philic competition from acetate, an overall amidoglycosy-
lation process.8,9,17
Table 1. Protecting Group and Solvent Effects on Stereo- and
Chemoselectivity of Glucal 3-Carbamate Amidoglycosylation
Allal frameworks (e.g., 4, Scheme 1) provided high 1,2-trans
selectivity, offering a concise route to ꢀ-linked 2-amidoallopy-
Scheme 1. ꢀ-Selective Allal 3-Carbamate Amidoglycosylation
ranosides as found in allosamidin.7,8 However, in the C3-
epimeric series, our one-pot amidoglycosylation process
applied to glucal 3-carbamates 6a and 6b, having 4O,6O
acetonide or di-tert-butylsilylene protection, gave anomeric
mixtures only slighly favoring the 1,2-trans products 7-r and
also generated dihydropyranone byproducts 8a and 8b via
oxidation at the C3-H bond (Table 1, entries 1 and 5).9
Using 4-penten-1-ol as the acceptor, we were able to
stereoconvergently advance either anomer of n-pentenyl
(4) (a) Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res. 2007, 342,
374–406. (b) Griffith, D. A.; Danishefsky, S. J. J. Am. Chem. Soc. 1990,
112, 5811–5819. (c) Dahl, R.; Finney, N. S. J. Am. Chem. Soc. 2004, 126,
8356–8357. (d) Leblanc, Y.; Fitzsimmons, B. J.; Springer, J. P.; Rokach, J.
J. Am. Chem. Soc. 1989, 111, 2995–3000. (e) Lemieux, R. U.; Ratcliffe,
R. M. Can. J. Chem. 1979, 57, 1244–1251. (f) Lafont, D.; Guilloux, P.;
Descotes, G. Carbohydr. Res. 1989, 193, 61–73. (g) Du Bois, J.; Tomooka,
C. S.; Hong, J.; Carreira, E. M. J. Am. Chem. Soc. 1997, 119, 3179–3180.
(h) Guthikonda, K.; Wehn, P. M.; Caliando, B. J.; Du Bois, J. Tetrahedron
2006, 62, 11331–11342.
a In Hz, CDCl3 unless otherwise noted. b From 1H and 13C NMR of the
crude reaction mixture. c Isolated yield of the R anomer. d Data from ref 9.
e In DMSO-d6. f NMR yield of the R anomer vs mesitylene as an internal
standard. g In C6D6. h In acetone-d6. i Calcd from the total yield (54%) of
inseparable anomeric mixture.
glycoside18 7a, but the lack of amidoglycosylation selectivity
stymied direct access to R-linked ManNAc derivatives.9
Herein we report that proper choice of 4O and 6O protecting
groups and solvent enables high levels of stereocontrol and
chemoselectivity in amidoglycosylation of glucal 3-carbamates.
Our studies also illuminate electronic and conformational
aspects of both amidoglycosylation and the competing C3-H
oxidation.
For comparison, we began by treating benzylidene-protected
allal 3-carbamate 48 under our standard conditions with
4-penten-1-ol as the acceptor (Scheme 1). As in our previous
study with other acceptors,8 only ꢀ product 5, unaccompanied
by dihydropyranone, was observed. The outcome was compa-
rable in the three solvents tested.
(5) (a) Liu, J.; Gin, D. Y. J. Am. Chem. Soc. 2002, 124, 9789–9797. (b)
Di Bussolo, V.; Liu, J.; Huffman, L. G., Jr.; Gin, D. Y. Angew. Chem., Int.
Ed. 2000, 39, 204–207. (c) Liu, J.; Di Bussolo, V.; Gin, D. Y. Tetrahedron
Lett. 2003, 44, 4015–4018.
(6) For a strategy of internally directed glycal aminohydroxylation, see:
(a) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Vega, J. A. Angew. Chem.,
Int. Ed. 2000, 39, 2525–2529. (b) Nicolaou, K. C.; Baran, P. S.; Zhong,
Y.-L.; Barluenga, S.; Hunt, K. W.; Kranich, R.; Vega, J. A. J. Am. Chem.
Soc. 2002, 124, 2233–2244.
(7) (a) Kan, C.; Long, C. M.; Paul, M.; Ring, C. M.; Tully, S. E.; Rojas,
C. M. Org. Lett. 2001, 3, 381–384. (b) Churchill, D. G.; Rojas, C. M.
Tetrahedron Lett. 2002, 43, 7225–7228.
(8) Levites-Agababa, E.; Menhaji, E.; Perlson, L. N.; Rojas, C. M. Org.
Lett. 2002, 4, 863–865.
(9) Bodner, R.; Marcellino, B. K.; Severino, A.; Smenton, A. L.; Rojas,
C. M. J. Org. Chem. 2005, 70, 3988–3996.
(10) Espino, C. G.; Du Bois, J. Angew. Chem., Int. Ed. 2001, 40, 598–
600.
(11) (a) Padwa, A.; Stengel, T. Org. Lett. 2002, 4, 2137–2139. (b) Padwa,
A.; Flick, A. C.; Leverett, C. A.; Stengel, T. J. Org. Chem. 2004, 69, 6377–
6386.
By analogy with our earlier results7,8 and Padwa’s studies,11
we attribute high 1,2-trans selectivity to nucleophilic opening
of a glycosyl aziridine.4c,17,19 In the glucal series, low
anomeric stereocontrol might be due to glycosylation via an
oxocarbenium intermediate. Padwa has invoked aziridine-
opened zwitterions in reactions of indolyl and benzofuranyl
carbamates.11
(12) Related aziridinations: (a) Wehn, P. M.; Lee, J.; Du Bois, J. 2003,
5, 4823–4826. (b) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002,
124, 13672–13673. (c) Duran, F.; Leman, L.; Ghini, A.; Burton, G.; Dauban,
P.; Dodd, R. H. Org. Lett. 2002, 4, 2481–2483. (d) Liang, J.-L.; Yuan,
S.-X.; Chan, P. W. H.; Che, C.-M. Tetrahedron Lett. 2003, 44, 5917–5920.
(13) (a) Knapp, S.; Yu, Y. Org. Lett. 2007, 9, 1359–1362. (b) Donohoe,
T. J.; Johnson, P. D.; Cowley, A.; Keenan, M. J. Am. Chem. Soc. 2002,
124, 12934–12935. (c) Lebel, H.; Huard, K.; Lectard, S. J. Am. Chem. Soc.
2005, 127, 14198–14199.
(14) Fiori, K. W.; Du Bois, J. J. Am. Chem. Soc. 2007, 129, 562–568.
(15) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds; Wiley: New York, 1998.
(16) Dauban, P.; Sanie`re, L.; Tarrade, A.; Dodd, R. H. J. Am. Chem.
Soc. 2001, 123, 7707–7708.
(17) Another Rh-nitrenoid approach to 2-amino glycosides, using glucal
sulfamates: Lorpitthaya, R.; Xie, Z.-Z.; Kuo, J.-L.; Liu, X.-W. Chem. Eur.
J. 2008, 14, 1561–1570.
(18) Fraser-Reid, B.; Madsen, R. In PreparatiVe Carbohydrate Chem-
istry; Hanessian, S., Ed.; Marcel Dekker: New York, 1997; pp 339-356.
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