An alternative synthesis of 1,1′-Bis-valienamine from d -glucose

Article abstract of DOI:10.1021/jo100474p

An alternative synthesis of 1,1′-bis-valienamine 5, which was demonstrated to be a potent trehalase inhibitor, has been achieved from d-glucose in 12 steps with 15% overall yield via enone 12 as the key intermediate, involving a direct aldol reaction of a glucose-derived diketone and a palladium-catalyzed allylic coupling reaction as the key steps.

Full text of DOI:10.1021/jo100474p

pubs.acs.org/joc
0
An Alternative Synthesis of 1,1 -Bis-valienamine
from D-Glucose
Tony K. M. Shing* and Hau M. Cheng
Department of Chemistry and Center of Novel Functional
Molecules, The Chinese University of Hong Kong, Shatin,
Hong Kong
tonyshing@cuhk.edu.hk
Received March 15, 2010
FIGURE 1. Valienamine and its related compounds.
-
8
7
a strong and specific inhibitor (IC 1.7 ꢀ 10 M) against
5
0
8
trehalase and, therefore, has the potential to be developed as
a human-safe insecticide.
A few years ago, we published a facile, regio- and stereo-
0
0
An alternative synthesis of 1,1 -bis-valienamine 5, which
specific synthesis of 1,1 -bis-valienamine 5 in 16 steps from
7
0
was demonstrated to be a potent trehalase inhibitor, has
been achieved from D-glucose in 12 steps with 15% overall
yield via enone 12 as the key intermediate, involving a
direct aldol reaction of a glucose-derived diketone and
a palladium-catalyzed allylic coupling reaction as the
key steps.
(-)-quinic acid with an overall yield of 12%. This 1,1 -
N-linked-pseudodisaccharide 5 was demonstrated to be a
potent trehalase inhibitor and was assembled by a key
palladium-catalyzed coupling reaction of 2,3:4,6-diaceto-
nated allylic chloride 6 and allylic amine 7, both of which
7
were transformed from allylic alcohol 8 (Scheme 1). How-
ever, during the palladium-catalyzed coupling reaction, an
undesirable β-hydride elimination to alleviate the trans-
isopropylidene ring strain in the allylic chloride 6 to give diene
Sugar-mimicking glycosidase inhibitors as potential anti-
diabetic, anticancer, and antiviral agents have stimulated
9
was a competitive reaction against the nucleophilic substitu-
tion with the allylic amine 7. Hence, dropwise addition of the
allylic chloride 6 into a mixture of an excess amount (ca. 4
equiv) of the precious amine 7 and the palladium complex was
1
great demand of these compounds for biological studies.
Immense efforts have been dedicated to the construction
2-4
2
of R-D-glucosidase inhibitor valienamine (1) since its isola-
tion in 1972. Valienamine (1) is an essential core unit in
7
required in order to attain a good chemical yield (78%).
5
However, the drawback of this protocol is the need of a much
larger quantity of the allylic amine 7 and the laborious recovery
of the unreacted 7 by chromatography.
many kinds of pseudo-oligosaccharidic R-D-glucosidase in-
hibitors such as methyl acarviosin (2) and acarbose (3)
6
Figure 1). The constitution of 1,1 -N-linked-pseudodisac-
0
(
charide 5, i.e., 1,1 -bis-valienamine, resembles trehalose (4)
(
The great demand of 5 for detailed biological evaluation
and the high cost of (-)-quinic acid as the starting material
prompted us to investigate a shorter, more efficient, and
economical synthetic route. This paper describes an efficient
0
0
1,1 -bis-R-D-glucose) structurally and has been shown to be
(1) (a) Asano, N.; Kato, A.; Watson, A. A. Mini-Rev. Med. Chem. 2001, 1,
45–154. (b) Watson, A. A.; Fleet, G. W. J.; Asano, N.; Molyneux, R. J.;
0
1
construction of 1,1 -bis-valienamine 5 from cheap and read-
Nash, R. J. Phytochemistry 2001, 56, 265–295. (c) Asano, N.; Nash, R. J.;
Molyneux, R. J.; Fleet, G. W. J. Tetrahedron: Asymmetry 2000, 11, 1645–
ily available D-glucose using an intramolecular aldol cycliza-
tion of a diketone and a palladium-catalyzed allylic coupling
reaction as the key steps.
