Halopalladation Cyclization
of Alkynes with Azides: Selective Synthesis of 4-Haloisoquinolines
and 3-Haloindoles

Hong-Ping Zhang; Shang-Ci Yu; Yun Liang; Peng Peng; Bo-Xiao Tang; Jin-Heng Li

doi:10.1055/s-0030-1259722

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 2011(7): 982-988
DOI: 10.1055/s-0030-1259722

LETTER

Halopalladation Cyclization of Alkynes with Azides: Selective Synthesis of 4-Haloisoquinolines and 3-Haloindoles

Hong-Ping Zhang^a,b, Shang-Ci Yu^a, Yun Liang^a, Peng Peng^a, Bo-Xiao Tang^a, Jin-Heng Li*^a
^a Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), Hunan Normal University, Changsha 410081, P. R. of China
Fax: +86(731)88872101; e-Mail: jhli@hunnu.edu.cn;
^b Department of Biology and Chemical Engineering, Shaoyang University, Shaoyang 422000, P. R. of China

Further Information

Publication History

Received 8 August 2010
Publication Date:
10 March 2011 (online)

Abstract
Full Text
References
Supplementary Material

Permissions and Reprints All articles of this category

Abstract

A new, selective method for the synthesis of 4-haloisoquinolines and 3-haloindoles is presented by the halopalladation cyclizations of alkynes with azides. In the presence of PdX₂ (X = Br, Cl) and halide sources, a variety of 2-alkynyl benzyl azides or 2-alkynyl aryl azides smoothly underwent the halopalladation cyclization reaction to afford the corresponding 3-substituted 4-haloisoquinolines and 2-substituted 3-haloindoles in moderate to good yields.

Key words

palladium - halopalladation - cyclization - 2-alkynyl azide - 4-haloisoquinoline - 3-haloindole

Supporting Information

References and Notes

1a The Chemistry of Heterocyclic Compounds: Isoquinolines Vol. 38, Part 3: Coppola GM. Schuster HF. John Wiley & Sons; New York: 1981.

Google Scholar
1b Bentley KW. The Isoquinoline Alkaloids Vol. 1: Harwood Academic; Amsterdam: 1998.

Google Scholar
1c Bentley KW. Nat. Prod. Rep. 2005, 22: 249

Google Scholar
1d Bentley KW. Nat. Prod. Rep. 2006, 23: 444

Google Scholar
1e Delcey MC. Croisy A. Carrez D. Huel C. Chiaroni A. Ducrot P. Bisagni E. Jin L. Leclercq G. Bioorg. Med. Chem. 2000, 8: 2629

Google Scholar
2a Whaley WM. Govindachari TR. In Organic Reactions Vol. 6: Adams R. Wiley; New York: 1951. p.151-190

Google Scholar
2b Sotomayor N. Dominguez E. J. Org. Chem. 1996, 61: 4062

Google Scholar
2c Ishikawa T. Shimooka K. Narioka T. Noguchi S. Saito T. Ishikawa A. Yamazaki E. Harayama T. Seki H. Yamaguchi K. J. Org. Chem. 2000, 65: 9143

Google Scholar
3a Whaley WM. Govindachari TR. In Organic Reactions Vol. 6: Adams R. Wiley; New York: 1951. p.74-150

Google Scholar
3b Youn SW. J. Org. Chem. 2006, 71: 2521

Google Scholar
3c Chrzanowska M. Rozwadowska MD. Chem. Rev. 2004, 104: 3341

Google Scholar
3d Cox ED. Cook JM. Chem. Rev. 1995, 95: 1797

Google Scholar
4a Gensler WJ. In Organic Reactions Vol. 6: Adams R. Wiley; New York: 1951. p.191-206

Google Scholar
4b Boudou M. Enders D. J. Org. Chem. 2005, 70: 9486

Google Scholar
4c Walker ER. Leung SY. Barrett AGM. Tetrahedron Lett. 2005, 46: 6537

