[RuIV(F20-TPP)Cl2]efficiently catalysed inter- and intra-molecular nitrene insertion into sp3 C-H bonds of hydrocarbons using phosphoryl azides as nitrene sources

Article abstract of DOI:10.1039/c3cc41110a

[Ru^IV(F₂₀-TPP)Cl₂][H₂(F ₂₀-TPP) = meso-tetrakis(pentafluorophenyl)porphyrin] is an active catalyst for both inter- and intra-molecular nitrene insertion into sp ³ C-H bonds of hydrocarbons in good to high product yields using phosphoryl azides as nitrene sources. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3cc41110a

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[RuIV(F20-TPP)Cl2] efficiently catalysed inter- and
intra-molecular nitrene insertion into sp3 C–H bonds
of hydrocarbons using phosphoryl azides as
nitrene sources†
Cite this: Chem. Commun., 2013,
49, 4619
Received 9th February 2013,
Accepted 28th March 2013
Wenbo Xiao,a Jinhu Wei,a Cong-Ying Zhou*ab and Chi-Ming Che*ab
DOI: 10.1039/c3cc41110a
www.rsc.org/chemcomm
[RuIV(F20-TPP)Cl2][H2(F20-TPP) = meso-tetrakis(pentafluorophenyl)-
porphyrin] is an active catalyst for both inter- and intra-molecular provided in the literature.10,11 [Ru(F20-TPP)Cl2] was prepared by
nitrene insertion into sp3 C–H bonds of hydrocarbons in good to the reaction of [Ru(F20-TPP)O2] with HCl.11 It was characterized using
The [RuIV(Por)Cl2] complexes (Fig. 1) were prepared by methods
high product yields using phosphoryl azides as nitrene sources.
ESI-MS (peaks at 1144.0 and 1109.0 attributed to [Ru(F20-TPP)Cl2]+
and [Ru(F20-TPP)Cl]+), UV-visible absorption spectroscopy (lmax(log e):
The construction of C–N bonds is of paramount importance in 406 nm (5.01), 507 nm (3.91)), 1H NMR (pyrrolic protons (Hb) at
organic synthesis due to the prevalence of amino groups in d = À51.9 ppm) and 19F NMR (three sets of peaks at d = À129.7,
biologically active natural products and pharmaceuticals. Transi- À148.9, À158.9 ppm). In our preliminary study, we examined the
tion metal catalysed nitrene insertion into saturated C–H bonds is reactivities of a panel of stabilized organic azides including
an appealing strategy for C–N bond formation.1 Using this phosphoryl azides, sulfonyl azides and acyl azides used in limiting
approach, the robust sp3 C–H bonds could be used as functionality amounts towards C–H amination of cyclohexanes used in excess
for the construction of C–N bonds thereby obviating multi-step with [RuIV(TDCPP)Cl2] as catalyst (Table 1). Treatment of cyclo-
group transformations and allowing installation of nitrogen func- hexane (20 equiv.) with 4-nitrobenzenesulfonyl azide 2a (1 equiv.)
tionality in a selective manner. While iminoiodanes such as PhI = in the presence of [RuIV(TDCPP)Cl2] (2 mol%) in 1,2-dichloro-
NTs and their in situ variants are the most commonly used nitrene ethane under reflux (84 1C) for 12 h afforded the amination product
sources for C–H amination, the generation of PhI as a byproduct 3a in 25% yield based on 60% substrate (4-nitrobenzenesulfonyl
renders the reaction less eco-friendly. Recently, the use of organic azide 2a) conversion (Table 1, entry 1). When 2,2,2-trichloroethyl
azides in nitrene transfer and insertion reactions has received a sulfazidate 2b was used, the corresponding amination product was
surge of interest as only nitrogen gas is produced as a byproduct. In obtained in 40% isolated yield (entry 2). Compared to 2a and 2b,
addition, the stability and diversity of organic azides also render 2,2,2-trichloroethoxycarbonyl azide 2c was more effective giving the
them promising nitrene sources for C–N bond forming reactions. amination product 3c in 90% yield and with 70% substrate
Dirhodium(II) carboxylates,2 ruthenium(II)3 and iridium(III)4 Schiff conversion (entry 3). Phosphoryl azide 2d, which was previously
base complexes, copper b-diketiminates,5 and the porphyrin com- reported to be effective for ruthenium porphyrin catalysed nitrene
plexes of ruthenium(II),6 iron(III)7 and cobalt(II),8 all have been insertion into C–H bonds of aldehydes, failed to induce sp3 C–H
demonstrated to be effective catalysts for nitrene insertion into amination of cyclohexane (entry 4). In contrast, phosphoryl azide 2e
sp3 C–H bonds using organic azides. We recently reported that bearing the 2,2,2-trichloroethyl electron-withdrawing substituent
dichlororuthenium(IV) porphyrins such as [RuIV(TTP)Cl2] (H2TTP =
meso-tetrakis(4-tolyl)porphyrin) are effective catalysts for nitrene
insertion into aldehyde C–H bonds to give N-acylphosphoramidates
in good to high yields using phosphoryl azides as nitrene sources.9
These findings prompted us to examine the feasibility of using
[RuIV(por)Cl2] [H2Por = porphyrin] as catalyst for amination of
saturated alkanes.
a Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The
University of Hong Kong, Pokfulam Road, Hong Kong, China.
E-mail: cmche@hku.hk, cyzhou@hku.hk; Fax: +85228571586; Tel: +85228592154
b HKU Shenzhen Institute of Research & Innovation, Shenzhen, China
† Electronic supplementary information (ESI) available: Experimental procedures
Fig. 1 Dichlororuthenium(IV) porphyrins.
and compound characterization. See DOI: 10.1039/c3cc41110a
c
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Table 1 [RuIV(TDCPP)Cl2]-catalysed C–H amination of cyclohexane with stabi-
lized organic azidesa
to catalyse this reaction under the same conditions (entries 6–9). No
reaction was observed in the absence of a metal catalyst.
With the optimized reaction conditions, the substrate scope
of [RuIV(F20-TPP)Cl2]-catalysed nitrene insertion into sp3 C–H bonds of
hydrocarbons with 2e was examined. As depicted in Table 3, a variety
of hydrocarbons including aliphatic and benzylic ones underwent
C–H amination in good to high product yields. For example, cyclo-
pentane and cyclooctane displayed similar activity to cyclohexane
giving the corresponding aminated products in 81% and 86% yields
respectively (entries 1 and 2). The reaction of ethylbenzene with 2e
afforded benzylic C–H amination product 3h in 81% yield (entry 3).
Likewise, when tetralin and indane were subjected to the Ru(IV)-
catalysed amination, the benzylic C–H amination products 3j and
3k were obtained in 81% and 85% yields, respectively (entries 5 and 6).
The use of sterically hindered diphenylmethane as a substrate led to
slightly lower product yield (64%, entry 7). It is worth noting that the
benzylic 11 C–H bonds of toluene compounds could be aminated
in 62–85% yields (entries 8–10). When cyclohexene was used, allylic
C–H amination product 3p was obtained in 76% yield without
aziridination detected (entry 11). The reactivity of acyclic
alkanes towards the Ru(IV)-catalysed C–H amination has also been
examined. The reaction of hexane with 2e afforded a mixture of
regioisomeric aminated products in an overall 76% yield with low
regioselectivity (entry 12). When the branched alkane 2,3-dimethylbu-
Entry
1
Azide
Product
Conv.b (%)
60
Yieldc (%)
25
3a
2
3b
3c
42
70
95
90
3
4
3d
3e
o10
Trace
83
5
95
a
Organic azide (0.1 mmol), cyclohexane (2 mmol, 20 equiv.),
[Ru(TDCPP)Cl2] (2 mol%), 4 Å MS (50 mg), DCE (1.5 mL), argon, reflux
(84 1C) for 12 h. Determined using 1H NMR based on organic azide.
b
c
Based on substrate conversion.
displayed the best performance affording product 3e in 83% tane was employed as the substrate, only a trace amount of amination
yield and with 95% substrate conversion (entry 5).
