J. Hsung RP. Figueroa R. Johnson WL. Org. Lett. 2007, 9: 3969

Crossref PubMed Google Scholar
For our accounts, see:
12a Tanaka K. Synlett 2007, 1977

Google Scholar
12b Tanaka K. Nishida G. Suda T. J. Synth. Org. Chem. Jpn. 2007, 65: 862

Google Scholar
13 For Rh(I)⁺-modified-BINAP-catalyzed [2+2+2] cyclo-addition of alkynes with isocyanates, see: Tanaka K. Wada A. Noguchi K. Org. Lett. 2005, 7: 4737

Google Scholar
14 A neutral rhodium(I)-complex-catalyzed [2+2+2] cycloaddition of alkynes with isocyanates, see: Kondo T. Nomura M. Ura Y. Wada K. Mitsudo T. Tetrahedron Lett. 2006, 47: 7107

Crossref Google Scholar
Neutral rhodium(I)-complex-catalyzed enantioselective [2+2+2] cycloadditions of alkenyl isocyanates with alkynes, see:
15a Yu RT. Rovis T. J. Am. Chem. Soc. 2006, 128: 2782

Crossref Google Scholar
15b Yu RT. Rovis T. J. Am. Chem. Soc. 2006, 128: 12370

Crossref Google Scholar
15c Lee EE. Rovis T. Org. Lett. 2008, 10: 1231

Crossref Google Scholar
For recent reviews of pyridone synthesis by transition-metal-catalyzed [2+2+2] cycloadditions, see:
16a Heller B. Hapke M. Chem. Soc. Rev. 2007, 36: 1085

Crossref PubMed Google Scholar
16b Chopade PR. Louie J. Adv. Synth. Catal. 2006, 348: 2307

Crossref PubMed Google Scholar
16c Nakamura I. Yamamoto Y. Chem. Rev. 2004, 104: 2127

Crossref PubMed Google Scholar
16d Varela JA. Saà C. Chem. Rev. 2003, 103: 3787

Crossref PubMed Google Scholar
19 Kitagawa O. Izawa H. Sato K. Dobashi A. Taguchi T. J. Org. Chem. 1998, 63: 2634

