1364
LETTERS
SYNLETT
Four Chiral Centers in a One Pot Procedure. Analogues of Isosorbide
Julio G. Urones, Isidro S. Marcos, Narciso M. Garrido, P. Basabe, Sonia G. San Feliciano, Raquel Coca and David Díez*
Dpto. de Química Orgánica, Universidad de Salamanca. Plaza de los Caídos 1–5, 37008 Salamanca, SPAIN.
Received 28 September 1998
Abstract: Synthesis of analogues of isosorbide in one pot from
1-hydroxymethyl-4-phenylsulfonylbutadienes has been achieved.
In the previous paper, we have described a simple way to obtain
1-sulfonyl-1,3-dienes with adequate functionalization. These
compounds have been the object of numerous studies in the last years,
1
above all as dienes or dienophiles. Furthermore, it should be noted that
there are more examples with sulfoxides rather than sulfones due to the
2
potential chirality that these substrates can possess.
In our case, having developed a very easy way to get 1-sulfonyl-1,3-
dienes with an allylic alcohol, we wanted to exploit this feature to
produce chiral compounds by way of the Sharpless enantioselective
3
epoxidation.
In this way, we planned to develop a short synthesis of analogues of
4
isosorbide 1. Amino derivatives of 1 are being used as chiral auxiliaries
in asymmetric synthesis while the dinitro derivative 2 and the piperazine
5
derivative 3 possess antianginal activity . 1, has been used recently as
the starting material for the synthesis of novel bicyclic
6
dideoxynucleosides as potential antiviral agents 4.
Scheme 1
between them. The stereochemistry of H-8 was based on its coupling
constant with H-1 ( J = 5.8 Hz ), the other stereochemistry would give a
nearly zero coupling constant, (see ref 4). This was confirmed by the
existence of n.O.e between H-1 and H-8 in the bencil derivative.
So, in conclusion we have developed a short, and stereocontrolled way
to obtain analogues of isosorbide. At the moment, we are trying to
introduce further functionalization at C-8, and a range of electrophiles
are being used in the addition step.
Acknowledgement: This work was supported by Junta de Castilla y
Leon (SA 44-96); M.E.C. and CICYT.
All different routes to isosorbide analogues start from isosorbide 1 as
the starting material. In this context, we have found a new and versatile
method to obtain analogues with different stereochemistry and
functionalization, which allows not only the use of SN type reactions
but also the use electrophilic reagents.
References and Notes
2
(1) a) Backwall, J.E.; Löfstrom, C.; Maffesal, M.; Lauger, V.
Tetrahedron Lett. 1992, 33, 2417. b) Padwa, A.; Gareau, Y.;
Harrison, B.; Norman, B.H. J. Org. Chem. 1991, 56, 2713.
Results and discussion
(2) a) Aversa, M. C.; Baratucci, A.; Bonaccorsi, P.; Gianneto, P.
Tetrahedron Asymm. 1997, 9, 1339. b) Carreño, M. C. Chem. Rev.
1995, 95, 1717.
Compound 6 was easily obtained as described in the previous paper by
treatment of sulfone 5 with n-BuLi/THF at -78° C (Scheme I).
Treatment of 6 with n-BuLi/THF followed by addition of acetone as the
electrophile gives compound 7 in excellent yields (90%). When 7 reacts
with m-CPBA it afford compound 8 directly (77%). The second
cyclization proved to be difficult, with bases such as NaH or KH giving
(3) Gao, Y.; Hauson, R.M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.;
Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765
(4) Tamion, R.; Marsais, F.; Ribereau, P.; Queguiner, G.; Abenhaim,
D.; Loupy, A.; Munnier, L. Tetrahedron Asymm. 1993, 8, 1879.
7
t
inconsistant results. However, use of Craig´s conditions ( BuOH/
(5) Hayashi, H.; Keolo, J. I.; Kubo, K.; Mokiyama, J.; Karasama, A.;
t
BuOK 5:1) gave satisfactory yields of 9 (83%).
Suzuki, F. Chem. Pharm. Bull. 1993, 41, 1100
When 7 reacts under Sharpless conditions with L-(+)-DET, after the
usual work up of the reaction only homochiral (-)-9 is isolated. The
stereochemistry was established by study of N.M.R. spectra and n.O.e.
studies. The CIS relationship between H-4 and H-5 (mechanism) was
confirmed by the n.O.e observed (Scheme I) and the same relationship
of H-5 and H-1 was established for the existence of another n.O.e.
(6) Chao, Q.; Zhang, J.; Pickening, T. S.; Jahande, M.; Nair, V.
8
Tetrahedron 1998, 54, 3113.
(7) a) Craig, D.; Ikin, M. J.; Mathews, N.; Smith, A. M. Tetrahedron
Lett. 1995, 41, 7531. b) Padwa, A.; Gareau, Y.; Harrison, B.;
Norman, B. H. J. Org. Chem. 1991, 56, 2713.
Urones, Julio G.
