Selective Wittig olefination in aqueous media for the rapid preparation of unsaturated 7,3-lactone-α-d-xylofuranose derivatives

Article abstract of DOI:10.1016/j.tetlet.2010.02.094

A highly efficient and rapid protocol for the preparation of the title compounds 1a and 1b from d-glucose derivatives 2a and 2b, respectively, is reported. To this end, highly selective Wittig olefination in aqueous media was developed for the elaboration

Full text of DOI:10.1016/j.tetlet.2010.02.094

Tetrahedron Letters 51 (2010) 2178–2180
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Tetrahedron Letters
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Selective Wittig olefination in aqueous media for the rapid preparation
of unsaturated 7,3-lactone-
a-D-xylofuranose derivatives
a,
a,
*
Elsie Ramirez a, Mario Sánchez b, Rosa L. Meza-León a, , Leticia Quintero , Fernando Sartillo-Piscil
*
*
a Centro de Investigación de la Facultad de Ciencias Químicas, BUAP, C. P.72570, Puebla, Mexico
b Centro de Investigación en Materiales Avanzados, S. C. Alianza Norte 202, Carretera Monterrey-Aeropuerto Km. 10, PIIT. C. P. 66600, Apodaca NL, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient and rapid protocol for the preparation of the title compounds 1a and 1b from D-glucose
Received 18 November 2009
Revised 11 February 2010
Accepted 16 February 2010
Available online 20 February 2010
derivatives 2a and 2b, respectively, is reported. To this end, highly selective Wittig olefination in aqueous
media was developed for the elaboration of ,b-unsaturated acids 5a and 5b, which when treated with
DCC, lactonization was accomplished and the title compounds 1a and 1b were obtained in only three
sequential steps with overall yields of 85% and 88%, respectively. Additionally, the Z-selectivity was stud-
ied by analyzing conformational models of its corresponding oxophosphorinane intermediaries.
Ó 2010 Elsevier Ltd. All rights reserved.
a
When an organic chemist has the need for the synthesis of
unsaturated compounds, always has in mind the very well-known
Wittig olefination.1 There are a number of positive reasons that
confer to this reaction the privilege of being the first choice (among
other synthetic methods),2 however, there still are issues for this
reaction, such as selectivity3 and environmental concerns4 that re-
main challenging with certain substrates. Under traditional condi-
tion reactions, E-olefins are the major product for stabilized ylides,
whereas Z-olefins are preferred for nonstabilized ylides.3c-e
Although many reaction conditions have been reported to improve
the chemoselectivity of the Wittig olefination (such as tempera-
ture,5 pressure,6 silica gel,7 additives,8 and solvents,4,9) the ability
reported good Z-selectivities for a-alkoxy-b-hydroxyaldehydes
with also stabilized ylides in dry methanol. Apparently, two
requirements are necessary for achieving high Z-selectivity: (a) a
polar or donor group placed at b-position to aldehyde, and, (b)
an anhydrous alcoholic solvent.14,15,3c It seems that the polar med-
ia contribute to stabilize the formation of a chelating ‘anti-betaine’
leading thus to the preferential occurrence of high Z-selectivities
(Scheme 2).16
Therefore, if we considered the fact that the anti-betaine struc-
ture is stabilized by solvating effect from methanol, then water
for full selectivity control is hardly achieved for those a-alkoxyal-
EtOOC
O
O
O
dehydes.10 In this sense, some years ago we faced this problem
when we reported11 the sequential hydrolysis-oxidation-Wittig
O
O
O
1. H5IO6/AcOEt
5
HO
O
O
olefination (SHOWO12) protocol for the synthesis of
a
,b-unsatu-
2. Ph3P=CHCOOEt
+
HO
O
O
86%, ratio 5/1a = 4/1
rated esters derived from diacetone-D-glucose (Scheme 1).
2a
O
Although the selectivity was modest, the global yield was good,
especially if we take into consideration the synthetic importance
O
1a
O
Versatile chiral synthon
for naturally important
compounds
of the
a,b-unsaturated lactone 1a as versatile chiral synthon for
the preparation of various biologically important compounds.13
Therefore, we now report the efficient synthesis of 1a and another
lactone analogous 1b by means of a selective Wittig olefination in
aqueous media.4
Scheme 1. Sequential hydrolysis-Oxidation-Wittig Olefination protocol (SHOWO).
