Angewandte
Chemie
DOI: 10.1002/anie.201407233
Allylrhodium Isomerization
The Isomerization of Allylrhodium Intermediates in the Rhodium-
Catalyzed Nucleophilic Allylation of Cyclic Imines**
Hamish B. Hepburn and Hon Wai Lam*
Abstract: Allylrhodium species generated from potassium
allyltrifluoroborates can undergo isomerization by 1,4-rho-
dium(I) migration to give more complex isomers, which then
react with cyclic imines to provide products with up to three
new stereochemical elements. High enantioselectivities are
obtained using chiral diene–rhodium complexes.
T
he catalytic enantioselective nucleophilic allylation of
aldehydes and imines is a useful route to homoallylic alcohols
and amine derivatives.[1] Recently, we described the enantio-
selective rhodium-catalyzed nucleophilic allylation[2] of cyclic
imines[3,4] using the chiral dienes L1/ent-L1[5] which, to our
knowledge, are the first examples of rhodium-catalyzed
enantioselective additions of allylboron reagents to p-electro-
philes.[6] These reactions enable the formation of products
with up to two stereocenters with high diastereo- and
enantioselectivities.[2] Herein, we report the discovery of an
isomerization of allylrhodium intermediates, resulting in
more complex allylrhodium species that would otherwise be
difficult to access. This isomerization allows the formation of
products containing up to three new stereochemical elements
(two stereocenters and an alkene of defined geometry) with
high diastereo- and enantiocontrol.
Scheme 1. The enantioselective Rh-catalyzed allylation of cyclic imines.
Previously, we demonstrated that the cyclic aldimine 1a
reacted with the prenyltrifluoroborate 2a (Scheme 1a)[2a] or
its isomer 2b (Scheme 1b)[2b] to give the same reverse
prenylation product 3a, thus suggesting the involvement of
a common allylrhodium intermediate. In further experiments,
the racemic allylation of the saccharin-derived cyclic ketimine
4a with the prenyltrifluoroborate 2a was attempted
(Scheme 2). Surprisingly, a 70% yield of a mixture of
products was obtained, in which the expected reverse
prenylation product 6a was only the minor component (5a/
Scheme 2. The allylation of ketimine 4a with 2a or 2b.
6a = 74:26 by 1H NMR analysis). The major product was the
homoallylic sulfonamide 5a, obtained in > 95:5 d.r.,[7] which
presumably results from an isomerization of the allylrhodium
intermediate. A second purification of this mixture led to the
isolation of 5a in 48% yield. Very similar results were
obtained with the isomeric allyltrifluoroborate 2b.
A mechanism that is consistent with these observations
and also explains the stereochemical outcome is presented in
Scheme 3. First, the transmetalation of the trifluoroborates 2a
or 2b with rhodium is expected to result in the allylrhodium
species 7, as described previously.[2] With more reactive cyclic
imines such as 1a (Scheme 1), the reaction with the allylrho-
dium species 7 proceeds readily to provide the expected
reverse prenylation products such as 3a. However, the
saccharin-derived imine 4a is considerably less reactive than
the aldimine 1a, and the formation of the sterically congested
reverse prenylation product 6a is less favored. Instead, we
hypothesize that a reversible 1,4-rhodium migration[8–10] of 7,
[*] H. B. Hepburn, Prof. H. W. Lam
EaStCHEM, School of Chemistry, University of Edinburgh
Joseph Black Building, The King’s Buildings
West Mains Road, Edinburgh, EH9 3JJ (UK)
and
School of Chemistry, University of Nottingham
University Park, Nottingham, NG7 2RD (UK)
E-mail: hon.lam@nottingham.ac.uk
[**] We thank the ERC (Starting Grant No. 258580), the EPSRC
(Leadership Fellowship to H.W.L.), and GlaxoSmithKline for
financial support. We thank Nawasit Chotsaeng (University of
Edinburgh) for preliminary experiments. Dr. William Lewis (Uni-
versity of Nottingham) is acknowledged for assistance with X-ray
crystallography.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2014, 53, 11605 –11610
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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