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Synthesis 2009(8): 1265-1270  
DOI: 10.1055/s-0028-1088029
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Masked Vicinal Amino Aldehydes of Pyrrolizine and Pyrrolo [1,2-c]thiazole Series

Anton V. Tverdokhlebov*a, Alexander V. Denisenkob, Andrey A. Tolmacheva,b, Yulian M. Volovenkob, Svetlana V. Shishkinac, Oleg V. Shishkinc
a Enamine Ltd., Alexandra Matrosova str. 23, 01103, Kiev, Ukraine
Fax: +38(044)5373253; e-Mail: atver@univ.kiev.ua;
b Kiev National Taras Shevchenko University, Volodimirska str. 62, 01033, Kiev, Ukraine
c STC ‘Institute for Single Crystals’, NAS of Ukraine, 60 Lenina ave., 61001, Kharkiv, Ukraine
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Publication History

Received 29 September 2008
Publication Date:
25 March 2009 (online)

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Abstract

Acylation of (1,3-dihydro-1,3-dimethyl-2H-benzimidazol-2-ylidene)acetonitrile with mixed anhydrides of N-Boc proline and 4-thiazolidinecarboxylic acid was found to proceed at the exocyclic carbon atom yielding the corresponding C-acyl derivatives. Removal of the protecting group with equimolar amount of hydrochloric acid effected simultaneous cyclization affording 2-(3-amino-5,6,7,7a-tetrahydro-1-oxo-1H-pyrrolizin-2-yl)- and 2-(5-amino-7,7a-dihydro-7-oxo-1H,3H-pyrrolo[1,2-c]thiazol-6-yl)-1,3-dimeth­ylbenzimidazolium chlorides. Reduction of the prepared salts with sodium borohydride resulted in 3-amino-2-(2,3-dihydro-1,3-di­methyl-1H-benzimidazol-2-yl)-5,6,7,7a-tetrahydro-1H-pyrrolizin-1-one and 5-amino-6-(2,3-dihydro-1,3-dimethyl-1H-benzimidazol-2-yl)-1,7a-dihydro-3H,7H-pyrrolo[1,2-c]thiazol-7-one, respectively. These compounds were shown to be masked aldehydes. Their reactions with phenylhydrazine and hydroxylamine yielded corresponding hydrazones and oximes, whereas condensation with malononitrile furnished 2-amino-5a,6,7,8-tetrahydro-5-oxo-5H-pyrido[3,2-b]pyrrolizine-3-carbonitrile and 2-amino-5a,6-dihydro-5H,8H-thiazolo[3′,4′:1,5]pyrrolo[2,3-b]pyridine-3-carbonitrile.