1
680. (d) Ossork, A.; Elbein, A. D. In Carbohydrates in Chemistry and Biology;
Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, 2000; Part II, pp
5
13-531.
Our endeavors in amino pseudosugar synthesis from
9
D-glucose have already produced pseudoacarviosin, valiol-
(
977.
2) Chen, X.; Fan, Y.; Zheng, Y.; Shen, Y. Chem. Rev. 2003, 103, 1955–
1
1
0
(
3) (a) Shing, T. K. M.; Li, T. Y.; Kok, S. H.-L. J. Org. Chem. 1999, 64,
amine, and validoxylamine G. The present paper further
demonstrates the versatility of this avenue for the efficient
1
6
941–1946. (b) Kok, S. H.-L.; Lee, C. C.; Shing, T. K. M. J. Org. Chem. 2001,
6, 7184–7190.
(
4) (a) Chang, Y.-K.; Lee, B.-Y.; Kim, D. J.; Lee, G. S.; Jeon, H. B.; Kim,
K. S. J. Org. Chem. 2005, 70, 3299–3302. (b) Cumpstey, I. Tetrahedron Lett.
005, 46, 6257–6259.
2
(8) Ogawa, S.; Sato, K.; Miyamoto, Y. J. Chem. Soc., Perkin Trans. 1
1993, 691–696.
(9) Shing, T. K. M.; Cheng, H. M.; Wong, W. F.; Kwong, C. S. K.; Li, J.;
Lau, C. B. S.; Leung, P. S.; Cheng, C. H. K. Org. Lett. 2008, 10, 3145–3148.
(10) Shing, T. K. M.; Cheng, H. M. Org. Lett. 2008, 10, 4137–4139.
(5) Kameda, Y.; Horii, S. J. Chem. Soc., Chem. Commun. 1972, 746–747.
(6) Mahmud, T. Nat. Prod. Rep. 2003, 20, 137–166.
(7) Shing, T. K. M.; Kwong, C. S. K.; Cheung, A. W. C.; Kok, S. H.-L.;
Yu, Z.; Li, J.; Cheng, C. H. K. J. Am. Chem. Soc. 2004, 126, 15990–15992.
3
522 J. Org. Chem. 2010, 75, 3522–3525
Published on Web 04/14/2010
DOI: 10.1021/jo100474p
r 2010 American Chemical Society

Shing and Cheng
SCHEME 1. Previous Synthesis of 1,1 -Bis-valienamine 5 from
JOCNote
0
TABLE 1. Reduction of Enone 12 to Allylic Alcohols 13 and 14
7
(
-)-Quinic Acid via Allylic Alcohol 8.
ratio of
13:14
a
entry
conditions
, MeOH, 0 °C
yield (%)
1
2
3
4
5
6
7
a
NaBH
NaBH
NaBH
NaBH
NaBH
4
4
4
4
4
1:1
1:1
4:1
5:1
5:1
5:1
0:1
98
97
99
99
98
98
99
, MeOH, -10 °C
, CeCl
, CeCl
, CeCl
3
3
3
7H
7H
7H
2
2
2
O, MeOH, -10 °C
O, MeOH, -30 °C
O, MeOH, -78 °C
3
3
3
DIBAL-H, THF, -78 °C to rt
K-Selectride, THF, -78 °C
1
Ratio was determined by H NMR spectroscopy.
SCHEME 3. Synthesis of Amine 19
9,10
SCHEME 2. Preparation of Allylic Chloride 16 from D-Glucose
The synthesis of the coupling donor, the acetal protected
valienamine 19, is shown in Scheme 3. The allylic R-alcohol
1
4 was esterified with mesyl chloride. The resultant mesylate
was too unstable to be isolated but reactive enough to be
displaced by the chloride ion formed in situ to give allylic
chloride 17 in one pot. The allylic β-chloride 17 was readily
displaced with LiN to afford allylic R-azide 18 in a quanti-
3
1
2
tative yield. Staudinger reduction of the azide 18 with
triphenylphosphine/aqueous ammonia furnished the desired
coupling partner R-allylic amine 19 in an excellent yield
without incident.
1
3
Palladium-catalyzed coupling reaction of allylic chloride
0
0
synthesis of 1,1 -bis-valienamine (5) via enone 12 as the key
intermediate.
