Synthesis of silylallene glycosides and diene diglycosides by C-glycosidation of D-glucal with 1,4-bis(trimethylsilyl)-2-butyne

Article abstract of DOI:10.1021/ol050265o

(Chemical Equation Presented) Silylmethylallenyl glycosides, symmetrical and unsymmetrical diene glycosides, were synthesized by C-glycosidation with 1,4-bis(trimethylsilyl)-2-butyne in good yield. The nature of the product is controlled by the choice of Lewis acid, BF₃·OEt₂, or SnCl₄. The efficient construction of unsymmetrical diene glycosides was achieved in one pot on the basis of the order of addition of sugar starting materials.

Full text of DOI:10.1021/ol050265o

ORGANIC
LETTERS
2005
Vol. 7, No. 8
1585-1588
Synthesis of Silylallene Glycosides and
Diene Diglycosides by C-Glycosidation of
D
-Glucal with 1,4-Bis(trimethylsilyl)-2-butyne
Rungnapha Saeeng*,† and Minoru Isobe*,‡
Department of Chemistry, Faculty of Science, Burapha UniVersity, Sangsook,
Chonburi 20131, Thailand, and Laboratory of Organic Chemistry, Graduate School of
Bioagricultural Sciences, Nagoya UniVersity, Chikusa, Nagoya 464-8601, Japan
rungnaph@buu.ac.th; isobem@agr.nagoya-u.ac.jp
Received February 8, 2005
ABSTRACT
Silylmethylallenyl glycosides, symmetrical and unsymmetrical diene glycosides, were synthesized by C-glycosidation with 1,4-bis(trimethylsilyl)-
2-butyne in good yield. The nature of the product is controlled by the choice of Lewis acid, BF3 OEt2, or SnCl4. The efficient construction of
‚
unsymmetrical diene glycosides was achieved in one pot on the basis of the order of addition of sugar starting materials.
We previously demonstrated the C-glycosidation of glucal
1 with bis-silylacetylenes (2, R ) SiMe3) under acidic
conditions (Scheme 1).1 For the functionalization of tetrahy-
dropyran rings, C-glycosidation of alkynyl or propargyl
silanes by oxocarbenium ion intermediates has proven to be
a useful method. We have extended this stereoselective
C-glycosidation methodology using terminal alkynyl silanes
2 with various R groups to obtain different types of acetylenic
glycosides,2 as well as using propargyl silanes 3 to introduce
the allenyl group to sugar nuclei.3 We have also been able
to select for the formation of allenic, acetylenic or propargylic
glycosides by choice of silyl groups on each side of the
acetylene nucleophile 4.4 While most of these approaches
have been developed to provide sugar fragments for bioactive
Scheme 1. C-Glycosidation of D-Glucal
† Burapha University.
‡ Nagoya University.
(1) (a) Ichikawa, Y.; Isobe, M.; Konobe, M.; Goto, T. Tetrahedron Lett.
1984, 25, 5049-5052. (b) Ichikawa, Y.; Isobe, M.; Konobe, M.; Goto, T.
Carbohydr. Res. 1987, 171, 193-199. (c) Tsukiyama, S.; Isobe, M.
Tetrahedron Lett. 1992, 33, 7911-7914.
(2) Isobe, M.; Saeeng, R.; Nishizawa, R.; Konobe, M.; Nishikawa, T.
Chem. Lett. 1999, 467-468.
(3) Huang, G.; Isobe, M. Tetrahedron 2001, 57, 10241-10246.
10.1021/ol050265o CCC: $30.25
© 2005 American Chemical Society
Published on Web 03/18/2005

types of glycosides, diene diglycosides and silylmethylallene
glycosides, is now reported here by C-glycosidation with 1,4-
bis(trimethylsilyl)-2-butyne 5.
Table 1. Silylallene Glycosides from C-Glycosidation with
1,4-Bis(trimethylsilyl)-2-butynea
The nucleophile, 1,4-bis(trimethylsilyl)-2-butyne 5, was
prepared by metal-halogen exchange of 1,4-dichloro-2-
butyne with lithium dispersion (30% in paraffin liquid) in
the presence of a catalytic amount of DTBB, followed by
silylation with trimethylsilyl chloride.
Initially, 1 equiv of D-glucal 1 reacted with 1 equiv of 5
in the presence of BF3‚OEt2 (Table 1, entry 1). The reaction
led to the silylallene glycoside 6 with R-orientation in 66%
yield with high selectivity (condition A). Use of 1.2 equiv
of 5 raised the yield to 82% (condition B). In the presence
of SnCl4, C-glycosidation gave only a low yield of the
expected product (condition C). The C-glycosidation was
then performed under condition B with a range of carbohy-
drates (entries 2-4), and these reactions led to the silylallene
glycoside products 8, 10, and 12 in moderate to good yields.
In the case of D-galactal 7, the product was obtained in 73%
yield after 3 h whereas for C-glycosidation of 2-acetoxy-D-
glucal 11, the glycoside product was formed in only 34%
yield after conducting the reaction for as long as 7 h. On
the basis of these results, the rate of C-glycosidation of
D-glucal is suggested to be similar to that of D-xylal but faster
than both D-galactal and 2-acetoxy-D-glucal.
a Conditions: (A) sugar/5 ) 1:1, Lewis acid ) BF3‚OEt2; (B) sugar/5
) 1:1.2, Lewis acid ) BF3‚OEt2; (C) sugar/5 ) 1:1, Lewis acid ) SnCl4.
To further extend the scope to double glycosidation, 2
equiv of D-glucal was employed with 1 equiv of 1,4-bis-
(trimethylsilyl)-2-butyne 5. The reaction was carried out
using BF3‚OEt2 as Lewis acid to provide a new type of
symmetrical diene glycoside 13 with the monoglycosidation
natural product synthesis, none have involved the construc-
tion of new types of glycosides. The synthesis of those new
Table 2. Symmetric Diene Glycosides from C-Glycosidation with 1,4-Bis(trimethylsilyl)-2-butynea
a Conditions: (A) sugar/5 ) 1:2; (B) sugar/5 ) 1:3; (C) sugar/5 ) 1:2; (D) sugar/5 ) 1:2.
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Org. Lett., Vol. 7, No. 8, 2005

