Selective formation of β-O-aryl glycosides in the absence of the C(2)-ester neighboring group

Article abstract of DOI:10.1021/jo9002807

(Chemical Equation Presented) The development of a general and practical method for the stereoselective synthesis of β-O-aryl glycosides that exploits the nature of a cationic palladium(II) catalyst, instead of a C(2)-ester directing group, to control the

Full text of DOI:10.1021/jo9002807

Selective Formation of ꢀ-O-Aryl Glycosides in the Absence of the
C(2)-Ester Neighboring Group
Matthew J. McKay, Benjamin D. Naab, Gregory J. Mercer, and Hien M. Nguyen*
Department of Chemistry and Biochemistry, Montana State UniVersity, Bozeman, Montana 59717
hmnguyen@chemistry.montana.edu
ReceiVed February 9, 2009
The development of a general and practical method for the stereoselective synthesis of ꢀ-O-aryl glycosides
that exploits the nature of a cationic palladium(II) catalyst, instead of a C(2)-ester directing group, to
control the ꢀ-selectivity is described. This ꢀ-glycosylation reaction is highly diastereoselective and requires
2-3 mol % of Pd(CH3CN)4(BF4)2 to activate glycosyl trichloroacetimidate donors at room temperature.
The current method has been applied to D-glucose, D-galactose, and D-xylose donors with a nondirecting
group incorporated at the C(2)-position to provide the O-aryl glycosides with good to excellent ꢀ-selectivity.
In addition, its application is widespread to electron-donating, electron-withdrawing, and hindered phenols.
The reaction is likely to proceed through a seven-membered ring intermediate, wherein the palladium
catalyst coordinates to both C(1)-trichloroacetimidate nitrogen and C(2)-oxygen of the donor, blocking
the R-face. As a result, the phenol nucleophile preferentially approaches to the top face of the activated
donor, leading to formation of the ꢀ-O-aryl glycoside.
Introduction
aryl glycosides with lower yields than trichloroacetimidates due
to anomerization of both the glycosyl donor and the coupling
product.2 For instance, ꢀ-D-glucose pentaacetate undergoes
anomerization to the corresponding R-D-glucose pentaacetate
in the presence of 3 equiv of BF3 ·OEt2.5 High temperature and
long reaction time also facilitate anomerization to give the
thermodynamic R-coupling product.6 The resulting R-O-aryl
glycosides are, however, often obtained in low yields due to
the formation of the undesired C-aryl glycosides. On the other
hand, glycosyl halides are strongly preferred for electron-
withdrawing phenols.2 In general, the ꢀ-O-aryl glycosides can
be formed in the glycosylation reaction by employing ester
functionalities as the directing group at the C(2)-position of
glycosyl donors.7 This approach, however, is not without its
limitations. In some cases, formation of ortho ester side
products8 and migration of the C(2)-acyl functionality9 are also
observed in the reaction.
The stereoselective synthesis of O-aryl glycosides has recently
received considerable attention because these compounds are
known to exhibit antitumor, anti-HIV, and antibiotic activities.1
The synthesis of O-aryl glycosides, however, can be difficult
to achieve due to the electron-withdrawing properties of
aromatic rings2 and the facile rearrangement of the resulting
O-aryl glycosides to their corresponding C-aryl glycosides.3
Additionally, steric hindrance from substituents on phenolic
compounds makes them unreactive in many glycosylation
methods.4 Glycosyl acetates, halides, and trichloroacetimidates
have been used as donors in the formation of ꢀ-O-aryl
glycosides.2 These glycosyl donors, however, only work well
with specific phenol nucleophiles. For instance, glycosyl acetates
and trichloroacetimidates are preferred for electron-donating
phenol substrates. Glycosyl acetates usually provide the ꢀ-O-
(1) Bililign, T.; Griffith, B. R.; Thorson, J. S. Nat. Prod.Prep. 2005, 22, 475–
516.
(2) Jacobsson, M.; Malmberg, J.; Ellervik, U. Carbohydr. Res. 2006, 341,
1266–1281.
(5) Ellervik, U.; Jansson, K.; Magnusson, G. J. Carbohydr. Chem. 1998,
17, 777–784.
(6) Sokolov, V. M.; Zakharov, V. I.; Studentsov, E. P. Russ J. Gen. Chem.
2002, 72, 806–811.
(3) Mahling, J.-A.; Schmidt, R. R. Synthesis 1993, 325–328.
(4) (a) Ogawa, T.; Matsui, M. Carbohydr. Res. 1976, 51, C13-C18. (b)
Clerici, F.; Gelmi, M. L.; Mottadelli, S. J. Chem. Soc., Perkin Trans.1 1994,
985–988. (c) Mukaiyama, T.; Katsurada, M.; Iida, Y. Chem. Lett. 1992, 2105–
2108. (d) Kroger, L.; Thiem, J. J. Carbohydr. Chem. 2003, 22, 9–23.
(7) (a) Nukada, T.; Berces, A.; Zgierski, M. Z.; Whitfield, D. M. J. Am.
Chem. Soc. 1998, 120, 13291–13295. (b) Barresi, F.; Hindsgaul, O. J. Carbohydr.
Chem. 1995, 14, 1043. (c) Schmidt, R. R.; Kinzy, W. AdV. Carbohydr. Chem.
Biochem. 1994, 50, 21–123. (d) Schmidt, R. R.; Michel, J. Angew. Chem., Int.
Ed. 1980, 19, 731–732.
10.1021/jo9002807 CCC: $40.75  2009 American Chemical Society
Published on Web 06/01/2009
J. Org. Chem. 2009, 74, 4705–4711 4705

McKay et al.
FIGURE 1. Cationic Pd(II)-catalyzed ꢀ-selective glycosylation.
TABLE 1. Stereoselective Formation of ꢀ-O-Aryl Glycoside 5a
We report herein a new method for the stereoselective
synthesis of ꢀ-O-aryl glycosides in the absence of the C(2)-
ester directing group. This approach relies only on the nature
of the cationic palladium catalyst, Pd(CH3CN)4(BF4)2, to control
the ꢀ-selectivity at the newly formed glycosidic bond. The
current method has been applied to a number of glycosyl
trichloroacetimidate donors with a nondirecting group incor-
porated at the C(2)-position as well as electron-donating,
electron-withdrawing, and hindered phenols to provide access
to a variety of ꢀ-O-aryl glycosides. In general, the coupling
proceeds under mild conditions with 2-3 mol % of
Pd(CH3CN)4(BF4)2 at room temperature. In all cases, the
undesired C-aryl glycosides are not observed in the reaction.
Pd(II)
loading
T
time yield
entry
sources
(mol %) (°C)
(h)
(%)
ꢀ:R
1
2
3
4
5
6
Pd(PhCN)2(OTf)2
Pd(PhCN)2(OTf)2
Pd(PhCN)2(OTf)2
Pd(CH3CN)4(BF4)2
AgOTf
2
2
2
2
4
4
-78
0
25
25
25
25
6
3
1
2
12
6
60
76
75
80
68
66
2:1
1:1
1:1
11:1
1:1
BF3 ·OEt2
3:1
a All reactions were performed in CH2Cl2 (0.2 M) with 2-4 mol % of
c
the catalyst. b Isolated yield. 1H NMR ratio.