16 with amine 19 produced 1,1 -N-linked pseudodisacchar-
ide 20 in an excellent yield. The cis-orientation of NH-1 and
OR-2 in adduct 20 is evident from the coupling constants
(J1,2 = 4.8; J2,3 = 10.8 Hz), and thus, the coupling reaction
occurred with retention of configuration of the allylic
R-chloride 16 (Scheme 4). From our experience, an excess
amount (ca. 2 equiv) of the nucleophilic amine 19 should be
used to ensure a rapid reaction and suppress the formation of a
In our previous investigation on the construction of
carbocycles from carbohydrates, diketone 10 (prepared from
D-glucose in 6 steps with 31% overall yield) was employed to
undergo the intramolecular aldol cyclization to give enone 12
9
,10
(Scheme 2).
Attempts toward regio- and diastereoselec-
tive 1,2-reduction of enone 12 were investigated, and the
results are shown in Table 1. The best conditions for the
formation of β-alcohol 13 was sodium borohydride reduction
assisted by cerium(III) chloride heptahydrate (CeCl 7H O)
8
diene side product. Fortunately, under these conditions, no
sign of an elimination diene related to 9 was observed. Acidic
0
hydrolysis then afforded the target molecule 1,1 -N-linked
7,8,14
pseudodisaccharide 5.
3
3
2
1
The H and C NMR spectral data
13
at -30 °C, affording a mixture of inseparable allylic alcohols
11
0
1
3 and 14 in a 5:1 ratio, respectively (entry 4). The β-alcohol
3 proved difficult to obtain pure by chromatography, but its
of 1,1 -bis-valienamine 5 are in agreement with those in the
8
literature, and the specific rotation value was found to be
consistent with that reported recently. One reviewer inquired
1
corresponding acetate 15 was readily isolated clean and was
14
converted smoothly into R-allylic chloride 16 as reported
previously by us.
On the other hand, exclusive formation of R-alcohol 14
from enone 12 was feasible with K-Selectride in excellent
yield (entry 7).
9
(
12) Gololobov, Yu. G.; Zhmurova, I. N.; Kasukhin, L. F. Tetrahedron
1981, 37, 437–472.
13) (a) Trost, B. M.; Cossy, J. J. Am. Chem. Soc. 1982, 104, 6881–6882.
b) Gen ^e t, J. P.; Balabane, M. Tetrahedron Lett. 1983, 24, 2745–2748. (c)
(
(
Heumann, A.; R ꢀe glier, M. Tetrahedron 1995, 51, 975–1015. (d) Kim, K. S.;
Choi, S. O.; Park, J. M.; Lee, Y. J.; Kim, J. H. Tetrahedron: Asymmetry 2001,
1
2, 2649–2655. (e) Tsuji, J. Palladium Reagents and Catalysts-Innovations in
(
11) (a) Gemal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103, 5454–
Organic Synthesis, 2nd ed.; John Wiley: Chicester, U.K., 1995; p 9.
(14) Xu, H.; Yang, J.; Bai, L.; Deng, Z.; Mahmud, T. Appl. Microbiol.
Biotechnol. 2009, 81, 895–902.
5
1
459. (b) Krief, A.; Surleraux, D.; Ropson, N. Tetrahedron: Asymmetry
993, 4, 289–293.
J. Org. Chem. Vol. 75, No. 10, 2010 3523

Shing and Cheng
JOCNote
SCHEME 4. Synthesis of 1,1 -Bis-valienamine 5
0
13
C NMR (75 MHz, CDCl ) δ 18.1 (CH ), 18.2 (CH ), 20.8
3
3
3
(
(
(
CH
CH), 67.2 (CH), 68.3 (CH), 70.3 (CH), 99.4 (C), 99.7 (C), 100.1
3
), 28.3 (CH
3
), 48.4 (CH
3
), 48.6 (CH
3
), 63.2 (CH
2
), 65.6
þ
C), 119.6 (CH), 136.8 (C); m/z (ESI) 353 ([M þ Na] , 100);
þ
HRMS (ESI, [M þ Na] ) found 353.1579, calcd for C16
H
26
O
7
3
53.1571.