product 6 in similar amounts (50:50) after stirring the reac-
tion for 3.5 h (entry 1, Table 2). On changing from
BF3‚OEt2 to TMSOTf and SnCl4, only low to moderate
yields of the diene glycoside product were observed, but
without the silylallene glycoside. However when 3 equiv of
D-glucal were used in the presence of SnCl4, there was a
dramatic change in the outcome of the reaction, and
diene glycoside 13 was obtained in 92% in 15 min (condition
B).
C-Glycosidation of D-glucal with 1,4-bis(trimethylsilyl)-2-
butyne 5 was first carried out in the presence of BF3‚OEt2,
followed by addition of D-galactal 7 and SnCl4. On the other
hand, a better yield (53%) of 16 was observed by reversing
the order of addition of the sugar starting materials. Thus,
D-galactal first reacted with alkyne 5, followed by addition
of D-glucal. Scheme 4 shows two examples of unsymmetrical
D-Galactal and D-xylal were also employed in the C-
glycosidation using condition B to produce the diene
glycosides 14 and 15 steroselectively and in good yields.
The 2-acetoxy-D-glucal failed to afford the diene glycoside.
It was found that either the silylallene glycoside or the diene
glycoside could be accessed in excellent yield as the sole
product by using either BF3‚OEt2 or SnCl4 as the Lewis
acid.
Scheme 4. One-Pot Synthesis of Unsymmetrical Diene
Glycosides
The scope was further extended to unsymmetrical diene
glycosides by reaction of silylallene glycosides with different
glycals. Initially, D-galactal was employed to react with
silylallene glycoside 6 in the presence of SnCl4 to give the
unsymmetrical diene glycoside 16 in 30% yield in two steps
(Scheme 2). Alternatively, this reaction could be performed
Scheme 2. Two-Step Synthesis of Asymmetric Diene
Glycoside
diene glycosides that can be formed by this one pot reaction.
Interestingly, all of the unsymmetrical diene glycosides could
be produced in improved yields when the reaction was
performed first with the C-glycosidation of the faster-reacting
sugar followed by the slower one (using the results from
Table 1).
in one pot without isolation of the silylallene glycoside,
resulting in an increased yield of 37% (Scheme 3). The
The stereochemistry of the silylallene glycosides and diene
glycosides was supported by spectroscopic analyses. The
configurations at C1 of silylallene glycosides 6 and 8 were
both determined to be R on the basis of the observation of
NOESY cross-peaks between H5 and H2′ and the coupling
constants of H4 and H5 (Figure 1). Glycoside 10 is proposed
to have a 1,4-anti configuration5 based on the previous work
on C-glycosidation of D-xylal.6
Scheme 3. One-Pot Synthesis of 16 with Different Orders of
Addition
In diene glycosides 13 and 14, an additional cross-peak
was observed between H1 and H2′b. The 1,4-anti configu-
(4) Isobe, M.; Phoosaha, W.; Saeeng, R.; Kira, K.; Yenjai, C. Org. Lett.
2003, 5, 4883-4885.
(5) Miljkovic, M.; Yeagley, D.; Deslongchamp, P.; Dory, Y. L. J. Org.
Chem. 1997, 62, 7597-7604. For other examples of 4-substituted tetrahy-
dropyran acetals, see: Ayala, L.; Lucero, C. G.; Romero, J. C.; Tabacco, S.
A.; Woerpel, K. A. J. Org. Chem. 2003, 125, 15521-15528.
(6) Hosokawa, S.; Kirschbaum, B., Isobe, M. Tetrahedron Lett. 1998,
39, 1917-1920.
Org. Lett., Vol. 7, No. 8, 2005
1587

the xylyl-derived moiety is confirmed by the X-ray crystal-
lographic data of compounds 17 and 18.
In conclusion, we have established a synthesis of new
types of symmetric and unsymmetrical diene glycosides and
silylallene glycosides.
Acknowledgment. This research was financially
supported by a MEXT Grant-in-Aid for Specially Pro-
moted Research (16002007). Special thanks are due to
Dr. Kenji Yoza (Bruker AXS Co. Ltd.) for X-ray crystal-
lographic analysis, Dr. Toshio Nishikawa (Nagoya Uni-
versity) for helpful discussions, and Dr. Roderick W.
Bates (Exter University, UK) for correction of this manu-
script.
Supporting Information Available: Experimental pro-
cedures and full spectroscopic data for 6, 8, 10, and 13-18.
Details of the X-ray crystallographic analysis of 15, 17, and
18. This material is available free of charge via the Internet
at http://pubs.acs.org.
Figure 1. Stereochemistry of glycosides.
ration of 15 can be deduced from the X-ray structure shown
in the Supporting Information. The 1,4-anti configuration of
OL050265O
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Org. Lett., Vol. 7, No. 8, 2005