Palladium-catalyzed directing group-assisted C8-triflation of naphthalenes

Article abstract of DOI:10.1039/c6cc01732k

The transition-metal-catalyzed direct triflation of naphthyl amides and naphthyl ketones has been accomplished for the first time. Benzophenone (BP) was found to be a suitable ligand for the cross-coupling reactions. Density functional theory (DFT) calculations revealed that excessive amounts of HOTf inhibit the reductive elimination of the C-F bond to realize the unusual reductive elimination of the C-OTf bond.

Full text of DOI:10.1039/c6cc01732k

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Palladium-catalyzed directing group-assisted
C8-triflation of naphthalenes†
Cite this:DOI: 10.1039/c6cc01732k
Zhi-Wei Yang, Qi Zhang, Yuan-Ye Jiang, Lei Li, Bin Xiao* and Yao Fu*
Received 26th February 2016,
Accepted 18th April 2016
DOI: 10.1039/c6cc01732k
www.rsc.org/chemcomm
The transition-metal-catalyzed direct triflation of naphthyl amides and the C–OTf bond-formation via reductive elimination from the
naphthyl ketones has been accomplished for the first time. Benzo- transition metal center has no precedent in the literature,12
phenone (BP) was found to be a suitable ligand for the cross-coupling although the trifluoromethane sulfonyl moiety has received
reactions. Density functional theory (DFT) calculations revealed that great attention.13 Herein we report the Pd-catalyzed naphthyl
excessive amounts of HOTf inhibit the reductive elimination of the C–F C–H activation/C–OTf bond-forming reaction with the combi-
bond to realize the unusual reductive elimination of the C–OTf bond. nation of NFTPT, HOTf and a necessary benzophenone-type
ligand (eqn (3)).
Reductive elimination is a fundamentally important step in
transition-metal-catalyzed cross-coupling reactions for the
construction of various chemical bonds.1 Although a lot of
(1)
carbon–carbon and carbon–heteroatom bond-forming reactions
have been reported,2 the formation of some bonds, e.g. C–F3,4
and C–CF3,5 is challenging mainly because of the high kinetic
barrier for the reductive elimination of these bonds from
(2)
transition-metal centers.3a To circumvent this problem, two
strategies are usually employed.6 The first is to perform reductive
elimination on high oxidation state metal species3a,b,7 and the
other is to develop suitable ligands to facilitate this process.3b,8
With the aid of these two strategies, the generation of C–F and
C–CF3 bonds has been realized. For example, Ar–CF3 was
obtained via reductive elimination from the Pd(IV) complex,
which was a Pd(IV) intermediate coordinated with CF3À, FÀ and
(3)
Inspired by the work of Sanford’s group on competing
TfOÀ and was separated by Sanford’s group.6 Yu’s group used sp3-C–F and sp3-C–NHT bond-forming reductive elimination
NFTPT (N-fluoro-1,3,5-trimethylpyridinium triflate) as the fluori- from Pd(IV),14 and our group’s previous work on the directed
nating reagent to realize the ortho-fluorination of triflamide- C–H amidation of aromatic ketones,15 we originally attempted
protected benzylamines. It was proposed that the fluorinated to explore Pd(OAc)2-catalyzed triflation of aryl C–H bonds of
product was formed via the C–F bond-forming reductive elimina- aryl ketones and aryl amides separately. As shown in Scheme 1,
tion from the TfOÀ, FÀ coordinated Pd(IV) complex (eqn (1)).4,9 Of the reaction of benzophenone (BP) as a substrate (0.1 mmol)
particular note is that Sanford’s group10 and Dong’s group11 with NFTPT (2) (0.2 mmol) was conducted in the presence of
recently realized C(sp3)–OTs bond formation via SN2-type C(sp3)–O Pd(OAc)2 (0.01 mmol, 10 mol%) and HOTf (0.05 mmol)14,16 in
coupling from Pd(IV) complexes (eqn (2)). But to our knowledge, DCE at 80 1C for 8 hours in air. Unfortunately, no triflation
product was detected. The triflation of 1a also failed to afford
Hefei National Laboratory for Physical Sciences at the Microscale, iChEM, CAS Key
Laboratory of Urban Pollutant Conversion, Anhui Province Key Laboratory of
Biomass Clean Energy, Department of Chemistry, University of Science and
Technology of China, Hefei 230026, China. E-mail: binxiao@ustc.edu.cn,
fuyao@ustc.edu.cn
