Cobalt-catalyzed hydroazidation of olefins: Convenient access to alkyl azides

Article abstract of DOI:10.1021/ja052164r

Conversion of olefins to azides was achieved with high Markovnikov selectivity for a broad range of alkenes using 6 mol % Co(BF₄)·6H₂O and ligand 1, with 3 equiv of TsN₃ as nitrogen source and simple silanes (PhSiH₃, TMDSO). Copyright

Full text of DOI:10.1021/ja052164r

Published on Web 05/21/2005
Cobalt-Catalyzed Hydroazidation of Olefins:
Convenient Access to Alkyl Azides
Je´roˆme Waser, Hisanori Nambu, and Erick M. Carreira*
Laboratorium fu¨r Organische Chemie, ETH Ho¨nggerberg, CH-8093 Zu¨rich, Switzerland
Received April 5, 2005; E-mail: carreira@org.chem.ethz.ch
Chart 1
Amines and related functional groups are ubiquitous in natural
products as well as pharmaceutical substances. Consequently, the
development of methods for the introduction of nitrogen in simple
organic compounds is an intense focus of research.1 Azides are
easily converted into either amines2a or pharmaceutically relevant
heterocycles.2b,c Furthermore, they have recently generated much
interest due to their stability under physiological conditions and
their unique reactivity, which permits their use in bioconjugation
via Staudinger ligation2d or click chemistry.2e The most common
access route to alkyl azides involves the substitution reaction of
primary or secondary alkyl halides with inorganic azides.3 The direct
reaction of alkenes with hydrazoic acid sources is limited to alkenes
that give rise to stabilized carbocations and require excess HN3,4a
TMSN3,4b or zeolite-supported NaN3,4c unactivated monosubstituted
olefins being described as unreactive in these processes.4 Herein
we report the functionalization reaction of unactivated olefins to
the corresponding azides with high Markovnikov selectivity using
tosyl azide (TsN3) and a silane. The reaction is mediated by a simple
cobalt catalyst prepared in situ from Schiff base 1 and Co(BF4)2‚
6H2O (eq 1).
complex 5 (Chart 1), which we thought to be the active catalyst
for the hydrohydrazination reaction; however, this complex was
inactive in olefin hydroazidation. Analysis of the mass spectrum
revealed complex 6 to be present in the mixture obtained via the
in situ oxidation procedure en route to 5. Complex 6 could be
prepared by refluxing a 1:1:1 mixture of salicylaldehyde, 2-ami-
noisobutyric acid, and Co(OAc)2‚4H2O in water under argon,
collecting the precipitating solid and oxidizing it in air in the
presence of 1 equiv of 2-amino-isobutyric acid in ethanol. The
activity of the complex obtained was comparable to that observed
with the mixture isolated using our original protocol.
The identification of a cobalt complex incorporating a single
tridentate ligand in the active catalyst presented new opportunities
for catalyst design. We speculated that increasing the steric bulk
around the tridentate ligand could lead to a complex with enhanced
stability and perhaps greater activity. With this design strategy in
mind, 7 was synthesized. Preformation of Schiff base 1 derived
from 3,5-di-tert-butyl salicylaldehyde and R,R-diphenyl glycine
followed by reaction with Co(NO3)2‚6H2O and oxidation with H2O2
proved crucial to the isolation of 7. Interestingly, coordination of
a second molecule of R,R-diphenyl glycine to the cobalt center was
never observed by NMR and mass spectroscopy. Nonetheless, we
observed that 7 was indeed a better catalyst, converting 4-phenyl-
butene (4) to the desired azide in 12 h in 60% yield. Further
investigations revealed a batch-to-batch dependency with some
catalyst preparations showing lower reactivity and long (up to 12
h) initiation period. Inspired by Mukaiyama’s work in olefin
hydration,6 we used 30% t-BuOOH as an additive to facilitate
initiation of the reaction. We were gratified to observe full
conversion to product in 2-8 h under otherwise identical conditions.
In the optimal procedure, in situ preparation of the catalyst from
Co(BF4)2‚6H2O and 1 gave 70% of the desired azide in 1.5 h,
allowing reproducible yields and reaction times.
We have recently documented the Co- and Mn-catalyzed
hydrohydrazination reaction of alkenes (RO2CNdNCO2R + alkene
f N-alkyl hydrazine).5 This reaction is the nitrogen equivalent of
the olefin hydration reaction developed by Mukaiyama and
Isayama6a and displays broad substrate scope. In our ongoing search
for other nitrogen sources that would be amenable for use in olefin