product was detected using 31P NMR and 1H NMR, revealing a
Having established bis(2,2,2-trichloroethyl) phosphorazidate 2e predominant steric effect of phosphoryl azides on the nitrene C–H
as a suitable nitrene source for the amination of cyclohexane, we insertion since a 31 C–H bond should be the site of attack as it has
turned to examine the catalytic activity of other transition metal been reported to be more reactive than the 11 and 21 ones in C–H
complexes for the reaction depicted in Table 2. While [RuIV(TTP)Cl2] amination reactions with sulfonylamides and carbamates as nitrene
and [RuIV(p-ClTPP)Cl2] displayed modest catalytic activity (Table 2, sources.1
entries 1 and 2), [RuIV(F20-TPP)Cl2] was found to efficiently catalyse
The intramolecular version of this Ru(IV)-catalysed nitrene inser-
amination of cyclohexane in 93% product yield and with 100% tion into sp3 C–H bonds has been examined. Treatment of 4a with
conversion of phosphoryl azide 2e (entry 3). The ruthenium(II) [RuIV(F20-TPP)Cl2] (2 mol%) in dichloroethane under reflux for 12 h
porphyrins [RuII(TDCPP)(CO)] and [RuII(F20-TPP)(CO)] were less afforded benzylic C–H amination product 5a in 99% yield
effective than their Ru(IV) counterparts giving 3e in low yields (entries (Scheme 1, eqn (1)). Likewise, when 4b was used, nitrene insertion
4 and 5). The iron(III) porphyrins ([Fe(TTP)Cl] and [Fe(F20-TPP)Cl]) into aliphatic C–H bonds giving 5b in 80% yield was observed. In
and dirhodium(II) carboxylates (Rh2(OAc)4 and Rh2(esp)212) all failed these two examples, no five-membered cyclic product was observed.
However, when the phosphoryl azide 4c lacking the 21 C–H bond
at the g position was subjected to this Ru(IV)-catalysis, a five-
Table 2 Screening of catalysts for C–H amination of cyclohexane with phos-
membered amination product 5c was selectively formed in 96%
phoryl azide 2ea
yield via nitrene insertion into the 31 C–H bond at the b position
(Scheme 1, eqn (2)); the 11 C–H amination at the g position was not
observed. This result is in line with the order of reactivity of 31 > 21
> 11 C–H bonds. Similarly, 5d was obtained in 91% yield via nitrene
Entry
Catalyst
Conv.b (%)
Yieldc (%)
insertion into benzylic C–H bonds.
To gain insight into the reaction mechanism, the reaction of a
mixture of cyclohexane and cyclohexane-d12 with N3P(O)(OCH2CCl3)2
(2e) was performed under the employed reaction conditions. A kH/kD
value of 5.1 was obtained revealing that C–H bond cleavage is the
rate determining step. This KIE value is in the range of 4.8–11
observed in stoichiometric C–H amination reactions of ethylbenzene
and cyclohexene by bis(imido)ruthenium(VI) porphyrins, in which
cases a H-atom abstraction mechanism has been suggested.13
In conclusion, an efficient intermolecular nitrene insertion
into sp3 C–H bonds of hydrocarbons using phosphoryl azides
has been developed. With [RuIV(F20-TPP)Cl2] as catalyst and
1
2
3
4
5
6
7
8
9
[RuIV(TTP)Cl2]
[RuIV(p-ClTPP)Cl2]
[RuIV(F20-TPP)Cl2]
[RuII(TDCPP)(CO)]
[RuII(F20-TPP)(CO)]
[Fe(TTP)Cl]
[Fe(F20-TPP)Cl]
[Rh2(OAc)4]
[Rh2(esp)2]
42
77
100
94
40
41
93
39
57
47
NRd
NR
NR
NR
a
2e (0.1 mmol), cyclohexane (2 mmol, 20 equiv.), catalyst (2 mol%), 4 Å
b
MS (50 mg), DCE (1.5 mL), argon, reflux (84 1C) for 12 h. Conversion
was determined based on 2e using 1H NMR and 31P NMR. Based on
c
d
substrate conversion. NR = no reaction.
c
4620 Chem. Commun., 2013, 49, 4619--4621
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Table 3 [RuIV(F20-TPP)Cl2]-catalysed C–H amination of hydrocarbons with phos-
phoryl azide 2ea
Entry
1
Hydrocarbons
Product
Yieldb (%)
81
Scheme 1
high yields. Intramolecular nitrene C–H insertion has also been
achieved in high product yields with [RuIV(F20-TPP)Cl2] as catalyst.
We thank the financial support from NSFC (21272197) and Hong
Kong Research Grant Council (HKU 700708P, HKU1/CRF/08).
2
3
4
86
81
62
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bis(2,2,2-trichloroethyl) phosphorazidate 2e as a nitrene source, sp3
C–H bonds of hydrocarbons can be efficiently aminated in good to
c
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Chem. Commun., 2013, 49, 4619--4621 4621