Results and Discussion
We have recently reported a cationic palladium(II)-directed
ꢀ-selective glycosylation in the absence of the traditional C(2)-
ester neighboring group effect.10 This method relies on the
ability of the palladium(II) catalyst, Pd(PhCN)2(OTf)2 or
Pd(CH3CN)4(BF4)2, to direct ꢀ-selectivity. This reaction has been
applied to a variety of primary, secondary, and tertiary aliphatic
alcohols to provide the desired products with excellent ꢀ-se-
lectivity. Mechanistic studies suggest that the cationic palla-
dium(II) catalyst reversibly coordinates to both the C(1)-
trichloroacetimidate nitrogen and the C(2)-ether oxygen of the
glycosyl donor 1 to form a seven-membered ring intermediate
2 (Figure 1). Formation of this seven-membered ring species
blocks the R-face. As a result, the oxygen nucleophile prefer-
entially approaches to the top face of the activated donor, leading
to the formation of ꢀ-O-glycoside 3.
With the success of these glycosylation processes, we seek to
further explore the scope of this reaction with phenol nucleophiles
to form ꢀ-O-aryl glycosides. Our main concern in this investigation
is the ability of the cationic palladium(II) catalyst to promote the
rearrangement of the resulting O-aryl-glycosides to the correspond-
ing C-aryl glycosides at high temperature. Thus, we initially
explored the feasibility of this concept with Pd(PhCN)2(OTf)2,
which is more reactive than Pd(CH3CN)4(BF4)2.10b Treatment of
both D-glucose trichloroacetimidate donor 111 and 2-naphthol (4)
with 2 mol % of Pd(PhCN)2(OTf)2, generated in situ from AgOTf
and Pd(PhCN)2Cl2 at -78 °C, provided the desired O-aryl
glycoside 5 as a 2:1 mixture of R- and ꢀ-isomers (Table 1, entry
1). However, it took 6 h for the reaction to go to completion at
-78 °C. Raising the temperature shortened the reaction time
(entries 2 and 3). Since the C-aryl glycoside was not observed in
the coupling reaction with Pd(PhCN)2(OTf)2 at high temperature,
we decided to explore with Pd(CH3CN)4(BF4)2. To our delight,
exposure of both 1 and 4 to 2 mol % of Pd(CH3CN)4(BF4)2 at 25
°C afforded the desired O-aryl glycoside 5 in 80% yield with
excellent ꢀ-selectivity (ꢀ:R ) 11:1) (entry 4). The significant
increase in ꢀ-selectivity with use of Pd(CH3CN)4(BF4)2 suggests
that these two cationic palladium catalysts operate through different
mechanisms. Since Pd(PhCN)2(OTf)2 is more reactive than Pd-
(CH3CN)4(BF4)2, it promotes ionization of trichloroacetimidate
donor 1 to form an oxocarbenium intermediate; therefore, a mixture
of R- and ꢀ-isomers 5 was observed in the reaction. On the other
hand, Pd(CH3CN)4(BF4)2 promotes a seven-membered ring inter-
mediate (Scheme 1), wherein 2-naphthol (4) preferentially ap-
proaches the ꢀ-face of the activated donor, leading to the formation
of ꢀ-O-aryl glycoside 5. Compared to other activating reagents,
Pd(CH3CN)4(BF4)2 is more ꢀ-selective. Additionally, lower catalyst
loading and shorter reaction time were observed with use of this
cationic palladium as the activator. For example, when 4 mol %
of AgOTf was employed as the activator in the coupling process,
it took 12 h for the reaction to go to completion (entry 5). The
desired O-aryl glycoside 5 was isolated in 68% yield as a mixture
of R- and ꢀ-isomers. Employing BF3 ·OEt2 as the activating reagent
yielded 5 in 66% yield with R:ꢀ ) 3:1 (entry 6). It has also been
reported that glycosylation of 2-naphthol (4) with tetrabenzylated-
D-glucopyranose in the presence of dicylohexylcarbodiimide
(1 equiv.) and CuCl (2 mol %) at 80 °C provided the coupling
product 5 as 2.4:1 mixture of ꢀ- and R-isomers.12
With the optimal conditions at hands, we set out to define
the scope of the phenol nucleophiles with this D-glucose
trichloroacetimidate donor 1 (Table 2). The cationic pal-
ladium-catalyzed ꢀ-selective glycosylation reaction is effec-
tive for a variety of electron-rich and electron-withdrawing
phenols, and the desired O-aryl glycoconjugates 12-15 were
isolated in good yields and ꢀ-selectivity (entries 1-4).13
Likewise, tyrosine amino acid 10 was able to couple with
trichloroacetimidate donor 1 to provide the O-aryl glyco-
peptide 16 in excellent yield and good ꢀ-diastereoselectivity
(8) (a) Seeberger, P. H.; Eckhardt, M.; Gutteridge, C. E.; Danishefsky, S. J.
J. Am. Chem. Soc. 1997, 119, 10064–10072. (b) Crich, D.; Dai, Z.; Gastaldi, S.
J. Org. Chem. 1999, 64, 5224–5229.
(9) Yu, H.; Ensley, H. E. Tetrahedron Lett. 2003, 4, 9363–9366.
(10) (a) Yang, J.; Cooper-Vanosdell, C.; Mensah, E. A.; Nguyen, H. M. J.
Org. Chem. 2008, 73, 794–800. (b) Mensah, E. A.; Azzarelli, J. M.; Nguyen,
H. M. J. Org. Chem. 2009, 74, 1650–1657.
(11) (a) Zhang, J.; Yergey, A.; Kowalak, J.; Kovac, P. Tetrahedron 1998,
54, 11783–11792. (b) Nakanishi, N.; Nagafuchi, Y.; Koizumi, K. J. Carbohydr.
Chem. 1994, 13, 981–990. (c) Rathore, H.; Hashimoto, T.; Igarashi, K.; Nukaya,
H.; Fullerton, D. Tetrahedron 1985, 41, 5427–5438.
(12) Tsutsumi, H.; Ishido, Y. Carbohydr. Res. 1981, 88, 61–75.
4706 J. Org. Chem. Vol. 74, No. 13, 2009

Formation of ꢀ-O-Aryl Glycosides
TABLE 2. Coupling of Phenol Nucleophiles with Glucose Donora
TABLE 3. Coupling of Phenol Nucleophiles with Galactose
Donora
a All reactions were carried out in CH2Cl2 with
2 mol % of
c
Pd(CH3CN)4(BF4)2 at 25 °C. b Isolated yield. 1H NMR ratio.
a All reactions were carried out in CH2Cl2 with
2 mol % of
c
Pd(CH3CN)4(BF4)2 at 25 °C. b Isolated yield. 1H NMR ratio.
(entry 5). While other glycosylation methods slightly favor
R-selectivity,14 this palladium-catalyzed glycosylation reac-
tion is ꢀ-selective. For example, glycosylation of 2-meth-
ylphenol (6) with tetrabenzylated D-glucose in the presence
of p-nitrobenzenesulfonyl chloride (1.1 equiv) and AgOTf
(1.1 equiv) at 25 °C gave O-aryl glycoside 12 in 65% yield
little effect on the outcome of the stereoselectivity at the newly
formed glycosidic bond.
Similarly, tetrabenzyl D-galactose trichloroacetimidate sub-
strate was found to be a viable donor (Table 3). It was able to
couple to a variety of phenol nucleophiles to provide the desired
O-aryl galactosides 19-23 in good yields and ꢀ-selectivity
(entries 1-5). Notably, the efficiency of this palladium meth-
odology is demonstrated by its ability to direct the relatively
hindered 2-methylphenol (6) to the top face of tetrabenzyl-D-
galactose trichloroacetimidate donor to exclusively form ꢀ-O-
aryl galactoside 19 in 73% yield (entry 1). The current method
was further explored with D-galactose donor incorporated with
the benzoyl group at the C(4)- and C(6)-positions, even though
participation of the axial C(4)-ester group to an activated
with R:ꢀ ) 3:1.14 Under our conditions, coupling of 6 with
a
tetrabenzylated D-glucose trichloroacetimidate 1 provided 12
in 75% yield with R:ꢀ ) 1:11 (Table 2, entry 1). It has been
reported that coupling of 1-naphthol nucleophile (8) with
dimethylphosphinothioate donor using AgClO4 (1 equiv) as
the activating reagent provided 14 in 65% yield as a 3:1
mixture of R- and ꢀ-isomers.14 On the other hand, our
b
method provided 14 in 87% yield with 7:1 ꢀ-selectivity
(entry 3).