Crossref Google Scholar

17

General Procedure for the [2+2+2] Cycloaddition (Tables 2 and 3) Under an Ar atmosphere, a CH₂Cl₂ solution (0.5 mL) of (R)-BINAP (0.010-0.040 mmol, 5-20 mol%) was added to a CH₂Cl₂ solution (0.5 mL) of [Rh(cod)₂]BF₄ (0.010-0.040 mmol, 5-20 mol%) at r.t., and the mixture was stirred for 5 min. The resulting solution was stirred under H₂ (1 atm) at r.t. for 1 h, concentrated to dryness, and dissolved in CH₂Cl₂ (0.4 mL). To this solution was added a CH₂Cl₂ solution (0.7 mL) of 2 (0.220 mmol) and then a CH₂Cl₂ solution (0.9 mL) of 1 (0.200 mmol) at r.t. After stirring at r.t. for 1-18 h, the resulting solution was concentrated and product 3 was isolated by a silica gel chromatography.
Compound (+)-3aa: colorless solid; mp 46.3-47.1 °C; [α]_D ²⁵ +44.7 (c 1.46, CHCl₃, 67% ee). IR (neat): 2959, 1737, 1666, 1617, 1573, 1265 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.49-7.33 (m, 2 H), 7.33-7.20 (m, 1 H), 7.04-6.91 (m, 1 H), 3.79 (s, 3 H), 3.78 (s, 3 H), 3.49 (s, 2 H), 3.40 (s, 2 H), 2.55 (sept, J = 6.9 Hz, 1 H), 2.06 (s, 3 H), 1.79 (s, 3 H), 1.16 (d, J = 6.9 Hz, 3 H), 1.14 (d, J = 6.9 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.65, 171.59, 163.7, 150.0, 145.6, 137.1, 136.2, 129.0, 127.9, 126.9, 126.8, 120.6, 116.3, 59.2, 53.20, 53.17, 39.4, 37.6, 27.9, 24.0, 23.1, 18.0, 13.3. HRMS-FAB: m/z calcd for C₂₃H₂₈NO₅ [M + H]⁺: 398.1967; found: 398.1996. CHIRALPAK AD, hexane-2-PrOH (90:10), 1 mL/min, t _R = 8.21 min (major isomer) and 18.0 min (minor isomer).
Compound (+)-3ab: colorless solid; mp 161.1-161.8 °C; [α]_D ²⁵ +20.1 (c 1.63, CHCl₃, 30% ee). IR (neat): 2954, 1739, 1732, 1667, 1615, 1575, 1265 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.39-7.20 (m, 3 H), 7.08-6.98 (m, 1 H), 3.79 (s, 6 H), 3.48 (s, 2 H), 3.40 (s, 2 H), 2.07 (s, 3 H), 2.02 (s, 3 H), 1.79 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.6, 171.5, 163.3, 150.1, 138.5, 135.9, 135.2, 131.1, 128.6, 127.8, 127.2, 120.7, 116.5, 59.2, 53.19, 53.17, 39.3, 37.6, 17.7, 17.3, 13.2. HRMS-FAB: m/z calcd for C₂₁H₂₄NO₅ [M + H]⁺: 370.1654; found: 370.1613; CHIRALPAK AD, hexane-2-PrOH (90:10), 1.0 mL/min, t _R = 12.5 min (major isomer) and 16.0 min (minor isomer).
Compound (+)-3ac: colorless solid; mp 111.0-111.6 °C; [α]_D ²⁵ +28.8 (c 1.33, CHCl₃, 39% ee). IR (neat): 2955, 1736, 1667, 1617, 1574, 1264 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.41-7.22 (m, 3 H), 7.01 (d, J = 7.5 Hz, 1 H), 3.791 (s, 3 H), 3.785 (s, 3 H), 3.49 (s, 2 H), 3.40 (s, 2 H), 2.38 (dq, J = 7.5, 7.5 Hz, 1 H), 2.28 (dq, J = 7.5, 7.5 Hz, 1 H), 2.06 (s, 3 H), 1.79 (s, 3 H), 1.13 (t, J = 7.5 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.6, 171.5, 163.5, 150.1, 140.6, 138.0, 136.1, 128.9, 128.8, 127.9, 127.0, 120.7, 116.5, 59.2, 53.19, 53.15, 39.4, 37.6, 23.4, 17.9, 13.3, 13.2. HRMS-FAB: m/z calcd for C₂₂H₂₆NO₅ [M + H]⁺: 384.1811; found: 384.1783. CHIRALPAK AD, hexane-2-PrOH (90:10), 1 mL/min, t _R = 9.74 min (major isomer) and 14.1 min (minor isomer).
Compound (+)-3ae: mp 134.8-136.2 °C; [α]_D ²⁵ +9.34 (c 1.88, CHCl₃, 58% ee). IR (neat): 2954, 1735, 1667, 1617, 1575, 1266 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.48-7.28 (m, 1 H), 7.16-6.91 (m, 3 H), 3.79 (s, 3 H), 3.78 (s, 3 H), 3.76 (s, 3 H), 3.47 (s, 2 H), 3.40 (s, 2 H), 2.06 (s, 3 H), 1.82 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.7, 171.6, 163.5, 154.6, 150.1, 136.7, 129.9, 129.4, 128.0, 121.1, 120.3, 116.1, 112.0, 59.2, 55.7, 53.2, 53.1, 39.4, 37.6, 17.4, 13.2. CHIRALPAK AD-H, hexane-2-PrOH (90:10), 1.0 mL/min, t _R = 15.3 min (major isomer) and 36.6 min (minor isomer).
Compound (+)-3af: colorless solid; mp 126.8-127.6 °C; [α]_D ²⁵ +29.6 (c 1.89, CHCl₃, 56% ee). IR (neat): 2954, 2924, 1735, 1670, 1621, 1575, 1266 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.58-7.49 (m, 1 H), 7.43-7.33 (m, 2 H), 7.25-7.17 (m, 1 H), 3.79 (s, 3 H), 3.78 (s, 3 H), 3.49 (s, 2 H), 3.41 (s, 2 H), 2.07 (s, 3 H), 1.84 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.6, 171.4, 163.2, 150.6, 137.2, 135.7, 132.5, 130.4, 129.9, 128.0, 120.8, 116.6, 59.2, 53.20, 53.19, 39.4, 37.5, 17.4, 13.1. CHIRALPAK AD, hexane-2-PrOH (80:20), 1.0 mL/min, t _R = 6.48 min (major isomer) and 9.49 min (minor isomer).
