C2-acyloxyglycosylation with glycal donors

Full text of DOI:10.1021/ja015991a

J. Am. Chem. Soc. 2001, 123, 6939-6940
6939
sitates an additional C2-O-protection step prior to subsequent
anomeric bond formations.7 We now report a new method for
oxidative glycosylation that effects the stereoselective installation
of a carboxylate functionality onto the C2-position of glycal
donors with concomitant glycosidic bond formation. The novel
method allows for the preparation of C2-acyloxy glycosides
directly from glycal donors in a one-pot procedure employing
readily available IIII reagents.
C2-Acyloxyglycosylation with Glycal Donors
Lei Shi, Yong-Jae Kim, and David Y. Gin*
Department of Chemistry, Roger Adams Laboratory
UniVersity of Illinois, Urbana, Illinois 61801
ReceiVed April 10, 2001
ReVised Manuscript ReceiVed June 6, 2001
Scheme 1
Glycals have proven to be extremely useful carbohydrate
building blocks in the preparation of biologically important
oligosaccharides and glycoconjugates.1 This is a direct result of
the versatile reactivity of the glycal enol ether functionality, which
allows for the introduction of various functionalities at the C2-
position as well as formation of the glycosidic bond at C1. In
this context, a variety of substituents have been introduced at the
C2-position of glycals, including hydroxyl,2 nitrogen,3 halides,4
sulfur,5 selenium,5 and carbon functionalities.6 Among these, the
introduction of the hydroxyl group at C2 in combination with
glycosidic bond formation has been highlighted in numerous
elegant syntheses of complex carbohydrates.7 In this regard, the
strategy involves the epoxidation of glycal substrates to generate
1,2-anhydropyranosides that serve as effective glycosyl donors
via epoxide ring opening. This strategy serves to install an
unprotected hydroxyl substituent at the C2-position of the glycal
donor, and thus is ideal for the preparation of C2-branched
carbohydrate residues.
Polycoordinate iodine reagents are well-known to engage in a
variety of oxidative transformations with electron-rich π-systems;8
however, reports on reactions with IIII reagents on glycal substrates
have been comparatively limited.9,10 Transformations involving
glycal oxidation by IIII reagents have included selective C3-O-
oxidation11 as well as installation of several heteroatom substit-
uents, such as halides,12 and azides13 at the C2-position of glycals;
yet, the efficient installation of a protected oxygen substituent
onto the C2-position of glycals has remained elusive.14 In our
efforts to explore new approaches to glycal assembly for the
synthesis of complex carbohydrates, we have developed a simple
C2-acyloxyglycosylation procedure (Scheme 1) in which IIII
reagents, in combination with the appropriate Lewis acid catalyst,
serve as ideal glycal oxidants. In this procedure, a solution of
the glycal donor (1, 1.3 equiv) and a (diacyloxyiodo)benzene
reagent (1.3 equiv) in dichloromethane at -45 °C is treated with
BF3‚OEt2 (0.26 equiv). After allowing the reaction to warm to
-25 °C, the glycosyl acceptor (Nu-H, 1 equiv) and TfOH (0.26
equiv) are introduced at -45 °C to provide the 1,2-trans-
disubstituted C2-acyloxylglycoside 2.
However, application of this glycal assembly strategy to the
construction of non-C2-branched oligosaccharides usually neces-
(1) Review: Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed.
Engl. 1996, 35, 1380-1419.
(2) (a) Sondheimer, S. J.; Yamaguchi, H.; Schuerch, C. Carbohydr. Res.
1979, 74, 327-332. (b) Klein, L. L.; McWhorter, W. W., Jr.; Ko, S. S.; Pfaff,
K. P.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7362-
7364. (c) Trumbo, D. L.; Schuerch, C. Carbohydr. Res. 1985, 135, 195-202.
(d) Bellosta, V.; Czernecki, S. J. Chem. Soc., Chem. Commun. 1989, 199-
200. (e) Bellucci, G.; Catelani, G.; Chiappe, C.; D’Andrea, F. Tetrahedron
Lett. 1994, 35, 8433-8436. (f) Halcomb, R. L.; Danishefsky, S. J. J. Am.
