Additions of Lithiated Alkoxyallenes to Phthalimide: A New Synthesis of Pyrroloisoindolones and an Unusual Olefination Reaction

Abstract

Addition of an excess of lithiated alkoxyallenes to phthalimide­ 5 provided the expected primary adducts 7a-c, which could be cyclized via their oxygen moiety to furnish spirofuran derivatives 8a-c. After selective protection of the hydroxyl function of 7a-c the resulting siloxy derivatives 11a-c were transformed by gold(III) catalysis into pyrroloisoindolones 13a-c in moderate yields. This establishes a new approach to this class of heterocycles in a [3+2] fashion with the alkoxyallenes as functionalized C-3 unit and phthalimide 5 providing the CN moiety. Treatment of primary adducts 7a-c with aqueous sulfuric acid surprisingly led to compounds 14a-c in good yields. The constitution of these products was proved by an X-ray analysis of derivative 15a. Aqueous hydrochloric acid converted 7a into a similar product 17 containing a chlorine substituent. These reactions can be considered as olefination reactions of phthalimide.

allenes - lithium - imide - pyrroloisoindolones - gold catalysis

References

<A NAME="RT14105SS-1A">1a</A> Hoff S. Brandsma L. Arens JF. Recl. Trav. Chim. Pays-Bas  1969,  88:  609 

<A NAME="RT14105SS-1B">1b</A> Hormuth S. Reissig H.-U. Synlett  1991,  179 

<A NAME="RT14105SS-1C">1c</A> Hormuth S. Reissig H.-U. J. Org. Chem.  1994,  59:  67 

<A NAME="RT14105SS-1D">1d</A> Hormuth S. Schade W. Reissig H.-U. Liebigs Ann. Chem.  1996,  2001 

<A NAME="RT14105SS-2">2</A> Okala Amombo GM. Hausherr A. Reissig H.-U. Synlett  1999,  1871 

<A NAME="RT14105SS-3A">3a</A> Schade W. Reissig H.-U. Synlett  1999,  632 

<A NAME="RT14105SS-3B">3b</A> Helms M. Schade W. Pulz R. Watanabe T. Al-Harrasi A. Fisera L. Hlobilova I. Zahn G. Reissig H.-U. Eur. J. Org. Chem.  2005,  1003 

<A NAME="RT14105SS-4A">4a</A> Reissig H.-U. Hormuth S. Schade W. Okala Amombo GM. Watanabe T. Pulz R. Hausherr A. Zimmer R. Lectures in Heterocyclic Chemistry Vol. XVI, In J. Heterocycl. Chem.  2000,  37:  597 

<A NAME="RT14105SS-4B">4b</A> Reissig H.-U. Schade W. Okala Amombo GM. Pulz R. Hausherr A. Pure Appl. Chem.  2002,  74:  175 

<A NAME="RT14105SS-5A">5a</A> Zimmer R. Synthesis  1993,  165 

<A NAME="RT14105SS-5B">5b</A> Zimmer R. Reissig H.-U. Donor-Substituted Allenes, In Modern Allene Chemistry   Krause N. Hashmi ASK. Wiley-VCH; Weinheim: 2004.  Chap. 8. p.425 

<A NAME="RT14105SS-6A">6a</A> Hausherr A. Ph.D. Dissertation   Freie Universität Berlin; Germany: 2001. 

<A NAME="RT14105SS-6B">6b</A> Flögel O. Okala Amombo GM. Reissig H.-U. Zahn G. Brüdgam I. Hartl H. Chem. Eur. J.  2003,  9:  1405 

<A NAME="RT14105SS-6C">6c</A> Kaden S. Brockmann M. Reissig H.-U. Helv. Chim. Acta  2005,  88:  1826 

<A NAME="RT14105SS-7">7</A> Al-Harrasi A. Reissig H.-U. Angew. Chem. Int. Ed.  2005,  44:  6227 ; Angew. Chem. 2005, 117, 6383

