ORGANIC
LETTERS
2007
Vol. 9, No. 8
1613-1615
Stereocontrolled Glycoside and Glycosyl
Ester Synthesis. Neighboring Group
Participation and Hydrogenolysis of
3-(2′-Benzyloxyphenyl)-3,3-dimethylpropanoates
David Crich* and Feng Cai
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
Received February 21, 2007
ABSTRACT
The 2-O-[3-(2
′
-benzyloxyphenyl)-3,3-dimethylpropanoate] and 2-O-[3-(2′-benzyloxy-4′,6′-dimethylphenyl)-3,3-dimethylpropanoate] esters enable
the synthesis of a range of
â
-glucosides and -mannosides through neighboring participation in excellent yield, and are removed by
r
hydrogenolysis in concert with the cleavage of benzyl esters in the presence of other esters making them particularly well suited to the
stereocontrolled synthesis of glycosyl esters.
The science of stereocontrolled oligosaccharide synthesis has
advanced to a level at which targets of considerable
complexity may be undertaken with confidence,1 permitting
the development of actual therapeutic agents,2 as well as of
clinical candidates,3 and even detection kits for biological
warfare agents.4 With the potential for significant biomedical
applications, efficiency becomes increasingly important, and
one approach to this problem is through the development of
minimalist protecting group strategies. We describe two
related ester-type protecting groups, affording full stereo-
control through classical neighboring group participation
under standard glycosylation conditions, which are cleaved
by hydrogenolysis in concert with the removal of benzyl
ethers. Following earlier work from our laboratory on the
use of picolinyl esters in oligosaccharide synthesis,5 the 2-O-
picolinyl ethers have recently been introduced with similar
aims in mind;6 however, the low reactivity of the intermediate
glycosyl pyridinium results in long reaction times and
severely compromises the otherwise armed nature of these
systems.7
(1) Recent syntheses: (a) Crich, D.; Banerjee, A. J. Am. Chem. Soc.
2006, 128, 8078. (b) Crich, D.; Bowers, A. A. Org. Lett. 2006, 8, 4327. (c)
Kim, Y.-J.; Wang, P.; Navarro-Villalobos, M.; Rohde, B. D.; Derryberry,
J.; Gin, D. Y. J. Am. Chem. Soc. 2006, 128, 11906. (d) Taylor, J. G.; Li,
X.; Oberthu¨r, M.; Zhu, W.; Kahne, D. E. J. Am. Chem. Soc. 2006, 128,
15084. (e) Zhu, X.; Kawatkar, S. P.; Rao, Y.; Boons, G.-J. J. Am. Chem.
Soc. 2006, 128, 11948.
Numerous studies have focused on the development of
ester protecting groups that are cleaved other than by direct
(5) Crich, D.; Dudkin, V. J. Am. Chem. Soc. 2001, 121, 6819.
(6) Smoot, J. T.; Pomsuriyasak, P.; Demchenko, A. V. Angew. Chem.,
Int. Ed. 2005, 44, 7123.
(2) Petitou, M.; van Boeckel, C. A. A. Angew. Chem., Int. Ed. 2004, 43,
3118.
(3) (a) Werz, D. B.; Seeberger, P. H. Angew. Chem., Int. Ed. 2004, 44,
6315. (b) Wu, X.; Bundle, D. R. J. Org. Chem. 2005, 70, 7381. (c)
Ragupathi, G.; Koide, F.; Livingston, P. O.; Cho, Y. S.; Endo, A.; Wan,
Q.; Spassova, M. K.; Keding, S. J.; Allen, J.; Ouerfelli, O.; Wilson, R. M.;
Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 2715.
(4) Tamborrini, M.; Werz, D. B.; Frey, J.; Pluschke, G.; Seeberger, P.
H. Angew. Chem., Int. Ed. 2006, 45, 6581.
(7) Other stereodirecting protecting groups. (a) Yamada, T.; Takemura,
K.; Yoshida, J.-i.; Yamago, S. Angew. Chem., Int. Ed. 2006, 45, 7575. (b)
Kim, J. H.; Yang, H.; Park, J.; Boons, G.-J. J. Am. Chem. Soc. 2005, 127,
12090. (c) Kim, J. H.; Yang, H.; Boons, G.-J. Angew. Chem., Int. Ed. 2005,
44, 947. (d) Kulkarni, S. S.; Liu, S.-H.; Hung, S.-C. J. Org. Chem. 2005,
70, 2808. (e) Jiao, H.; Hindsgaul, O. Angew. Chem., Int. Ed. 1999, 38,
346. (f) Ziegler, T.; Pantkowski, G. Liebigs Ann. Chem. 1994, 659.
10.1021/ol070449y CCC: $37.00
© 2007 American Chemical Society
Published on Web 03/09/2007