Our next step was to determine whether the electron-
withdrawing protecting groups on the D-glucose donor would
affect the ꢀ-selectivity. Accordingly, D-glucose donor 11 with
the benzoyl group incorporated at the C(4)- and C(6)-positions
was examined with phenol nucleophiles 4 and 6 (Table 2, entries
6 and 7). The desired O-aryl glucosides 17 and 18 were obtained
in good yields and diasteroselectivity. These results suggest that
the nature of the protecting group on the D-glucose donors has
(13) These compounds were relatively stable on silica gel flash chromatog-
raphy. Since we were not able to separate the major ꢀ-isomer from the minor
a-isomer for spectral analysis, the products were subjected to preparative TLC.
We found, however, that these O-aryl glycosides slowly decomposed on
preparative TLC, particularly with compounds 5, 14, and 15. As a result, it is
difficult to get clean 1H and 13C NMR spectra for these molecules.
(14) (a) Koto, S.; Morishima, N.; Araki, M.; Tsuchiya, T. Bull. Chem. Soc.
Jpn. 1981, 54, 1895–1896. (b) Yamanoi, T.; Fujioka, A.; Inazu, T. Bull. Chem.
Soc. Jpn. 1994, 67, 1488–1491.
J. Org. Chem. Vol. 74, No. 13, 2009 4707

McKay et al.
TABLE 4. Coupling of Phenol Nucleophiles with Xylose Donora
TABLE 5. Selective Glycosylation of Hindered Phenol
Nucleophilesa
a All reactions were carried out in CH2Cl2 with
2 mol % of
a The glycosylations were performed with
2
mol
%
of
c
Pd(CH3CN)4(BF4)2 at 25 °C. b Isolated yield. 1HNMR ratio.
Pd(CH3CN)4(BF4)2. b The reactions were performed with 3 mol % of
d
Pd(CH3CN)4(BF4)2. c Isolated yield. 1H NMR ratio.
anomeric center has previously been invoked.15 When 2-me-
thylphenol (6) was employed as the nucleophilic acceptor (entry
6), O-aryl galactoside 24 was isolated in 87% yield and good
ꢀ-selectivity (ꢀ:R ) 7:1). Use of 2-naphthol gave exclusively
ꢀ-isomer 25 in 78% yield (entry 7).
Encouraged by the results obtained with both D-glucose and
D-galactose donors, we decided to expand the scope of this
reaction with tribenzyl D-xylose trichloroacetimidate 26 (Table
4). Since this xylose donor lacks the C(6)-methoxyl functional-
ity, its ꢀ-face is likely to be less sterically hindered than that of
D-glucose and D-galactose donors. Thus, the coupling products
are expected to form with higher ꢀ-selectivity than those
obtained from D-glucose and D-galactose donors. Accordingly,
D-xylose donor 26 was coupled to an array of electron-rich and
electron-poor phenolic compounds to provide the corresponding
O-aryl glycosides 28-32 in good yields and almost exclusively
as ꢀ-isomers (Table 4).
dimethylphenol (33) with tetrabenzyl D-glucose thioglycoside
donor afforded the coupling product 35 in excellent yield (93%),
albeit in low selectivity (R:ꢀ ) 2.6:1).15 With the sulfoxide
b
method, the O-aryl glucoside 35 was obtained in 70% yield as
a 2:1 mixture of R- and ꢀ-isomers.15a Similar result was obtained
with use of tetrabenzylated D-galactose trichloroacetimidate
donor (entry 2). Interestingly, coupling of tribenzyl D-xylose
donor 26 with 2,6-dimethylphenol (33) only yielded the
ꢀ-isomer 37 (entry 3). Encouraged by these results, we explored
the generality and applicability of this cationic palladium method
with 2,6-dichlorophenol (34). Gratifyingly, it was found that
this phenol acceptor was able to couple with D-glucose donor 1
and D-xylose donor 26 to provide the corresponding O-aryl
glycosides 38 and 39 in moderate to good yield with good
ꢀ-selectivity (entries 4 and 5).
The cationic palladium-catalyzed glycosylation protocol is
not limited to unhindered electron-donating and electron-
withdrawing phenol nucleophiles. Table 5 sets out several
examples of selective formation of ꢀ-O-aryl glycosides using
sterically hindered phenols 33 and 34. These phenol acceptors
have been chosen for ease of comparison of this method with
the existing glycosylation procedures in terms of yields and
anomeric selectivity.16 In these reactions, 2-3 mol % of
Pd(CH3CN)4(BF4)2 is required for the reaction to go to comple-
tion. Accordingly, coupling of 2,6-dimethylphenol (33) with
tetrabenzyl D-glucose trichloroacetimidate donor 1 provided the
desired O-aryl glucoside 35 in 75% yield with ꢀ:R ) 10:1 (Table
5, entry 1). It has been reported that coupling of 2,6-
Conclusion
In summary, we have developed an efficient method for the
stereoselective synthesis of ꢀ-O-aryl glycosides in the absence
of the traditional ester directing group at the C(2)-position of
D-glucose, D-galactose, and D-xylose donors. Advantages of the
cationic palladium method include its operational simplicity,
using a catalytic amount of commercially available cationic
palladium, Pd(CH3CN)4(BF4)2, as the activating reagent at
ambient temperature, the applicability to a broader scope of
phenol nucleophiles, and the high ꢀ-selectivity without the need
of using the anchimeric assistance. In all cases, the facile
(16) (a) Kahne, D.; Walker, S.; Cheng, Y.; Van Engen, D. J. Am. Chem.
Soc. 1989, 111, 6881–6882. (b) Crich, D.; Sun, S. J. Am. Chem. Soc. 1998, 120,
435–436.
(15) Zinner, H.; Thielebeule, W. Chem. Ber. 1960, 93, 2791–2803.
4708 J. Org. Chem. Vol. 74, No. 13, 2009

Formation of ꢀ-O-Aryl Glycosides
138.6, 138.1, 138.0, 134.6, 128.5, 128.4, 128.3, 128.1, 127.9, 127.8,
127.6, 126.4, 125.9, 125.6, 122.4, 122.1, 109.6, 101.5, 84.9, 82.3,
77.8, 75.9, 75.2, 75.1, 73.6, 73.1, 68.8. IR (film, cm-1): ν 3062,
3030, 2905, 2865, 1596, 1578, 1462, 1454, 1395, 1361, 1263, 1239,
1085, 1071, 1027, 772, 735, 697. HRMS (ESI): calcd for
C44H42O6Na (M + Na) 689.2879, found 689.2861.
rearrangement of the resulting ꢀ-O-aryl glycosides to the
corresponding C-aryl glycosides is not observed in the coupling,
a drawback of other methodologies when the reactions were
performed at high temperature. The current method is likely to
operate through a seven-membered ring intermediate, wherein
Pd(CH3CN)4(BF4)2 coordinates to both the C(1)-trichloroace-
timidate nitrogen and the C(2)-oxygen of glycosyl donors.
Formation of this seven-membered ring intermediate blocks the
bottom of the activated glycosyl donor. As a result, the phenol
nucleophiles preferentially approach to the top face, leading to
formation of the ꢀ-O-aryl glycosides.
