ORGANIC
LETTERS
2003
Vol. 5, No. 25
4899-4902
Enantioselective Synthesis of Cyclic
Secondary Amines through
Mo-Catalyzed Asymmetric Ring-Closing
Metathesis (ARCM)
,†
,‡
Sarah J. Dolman,† Richard R. Schrock,* and Amir H. Hoveyda*
Department of Chemistry, Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139, and Department of Chemistry,
Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467
Received October 16, 2003
ABSTRACT
Carboyclic amines are synthesized efficiently in up to 93% ee by asymmetric ring-closing metathesis (ARCM) with 2−5 mol % chiral Mo
complexes. An example is provided where the catalyst is prepared in situ (catalyst isolation not needed) to afford secondary amines that
cannot be prepared by alternative methods.
During the past several years, research in these laboratories
has focused on the design and synthesis of new chiral Mo-
and W-based catalysts for enantioselective olefin metathesis.1
These investigations are concerned with the preparation of
molecules that cannot be easily synthesized in the nonracemic
form by alternative methods or through catalytic metathesis
of optically pure olefin-containing substrates promoted by
achiral metathesis catalysts.2 Our efforts have so far led to
the introduction of protocols through which, by catalytic
asymmetric ring-closing (ARCM)3 or ring-opening (AROM)4
metathesis, a range of optically enriched or pure organic
molecules can be accessed.
One class of compounds that is of particular significance,
due to their relevance to the synthesis of biologically active
molecules and the paucity of effective related asymmetric
methods, are acyclic and cyclic amines.5 Within this context,
we recently disclosed an efficient and highly enantioselective
(3) For examples of Mo-catalyzed ARCM, see: (a) Alexander, J. B.;
La, D. S.; Cefalo, D. R.; Hoveyda, A. H.; Schrock, R. R. J. Am. Chem.
Soc. 1998, 120, 4041-4042. (b) La, D. S.; Alexander, J. B.; Cefalo, D. R.;
Graf, D. D.; Hoveyda, A. H.; Schrock, R. R. J. Am. Chem. Soc. 1998, 120,
9720-9721. (c) Zhu, S. S.; Cefalo, D. R.; La, D. S.; Jamieson, J. Y.; Davis,
W. M.; Hoveyda, A. H.; Schrock, R. R. J. Am. Chem. Soc. 1999, 121,
8251-8259. (d) Cefalo, D. R.; Kiely, A. F.; Wuchrer, M.; Jamieson, J. Y.;
Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2001, 123, 3139-3140.
(e) Keily, A. F.; Jernelius, J. A.; Schrock, R. R.; Hoveyda, A. H. J. Am.
Chem. Soc. 2002, 124, 2868-2869.
(4) For examples of Mo-catalyzed AROM, see: (a) La, D. S.; Ford, J.
G.; Sattely, E. S.; Bonitatebus, J. P.; Schrock, R. R.; Hoveyda, A. H. J.
Am. Chem. Soc. 1999, 121, 11603-11604. (b) Weatherhead, G. S.; Ford,
J. G.; Alexanian, E. J.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc.
2000, 122, 1828-1829. (c) La, D. S.; Sattely, E. S.; Ford, J. G.; Schrock,
R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2001, 123, 7767-7778. (d) Tsang,
W. C. P.; Jernelius, J. A.; Cortez, A. G.; Weatherhead, G. W.; Schrock, R.
R.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 2652-2666.
† Massachusetts Institute of Technology.
‡ Boston College.
(1) For reviews of catalytic asymmetric olefin metathesis, see: (a)
Hoveyda, A. H.; Schrock, R. R. Chem. Eur. J. 2001, 7, 945-950. (b)
Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592-
4633.
(2) For selected reviews on catalytic olefin metathesis, see: (a) Grubbs,
R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446-452. (b)
Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34, 1833-1836. (c)
Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 2036-
2056. (d) Alkene Metathesis in Organic Synthesis; Furstner, A., Ed.;
Springer: Berlin, 1998. (e) Armstrong, S. K. J. Chem. Soc., Perkin Trans.
1 1998, 371-388. (f) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413-4450. (g) Furstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012-3043.
(h) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29. (i) Ref
1b.
10.1021/ol036026n CCC: $25.00 © 2003 American Chemical Society
Published on Web 11/19/2003