Chem. Soc. 1989, 111, 6661-6666. (g) Di Bussolo, V.; Kim, Y.-J.; Gin, D.
Y. J. Am. Chem. Soc. 1998, 120, 13515-13516. (h) Kim, J.-Y.; Di Bussolo,
V.; Gin, D. Y. Org. Lett. 2001, 3, 303-306. (i) Kim, Y.-J.; Gin, D. Y. Org.
Lett. 2001, 3, 1801-1804.
A possible pathway for this reaction involves activation of
glycal 1 by PhI(OCOR′)2 to generate the glycosyl ester intermedi-
ate 3 (Scheme 2), incorporating a phenyl iodonium (IIII) func-
tionality at C2. Transfer of a carboxylate functionality to the C2-
position of 3 would then provide 4,15 an intermediate that can
effectively glycosylate the appropriate acceptor in the presence
(3) (a) Lemieux, R. U.; Ratcliffe, R. M. Can. J. Chem. 1979, 57, 1244-
1251. (b) Leblanc, Y.; Fitzsimmons, B. J.; Springer, J. P.; Rokach, J. J. Am.
Chem. Soc. 1989, 111, 2995-3000. (c) Griffith, D. A.; Danishefsky, S. J. J.
Am. Chem. Soc. 1990, 112, 5811-5819. (d) Czernecki, S.; Ayadi, E. Can. J.
Chem. 1995, 73, 343-350. (e) Rubinstenn, G.; Esnault, J.; Mallet, J.-M.; Sinay¨,
P. Tetrahedron: Asymmetry 1997, 8, 1327-1336. (f) Du Bois, J.; Tomooka,
C. S.; Hong, J.; Carreira, E. M. J. Am. Chem. Soc. 1997, 119, 3179-3180.
(g) Das, J.; Schmidt, R. R. Eur. J. Org. Chem. 1998, 1609-1613. (h) Di
Bussolo, V.; Liu, J.; Huffman, L. G.; Gin, D. Y. Angew. Chem., Int. Ed. 2000,
39, 204-207. (i) Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Vega, J. A.
Angew. Chem., Int. Ed. 2000, 39, 2525-2529. (j) Kan, C.; Long, C. M.; Paul,
M.; Ring, C. M.; Tully, S. E.; Rojas, C. M. Org. Lett. 2001, 3, 381-384.
(4) (a) Lemieux, R. U.; Morgan, A. R. Can. J. Chem. 1965, 43, 2190-
2198. (b) Tatsuta, K.; Fujimoto, K.; Kinoshita, M.; Umezawa, S. Carbohydr.
Res. 1977, 54, 85-104. (c) Thiem, J.; Karl, H.; Schwentner, J. Synthesis 1978,
696-700. (d) Burkart, M. D.; Zhang, Z.; Hung, S.-C.; Wong, C.-H. J. Am.
Chem. Soc. 1997, 119, 11743-11746.
(5) For C2-sulfur/selenium substituents, see: (a) Jaurand, G.; Beau, J.-M.;
Sinay¨, P. J. Chem. Soc., Chem. Commun. 1981, 572-573. (b) Ito, Y.; Ogawa,
T. Tetrahedron Lett. 1987, 28, 2723-2726. (c) Preuss, R.; Schmidt, R. R.
Synthesis 1988, 694-697. (d) Perez, M.; Beau, J.-M. Tetrahedron Lett. 1989,
30, 75-78. (e) Grewal, G.; Kaila, N.; Franck, R. W. J. Org. Chem. 1992, 57,
2084-2092. (f) Roush, W. R.; Sebesta, D. P.; James, R. A. Tetrahedron 1997,
53, 8837-8852.
(6) (a) Linker, T.; Sommermann, T.; Kahlenberg, F. J. Am. Chem. Soc.
