Angewandte
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[a]
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Table 1: Evaluation of reaction conditions for Si H insertion.
Entry
Catalyst (mol%)
Conditions[b]
Solvent
Yield [%][c]
1
2
3
4
5
6
7
8
9
[Rh2(OAc)4] (5)
[Rh2(OAc)4] (5)
A
A
A
A
B
B
B
B
B
B
B
B
CH2Cl2
DMB
CH2Cl2
DMB
CH2Cl2
toluene
CH2Cl2
CH2Cl2
CH2Cl2
DCE
16
15
44
34
87
61
(88)
32
61
0
[Cu(CH3CN)4]PF6 (5)
[Cu(CH3CN)4]PF6 (5)
[Cu(CH3CN)4]PF6 (5)
[Cu(CH3CN)4]PF6 (5)
[Cu(CH3CN)4]PF6 (2)
Cu(OTf)2 (2)
[Cu(CH3CN)4]PF6 (1)
AgSbF6 (5)
–
10[d]
11
12
CH2Cl2
CH2Cl2
0
[Cu(CH3CN)4]PF6 (2)
(77)[e]
[a] Reaction conditions: PhMe2SiH (1.0 equiv), 1a (2.3 equiv). [b] Con-
ditions A: manual addition of 1a; conditions B: slow addition of 1a over
0.5 h with a syringe pump. [c] The yield was determined by 19F NMR
spectroscopy with trifluorotoluene as an internal reference. Values in
parenthesis indicate the yield of the isolated product. [d] The reaction
was performed at 608C. [e] The reaction was performed with triphenyl-
silane. The product is triphenyl(2,2,2-trifluoroethyl)silane (2ab).
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Scheme 2. Copper-catalyzed Si H, B H, P H, S H, and N H bond
insertion with 2,2,2-trifluoro-1-diazoethane (1a). Reaction conditions:
Slow addition of 1a, then stirring for 18 h at room temperature. Yields
given are for the isolated product. [a] The reaction was performed with
NaBArF (2.2 mol%). [b] [Cu(CH3CN)4]PF6: 4 mol%.
anilines and amides.[9] As expected, the catalyst was essential
À
for Si H insertion (Table 1, entry 11). The optimal reaction
the reaction was performed with an excess of the nucleophilic
component, and the catalyst loading was typically increased
to 4 mol% (Scheme 3).
The reaction scope is very broad, and a large collection of
novel chiral products with a CF3 substituent located at the
benzylic position were synthesized. Similarly to the reactions
conditions therefore consist of treating dimethylphenylsilane
with an excess of the diazo reagent (2.3 equiv) in dichloro-
methane at room temperature in the presence of [Cu-
(CH3CN)4]PF6 (2 mol%) for 18 h. Under these conditions,
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the product of Si H insertion 2aa was isolated in 88% yield
(Table 1, entry 7). Pleasingly, Si H insertion of more steri-
cally demanding triphenylsilane was also successful and led to
product 2ab in 77% yield (Table 1, entry 12).
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with 2,2,2-trifluoro-1-diazoethane (1a), Si H, B H, and P H
insertion reactions were feasible; the corresponding products
were isolated in 61–98% yield. A detailed investigation of
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After establishing these conditions for copper-catalyzed
Si H insertion with 2,2,2-trifluoro-1-diazoethane (1a), we
S H insertion reactions revealed that aryl, heteroaryl,
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primary, secondary, and tertiary alkyl groups are all tolerated
on the sulfur atom. Only strongly electron donating (OMe) or
electron withdrawing (NO2) groups located in the para
position of benzenethiol are not compatible. All 1-aryl
2,2,2-trifluoro-1-diazoethanes tested were competent sub-
strates with the exception of the nitro-substituted derivative
1 f. For the parent benzenethiol, we found that [Cu-
(CH3CN)4]PF6 was superior to [Cu(CH3CN)4]BArF, and
AgSbF6 was not effective. In contrast to the product outcome
observed with 2,2,2-trifluoro-1-diazoethane (1a), aniline
derivatives underwent monoinsertion with no detectable
products resulting from undesired double insertion. Primary
alkyl and cycloalkyl amines also reacted with 1b as demon-
strated with the synthesis of 6be and 6bf, which were isolated
in 40% and 92% yield, respectively. For reactions with 1b
leading to lower yields, 1-[(1,1’-biphenyl)-4-yl]-2,2-difluoro-
ethan-1-one was the main side product isolated after work-up;
this observation indicates that hydrolysis of the unreacted
diazo precursor occurs to afford 1-[(1,1’-biphenyl)-4-yl]-2,2,2-
trifluoroethan-1-ol, an intermediate prone to HF elimination.
The ability of [Cu(CH3CN)4]PF6 to catalyze efficiently
a range of heteroatom–hydrogen insertion reactions led us to
carry out a series of competition experiments with the diazo
examined the reactivity of triphenylphosphine-protected
borane, dimethyl phosphonate, diphenylphosphine oxide,
thiols, and 4-methoxyaniline, and found that the generality
of the heteroatom–hydrogen insertion process is striking
(Scheme 2). Triphenylphosphine borane is a suitable sub-
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strate and was converted into the B H insertion product 3aa
in 52% yield. Dimethyl phosphonate and diphenylphosphine
oxide also reacted under CuI catalysis to afford 4aa and 4ab in
33 and 89% yield, respectively, thereby establishing the
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feasibility of P H insertion. The reaction tolerates a range of
aryl, heteroaryl, and alkyl thiols, thus leading to the 2,2,2-
trifluoroethyl-substituted sulfides 5aa–ah in up to 90% yield.
Under the standard reaction conditions, the reaction of 2,2,2-
trifluoro-1-diazoethane with 4-methoxyaniline led to the
product of double insertion 6aa. The product of the O H
insertion of phenol was not observed with either [Cu-
(CH3CN)4]PF6 or AgSbF6.
The broad scope of this method encouraged further
studies on the installation of branched trifluoroalkyl frag-
ments. We probed the reactivity of the model 1-aryl 2,2,2-
trifluoro-1-diazoethanes 1b–f[8] in a range of heteroatom–
hydrogen insertion reactions. For this class of diazoethanes,
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 3785 –3789