Note Studies on the Zn(II)-mediated electrophilic selenocyclization and elimination of 3,4-O-isopropylidene-protected hydroxyalkenyl sulfides: synthesis of a 2-phenylselenenyl glycal Omar Boutureira * , Miguel A. Rodríguez, Yolanda Díaz, M. Isabel Matheu, Sergio Castillón * Departament de Química Analítica i Química Orgànica, Universitat Rovira i Virgili, C/Marcellí Domingo s/n, 43007 Tarragona, Spain article info Article history: Received 17 January 2010 Received in revised form 17 February 2010 Accepted 1 March 2010 Available online 4 March 2010 Keywords: Thioglycosides Glycals Cyclization Elimination Selenium Selenoglycals abstract Herein, we describe a mild and efficient Zn(II)-mediated electrophilic selenocyclization reaction of read- ily available and stable 3,4-O-isopropylidene-protected hydroxyalkenyl sulfides to 2-deoxy-2-phenylse- lenenyl-1-thio-glycosides. This material was transformed into a 2-phenylselenenyl glycal in a controlled manner using an activation–elimination sequence. Ó 2010 Elsevier Ltd. All rights reserved. Selenonium-induced cyclization of functionalized hydroxyl- and carboxylic acid-alkenes leading to cyclic ethers and lactones, as well as several cyclization reactions leading to nitrogen hetero- cycles, are useful methods for the construction of complex organic molecules. 1 Recently, in the context of our ongoing program on the stereoselective synthesis of 2-deoxyglycosides, we have described mechanistic and synthetic studies toward the preparation of 2- deoxy-2-iodo- and 2-deoxy-2-phenylselenenyl-1-thio-glycosides III and IV from furanoses I through a sequence involving olefination and electrophile-induced 6-endo cyclization reactions 2 (Scheme 1). In particular, although we have successfully demonstrated high regio- and stereoselectivity in the preparation of 2-deoxy-2-phe- nylselenenyl-1-thio-glycosides IV enhanced by employing 3,4-O- isopropylidene as a cyclic bifunctional protecting group, there are some limitations associated with the complex product distribution (thioglycosides, glycals, and 2-phenylselenenyl glycals) obtained under certain conditions (i.e., using ZnI 2 as a promoter) giving low overall preparative yields. 2a We have also demonstrated that 2-deoxy-2-iodopyranoses V can be efficiently converted into 2-iod- oglycals VII (Scheme 1). Interestingly, glycals and 2-substituted glycals are useful building blocks in the preparation of biologically important molecules especially those with configurations difficult to access (e.g., D-talal, D-gulal, and D-allal). 3 However, only one pub- lication dealing with the synthesis of 2-phenylselenenyl glycals have been reported to date despite the fact that these products are good candidates for a wide range of selenium-based organic transformations. 4 Herein, we present the results of our studies aimed toward the development of a mild and efficient Zn(II)-mediated 5 electrophilic selenocyclization of readily available and stable 3,4-O-isopropyli- dene-protected hydroxyalkenyl sulfides. Furthermore, we also report our preliminary results on the sulfonium-mediated elimination of 1- thioglycosides that provide access to 2-phenylselenenyl glycals. Encouraged by the previous results, 2a we postulated that the presence of a non-nucleophilic counter-ion in the Lewis acid would provide milder cyclization conditions in order to improve the yield and control the product distribution. Initial cyclization reactions were carried out using hydroxyalke- nyl sulfide 1 and N-(phenylselenenyl)phthalimide (NPSP)   in the absence of a promoter (Table 1, entry 1). Under these conditions, heptopyranoside 3 (11%) was obtained with complete a-selectivity together with 2-phenylselenenyl glycal 5b (34%). Cyclization with ZnI 2 (2 equiv) as the promoter proceeded smoothly and afforded de- sired product 3 in good yield (60%) maintaining the same regio- and 0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.carres.2010.03.001 * Corresponding authors. Tel.: +34 977 559556; fax: +34 977 558446. E-mail addresses: omar.boutureira@urv.cat (O. Boutureira), sergio.castillon@ urv.cat (S. Castillón).   Other selenenylating agents (e.g., PhSeOTf) in combination with promoters such as (±)-camphor-10-sulfonic acid (CSA), Mg(ClO 4 ) 2 , SnCl 4 , and I 2 proved ineffective for the cyclization of the corresponding tri-O-benzyl-protected hydroxyalkenyl derivatives. Carbohydrate Research 345 (2010) 1041–1045 Contents lists available at ScienceDirect Carbohydrate Research journal homepage: www.elsevier.com/locate/carres