At first glance, we thought that the quest for the Z-selectivity in
this kind of substrate would be difficult, since Trouchet and Gentile
were first in report poor Z-selectivity in a series of a-alkoxyaldehy-
MeOH
OH
R
RO
OH
Ph
R
Ph
Ph
Ph3P CHCO2R
dry MeOH
des derived from 1,2-O-isopropylidene-a-D-furanoses with stabi-
R
P
O
O
lized ylides,14 however, Brimacombe et al.,15 and Shing et al.16
O
CO2R
CO2R
R
O
O
R
Z-selectivity
HOMe
MeOH
α-alkoxyaldehyde
having a polar group
* Corresponding authors. Tel.: +52 2222 295500x7391; fax: +52 2222
295500x7391 (F.S.-P).
on β position
"anti-betaine"
E-mail address: fsarpis@siu.buap.mx (F. Sartillo-Piscil).
Scheme 2. Putative anti-betaine model that explain Z-selectivities.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.094

E. Ramirez et al. / Tetrahedron Letters 51 (2010) 2178–2180
2179
O
O
Thus, in an attempt to generalize this methodology by using
similar substrate and non-cyclic substrate, we treated -ribofura-
nose derivative 7 (which was also generated in straightforward
COOH
O
O
O
D
O
O
O
Ph3P
H5IO6
OEt
O
O
R2
R2
R1
4
R2
HO
O
manner from D-allofuranose 6 and H5IO6) and D-threose derivative
HO
AcOEt
H2O/NaOH
HO
O
O
R1
R1
919 under the same Wittig olefination conditions, and complete
5a
5b
R1= R2= Me (2a)
R1= H, R2 = CCl3 (2b)
DCC
3a
3b
O
erosion of the Z-selectivity was observed, giving thus an almost
equimolar mixture of a,b-unsaturated acids (Scheme 4).
O
R2
O
O
This unexpected result suggests that: the presence of a hydroxyl
group (or related functional group) in b-position is insufficient to
lead Z-selectivity, but stereochemistry and conformational restric-
tion are also key factors. Therefore, in such cases to get higher Z-
selectivities, anhydrous methanolic conditions are mandatory.15,16
In order to give a rational explanation for Z-selectivity in the
cases of 5a and 5b, anti-betaine A (derived from the reaction be-
tween 3a or 3b plus 4) is proposed, and anti-betaine B along with
its normal syn-betaine C (derived from 7 plus 4) are also proposed
(Scheme 5). Thus, the apparent dependence of Z-selectivity with
respect to stereochemistry of b-hydroxy group was investigated
by theoretical conformational study for oxaphosphorinane struc-
tures A and B (as anti-betaine models). In fact, by taking into con-
sideration the aqueous (protic) conditions, it seems logical to
postulate the existence of oxaphosphorinanes as intermediaries
O
R1
1a (85%, from 2a)
1b (88% from 2b)
Scheme 3. Selective Z-olefination and DCC-mediated lactonization to obtain
desired unsaturated lactones 1a and 1b.
O
HOOC
O
O
COOH
O
O
O
O
O
O
Ph3P
OEt
H5IO6
AcOEt
O
O
4
O
HO
O
+
HO
HO
H2O/NaOH
6
O
HO
O
7
O
E-8
82% from 6
Z-8
E-8/Z-8 =1.5/1
O
OH
OH
BnO
BnO
OH
Ph3P
OEt
BnO
BnO
4
+
O
COOH
BnO
BnO
H2O/NaOH
COOH
9
E-10
75%
Z-10
for Wittig olefinations. Besides, in a similar manner, c-oxido ylides
E-10/Z-10 =1.2/1
afford oxaphospholanes (five-membered ring P-heterocyclic) as
stable intermediaries during the Wittig reaction.20 Investigating
conformational studies reported in the literature for that six-mem-
bered ring P-heterocyclic xylo and ribofuranoses,21 we found that,
chair-boat equilibrium operates in xylofuranose derivatives22
meanwhile chair–boat-twisted equilibrium for those ribofuranose
derivatives.23
The geometry of oxaphosphorinane conformers Bc and Bb de-
rived from xylofuranose derivatives, and Cc and Cbt from ribofura-
nose derivatives were fully optimized by using GAUSSIAN 03 software
package with the Density Functional Theory (DFT) in combination
with the 6-31G(d) basis set.24 All The structures were character-
ized as true minima by calculating their respective vibrational fre-
quencies at the same level of theory (Scheme 6).
