Hydrous zinc halide-catalyzed aminosulfonation of hydrocarbons

Article abstract of DOI:10.1039/b805783d

Benzylic and allylic hydrocarbons are selectively converted to the corresponding sulfonamides by a ZnBr₂-H₂O-catalyzed reaction with PhI=NTs; saturated adamantane is aminosulfonated at the tertiary C-H bond. The Royal Society of Chemistry.

Full text of DOI:10.1039/b805783d

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Hydrous zinc halide-catalyzed aminosulfonation of hydrocarbonsw
Biswajit Kalita, Angus A. Lamar and Kenneth M. Nicholas*
Received (in College Park, MD, USA) 8th April 2008, Accepted 16th June 2008
First published as an Advance Article on the web 5th August 2008
DOI: 10.1039/b805783d
Benzylic and allylic hydrocarbons are selectively converted to
the corresponding sulfonamides by a ZnBr2–H2O-catalyzed
reaction with PhIQNTs; saturated adamantane is aminosulfo-
nated at the tertiary C–H bond.
ð1Þ
The direct N-functionalization of hydrocarbons by the activa-
tion of C–H and CQC bonds is
a challenging and
important goal because of the value of the derived
amines and the abundance of the hydrocarbon substrates.
The most well-developed of these reactions are the
transition metal-catalyzed hydroamination,1 aziridination2
and allylic amination3 of alkenes. Reactions that effect
direct benzylic C–H amination are receiving increasing
attention, employing imido-iodinanes (TsNQIAr), chlora-
mine-T (TsNNaCl) or tosyl azide as aminating agents
in combination with various transition metal catalysts,
including rhodium-carboxylates,4 ruthenium- and cobalt-
porphyrins,5,6 manganese–Schiff base complexes,7 silver-
phenanthrolines,8 gold(III) salts,9 and copper-pyrazolylborates10
and -salts.11 The efficiency and scope of these reactions
vary widely, hence there is a need for improved and
general reactions of this type. Moreover, the reactive
aminating species involved in these processes are
unknown, but often are presumed to be ‘‘metal-
nitrenoids’’ formed via redox transformations of the
transition metal complexes with the N-reagent. Herein, we
report what appear to be the first hydrocarbon C–H
aminations catalyzed by non-transition metal (redox-inactive)
salts.
Economic and toxicity considerations caused us to optimize
and explore the scope of the Zn-catalyzed reactions. Using 4-
ethyl anisole (eqn (1), X = OMe) as a test substrate, a survey
of N-reagents, ZnII salts, solvents, temperature and stoichio-
metry (see ESIw) found the best conversion and yield with 2–3
equivalents of PhIQNTs,13 15 mol% ZnBr2 with oven dried
(110 1C) 4 A molecular sieves in benzene at rt (24–30 h) or
50 1C (12 h), providing the amidation product in 71% isolated
yield.z A survey of the reactions with other benzylic substrates
under these conditions was conducted, with the results being
summarized in Table 1 (entries 1–8). It can be seen that the
reaction is moderately effective and highly regioselective with a
variety of secondary benzylic reactants (entries 1–6). Sub-
strates with p-electron-releasing substituents (e.g. entries 1,
3) react faster and give higher conversions and yields than
those with electron-withdrawing groups (entries 4, 5); the
amount of the TsNH2 by-product increased in the latter cases.
Small amounts (o10%) of ArCH(OH)Me or ArC(O)Me were
detected as well. Substrates with tertiary benzylic C–H bonds
are also aminated with moderate efficiency (entries 7, 8).
The scope of the Zn-catalyzed aminosulfonation goes be-
yond benzylic substrates. Thus, representative allylic sub-
strates such as 1,3-diphenylpropene and cyclohexene
undergo primarily allylic amination (entries 9, 10) rather than
addition to the double bond (to form aziridines), often a major
pathway with transition metal-catalyzed reactions. A minor
addition product, cis-1-bromo-2-sulfonamidocyclohexane,
was isolated from the reaction with cyclohexene. Finally,
and perhaps most remarkably, the imido-iodinane–ZnBr2
system is even capable of aminating the 31 C–H bonds of
saturated hydrocarbons as illustrated by the reaction with
adamantane, which produced 1-tosylaminoadamantane in
modest yield (entry 11). However, under similar conditions,
neither cyclohexane nor benzene, both with stronger C–H
bonds, were amidated.
Following our recent development of CuI-catalyzed
aminosulfonation of benzylic hydrocarbons and ethers
employing anhydrous chloramine-T,11b we investigated
the possibility of catalyzing such reactions with isoelec-
tronic, but presumably redox-inactive, ZnII salts. To
our surprise and satisfaction, the reaction between
chloramine-T and ethylbenzene (1.2 : 1) in the presence
12
of 15 mol% ZnBr2 (CH3CN, 70 1C, 12 h) produced
the benzylic sulfonamide (X = H, 25% yield) accompanied
by TsNH2 (eqn (1)).
Department of Chemistry and Biochemistry, University of Oklahoma,
Norman, OK 73019, USA. E-mail: knicholas@ou.edu;
Fax: +1 405 325 6111; Tel: +1 405 325 3696
w Electronic supplementary information (ESI) available: Detailed
experimental procedures and characterization data, including product
NMR spectra. See DOI: 10.1039/b805783d
Although the chemo- and regioselectivity for the Zn-cata-