<A NAME="RT14105SS-8">8</A> Honma T. Hayashi K. Aoyama T. Hashimoto N. Machida T. Fukasawa K. Iwama T. Ikeura C. Suzuki-Takahashi I. Iwasawa Y. Hayama T. Nishimura S. Morishima H. J. Med. Chem.  2001,  44:  4615 

<A NAME="RT14105SS-9">9</A> Grigg R. Sridharan V. Stevenson P. Sukirthalingam S. Worakun T. Tetrahedron  1990,  46:  4003 

<A NAME="RT14105SS-10A">10a</A> Itahara T. J. Chem. Soc., Chem. Commun.  1981,  254 

For photoinduced cyclizations, see also:

<A NAME="RT14105SS-10B">10b</A> Schmickler H. Bartoschek A. Kramer W. Griesbeck AG. Org. Lett.  2001,  3:  537 

<A NAME="RT14105SS-11">11</A> Wang E.-C. Chen H.-F. Feng P.-K. Lin Y.-L. Hsu M.-K. Tetrahedron Lett.  2002,  43:  9163 

<A NAME="RT14105SS-12A">12a</A> Claesson A. Sahlberg C. Luthman K. Acta Chem. Scand. Ser. B  1979,  33:  309 

<A NAME="RT14105SS-12B">12b</A> Robinson ED. Marshall JA. J. Org. Chem.  1990,  55:  3450 

<A NAME="RT14105SS-12C">12c</A> Bartley GS. Marshall JA. J. Org. Chem.  1994,  59:  7169 

<A NAME="RT14105SS-13">13</A> Okala Amombo GM. Ph.D. Dissertation   Technische Universität Dresden; Germany: 2000. 

<A NAME="RT14105SS-14A">14a</A> Frost TM. Choi J.-H. Schwarz L. Hashmi ASK. Angew. Chem. Int. Ed.  2000,  39:  2285 ; Angew. Chem. 2000, 112, 2382

<A NAME="RT14105SS-14B">14b</A> Gagosz F. Org. Lett.  2005,  7:  4129 

For reviews see:

<A NAME="RT14105SS-14C">14c</A> Dyker G. Angew. Chem. Int. Ed.  2000,  39:  4237 ; Angew. Chem. 2000, 112, 4407

<A NAME="RT14105SS-14D">14d</A> Hashmi ASK. Gold Bull.  2003,  36:  3 

<A NAME="RT14105SS-14E">14e</A> Echavarren AM. Nevado C. Chem. Soc. Rev.  2004,  33:  431 

<A NAME="RT14105SS-15A">15a</A> Hoffmann-Röder A. Krause N. Org. Lett.  2001,  3:  2537 

<A NAME="RT14105SS-15B">15b</A> Morita N. Krause N. Org. Lett.  2004,  6:  4121 

<A NAME="RT14105SS-15C">15c</A> See also: Lee PH. Kim H. Lee K. Kim M. Noh K. Kim H. Seomon D. Angew. Chem. Int. Ed.  2005,  44:  1840 ; Angew. Chem. 2005, 117, 1874

<A NAME="RT14105SS-16">16</A> Flögel O. Dash J. Brüdgam I. Hartl H. Reissig H.-U. Chem. Eur. J.  2004,  10:  4283 

<A NAME="RT14105SS-17A">17a</A> Reppe W. Liebigs Ann. Chem.  1955,  596:  1 

<A NAME="RT14105SS-17B">17b</A> Weiberth FJ. Hall SS. J. Org. Chem.  1985,  50:  5308 

<A NAME="RT14105SS-18">18</A> Sheldrick GM. SHELX97 (includes SHELXS97, SHELXL97, and CIFTAB) Programs for Crystal Structure Analysis (Release 97-2)   Universität Göttingen; Germany: 1998. 

<A NAME="RT14105SS-19">19</A>

Crystallographic data for 15a can be obtained from Cambridge Crystallographic Data Centre, CCDC reference number: 286363.