Scheme 4. Erosion of the Z-selectivity for
D
-ribofuranose and D-threose derivatives.
should be also a good medium for the same synthetic purpose, and
also it would be partially in accordance with the recent report on
the use of water as an efficient medium for selective Wittig olefin-
ation.17 With this in mind, we proceeded to prepare the stabilized
ylide 4 in aqueous medium and adding to the corresponding
b-hydroxyaldehydes 3a and 3b, which were prepared in straight-
forward manner from
H5IO6.18 Results were as we expected, high yield and complete Z-
selectivity for the formation of ,b-unsaturated acids 5a and 5b
D-glucose derivatives 1a and 1b and
a
was observed. Then, without any purification processes, 5a and
5b were treated with N,N0-dicyclohexylcarbodiimide (DCC) in
By analyzing their relative energies we found that boat confor-
mation (Bb), corresponding to xylo derivative, is 6.13 kcal/mol
more stable than its chair conformer (Bc), meanwhile chair
CH2Cl2 to afford the desired
in high yields (Scheme 3).
a,b-unsaturated lactones 1a and 1b
O
H
O
H
H
H
O
O
H
O
O
H
O
OEt
O
O
O
O
R2
R1
EtO
O
EtO
Ph
Ph
P
3a or 3b
O
R2
R1
O
O
P
Ph
O
R2
R1
+
Ph
H
Ph
Ph
H
4
O
O
O
H
O
O
H
H
O
H
H
5a or 5b
A
H
O
O
O
H
H
H
OEt
O
O
O
H
O
H
O
O
O
EtO
O
EtO
O
P
Ph
Ph
Ph
P
Ph
Ph
O
O
O
O
O
O
Ph
H
H
H
H
Z-8
O
H
O
H
H
B
7
+
4
Ph
Ph
Ph
Ph
O
O
P
O
Ph
EtO
H
P
EtO
O
Ph
EtO
O
O
O
O
O
O
H
O
H
O
O
O
O
O
H
E-8
O
H
H
C
Scheme 5. Proposed intermediaries in Wittig olefination of xylo and ribofuranose derivatives.

2180
E. Ramirez et al. / Tetrahedron Letters 51 (2010) 2178–2180
2. (a) Kolodiazhnyi, O. I. Phosphorus Ylides: Chemistry and Applications in Organic
OH
H
O
H
Ph
Ph
Ph
O
OH
H
Chemistry; Wiley-VCH: New York, 1999; (b) Takeda, T. In Modern Carbonyl
Olefination; Wiley-VCH: Weinheim, Germany, 2004.
R
O
P
O
O
Ph
O
R
P
3. (a) Guo, X.; Wang, J.; Li, C.-H. J. Am. Chem. Soc. 2009, 131, 15092–15093; (b)
Nicolaou, K. C.; Härter, M. W.; Gunzner, J. L.; Nadin, A. Liebigs Ann. Recl. 1997,
1283–1301; (c) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863–927; (d)
Vedejs, E.; Peterson, M. J. Top. Stereochem. 1994, 21, 1–57; (e) Walker, B. J.
Organophosphorus Chem. 1996, 27, 264–307.
H
Ph
O
O
Ph
Bb
(0.00 kcal/mol)
Bc
(6.13 kcal/mol)
Relative Energies in parenthesis
4. (a) El-Batta, A. M.; Jiang, C.; Zhao, W.; Anness, R.; Cooksy, A. L.; Bergdahl, M. J.
Org. Chem. 2007, 72, 5244–5259; (b) Dambacher, J.; Zhao, W.; El-Batta, A.;
Anness, R.; Jiang, C.; Bergdahl, M. Tetrahedron Lett. 2005, 46, 4473–4477.
5. Fodor, G.; Tömösközi, I. Tetrahedron Lett. 1961, 2, 579–582.
Ph
P
O
H
R
H
H
R
Ph
Ph
Ph
OH
O
OH
O
P
Ph
O
H
Ph
6. (a) Nonnenmacher, A.; Mayer, R.; Plieninger, H. Liebigs Ann. Chem. 1983, 2135–
2140; (b) Isaacs, N. S.; El-Din, G. N. Tetrahedron Lett. 1987, 28, 2191–2192.