Google Scholar
5a Ni: Korivi RP. Cheng C.-H. Org. Lett. 2005, 7: 5179

Google Scholar
5b Pt: Bajracharya GB. Pahadi NK. Gridnev ID. Yamamoto Y. J. Org. Chem. 2006, 71: 6204

Google Scholar
5c Ag: Niu Y.-N. Yan Z.-Y. Gao G.-L. Wang H.-L. Shu X.-Z. Ji K.-G. Liang Y.-M. J. Org. Chem. 2009, 74: 2893

Google Scholar
5d Rh: Lim S.-G. Lee JH. Moon CW. Hong J.-B. Jun C.-H. Org. Lett. 2003, 5: 2759

Google Scholar
5e See also: Guimond N. Fagnou K. J. Am. Chem. Soc. 2009, 131: 12050

Google Scholar
5f Cu: Wang B. Lu B. Jiang Y. Zhang Y. Ma D. Org. Lett. 2008, 10: 2761

Google Scholar
5g Au/Ag: Huo Z. Yamamoto Y. Tetrahedron Lett. 2009, 50: 3651

Google Scholar
5h Zr: Ramakrishna TVV. Sharp PR. Org. Lett. 2003, 5: 877

Google Scholar
6a Roesch KR. Larock RC. J. Org. Chem. 1998, 63: 5306

Google Scholar
6b Roesch KR. Larock RC. Org. Lett. 1999, 1: 553

Google Scholar
6c Dai G. Larock RC. Org. Lett. 2001, 3: 4035

Google Scholar
6d Roesch KR. Zhang H. Larock RC. J. Org. Chem. 2001, 66: 8042

Google Scholar
6e Huang Q. Hunter JA. Larock RC. J. Org. Chem. 2002, 67: 3437

Google Scholar
6f Dai G. Larock RC. J. Org. Chem. 2002, 67: 7042

Google Scholar
6g Huang Q. Hunter JA. Larock RC. J. Org. Chem. 2003, 68: 980

Google Scholar
6h Konno T. Chae J. Miyabe T. Ishihara T. J. Org. Chem. 2005, 70: 10172

Google Scholar
For papers on constructing the 4-iodoisoquinoline skeleton by the electrophilic iodocyclization, see:
7a Iminoalkynes: Huang Q. Hunter JA. Larock RC. J. Org. Chem. 2002, 67: 3437

Google Scholar
Azides:
7b Fischer D. Tomeba H. Pahadi NK. Patil NT. Yamamoto Y. Angew. Chem. Int. Ed. 2007, 46: 4764

Google Scholar
7c Fischer D. Tomeba H. Pahadi NK. Patil NT. Huo Z. Yamamoto Y. J. Am. Chem. Soc. 2008, 130: 15720

Google Scholar
7d Huo Z. Gridnev ID. Yamamoto Y. J. Org. Chem. 2010, 75: 1266

Google Scholar
For selected examples of constructing the isoquinoline skeleton by the other transformations, see:
8a Yang Y.-Y. Shou W.-G. Chen Z.-B. Hong D. Wang Y.-G. J. Org. Chem. 2008, 73: 3928

Google Scholar
8b Pandy G. Balakrishnan M. J. Org. Chem. 2008, 73: 8128

Google Scholar
8c Hashmi ASK. Schaefer S. Woelfe M. DiezGil C. Fischer P. Laguna A. Blanco MC. Gimeno MC. Angew. Chem. In. Ed. 2007, 46: 6184

Google Scholar
8d Konno T. Chae J. Miyabe T. Ishihara T. J. Org. Chem. 2005, 70: 10172

Google Scholar
8e Palacios F. Alonso C. Rodríguez M. de Marigorta EM. Rubiales G. Eur. J. Org. Chem. 2005, 1795

Google Scholar
For reviews, see:
9a Lu X. Handbook of Organopalladium Chemistry for Organic Synthesis Vol. 2: Negishi E. Wiley Interscience; New York: 2002. p.2267-2288

Google Scholar
9b Tsuji J. Palladium Reagents and Catalysts: Innovations in Organic Synthesis Wiley and Sons; New York: 1995.