functionalization processes, we have examined sulfonyl azides, as
they are convenient, readily available, and widely handled reagents
in the laboratory.7 Moreover, we speculated that sulfonyl azides
could display parallel reactivity to that observed with azodicar-
boxylates in the cobalt- and manganese-mediated processes.
8
Given our prior success with Mn(dpm)3 and cobalt complexes
in the hydrohydrazination reaction, we first examined their use
together with 1.6 equiv of phenylsilane and 3 equiv of ethyl sulfonyl
azide for the hydroazidation of 4-phenylbutene (4) as a test
substrate. The manganese complex failed to provide azide product,
and the cobalt complex obtained from Co(NO3)‚6H2O, 2-ami-
noisobutyric acid, salicylaldehyde, NaOH, and H2O2 in ethanol9
afforded 4-phenyl-2-azidobutane in 50% yield after 48 h. Further
extensive optimization of the reaction conditions did not lead to
any improvements. Knowing that the catalyst used still contains
impurities, we re-examined the preparation of the complex, with
the hope that greater purity would result in increased reactivity.
Using Co(OH)3 as catalyst precursor,9 we succeeded in isolating
Analysis of the reaction mixture led to the identification of
4-phenylbutane as the major side product (28% yield). At this point,
we decided to vary the structure of both silane and sulfonyl azide,
hoping to increase the ratio of products in favor of the alkyl azide.
Tosyl azide proved to be best, increasing the azide/alkane ratio from
3:1 to 9:1 (as determined by GC). Finally, using tetramethyldisi-
loxane (TMDSO) and tosyl azide, we found that the ratio was
increased to 20:1, albeit with slight attenuation of reactivity (reaction
time 3 h instead of 2 h). Using the optimized procedure, we
routinely obtained 4-phenyl-2-azido-butane in 85-90% yield.
With a reliable procedure in hand, we proceed to examine the
scope of the hydroazidation reaction, with both phenylsilane and
9
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C O M M U N I C A T I O N S
Sharpless’ procedure2b (eq 3) were feasible in useful yields for
4-phenylbutene (4) as the prototypical substrate. In the reduction
reaction, a simple extraction procedure sufficed to allow isolation
of the free amine in 76% yield and 95% purity, as determined by
NMR.
Table 1. Hydroazidation Reaction of Olefins (Eq 1)
We have documented the cobalt-catalyzed hydroazidation reac-
tion as a new entry to alkyl azides directly from unactivated olefins.
The method complements existing approaches based on substitution
of alkyl halides or hydrazoic acid addition to activated olefins. In
addition to the azides that can be generated, the reaction can be
coupled to processes such as reduction to give rise to amines and
cycloaddition giving useful heterocycles. Further studies are being
conducted to better understand the similarities and differences
between this process and the hydrohydrazination reaction, with the
aim of discovering more efficient and versatile catalytic systems.
Acknowledgment. We thank the Swiss National Foundation
for support of this research and the Roche Research Foundation
for the support of J.W. H.N. thanks the Japan Society for the
Promotion of Science (JSPS) for a postdoctoral fellowship.
Supporting Information Available: Experimental procedures and
spectral data for all products. This material is available free of charge
via the Internet at http://pubs.acs.org.
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a General procedure A: 0.5 mmol alkene, 0.8 mmol PhSiH3, 1.5 mmol
TsN3, 30 mol % t-BuOOH, 6 mol % ligand 1, 6 mol % Co(BF4)2‚6H2O,
2.5 mL of ethanol at 23 °C under argon. b General procedure B: 1.0 mmol
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TMDSO (Table 1). All the terminal olefins tested (entries 1-8)
showed excellent Markovnikov selectivity. TMDSO is generally
better for this class of olefins as less alkane side products are
formed; when this observation is coupled with the fact that it is
also inexpensive, it is rendered the more convenient reagent for
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was well-tolerated (entries 1-3), but styrene derivatives (not shown)
were not active, although they had proven to be excellent substrates
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inactive. Esters and ketones were tolerated (entries 7 and 8).
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