1997, 119, 9377-9384. (b) Beyer, J.; Madsen, R. J. Am. Chem. Soc. 1998,
120, 12137-12138.
(8) (a) Varvoglis, A. The Organic Chemistry of Polycoordinated Iodine;
VCH: New York, 1992. (b) Moriarty, R. M.; Prakash, O. Org. React. 1999,
54, 273-418.
(9) Kirschning, A. Eur. J. Org. Chem. 1998, 2267-2274.
(10) Engstrom, K. M.; Mendoza, M. R.; Navarro-Villalobos, M.; Gin, D.
Y. Angew. Chem., Int. Ed. 2001, 40, 1128-1130.
(11) (a) Kirschning, A. J. Org. Chem. 1995, 60, 1228-1232. (b) Kirshning,
A. Liebigs Ann. 1995, 2053-2056.
(12) (a) Kirschning, A.; Plumeier, C.; Rose, L. Chem. Commun. 1998, 33-
34. (b) Kirschning, A.; Abul, Md. H.; Monenschein, H.; Rose, L.; Schoning,
K.-U. J. Org. Chem. 1999, 64, 6522-6526. (c) Muraki, T.; Yokoyama, M.;
Togo, H. J. Org. Chem. 2000, 65, 4679-4684.
(13) (a) Santoyo-Gonzalez, F.; Calvo-Flores, F. G.; Garcia-Mendoza, P.;
Hernandez-Mateo, F.; Isac-Garcia, J.; Robles-Diaz, R. J. Org. Chem. 1993,
58, 6122-6125. (b) Czernecki, S.; Ayadi, E.; Randriamandimby, D. J. Chem.
Soc., Chem. Commun. 1994, 35-36.
(14) 1,2-Bis(tosyloxylation) and 1,2-dihydroxylation of glycals have been
reported as byproducts associated with C3-O-oxidation of glycals with the
Koser reagent. See: (a) Kirschning, A. J. Org. Chem. 1995, 60, 1228-1232.
(b) Harders, J.; Garming, A.; Jung, A.; Kaiser, V.; Monenschein, H.; Ries,
M.; Rose, L.; Schoning, K. U.; Weber, T.; Kirschning, A. Liebigs Ann./Recl.
1997, 2125-2132.
(15) Glycal activation to generate 4 may proceed by â-approach of the IIII
reagent to afford the C2-â-iodonium-C1-R-glycosyl ester stereoisomer of 3.
Migration of the C1-ester group to the C2-position via reductive elimination
of iodobenzene and substitution of the second carboxylate group onto C1 would
provide 4. Conversely, another possibility might involve initial R-approach
of the IIII reagent (see ref 14b), generating the C2-R-iodonium-C1-â-glycosyl
ester stereoisomer of 3. Transfer of the carboxylate group to C2 via SNi-type
rearrangement of the R-C2-IIII functionality with retention of configuration
would then afford 4.
(7) (a) Park, T. K.; Kim, I. J.; Hu, S.; Bilodeau, M. T.; Randolph, J. T.;
Kwon, O.; Danishefsky, S. J. J. Am. Chem. Soc. 1996, 118, 11488-11500.
(b) Seeberger, P. H.; Eckhardt, M.; Gutteridge, C. E.; Danishefsky, S. J. J.
Am. Chem. Soc. 1997, 119, 10064-10072. (c) Deshpande, P. P.; Danishefsky,
S. J. Nature 1997, 387, 164-166. (d) Kuduk, S. D.; Schwarz, J. B.; Chen,
X.-T.; Glunz, P. W.; Sames, D.; Ragupathi, G.; Livingston, P. O.; Danishefsky,
S. J. J. Am. Chem. Soc. 1998, 120, 12474-12485.
10.1021/ja015991a CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/20/2001

6940 J. Am. Chem. Soc., Vol. 123, No. 28, 2001
Communications to the Editor
Table 1
Scheme 2
Chart 1
a Product isolated as a 5:1 mixture of diastereomers (â-glucopyrano-
side:R-mannopyranoside). b Product isolated as a 6:1 mixture of dia-
stereomers (â-glucopyranoside:R-mannopyranoside).
acetate or benzoate functionality, respectively, at the C2-position
of the glycal donor. Both glucal and galactal donors are amenable
to this oxidative glycosylation reaction in which an R-C2-acyloxy
substituent is installed with high stereoselectivity, yielding a
variety of selectively protected â-glycoconjugates.