Google Scholar
9c Li JJ. Gribble GW. Palladium in Heterocyclic Chemistry Pergamon; New York: 2000.

Google Scholar
9d Heck RF. Palladium Reagents in Organic Synthesis Academic Press; New York: 1985.

Google Scholar
9e Han XL. Liu GX. Lu XY. Chin. J. Org. Chem. 2005, 25: 1182

Google Scholar
9f Tang S. Wang N.-X. Li J.-H. Chin. J. Org. Chem. 2007, 27: 819

Google Scholar
For pioneering papers on the halopalladation reactions, see:
10a Kanada K. Uchiyama T. Fujiwara Y. Imanaka T. Teranish S. J. Org. Chem. 1979, 44: 55

Google Scholar
10b Ma S. Lu X. J. Chem. Soc., Chem. Commun. 1990, 733

Google Scholar
10c Ma S. Lu X. J. Org. Chem. 1991, 56: 5120

Google Scholar
10d Ma S. Lu X. J. Org. Chem. 1993, 58: 3692

Google Scholar
10e Zhu G. Lu X. Organometallics 1995, 14: 4899

Google Scholar
For other papers on the halopalladation reactions using PdX₂/CuX₂ as the catalytic system, see:
11a Bäckvall JE. Nordberg RE. J. Am. Chem. Soc. 1980, 102: 393

Google Scholar
11b Ji J. Zhang C. Lu X. J. Org. Chem. 1995, 60: 1160

Google Scholar
11c Ma S. Lu X. J. Org. Chem. 1993, 58: 1245

Google Scholar
11d Li J.-H. Jiang H.-F. Feng A.-Q. Jia L.-Q. J. Org. Chem. 1999, 64: 5984

Google Scholar
11e Li J.-H. Jiang H.-F. Chen M.-C. J. Org. Chem. 2001, 66: 3627

Google Scholar
11f Li J.-H. Liang Y. Xie Y.-X. J. Org. Chem. 2004, 69: 8125

Google Scholar
11g Li J.-H. Tang S. Xie Y.-X.
J. Org. Chem. 2005, 70: 477

Google Scholar
11h Ma S. Wu B. Zhao S. Org. Lett. 2003, 5: 4429

Google Scholar
11i Ma S. Wu B. Jiang X. Zhao S. J. Org. Chem. 2005, 70: 2568

Google Scholar
11j Huang J. Zhou L. Jiang H. Angew. Chem. Int. Ed. 2006, 45: 1945

Google Scholar
11k Liang Y. Tang S. Zhang X.-D. Mao L.-Q. Xie Y.-X. Li J.-H. Org. Lett. 2006, 8: 3017

Google Scholar
11l Tang S. Xie Y.-X. Li J.-H. Wang N.-X. Synthesis 2007, 1841

Google Scholar
11m Tang S. Yu Q.-F. Peng P. Li J.-H. Zhong P. Tang R.-Y. Org. Lett. 2007, 9: 3413

Google Scholar
11n Huang X.-C. Wang F. Liang Y. Li J.-H. Org. Lett. 2009, 11: 1139

Google Scholar
For selected recent reviews, see:
12a Weng J.-R. Tsai C.-H. Kulp SK. Chen C.-S. Cancer Lett. 2008, 262: 153

Google Scholar
12b Rieck GC. Fiander AN. Mol. Nutr. Food Res. 2008, 52: 105

Google Scholar
12c Brancale A. Silvestri R. Med. Res. Rev. 2007, 27: 209

Google Scholar
For selected recent reviews, see:
13a Cacchi S. Fabrizi G. Chem. Rev. 2005, 105: 2873

Google Scholar
13b Krüger K. Tillack A. Beller M. Adv. Synth. Catal. 2008, 350: 2153