Compound 15. 1H NMR (CDCl3, 500 MHz): δ ) 8.29 (d, J )
8.4 Hz, 1H), 8.21 (d, J ) 8.4 Hz, 1H), 7.60 (t, J ) 7.5 Hz, 1H),
7.48 (t, J ) 7.5 Hz, 1H), 7.40 (d, J ) 8 Hz, 1H), 7.35-7.17 (m,
20H), 7.05 (d, J ) 8.8 Hz, 1H), 5.16 (d, J ) 7.7 Hz, 1H), 5.11 (d,
J ) 10.6 Hz, 1H), 4.96 (d, J ) 10.8 Hz, 1H), 4.92 (d, J ) 10.6
Hz, 1H), 4.85 (d, J ) 10.9 Hz, 2H), 4.62 (t, J ) 12.1 Hz, 2H),
4.49 (d, J ) 11.8 Hz, 1H), 3.93 (t, J ) 8.4 Hz, 1H), 3.79-3.68
(m, 3H), 3.67-3.63 (m, 2H). 13C NMR (CDCl3, 125 MHz): δ )
137.9, 131.4, 128.4, 128.0, 127.9, 127.84, 127.8, 127.72, 127.7,
127.6, 127.5, 127.4, 126.3, 125.8, 124.3, 122.5, 109.7, 101.5, 84.8,
82.1, 77.7, 75.8, 75.4, 75.2, 75.1, 73.5, 66.2. IR (film, cm-1): ν
2912, 2870, 1592, 1455, 1376, 1260, 1239, 1072, 751, 696. HRMS
(ESI): calcd for C44H41ClO6Na (M + Na) 723.2489, found
723.2489.
Experimental Section
General Glycosylation Procedure with Pd(CH3CN)4(BF4)2:
Preparation of Compound 5. A 10 mL Schlenk flask was charged
with 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl trichloroacetimidate
1 (158 mg, 0.23 mmol, 1 equiv), 2-naphthol (4) (35 mg, 0.24 mmol,
1.04 equiv), and CH2Cl2 (1.1 mL). Pd(CH3CN)4(BF4)2 (2 mg,
0.0046 mmol, 2 mol %) was then added to the solution. The
resulting mixture was stirred under argon at 25 °C for 2 h, diluted
with benzene (2 mL), and purified by silica gel flash chromatog-
raphy (6/1, hexane/ethyl acetate) to give the desired O-aryl glycoside
5 (123 mg, 80%). Rf ) 0.40 (hexanes/ethyl acetate, 4/1). 1H NMR
(CDCl3, 500 MHz): δ ) 7.79-7.77 (m, 2H), 7.64 (d, J ) 8.0 Hz,
1H), 7.43-7.19 (m, 24H), 5.15 (d, J ) 7.5 Hz, 1H), 5.09 (d, J )
11 Hz, 1H), 4.96 (d, J ) 11 Hz, 1H), 4.87 (d, J ) 11 Hz, 1H),
4.86 (d, J ) 12 Hz, 1H), 4.83 (d, J ) 11.5 Hz, 1H), 4.60 (d, J )
12 Hz, 1H), 4.58 (d, J ) 11 Hz, 1H), 4.53 (d, J ) 12 Hz, 1H),
3.84-3.76 (m, 3H), 3.72-3.70 (m, 3H). 13C NMR (CDCl3, 125
MHz): δ ) 155.2, 138.5, 138.1, 138.0, 134.4, 129.9, 129.5, 128.4,
128.3, 128.2, 128.0, 127.9, 127.8, 127.78, 127.7, 127.6, 127.3,
126.4, 124.3, 119.1, 111.5, 101.8, 84.8, 82.1, 77.8, 75.8, 75.3, 75.1,
73.6, 69.0. IR (film, cm-1): ν ) 2919, 2862, 1465, 1453, 1359,
1310, 1252, 1214, 1070, 1027, 734, 697, 659. HRMS (ESI): calcd
for C44H42O6Na (M + Na) 689.2879, found 689.2860.
Compound 16. 1H NMR (CDCl3, 500 MHz): δ ) 7.72 (d, J )
7.2 Hz, 2H), 7.49 (t, J ) 7.3 Hz, 1H), 7.41 (t, J ) 7.5 Hz, 2H),
7.32-7.14 (m, 20H), 7.03 (d, J ) 8.5 Hz, 1H), 6.96 (d, J ) 8.5
Hz, 1H), 6.57 (d, J ) 7.5 Hz, 1H), 5.02 (d, J ) 12 Hz, 1H), 4.95
(d, J ) 7.2 Hz, 1H), 4.92 (d, J ) 10.9 Hz, 1H), 4.85-4.77 (m,
3H), 4.56 (d, J ) 17 Hz, 1H), 4.51 (d, J ) 9.4 Hz, 1H), 4.47 (d,
J ) 10.9 Hz, 1H), 4.19-4.14 (m, 2H), 3.80-3.66 (m, 4H),
3.58-3.56 (m, 1H), 3.25-3.18 (m, 2H), 1.26 (t, J ) 7.1 Hz, 3H).
13C NMR (CDCl3, 125 MHz): δ ) 171.7, 166.8, 156.5, 138.4,
138.1, 138.0, 137.9, 133.8, 131.8, 130.5, 129.7, 128.4, 128.3, 128.2,
128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.0, 116.9, 101.6, 84.6,
81.9, 77.6, 75.8, 75.1, 73.4, 68.7, 61.7, 53.6, 37.1, 14.2. IR (film,
cm-1): ν 3347, 3063, 3029, 2911, 2867, 1730, 1649, 1509, 1453,
1353, 1231, 1070, 1027, 824, 737, 697. HRMS (ESI): calcd for
C52H53NO9Na (M + Na) 858.3618, found 858.3605.
1
Compound 17. H NMR (CDCl3, 500 MHz): δ ) 8.00-7.92
(m, 4H), 7.58-7.51 (m, 2H), 7.31-7.27 (m, 12H), 7.13-7.07 (m,
6H), 5.50 (t, J ) 10 Hz, 1H), 5.32 (d, J ) 10 Hz, 1H), 4.84 (d, J
) 10 Hz, 1H), 4.75 (d, J ) 10 Hz, 1H), 4.71 (d, J ) 10 Hz, 1H),
4.61 (d, J ) 10 Hz, 1H), 4.57 (dd, J ) 15, 5 Hz, 1H), 4.36 (dd, J
) 10, 5 Hz, 1H), 4.02 (dt, J ) 10, 5 Hz, 1H), 3.82 (t, J ) 10 Hz,
1H), 3.76-3.71 (m, 1H), 2.19 (s, 3H). 13C NMR (CDCl3, 125 MHz):
δ ) 166.2, 165.1, 137.4, 137.3, 133.4, 133.1, 129.9, 129.8, 129.7,
129.5, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 110.3, 108.5,
81.2, 81.1, 74.9, 74.5, 72.1, 69.8, 63.0, 16.7. IR (film, cm-1): ν
3708, 3582, 2920, 1724, 1452, 1270, 1106, 1067, 1026, 911, 751,
708. HRMS (ESI): calcd for C41H42NO8 (M + NH4) 676.2095,
found 676.2907.