Allylic Chloride 17. To a solution of the R-alcohol 14 (177 mg,
0
.536 mmol) in CH Cl (8 mL) and Et N (0.45 mL, 3.22 mmol)
2
2
3
was added methanesulfonyl chloride (MsCl) (0.13 mL, 1.68
mmol) at 0 °C. The mixture was stirred for 7 days at room
temperature. The mixture was then filtered through a thin pad of
silica gel topped with Celite, and the residue was washed with
diethyl ether until no product was observed in the eluent
(
checked with TLC). Concentration of the filtrate followed by
flash chromatography (n-hexane/Et O, 3:1) yielded allylic
chloride 17 (139 mg, 74%) as a colorless oil: [R]
c 0.62, CHCl ); R 0.53 (n-hexane/Et O, 1:1); IR (thin film) 2937,
355, 1174 cm ; IR (thin film) 2951, 2912, 1457, 1380, 1135, 1034,
2
about the feasibility of the conversion of allylic alcohol 14 into
chloride 16, which would render the synthesis more efficient.
We reckon that this is feasible. The configuration of the free
R-alcohol in 14 could be inverted by Mitsunobu reaction
followed by de-esterification and chlorination to give β-chloride
2
0
D
-252
(
1
3
-1
f
2
-1 1
7
58 cm ; H NMR (300 MHz, CDCl ) δ 1.33 (s, 3H), 1.34 (s, 3H),
3
1
.39 (s, 3H), 1.51 (s, 3H), 3.27 (s, 3H), 3.33 (s, 3H), 3.77 (dd, J =
10.8, 7.8 Hz, 1H), 3.85 (dd, J = 10.8, 8.4 Hz, 1H), 4.10 (d, J =
13.2 Hz, 1H), 4.47 (d, J = 12.9 Hz, 1H), 4.56 (d, J = 8.1 Hz, 1H),
1
6. Research in this direction is in progress.
0
To conclude, 1,1 -bis-valienamine 5 was synthesized from
D-glucose in 12 steps with 15% overall yield involving enone
1
3
5.45 (s, 1H); C NMR (75 MHz, CDCl
28.7 (CH ), 48.5 (CH ), 57.5 (CH), 63.1 (CH
3 3 3
) δ 18.0 (CH ), 20.3 (CH ),
), 69.6 (CH), 71.2
CH), 72.9 (CH), 99.4 (C), 99.7 (C), 99.8 (C), 121.5 (CH), 133.7 (C);
1
2 as the key intermediate. This route offers improvement
3
3
2
(
over our previous endeavor in terms of a shorter sequence
and with a higher overall yield. Furthermore, in the key
palladium-catalyzed allylic substitution, we have success-
fully reduced the amount of amine 19 from 4 to ca. 2 equiv,
which enables the protocol to be more efficient and con-
venient. The change of the 2,3-O-acetonide group in allylic
chloride 6 to the trans-diacetal blocking group in 16 ob-
viously renders the chloride 16 stability to avoid the undesir-
able β-hydride elimination. The use of cheap and virtually
inexhaustible starting material D-glucose as oppose to quinic
acid is also noteworthy.
þ
þ
m/z (ESI): 371 ([M þ Na] , 100); HRMS (ESI, [M þ Na] ) found
3
6
71.1246, calcd for C16H25ClO 371.1232.
Azide 18. To a solution of the allylic chloride 17 (115 mg, 0.329
mmol) in DMF (4 mL) was added LiN (115 mg, 0.329 mmol) at
room temperature. The resultant solution was stirred for 3 h at
3
8
0 °C. The mixture was then cooled to 0 °C, diluted with EtOAc
(10 mL), washed with brine (2 ꢀ 10 mL), dried over MgSO , and
4
filtered. Concentration of the filtrate followed by flash chromato-
graphy (n-hexane/Et
2
O, 1:1) gave azide 18 (119 mg, 100%) as a
-24.7 (c 0.71, CHCl ); R = 0.37 (n-hexane/
O, 1:1); IR (thin film) 2993, 2949, 2111, 1456, 1375, 1137 cm
H NMR (300 MHz, CDCl ) δ 1.32 (s, 3H), 1.34 (s, 3H), 1.38 (s,
H), 1.49 (s, 3H), 3.27 (s, 3H), 3.29 (s, 3H), 3.80 (dd, J = 10.8, 4.5
20
D
colorless oil: [R]
Et
3
f
-
1
;
2
1
3
3
Experimental Section
Hz, 1H), 4.00 (dd, J = 11.1, 8.1 Hz, 1H), 4.11-4.16 (m, 2H),
0
13
1,1 -Bis-valienamine 5. To a solution of amine 20 (56.7 mg,
.088 mmol) in CH
(
resultant solution was stirred for 4 days at room temperature.