lyzed amination reactions are similar to the CuI-catalyzed
counterparts,11 some significant differences are evident. For
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Table 1 Zn-catalyzed aminosulfonation of representative hydrocar-
bons
and the counter anion. An initial survey of other group 12 salts
revealed that ZnCl2, ZnI2, CdCl2, and HgCl2 also promote the
amidation of ethylbenzene under similar conditions; the yield
increased in the order ZnCl2 o ZnBr2 o ZnI2. In contrast,
Zn(OTf)2 and neutral bromide ion sources, e.g. Bu4N+Brꢁ, NaBr,
are ineffective. When rigorously dry conditions were employed for
the reaction of PhINTs with ethylbenzene promoted by ZnBr2,15
the yields of the amination product (ca. 3%) and TsNH2 were
greatly reduced, while inclusion of a controlled amount of water
(0.1–1.0 equiv.), together with ZnBr2, provided the product in
20–40% yield. The more economical use of PhINTs (1 : 10
iodinane–hydrocarbon) was enabled by employing 0.15 equiva-
lents of ZnBr2 and 1.0 equivalents of H2O (50 1C, 12 h, benzene)
to afford moderate yields of the amination products derived from
ethylbenzene (45%), ethylanisole (54%) and adamantane (32%).
Since ZnII–H2O-containing systems can be acidic,16 we tested and
confirmed that HBr–H2O and HBr–HOAc also promote the
amidation of ethylbenzene (10–20% yield), apparently the first
example of a protic acid-catalyzed C–H amination. Finally, p-
methoxyphenol was found to strongly inhibit the hydrous
ZnBr2–PhINTs amidation of ethylbenzene, suggestive of a radical
process,17 consistent with the observed anion effects. The viability
of a Zn-amido intermediate, e.g. XZn–NBrTs, and its potential for
C–H insertion is supported by: (1) the isolable (ArSO2NCl)2Zn;18
(2) the formation of TsNHC6H11 from TsNCl2 + Zn in cyclohex-
ane;19 and (3) the ZnI2-promoted conversion of dienyl azides to
pyrroles.20
Temp-
erature/1C (conversion)b
Yielda
Entry Substrate
1
Product
RT
71 (81)
2
3
4
RT
50
40
48 (75)
50
50
52 (75)
42 (50)
5
50
10
6
7
8
50
50
50
41
38
38
Although the nature of the active aminating species in these
reactions is as yet uncertain, our initial experiments suggest
that a free nitrene is not involved. Since TsN: itself is known to
undergo C–H insertion and addition reactions with benzene,21
we examined the reaction of ZnBr2 with PhIQNTs in benzene
at 20–50 1C in the absence of a benzylic substrate (eqn (2)).
The only organic products detected were PhI, TsNH2 and
TsNQNTs. Neither of the established nitrene-trapping pro-
ducts, PhNHTs or the azepine, was found, providing evidence
against the intervention of the free nitrene.
9
50
50
50
28
10
11
50 (40, 10)
22
ð2Þ
a
b
% Isolated yield. % Conversion of hydrocarbon substrate.
In conclusion, we have found that benzylic, allylic and
tertiary aliphatic C–H bonds can be amino-functionalized by
PhIQNTs and zinc halide salts. That such transformations are
not the exclusive domain of transition metal catalysts may
presage the development of more efficient and uniquely selective
reactions for the preparation of diverse organonitrogen com-
pounds from abundant, yet typically unreactive hydrocarbons.
We are grateful for financial support provided by the US
National Science Foundation.
example, the ZnII-promoted reaction with p-ethyltoluene (en-
try 3) is completely selective for the 21 C–H bond, whereas the
[Cu(CH3CN)4]PF6-catalyzed reaction gives a 3 : 1 ratio of 21 : 11
amination products.14 Cumene (entry 7) is aminated comple-
tely selectively by the Zn catalyst, whereas the CuI-promoted
reaction also produces some of the corresponding allyl amine
from dehydrogenation.11b Additionally, although the satu-
rated adamantane is aminated by the Zn-catalyst (entry 11),
it is unreactive towards chloramine-T–[Cu(CH3CN)4]-
PF6.14
Notes and references
With an eye to determining the origin of the TsNH2 by-product,
enhancing the reaction’s efficiency, and gaining mechanistic
insights, we briefly examined the role of the metal ion, water,
z Caution: the dry solids TsNQIPh and ZnBr2 should not be mixed
together as a strongly exothermic process has been observed upon
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combining the two compounds in mmol quantities. Representative
procedure: to an oven-dried Schlenk tube (or a test tube) under N2 was
transferred anhydrous ZnBr2 (15 mol% of the substrate) and 2 mL of
dry benzene. To this was added TsNQIPh (1.0 mmol), oven dried
(110 1C) 4 A molecular sieves or 1.0 mmol H2O, 4-ethyl anisole
(0.50 mmol), and another 3 mL of dry benzene by syringe. The
suspension was stirred at room temperature (or at 50 1C, Table 1)
under N2. Another 0.5 mmol of TsNQIPh was added to the reaction
mixture after 5–6 h and stirring was continued for the specified time.
When TLC analysis indicated no further conversion, the reaction
mixture was filtered, the solid collected, washed with CHCl3
(B15–20 mL), and the filtrate concentrated by rotary evaporation.
The residue was purified by flash chromatography or preparative TLC
on silica gel eluting with 1 : 10 ethyl acetate–petroleum ether.
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