To identify improved catalysts for ketone allylation, we
examined other d8 transition metal complexes, including
iridium complexes.6 We hypothesized that allyliridium(I)
complexes would be sufficiently nucleophilic to react with
ketones, in part due to the low oxidation state of the metal.
We designed an iridium-catalyzed reaction of ketones with
allylboronic ester (Scheme 1). The transformation would
Table 1. Allylboration of Acetophenone Catalyzed by Iridium
Complexesa
entry
catalyst
conversion (%)b
Scheme 1. Iridium-Catalyzed Allylation Reaction
2
3
[Ir(cod)Cl]2
[Ir(coe)2Cl]2
[Ir(coe)2Cl]2 + Cy2PCH2CH2PCy2 (7)
[Ir(cod)Cl]2 + phosphine 7
[Ir(coe)2Cl]2 + (R)-BINAP
[Ir(coe)2Cl]2 + (R,R)-Me-DUPHOS
[Ir(coe)2Cl]2 + norbornadiene
[Ir(coe)2Cl]2 + cod
100
<5
27
44
31
44
15
100
3c
4c
5c
6c
7c
8c
a See Supporting Information for full experimental details. b Conversion
1
to 6a was measured by H NMR spectroscopy using an internal standard,
1,4-bistrifluoromethylbenzene. c 5 mol % of the indicated ligand was
employed.
alcohol with no preference for either enantiomer (entries 5
and 6). Iridium complexes that are not ligated by a diene or
phosphine, such as [Ir(coe)2Cl]2, do not catalyze the reaction
(entry 2).
initiate by a transmetalation reaction to generate a nucleo-
philic allyliridium(I) complex (2). This complex would react
with the ketone to provide an iridium alkoxide complex (3).
A subsequent transmetalation reaction would regenerate the
catalyst and liberate the product (4). We have validated this
hypothesis and found that [Ir(cod)Cl]2 is a highly reactive
catalyst for ketone allylation using allylboronic esters at room
temperature. In related studies, Krische has achieved ally-
lation of aldehydes using allyl acetate at 100 °C using
[Ir(cod)Cl]2 in the presence of bidentate phosphine ligands.7,8
Mechanistic studies determined that these reactions proceed
via nucleophilic allyliridium(III) intermediates.
In mechanistic studies, we have determined that ligation
of IrI by either a diene or a bidentate phosphine provides a
catalyst for ketone allylation (Table 1). [Ir(cod)Cl]2 catalyzes
allylation of acetophenone in three hours at room tempera-
ture, using 1.2 equiv of allylboronic ester. Iridium phosphine
complexes, prepared from [Ir(coe)2Cl]2 and a bidentate
phosphine, such as 7, also catalyze the transformation, albeit
with slower rates of reaction (entries 3, 5, and 6). Ligation
by both cyclooctadiene and a phosphine slows the reaction
(entry 4). Chiral phosphines screened yielded the homoallylic
With a highly reactive catalyst identified, we examined
allylation of a series of ketones (Table 2). A combination of
KOt-Bu and boric acid as additives provided the highest yield
of tertiary homoallylic alcohols.9 A variety of aromatic and
heteroaromatic ketones react under these reaction conditions.
Substrates with either electron-withdrawing or electron-
donating substituents reacted within 3 h. Halide substituents
including bromide were tolerated, and no products resulting
from oxidative addition into the C-X bond were observed.10
Aliphatic ketones also reacted, although with a slight decrease
in yield. Reactions of aldimines were slower than reactions
of ketones and required increased reaction times. Nonethe-
less, p-methoxyphenyl (PMP) protected imines (8) reacted
to afford homoallylic amines (9) in good yields.
Mechanistic experiments were consistent with our working
hypothesis shown in Scheme 1. Allylation of acetophenone
with deuterated boronic ester 10 provided a mixture of
products, 11a and 11b (Scheme 2). This result is consistent
(5) (a) Barczak, N. T.; Grote, R. E.; Jarvo, E. R. Organometallics 2007,
26, 4863–4865. (b) Grote, R. E.; Jarvo, E. R. Org. Lett. 2009, 11, 485–
488. (c) Shaghafi, M. B.; Kohn, B. L.; Jarvo, E. R. Org. Lett. 2008, 10,
4743–4746. (d) Waetzig, J. D.; Swift, E. C.; Jarvo, E. R. Tetrahedron 2008
64, in press.
Scheme 2. Deuterium Scrambling Experiments are Consistent
with Intermediacy of Nucleophilic Allyliridium(I) Complexes
(6) (a) Takeuchi, R.; Kashio, M. J. Am. Chem. Soc. 1998, 120, 8647–
8655. (b) Markovic, D.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 11680–
11681.
(7) (a) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc.
2008,ASAP. (b) Kim, I. S.; Ngai, M.-Y.; Krische, M. J. J. Am. Chem. Soc.
2008, 130, 6340–6341. See also: Masuyama, Y.; Chiyo, T.; Kurusu, Y.
Synlett 2005, 2251–2253
.
(8) Iridium-catalyzed allylation of aldehydes using allenes and dienes:
(a) Skucas, E.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc. 2007, 129,
12678–12679. (b) Bower, J. F.; Skucas, E.; Patman, R. L.; Krische, M. J.
J. Am. Chem. Soc. 2007, 129, 15134–15135. (c) Bower, J. F.; Patman, R. L.;
Krische, M. J. Org. Lett. 2008, 10, 1033–1035
.
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