4.37-4.41 (m, 2H), 5.47 (d, J = 5.1 Hz, 1H); C NMR (75 MHz,
0
2
Cl
2
(5 mL) were added trifluoroacetic acid
TFA) (0.5 mL) and water (0.05 mL) at room temperature. The
CDCl
(CH ), 48.6 (CH
70.3 (CH), 99.3 (C), 99.8 (C), 100.1 (C), 116.6 (CH), 137.6 (C); m/z
3
) δ 17.9 (CH
3
), 18.2 (CH
3
), 20.7 (CH
), 28.3 (CH ), 48.5
3 3
), 57.8 (CH), 63.1 (CH
), 67.7 (CH), 68.2 (CH),
2
3
3
þ
þ
Concentration of the solution followed by flash chromatogra-
0
(ESI): 353 ([M þ Na] , 100); HRMS (ESI, [M þ Na] ) found
378.1639, calcd for C16 378.1636.
Amine 19. To a solution of the azide 18 (120 mg, 0.338 mmol)
in pyridine (3 mL) and aqueous NH (32%, 2 mL) was added
PPh (176 mg, 0.672 mmol), and the mixture was stirred for 24 h
phy (CHCl :MeOH, 2:1) yielded 1,1 -bis-valienamine 5 (27.7
mg, 94%) as a colorless oil: [R]
3
25 3 6
H N O
2
0
14
þ148 (c 0.38, MeOH) [lit. [R]
D
2
0
þ143.9 (c 0.2, MeOH)]; R = 0.29 (CHCl /MeOH/32% aq
3
D
f
3
8
, 1.6:1.2:0.6); H NMR (400 MHz, CD
1
NH
(
4
3
3
OD) δ 3.65-3.75
m, 4H), 3.73 (dd, J = 8.1, 6.1 Hz, 2H), 3.96 (d, J = 6.0 Hz, 2H),
3
at room temperature. The resultant solution was diluted with
EtOAc (10 mL) and washed with brine (2 ꢀ 5 mL). The aqueous
layer was extracted with EtOAc (2 ꢀ 15 mL). The combined
13
.17 (t, J = 15.3 Hz, 2H), 3.88 (t, J = 1.5 Hz, 2H); C NMR
(
100 MHz, CD OD) δ 53.6, 61.8, 69.1, 71.0, 72.7, 119.9, 141.8;
3
þ
þ
m/z (ESI) 334 ([M þ H] , 100); HRMS (ESI, [M þ H] ) found
34.1498, calcd for C14 334.1496.
Alcohol 14. To a solution of the enone 12 (2.01 g, 6.12 mmol)
4
organic extracts were dried over MgSO and filtered. Concen-
3
H23NO
8
tration of the filtrate followed by flash chromatography
(CHCl /MeOH, 30:1) gave amine 19 (102 mg, 92%) as a color-
less oil: [R]
20:1); IR (thin film) 3377, 2992, 2917, 1456, 1134, 1035 cm ; H
NMR (300 MHz, CD OD) δ 1.29 (s, 3H), 1.31 (s, 3H), 1.33 (s,
3
2
0
in THF (35 mL) at -78 °C was added 1 M THF solution of
K-Selectride (9 mL, 9 mmol) over 30 min, and the mixture was
stirred for 12 h at room temperature. The reaction was quenched
D
3 f 3
-86.2 (c 0.32, CHCl ); R = 0.33 (CHCl /MeOH,
-
1 1
3
with saturated NH Cl solution (20 mL). The aqueous layer was
4
3H), 1.53, (s, 3H), 3.24 (s, 3H), 3.27 (s, 3H), 3.39 (t, J = 4.8 Hz,
1H), 3.64 (dd, J = 11.4, 5.1 Hz, 1H), 3.93 (dd, J = 11.1, 8.1 Hz,
1H), 4.09 (d, J = 13.8 Hz, 1H), 4.45-4.52 (m, 2H), 5.57 (d, J =
extracted with EtOAc (3 ꢀ 30 mL). The combined organic
extracts were washed with brine (2 ꢀ 10 mL), dried over MgSO
4
,
1
3
and filtered. Concentration of the filtrate followed by flash
chromatography (n-hexane/EtOAc, 1:1) gave R-alcohol 14
4.8 Hz, 1H); C NMR (75 MHz, CDCl
) δ 18.2 (CH ), 18.3
3 3
(CH ), 20.2 (CH ), 29.0 (CH ), 48.4 (CH ), 49.3 (CH), 63.7
3
3
3
3
2
0
(
R
2.00 g, 99%) as a colorless oil: [R]
f
D
-118 (c 1.51, CHCl
= 0.33 (n-hexane/EtOAc, 1:1); IR (thin film) 3469, 2994,
3
);
(CH ), 67.3 (CH), 68.0 (CH), 70.6 (CH), 99.3 (C), 99.5 (C), 99.8
2
þ
(C), 122.9 (CH), 133.1 (C); m/z (ESI) 330 ([M þ H] , 100);
-
1
1
950, 1645, 1455, 1376, 1140, 754 cm ; H NMR (300 MHz,
þ
2
HRMS (ESI, [M þ H] ) found 330.1905, calcd for C H NO
1
6
27
6
CDCl ) δ 1.33 (s, 6H), 1.38 (s, 3H), 1.49 (s, 3H), 3.27 (s, 6H), 3.62
330.1911.
