Communications
DOI: 10.1002/anie.201005552
Synthetic Methods
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Selective Intramolecular C H Amination through the Metalloradical
Activation of Azides: Synthesis of 1,3-Diamines under Neutral and
Nonoxidative Conditions**
Hongjian Lu, Huiling Jiang, Lukasz Wojtas, and X. Peter Zhang*
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Amino groups exist ubiquitously in natural products and
synthetic molecules, and play key roles in a wide range of
important applications. Consequently, immense effort has
been devoted to the development of efficient and selective
processes for the preparation of amines.[1] Among different
system that is highly effective for the intramolecular 1,6-C H
amination of sulfamoyl azides to furnish six-membered cyclic
sulfamides. Not only excellent regioselectivity, but also high
diastereoselectivity and stereospecificity were observed with
the catalytic system. The cobalt(II)-catalyzed amination is
operationally simple, as it proceeds under neutral and non-
oxidative conditions without the need for other reagents, and
N2 is the only byproduct. Consequently, the degree of
functional-group tolerance is high, and the reaction can be
applied to substrates with various substituents, such as
oxidizable amide and sulfide groups. An important feature
of this catalytic system is the effective amination of strong
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approaches, the catalytic amination of abundant C H bonds
on the basis of a metal-mediated nitrene-insertion pathway is
one of the most general and direct methods for installing
nitrogen functionalities.[2] The promise of this approach as a
synthetically useful methodology has been demonstrated with
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a number of intramolecular C H amination processes
through the combined use of RhII -based catalysts and
2
iminoiodane nitrene sources.[2,3] Notably, Du Bois and co-
workers elegantly demonstrated that N-Boc-protected sulfa-
mides could be selectively converted into cyclic sulfamides by
[Rh2(esp)2] in combination with PhI(OAc)2 and MgO to
provide access to synthetically useful 1,3-diamines (esp =
primary C H bonds, as well as secondary and tertiary C H
bonds.
À
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a,a,a’,a’-tetramethyl-1,3-benzenedipropionate).[4] The RhII -
2
based intramolecular amination was shown to be effective for
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both secondary and tertiary C H bonds with stereospecificity
and high diastereoselectivity. However, the amination of
[5]
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strong primary C H bonds had yet to be demonstrated.
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Scheme 1. Cobalt(II)-catalyzed intramolecular C H amination of sulfa-
Moreover, the catalytic system was unsuitable for simple N-
alkyl sulfamides, which were oxidatively degraded by the
stoichiometric oxidant, PhI(OAc)2.[4]
moyl azides under neutral and nonoxidative conditions: general
synthetic strategy for 1,3-diamine derivatives.
As stable metalloradicals, cobalt(II) complexes of por-
phyrins, [Co(Por)], have emerged as a new class of catalysts
[6]
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for C H amination. The cobalt(II)-based metalloradical
A wide range of sulfamoyl azides 2 were conveniently
prepared from the corresponding amines 1 on the basis of
reported procedures (see the Supporting Information).[12,13]
At the outset of this project, we selected the simple azide 2a
as a model substrate to explore the possibility of the
amination (MRAm) is different from the commonly studied
Rh2 system, as it can operate effectively with various azide
substrates without the need for terminal oxidants and other
additives.[7–11] To further validate the utility of C H amination
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methodology based on a cobalt(II) catalyst and azides, we
envisioned a general strategy for the synthesis of 1,3-diamines
from monoamines through the key step of the intramolecular
C H amination of sulfamoyl azides with [Co(Por)]
(Scheme 1). We report herein a cobalt(II)-based catalytic
cobalt(II)-catalyzed intramolecular C H amination of sulfa-
moyl azides and to establish effective reaction conditions
(Scheme 2). Although nonfunctionalized [Co(TPP)] was
found to be an ineffective catalyst, [Co(P1)], in which the
D2h-symmetric porphyrin 3,5-DitBu-IbuPhyrin, P1, has amide
functionalities at the ortho positions of two meso phenyl
groups, effectively catalyzed the intramolecular amination of
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[*] Dr. H. Lu, Dr. H. Jiang, Dr. L. Wojtas, Prof. Dr. X. P. Zhang
Department of Chemistry, University of South Florida
Tampa, FL 33620-5250 (USA)
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2a through a selective 1,6-C H nitrene-insertion process
under mild conditions (Scheme 2). Owing to the absence of
oxidants or other additives, the cobalt(II)-catalyzed reaction
proceeded cleanly to afford the desired six-membered cyclic
sulfamide 3a as essentially the only product in 95% yield (the
by-product was nitrogen gas). The difference in catalytic
reactivity between [Co(TPP)] and [Co(P1)] can be considered
as a dramatic demonstration of ligand-accelerated catalysis
and could be rationalized as the outcome of a potential
Fax: (+1)813-974-1733
E-mail: xpzhang@usf.edu
[**] We are grateful for financial support by the National Science
Foundation (CAREER Award: CHE-0711024).
Supporting information for this article is available on the WWW
10192
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 10192 –10196