Ruthenium porphyrin catalysed intermolecular amino-oxyarylation of alkenes to give primary amines: Via a ruthenium nitrido intermediate

Article abstract of DOI:10.1039/c9cc08043k

Ruthenium porphyrin catalysed direct intermolecular amino-oxyarylation of alkenes including styrenes and 1,3-dienes to give primary amines with O-(2,4-dinitrophenyl)hydroxylamine as the amine source was achieved in moderate to good yields under mild reaction conditions. Spectroscopic analyses revealed that a ruthenium nitrido complex was the key reaction intermediate for the amino-oxyarylation reaction.

Full text of DOI:10.1039/c9cc08043k

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Ruthenium porphyrin catalysed intermolecular
amino-oxyarylation of alkenes to give primary
amines via a ruthenium nitrido intermediate†
Cite this: Chem. Commun., 2020,
56, 137
Received 15th October 2019,
Accepted 21st November 2019
ab
a
b
Daohong Yu,
Chi-Ming Che
Ka-Pan Shing,cd Yungen Liu,
Haiyang Liu
and
acd
*
DOI: 10.1039/c9cc08043k
rsc.li/chemcomm
Ruthenium porphyrin catalysed direct intermolecular amino-
oxyarylation of alkenes including styrenes and 1,3-dienes to give
primary amines with O-(2,4-dinitrophenyl)hydroxylamine as the
amine source was achieved in moderate to good yields under
mild reaction conditions. Spectroscopic analyses revealed that a
ruthenium nitrido complex was the key reaction intermediate for
the amino-oxyarylation reaction.
Amines are among the most important chemicals commonly
encountered in natural products, agrochemicals and industrial
fine chemicals.1 For instance, 2-phenylethanamine is an important
sub-structure found in natural products and in pharmaceuticals
marketed globally (Fig. 1). Classical access to primary amines
Fig. 1 Pharmaceutical products containing the 2-phenylethanamine unit.
necessitates pre-functionalisation, and they are synthesised amino-oxyarylation being the major reaction pathway. They
by further organic transformation reactions such as the Gabriel found that other metal complexes, including those of copper,
reaction, the Leuckart reaction, the Curtius arrangement, the cobalt, iridium, nickel, gold and ruthenium, could not catalyse
Schmidt reaction, and reduction of nitro, cyano or azido groups.2 the same or similar reactions to give the desired products.
In view of high atom economy, catalytic group transfer reactions are Recently, they have realised the dirhodium-catalysed amination
very efficient in the preparation of (protected) primary amines of aromatic C–H bonds in the presence of a Brønsted acid,7 and
directly from alkenes,3 as exemplified by the Sharpless asymmetric suggested that a highly reactive protonated rhodium-nitrene
amino-hydroxylation for the synthesis of amino alcohols.4
species was the reaction intermediate.
To date there have been only a few reports of the direct
We are interested in reactive metal nitrido complexes that
synthesis of unprotected primary amines.3g,j,5 Morandi and could react with simple alkenes. We previously reported some
co-worker reported the synthesis of 2-amino-1-phenylethanols structurally defined ruthenium porphyrin imido/nitrene com-
from alkenes using PivONH3OTf as the aminating reagent.3j plexes for stoichiometric and catalytic C–N bond formation
Flack, Ku¨rti, Ess and co-workers reported the dirhodium catalysed reactions.8 Here, we report that ruthenium porphyrins are also
functionalisation of alkenes using O-(2,4-dinitro-phenyl)- competent for the direct intermolecular amino-oxyarylation of
hydroxylamine (DPH)6 as the nitrogen source,3g with styrene alkenes with DPH as the nitrogen source. High-resolution electro-
spray ionisation mass spectrometry (ESI-HRMS) and infrared (IR)
and ultraviolet-visible (UV-vis) spectroscopic analysis revealed a
ruthenium nitrido intermediate to be responsible for the amino-
a Department of Chemistry, Southern University of Science and Technology,
Shenzhen, Guangdong 518055, P. R. China
b Department of Chemistry, South China University of Technology, Guangzhou,
oxyarylation reaction. In this context, Lau and co-workers pre-
viously reported9 that ruthenium nitride can stoichiometrically
aminate alkenes in the presence of a strong electrophile (trifluoro-
acetic anhydride or p-toluenesulfonic anhydride).10
At the outset, the reaction of 4-methoxy styrene 1a and DPH
(2) with a panel of metal porphyrin catalysts was screened for
reaction optimisation. Interestingly, the ruthenium porphyrin
Guangdong 510641, P. R. China
c HKU Shenzhen Institute of Research and Innovation, Shenzhen, Guangdong
518057, P. R. China. E-mail: cmche@hku.hk
d Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The
University of Hong Kong, Hong Kong, P. R. China
† Electronic supplementary information (ESI) available: Details of experiments
and additional figures. See DOI: 10.1039/c9cc08043k
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complexes [Ru(TPP)(CO)] (H2TPP = meso-tetraphenylporphyrin),
[Ru(TDCPP)(CO)] (H2TDCPP = meso-tetrakis(2,6-dichlorophenyl)-
porphyrin) and [Ru(F20TPP)(CO)] (H2F20TPP = meso-tetrakis-
(pentafluorophenyl)porphyrin) showed high catalytic activity
and 3a was obtained in 33–78% yields (Table S1, entries 1–3,
ESI†). After further optimisation of the reaction conditions
(Table S1, entries 4–15, ESI†), we found that the reaction without
inert atmosphere protection ([Ru(F20TPP)(CO)] : 1a :2a = 0.05:1:1.5)
gave 3a in 86% yield. However, other ruthenium porphyrin
complexes [Ru(TPP)Cl2], [Ru(TDCPP)Cl2], and [Ru(TMP)(CO)]
(H2TMP = meso-tetramesitylporphyrin) gave 3a in r43% yields
(Table S1, entries 17–19, ESI†). The non-porphyrin ruthenium com-
plexes Ru(PPh3)3Cl2, [Ru(p-cymene)Cl2]2 and [Ru(tBu-Salen)(PPh3)2]
exhibited low activity, with 3a being obtained in r28% yields
(Table S1, entries 20–22, ESI†).
