Protecting group-directed, diastereoselective samarium diiodide-promoted carbocyclization: Application to the synthesis of cyclitols

Full text of DOI:10.1021/jo9623898

1916
J . Org. Chem. 1997, 62, 1916-1917
Sch em e 1
P r otectin g Gr ou p -Dir ected ,
Dia ster eoselective Sa m a r iu m
Diiod id e-P r om oted Ca r bocycliza tion :
Ap p lica tion to th e Syn th esis of Cyclitols†
Mercedes Carpintero,
Alfonso Ferna´ndez-Mayoralas,* and Carlos J aramillo
Instituto de Qu´ımica Orga´nica General, CSIC, J uan de la
Cierva, 3, E-28006 Madrid, Spain
Received December 20, 1996
The recognition of elements of symmetry1,2 in organic
synthesis is extremely useful for the efficient preparation
of complex chiral molecules. The existence of a latent
plane of symmetry1 allows the enantiodivergent synthesis
of both enantiomers of a given molecule from a common
precursor, while the presence of a C2 axis of symmetry3
greatly simplifies the number of steps of a synthetic
sequence.
We would like to report our preliminary work on the
application of this strategy to the synthesis of cyclitols 6
and 9 as key intermediates for the preparation of the
carbasugar-containing pseudotrisaccharide 1. This trisac-
charide is a hydrolytically stable analog4 of the previously
described trisaccharide 2, found to inhibit neural cell
division,5 and is closely related to the biologically impor-
tant6 Lewis X and sialyl Lewis X oligosaccharides. Apart
from the intrinsic interest of this pseudotrisacchride,7 its
synthesis would be also valuable for structural studies,
since it has been shown that the conformation of C-8 or
S-disaccharides9 can be different from that of O-disac-
charides.10
which in turn, can be derived from inositol 6 due to the
presence of a latent plane of symmetry.1,11 On the other
hand, the presence of a C2 axis of symmetry in 6 would
result in a significant simplification of the synthesis,3 and
D-mannitol (7; R ) R2 ) H) could be used as starting
material.
In principle, 6 could be prepared through the sa-
marium diiodide-promoted pinacol coupling12,13 of the
dialdehyde derived from 7, but the stereochemical out-
come of such a reaction is usually opposite to that
required.14,15 However, we have found (Scheme 2) that
The carbasugar components of 1, cyclitols 3 and 4,
belong to the D-galacto and L-fuco series, respectively
(Scheme 1). A closer look at them shows that they could
be prepared from the enantiomeric pair of conduritols 5,
(7) For the chemistry of pseudosugars, see: (a) Suami, T.; Ogawa,
S. Adv. Carbohydr. Chem. Biochem. 1990, 48, 21-90. (b) Hudlicky,
T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe, A. J . Chem. Rev. 1996, 96,
1195-1220.
(8) Espinosa, J .-F.; Can˜ada, F. J .; Asensio, J . L.; Mart´ın-Pastor, M.;
Dietrich, H.; Mart´ın-Lomas, M.; Schmidt, R. R.; J ime´nez-Barbero, J .
J . Am. Chem. Soc. 1996, 118, 10862-10871.
† Dedicated to Prof. Hans Paulsen on the occasion of his 75th
birthday.
* To whom correspondence should be addressed. Fax: 34-1-5644853.
E-mail: iqofm68@ fresno.csic.es.
(9) Geyer, A.; Hummel, G.; Eisele, T.; Reinhardt, S.; Schmidt, R. R.
Chem. Eur. J . 1996, 2, 981-988.
(1) (a) Hudlicky, T. Chem. Rev. 1996, 96, 3-30. (b) Hudlicky, T.;
Natchus, M. G. In Organic Synthesis: Theory and Applications;
Hudlicky, T., Ed.; J AI Press: Greenwich, CT, 1993; Vol. 2, pp 1-25.
(2) Bertz, S. H.; Sommer, T. J . In Organic Synthesis: Theory and
Applications; Hudlicky, T., Ed.; J AI Press: Greenwich, CT, 1993; Vol.
2, pp 67-92.
(10) The conformational study of pseudodisaccharides bearing a
carbasugar in the reducing end has been reported: Duus, J . Ø.; Bock,
K.; Ogawa, S. Carbohydr. Res. 1994, 252, 1-18.
