Palladium-catalyzed carboamination of alkenes promoted by N-fluorobenzenesulfonimide via C-H activation of arenes

Article abstract of DOI:10.1021/ja9031659

(Chemical Equation Presented) This report describes a unique Pd-catalyzed oxidative carboamination of protected aminoalkenes in which inexpensive unactivated nucleophilic arenes are incorporated to give carboamination products in good yields. A variety of

Full text of DOI:10.1021/ja9031659

Published on Web 06/22/2009
Palladium-Catalyzed Carboamination of Alkenes Promoted by
N-Fluorobenzenesulfonimide via C-H Activation of Arenes
Carolyn F. Rosewall, Paul A. Sibbald, Dmitry V. Liskin, and Forrest E. Michael*
Department of Chemistry, UniVersity of Washington, Box 351700, Seattle, Washington 98195-1700
Received April 21, 2009; E-mail: michael@chem.washington.edu
Table 1. Optimization of Reaction Conditions
The intramolecular oxidative difunctionalization of alkenes is a
powerful method for the introduction of diverse functional groups
into organic molecules.1 Simultaneous formation of C-N and C-C
bonds from an olefin (carboamination) is particularly appealing, in
part because of the rarity of this transformation.2 Pd-catalyzed
aminocarbonylation of alkenes using CO as the carbon source was
extensively developed by Hegedus and Tamaru.3 Wolfe has shown
that aryl bromides can be used to form C-C bonds via Pd-catalyzed
carboamination of aminoalkenes.4 Chemler has reported a doubly
intramolecular Cu-catalyzed bicyclization of arylsulfonamidoalkenes
and arylamidoalkenes to give products resulting from carboami-
nation of the olefin.5 In the latter two reactions, the aryl group to
be incorporated must be preactivated as its halide or present
intramolecularly as a sulfonamide or amide. In this report, we
describe a unique Pd-catalyzed oxidative carboamination of pro-
tected aminoalkenes in which inexpensive unactivated nucleophilic
arenes are incorporated to give carboamination products.
We reported previously that treatment of a variety of protected
aminoalkenes with N-fluorobenzenesulfonimide (NFBS) in the
presence of a Pd catalyst in EtOAc affords the products of alkene
diamination in good yields. In these reactions, NFBS acts as an
intermolecular source of electrophilic nitrogen (eq 1 in Scheme 1).6
During the course of that study, a remarkable solvent effect was
discovered: treatment of Cbz-protected aminoalkene 1 under
diamination conditions in toluene instead of EtOAc afforded poor
yields of the expected diamination product 2. Surprisingly, com-
pound 3 was isolated as a significant byproduct resulting from
incorporation of 1 equiv of toluene (eq 2 in Scheme 1).
entry
additive(s)a
% yieldb
1
2
3
4
5
6
7
none
50
43
46
68
51
65
75
2,6-di-tert-butylpyridine
Cs2CO3
BHT
TEMPO (20 mol %)
dihydroanthracene
BHT/3 Å molecular sieves
a Unless otherwise specified, 1 equiv was used. b Determined by
HPLC.
of carboamination products were observed with both carbamates
(5a-d) and amides (5e, 5f).
Table 2. Nitrogen Protecting Group Scope
entry
PG
% yield (isolated)
1
2
3
4
5
6
Cbz (5a)
Boc (5b)
Troc (5c)
CO2Et (5d)
Ac (5e)
82
62
56
73
84
81
Scheme 1. Pd-Catalyzed Diamination Promoted by NFBS
p-toluoyl (5f)
A variety of aminoalkene substrates were able to participate in
the carboamination with toluene in good yields (Scheme 2). In
addition to the geminally disubstituted products (3, 5a, 6), mono-
and unsubstituted carbon backbones could also be cyclized under
these conditions (7-9), albeit with moderate diastereoselectivity.
Additionally, six- and seven-membered rings with various substitu-
tion patterns (10-12) could also be formed.8
Several different arenes were suitable for use in the carboami-
nation reaction (Scheme 3). Electron-rich aromatics, such as anisole
and alkylbenzenes, were effectively incorporated.8 Halobenzenes
were also suitable reagents but gave somewhat lower yields. It is
noteworthy that no participation of the Ar-Br bond was observed
under these conditions. The regioselectivity was uniformly high:
monosubstituted arenes exclusively gave para substitution products,
and o- and m-xylene exclusively gave the regioisomers coupled
para to one of the methyl groups.
Several avenues for optimizing the yield of this remarkable
transformation were explored. The use of other Pd sources and basic
additives uniformly failed to improve upon the initial conditions
(Table 1). Radical scavengers had previously proved beneficial in
the NFBS-promoted diamination reaction,6 so a variety of these
were investigated (entries 5-7) and once again found to improve
the yield. The optimal conditions for substrate 1 proved to be use
of Pd(TFA)2 as the catalyst, 3 Å molecular sieves, and 1 equiv of
BHT at room temperature, which gave a 75% yield of product 3.7
A number of synthetically useful nitrogen protecting groups were
found to be compatible with these conditions (Table 2). Good yields
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9488 J. AM. CHEM. SOC. 2009, 131, 9488–9489
10.1021/ja9031659 CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2. Aminoalkene Substrate Scopea
Scheme 4. Proposed Mechanistic Cycle
activations at both Pd(II) and Pd(IV) are generally poorly regiose-
lective.12 The fact that radical scavengers substantially increase the
yield of carboamination argues strongly against a radical mechanism.
In summary, we have demonstrated a novel method for Pd-
catalyzed carboamination of alkenes using NFBS as an oxidant to
incorporate weakly nucleophilic arenes. A variety of synthetically
useful five-, six- and seven-membered-ring nitrogen heterocycles
can be formed under these conditions.
a Conditions: 10 mol % Pd(TFA)2, 2 equiv of NFBS, 1 equiv of BHT,
3 Å molecular sieves, toluene, rt.
Scheme 3. Scope of Arene Incorporationa
Acknowledgment. The University of Washington and the
National Science Foundation are acknowledged for financial
support.
Supporting Information Available: Reaction conditions and ex-
perimental data for the syntheses of all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
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