1-Naphthylpropargyl ether group: A readily cleaved and sterically minimal protecting system for stereoselective glycosylation

Article abstract of DOI:10.1021/ol061938l

(Chemical Equation Presented) The (1-naphthyl)propargyl group is introduced as a sterically unobtrusive alcohol protecting group that is cleaved in a single step by exposure to dichlorodicyanoquinone in wet dichloromethane. In conjunction with the 4,6-O-b

Full text of DOI:10.1021/ol061938l

ORGANIC
LETTERS
2006
Vol. 8, No. 21
4879-4882
1-Naphthylpropargyl Ether Group: A
Readily Cleaved and Sterically Minimal
Protecting System for Stereoselective
Glycosylation
David Crich* and Baolin Wu
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607-7061
dcrich@uic.edu
Received August 4, 2006
ABSTRACT
The (1-naphthyl)propargyl group is introduced as a sterically unobtrusive alcohol protecting group that is cleaved in a single step by exposure
to dichlorodicyanoquinone in wet dichloromethane. In conjunction with the 4,6-O-benzylidene protecting group, and the use of the sulfoxide
glycosylation method, 3-O-naphthylpropargyl-protected mannosyl donors are extremely
â-selective.
The apposite use of protecting groups continues to be an
essential element in preparative carbohydrate and oligosac-
charide synthesis, with considerable effort devoted to their
development in recent years.1 This is due to the central role
of protecting groups in modulating reactivity of both glycosyl
donors and acceptors and, critically, in the control of
regioselectivity2 and stereoselectivity.3 In response to a
problem arising from the influence of protecting group size
on the stereoselectivity of a glycosylation reaction,4 we
recently described the successful application of propargyl
ethers as sterically unobtrusive donor protecting groups for
â-mannosylation.5 While, although the propargyl ethers were
readily introduced and had the anticipated effect on stereo-
selectivity, they required a two-step deprotection protocol:
an initial treatment with base followed by catalytic osmoy-
lation of the resulting allenyl ether (Scheme 1).
Scheme 1. Deprotection of Propargyl Ethers
(1) (a) Grindley, T. B. In Modern Methods in Carbohydrate Chemistry;
Khan, S. H., O’Neill, R. A., Eds.; Harwood Academic: Amsterdam, 1996;
p 225. (b) Green, L. G.; Ley, S. V. In Carbohydrates in Chemistry and
Biology; Ernst, B., Hart, G. W., Sinay¨, P., Eds.; Wiley-VCH: Weinheim,
2000; Vol. 1, p 427. (c) Fraser-Reid, B.; Lopez, J. C.; Gomez, A. M.; Uriel,
C. Eur. J. Org. Chem. 2004, 1387.
(2) Ley, S. V.; Baeschlin, D. K.; Dixon, D. J.; Foster, A. C.; Ince, S. J.;
Priepke, H. W. M.; Reynolds, D. J. Chem. ReV. 2001, 101, 53.
(3) (a) Crich, D.; Vinod, A. U. J. Org. Chem. 2005, 70, 1291. (b) Crich,
D.; Dudkin, V. J. Am. Chem. Soc. 2001, 123, 6819. (c) Crich, D.; Jayalath,
P. J. Org. Chem. 2005, 70, 7252. (d) Crich, D.; Yao, Q. J. Am. Chem. Soc.
2004, 126, 8232. (e) Crich, D.; Hutton, T. K.; Banerjee, A.; Jayalath, P.;
Picione, J. Tetrahedron: Asymmetry 2005, 16, 105. (f) Crich, D.; Vinod,
A. U.; Picione, J. J. Org. Chem. 2003, 68, 8453. (g) Crich, D.; Vinod, A.
U.; Picione, J.; Wink, D. J. ARKIVOC 2005, Vi, 339. (h) Kim, J.-H.; Yang,
H.; Boons, G.-J. Angew. Chem., Int. Ed. 2005, 44, 947. (i) Kim, J.-H.; Yang,
H.; Park, J.; Boons, G.-J. J. Am. Chem. Soc. 2005, 127, 12090. (j) Smoot,
J. T.; Pornsuriyasak, P.; Demchenko, A. V. Angew. Chem., Int. Ed. 2005,
44, 7123. (k) Bowers, S. G.; Coe, D. M.; Boons, G.-J. J. Org. Chem. 1998,
63, 4570. (l) Jiao, H.; Hindsgaul, O. Angew. Chem., Int. Ed. 1999, 38, 346.
(m) Crich, D.; Banerjee, A. J. Am. Chem. Soc. 2006, 128, 8078. (n) Crich,
D.; Bowers, A. A. J. Org. Chem. 2006, 71, 3452.
We considered that the advantages of the propargyl ether
protecting system would be significantly enhanced if it could
be modified in such a way as to be cleavable in a single
step, orthogonal to the ubiquitous benzyl ethers. We report
here on the successful accomplishment of this goal through
the use of the naphthylpropargyl system.
The p-methoxybenzyl6 and naphthylmethyl7 ethers are
widely employed as benzyl ether surrogates, cleavable under
oxidative conditions. We reasoned that the insertion of an
(5) (a) Crich, D.; Jayalath, P. Org. Lett. 2005, 7, 2277. (b) Crich, D.;
Jayalath, P.; Hutton, T. K. J. Org. Chem. 2006, 71, 3064.
(4) Crich, D.; Dudkin, V. Tetrahedron Lett. 2000, 41, 5643.
10.1021/ol061938l CCC: $33.50
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Published on Web 09/23/2006

acetylenic group into the aryl-methylene bond of either the
PMB or naphthylmethyl system would afford a system
combining the steric advantages of the propargyl ether with
the facile oxidative cleavage of the PMB and naphthylmethyl
ethers. This line of thought led us to the ethers 1 and 2, which
we assumed could be assembled from the known bromides
3 and 4.8,9
Scheme 3. Preparation of Donors 9 and 10
Attempted activation of donors 9 and 10 by our standard
treatment with 1-benzenesulfinyl piperidine (BSP) and tri-
fluoromethanesulfonic anhydride11 in the presence of the
hindered base tri-tert-butylpyrimidine (TTBP)12 was unpro-
ductive, resulting in either no reaction or complex mixtures.
We turned, therefore, to the more potent combination of
diphenyl sulfoxide (DPSO) and triflic anhydride13 when
consumption of the donors was observed, but complex
reaction mixtures were obtained. Study of the byproducts
indicated that electrophilic attack on the arylpropargyl system
was the root of the problem.
Alkylation of 1,2;5,6-diacetone-D-glucofuranose with so-
dium hydride and bromide 4 gave the model ether 5 (Scheme
2). Treatment of this compound with DDQ in wet dichlo-
romethane, typical conditions for the removal of PMB and
naphthylmethyl ethers, returned the alcohol in 83% yield,
thereby establishing proof of principle. Directly analogous
transformations with the p-methoxyphenylpropargyl-pro-
tected system were also successful. However, it subsequently
became clear that the more electron-rich p-methoxyphenyl-
propargyl group 1 was incompatible with various glycosyl-
ation conditions leading to our subsequent preference for
system 2.
Scheme 2. Deprotection of a Naphthylpropargyl Ether
Precedent suggested, however, the activation of glycosyl
sulfoxides with Tf2O to be compatible with electron-rich
aromatic systems, especially when used in conjunction with
an electrophile scavenger.14 Accordingly, donor 9 was
oxidized to the sulfoxide 11 (Scheme 4), which was formed
as a single diastereomer whose configuration rests on
analogy.15
To examine the effect of the new protecting group 2 on
the stereoselectivity of glycosylation reactions, when located
at both O2 and O3, we prepared donors 9 and 10 from known
diol 610 by standard means as set out in Scheme 3.
Scheme 4. Preparation of Sulfoxide 11
(6) (a) Bhattacharyya, S.; Magnusson, B.; Wellmar, U. J. Chem. Soc.,
Perkin Trans. 1 2000, 8, 886. (b) Maruyama, M.; Takeda, T.; Shimizu, N.
Carbohydr. Res. 2000, 325, 83. (c) Yan, L.; Kahne, D. Synlett 1995, 523.
(d) Greene, T. W.; Wuts, P. G. M. In ProtectiVe Groups in Organic
Synthesis, 3rd ed.; John Wiley & Sons: Hoboken, 1991; p 86. (e) Kocienski,
P. J. Protecting Groups, 3rd ed.; Thieme: Stuttgart, Germany, 2005; Chapter
4, p 257. (f) Wuts, P. G. M. In Handbook of Reagents for Organic Synthesis;
Crich, D., Ed.; Wiley: Chichester, 2005; p 425.
(7) (a) Wright, J. A.; Yu, J.; Spencer, J. B. Tetrahedron Lett. 2001, 42,
4033. (b) Csa´va´s, M.; Szabo´, Z. B.; Borba´s, A.; Lipta´k, A. In Handbook of
Reagents for Organic Synthesis; Crich, D., Ed.; Wiley: Chichester, 2005;
p 459. (c) Szabo, Z. B.; Borbas, A.; Bajza, I.; Liptak, A. Tetrahedron:
Asymmetry 2005, 16, 83. (d) Csavas, M.; Borbas, A.; Szilagyi, L.; Liptak,
A. Synlett 2002, 6, 887.
Treatment of 11 with triflic anhydride in the presence of
TTBP at -78 °C in a 3:1 mixture of CH2Cl2 and 1-octene,
to give an intermediate glycosyl triflate,16 followed by
addition of 1-adamantanol, finally resulted in the formation
(11) Crich, D.; Smith, M. J. Am. Chem. Soc. 2001, 123, 9015.
(12) Crich, D.; Smith, M.; Yao, Q.; Picione, J. Synthesis 2001, 2, 323.
(13) Code´e, J. D. C.; Litjens, R. E. J. N.; Den Heeten, R.; Overkleeft,
H. S.; van Boom, J. H.; van der Marel, G. A. Org. Lett. 2003, 5, 1519.
(14) (a) Yan, L.; Kahne, D. J. Am. Chem. Soc. 1996, 118, 9239. (b)
Gildersleeve, J.; Smith, A.; Sakurai, k.; Raghavan, S.; Kahne, D. J. Am.
Chem. Soc. 1999, 121, 6176.
(8) Bromide 3 was prepared according to: Batey, R. A.; Shen, M.; Lough,
A. J. Org. Lett. 2002, 4, 1411.
(9) Bromide 4 was prepared according to: Banerjee, M.; Roy, S. Org.
Lett. 2004, 6, 2137.
(10) Crich, D.; Li, W.; Li, H. J. Am. Chem. Soc. 2004, 126, 15081.
4880
Org. Lett., Vol. 8, No. 21, 2006