Under the optimised reaction conditions, we examined the
substrate scope of ruthenium porphyrin catalysed amino-
oxyarylation (Scheme 1). In general, styrenes with the electron-
donating 4-methoxy or 4-phenyl group gave the corresponding
products in high yields whereas those with electron-withdrawing
groups such as 4-CO2Me or a ketone moiety gave the corresponding
Scheme 2 [Ru(F20TPP)(CO)] catalysed amino-oxyarylation of 1,3-dienes.
The reaction of 1,3-dienes 4 and DPH was also studied
products in low yields. The reactions of sterically encumbered (Scheme 2). Trans-Allylic amino oxyarylation products 5 were
styrenes such as o-methoxy, a-methyl and a-phenyl styrenes also exclusively obtained irrespective of the trans-, cis- or mixed
proceeded smoothly, albeit in 22–52% yields for the corresponding trans-/cis-dienes as the substrate. Specifically, both (E)-4-
products (3j, 3m, 3t and 3u). Di- or trisubstituted styrenes also (30,40,50-trimethylphenyl)-buta-1,3-diene (trans : cis = 10 : 1) and
afforded products in 52–72% yields (Scheme 1, 3k–m). Electron- (Z)-4-(30,40,50-trimethylphenyl)-buta-1,3-diene (trans : cis = 1 : 7.5)
rich heterocyclic alkenes, including 2-vinylbenzofuran and gave trans-allylic amino-oxyarylation product 5a as the sole
2-vinylnaphthalene, also reacted efficiently to give products in product in 67% and 69% yields, respectively. The other nine
73% and 75% yields, respectively. Additionally, the reaction of diene mixtures (5b–j, trans : cis = 1.7 : 1–2.1 : 1) with an electron-
b-methyl styrene yielded the isomers 3s and 3s0 in a ratio of rich or electron-deficient substituent afforded the corresponding
2.4 : 1 with an 84% overall yield.
trans-allylic products in 30–88% yields. Notably, the tolerance of
functional groups such as ester, halogen and alkoxy groups is
beneficial for further synthetic manipulation. We speculated
that the cis-dienes were isomerised to trans-dienes under
the reaction conditions, as only residual trans-dienes were
detected in the reaction mixture by 1H NMR analysis even when
(Z)-4-(30,40,50-trimethylphenyl)-buta-1,3-diene (trans : cis = 1 : 7.5)
was employed.
To understand the mechanism of the nitrogen atom transfer
reaction, we examined the reaction of [Ru(F20TPP)(CO)], DPH
and styrene in MeCN by ESI-HRMS (Fig. 2). The mixture
containing 10 equiv. of DPH and 100 equiv. of styrene was
added to an MeCN solution of [Ru(F20TPP)(CO)]. After 1 min,
three new and intense cluster peaks at m/z 1088, 1132 and
1156 (C) were detected. The m/z 1088 ion signal was attributed
to the ruthenium nitride ion [Ru(F20TPP)(N)]+ (A) by comparing
the experimental signal with a simulated pattern (for details,
see the ESI,† Fig. S1 and S2). The collision-induced dissociation
experiment further substantiated this assignment. The m/z
1132 ion could be attributed to [Ru(F20TPP)(N)(MeCN)]+ (B) and
the m/z 1156 ion could be attributed to [Ru(F20TPP)(N)(MeCN)2]+ (C)
(Fig. S3 and S4, ESI†). The m/z 1088 signal decreased significantly
after prolonging the reaction time to 6.5 h. This implied that m/z
1088 corresponded to a reactive species tentatively assigned as
[Ru(F20TPP)(N)]+. After 1.5 h, a new signal at m/z 1282 was detected,
which was assigned to [Ru(F20TPP)(MeCN)(amino alcohols)]+ (D)
Scheme 1 [Ru(F20TPP)(CO)] catalysed amino-oxyarylation of styrenes.
