Silver-catalysed intramolecular hydroamination of alkynes with trichloroacetimidates

Article abstract of DOI:10.1039/c3cc45500a

Silver(i) complexes catalyse the intramolecular addition of trichloroacetimidates to alkynes. In the absence of a ligand, the selectivity of the reaction is dependent upon the nature of the counter-anion and solvent. The introduction of non-chelating nitrogeneous ligands suppresses competitive Bronsted acid catalysis, improving the yield and selectivity of the reaction.

Full text of DOI:10.1039/c3cc45500a

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Silver-catalysed intramolecular hydroamination
of alkynes with trichloroacetimidates†
Valerie H. L. Wong,ab T. S. Andy Horb and King Kuok (Mimi) Hii*a
Cite this: Chem. Commun., 2013,
49, 9272
Received 19th July 2013,
Accepted 9th August 2013
DOI: 10.1039/c3cc45500a
www.rsc.org/chemcomm
Silver(I) complexes catalyse the intramolecular addition of trichloro-
acetimidates to alkynes. In the absence of a ligand, the selectivity of
the reaction is dependent upon the nature of the counter-anion and
solvent. The introduction of non-chelating nitrogeneous ligands
suppresses competitive Brønsted acid catalysis, improving the yield
and selectivity of the reaction.
The intramolecular cyclisation of (homo)propargylic trichloro-
acetimidates 1 can occur via a hydroamination reaction to
furnish heterocycles 2, 3 (n = 0) and 4 (n = 1) (Scheme 1). To
date, only gold catalysts have been reported to be effective for
these reactions: Shin and co-workers1 were the first to report
the use of a cationic phosphine–gold(I) complex to effect the
cyclisation of sixteen acyclic substrates to exo-methylene-
substituted heterocycles 2 and 4 with good to excellent yields.
In contrast, the catalytic activity of AuCl3 is limited to the
cyclisation of just two substrates,2 proceeding via the exo-methylene
2 intermediate to afford oxazole 3 as the final product.
Scheme 1 Previous reports of intramolecular hydroamination of alkynes by
trichloroacetimidates.
As part of our programme to explore the use of less expensive
coinage metal catalysts for the heterofunctionalisation of CQC
bonds, we investigated the application of Ag catalysis to this of 1a within 6 h at room temperature. Notably, the selectivity of
particular type of hydroamination reaction.3–9 Prior to this, the reaction is also dictated by the counteranion X. For example,
Ag-catalysed reactions of (relatively unactivated) alkynes were the use of AgTFA afforded the 4-methylene-dihydrooxazole
limited to the addition of alkyl and aryl amine substrates.10–16 product 2a exclusively (Table 1, entry 1), while the use of AgOTf
Using unsubstituted 1a as the model substrate, a total of favoured the formation of the aromatic oxazole 3a (entry 2). In
eleven silver salts AgX or Ag2Y were initially assessed using DCE all cases, only low to moderate yields were obtained for the
as the solvent, where X = OAc, TFA, NO3, SbF6, PF6, BF4, OTf, reactions performed in DCE, due to formation of intractable
OTs; Y = CO3, O, SO4 (Table S1 in the ESI,† with selected side products. In an attempt to suppress the side reactions,
examples given in Table 1). The preliminary study revealed a the experiments were repeated using other solvents (see also
strong counteranion effect on catalytic activity. None of the Table S1, ESI†); the use of acetonitrile facilitated the reaction
di-silver salts (Ag2Y) were active and, with the exception of AgNO3 catalysed by AgTFA, where the formation of 2a improved from
and AgPF6, all other AgX salts afforded quantitative conversion 14 to 76% (entry 1 vs. entry 3). On the other hand, switching
between DCE and acetone prompted a change in selectivity
a Department of Chemistry, Imperial College London, Exhibition Road,
South Kensington, London SW7 2AZ, UK. E-mail: mimi.hii@imperial.ac.uk
b Department of Chemistry, National University of Singapore, 3 Science Drive 3,
Singapore 117543
from 3a to 2a in the AgOTf-catalysed reaction (entries 2 and 6).
The isomerisation of 2a to 3a was reported to occur slowly
under ambient conditions.1 In this study, it was found that
while TfOH is not catalytically active in the cyclisation (Table 1,
entry 8), the aromatisation of 2a to 3a was complete within 5 h
in the presence of 5 mol% of TfOH. With this in mind, the
† Electronic supplementary information (ESI) available: Experimental procedures,
extensive optimisation tables and copies of 1H and 13C NMR spectra. See DOI:
10.1039/c3cc45500a
c
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Table 1 Initial screening of catalytic conditionsa
Table 2 5- and 6-exo-dig cyclisations of (homo)propargylic trichloroacetimidatesa
Entry
[Cat.]
Solvent
Conversionb/%
2ab/%
3ab/%
1
2
3
4
5
6
7
8
AgTFA
AgOTf
AgTFA
AgOTf
DCE
DCE
MeCN
MeCN
Acetone
Acetone
DCE
DCE
DCE
MeCN
Acetone
CH2Cl2
100
100
100
100
62
100
100
—
100
100
100
100
14
—
76
18
22
40
80
—
83
83
87
83
—
46
—
15
—
—
—
—
—
—
—
—
AgTFA
AgOTf
Entry R1, R2, R3
n
Solvent T/1C t/h Product Yieldb
AgOTf/PSc
TfOHd
1
2
3
4
5
6
7
8
H, H, H
Me, H, H
Et, H, H
i-Pr, H, H
Me, Me, H
H, H, Ph
H, H, SiMe3
H, H, Br
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
Acetone 23
Acetone 23
Acetone 23
Acetone 23
Acetone 23
6
6
6
6
6
7
7
6
6
6