In the reaction pathway proposed in Scheme 2, the 1,2-bis-
(acyloxy)glycoside 4 is presumably formed during the course of
glycal oxidation and carboxylate transfer. Indeed, when the glycal
donors are simply activated with the (diacyloxyiodo)benzene
reagent (1.2 equiv, -45 to -25 °C) in the presence of a catalytic
quantity of BF3‚OEt2 (0.2 equiv), the corresponding 1,2-trans-
bis(acyloxy)glycosides can be isolated in high yields (Table 1).18
As a result, this method also serves as a direct route to 1,2-bis-
(acyloxy) glycosides from glycal substrates to generate selectively
protected glycosyl esters.
In summary, a new method for oxidative glycosylation is
described. By employing readily available (diacyloxyiodo)benzene
reagents and catalytic quantities of an appropriate acid, one-pot
glycosylations can be performed in which a carboxylate func-
tionality is stereoselectively installed at the C2 position of glycal
donors.
Acknowledgment. This research was supported by the National
Institutes of Health (GM-58833), the Arnold and Mabel Beckman
Foundation (BYI), and the Alfred P. Sloan Foundation. Y.J.K. thanks
Lubrizol and Pharmacia for predoctoral fellowships. D.Y.G. is a Cottrell
Scholar of Research Corporation.
a The oxidative glycosylation was performed with 1.8 equiv of the
glycal donor. b Yield refers to formation of the C1′′-anomeric linkage
employing 2.4 equiv of the glucal donor.
of catalytic TfOH16 to afford the C2-acyloxyglycoside 2 with good
anomeric selectivity as a consequence of C2-neighboring group
participatory effects.
Supporting Information Available: Experimental details and spectral/
analytical data for the glycoside products (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
A series of couplings were performed with a variety of glycal
donors employing several carbohydrate glycosyl acceptors (Chart
1) to prepare a series of C2-acyloxy glycosides. In these
investigations, both commercially available (diacetoxyiodo)-
benzene and readily available (dibenzoyloxyiodo)benzene17 served
as comparably efficient IIII oxidants, thereby installing either the
JA015991A
(17) Stang, P. J.; Boehshar, M.; Wingert, H.; Kitamura, T. J. Am. Chem.
Soc. 1988, 110, 3272-3278.
(18) Although the bis(acyloxylation) of tri-O-benzyl-D-glucal led to the
formation of small amounts of the corresponding R-manno isomer (entries 1
and 2), use of this donor (∼1.3 equiv) in the C2-acyloxyglycosylation reactions
(Chart 1) still led to the exclusive formation of the â-glucopyranosides due
to the lower reactivity of the minor quantities of the R-glycosyl ester donor.
(See, for example, ref 16c.) It is worth noting that if the 1,2-bis(acyloxylation)
procedure is performed on tri-O-benzyl-D-glucal at -60 °C with 1.2 equiv of
BF3‚OEt2, the corresponding 1,2-diacetate (65%) and 1,2-dibenzoate (75%)
are isolated with >20:1 (gluco:manno) diastereoselectivities.
(16) Catalytic quantities of TMSOTf can also be employed to effect
glycosylation. See: (a) Ogawa, T.; Beppu, K.; Nakabayashi, S. Carbohydr.
Res. 1981, 93, C6-C9. (b) Kimura, Y.; Suzuki, M.; Matsumoto, T.; Abe, R.;
Terashima, S. Chem. Lett. 1984, 501-504. (c) Roush, W. R.; Bennett, C. E.
J. Am. Chem. Soc. 1999, 121, 3541-3542.