1
30
U. Groth, M. Jeske
LETTER
above described systems allows for the first time the dias- References and Notes
tereoselective coupling of hexanal. The 1,2-diol was iso-
(
1) Lanthanides in Organic Synthesis, part 4. For part 3, see ref.
3.
lated in yields of up to 82% and diastereoselectivities of
up to 85: 15 (entry 3). The reductive coupling of pentanal
and heptanal gave similar results. To the best of our
knowledge this reaction achieves the highest diastereose-
lectivities in the coupling of sterically non demanding al-
iphatic aldehydes published until now. Based on its ability
of highly diastereoselective pinacol couplings manganese
was favored over magnesium and zinc (entries 1-3). Con-
sequently, all further coupling reactions were carried out
1
(
2) a) Kropf, H.; Thiem, J. Houben-Weyl, Methoden der
Organischen Chemie, Vol. 6/1a/1 (Ed. Müller, E.), Thieme-
Verlag, Stuttgart 1984, 592; b) Kolb, H. C.; VanNieuwenhze,
M.S.; Sharpless, K. B. Chem. Rev. 1994, 94, 2483; c) Becker,
H.; Sharpless, K. B. Angew. Chem. Int. Ed. Engl. 1996, 35,
448.
(
3) a) House, H.O. Modern Synthetic Reactions, Benjamin, New
York 1965, 59; b) Kropf, H.; Thiem, J. Houben-Weyl,
Methoden der Organischen Chemie Vol. 6/1a/2 (Ed. Müller,
E.), Thieme-Verlag, Stuttgart 1984, 1485; c) Robertson, G. M.
Comprehensive Organic Synthesis, Vol. 3 (Ed. Trost, B.M.;.
Fleming, I.; Pattenden, G.), Pergamon Press, Oxford 1991,
563.
1
5
with manganese.
Since all above mentioned studies were carried out with
Ce(OiPr) the influence of the cerium ligand was investi-
3
gated next.
(
4) a) Kammermeier, B.; Beck, G.; Jacobi, D.; Jendralla, H.
Angew. Chem. Int. Ed. Engl. 1994, 33, 685; b) Reetz, M.T.;
Griebenow, N. Liebigs Ann. Chem. 1996, 335.
Table 2 Cerium(III)-Catalyzed Pinacol Couplings of Benzaldehyde
and Hexanal by Variation of the Cerium Ligand.
(5) a) Shiina, I.; Nishimura, T.; Ohkawa, N.; Sakoh, H.;
Nishimura, K.; Saitoh, K.; Mukaiyama, T. Chem. Lett. 1997,
419; b) Nicolaou, K.C.; Yang, Z.; Liu, J.J.; Ueno, H.;
Nantermet, P.G.; Guy, R.K.; Claiborne, C.F.; Renaud, J.;
Couladouros, E.A.; Paulvannan, K.; Sorensen, E.J. J. Am.
Chem. Soc. 1995, 117, 634; c) Nazare, M.; Waldmann, H.
Angew. Chem. Int. Ed. Engl. 2000, 39, 1125; d) Kim, S. M.;
Byun, I. S.; Kim, Y. H. Angew. Chem. Int. Ed. Engl. 2000, 39,
728.
(
6) a) Hirao, T.; Asahara, M.; Muguruma, Y.; Ogawa, A. J. Org.
Chem. 1998, 63, 2812; b) Hirao, T.; Hatano, B.; Imamoto, Y.;
Ogawa, A. J. Org. Chem. 1999, 64, 7665.
(
(
(
7) Nomura, R.; Matsuno, T.; Endo, T. J. Am. Chem. Soc. 1996,
118, 11666.
8) Wild, F.R.W.P.; Zsolnai, L.; Huttner, G.; Brintzinger, H.H. J.
Organomet. Chem. 1982, 232, 233.
9) a) Gansäuer, A. Synlett 1997, 363; b) Gansäuer, A.;
Moschioni, M.; Bauer, D. Eur. J. Org. Chem. 1998, 1923;
c) Gansäuer, A.; Bauer, D. J. Org. Chem. 1998, 63, 2070; d)
Gansäuer, A. Synlett 1998, 801.
As shown in Table 2 remarkable differences between ce-
rium chlorides and cerium alkoxides were observed. Ac-
cordingly, the use of catalytic amounts of CeCl leads to
3
acceptable yields but very low diastereoselectivities (en- (10) Bandini, M.; Cozzi, P.G.; Morganti, S.; Umani-Ronchi, A.
Tetrahedron Lett. 1999, 40, 1997.
try 1). Similar results were obtained using ClCe(OiPr)2
(
(
(
11) Dunlap. M.S.; Nicholas, K.M. Synth. Commun. 1999, 29,
097.
12) Eckenberg, P.; Groth, U.; Köhler, T. Liebigs Ann. Chem.
994, 673.
(
entry 2). Nevertheless the yield and especially the diaste-
1
reoselectivity were increased by changing from ceri-
um(III)chlorides to cerium(III)alkoxides (entries 3-5).
Best results could be achieved by using more bulky
ligands such as tert-butoxide (entry 5).1
1
13) Groth, U.; Jeske, M. Angew. Chem. Int. Ed. Engl. 2000, 39,
574.
6
(
(
14) Fürstner, A. Chem. Eur. J. 1998, 4, 567.
In summary, we have presented an efficient method for
the highly diastereoselective pinacol coupling of alde-
15) a) Fürstner, A.; Chem. Rev. 1999, 99, 991; b) Li, C.-J.; Meng,
Y.; Yi, X.-H. J. Org. Chem. 1997, 62, 8632; c) Svatos, A.;
Boland, W. Synlett 1998, 549; d) Rieke, R.D.; Kim, S.-H. J.
Org. Chem. 1998, 63, 5235; e) Li, C.-J.; Meng, Y.; Yi, X.-H.
J. Org. Chem. 1998, 63, 7498.
hydes. Best results were obtained by using Ce(OtBu) as
3
catalyst. To the best of our knowledge aliphatic a-unsub-
stituted aldehydes could be coupled with high diastereose-
lectivity for the first time. The pinacol coupling of
functionalized aldehydes is under current investigation in
our group. These results should be of broad interest in nat-
ural product synthesis.
(
16) Typical Experimental Procedure:
The reactions were carried out under argon atmosphere using
Schlenk techniques. Substances which are sensitive against
moisture and oxidation were stored in a glove box.
The cerium alkoxides Ce(OtBu) and Ce(OCHiPr ) were
3
2 3
synthesized by refluxing Ce(OiPr) with 10 equivalents of the
3
corresponding alcohol in toluene. After 15 h the excess of
alcohol was removed in vacuo.
Acknowledgement
This work has been supported by the Fonds der Chemischen Indu-
strie and by the EU Commission, Directorate General XII. M. J.
thanks the Stiftung Stipendienfonds des Verbandes der Chemischen
Industrie for a doctoral fellowship.
In a Schlenk tube 5 mL THF were added to 32 mg (0.1 mmol;
3 mol%) Ce(OtBu) and 326 mg (6.0 mmol; 2.0 equivalents)
3
manganese powder. Subsequently, 3.0 mL (3.0 mmol) of an
1.0M aldehyde solution in THF and 3.0 ml (4.5 mmol;
1.5 equivalents) of an 1.5 M TMSCl solution in THF were
added slowly by use of a syringe pump. After 24 h 25 mL of
Synlett 2001, No. 1, 129–131 ISSN 0936-5214 © Thieme Stuttgart · New York