SCHEME 1. Problems Associated with the Hydrolytic
Cleavage of Dithioacetals Like 1a
Polymer-Assisted Dithane Hydrolysis with
Minimum Workup
Silke Luiken and Andreas Kirschning*
Institut fu¨r Organische Chemie and Center of Biomolecular
Drug Research (BMWZ), Leibniz UniVersita¨t HannoVer,
Schneiderberg 1b, 30167 HannoVer, Germany
During the course of a synthetic project in the field of
prostaglandin chemistry,8 we had to find conditions for the
hydrolytic cleavage of dithioacetals like 1a, 1h, and 1i.
Unfortunately, all common homogeneous conditions tested
(transition metals, oxidative and alkylation conditions) failed
or at best afforded vinyl sulfide 2 in maximum 22% yield
(Scheme 1).9
andreas.kirschning@oci.uni-hannoVer.de
ReceiVed NoVember 22, 2007
Therefore, we had to search for a method for cleaving
dithioacetals that only requires mild workup conditions. Ideally,
chromatographic purification should be avoided. On the basis
of our experience in the development of polymer-bound reagents
and scavengers10 we devised a concept that relies on a polymer-
bound thiophilic reagent based on iodine and two scavenger
resins (Scheme 2). In fact, the bistrifluoroacetoxy iodate(I) ion11
is highly thiophilic as we demonstrated before for the activation
of thioglycosides.12 The anionic character can be used to create
the corresponding exchange resin 3. In this paper the first solid
phase assisted concept of dithioacetal hydrolysis is disclosed
The first solid-phase-assisted protocol for the hydrolysis of
dithioacetals is described using three different functionalized
ion exchange resins. The hydrolysis and the purification
proceed under milder conditions than common homoge-
neously employed reagents so that very reactive carbonyl
compounds can be prepared.
(7) (a) Smith, A. B., III; Pitram, S. M. Org. Lett. 1999, 1, 2001-2004.
(b) Smith, A. B., III; Zhuang, L. L.; Brook, C. S. C. S.; Lin, Q. Q.; Moser,
W. H.; Lee, W. H.; Trout, R. E.; Boldi, A. M. Tetrahedron Lett. 1997, 38,
8671-8674. (c) Smith, A. B., III; Lin, Q.; Nakayama, K.; Boldi, A. M.;
Brook, C. S.; McBriar, M. D.; Moser, W. H.; Sobukawa, M.; Zhuang, L.
Tetrahedron Lett. 1997, 38, 8675-8678. (d) Smith, A. B., III; Zhu, W.;
Shirakami, S.; Sfouggatakis, C.; Doughty, V. A.; Bennett, C. S.; Sakamoto,
Y. Org. Lett. 2003, 5, 761-764. (e) Smith, A. B., III; Doughty, V. A.; Lin,
Q.; Zhuang, L.; McBriar, M. D.; Boldi, A. M.; Moser, W. H.; Murase, N.;
Nakayama, K.; Sobukawa, M. Angew. Chem. 2001, 113, 197-201; Angew.
Chem., Int. Ed. 2001, 40, 191-195. (f) Smith, A. B., III; Doughty, V. A.;
Sfouggatakis, C.; Bennett, C. S.; Koyanagi, J.; Takeuchi, M. Org. Lett.
2002, 4, 783-786. (g) Smith, A. B., III; Kim, D.-S. Org. Lett. 2004, 6,
1493-1495.
(8) Michel, T. Ph.D. Thesis, Technical University Clausthal, 1995.
(9) Different methods were investigated including the most common
strategy with mercury salts like mercury(II) chloride, red mercury oxide,
and HgO/BF3‚OEt2. Further experiments were conducted with “claycop”
(copper(II) nitrate and clay with the active species NO+), NBS, DMSO, hν
activated magnesium perchlorate, and alkylating reagents like methyl iodide.
(a) Corey, E. J.; Erickson, B. W. J. Org. Chem. 1971, 36, 3553-3560. (b)
Seebach, D. Synthesis 1969, 17-36. (c) Katzenellenbogen, J. A.; Bowlus,
S. B. J. Org. Chem. 1973, 38, 627-632. (d) Woessner, W. D.; Ellison, R.
A. Tetrahedron Lett. 1972, 35, 3735-3738. (e) Vedejs, E.; Fuchs, P. L. J.
Org. Chem. 1971, 36, 366-367. Balogh, M.; Corne´lis, A.; Laszlo, P.