Key words

acylations - amino aldehydes - heterocycles - nitriles - reduction

    References

  • 1 For a review, see: Caluwe P. Tetrahedron  1980,  36:  2359 
    CrossrefSearch in Google Scholar
  • 2 Eger K. Pfahl JG. Folkers G. Roth HJ. J. Heterocycl. Chem.  1987,  24:  425 
    CrossrefSearch in Google Scholar
  • 3a Snider BB. Duvall JR. Sattler I. Huang X. Tetrahedron Lett.  2004,  45:  6725 
    Search in Google Scholar
  • 3b Snider BB. Duvall JR. Org. Lett.  2005,  7:  4519 
    Search in Google Scholar
  • 3c Duvall JR. Wu F. Snider BB. J. Org. Chem.  2006,  71:  8579 
    Search in Google Scholar
  • 4a Volovenko YuM. Shokol TV. Babichev FS. Dopov. Akad. Nauk Ukr. RSR, Ser. B.  1986,  2:  35 ; Chem. Abstr. 1987, 107, 163331
    Search in Google Scholar
  • 4b Volovenko YuM. Chem. Heterocycl. Compd. (Engl. Transl.)  1997,  33:  854 ; Khim. Geterotsikl. Soedin. 1997, 975
    Search in Google Scholar
  • 4c Hartke K. Radau S. Liebigs Ann. Chem.  1974,  2110 
  • 4d Fares V. Flamini A. Poli N. J. Am. Chem. Soc.  1995,  117:  11580 
    Search in Google Scholar
  • 4e Bonamico M. Fares V. Flamini A. Imperatori P. Poli N. Angew. Chem., Int. Ed. Engl.  1989,  28:  1049 
    Search in Google Scholar
  • 4f Fares V. Flamini A. Poli N. J. Chem. Res., Synop.  1995,  228 
  • 4g Bonamico M. Fares V. Flamini A. Giuliani AM. Imperatori P. J. Chem. Soc., Perkin Trans. 2  1988,  1447 
  • 4h Collange E. Flamini A. Poli R. J. Phys. Chem.  2002,  A106:  200 
    Search in Google Scholar
  • 4i Flamini A. Fares V. Capobianchi A. Valentini V. J. Chem. Soc., Perkin Trans. 1  2001,  3069 
  • 5a Yang Z. Zhang S. J. Indian Chem. Soc.  2002,  79:  698 
    Search in Google Scholar
  • 5b Sun G. Yang Z. Zhang S. J. Indian Chem. Soc.  2003,  80:  851 
    Search in Google Scholar
  • 6a Varlamov AV. Borisova TN. Bonifas N. Chernyshev AI. Alexandrov GG. Voskresensky LG. Chem. Heterocycl. Compd. (Engl. Transl.)  2004,  40:  166 ; Khim. Geterotsikl. Soedin. 2004, 201
    Search in Google Scholar
  • 6b Clare BW. Ferro V. Skeleton BW. Stick RV. White AH. Aust. J. Chem.  1993,  46:  805 
    Search in Google Scholar
  • 6c Abbiati G. Casoni A. Canevari V. Nava D. Rossi E. Org. Lett.  2006,  8:  4839 
    Search in Google Scholar
  • 6d Hamersma JAM. Nossin PMM. Speckamp WN. Tetrahedron  1985,  41:  1999 
    Search in Google Scholar
  • 6e Dannhardt G. Lehr M. Arch. Pharm. (Weinheim, Ger.)  1988,  321:  545 
    Search in Google Scholar
  • 7a Craig JC. Ekwuribe NN. Fu CC. Walker KAM. Synthesis  1981,  303 
  • 7b Ramos JM. Tarazi M. Wuest JD. J. Org. Chem.  1987,  52:  5437 
    Search in Google Scholar
  • 7c Katritzky AR. Aslan DC. Oniciu DC. Tetrahedron: Asymmetry  1998,  2245 
  • 7d Lee I.-SH. Jeoung EH. Kreevoy MM. J. Am. Chem. Soc.  1997,  119:  2722 
    Search in Google Scholar
  • 7e Lee I.-SH. Jeoung EH. J. Org. Chem.  1998,  63:  7275 
    Search in Google Scholar
  • 8 Tverdokhlebov AV. Denisenko AV. Tolmachev AA. Volovenko YuM. Synthesis  2007,  1811 
    Thieme Connect
  • 9a Rudnev MI. Kurbatov VP. Chub NK. Osipov OA. J. Gen. Chem. USSR (Engl. Transl.)  1988,  58:  2077 ; Zh. Obshch. Khim. 1988, 58, 2334
    Search in Google Scholar
  • 9b Zakhs ER. Ponyaev AI. Subbotina MA. El’tsov AV. Russ. J. Gen. Chem. (Engl. Transl.)  2001,  71:  1076 ; Zh. Obshch. Khim. 2001, 71, 1142
    Search in Google Scholar
  • 9c Zakhs ER. Subbotina MA. El’tsov AV. J. Org. Chem. USSR (Engl. Transl.)  1979,  15:  178 ; Zh. Org. Khim. 1979, 15, 200
    Search in Google Scholar
  • 10a Gavai AV. Vaz RJ. Mikkilineni AM. Roberge JY. Liu Y. Lawrence RM. Corte JR. Yang W. Bednarz M. Dickson JK. Ma Z. Seethala R. Feyen JHM. Bioorg. Med. Chem. Lett.  2005,  15:  5478 
    Search in Google Scholar
  • 10b Bures F. Kulhanek J. Tetrahedron: Asymmetry  2005,  16:  1347 
    Search in Google Scholar
  • 10c Bernard E. Vanderesso R. Tetrahedron Lett.  2004,  45:  8603 
    Search in Google Scholar
  • 10d Vasanthakumar G.-R. Patil BS. Suresh Babu VV. J. Chem. Soc., Perkin Trans. 1  2002,  2087 
  • 10e Lakeev SN. Mullagalin IZ. Galin FZ. Majdanova IO. Abdullin MF. Russ. Chem. Bull.  2002,  51:  2230 ; Izv. Akad. Nauk Ser. Khim. 2002, 2071