Table 1. Coupling Reactions of Donor 11
1
a Isolated yields after column chromatography. b Ratio was determined by H NMR of crude reaction mixtures.
of the â-mannoside 12a with impeccable selectivity (Table
1, entry 1). That 1-octene fulfilled its role of trapping
extraneous thiophilic species was established by isolation of
13 from the reaction mixture.
Table 2. Coupling Reactions of Donor 14
A number of couplings were then conducted with more
standard glycosyl acceptors, leading to the yields and
selectivities collected in Table 1. The influence of the 3-O-
naphthylpropargyl group on selectivity is best illustrated in
entry 4 (Table 1): previously, coupling of the identical
acceptor to the 3-O-tert-butyldimethylsilyl analogue of 11
resulted in the formation of a 1.8:1 mixture of glycosides
favoring the R-anomer.4
Oxidation of thioglycoside 10 afforded the sulfoxide 14,
as a single diastereomer, in 94% yield. Activation of 14 under
the conditions employed for 11 afforded â-mannosides with
excellent selectivity (Table 2). Unfortunately, the reaction
mixtures were relatively complex and included a significant
byproduct, ketone 15, resulting from cyclization of the
protecting group onto the activated glycosyl donor. In the
face of this problem, couplings to donor 14 were not pursued
further.
a Isolated yields after column chromatography. b Ratio was determined
by H NMR of crude reaction mixtures.
1
(15) (a) Crich, D.; Mataka, J.; Zakharov, L. J. Am. Chem. Soc. 2002,
124, 6028. (b) Crich, D.; Mataka, J.; Sun, S.; Lam, K. C.; Rheingold, A.
R.; Wink, D. J. J. Chem. Soc., Chem. Commun. 1998, 24, 2763.
(16) Crich, D.; Sun, S. J. Am. Chem. Soc. 1997, 119, 11217.
The excellent stereoselectivity obtained with the 3-O-
naphthylpropargyl-protected donor 11 contrasts with the poor
selectivity delivered by the corresponding 3-O-propargyl
Org. Lett., Vol. 8, No. 21, 2006
4881

to their different requirements for deprotection, the propargyl
and naphthylpropargyl systems are highly complementary.
In accordance with the model experiments (Scheme 2),
selective deprotection of the glycosides 12 was accomplished
with DDQ in CH2Cl2/H2O (20:1) over a period of 2-3 h at
room temperature in excellent yield as reported in Table 3.
The employment of other solvent systems recommended for
the cleavage of 2-naphthylmethyl ethers, such as CH2Cl2/
CH3OH,17 CHCl3/ H2O, and CH2Cl2 alone,18 was less
satisfactory.
Table 3. Cleavage of Naphthylpropargyl Ethers
To conclude, we report the development of the naphth-
ylpropargyl ether system. In conjunction with the sulfoxide
glycosylation method, when introduced on the 3-position of
4,6-O-benzylidene-protected mannosyl donors, this system
affords extremely â-selective coupling reactions and the
possibility of orthogonal cleavage in a single step with DDQ.
We anticipate that this group will find application in
oligosaccharide synthesis and, because of its minimal steric
character and ease of deprotection, beyond the confines of
carbohydrate chemistry.
Acknowledgment. We thank the NIH (GM 57335) for
support of our work in this area.
Supporting Information Available: Full experi-
mental details and characterization data. This material is
available free of charge via the Internet at http://
pubs.acs.org.
a Isolated yields after column chromatography.
donor.5b On the other hand, 4,6-O-benzylidene mannosyl
donors carrying a 2-O-propargyl group were previously found
to be highly efficient, in contrast to the 2-O-naphthylpro-
pargyl system 14, and highly â-selective.5 Thus, in addition
OL061938L
(17) Xia, J.; Matta, K. L.; Abbas, S. A. Tetrahedron Lett. 2000, 41, 169.
(18) Oikawa, Y.; Yoshioka, T.; Yonemitsu, O. Tetrahedron Lett. 1982,
23, 889.
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