Journal of the American Chemical Society
COMMUNICATION
the carbohydrate recognition chemistry of organoboron species
for applications in catalysis offers opportunities for the develop-
ment of new stereo- and regioselective processes. Efforts to
expand the scope of boron-catalyzed manipulations of sugars,
and to explore chiral organoboron derivatives for enantioselec-
tive transformations, are underway.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental procedures and
b
characterization data for all new compounds. This material is
’ AUTHOR INFORMATION
Corresponding Author
Figure 1. DFT-calculated structures, condensed Fukui functions, and
proton affinities of diphenylborinate adducts of representative hexopyr-
anoses (see the text and Supporting Information for details).
’ ACKNOWLEDGMENT
This work was funded by NSERC (Discovery Grants Pro-
gram, Graduate Scholarship to D.L.), the Canadian Foundation
for Innovation, the Province of Ontario, and the University of
Toronto. We are grateful to Prof. M. Nitz for his advice and
valuable comments on this study.
position (entries 5 and 11 vs 6). Acid chlorides and chlorofor-
mates with varied steric and electronic properties reacted regio-
selectively with carbohydrate derivatives in the presence of
catalyst 4a (entries 12-17). The compatibility of this method
with sterically unhindered electrophiles such as R-unbranched
aliphatic acid chlorides (entries 12, 13) and chloroformates
(entries 15-17) is noteworthy, as reagents of this type have
not been employed in Me2SnCl2-catalyzed acylation protocols.
Reactions of chloroformates posed a particular challenge, as the
products were prone to base-catalyzed acyl migration. Although
the formation of regioisomeric byproducts by acyl migrations of
this type resulted in modest yields,25 this represents the first
catalytic method for the selective introduction of these useful
carbonate protective groups.26
’ REFERENCES
(1) (a) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. Angew.
Chem., Int. Ed. 1996, 35, 1910–1922.(b) Davis, A. P.; James, T. D. In
Functional Synthetic Receptors; Schrader, T., Hamilton, A. D., Eds.; Wiley:
Weinheim, 2005; pp 45-109.
(2) (a) Gꢀomez, A. M. In Glycoscience; Fraser-Reid, B., Tatsuka, K.,
Thiem, J., Eds.; Springer-Verlag: Berlin, 2008; pp 103-177. (b) Wuts,
P. G. M.; Greene, T. W. Greene’s Protective Groups in Organic Synthesis,
4th ed.; John Wiley & Sons, Inc.: Hoboken, NJ, 2007.
(3) (a) Therisod, M.; Klibanov, A. M. J. Am. Chem. Soc. 1987,
109, 3977–3981. (b) Wang, Y.-F.; Lalonde, J. J.; Momongan, M.;
Bergbreiter, D. E.; Wong, C.-H. J. Am. Chem. Soc. 1988, 110, 7200–
7205. For selective demethylations:(c) Lewis, J. C.; Bastian, S.; Bennett,
C. S.; Fu, Y.; Mitsuda, Y.; Chen, M. M.; Greenberg, W. A.; Wong, C.-H.;
Arnold, F. H. Proc. Natl. Acad. Sci. U.S.A. 2009, 106, 16550–16555.
(4) (a) Griswold, K. S.; Miller, S. J. Tetrahedron 2003,
59, 8869–8875. (b) Kawabata, T.; Muramatsu, W.; Nishio, T.; Shibata,
T.; Schedel, H. J. Am. Chem. Soc. 2007, 129, 12890–12895.
(5) Sn(IV) derivatives: (a) Iwasaki, F.; Maki, T.; Onomura, O.;
Nakashima, W.; Matsumura, Y. J. Org. Chem. 2000, 65, 996–1002. (b)
Martinelli, M. J.; Vaidyanathan, R.; Pawlak, J. M.; Nayyar, N. K.; Dhokte,
U. P.; Doecke, C. W.; Zollars, L. M. H.; Moher, E. D.; Van Khau, V.;
Kosmrjl, B. J. Am. Chem. Soc. 2002, 124, 3578–3585. (c) Demizu, Y.;
Kubo, Y.; Miyoshi, H.; Maki, T.; Matsumura, Y.; Moriyama, N.;
Onomura, O. Org. Lett. 2008, 10, 5075–5077.
Computational studies of the putative diphenylborinic acid
adducts of representative pyranosides (derived from fucose and
rhamnose) suggest an electronic basis for the observed regio-
selectivity (Figure 1). For each adduct, the DFT-calculated
(B3LYP/6-311þG**) condensed Fukui index f- (a measure
k
of relative nucleophilic reactivity27) and proton affinity are
highest at O-3, the observed site of acylation. Interaction with
tetracoordinate boron increases the electron density of the two
bound oxygen atoms, and the relative reactivity of these appears
to reflect dipole-dipole interactions (opposition of the C4-O
and C5-O bonds and of the C2-O and C1-O bonds in the
fucose and rhamnose adducts, respectively).28 Steric factors may
also contribute to the observed selectivity: for example, compet-
ing acylation at O4 in the galacto series is likely suppressed as the
size of the C5 substituent increases.
(6) La(III) salts: Dhiman, R. S.; Kluger, R. Org. Biomol. Chem. 2010,
8, 2006–2008.
In conclusion, organoboron catalysis represents a novel
method to activate cis-1,2-diol groups toward electrophilic attack.
The broad scope of this reaction with respect to both carbohy-
drate substrate and acylating agent, as well as the low toxicity of
the borinate ester catalyst and its straightforward removal from
reaction mixtures, represent attractive features in comparison to
previous protocols employing organotin reagents. Competition
experiments demonstrate that borinic acids are able to achieve
selectivity based on subtle structural differences that are not
easily distinguished by other methods. In light of increasing
appreciation of the potential for connections between the fields
of supramolecular chemistry and catalysis,29 the ability to exploit
(7) (a) Wang, C.-C.; Lee, J.-C.; Luo, S.-Y.; Kulkami, S. S.; Huang,
Y.-W.; Lee, C.-C.; Chang, K.-L.; Hung, S.-C. Nature 2007, 446, 896–899.
(b) Franc-ais, A.; Urban, D.; Beau, J.-M. Angew. Chem., Int. Ed. 2007,
46, 8662–8665.
(8) Duggan, P. J.; Tyndall, E. M. J. Chem. Soc., Perkin Trans. 1
2002, 1325–1339.
(9) (a) Oshima, K.; Kitazono, E.; Aoyama, Y. Tetrahedron Lett. 1997,
38, 5001–5004. See also:(b) Li, D. R.; Murugan, A.; Falck, J. R. J. Am.
Chem. Soc. 2008, 130, 46–48.
(10) Oshima, K.; Aoyama, Y. J. Am. Chem. Soc. 1999, 121, 2315–
2316.
(11) The boronate ester generated from 1a and 3c was unreactive
with PhCOCl under the conditions shown in Scheme 1. Addition of
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dx.doi.org/10.1021/ja110332r |J. Am. Chem. Soc. 2011, 133, 3724–3727