Tetrahedron Lett. 1984, 25, 3313-3316. (f) Cornelis, A.; Laszlo, P.
Synthesis 1985, 909-918. (g) Rao, C. S.; Chandrasekharam, M.; Ila, H.;
Junjappa, H. Tetrahedron Lett. 1992, 33, 8163-8164. (h) Epling, G. A.;
Wang, Q. Synlett 1992, 335-336. (i) Trost, B. M.; Preckel, M.; Leichter,
L. M. J. Am. Chem. Soc. 1975, 97, 2224-2232.
(10) (a) Kirschning, A.; Wittenberg, R.; Monenschein, H. Angew. Chem.
2001, 113, 670-701; Angew. Chem., Int. Ed. 2001, 40, 650-679. (b) Ley,
S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.;
Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J.
Chem. Soc., Perkin Trans. 1 2000, 3815-4195.
(11) (a) Kirschning, A.; Jesberger, M.; Monenschein, H. Tetrahedron
Lett. 1999, 40, 8999-9002. (b) Monenschein, H.; Sourkouni, G.; Schubothe,
K. M.; O’Hare, T.; Kirschning, A. Org. Lett. 1999, 1, 2101-2104.
(12) (a) Jaunzems, J.; Sourkouni-Argirusi, G.; Jesberger, M.; Kirschning,
A. Tetrahedron Lett. 2003, 44, 637-639. (b) Jaunzems, J.; Hofer, E.;
Jesberger, M.; Sourkouni-Argirusi, G.; Kirschning, A. Angew. Chem. 2003,
115, 1198-1202; Angew. Chem., Int. Ed. 2003, 42, 1166-1170.
Dithioacetals have recently experienced a renewed interest
in synthetic organic chemistry partly because new, highly
efficient methods for their preparation starting from propargylic
carbonyl compounds and bis-ynones have been developed.1
Furthermore, Schaumann and Kirschning2 have developed a new
tandem reaction that is based on the silyl dithioacetal moiety.3,4
It has seen diverse applications in the synthesis of KDO,5
apicularen A,6 and polyketide chains found in the mycoticins
and in spongistatin7
* Address correspondence to this author.
(1) (a) Sneddon, H. F.; Gaunt, M. J.; Ley, S. V. Org. Lett. 2003, 5, 1147-
1150. (b) Sneddon, H. F.; van den Heuvel, A.; Hirsch, A. K. H.; Booth, R.
A.; Shaw, D. M.; Gaunt, M. J.; Ley, S. V. J. Org. Chem. 2006, 71, 2715-
2725. (c) Gaunt, M. J.; Hook, D. F.; Tanner, H. R.; Ley, S. V. Org. Lett.
2003, 5, 4815-4818. (d) Gaunt, M. J.; Sneddon, H. F.; Hewitt, P. R.; Orsini,
P.; Hook, D. F.; Ley, S. V. Org. Biomol. Chem. 2003, 1, 15-16. (e) Ball,
M.; Gaunt, M. J.; Hook, D. F.; Jessiman, A. S.; Kawahara, S.; Orsini, P.;
Scolaro, A.; Talbot, A. C.; Tanner, H. R.; Yamanoi, S.; Ley, S. V. Angew.
Chem. 2005, 117, 5569-5574; Angew. Chem., Int. Ed.2005, 44, 5433-
5438.
(2) (a) Kirschning, A.; Kujat, C.; Luiken, S.; Schaumann, E. Eur. J. Org.
Chem. 2007, 2387-2400. (b) Schaumann, E.; Kirschning, A. Synlett 2007,
177-190.
(3) Fischer, M.-R.; Kirschning, A.; Michel, T.; Schaumann, E. Angew.
Chem. 1994, 106, 220-221; Angew. Chem., Int. Ed. Engl. 1994, 33, 217-
218.
(4) Tietze, L. F.; Geissler, H.; Gewert, J. A.; Jakobi, U. Synlett 1994,
511-512.
(5) Bra¨uer, N.; Kirschning, A.; Schaumann, E. Eur. J. Org. Chem. 1998,
2729-2732.
(6) Petri, A. F.; Bayer, A.; Maier, M. E. Angew. Chem. 2004, 116, 5945-
5947; Angew. Chem., Int. Ed. 2004, 43, 5821-5823.
10.1021/jo7025146 CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/14/2008
2018
J. Org. Chem. 2008, 73, 2018-2020