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Journal of the American Chemical Society
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substrate 1e with benzyl (Bn) protecting group were ineffective
(entry 5). Furthermore, various gem-disubstituted substrates (1f-
1j and 1l-1m) were suitable for the reaction to provide
corresponding products in moderate to good yields (55-80%,
entries 6-10, 12-13). But substrate 1k with bis-ester group yielded
2k in low yield (37%, entry 11). Interestingly, the
trifluoromethoxylated spiro-products 2n-2p could be obtained in
moderated to good yields (60-71%, entries 14-16). Furthermore,
when a substituent was introduced to the carbon adjacent to
nitrogen, the reaction also proceeded very well to produce desired
products 3q-3r in good yields with excellent regioselectivities, but
with poor diastereoselectivities (entries 17-18). Similarly,
substrate with substituents on allylic position was also compatible
to the reaction conditions to afford product 2s in 62% yield with
slightly better diastereoselectivity (5.3:1, entry 19). Finally, for
the cyclic substrates trans-1t and cis-1t, both reactions proceeded
very well to give the corresponding products 2t and 2u in good
yields, and cis-1t provided a better diastereoselectivity (entries
20-21). It is worth noting that a significant thrope-ingold-effect
was observed in this transformation, and the linear substrate N-Ts-
4-pentenylamine failed to produce the desired aminotrifluoro-
methoxylation product. The configuration of product 2f and 2r
were determined by X-ray analysis (Figure 1).
the sequential
β-fluoride elimination and reductive elimination.
Very interesting, when the reaction of 6 was conducted in the
mixture solvent of CH3CN and THF, the formation of complex 8
was significantly diminished, which is consistent with the results
in the catalytic reaction. These observations indicated that high-
valent palladium exhibited better stability than that of low-valent
metal,14 and the reductive elimination of RPdIVOCF3 is indeed
faster than
complexes
β
7
-fluoride elimination. The structure of palladium
was unambiguously determined by following
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experiments: (1) treatment of palladium complex 7 by HCO2Na,
the related hydrogenation product 11 was obtained; (2) in order to
get single crystal of palladium complex, pyridine and chloride
were added respectively to provide palladium complexes 9 and 10,
which were characterized by NMR as well as high solution mass
spectroscopy. After several tentative efforts, we were delighted to
obtain the single crystal of complex 10, which confirmed its
structure by X-ray spectroscopy.
Scheme 2. Trifluoromethoxylation of palladium complex 4.
BF4
BF4
AgOCF3
SelectFluor
CH3CN
N
N
N
N
N
N
Pd
Pd
X
Pd
0 o
C
w/wo THF
OCF3
F
NCCH3
0 o
C
4
(X = CH3CN or OCF3)
6 (in situ)
quantitative yield
To illustrate the mechanism of aminotrifluoromethoxylation
reaction, the stereochemistry was first investigated by employing
deuterium-labelled substrates trans-1a-d1. The reaction afforded
trans-2a-d1 as a single isomer, which is similar to the previous
aminochlorination13a and aminoacetoxylation13d reactions (eq 1).
We believed that the reaction could involve a reversible trans-
aminopalladation, and the formed secondary alkyl-Pd
intermediate was oxidized to give a high-valent alkyl-Pd(OCF3)
complex, which undergoes direct reductive elimination to yield
trans-2a-d1.
5 (in situ)
quantitative yield
warm to
25 o
C
F3CO
F3CO
F
BF4
BF4
BF4
N
N
Py
N
Pd
N
N
+
Pd
Pd
N
Py
NCCH3
NCCH3
9
in pure CH3CN
in CH3CN/THF
7 (43% from 4)
7 (46% from 4)
8 (20%)
8 (<3%)
(39% from 4)
NMR, HRMS
HCO2Na
(from 7)
NaCl
F3CO
N
OCF3
Pd
N
Cl
11 (34%)
10(40% from 4)
X-ray of 10
NMR, HRMS
In conclusion, we have developed a novel palladium-
catalyzed intramolecular aminotrifluoromethoxylation reaction of
unactivated alkenes.
piperidines were selectively obtained in good yields. Mechanistic
study revealed that involvement of high-valent palladium
intermediate was likely in the catalytic system. The related
PdIVOCF3 exhibited better stability and its facile reductive
elimination over β-fluoride elimination led to the formation of C-
OCF3 bond. Further exploration of new trifluoromethoxylation
reaction is in progress in our laboratory.
A variety of 3-trifluoromethoxylated
In order to gain direct evidence on the reductive elimination
of high-valent palladium complex for the C-OCF3 bond
formation, palladium complex 4 was synthesized and employed to
the trifluoromethoxylation reaction (Scheme 2).15 First, treatment
by SelectFluor at 0 oC, PdIVF complex 5 was formed in
quantitative yield.15a After addition of AgOCF3 into system, the
signals of 5 (at -334.8 ppm for 19F-NMR, 4.2 and 4.8 ppm for 1H-
NMR) were diminished immediately, and a new broad signal at -
31.4 ppm (19F-NMR) and two new methylene signals at 4.0 and
4.6 ppm (1H-NMR) were observed, which possibly belongs to the
PdIVOCF3 complex 6. Interestingly, when the solution of complex
6 in pure CH3CN was warmed to room temperature, the reductive
elimination proceeded to generate the desired sp3 C-OCF3 bond,
and the related Pd(II) complex 7 was observed in 43% yield. In
addition, the reaction also provided a small amount of Pd(II)
complex 8 bearing C-F bond (20% yield),15a which derived from
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