(11) The plane of symmetry is defined by the different protecting
groups (R1 and R2) at both sides of the molecule. A further simplifica-
tion of the synthesis could be imagined if the olefin and trans-diol
functional groups in 5 and ent-5 were interconvertible with each other,
defining then a latent plane of symmetry that would make possible
the use of any of these compounds as a more advanced intermediate
in the synthesis. Efforts in this direction will be addressed in the near
future.
(3) The simplification of a synthesis taking advantage of elements
of symmetry is based on the concept of reflexivity.2
(4) For other recent approaches to the synthesis of hydrolytically
stable analogs, see, for example: (a) Wei, A.; Haudrechy, A.; Audin,
C.; J un, H.-S.; Haudrechy-Bretel, N.; Kishi, Y. J . Org. Chem. 1995,
60, 2160-2169. (b) Aguilera, B.; Ferna´ndez-Mayoralas, A. Chem.
Commun. 1996, 127-128. (c) Eisele, T.; Toepfer, A.; Kretzscmar, G.;
Schmidt, R. R. Tetrahedron Lett. 1996, 37, 1389-1392. (d) Sutherlin,
D. P.; Armstrong, R. W. J . Am. Chem. Soc. 1996, 118, 9802-9803.
(5) Cotero´n, J . M.; Singh, K.; Asensio, J . L.; Dom´ınguez-Dalda, M.;
Ferna´ndez-Mayoralas, A.; J ime´nez-Barbero, J .; Mart´ın-Lomas, M.;
Abad-Rodr´ıguez, J .; Nieto-Sampedro, M. J . Org.Chem. 1995, 60, 1502-
1519.
(6) (a) Yuen, C. T.; Lawson, A. M.; Chai, W.; Larkin, M.; Stoll, M.
S.; Stuart, A. C.; Sullivan, F. X.; Ahern, T. J .; Feizi, T. Biochemistry
1992, 31, 9126-9131. (b) Lasky, L. A. Science 1992, 258, 964-969. (c)
Kojima, N.; Fenderson, B. A.; Stroud, M. R.; Goldberg, R. I.; Haber-
mann, R.; Toyokuni, T.; Hakomori, S.-I. Glycoconjugate J . 1994, 11,
238-248. (d) Streit, S.; Stern, C. D. Biol. Cell 1995, 84, 63-67.
(12) For recent reviews on applications of samarium diiodide in
organic synthesis, see: Molander, G. A. Chem. Rev. 1996, 96, 307-
338.
(13) For samarium diiodide-promoted pinacol coupling of related
carbohydrate derivatives, see: (a) Chiara, J . L.; Mart´ın-Lomas, M.
Tetrahedron Lett. 1994, 35, 2969-2972. (b) Guidot, J . P.; Le Gall, T.;
Mioskowski, C. Tetrahedron Lett. 1994, 35, 6671-6672. (c) Chiara, J .
L., Valle, N. Tetrahedron: Asymmetry 1995, 6, 1895-1898. (d) Sawada,
T.; Shirai, R.; Iwasaki, S. Tetrahedron Lett. 1996, 37, 885-886.
(14) A cis-diol is usually the main stereoisomer in intramolecular
pinacol coupling reactions,13 although the opposite stereochemistry has
been observed in acyclic systems: Taniguchi, N.; Kaneta, N.; Uemura,
M. J . Org. Chem. 1996, 61, 6088-6089. See also: Kang, M.; Park, J .;
Konradi, A. W.; Pedersen, S. F. J . Org. Chem. 1996, 61, 5528-5531.
S0022-3263(96)02389-4 CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 7, 1997 1917
protected diol 7b,16 when submitted to the two-step
procedure, gave the expected diastereoselectivity, leading
to allo-inositol 9b. To our knowledge, this is the first
example of a pinacol coupling where stereoselectivity can
be driven by the appropriate choice of the protecting
groups at the adjacent positions. An additional proof of
the structures of inositols 6a and 9b was obtained
(Scheme 2) by its conversion into peracetates 10 and 11,
whose physical properties matched those previously
described.18
Sch em e 2a
Once the diastereoselective cyclitol formation was
attained, we focused on the dihydroxy-elimination of 6a ,
which turned out to be difficult due to both the trans-
diequatorial configuration of the diol system and the
presence of the relatively labile silyl protecting groups.