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Fig. 2 ESI-MS study of the reaction intermediate.
(Fig. S5 and S6, ESI†). We proposed that water served as a
In the presence of [Ru(F20TPP)(CO)], adding 2,2,6,6-tetra-
nucleophile to attack the ruthenium-aziridino intermediate, to methylpiperidine nitroxide (TEMPO, 1.5 equiv.) to the reaction
form aminoalcohols. As a result, we speculated that a ruthe- of 4-methoxy styrene 1a and DPH (1.5 equiv.) in MeCN at 30 1C
nium terminal nitride was one of the reactive intermediates. On decreased the product yield of 3a from 78% to 38%; adding
the other hand, IR spectroscopic studies (Fig. S7 and S8, ESI†) NaN3 as an extra nucleophile or using a mixed solvent MeCN/
revealed that the CO stretching band (1965 cmꢀ1) vanished MeOH (9 : 1) could not achieve the azido- or methoxylated
immediately after addition of DPH. Removal of the p-acid (CO) is a products, and 3a was obtained as the sole product but with
prerequisite to obtain ruthenium high-valent species. Regarding the decreased yields (Scheme 3).
nature of this species, we gained insight using UV-vis spectroscopy
Based on the aforementioned experiments, we surmise that
(Fig. S9–S11, ESI†). Over 10 min, gradual decay of [RuII(F20TPP)(CO)] [Ru(Por)(NH)(X)] (X = MeCN or vacant) was generated by adding
at 403, 524 and 556 nm (Soret and Q bands) was observed in the DPH immediately, and then [Ru(Por)(NH)(X)] was transformed
presence of excess DPH. However, further spectral changes were also to [Ru(Por)(N)(X)], the key reactive intermediate, by deprotona-
observed after another 15 min (simultaneous decay and growth tion (Scheme 4). The reactive intermediate ([Ru(Por)(N)(X)]) was
of the bands at 403 and 418 nm), suggesting that there should be trapped by alkenes (styrenes or 1,3-dienes) to give an aziridino
at least two precursors to the ruthenium high-valent species, intermediate E. E was unstable and readily attacked by phenolate
[Ru(Por)(CO)] (precursor 1) - ‘precursor 2’ - [Ru(Por)(N)(L)] to form the final amino-oxyarylation product. The formation of
(L = ligand or vacant). The band at 418 nm was likely to have 3s and 3s0 simultaneously (Scheme 1) lends support to the
originated from the well-documented RuVI terminal nitrido involvement of the aziridino intermediate E.
porphyrin ([RuVI(Por)(N)(L)]),10a (e.g. [RuVI(TMP)(N)(OH)], 416,
In the literature, most studies on nitrogen atom transfer
reactions of metal nitrido complexes are confined to nitrido
485 nm; [RuVI(3,4,5-MeO-TPP)(N)(OH)], 421, 488 nm).
Scheme 3 Amino-oxyarylation of 4-methoxy styrene in the presence of
NaN3, MeOH or TEMPO.
Scheme 4 Proposed reaction pathway.
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complexes of manganese and ruthenium.10a,11 The aziridina-
tion/amination reactions of metal nitrido complexes typically
require an acid anhydride, such as trifluoroacetic anhydride or
4-methylbenzenesulfonic anhydride, as a strong electrophile to
elevate nitrido electrophilicity.9a–c,e,10b–d,12 A few metal nitrido
complexes were reported to directly undergo a nitrogen atom
transfer reaction to nucleophiles such as alkenes in the absence
of an acid anhydride or other strong electron-withdrawing
reagents.9a,f,13 In this study, we proposed that ruthenium
nitrido complexes ([Ru(Por)(N)]) bearing a fluorinated porphyrin
ligand (F20TPP) could directly transfer a nitrogen atom to styrenes
and terminal 1,3-dienes. We found that the in situ generated
[Ru(TMP)(N)(OH)] (from the reaction of [Ru(TMP)(O)2] with
HN = CtBu2)10a did not react with styrene to give the corres-
ponding product, which was consistent with the findings that
[Ru(TMP)(CO)] could not catalyse such reactions (Table S1,
entry 19, ESI†) because the TMP ligand is more electron rich.
In summary, our catalytic and mechanistic studies revealed
that ruthenium porphyrins can be developed as efficient cata-
lysts for amino-oxyarylation of alkenes to obtain primary
amines. The reaction can be performed under mild conditions
without protection by an inert gas, and affords the desired
products in good yields.
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This work was supported by the China Postdoctoral Science
Foundation (2018M633043) and the Shenzhen Science and
Technology Innovation Commission (JCYJ20170307104939529
and JCYJ20170412140251576). We thank the Southern Univer-
sity of Science and Technology for financial support.
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There are no conflicts to declare.
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