Reactivity of sugar a-aminonitrile derivatives under titanium-mediated cyclopropanation conditions Delphine Declerck a , Solen Josse a , Albert Nguyen Van Nhien a , Jan Szymoniak b , Philippe Bertus c , Denis Postel a, * a Laboratoire des glucides UMR6219, Universit e de Picardie Jules Verne, Facult e des Sciences, 33 rue Saint-Leu, 80039 Amiens, France b Universit e de Reims Champagne-Ardenne, UMR-CNRS 6229, Institut de Chimie Mol eculaire de Reims, BP 1039, 51687 Reims Cedex 02, France c Universit e du Maine, UMR-CNRS 6011, Unit e de Chimie Organique Mol eculaire et Macromol eculaire, Avenue Olivier Messiaen, 72085 Le Mans Cedex 9, France article info Article history: Received 4 October 2011 Received in revised form 8 November 2011 Accepted 23 November 2011 Available online 4 December 2011 Keywords: Nitriles Cyclopropylamine Titanium-catalyzed cyclopropanation Imidazoline abstract The reactivity of different sugar a-aminonitriles has been studied under titanium-mediated cyclo- propanation conditions. This study has been performed on amide, lactam, and imide derivatives. It has been possible to obtain spiro[furanose-3,3 0 -(3 0 ,5 0 ,6 0 ,7 0 -tetrahydrospiro[cyclopropane-1,2 0 -pyrrolo[1,2-a] imidazole])] derivatives. Ó 2011 Elsevier Ltd. All rights reserved. 1. Introduction The aminocyclopropyl framework is present in many bi- ologically active compounds. 1e3 Among the various ways of pre- paring the cyclopropylamine moiety, the titanium-mediated cyclopropanation of nitriles 4,5 has been widely used, particularly in carbohydrate chemistry, largely due for the relatively easy access of the parent nitriles and to the reaction’s high tolerance for pro- tecting groups and other functionnalities. 6e11 Spirocyclic poly- hydroxypyrrolidines A 7,8 and piperidines B 9,11 have been prepared by this method and were evaluated as potential glycosidase in- hibitors (Fig. 1). Moreover, this reaction is also useful for 1-C-gly- cofuranosyl cyanides, affording the corresponding 1-C- aminocyclopropyl glycofuranose derivatives C. 6 Very recently, we have shown that polyhydroxy 2-(1-aminocyclopropyl) pyrrolidines D could be obtained from the corresponding nitriles, 12 accessible in diastereomerically pure form by aminocyanation. 13 In the continuation of this work, we were interested in the synthesis of 3-amino-3-C-(1-aminocyclopropyl)-3-deoxyglyco- furanose derivatives E, which would be accessible from the corre- sponding a-aminonitriles F (Scheme 1). 2. Results and discussions In order to evaluate the cyclopropanation reaction, diversely protected a-aminonitriles 1aed were prepared using a strategy developed few years ago in our laboratory (Scheme 2). 14 The a- aminocyanation reaction was carried out on ulose derivatives (prepared according to standard procedures described in the A B C D Fig. 1. Type of heterocyclic derivatives with a cyclopropyl moiety. E F Scheme 1. Sugar a-aminonitrile as precursor for aminicyclopropyl derivatives. * Corresponding author. Tel.: þ33 322827570; fax: þ33 322827568; e-mail address: denis.postel@u-picardie.fr (D. Postel). Contents lists available at SciVerse ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2011.11.067 Tetrahedron 68 (2012) 1145e1152