Compound (+)-3ag: colorless solid; mp 159.8-161.1 °C; [α]_D ²⁵ +60.0 (c 1.29, CHCl₃, 87% ee). IR (neat): 2954, 2924, 1735, 1669, 1620, 1574, 1263 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.72 (dd, J = 7.5, 1.2 Hz, 1 H), 7.45 (dt, J = 7.5, 1.2 Hz, 1 H), 7.30 (dt, J = 7.5, 1.5 Hz, 1 H), 7.23 (dd, J = 7.5, 1.5 Hz, 1 H), 3.80 (s, 3 H), 3.79 (s, 3 H), 3.50 (s, 2 H), 3.42 (s, 2 H), 2.08 (s, 3 H), 1.84 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 171.6, 171.4, 163.1, 150.6, 138.9, 135.6, 133.6, 130.0, 129.9, 128.7, 122.8, 120.9, 116.7, 59.2, 53.22, 53.19, 39.4, 37.5, 17.6, 13.1. CHIRALPAK AD, hexane-2-PrOH (90:10), 1.0 mL/min, t _R = 13.9 min (major isomer) and 23.8 min (minor isomer).
Compound (+)-3be: colorless solid; mp 120.0-121.2 °C; [α]_D ²⁵ +14.7 (c 2.30, CHCl₃, 68% ee). IR (neat): 2923, 1666, 1614, 1574, 1500, 1109 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.42-7.31 (m, 1 H), 7.14-6.95 (m, 3 H), 3.77 (s, 3 H), 3.39 (s, 5 H), 3.37 (s, 3 H), 3.34 (s, 2 H), 2.72 (s, 2 H), 2.64 (s, 2 H), 2.03 (s, 3 H), 1.78 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.6, 154.7, 152.9, 136.6, 129.7, 129.5, 128.3, 121.1, 120.4, 118.2, 111.9, 75.9, 75.7, 59.2, 55.7, 47.3, 37.7, 35.7, 30.3, 17.3, 13.1. CHIRALPAK AD, hexane-2-PrOH (90:10), 1.0 mL/min, t _R = 7.71 min (major isomer) and 11.6 min (minor isomer).
Compound (+)-3ce: colorless solid; mp 143.0-143.3 °C; [α]_D ²⁵ +15.8 (c 1.34, CHCl₃, 55% ee). IR (neat): 2930, 1644, 1581, 1528, 1500, 1277, 1246 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.44-7.31 (m, 1 H), 7.13-6.96 (m, 3 H), 3.77 (s, 3 H), 2.62 (s, 2 H), 2.50 (s, 2 H), 2.08 (s, 3 H), 1.84 (s, 3 H), 1.81-1.62 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 162.2, 154.5, 147.3, 138.9, 129.7, 129.3, 128.7, 122.5, 121.1, 113.0, 111.9, 55.7, 28.2, 26.3, 22.9, 22.4, 16.2, 12.0. CHIRALPAK AD-H, hexane-2-PrOH (90:10), 1.0 mL/min, t _R = 7.19 min (major isomer) and 10.3 min (minor isomer).
Compound (+)-3de: pale yellow solid; mp 138.5-139.9 °C; [α]_D ²⁵ +18.9 (c 1.09, CHCl₃, 40% ee). IR (neat): 2922, 2843, 1676, 1581, 1499 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.46-7.34 (m, 1 H), 7.15-6.95 (m, 3 H), 4.95 (m, 2 H), 4.92 (m, 2 H), 3.79 (s, 3 H), 2.03 (s, 3 H), 1.80 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.7, 154.5, 149.4, 134.8, 130.1, 129.4, 127.4, 121.2, 117.6, 115.8, 112.0, 72.1, 71.2, 55.7, 17.7, 13.2. CHIRALPAK AD-H, hexane-2-PrOH (90:10), 1.0 mL/min, t _R = 11.3 min (major isomer) and 16.2 min (minor isomer).
Compound (+)-3ee: colorless solid; mp 280 °C (dec.); [α]_D ²⁵ +12.2 (c 0.319, CHCl₃, 34% ee). IR (neat): 2921, 2851, 1674, 1624, 1579, 1343 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.79 (d, J = 8.1 Hz, 2 H), 7.47-7.28 (m, 1 H), 7.37 (d, J = 8.1 Hz, 2 H), 7.11-6.94 (m, 3 H), 4.43 (s, 3 H), 4.40 (s, 3 H), 3.75 (s, 3 H), 2.45 (s, 3 H), 1.99 (s, 3 H), 1.77 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.2, 154.4, 146.0, 144.0, 136.8, 133.2, 130.2, 129.9, 129.2, 127.6, 127.1, 121.2, 120.0, 112.8, 112.1, 55.7, 52.2, 51.1, 21.5, 17.5, 13.1. CHIRALPAK IA, hexane-CH₂Cl₂ (50:50), 0.8 mL/min, t _R = 27.5 min (major isomer) and 34.0 min (minor isomer).
Compound (-)-5: pale yellow oil; [α]_D ²⁵-17.2 (c 0.330, CHCl₃, 79% ee). IR (neat): 2925, 2853, 1669 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 7.47-7.35 (m, 1 H), 7.17-6.95 (m, 3 H), 6.33 (s, 1 H), 5.94 (d, J = 1.2 Hz, 1 H), 3.78 (s, 3 H), 2.43 (t, J = 7.5 Hz, 2 H), 2.33-1.99 (m, 2 H), 1.71-1.50 (m, 2 H), 1.45-0.99 (m, 30 H), 0.97-0.72 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 163.9, 155.4, 154.8, 149.7, 130.1, 129.7, 127.0, 121.1, 115.8, 112.2, 106.6, 55.8, 35.5, 33.0, 31.90, 31.87, 29.61, 29.55, 29.49, 29.45, 29.4, 29.33, 29.29, 29.26, 29.1, 29.0, 27.8, 22.68, 22.66, 14.12, 14.10. CHIRALPAK AD, hexane-2-PrOH (95:5), 0.8 mL/min, t _R = 18.5 min (minor isomer) and 21.2 min (major isomer).

18

The high enantioselectivity observed in the reaction of 1a with 2a might be ascribed to a larger steric hindrance of 2a than those of 2b and 2c.