Compound 12. Rf ) 0.44 (hexanes/ethyl acetate, 4/1). 1H NMR
(CDCl3, 500 MHz): δ ) 7.32-7.25 (m, 18H), 7.19-7.11 (m, 4H),
7.05 (d, J ) 8 Hz, 1H), 6.95 (t, J ) 7 Hz, 1H), 5.07 (d, J ) 11 Hz,
2H), 5.02 (d, J ) 7 Hz, 1H), 4.94 (d, J ) 11 Hz, 1H), 4.86-4.82
(m, 3H), 4.58 (d, J ) 12 Hz, 1H), 4.57 (d, J ) 11 Hz, 1H), 4.52
(d, J ) 12 Hz, 1H), 3.81-3.74 (m, 3H), 3.72-3.67 (m, 2H), 3.61
(dd, J ) 9.5, 4.5 Hz, 1H), 2.30 (s, 3H). 13C NMR (CDCl3, 125
MHz): δ ) 138.3, 130.9, 128.4, 128.3, 128.0, 127.8, 127.7, 127.0,
122.3, 114.9, 101.3, 84.9, 82.2, 77.8, 77.2, 75.8, 75.2, 73.5, 68.9,
16.7. IR (film, cm-1): ν 2916, 2862, 1493, 1454, 1359, 1237, 1069,
1027, 750, 735, 696. HRMS (ESI): calcd for C41H42O6Na (M +
Na) 653.2879, found 653.2862.
Compound 18. 1H NMR (CDCl3, 500 MHz): δ ) 7.98 (d, J )
10 Hz, 4H), 7.79-7.71 (m, 3H), 7.56 (t, J ) 10 Hz, 11H), 7.54 (t,
J ) 10 Hz, 1H), 7.49-7.26 (m, 12H), 7.20-7.07 (m, 6H), 5.47 (t,
J ) 10 Hz, 1H), 5.27 (d, J ) 10.0 Hz, 1H), 5.12 (d, J ) 15 Hz,
1H), 4.91 (d, J ) 10 Hz, 1H), 4.84 (d, J ) 10 Hz, 1H), 4.68 (d, J
) 10 Hz, 1H), 4.64 (dd, J ) 15, 5 Hz, 1H), 4.41 (dd, J ) 15, 10
Compound 13. 1H NMR (CDCl3, 500 MHz): δ ) 7.35 (d, J )
8.5 Hz, 2H), 7.33-7.25 (m, 18H), 7.16 (d, J ) 5.5 Hz, 1H), 6.92
(d, J ) 8.5 Hz, 1H), 4.97 (d, J ) 10.8 Hz, 1H), 4.95-4.90 (m,
2H), 4.83-4.78 (m, 3H), 4.55 (t, J ) 12.4 Hz, 2H), 4.49 (d, J )
12 Hz, 1H), 3.77-3.70 (m, 3H), 3.66-3.63 (m, 2H), 3.61-3.58
(m, 1H). 13C NMR (CDCl3, 125 MHz): δ ) 132.4, 128.43, 128.4,
128.36, 128.2, 128.0, 127.9, 127.8, 127.71, 127.7, 118.7, 101.6,
84.6, 81.9, 77.6, 75.8, 75.14, 75.11, 75.1, 73.5, 68.7. IR (film, cm-1):
ν 3030, 2913, 2867, 2454, 1453, 1233, 1064, 1002, 824, 747.
HRMS (ESI): calcd for C40H39Br O6Na (M + Na) 717.1828, found
717.1840.
Hz, 1H), 4.02 (dt, J ) 10.0, 5.0 Hz, 1H), 3.99-3.93 (m, 2H). 13
C
NMR (CDCl3, 125 MHz): δ ) 166.2, 165.4, 134.1, 130.5, 130.3,
130.2, 129.1, 128.7, 127.8, 127.7, 123.8, 119.4, 118.2, 111.7, 110.4,
102.3, 81.8, 81.2, 76.4, 75.3, 71.8, 71.7, 70.3. IR (film, cm-1): ν
3429, 3062, 3031, 2953, 2905, 2875, 1752, 1630, 1600, 1510, 1452,
1269, 1215, 1094, 1067, 1026, 909, 735, 711. HRMS (ESI): calcd
for C44H38O8Na (M + Na) 717.2459, found 717.2428.
Compound 14. 1H NMR (CDCl3, 500 MHz): δ ) 8.28 (d, J )
8.4 Hz, 1H), 7.81 (d, J ) 7.8 Hz, 1H), 7.53 (d, J ) 8.2 Hz, 1H),
7.46 (t, J ) 8.2 Hz, 1H), 7.41 (t, J ) 6.9 Hz, 1H), 7.36-7.23 (m,
19H), 7.19 (d, J ) 7.6 Hz, 1H), 7.12 (d, J ) 7.6 Hz, 1H), 5.21 (d,
J ) 7.7 Hz, 1H), 5.16 (d, J ) 10.6 Hz, 1H), 4.96 (d, J ) 10.8 Hz,
1H), 4.92 (d, J ) 10.7 Hz, 1H), 4.85 (dd, J ) 10.7, 3.6 Hz, 2H),
4.58 (d, J ) 10.8 Hz, 2H), 4.56 (d, J ) 12 Hz, 1H), 4.50 (d, J )
12.1 Hz, 1H), 3.94 (t, J ) 8.6 Hz, 1H), 3.80 (dd, J ) 17.6, 8.7 Hz,
2H), 3.74-3.66 (m, 3H). 13C NMR (CDCl3, 125 MHz): δ ) 153.0,
1
Compound 19. H NMR (CDCl3, 500 MHz): δ ) 7.39-7.27
(m, 20H), 7.14 (d, J ) 7 Hz, 1H), 7.10 (d, J ) 8.5 Hz, 1H), 7.05
(d, J ) 7.5 Hz, 1H), 6.93 (d, J ) 7 Hz, 1H), 5.04 (d, J ) 11 Hz,
1H), 5.01 (d, J ) 5.5 Hz, 1H), 4.99 (d, J ) 9 Hz, 1H), 4.90 (d, J
) 10.5 Hz, 1H), 4.79 (d, J ) 11.5 Hz, 1H), 4.76 (d, J ) 11.5 Hz,
1H), 4.67 (d, J ) 11.5 Hz, 1H), 4.47 (d, J ) 12 Hz, 1H), 4.41 (d,
J ) 11.5 Hz, 1H), 4.17 (dd, J ) 9.5, 8 Hz, 1H), 3.97 (d, J ) 3 Hz,
1H), 3.71 (t, J ) 6.5 Hz, 1H), 3.67-3.62 (m, 3H), 3.72-3.67 (m,
J. Org. Chem. Vol. 74, No. 13, 2009 4709

McKay et al.
2H), 3.61 (dd, J ) 9.5, 4.5 Hz, 1H), 3.59 (s, 3H). 13C NMR (CDCl3,
125 MHz): δ ) 155.5, 138.5, 138.4, 130.7, 128.4, 128.3, 128.2,
128.0, 127.8, 127.7, 127.6, 127.5, 127.3, 126.7, 121.9, 114.5, 101.3,
82.3, 79.2, 75.5, 74.5, 73.8, 73.6, 73.4, 73.1, 68.9, 16.6. IR (film,
cm-1): ν 2920, 2856, 1494, 1454, 1238, 1102, 1069, 752, 696.
HRMS (ESI): calcd for C41H42O6Na (M + Na) 653.2879, found
653.2853.
133.5, 133.3, 131.0, 130.1, 129.8, 128.3, 128.1, 127.7, 126.9, 114.8,
101.5, 79.4, 78.6, 75.7, 72.3, 71.4, 67.4, 62.9, 16.6. IR (film, cm-1):
ν 3063, 3031, 2953, 2915, 2871, 1724, 1601, 1493, 1452, 1314,
1271, 1108, 1069, 1026, 910, 735, 711. HRMS (ESI): calcd for
C41H38O8Na (M + Na) 681.2459, found 681.2479.
