A 2,4-O-[(Z)-2-butenylene]-bridged glucopyranose: efficient construction of the bicyclic skeleton and its axial-rich twist-boat conformation Yang Cao, Yusuke Kasai, Masafumi Bando, Mayumi Kawagoe, Hidetoshi Yamada * School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan article info Article history: Received 23 August 2008 Received in revised form 25 December 2008 Accepted 6 January 2009 Available online 14 January 2009 Keywords: Butenylene bridge Synthetic route Twist-boat conformation Axial rich abstract Synthesis and conformational analyses of 1-O-acetyl-3,6-di-O-benzyl-2,4-O-[(Z)-2-butenylene]-b-D- glucopyranose are described. The construction of the trioxabicyclo[6.3.1]dodecane skeleton of the compound was initiated from a ring-opened glucose, followed by the successive cyclization of first the nine-membered ring and then the six-membered ring. The pyranose of the compound was in 3 S 1 , an axial-rich twist-boat conformation. This result demonstrated an alternative method for the restriction of the pyranose into the axial-rich twist-boat conformation in contrast to the procedures that use bulky silyl protecting groups. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Conformation of a pyranose is generally in a chair form that has more equatorial substituents. Exceptions to this generality have sporadically occurred during synthetic studies to prove that the pyranose can stably attain an axial-rich conformer. 1 Intentional ring flips have also been investigated to control diastereoselectivity and reactivity in glycosidations and carbohydrate-related syntheses. 2 Recently, we have demonstrated the significance of twist-boat forms (e.g., 1 , Fig. 1) 3 in contrast to the initial concept of axial-rich conformation assuming the chair form. 4 As in 1 , steric hindrance due to bulky trialkylsilyl protecting groups has typically restricted the pyranose rings in the axial-rich sugars that have been used in glycosidations. Shoehorning the silyl groups into a tight space in- troduces these restrictions, and thus, vigorous reaction conditions are usually required. 5 Additionally, owing to the tensioned struc- ture, a part of the silyl group easily migrates to another hydroxy group. 3b To apply such conformational restriction without these disadvantages due to the silyl groups, further studies would be needed to look for alternative method for regulation of a pyranose into the axial-rich conformation, hopefully as a twist-boat structure. Construction of a bridged structure would be a simple solution for the restriction of pyranoses. 6 In the common bridged sugars, 1,6-anhydro-b-D-glucopyranose (2) and 1,2,4-O-ethylidyne-a- O OAc OBn O O OBn 6 4 HO OH O OH O O O O O HO OH Me O TIPSO OTIPS OTIPS PivO SEt BnO OBn O OPMB O O O BnO HO HO OBn OH OH 1 2 3 5 2 4 A B HO OH HO OH O OH OH HO HO O O O O O O OH OH OH 3 6 3 S 1 O OBn OAc BnO O O Figure 1. * Corresponding author. Tel.: þ81 79 565 8342; fax: þ81 79 565 9077. E-mail address: hidetosh@kwansei.ac.jp (H. Yamada). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2009.01.019 Tetrahedron 65 (2009) 2574–2578 Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet