Communications
DOI: 10.1002/anie.200800689
Indole Synthesis
ꢀ
Dirhodium(II)-Catalyzed Intramolecular C H Amination of Aryl
Azides**
Meihua Shen, Brooke E. Leslie, and Tom G. Driver*
The development of new transition-metal-catalyzed methods
for selective functionalization of carbon–hydrogen bonds
continues to be an active area of research.[1] Whereas many
transition-metal complexes exhibit activity,[1] rhodium(II)
dimers[1c,2] are well established to react with a-diazo com-
pounds[3,4] or sulfonyliminoiodinanes[5,6] to access metal
carbenoids or nitrenoids,which can functionalize proximal
would enable the rhodium-catalyzed synthesis of indoles by
ꢀ
the formation of either the aryl C N bond (from azidoacry-
ꢀ
lates) or the creation of the vinyl C N bond (from aryl azides;
Scheme 1). As the thermal variant of this reaction,the
Sundberg indole synthesis,[8e] requires heating of the poten-
ꢀ
ꢀ
ꢀ
aliphatic C H bonds to form new C C bonds or C N bonds
in a stereoselective manner. Transition-metal-mediated for-
ꢀ
mation of new carbon–nitrogen bonds from vinyl or aryl C H
bonds,however,is much less common.
[7]
Azides can be employed in the amination of aromatic or
ꢀ
vinyl C H bonds. Thermolysis or photolysis of azides
produces nitrenes,[8,9] which react with proximal C H bonds
ꢀ
to form N-heterocycles.[10] Nitrenes,however,are highly
reactive and can decompose into a variety of byproducts,
[8b]
including amines,azobenzenes,or tars.
Whereas metal-
Scheme 1. Complimentary rhodium(II)-catalyzed indole syntheses.
mediated nitrogen atom transfer reactions from azides are
well-known to attenuate this extreme nitrene reactivity,[11,12]
dirhodium(II) carboxylates have been rarely employed to
catalyze these processes[13–15] despite their proven utility in
other related atom transfer reactions. Since azides are readily
tially explosive aryl azide and produces indole in variable
yields,transition-metal-catalysis of this reaction at a reduced
temperature would enhance the synthetic utility of this
transformation.
available,[10c,16,17] their use in new transition-metal-mediated
[18]
ꢀ
methods that create new C N bonds is highly appealing.
We recently discovered that indoles could be generated
from azidoacrylates 2 through exposure to catalytic amounts
of rhodium(II) perfluorobutyrate.[18a] Whereas this reaction
exhibited a broad substrate scope,it required an a-azidome-
thylacetate,which restricted product formation to 2-indole-
carboxylate esters.[17c] Achievement of indole synthesis from
Toward this goal,the potential for a transition-metal-
ꢀ
mediated vinyl C H bond amination reaction of 4 was
investigated (Table 1). We found that the use of rhodium(II)
catalysts with electron-deficient carboxylate ligands afforded
promising yields and conversions (Table 1,entries 2–4). The
use of 100 wt% of crushed 4 molecular sieves enabled the
reduction of the catalyst loading to 2 mol%,and was required
to produce reproducible results (Table 1,entry 3). Exposure
of the aryl azide to the recovered molecular sieves did not
result in any indole production. The lack of reactivity by the
recovered molecular sieves indicates that rhodium is not
being deposited onto the solid support to create a new
heterogeneous catalyst. Whereas our earlier study identified
rhodium(II) perfluorobutyrate as the only competent cata-
lyst,[18a] indole formation from aryl azide 4 could be mediated
as well by rhodium(II) octanoate (Table 1,entry 6). With this
rhodium complex,12,-dichloroethane was found to be the
superior solvent (Table 1,entry 7). Employing other less
soluble or more sterically congested rhodium(II) carboxylate
or rhodium(II) lactamate complexes provided only trace
indole formation (Table 1,entries 5,8,and 9). As we observed
in our previous method,no reaction was detected with other
metal salts[11] (such as Ag,[21] Cu,[6b] Au,[22] Co,[23] and Fe
complexes[24]) or Lewis (or Brønsted) acids[25] reported to
catalyze nitrenoid formation from azides or other nitrene
equivalents.[20]
ꢀ
aryl azides 3 through rhodium-catalyzed vinyl C H bond
amination would address this limitation as a broader range of
aryl azides are readily available from commercial starting
materials in two mild,functional group tolerant steps:
palladium-catalyzed Suzuki cross-coupling of 2-bromoani-
lines[19] and subsequent diazo transfer would produce 3.[20] The
combination of this potential method with our earlier one
[*] Dr. M. Shen, B. E. Leslie, Prof. Dr. T. G. Driver
Department of Chemistry
University of Illinois at Chicago
845 W. Taylor St., Chicago, IL 60607 (USA)
Fax: (+1)312-996-0431
E-mail: tgd@uic.edu
[**] This research was financially supported by the Petroleum Research
Fund administered by the American Chemical Society (46850-G1)
and the University of Illinois at Chicago. We thank Dr. Dan McElheny
(UIC) for assistance with NMR spectroscopy, and Dr. Furong Sun
(UIUC) for mass spectrometry data.
Supporting information for this article is available on the WWW
5056
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2008, 47, 5056 –5059