Google Scholar
13c Thansandote P. Lautens M. Chem. Eur. J. 2009, 15: 5874

Google Scholar
15 Yu X. Wu J. J. Comb. Chem. 2009, 11: 895

Crossref Google Scholar

14

General Procedure for the Chloropalladation Reaction: To a flame-dried Schlenk tube equipped with a magnetic stirring bar were added azide 1 (0.3 mmol), PdCl₂ (5 mol%), CuCl₂ (3 equiv), Cy₂NH₂Cl (0.2 equiv) and CH₂ClCH₂Cl (5 mL). The reaction mixture was stirred at 80 ˚C for 24 h until complete consumption of starting material as monitored by TLC and GC-MS analysis. After the reaction was finished, the mixture was poured into EtOAc, washed with brine (3 × 10 mL), and extracted with EtOAc. The combined organic layers were dried over anhyd Na₂SO₄ and evaporated under vacuum. The residue was purified by flash column chromatography on silica gel (hexane-EtOAc) to afford the desired product.
4-Chloro-3-phenylisoquinoline (2a):^6g,¹5 colorless oil. ^¹H NMR (500 MHz, CDCl₃): δ = 9.24 (s, 1 H), 8.35 (d, J = 8.5 Hz, 1 H), 8.04 (d, J = 8.0 Hz, 1 H), 7.85 (t, J = 8.5 Hz, 1 H), 7.81 (d, J = 11.5 Hz, 2 H), 7.69 (t, J = 7.5 Hz, 1 H), 7.51 (t, J = 7.5 Hz, 2 H), 7.45 (t, J = 8.5 Hz, 1 H). ^¹³C NMR (125 MHz, CDCl₃): δ = 150.5, 150.1, 139.1, 134.7, 131.6, 130.0, 128.5, 128.4, 128.0, 127.9, 127.7, 124.1, 109.4. LRMS (EI, 70 eV): m/z (%) = 241 (21) [M⁺ + 2], 239 (67) [M⁺], 204 (100) [M⁺ - Cl].
General Procedure for the Bromopalladation Reaction: To a flame-dried Schlenk tube equipped with a magnetic stirring bar were added azide 1 (0.3 mmol), PdBr₂ (5 mol%), CuBr₂ (3 equiv), LiBr (2 equiv) and MeCN (5 mL). The reaction mixture was stirred at 80 ˚C for 24 h until complete consumption of starting material as monitored by TLC and GC-MS analysis. After the reaction was finished, the mixture was poured into EtOAc, washed with brine (3 × 10 mL), and extracted with EtOAc. The combined organic layers were dried over anhyd Na₂SO₄ and evaporated under vacuum. The residue was purified by flash column chromatography on silica gel (hexane-EtOAc) to afford the desired product.
4−Βροµο−3−πηενψλισοθυινολινε (3α):15 Χολορλεσσ οιλ. 1Η ΝΜΡ (500 ΜΗζ, ΧΔΧλ3): δ = 9.23 (σ, 1 Η), 8.33 (δ, ϑ = 8.5 Ηζ, 1 Η), 8.01 (δ, ϑ = 8.0 Ηζ, 1 Η), 7.84 (τ, ϑ = 8.0 Ηζ, 1 Η), 7.73 (δ, ϑ = 8.5 Ηζ, 2 Η), 7.68 (τ, ϑ = 8.0 Ηζ, 1 Η), 7.50 (τ, ϑ = 7.8 Ηζ, 2 Η), 7.45 (τ, ϑ = 8.0 Ηζ, 1 Η). 13Χ ΝΜΡ (125 ΜΗζ, ΧΔΧλ3): δ = 152.3, 151.1, 140.7, 136.0, 131.9, 129.9, 128.6, 128.3, 128.0, 127.9, 127.7, 127.0, 118.3. ΛΡΜΣ (ΕΙ, 70 ες): µ/ζ (%) = 285 (23) [Μ+ + 2], 283 (25) [Μ+], 204 (100) [Μ+ ∠ Βρ].

Supplementary Material

Supporting Information