6
6
6
6
7
8
2a
2b
2c
2d
2e
2f
2g
2h
4a
4b
4c
4d
4e
4f
87 (67)
85 (74)
>99 (86)
87 (82)
89 (79)
29
82 (72)
77 (30)
93 (76)
97 (93)
99 (91)
94 (90)
96 (87)
73 (70)
31
9
[Ag(py)2]OTf
[Ag(py)2]OTf
[Ag(py)2]OTf
[Ag(py)2]OTf
10
11
12
MeCN
MeCN
60
60
a
Substrate 1a (80.2 mg, 0.4 mmol), AgX (0.04 mmol, 10 mol%), solvent
(as indicated, 1 mL), room temperature, 6 h. Determined by 1H NMR
b
Acetone 23
Acetone 23
Acetone 23
Acetone 23
Acetone 23
Acetone 23
Acetone 23
Acetone 56
Acetone 56
spectroscopy, using 1,3,5-trimethoxybenzene as internal standard.
9
H, H, H
Me, H, H
Et, H, H
c
d
PS = proton sponge (5 mol%), 40 1C, 3 h. 10 mol%.
10
11
12
13
14
15
16c
Ph, H, H
AgOTf-catalysed cyclisation of 1a was performed in the presence
of a non-coordinating base (proton sponge), which afforded 2a
exclusively with 80% conversion (entries 2 vs. 7), showing that
selective formation of the exo-methylene product 2 can be
attained by Ag-catalysis, so long as the attendant Brønsted
acidity can be suppressed. Guided by this, [Ag(py)2][OTf]17 was
subsequently prepared and evaluated as a catalyst. Pleasingly,
the use of the pyridine-ligated silver salt afforded 2a as the sole
product. Furthermore, the catalyst is not only air- and moisture-
stable, but also readily soluble in a number of solvents, allowing
good results to be obtained consistently across a number of
different reaction media, with no deleterious effect on conversion
or selectivity (Table 1, entries 9–12).
4-ClC6H4, H, H
4-CF3C6H4, H, H
H, H, Ph
4g
4h
H, H, SiMe3
80 (71)
a
General reaction conditions: substrate 1 (0.4 mmol), [Ag(py)2][OTf]
(0.04 mmol, 10 mol%), solvent (1 mL). Determined by 1H NMR
spectroscopy, using 1,3,5-trimethoxybenzene as internal standard.
Isolated yields are indicated in parentheses. 20 mol% catalyst used.
b
c
product 4h (ESI†). This is commensurate with a mechanism
whereby the addition of the N–H bond occurs in an exo-metallic
fashion to a p-coordinated alkyne (Scheme 2). The putative
(vinyl)silver complex then undergoes protonolysis to afford an
overall anti-addition across the CRC bond.
The scope of the new catalyst was investigated with a
number of substrates (Table 2), and the results were compared
with those previously achieved using cationic gold complexes.
With substrates containing alkyl substituents at the propargylic
position (R1 and/or R2 = alkyl), very comparable results were
attained using the silver catalyst at ambient temperature
(entries 1–5). On the other hand, substrates 1 (where n = 0)
containing aryl substituents at the propargylic position (R1 = Ar)
or internal alkynes (R3 a H) were reported to be inert towards
gold catalysis.1 Thus, we were surprised to detect a low level of
conversion in the cyclisation of the phenyl-substituted 1f to 2f
(entry 6) at an elevated temperature of 60 1C. Even more
pleasingly, good conversions can be obtained with substrates
containing bromide and silyl substituents at the terminal alkyne
position in good conversions18 (entries 7 and 8, respectively).
In comparison, 6-exo-dig cyclisations with homopropargylic
substrates (where n = 1) were equally facile at room temperature
and the products can be isolated in good yields. Both alkyl
and aryl substituents can be accommodated at R1 (Table 2,
entries 9–14). Once again, conversions of internal alkyne substrates
1g and 1h were slow, which can be improved by increasing catalyst
loading (entries 15 and 16).
The ability of one of the pyridines to dissociate from the
metal during the reaction appears to be key to reactivity, as the
reaction did not proceed when a chelating ligand was used, i.e.
[(phen)Ag][OTf] (phen = phenanthroline, Table S1, ESI†). Inherently,
the dissociation of a pyridine is necessary to create a vacant
coordination site for effective catalysis. In this case, we believe that
the primary role of the liberated pyridine is to act as a Brønsted
base to sequester triflic acid, thus preventing isomerisation to
the aromatic heterocycles (3) and competitive side reactions,
The ability of the silver catalyst to promote reactions with
internal alkynes is particularly noteworthy. It also provides a means
of establishing the stereochemical pathway of the addition step.
The products were obtained as Z-isomers exclusively, determined
by NOE experiments performed on the trimethylsilyl-substituted
Scheme 2 Proposed mechanism leading to the observed stereoselectivity.
Chem. Commun., 2013, 49, 9272--9274 9273
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products. It may also have additional roles in the proton-
transfer processes, as indicated in Scheme 2.
The silver-catalysed intramolecular hydroamination addition
of trichloroacetimidates to alkynes has been achieved for the
first time, whereby the nature of the counteranion, solvent and
ligand was found to have profound effects on catalytic turnover
and selectivity. Encouragingly, the [Ag(py)2][OTf] complex is
found to be highly effective for the cyclisation of internal alkynes
to afford vinyl-bromide and silane products, which had not been
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18 The bromo-product 2h decomposes during the isolation procedure.
c
9274 Chem. Commun., 2013, 49, 9272--9274
This journal is The Royal Society of Chemistry 2013