All conventional methods tested19 met with failure, but
hydrogen telluride-mediated20 elimination of a cyclic
sulfate21 derived from 6a afforded (Scheme 3) conduritol
E derivative 5a , albeit in low yield. On the other hand,
access to conduritol 5b was easily achieved from cis-diol
9b by using the Corey-Winter method.22 Its structure
was secured by transformation into conduritol E perac-
etate 5c, whose physical properies matched those previ-
ously described.23
In summary, this paper describes a samarium diiodide-
mediated carbocyclization that allows the preparation,
for the first time, of a trans-diol by applying such
methodology. The cis-diol, arising from the usual dias-
tereoselectivity, can be obtained by simply changing the
protecting groups of the vicinal positions. Work directed
toward the synthesis of the target carbasugars, taking
advantage of the C2 axis of symmetry existent in 5, is
currently underway and will be reported in due course.
a
Key: (a) Swern oxidation; (b) SmI2, t-BuOH, THF, -60 °C;
(c) CF3CO2H, MeOH; (d) TBAF, THF; (e) Ac2O, Py; (f) H2, Pd(C),
AcOH, MeOH.
Sch em e 3a
Ack n ow led gm en t. Financial support by Comu-
nidad Auto´noma de Madrid and CSIC (to M.C. and C.J .,
respectively), and DGICYT (Grant No. PB93-0127-C02-
01), is greatly appreciated. Dr. J .-L. Chiara is gratefully
acknowledged for helpful discussions.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and spectroscopic data for the reported compounds (7
pages).
J O9623898
(17) All new compounds showed correct microanalytical and spec-
troscopic data.
(18) (a) Tschamber, T.; Backenstrass, F.; Fritz, H.; Streith, J . Helv.
Chim. Acta 1992, 75, 1052-1060. For other syntheses of neo- and allo-
inositol, see: (b) Hudlicky, T.; Cebulak, M. Cyclitols and Their
Derivatives. A Handbook of Physical, Spectral and Synthetic Data; VCH
Publishers: New York, 1993. (c) Hudlicky, T.; Mandel, M.; Rouden,
J .; Lee, R. S.; Bachmann, B.; Dudding, T.; Yost, K. J .; Merola, J . S. J .
Chem. Soc., Perkin Trans. 1 1994, 1553-1567 and references cited
therein.
(19) (a) Angyal, S. J .; Gilham, P. T. J . Chem. Soc. 1958, 375-379.
(b) Barrett, A. G. M.; Barton, D. H. R.; Bielski, R. J . Chem. Soc., Perkin
Trans. 1 1979, 2378-2381. (c) Garegg, P. J .; Samuelsson, B. Synthesis
1979, 469-470. (d) Beels, C. M. D.; Coleman, M. J .; Taylor, R. J . K.
Synlett 1990, 479-480. (e) Barton, D. H. R.; J ang, D. O.; J azsberenyi,
J . Ch. Tetrahedron Lett. 1991, 2569-2572.
(20) (a) Bargues, V.; Blay, G.; Ferna´ndez, I.; Pedro, J . R. Synlett
1996, 655-656. (b) Clive, D. L. J .; Wickens, P. L.; Sgarbi, P. W. M. J .
Org. Chem. 1996, 61, 7426-7437.
(21) Chao, B.; McNulty, K. C.; Dittmer, D. C. Tetrahedron Lett. 1995,
36, 7209-7212.
(22) Corey, E. J .; Winter, R. A. E. J . Am. Chem. Soc. 1963, 85, 2677-
2678. For an application of this methodology cyclitols, see ref 13e.
(23) See ref 18a. For other syntheses of conduritol E, see: Angelaud,
R.; Landais, Y. J . Org. Chem. 1996, 61, 5202-5203 and references cited
therein.
a
Key: (a) SOCl2, Et3N, CH2Cl2; (b) NaIO4, RuCl3, CH2Cl2, H2O;
(c) NaTeH, DMF, 70 °C; (d) Im2C(S), PhMe; (e) P(OEt)3, 165 °C;
(f) p-TsOH, MeOH; (g) Na, NH3, -78 °C; (h) Ac2O, Py.
the sequence of oxidation and samarium diiodide-
promoted carbocyclization of diol 7a 16 gives diastereose-
lectively neo-inositol 6a .17 On the other hand, benzyl-
(15) Typically, a trans-directing effect of adjacent alkoxy groups is
observed in intramolecular pinacol coupling reactions promoted by
samarium diiodide, and it has been attributed to steric and/or
electrostatic interactions involving the ketyl radical anion and the
alkoxy substituent.13
(16) 7a and 7b were prepared in five and four steps, respectively,
from D-mannitol. See the Supporting Information.