Synthesis of 4-Acetoxyindoles
and Related Derivatives by Means of Air Oxidation of 4-Oxo-4,5,6,7-tetrahydroindoles
Obtained from Nitroalkenes and Cyclohexane-1,3-diones

Masaki Arai; Yayoi Miyauchi; Tadashi Miyahara; Teruhiko Ishikawa; Seiki Saito

doi:10.1055/s-0028-1087386

LETTER

Synthesis of 4-Acetoxyindoles and Related Derivatives by Means of Air Oxidation of 4-Oxo-4,5,6,7-tetrahydroindoles Obtained from Nitroalkenes and Cyclohexane-1,3-diones

Masaki Arai^a, Yayoi Miyauchi^b, Tadashi Miyahara^b, Teruhiko Ishikawa*^a,b, Seiki Saito*^a
^a Department of Medical and Bioengineering Science, Graduate School of Natural Science and Technology, Okayama University, Tsushima, Okayama 700-8530, Japan
Fax: +81(86)2517639; e-Mail: teruhiko@cc.okayama-u.ac.jp;
^b Graduate School of Education, Okayama University, Tsushima, Okayama 700-8530, Japan

Abstract

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Abstract

A novel method for synthesizing 4-hydroxyindole derivatives from cyclohexane-1,3-diones and nitroalkenes have been developed in which a newly developed air oxidation of 4-oxo-4,5,6,7-tetrahydroindoles is playing a crucial role.

Key words

indoles - cyclohexane-1,3-diones - nitroalkenes - Michael additions - oxidations

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Referenzen

References and Notes

For recent syntheses for 4-hydroxyindoles, see:

<A NAME="RU07708ST-1A">1a</A> Gathergood N. Scammells PJ. Org. Lett. 2003, 5: 921

<A NAME="RU07708ST-1B">1b</A> Shirota O. Hakamata W. Goda Y. J. Nat. Prod. 2003, 66: 885 ; and references cited therein

<A NAME="RU07708ST-1C">1c</A> For the structure-activity relationship study of II, see: Repke DB. Grotjahn DB. Shulgin AT. J. Med. Chem. 1985, 28: 892

<A NAME="RU07708ST-2">2</A> Liou J.-P. Wu Z.-Y. Kuo C.-C. Chang C.-Y. Lu P.-Y. Chen C.-M. Hsieh H.-P. Chang J.-Y. J. Med. Chem. 2008, 51: 4351

<A NAME="RU07708ST-3A">3a</A> Ishikawa T. Kadoya R. Arai M. Takahashi H. Kaisi Y. Mizuta T. Yoshikai K. Saito S. J. Org. Chem. 2001, 66: 8000

<A NAME="RU07708ST-3B">3b</A> Ishikawa T. Miyahara T. Asakura M. Higuchi S. Miyauchi Y. Saito S. Org. Lett. 2005, 7: 1211

<A NAME="RU07708ST-4">4</A> For KF-catalyzed synthesis of 2-hydroxyiminodihydro-furans, see: Miyashita M. Kumazawa T. Yoshikoshi A. J. Org. Chem. 1980, 45: 2945

<A NAME="RU07708ST-5">5</A> Yanami T. Ballatore A. Miyashita M. Kato M. Yoshikoshi A. J. Chem. Soc., Perkin Trans. 1 1978, 1144

For the synthesis of 4-oxo-4,5,6,7-tetrahydroindoles, see:

<A NAME="RU07708ST-6A">6a</A> Leonarda P. Chiara G. Giacomo M. Maurizio T. Tetrahedron Lett. 2008, 49: 459

<A NAME="RU07708ST-6B">6b</A> Kathriarachchi KKADS. Siriwardana AI. Nakamura I. Yamamoto Y. Tetrahedron Lett. 2007, 48: 2267

<A NAME="RU07708ST-6C">6c</A> Nayyar NK. Hutchison DR. Martinelli MJ. J. Org. Chem. 1997, 62: 982

<A NAME="RU07708ST-6D">6d</A> Matsumoto M. Watanabe N. Heterocycles 1984, 22: 2313

<A NAME="RU07708ST-6E">6e</A> Bobbitt JM. Kulkarni CL. Dutta CP. Kofod H. Chiong KN. J. Org. Chem. 1978, 43: 3541

<A NAME="RU07708ST-7">7</A> 4-Oxo-4,5,6,7-tetrahydroindoles with no substituent at C(3) can be converted into 4-hydroxyindoles by Pd-catalyzed dehydrogenation or DDQ oxidation though in low yields, see: Remers WA. Roth RH. Gibs GJ. Weis MJ.
J. Org. Chem. 1971, 36: 1232

For aromatization of six-membered carbocycles by air oxidation, see:

<A NAME="RU07708ST-8A">8a</A> Kawashita Y. Nakamichi N. Kawabata H. Hayashi M. Org. Lett. 2003, 5: 3713

<A NAME="RU07708ST-8B">8b</A> Ishikawa T. Hino K. Yoneda T. Murota M. Yamaguchi K. Watanabe T. J. Org. Chem. 1999, 64: 5691

For the synthesis of 4-hydroxyindoles, see:

<A NAME="RU07708ST-9A">9a</A> Somei M. Yamada F. Heterocycles 2000, 53: 1573

<A NAME="RU07708ST-9B">9b</A> Matsumoto M. Ishoda Y. Watanabe N. Heterocycles 1986, 24: 165

<A NAME="RU07708ST-9C">9c</A> Hegedus LS. Mulhern TA. Mori A. J. Org. Chem. 1985, 50: 4282

<A NAME="RU07708ST-9D">9d</A> Remers WA. Weiss MJ. J. Am. Chem. Soc. 1965, 87: 5262

We are considering that transformation of I-A to I-C may involve an intermediary adduct I-B although nucleophilic attack of electron-rich dienamine function in I-A toward oxygen molecule, if any, might directly give I-C from I-A and could not be ruled out.

<A NAME="RU07708ST-11">11</A> Schreiber SL. Science 2000, 287: 1964

For general synthesis of cyclohexane-1,3-diones, see ref. 3a.

Table 5 Synthesis of 3-Substituted 4-Acetoxyindolines via Air
Oxidation

</TD><TD VALIGN="TOP"> Entry </TD><TD VALIGN="TOP"> Hydroindoles 10 </TD><TD VALIGN="TOP" COLSPAN="2"> Indoline 11 (yield, %)
</TD><TD VALIGN="TOP"> 1 </TD><TD VALIGN="TOP"> 10a </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> 11a (59) </TD><TD VALIGN="TOP"> 2 </TD><TD VALIGN="TOP"> 10b </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> 11b (63) </TD><TD VALIGN="TOP"> 3 </TD><TD VALIGN="TOP"> 10c </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> 11c (28) </TD><TD VALIGN="TOP"> 4 </TD><TD VALIGN="TOP"> 10d </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> 11d (33) </TD><TD VALIGN="TOP"> 5 </TD><TD VALIGN="TOP"> 10e </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> 11e (54) </TD><TD VALIGN="TOP"> 6 </TD><TD VALIGN="TOP"> 10f </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> 11f (42) </TD>

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