7. Patil, V. J.; Mävers, U. Tetrahedron Lett. 1996, 37, 1281–1284.
8. (a) House, H. O.; Jones, V. K.; Frank, G. A. J. Org. Chem. 1964, 29, 3327–3333; (b)
Fliszár, S.; Hudson, R. F.; Salvadori, G. Helv. Chim. Acta 1964, 47, 159–162; (c)
Rüchardt, C.; Panse, P.; Eichler, S. Chem. Ber. 1967, 100, 1144–1164; (d) Corey, E.
J.; Clark, D. A.; Goto, G.; Marfat, A.; Mioskowski, C.; Samuelsson, B.;
Hammarström, S. J. Am. Chem. Soc. 1980, 102, 1436–1439; (e) Marriott, D. P.;
Bantick, J. R. Tetrahedron Lett. 1981, 22, 3657–3658; (f) Stafford, J. A.; McMurry,
J. E. Tetrahedron Lett. 1988, 29, 2531–2534; (g) Westman, G.; Wennerström, O.;
Raston, I. Tetrahedron 1993, 49, 483–488; (h) Hooper, D. L.; Garagan, S.; Kayser,
M. M. J. Org. Chem. 1994, 59, 1126–1128; (i) Thiemann, T.; Thiemann, C.; Sasaki,
S.; Vill, V.; Mataka, S.; Tashiro, M. J. Chem. Res. Synop. 1997, 248–249.
9. Boulaire, V. L.; Grée, R. Chem. Commun. 2000, 2195–2196.
10. Harcken, C.; Martin, S. F. Org. Lett. 2001, 3, 3591–3593.
11. Sartillo-Piscil, F.; Vargas, M.; Anaya de Parrodi, C.; Quintero, L. Tetrahedron Lett.
2003, 44, 3919–3921.
12. Dr. Shaw has also used the term SHOWO for the same synthetic purpose:
Reddy, L. V. R.; Reddy, P. V.; Shaw, A. K. Tetrahedron: Asymmetry 2007, 18, 542–
546.
13. (a) Gesson, J. P.; Jacquesy, J. C.; Mondon, M. Tetrahedron Lett. 1987, 28, 3945–
3948; (b) Gesson, J. P.; Jacquesy, J. C.; Mondon, M. Tetrahedron 1989, 45, 2627–
2640; (c) Bessodes, M.; Benamghar, R.; Antonakis, K. Carbohydr. Res. 1990, 200,
493–496; (d) Dongsoo, K. Agric. Chem. Biotechnol. 2005, 49, 62–64; See also: (e)
Baskaran, S.; Vasu, J.; Kodukulla, R. P. K.; Trivedi, G. K. Tetrahedron 1996, 52,
4515–4526; (f) Subramanian, B.; Griski, K. T. J. Chem. Res. 1995, 308–309; (g)
Tadano, K.-i.; Shimada, K.-i.; Miyake, A.; Ishihara, J.; Ogawa, S. Bull. Chem. Soc.
Jpn. 1989, 62, 3978–3986.
14. Tronchet, J. M.; Gentile, B. Helv. Chim. Acta 1979, 62, 2091–2098.
15. (a) Brimacombe, J. S.; Hanna, R.; Kabir, A. K. M. S.; Bennett, F.; Taylor, I. D. J.
Chem. Soc., Perkin Trans. 1 1986, 815–821; (b) Brimacombe, J. S.; Kabir, A. K. M.
S. Carbohydr. Res. 1986, 150, 35–51.
O
O
O
O
Cbt
(13.02 kcal/mol)
Cc
(4.53 kcal/mol)
Scheme 6. Conformer energy values for proposed oxaphosphorinanes present in
Wittig olefination of xylo and ribofuranose derivatives.
conformer (Cc) for the ribo derivative is 8.49 kcal/mol more stable
than its boat-twisted conformer (Cbt). Furthermore, key finding of
this study comes from the energy gap of 4.53 kcal/mol among the
lowest conformers of both diastereoisomer oxaphosphorinanes
(Bb and Cc), being Bc the most stable oxaphosphorinanes.25 This
energy difference should be attributed to the energy strain caused
by the trans-fusion for ribofuranose derivative, as Gerlt et al. pre-
viously found,26 by thermodynamic experiments in trans-fused
six-membered ring phosphates (cAMP), that 5 kcal/mol of thermo-
dynamic instability is regarded to geometry strain resulting from
the trans-fusion. Therefore, on the basis of the above-mentioned
theoretical results, we can assume that the trans-fusion strain en-
ergy of ribofuranose derivative 7 destabilize the formation of the
anti-betaine (B) leading to the preferential formation of normal
betaine C and thus to produce higher E-selectivity than Z-selectiv-
ity. This result is actually interesting, because pointed out that the
conformation of the anti-betaine plays a key role in the Z-selectiv-
16. Shing, T. K. M.; Tsui, H.-Ch.; Zhou, Z.-H. J. Org. Chem. 1995, 60, 3121–3130.
17. We mean ‘partially’ because in those reports E-selectivities are observed: see
Ref. 4.