Compound 25. 1H NMR (CDCl3, 500 MHz): δ ) 8.15 (d, J )
10 Hz, 2H), 8.04 (d, J ) 10 Hz, 2H), 7.77-7.71 (m, 2H), 7.62-7.55
(m, 2H), 7.50-7.23 (m, 19H), 5.90 (d, J ) 5 Hz, 1H), 5.21 (d, J
) 10 Hz, 1H), 5.02 (d, J ) 15 Hz, 1H), 4.86 (d, J ) 15 Hz, 2H),
4.62 (d, J ) 15 Hz, 1H), 4.55-4.49 (m, 2H), 4.24 (t, J ) 15 Hz,
1H), 4.09 (t, J ) 15, 1H), 3.82 (dd, J ) 15, 5 Hz, 1H). 13C NMR
(CDCl3, 125 MHz): δ ) 166.2, 165.8, 155.4, 137.7, 134.2, 133.3,
133.2, 130.1, 129.8, 129.5, 129.4, 127.6, 127.1, 126.4, 124.4, 119.1,
111.2, 101.9, 79.2, 78.6, 75.7, 72.3, 71.7, 67.3, 63.2. IR (film, cm-1):
ν 3062, 3031, 2952, 2913, 2871, 1723, 1719, 1630, 1600, 1452,
1270, 1267, 1215, 1105, 1069, 1026, 910, 732, 711. HRMS (ESI):
calcd for C44H38O8Na (M + Na) 717.2459, found 717.2492.
1
Compound 20. H NMR (CDCl3, 500 MHz): δ ) 7.39-7.15
(m, 22H), 6.92 (d, J ) 9 Hz, 2H), 4.96 (t, J ) 11.5 Hz, 2H), 4.91
(d, J ) 7.5 Hz, 1H), 4.84 (d, J ) 10.5 Hz, 1H), 4.77 (d, J ) 11.5
Hz, 1H), 4.74 (d, J ) 12 Hz, 1H), 4.64 (d, J ) 11.5 Hz, 1H), 4.46
(d, J ) 11.5 Hz, 1H), 4.39 (d, J ) 11.5 Hz, 1H), 4.09 (dd, J ) 10,
8 Hz, 1H), 3.93 (d, J ) 2.5 Hz, 1H), 3.64 (dd, J ) 12.5, 6 Hz,
1H), 3.62-3.55 (m, 3H). 13C NMR (CDCl3, 125 MHz): δ ) 156.5,
138.4, 138.3, 138.2, 137.8, 132.3, 128.5, 128.4, 128.3, 128.2, 127.9,
127.71, 127.7, 127.6, 118.7, 114.8, 101.8, 82.1, 79.1, 75.5, 74.5,
73.9, 73.6, 73.2, 73.1, 68.9. IR (film, cm-1): ν 3029, 2916, 2867,
1486, 1454, 1236, 1158, 1100, 1062, 1027, 1006, 823, 734, 697.
HRMS (ESI): calcd for C40H39Br O6Na (M + Na) 717.1828, found
717.1804.
1
Compound 28. HNMR (CDCl3, 500 MHz): δ ) 7.50-7.29
(m, 14H), 7.19-7.16 (m, 2H), 7.06-6.93 (m, 2H), 5.04 (d, J ) 5
Hz, 1H), 5.02 (d, J ) 15 Hz, 1H), 4.91 (bs, 2H), 4.84 (d, J ) 10
Hz, 1H), 4.76 (d, J ) 10 Hz, 1H), 4.65 (d, J ) 15 Hz, 1H), 3.99
(dd, J ) 10, 5 Hz, 1H), 3.73 - 3.71 (m, 3H), 3.34 (t, J ) 10 Hz,
1H), 2.29 (s, 6H). 13C NMR (CDCl3, 125 MHz): δ ) 155.2, 138.6,
138.2, 138.1, 131.0, 127.7, 127.1, 126.3, 122.4, 114.4, 104.8, 86.8,
83.7, 77.2, 75.8, 74.2, 73.4, 63.7, 15.7. IR (film, cm-1): ν ) 3063,
3030, 2906, 2866, 1590, 1493, 1454, 1357, 1236, 1085, 1027, 997,
909, 751, 698. HRMS (ESI): calcd for C33H34O5Na (M + Na)
533.2304, found 533.2322.
1
Compound 21. H NMR (CDCl3, 500 MHz): δ ) 7.74 (dd, J
) 13.5, 8 Hz, 2H), 7.62 (d, J ) 8.5 Hz, 1H), 7.40-7.23 (m, 24H),
5.11 (d, J ) 7.5 Hz, 1H), 5.02 (d, J ) 10.5 Hz, 1H), 4.98 (d, J )
11.5 Hz, 1H), 4.87 (d, J ) 10.5 Hz, 1H), 4.78 (d, J ) 12 Hz, 1H),
4.74 (d, J ) 12 Hz, 1H), 4.65 (d, J ) 11.5 Hz, 1H), 4.45 (d, J )
11.5 Hz, 1H), 4.39 (d, J ) 11.5 Hz, 1H), 4.16 (dd, J ) 10, 8 Hz,
1H), 3.95 (d, J ) 2.5 Hz, 1H), 3.74 (t, J ) 6 Hz, 1H), 3.68-3.61
(m, 3H). 13C NMR (CDCl3, 125 MHz): δ ) 129.3, 128.4, 128.3,
128.2, 127.8, 127.6, 124.2, 118.5, 101.8, 82.0, 79.2, 75.5, 74.5,
74.0, 73.7, 73.3, 73.1, 69.1. IR (film, cm-1): ν 3061, 3029, 2920,
2862, 1509, 1496, 1454, 1362, 1253, 1214, 1101, 1065, 1027, 736,
696. HRMS (ESI): calcd for C44H42O6Na (M + Na) 689.2879,
found 689.2852.
1
Compound 29. H NMR (CDCl3, 500 MHz): δ ) 7.39-7.29
(m, 15H), 7.16 (d, J ) 10 Hz, 1H), 7.01 (d, J ) 10 Hz, 1H), 5.03
(d, J ) 10 Hz, 1H), 5.01 (d, J ) 10 Hz, 1H), 4.93 (d, J ) 15 Hz,
1H), 4.91 (d, J ) 15 Hz, 1H), 4.84 (d, J ) 10 Hz, 1H), 4.78 (d, J
) 10, 5 Hz, 1H), 4.67 (d, J ) 10 Hz, 1H), 4.01 (dd, J ) 10, 5 Hz,
1H), 3.75-3.63 (m, 3H), 3.35 (dd, J ) 10.5, 10 Hz, 1H), 2.64 (q,
J ) 10 Hz, 2H), 1.24 (t, J ) 10 Hz, 3H). 13C NMR (CDCl3, 125
MHz): δ) 155.2, 138.7, 138.6, 138.3, 138.1, 128.7, 128.4, 128.0,
127.9, 127.7, 116.9, 102.5, 83.6, 81.6, 7.7, 75.7, 75.1, 73.4, 28.1,
15.8. IR (film, cm-1): ν ) 3030, 2963, 2927, 2869, 1509, 1454,
1231, 1074, 1027, 997, 829, 735, 697. HRMS (ESI): calcd for
C34H36O5Na (M + Na) 547.2460, found 547.2477.
