Angewandte
Chemie
when electron-rich ligands are used. In these cases, 3 can be
converted into the thermodynamically more stable 4 by the
same intermediate B. p-Allylcomplex B is likely to be in
equilibrium with the s-allylcomplex C, which might even be
the resting state of this catalytic cycle, in agreement with
similar observation we have made in the related reaction of
alkynes and allenes with carboxylic acids as pronucleo-
philes.[13] In C, the previous chiral information of the O-
allylated product 3 is lost, and once again the chiral catalyst
has control of the enantioselectivity en route to the thermo-
dynamic product 4 by way of a dynamic kinetic asymmetric
transformation.[18]
4572 – 4585; b) J. A. Pfefferkorn, J. Lou, M. L. Minich, K. J.
Filipski, M. He, R. Zhou, S. Ahmed, J. Benbow, A.-G. Perez, M.
Tu, J. Litchfield, R. Sharma, K. Metzler, F. Bourbonais, C.
993 – 996; d) J. Golec, P. Charifson, J.-D. Charrier, H. Binch,
WO01042216, 2001.
[2] a) Y.-Q. Yang, M. M. Bio, K. B. Hansen, M. S. Potter, A.
Clausen, J. Am. Chem. Soc. 2010, 132, 15525 – 15527; b) F. G.
759 – 764; d) M. L. Minich, I. D. Watson, K. J. Filipski, J. A.
Verissimo, N. Berry, P. Gibbons, M. L. S. Cristiano, P. J. Rosen-
The new pyridone allylation can be applied to the
synthesis of the known glucokinase activators 6 (Scheme 8).
[3] For the only example with two-step asymmetric Overman-type
3,3-rearrangement, see: A. Rodrigues, E. E. Lee, R. A. Batey,
[4] For non-chiral transition-metal-catalyzed rearrangement of 2-
allyloxypyridines, see: a) H. F. Stewart, R. P. Seibert, J. Org.
R. V. Venkataratnam, Tetrahedron Lett. 1996, 37, 2829 – 2832;
[7] a) A. Lumbroso, P. Koschker, N. R. Vautravers, B. Breit, J. Am.
Scheme 8. The synthesis of glucokinase activators 6.
Rhodium-catalyzed selective addition of 2-pyridone 1p to
allene 2k afforded the key intermediate 4kp in 98% yield and
94% ee. Subsequent oxidation and methylation gave com-
pound 5 with 96% ee, which can be converted into com-
pounds 6 by aluminum-mediated amide formation with
a variety of aminoheterocycles.[1b]
In conclusion, we have developed the rhodium-catalyzed
direct chemo-, regio- and enantioselective allylation of 2-
pyridones with allenes in an atom-economic manner under
neutral conditions.[19] A broad range of 2-pyridones coupled
with functionalized allenes to give a-chiral N-allylic pyri-
dones. This reaction can be used in the synthesis of
biologically active molecules. Further studies will focus on
the selective allylation of other ambident nucleophiles.
[8] For details, see the Supporting Information.
[9] For a related steric effect on rearrangement of 6-substituted
alkoxylpyridine, see: a) C. S. Yeung, T. H. H. Hsieh, V. M. Dong,
[10] In Ref. [3], the cyclohexyl group stops the palladium-catalyzed
rearrangement for steric reasons. Phenyl allene was tested and it
gave low conversion. 1,3-Disubstituted allene gave low con-
version, and only O-allyl product was detected.
[11] For the crystal structure, see the Supporting Information.
CCDC 1016609 (R-4da) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
[12] Full conversion was obtained. Besides the N-allylated product,
the elimination products 2-pyridone and 1,3-diene were
observed in the 1H NMR of the crude mixture.
Received: August 4, 2014
Published online: October 8, 2014
Keywords: allenes · asymmetric allylation ·
.
reaction mechanisms · 2-pyridones · rhodium
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H. T. Luu, S. K. Sakata, E. L. Brown, F. C. Maldonado, T.
Tuntland, C. A. Lee, S. A. Fuhrman, L. S. Zalman, A. K. Patick,
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[13] For the related mechanism study, see: U. Gellrich, A. Meißner,
A. Steffani, M. Kꢁhny, H.-J. Drexler, D. Heller, D. A. Plattner, B.
[14] For stoichiometric studies of phenol with transition metal, see:
Angew. Chem. Int. Ed. 2014, 53, 13780 –13784
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