ity of
In summary, we have developed a highly efficient sequential
protocol for the synthesis of ,b-unsaturated-7,3-lactone-
xylofuranoses from -glucose derivatives, which are versatile chi-
a-alkoxy-b-hydroxyaldehydes with stabilized ylides.
18. Wu, W.; Wu, Y. J. Org. Chem. 1993, 58, 3586–3588.
a
a-D-
19. Bisseret, P.; Boiteau, J.-G.; Eustache, J. Tetrahedron Lett. 2003, 44, 2351–2354.
20. Maryanoff, B. E.; Reitz, A. B.; Duhl-Emswiler, B. A. J. Am. Chem. Soc. 1985, 107,
217–226.
D
ral synthons for the preparation of biologically important com-
pounds. The key step of the synthesis is the development of a
highly Z-selective Wittig olefination reaction in aqueous media.
Additionally, the anti-betaine model, which presumably provides
a rational explanation for Z-selectivities was studied by theoretical
methods and demonstrated that boat conformation of the cyclic
anti-betaine is crucial for the Z-selectivity.
21. (a) Gallagher, M. J. In Phosphorus-31 NMR Spectroscopy in Stereochemical
Analysis; Verkade, J. G., Quin, L., Eds.; VCH: Deerfield Beach, FL, 1987. Chapter 9;
(b) Bentrude, W. G. Steric and Stereoelectronic Effects in 1,3,2-
Dioxaphosphorinanes. In Methods in Stereochemical Analysis; Juaristi, E., Ed.;
VCH: New York, 1995; (c) Frank, É.; Wolfling, J. Curr. Org. Chem. 2007, 11, 1610.
22. (a) Sartillo-Piscil, S.; Cruz-Gregorio, S.; Sánchez, M.; Höpfl, H.; Anaya de
Parrodi, C.; Quintero, L. Tetrahedron 2003, 59, 4077–4083; (b) Cruz-Gregorio, S.;
Sánchez, M.; Clara-Sosa, A.; Bérnes, S.; Quintero, L.; Sartillo-Piscil, F. J. Org.
Chem. 2005, 70, 7107–7113; (c) Hermans, R. J. M.; Buck, H. M. J. Org. Chem.
1988, 53, 2077–2084; (d) Neeser, J.-T.; Tronchet, J. M. J.; Charollais, E. J. Can. J.
Chem. 1983, 61, 1387–1396.
Acknowledgments
23. Nelson, K. A.; Bentrude, W. G.; Setzer, W. N.; Hutchinson, J. P. J. Am. Chem. Soc.
1987, 109, 4058–4064.
We gratefully acknowledge the financial support from CONA-
CyT (Grant number: 62203), and Faculty of Chemistry of Benemé-
rita Universidad Autónoma de Puebla (BUAP). We also thank
Vladimir Carranza-Tellez and Dario Corte-Salazar for technical
assistance.
24. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. J. A.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.;
Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.;
Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe,
M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A.
GAUSSIAN 03, Revision E.01, Gaussian Inc., Wallingford CT, 2004.
Supplementary data
Supplementary data (general procedure for the preparation of
1a and 1b and Cartesian coordinates for conformers Bc, Bb, Cc,
and Cbt) associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2010.02.094.
25. Other phosphorinane conformations were found close in energy, however the
ones showed in Scheme 6 represent the conformation that either controlling or
destabilizing Z-selectivity.
References and notes
26. (a) Gerlt, J. A.; Gutterson, N. I.; Datta, P.; Belleau, B.; Penney, C. I. J. Am. Chem.
Soc. 1980, 102, 1655–1665; (b) Gerlt, J. A.; Gutterson, N. I.; Drews, R. E.;
Sokolow, J. A. J. Am. Chem. Soc. 1980, 102, 1655–1670.
1. (a) Wittig, G.; Geissler, G. Liebigs Ann. Chem. 1953, 580, 44–68; (b) Wittig, G.
Science 1980, 210, 600–604.