Compound 22. 1H NMR (CDCl3, 500 MHz): δ ) 8.31 (d, J )
8.5 Hz, 1H), 7.79 (d, J ) 8 Hz, 1H), 7.51-7.23 (m, 24H), 7.18 (d,
J ) 8.5 Hz, 1H), 5.19 (d, J ) 7.5 Hz, 1H), 5.12 (d, J ) 10.5 Hz,
1H), 5.01 (d, J ) 11.5 Hz, 1H), 4.96 (d, J ) 10.5 Hz, 1H), 4.80
(d, J ) 12 Hz, 1H), 4.77 (d, J ) 11.5 Hz, 1H), 4.68 (d, J ) 11.5
Hz, 1H), 4.45 (d, J ) 11.5 Hz, 1H), 4.39 (d, J ) 11.5 Hz, 1H),
4.31 (dd, J ) 10, 8 Hz, 1H), 3.99 (d, J ) 2.5 Hz, 1H), 3.74 (t, J
) 6.5 Hz, 1H), 3.70-3.61 (m, 3H). 13C NMR (CDCl3, 125 MHz):
δ ) 153.0, 138.5, 138.3, 137.8, 134.5, 128.4, 128.3, 128.2, 127.9,
127.8, 127.7, 127.6, 127.4, 127.3, 125.9, 125.7, 125.4, 122.3, 122.1,
109.2, 101.7, 82.4, 79.3, 75.7, 74.6, 74.0, 73.6, 73.3, 73.1, 68.9.
IR (film, cm-1): ν 3062, 3029, 2916, 2866, 1578, 1496, 1454, 1388,
1363, 1264, 1095, 1068, 1027, 736, 697. HRMS (ESI): calcd for
C44H42O6Na (M + Na) 689.2879, found 689.2851.
1
Compound 30. HNMR (CDCl3, 500 MHz): δ ) 7.49-7.28
(m, 17H), 6.91 (d, J ) 10 Hz, 1H), 4.95 (d, J ) 10 Hz, 2H), 4.90
(bs, 2H), 4.82 (d, J ) 10 Hz, 1H), 4.76 (d, J ) 10 Hz, 1H), 4.65
(d, J ) 10 Hz, 1H), 3.99 (dd, J ) 10, 5 Hz, 1H), 3.68-3.58 (m,
3H), 3.34 (t, J ) 10 Hz, 1H), 2.64 (q, J ) 10 Hz, 2H), 1.24 (t, J
) 10 Hz, 3H). 13C NMR (CDCl3, 125 MHz): δ ) 158.5, 138.1,
138.0, 137.8, 128.5, 128.1, 127.8, 126.8, 125.8, 118.5, 102.3, 83.5,
81.4, 77.3, 75.7, 75.0, 73.4, 63.6. IR (film, cm-1): ν ) 3088, 3063,
2903, 2867, 1590, 1486, 1454, 1357, 1235, 1085, 1027, 1006, 909,
823, 735, 698. HRMS (ESI): calcd for C32H31BrO5Na (M + Na)
597.1253, found 597.1275.
Compound 23. 1H NMR (CDCl3, 500 MHz): δ ) 8.29 (d, J )
8.5 Hz, 1H), 8.18(d, J ) 8.5 Hz, 1H), 7.57 (t, J ) 7.5 Hz, 1H),
7.46 (t, J ) 8 Hz, 1H), 7.37-7.20 (m, 21H), 7.01 (d, J ) 8.5 Hz,
1H), 5.12 (d, J ) 7.5 Hz, 2H), 5.06 (d, J ) 10.5 Hz, 1H), 4.99 (d,
J ) 11.5 Hz, 1H), 4.94 (d, J ) 10.5 Hz, 1H), 4.76 (t, J ) 12 Hz,
1H), 4.66 (d, J ) 11.5 Hz, 1H), 4.42 (d, J ) 11.5 Hz, 1H), 4.38
(d, J ) 11.5 Hz, 1H), 4.28 (dd, J ) 9.5, 8 Hz, 1H), 3.96 (d, J )
2.5 Hz, 1H), 3.71 (t, J ) 6 Hz, 1H), 3.66 (dd, J ) 10, 3 Hz, 1H),
3.54-3.59 (m, 2H). 13C NMR (CDCl3, 125 MHz): δ ) 152.1,
138.4, 138.2, 138.1, 137.8, 131.1, 128.5, 128.3, 128.0, 127.8, 127.6,
126.1, 125.7, 124.2, 122.6, 109.5, 101.7, 82.4, 79.1, 75.8, 74.6,
74.1, 73.7, 73.2, 73.1, 68.9. IR (film, cm-1): ν 3063, 3029, 2923,
2854, 2373, 2348, 2314, 1455, 1375, 1259, 1157, 1076, 1027, 734,
696. HRMS (ESI): calc. for C44H41ClO6Na (M + Na) 723.2489,
found 723.2468.
1
Compound 31. HNMR (CDCl3, 500 MHz): δ ) 8.32 (d, J )
10 Hz, 1H), 7.86 (d, J ) 10 Hz, 1H), 7.59 (d, J ) 10 Hz, 1H),
7.43-7.28 (m, 19H), 7.13 (d, J ) 10 Hz, 1H), 5.29 (d, J ) 5 Hz,
1H), 5.14 (d, J ) 10 Hz, 1H), 4.96 (d, J ) 15 Hz, 3H), 4.81 (d, J
) 10 Hz, 1H), 4.71 (d, J ) 15 Hz, 1H), 4.08 (dd, J ) 10, 5 Hz,
1H), 3.93 (t, J ) 5 Hz, 1H), 3.81-3.75 (m, 2H), 3.47-3.42 (m,
1H). 13C NMR (CDCl3, 125 MHz): δ ) 152.7, 138.6, 138.1, 134.6,
128.4, 127.8, 126.4, 125.7, 122.5, 122.4, 109.4, 101.8, 83.6, 81.5,
77.3, 76.8, 75.4, 73.4, 63.9. IR (film, cm-1): ν ) 3030, 2868, 1578,
1496, 1454, 1396, 1264, 1238, 937, 791, 771, 737, 697. HRMS
(ESI): calcd for C36H34O5Na (M + Na) 569.2304, found 569.2304.
Compound 32. 1HNMR (CDCl3, 500 MHz): δ ) 7.83 (dd, J )
10, 5 Hz, 2H), 7.80 (d, J ) 10 Hz, 1H), 7.52-7.29 (m, 19H), 5.21
(d, J ) 5 Hz, 1H), 5.09 (d, J ) 10 Hz, 1H), 4.99 (d, J ) 10 Hz,
1H), 4.97 (d, J ) 10 Hz, 1H), 4.91 (d, J ) 10 Hz, 1H), 4.82 (d, J
) 10 Hz, 1H), 4.71 (d, J ) 10 Hz, 1H), 4.10 (dd, J ) 10, 5 Hz,
1H), 3.79-3.73 (m, 3H), 3.49-3.45 (m, 1H). 13C NMR (CDCl3,
125 MHz): δ ) 154.9, 138.6, 138.3, 138.1, 134.3, 128.6, 127.9,
1
Compound 24. H NMR (CDCl3, 500 MHz): δ ) 81.6-7.98
(m, 4H), 7.62-7.55 (m, 2H), 7.50-7.42 (m, 4H), 7.30-7.21 (m,
10H), 7.15-6.91 (m, 4H), 5.89 (d, J ) 5 Hz, 1H), 5.06 (d, J ) 15
Hz, 1H), 4.99 (d, J ) 15 Hz, 1H), 4.85 (d, J ) 20 Hz, 2H), 4.60
(d, J ) 15 Hz, 1H), 4.51 (d, J ) 15 Hz, 2H), 4.15 (t, J ) 15 Hz,
1H), 4.04 (dd, J ) 15, 10 Hz, 1H), 3.81 (dd, J ) 15, 5 Hz, 1H),
2.32 (s, 3H). 13C NMR (CDCl3, 125 MHz): δ ) 166.2, 165.8, 155.4,
4710 J. Org. Chem. Vol. 74, No. 13, 2009

Formation of ꢀ-O-Aryl Glycosides
127.8, 127.7, 126.5, 124.5, 119.0, 111.38, 102.3, 83.6, 81.6, 77.7,
76.8, 75.7, 75.2, 73.4, 64.1. IR (film, cm-1): ν ) 3061, 3029, 2903,
2868, 1630, 1600, 1510, 1466, 1454, 1251, 1215, 1074, 1027, 998,
908, 843, 811, 747, 697. HRMS (ESI): calcd for C36H34O5Na (M
+ Na) 569.2304, found 569.2319.
