Gold(I)-catalyzed intra- and intermolecular hydroamination of unactivated olefins

Article abstract of DOI:10.1021/ja053864z

Ph₃PAuOTf catalyzes efficient intra- and intermolecular hydroamination of unactivated olefins with sulfonamides. Copyright

Full text of DOI:10.1021/ja053864z

Published on Web 01/25/2006
Gold(I)-Catalyzed Intra- and Intermolecular Hydroamination of Unactivated
Olefins
Junliang Zhang, Cai-Guang Yang, and Chuan He*
Department of Chemistry, The UniVersity of Chicago, 5735 South Ellis AVenue, Chicago, Illinois 60637
Received June 12, 2005; E-mail: chuanhe@uchicago.edu
Table 2. Gold(I)-Catalyzed Intramolecular Hydroamination of
Metal-catalyzed hydroamination of simple olefins is one of the
important strategies to prepare nitrogen-containing molecules.1,2
Despite significant efforts that have been devoted into this idea,2-4
only a few examples of intermolecular hydroamination of unacti-
vated olefins are known. On the basis of some recent studies,5 we
envisioned that hydroamination of unactivated olefins might be
catalyzed by gold complexes, as well. We report here the gold(I)-
mediated hydroamination of inert olefins to afford acyclic or cyclic
nitrogen-containing molecules. This discovery adds another new
methodology into the growing list of reactions that can be catalyzed
by gold ions.6
Tosylated Amino Olefinsa
In preliminary experiments, we tested reactions between cyclo-
hexene and various nitrogen nucleophiles. p-Toluenesulfonamide
(TsNH2) stands out as an excellent candidate for this reaction.
N-cyclohexyl-p-toluenesulfonamide could be prepared in 90%
isolated yield by reacting TsNH2 with 4 equiv of cyclohexene in
toluene with a catalytic amount (5 mol %) of Ph3PAuOTf (generated
Table 1. Intermolecular Hydroamination of Olefinsa
a Reactions were conducted with 0.5 mmol of substrate and 5 mol % of
Ph3PAuCl/AgOTf in 2 mL of toluene at 85 °C. b Isolated yield. c Ns)
2-nitrobenzenesulfonate.
by mixing equal equivalents of Ph3PAuCl and AgOTf) at 85 °C
for 15 h (eq 1). With the use of other nitrogen-based molecules,
such as amines, anilines, carboxyamides, carbamates, alkylsulfona-
mides, or sulfamates, the reactions gave none or very low yields
of the desired products. Other Lewis acids, such as Zn(OTf)2 and
Cu(OTf)2, could not catalyze the same reaction, and Sc(OTf)3 gave
less than 20% of the addition product under the same conditions.
This reaction works for a range of different olefins, as shown in
Table 1. Terminal olefins can serve as good substrates to afford
the Markovnikov addition products (Table 1, entries 6-9). N-
methyl-p-toluenesulfonamide (2b) as well as p-methoxyphenylsul-
fonamide could be used as the nucleophiles (Table 1, entries 2, 3,
8, and 12). The â-hydride elimination step that typically leads to
the unsaturated addition products with palladium-mediated reac-
tions3,7 does not occur with the use of gold(I) catalyst. Intramo-
lecular alkene hydroamination was also examined, and several
N-tosylated γ-amino olefins were efficiently cyclized to afford
pyrrolidines with gold(I) (Table 2). 2-Nitrobenzene sulfonamide
could also be employed as an efficient nucleophile (Table 2, entry
2). Amides did not work as nucleophiles for this reaction (one
example is shown in Table 2, entry 3). Preliminary studies indicate
that carbamates also work as nucleophiles in intramolecular
additions.
a Reactions were conducted with 1 mmol of nucleophiles, 4 mmol of
olefins (2.0-2.8 mmol could be recovered after the reaction in most cases),
and 5 mol % of Ph3PAuCl/AgOTf in 2 mL of toluene at 85 °C. b Isolated
yield. c The yield in parentheses refers to a reaction performed without
solvent. d At 95 °C. e R ) MeOC6H4. f 9c:9c′ ) 2:1. g A 1:1 ratio of TsNH2
and norbornene was used.
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J. AM. CHEM. SOC. 2006, 128, 1798-1799
10.1021/ja053864z CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
In summary, we demonstrate that gold(I) catalyzes intra- and
intermolecular hydroamination of unactivated olefins under rela-
tively mild conditions. Saturated products with tosyl-protected
amines were obtained with a range of olefins.
Acknowledgment. This research was supported by the Uni-
versity of Chicago, a Research Innovation Award (RI1179) from
Research Corporation, and a Research Fellowship from Alfred P.
Sloan Foundation (C.H.).
We further tested hydroamination of 1,5-dienes with TsNH2. The
first intermolecular hydroamination of a 1,5-diene by TsNH2 could
be followed by a second intramolecular hydroamination to produce
pyrrolidines in an “one-pot” operation (Scheme 1).3h A mixture of
cis and trans products was isolated in 64% yield with the use of
12a. Introduction of substitutions at the internal olefinic carbon
led to the higher product yields, as shown in Scheme 1 with 13a
and 14a.
A d2-labeled substrate 15a was synthesized to probe the reaction
(eq 2). Product 15b was isolated in 96% yield under the same
reaction conditions. The stereochemistry of the two protons in 15b
was assigned conclusively based on the measured coupling constant
and comparison to analogous compounds. This result suggests that
the sulfonamide attacks from the opposite face of a gold(I)-bound
olefin to give the trans-addition product after protonolysis of the
resulting gold(I)-C bond (a cis-addition mechanism would give
the product with the two protons trans to each other). A previous
calculation has suggested that gold(I)-mediated addition of water/
alcohol to alkynes may proceed through a cis-addition mechanism.6e
The sulfonamide used here is a weak ligand that appears to add
trans to the gold(I)-olefin complex. A similar anti-oxyauration has
also been shown recently.6n
Supporting Information Available: Experimental details and
Figure S1. This material is available free of charge via the Internet at
http://pubs.acs.org.
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The interaction between the catalyst and substrates was studied
by 31P NMR at 85 °C.8 Ph3PAuCl/AgOTf gave a peak at 25.8 ppm;
addition of 20 equiv of TsNH2 shifted the peak to 26.1 ppm (perhaps
there is a weak interaction between TsNH2 and gold). Addition of
20 equiv of norbornene to this solution further shifted the signal to
29.6 ppm (the same peak was observed if mixing just norbornene
with Ph3PAuOTf). This peak is assigned to a (Ph3PAu-olefin)+
complex, which shifted to 27.3 ppm if cyclohexene was used instead
of norbornene. In control experiments with an excess of TsNH2,
these peaks shifted back to 26.1 ppm after all olefins were
consumed, suggesting that these might be the active species during
the reaction. A small peak at 42.6 ppm was also observed and
assigned to (Ph3P)2Au+,9 which did not catalyze this reaction in
control experiments with an extra equivalent of Ph3P. An unlikely
mechanism involving formation of Ph3PAuNHTs and triflic acid
from reacting Ph3PAuOTf with TsNH2 can be ruled out.10 Ph3-
PAuNHTs was synthesized,10 which gives a 31P NMR signal at
30.9 ppm. This is very different from the 31P NMR signal observed
in the mixture of Ph3PAuOTf with TsNH2. In fact, we have never
observed this signal from our reactions.
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observed even when 30% of the catalyst was employed. These more
nucleophilic/basic molecules do not appear to inhibit the reaction
by simply shutting down the proton transfer pathway (work as bases
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