C O M M U N I C A T I O N S
Scheme 3. C26-C27 and C19-C20 Bond Formations
complete the coupling; (2) only negligible amounts of the dimers,
which are byproducts formed through the alkenyl Ni species, are
observed; (3) the coupling goes to completion even with a 1:1 molar
ratio of the coupling partners; and (4) the asymmetric induction is
practically identical with that obtained in the coupling with the Cr
catalysts prepared from (S)-sulfonamides 2a,b. The applicability
of these catalysts to polyfunctional substrates was demonstrated
using two C-C bond formations chosen from the halichondrin/
E7389 synthesis as examples. We are currently engaged in further
refinements of the tethered ligands as well as preparation of other
tethered heterobimetallic catalysts, including tethered Co/Cr catalysts.
Acknowledgment. We are grateful to the National Institutes
of Health (CA 22215) and the Eisai Research Institute for generous
financial support.
Supporting Information Available: Experimental details, charac-
terization data, and crystallographic data for 1a·NiCl2 (CIF). This
References
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(a) Saccomano, N. A. In ComprehensiVe Organic Synthesis; Trost, B. M.,
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(e) Hargaden, G. C.; Guiry, P. J. AdV. Synth. Catal. 2007, 349, 2407.
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Chem. Soc. 1972, 94, 9234.
19:1.15 The new Cr catalyst prepared from 1a·NiCl2 was found to
effect this coupling well, furnishing the desired allylic alcohol in
86% yield with dr ) 19:1. We should note, however, that a 3 mol
% catalyst loading was required to complete the coupling with an
acceptable rate. As reported previously, reductive cyclization of
the allylic alcohol stereoselectively gave 15 in 95% yield.6c
The second example was the C19-C20 bond formation employ-
ing aldehyde 16 (1.0 equiv) and vinyl iodide 17 (1.1 equiv) (Scheme
3).6c With the previous Cr catalyst (20 mol %) derived from the
antipode of 2a, the desired allylic alcohol 18 was obtained in ∼90%
yield with dr ) 20:1.15 Again, the new Cr catalyst prepared from
the antipode of 1a·NiCl2 was found to work well for this bond
formation, furnishing 18 in 91% yield with dr ) 19:1. It is
noteworthy that 2 mol % catalyst loading was sufficient to complete
the coupling with an acceptable rate. As previously reported, the
allylic alcohol was converted to 18 in 88% yield.6c
In conclusion, we have reported two new ligands 1a,b. Upon
treatment with 1 equiv of NiCl2 ·(MeOCH2)2, 1a,b give the
corresponding Ni complexes. X-ray analysis of 1a·NiCl2 established
that the NiCl2 is selectively coordinated to the phenanthroline
nitrogens. The Ni/Cr heterobimetallic catalysts 1a,b ·CrCl2/NiCl2
prepared from 1a,b ·NiCl2 behave exceptionally well in catalytic
asymmetric Ni/Cr-mediated couplings, with highlights including
the following: (1) 1-2 mol % 1a,b ·CrCl2/NiCl2 is sufficient to
(5) According to the mechanistic study by Tsou and Kochi (Tsou, T. T.; Kochi,
J. K. J. Am. Chem. Soc. 1979, 101, 7547.), the reactive intermediates
involved in this process are Ni(I) and Ni(III) species.
(6) (a) Guo, H.; Dong, C.-G.; Kim, D.-S.; Urabe, D.; Wang, J.; Kim, J. T.;
Liu, X.; Sasaki, T.; Kishi, Y. J. Am. Chem. Soc. 2009, 131, 15387. (b)
Kim, D.-S.; Dong, C.-G.; Kim, J. T.; Guo, H.; Huang, J.; Tiseni, P. S.;
Kishi, Y. J. Am. Chem. Soc. [Online early access]. DOI: 10.1021/ja9058475.
Published Online: Oct 6, 2009. (c) Dong, C.-G.; Henderson, J. A.; Kaburagi,
Y.; Sasaki, T.; Kim, D.-S.; Kim, J. T.; Urabe, D.; Guo, H.; Kishi, Y. J. Am.
Chem. Soc. [Online early access]. DOI: 10.1021/ja9058487. Published
online: Oct 6, 2009. Also see references cited therein.
(7) For recent reviews of bimetallic catalysts, see: (a) Shibasaki, M.; Matsunaga,
S.; Kumagai, N. Synlett 2008, 1583. (b) Ma, J.-A.; Cahard, D. Angew.
Chem., Int. Ed. 2004, 43, 4566.
(8) Namba, K.; Cui, S.; Wang, J.; Kishi, Y. Org. Lett. 2005, 7, 5417.
(9) Phenanthroline also forms the NiCl2 complex selectively. However, this
Ni complex causes a significant reduction in the asymmetric induction upon
translation from stoichiometric to catalytic conditions (see ref 8).
(10) Ligand-exchange rates on Cr(II) are known to be up to 15-16 orders of
magnitude faster than those on Cr(III) (see ref 3c).
(11) Wan, Z.-K.; Choi, H.-w.; Kang, F.-A.; Nakajima, K.; Demeke, D.; Kishi,
Y. Org. Lett. 2002, 4, 4431.
(12) It is not clear whether 8 formed after the complete consumption of 5 or
through a leakage of the alkenyl Ni complex. However, the latter seems to
be more likely, as a trace amount of 8 was observed even in the coupling
of 5 (1.1 equiv) and 6 (1.0 equiv).
(13) For the coupling of 5 with 6, the Cr catalysts derived from 2a,b gave er )
9.8:1 and 5.1:1 asymmetric inductions, respectively.
(14) For halichondrins and E7389, see refs 1-3 in ref 6b.
(15) Using the toolbox strategy for a ligand search, we recently identified two
sulfonamides that allow us to form the C26-C27 and C19-C20 bonds
with dr ≈ 50:1 and 26:1, respectively (see ref 6a, c).
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