75.4, 73.3, 64.1, 17.1. IR (film, cm-1): ν ) 3064, 3029, 2912, 2862,
1496, 1454, 1400, 1378, 1357, 1192, 1076, 1028, 994, 771, 736,
697. HRMS (ESI): calcd for C34H36O5Na (M + Na) 547.2460,
found 547.2469.
1
Compound 38. HNMR (CDCl3, 500 MHz): δ ) 7.39 (d, J )
1
Compound 35. H and 13C NMR of O-aryl glycoside 27 have
6.3 Hz, 2H), 7.34-7.18 (m, 20H), 7.02 (t, J ) 8.1 Hz, 2H), 5.24
(d, J ) 7.5 Hz, 1H), 5.17 (d, J ) 10.8 Hz, 1H), 4.97 (d, J ) 10.9
Hz, 1H), 4.82-4.78 (m, 3H), 4.59 (d, J ) 10.8 Hz, 1H), 4.55 (d,
J ) 12.2 Hz, 1H), 4.43 (d, J ) 12.2 Hz, 1H), 3.83 (t, J ) 8.4 Hz,
1H), 3.75-3.65 (m, 3H), 3.37 (dt, J ) 9.3, 3 Hz, 1H). 13C NMR
(CDCl3, 125 MHz): δ ) 138.7, 138.5, 138.1, 128.4, 128.0, 127.7,
127.5, 127.4, 125.7, 103.4, 84.5, 82.6, 77.4, 75.8, 75.1, 73.5, 68.7.
IR (film, cm-1): ν) 3029, 2913, 2876, 1566, 1494, 1448, 1079,
775, 735, 694. HRMS (ESI): calcd for C40H38Cl2O6Na (M + Na)
707.1943, found 707.1939.
been reported.13 1HNMR (CDCl3, 500 MHz): δ ) 7.35 (d, J ) 6.7
Hz, 2H), 7.29-7.24 (m, 16H), 7.17 (d, J ) 6.4 Hz, 2H), 7.01 (d,
J ) 7.1 Hz, 2H), 6.97-6.94 (m, 1H), 5.12 (d, J ) 10.8 Hz, 1H),
4.96 (d, J ) 11 Hz, 1H), 4.84-4.80 (m, 3H), 4.76 (d, J ) 7.3 Hz,
1H), 4.58 (d, J ) 10.7 Hz, 1H), 4.50 (d, J ) 12.1 Hz, 1H), 4.44
(d, J ) 12.1 Hz, 1H), 3.75-3.68 (m, 3H), 3.66-3.59 (m, 2H),
3.27 (d, J ) 6.6 Hz, 1H), 2.36 (s, 6H). 13C NMR (CDCl3, 125
MHz): δ ) 153.2, 138.7, 138.4, 138.2, 132.0, 128.8, 128.4, 128.3,
128.2, 128.0, 127.8, 127.7, 127.6, 127.5, 124.6, 104.2, 84.8, 82.9,
77.8, 75.8, 75.4, 75.0, 73.5, 68.9, 17.2. IR (film, cm-1): ν ) 3029,
2915, 2868, 1496, 1470, 1453, 1359, 1158, 1071, 1027, 734, 695.
1
Compound 39. HNMR (CDCl3, 500 MHz): δ ) 7.39-7.25
(m, 17H), 7.01 (t, J ) 8 Hz, 1H), 5.32 (d, J ) 7 Hz, 1H), 5.08 (d,
J ) 11 Hz, 1H), 4.88 (d, J ) 11 Hz, 1H), 4.81 (d, J ) 11 Hz, 1H),
4.78 (d, J ) 11 Hz, 1H), 4.67 (d, J ) 12 Hz, 1H), 4.60 (d, J ) 12
Hz, 1H), 4.05 (dd, J ) 12, 4.5 Hz, 1H), 3.80 (dd, J ) 9, 8 Hz,
1H), 3.76-3.68 (m, 2H), 3.29 (dd, J ) 12, 8 Hz, 1H). 13C NMR
(CDCl3, 125 MHz): δ ) 129.8, 129.1, 128.4, 128.3, 127.9, 127.8,
127.74, 127.7, 127.6, 125.6, 104.0, 82.8, 81.5, 77.9, 75.2, 74.9,
72.8, 64.1. IR (film, cm-1): ν ) 3030, 2905, 2871, 1566, 1496,
1451, 1439, 1241, 1089, 1073, 1050, 776, 741, 696. HRMS (ESI):
calcd for C32H30Cl2 O5Na (M + Na) 587.1368, found 587.1398.
1
Compound 36. H NMR (CDCl3, 500 MHz): δ ) 7.38-7.23
(m, 18H), 7.15-7.14 (m, 2H), 6.99-6.92 (m, 3H), 5.19 (d, J ) 11
Hz, 1H), 5.00 (d, J ) 11.5 Hz, 1H), 4.89 (d, J ) 11 Hz, 1H), 4.79
(d, J ) 12 Hz, 1H), 4.75 (d, J ) 10.5 Hz, 1H), 4.74 (d, J ) 8 Hz,
1H), 4.64 (d, J ) 12 Hz, 1H), 4.35 (d, J ) 12 Hz, 1H), 4.32 (d, J
) 11.5 Hz, 1H), 4.10 (dd, J ) 9.5, 7.5 Hz, 1H), 3.92 (d, J ) 2.5
Hz, 1H), 3.63-3.58 (m, 2H), 3.49 (dd, J ) 9.5, 5.5 Hz, 1H), 3.42
(t, J ) 6.5 Hz, 1H), 2.32 (s, 6H). 13C NMR (CDCl3, 125 MHz): δ
) 135.9, 132.1, 128.7, 128.1, 127.8, 127.7, 127.6, 127.5, 127.49,
127.43, 124.4, 82.5, 80.0, 76.7, 76.5, 76.4, 75.6, 74.5, 73.8, 73.5,
73.4, 73.1, 68.6, 17.2. IR (film, cm-1): ν 3029, 2921, 2864, 1495,
1454, 1361, 1263, 1195, 1097, 1059, 1027, 733, 697, 666. HRMS
(ESI): calcd for C42H44O6Na (M + Na) 667.3035, found 667.3015.
Acknowledgment. We thank Montana State University and
the National Science Foundation (CHEM-0809200) for financial
support.
1
Compound 37. HNMR (CDCl3, 500 MHz): δ ) 7.39-7.29
(m, 15H), 7.03-6.96 (m, 3H), 5.11 (d, J ) 10 Hz, 1H), 4.94 (d, J
) 10 Hz, 1H), 4.92 (d, J ) 10 Hz, 1H), 4.86 (d, J ) 10 Hz, 1H),
4.76 (d, J ) 10 Hz, 1H), 4.74 (d, J ) 10 Hz, 1H), 4.63 (d, J ) 10
Hz, 1H), 3.90 (dd, J ) 10, 5 Hz, 1H), 3.71-3.63 (m, 3H), 3.08 (t,
J ) 10 Hz, 1H), 2.34 (s, 6H). 13C NMR (CDCl3, 125 MHz): δ )
153.0, 138.7, 138.4, 138.2, 131.8, 128.8, 128.5, 128.4 128.2, 128.1,
127.9, 127.8, 127.7, 127.6, 127.5, 124.6, 84.1, 82.5, 78.1, 75.7,
Supporting Information Available: Experimental proce-
dures and 1H NMR and 13C NMR spectra of all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO9002807
J. Org. Chem. Vol. 74, No. 13, 2009 4711