    Search in Google Scholar
  • 10f Wallen EAA. Christiaans JAM. Saario SM. Forsberg MM. Venäläinen JI. Paso HM. Männistö PT. Gynther J. Bioorg. Med. Chem.  2002,  10:  2199 
    Search in Google Scholar
  • 10g Harrison JR. O’Brien P. Porter DW. Smith NM. J. Chem. Soc., Perkin Trans. 1  1999,  3623 
  • 10h Plucinska K. Liberek B. Tetrahedron  1987,  43:  3509 
    Search in Google Scholar
  • 10i Fujimoto K. Iwano Y. Hirai K. Sugawara S. Chem. Pharm. Bull.  1986,  34:  999 
    Search in Google Scholar
  • 11a Wada CK. Holms JH. Curtin ML. Dai Y. Florjancic AS. Garland RB. Guo Y. Heyman HR. Stacey JR. Steinman DH. Albert DH. Bouska JJ. Elmore IN. Goodfellow CL. Marcotte PA. Tapang P. Morgan DW. Michaelides MR. Davidsen SK. J. Med. Chem.  2002,  45:  219 
    Search in Google Scholar
  • 11b Koskinen AMP. Kallatsa OA. Tetrahedron  2003,  59:  6947 
    Search in Google Scholar
  • 11c Verbicky CA. Zercher CK. J. Org. Chem.  2000,  65:  5615 
    Search in Google Scholar
  • 11d Yuste F. Ortiz B. Carrasco A. Peralta M. Quintero L. Sanchez-Obregon R. Walls F. Garcia Ruano JL. Tetrahedron: Asymmetry  2000,  11:  3079 
    Search in Google Scholar
  • 11e Wittenberger SJ. J. Org. Chem.  1996,  61:  356 
    Search in Google Scholar
  • 12a Bal G. Van der Veken P. Antonov D. Lambeir A.-M. Grellier P. Croft SL. Augustyns A. Halmers A. Bioorg. Med Chem. Lett.  2003,  13:  2875 
    Search in Google Scholar
  • 12b Hoffman RV. Tao J. J. Org. Chem.  1999,  64:  126 
    Search in Google Scholar
  • 13a Chen P. Cheng PTN. Spergel SH. Zahler R. Wang X. Thottathil J. Barrish JC. Polniaszek RP. Tetrahedron Lett.  1997,  38:  3175 
    Search in Google Scholar
  • 13b De Luca L. Giacomelli G. Porcheddu A. Org. Lett.  2001,  3:  1519 
    Search in Google Scholar
  • 13c Heathcock CH. von Geldern TW. Heterocycles  1987,  25:  75 
    Search in Google Scholar
  • 13d Elliott RL. Kopecka H. Lin N.-H. He Y. Garvey DS. Synthesis  1995,  772 
  • 14a De Luca L. Giacomelli G. Taddei M. J. Org. Chem.  2001,  66:  2534 
    Search in Google Scholar
  • 14b Knight JG. Ley SV. Tetrahedron Lett.  1991,  32:  7119 
    Search in Google Scholar
  • 15a Overman LE. Lesuisse D. Tetrahedron Lett.  1985,  26:  4167 
    Search in Google Scholar
  • 15b Evans DA. Nelson JV. Vogel E. Taber TR. J. Am. Chem. Soc.  1981,  103:  3099 
    Search in Google Scholar
  • 15c Goldstein SW. Overman LE. Rabinowitz MH. J. Org. Chem.  1992,  57:  1179 
    Search in Google Scholar
  • 16a Aitken RA. Karodia N. Massil T. Young RJ. J. Chem. Soc., Perkin Trans. 1  2002,  533 
  • 16b Aitken RA. Karodia N. J. Chem. Soc., Chem. Commun.  1996,  2079 
  • 18a Nomura Y. Bando T. Takeuchi Y. Tomoda S. Bull. Chem. Soc. Jpn.  1984,  57:  1271 
    Search in Google Scholar
  • 18b Laduree D. Robba M. Heterocycles  1984,  22:  303 
    Search in Google Scholar
  • 19a Harris BD. Bhat KL. Joullie M. Heterocycles  1986,  24:  1045 
    Search in Google Scholar
  • 19b Swarbrick ME. Gosselin F. Lubell WD. J. Org. Chem.  1999,  64:  1993 
    Search in Google Scholar
  • 19c Oiry J. Pue JY. Fatome M. Sentenac-Roumanou H. Lion C. Imbach JL. Eur. J. Med. Chem.  1992,  27:  809 
    Search in Google Scholar
  • 21 Sheldrick G. M. SHELXTL PLUS. PC version. A System of Computer Programs for the Determination of Crystal Structure from X-ray Diffraction Data. Rev. 5.1.   University of Göttingen; Germany: 1998. 
17

To be precise, the material recovered from the reaction exhibited the same ¹H and ¹³C NMR spectra as that of compound 6b, but differed in melting point and elemental analysis, having significant lack of Cl. Probably, it was a mixture of the salts 6b with different counterions, namely chloride, hydroxide, and, maybe, borate. Treatment of this material with HCl afforded compound 6b identical with the authentic sample in all parameters.

20

Full crystallographic parameters have been deposited at the Cambridge Crystallographic Data Centre under reference number CCDC 702208. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44(1223)336-033; e-mail: deposit@ccdc.cam.ac.uk].