the desired product after extensive screening. To our surprise,
3a was obtained in 6% yield when the mixture of 1a and BP was
added into the reaction (Scheme 1). But the compound BP-OTf,
which was produced by ortho C–H bond triflation of BP, was not
detected at all. These results made us speculate that BP acts as
† Electronic supplementary information (ESI) available. CCDC 1455891. For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/c6cc01732k the ligand to promote the formation of 3a.
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Table 1 Pd(OAc)2-catalyzed direct triflation of naphthylamidesab
Scheme 1 The discovery of the reaction.
Encouraged by this result and our assumption, we turned to
explore this C–H bond triflation reaction by using 1a as the model
reactant and BP as the ligand. After screening of catalysts,
oxidants and solvents,17 we found that the reaction of 1a with
2.0 equiv. of NFTPT (2) in the presence of 10 mol% Pd(OAc)2,
50 mol% BP, 1.2 equiv. of HOTf18 and 0.8 equiv. of TMSOTf in
1,2-dichlorobenzene (ODCB) at 110 1C for 2 hours afforded the
desired product 3a in 74% 19FNMR yield. In addition, NMP,4
DMSO,19 CH3CN and DMF16 were also used as ligands to
conduct the reaction, but none of them were effective in this
reaction. Note that the desired triflation products cannot be
found when Pd(OAc)2 was absent in this reaction.17
a
Reaction conditions: substrate 1 (0.1 mmol), 2 (2.0 equiv.), Pd(OAc)2
We next examined the substrate scope of this process. 1a
was triflated smoothly to provide product 3a in 69% isolated
yield. A variety of N,N-disubstituted-1-naphthamides could
be undergo C–H triflation reaction smoothly and provide in
moderate to good yields (3b–h). The configuration of 3g was
confirmed via X-ray characterization (Fig. 1). Moreover, the
bromo, fluoro, methyl, methoxyl and ester substitutions (3i–o)
were tolerated (Table 1). N,N-Dimethy-9-phenanthramide was
also successfully functionalized to afford the corresponding
derivative 3p in 58% yield. Importantly, the cross-coupling
reactions using naphthalene-1-yl ketones as substrates were
also carried out in moderate yields (Table 2, 3q–s). It is worth
addressing the fact that upon increasing the substrates 1a and
1r scale to 1 mmol, the exact same yield was isolated with the
substrates added on the 0.1 mmol scale.
(10 mol%), BP (50 mol%), HOTf (1.2 equiv.), TMSOTf (0.8 equiv.), ODCB
(0.4 mL), 110 1C, 2 h. Isolated yield.
b
Table 2 Pd(OAc)2-catalyzed direct triflation of naphthylketonesab
N,N-Dicyclohexyl-3-methoxybenzamide was found to undergo
the desired triflation reaction successfully and provide 3t in 46%
yield. This result demonstrated that the present protocol could
also be applied to some benzamine derivatives (Scheme 2).
a
Reaction conditions: substrate 1 (0.1 mmol), 2 (2.0 equiv.), Pd(OAc)2
(10 mol%), BP (50 mol%), HOTf (0.5 equiv.), ODCB (0.4 mL), 110 1C, 2 h.
b
Isolated yield.
Based on literature precedents and our previous work,9,14,15
we proposed that the reaction proceeds through a Pd(II/IV)
catalytic cycle. First, Pd(OAc)2 is coordinated with BP and reacts
with HOTf to form the active catalyst Pd(II) species 4. 4 mediates
the C–H activation of 1, and then it was oxidized by NFTPT (2)
to produce the Pd(IV) species 5. Then 5 could undergo direct
C–OTf reductive elimination to obtain the product 3r (Path A2)
or further react with HOTf to generate 6 with the release of HF
Fig. 1 X-ray crystallographic structure of 3g.
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benzene derivatives like 3t and the details of reaction mechanism
are ongoing in our laboratory.
Financial support was received from the 973 Program
(2012CB215306), NSFC (21325208, 21572212, 21361140372,
21472181), IPDFHCPST (2014FXCX006), CAS (KFJ-EW-STS-051,
YIPA-2015371), FANEDD (201424), FRFCU and PCSIRT.
Scheme 2 Pd(OAc)2-catalyzed direct triflation of benzoyl amide.
Notes and references
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,
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Fig. 2 Energy profiles of Path A and Path B to generate the fluorination
product or triflation product. The relative free energies are given in kcal molÀ1
.
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