Amine 20. To a mixture of chloride 16 (49.2 mg, 0.141) and
amine 19 (88.7 mg, 0.269 mmol) in CH CN (2 mL) was added
3
(
4
dd, J = 11.1, 4.2 Hz, 1H), 4.06 (dd, J = 11.1, 8.1 Hz, 1H),
.14-4.22 (m, 2H), 4.38-4.43 (m, 2H), 5.59 (d, J = 4.2 Hz, 1H);
3
3
524 J. Org. Chem. Vol. 75, No. 10, 2010

Shing and Cheng
JOCNote
bis(dibenzylideneacetone)palladium(0) (4.1 mg, 0.007 mmol),
TMPP (3.4 mg, 0.02 mmol), and Et N (0.1 mL, 0.717 mmol).
(100 MHz, CDCl ) δ 18.2 (CH ), 18.3 (CH ), 20.4 (CH ), 28.9
3
3
3
3
3
(CH
70.6 (CH), 99.1 (C), 99.3 (C), 122.8 (CH), 131.5 (C); m/z (ESI)
3 3 2
), 48.4 (CH ), 55.9 (CH), 63.7 (CH ), 68.1 (CH), 69.6 (CH),
The resultant solution was stirred for 48 h at room temperature
under nitrogen. Concentration of the solution followed by flash
chromatography gave first (hexane/Et O, 1:1.5) the protected
þ
þ
642 ([M þ H] , 100); HRMS (ESI, [M þ H] ) found 642.3471,
calcd for C32 51NO12 642.3484.
2
H
0
1
(
,1 -bis-valienamine 20 (86.0 mg, 95%) as a colorless oil and
CHCl /MeOH, 30:1) second the starting amine 19 (39.1 mg).
Acknowledgment. This work was supported by a Strategic
Investments Scheme administrated by the Centre of Novel
Functional Molecules, The Chinese University of Hong Kong.
3
2
0
Data for 20: [R]
þ23.6 (c 0.39, CHCl ); R = 0.35 (n-hexane/
D
3
f
Et
1
2
O, 1:3); IR (thin film) 3370, 2992, 2923, 1457, 1373, 1120,
-
1 1
040, 756 cm ; H NMR (300 MHz, C D ) δ 1.23 (s, 3H), 1.36
6 6
(
(
1
4
s, 3H), 1.37 (s, 3H), 1.54 (s, 3H), 3.10 (s, 3H), 3.20 (s, 3H), 3.84
dd, J = 10.8, 4.5 Hz, 1H), 3.96 (brs, 1H), 4.03 (d, J = 13.5 Hz,
Supporting Information Available: General procedure and
1
13
copies of H and C NMR spectra of all new compounds. This
material is available free of charge via the Internet at http://
pubs.acs.org.
H), 4.16 (d, J = 13.8 Hz, 1H), 4.33 (dd, J = 10.8, 7.8 Hz, 1H),
.51 (d, J = 7.8 Hz, 1H), 5.80 (d, J = 4.2 Hz, 1H); C NMR
13
J. Org. Chem. Vol. 75, No. 10, 2010 3525