Organocatalytic decarboxylative alkylation of N-hydroxy-phthalimide esters enabled by pyridine-boryl radicals

Article abstract of DOI:10.1039/c8cc06152a

The decarboxylative alkylation of N-hydroxyphthalimide (NHPI) based reactive esters with olefins has been achieved via an organocatalytic strategy. Control experiments and density functional theory calculations suggest that these reactions involve a boryl-radical mediated decarboxylation pathway, which is different from the single electron transfer involved in decarboxylative alkylation reactions reported previously. This metal-free decarboxylative alkylation reaction features good functional compatibility, and broad substrate scope illustrated by the transformations of both the alkyl and aryl carboxylic acid derivatives.

Full text of DOI:10.1039/c8cc06152a

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Organocatalytic Decarboxylative Alkylation of N-Hydroxy-
phthalimide Esters Enabled by Pyridine-Boryl Radicals
Received 00th January 20xx,
Accepted 00th January 20xx
Liuzhou Gao,†a Guoqiang Wang,†a Jia Cao,a Dandan Yuan,a Xu Cheng,b Xuewen Guo,c and Shuhua
Li*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
a Photoredox-or Transition-metal catalyzed decarboxylative alkylation
The decarboxylative alkylation of N-hydroxyphthalimide (NHPI)
based reactive esters with olefins has been achieved via an
organocatalytic strategy. Control experiments and density
functional theory calculations suggest that these reactions involve
O
H
Photoredox catalyst, hv
R1 R2
R
R
O
R2 R1
or Ni-catalyst
R
SET
O
NPhth
R
O
a
boryl-radical mediated decarboxylation pathway, which is
b This work: pyridine-borylradicals promoted decarboxylative alkylation
R'
different from the single electron transfer involved
decarboxylative alkylation reactions reported previously. This
metal-free decarboxylative alkylation reaction features good
functional compatibility, and broad substrate scope illustrated by
the transformations of both the alkyl and aryl carboxylic acid
derivatives.
R'
O
N
B2(pin)2
N
N
cat.
O
D
(pin)B
O
B(pin)
A
O
O
O
O
N
R
O
N
R
O
R
O
O
B(pin)
C
B
O
1a
R1
R2
_
CO2
R1
R1
R2
H-Source
The decarboxylative alkylation via the addition of carbon
radicals to olefins is one of the most useful tools to construct
C-C bonds, due to the broad sources of carboxylic acids and
olefins. Recently, photoredox-mediated decarboxylation of
aliphatic acids1 or its activated esters,2 provide a facile access
for the C-C bond formation via the decarboxylation-radical
addition reaction of alkyl carboxylic acids to activated alkenes
(Fig. 1a). In addition, Ni-catalyzed decarboxylation Giese
reaction developed by Baran et al3 provides a thermally
induced radical pathway for the decarboxylative alkylation of
aliphatic acids with Michael acceptors. In photoredox
2
R
R
R2
R
3
E
F
Figure 1. Decarboxylative alkylation reactions.
this regard, the development of a new protocol utilizing both
alkyl and aryl radicals from their N-hydroxyphthalimide (NHPI)
esters derivatives in decarboxylative alkylation is still desirable.
Herein, we report an organocatalytic decarboxylative
alkylation of N-(acyloxy)phthalimides esters with alkenes (Fig.
1b), which, to the best of our knowledge, has not been
reported previously. This strategy is inspired by recent reports
that the carbonyl group of ketones or aldehydes is readily
associated pyridine-boryl radicals to initiate a radical addition
reaction7 and a recent pyridine-catalyzed decarboxylative
borylation of NHPI esters reported by Fu’s group.8 In Fu’s work,
the NHPI ester and a pyridine were assumed to be first
coordinated to the diboron complex, and then the B-B bond is
cleaved to generate a pyridine-boryl radical and a carboxylate
radical simultaneously via an intramolecular single electron
transfer step. However, we think that the NHPI ester is very
catalysis4-5
or
transition-metal
catalysis,6
N-
(acyloxy)phthalimide can accept an electron to form a radical
anion, which is then fragmented to afford alkyl radicals. These
alkyl radicals would then undergo conjugate addition with
electron-deficient olefins to provide conjugated addition
products. Although the photoredox- or Ni-catalyzed
decarboxylative alkylation reaction has been well established,
the scope of carboxylic acids is still limited to aliphatic acids. In
likely to coordinate with the pyridine-boryl radical (A) to form
a radical intermediate, which may trigger the fragmentation of
NHPI esters to generate a carbon radical for subsequent
radical addition reactions. The pyridine-boryl radical can be
easily generated using readily available (pinacolato)diboron
(B2pin2) and pyridines.7,
9-10
This strategy would provide an
alternative strategy for the decarboxylative alkylation using
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pyridine
benzo[d][1,3]dioxole
diarylethylenes with various substituents such as Br (24), SMe
25), CO2Et (26) and OCF3 (27) also reacted with 1, giving the
dicarboxylative adducts 21 29 in 72-90% yields. Other
alkenes such as benzyl methacrylate could also be employed
as the radical acceptor, as demonstrated by the formation of
30 in acceptable yield.
(
17), benzofuran
(
18), thiophene
(19), and
alkenes and readily available NHPI esters. In this work, a broad
range of aliphatic or aryl carboxylic acid based reactive esters
and alkenes are suitable in this transformation, affording the
C(sp3)-C(sp3) or C(sp3)-C(sp2) coupling products. We have also
demonstrated the utility of this method in the late-stage
modification of drug-relevant molecules. This protocol
provides a new approach for the construction of C-C bonds
from readily available materials without the use of transition-
metal or photoredox catalysts.
(
20). In addition, other 1,1-
(
(
-
)
Table 1. Substrate scope of alkene substrates.a
Our proposed catalytic cycle consists of the following steps
(Fig. 1b): (1) the generation of the pyridine-boryl radical
A
from B2pin2 and pyridine via the cooperative catalysis of two
pyridine molecules; (2) the migration of the pyridine-boryl
radical
species
A
to N-(acyloxy)phthalimide (1a) to form the radical
; (3) the dissociation of the pyridine molecule from
B
the radical
cleavage of the N-O bond in
and phthalimide-B(pin) ; (5) the extrusion of CO2 from
provide the carbon radical
intermediate from the addition of the carbon radical
alkene; and (7) the hydrogen abstraction of the intermediate
B to regenerate the catalyst; (4) the homolytic
B
to afford the aroyloxy radical
C
D
C
to
E
; (6) the formation of the radical
to
F
E
F
from a hydrogen source to give the desired decarboxylative-
radical addition product. Although 4-cyanopyridine has been
demonstrated to be a suitable Lewis base for the generation of
the pyridine-boryl radical A 7,
11
,
here other pyridines with
various substituents will also be explored experimentally.
aReaction conditions: NHPI ester 1 (0.2 mmol), B2(pin)2 (0.2 mmol), 4-
carboethoxypyridine (0.04 mmol), alkenes (0.4 mmol), PhCF3 (1.0 ml), 1,3,5-
trimethyl- 1,4-cyclohexadiene (0.3 mmol), 18 hours.
To explore the possibility of the proposed reaction, we
began our study by evaluating the reaction of N-
(acyloxy)phthalimides 1 and 1,1-diphenylethylene 2 as the
substrates (see Table S1 in Supporting Information for details).
In the presence of B2pin2 and 1,3,5-trimethyl-1,4-
cyclohexadiene, the optimal reaction conditions was achieved
through the use of 20 mol% of 4-carboethoxypyridine as the
catalyst and PhCF3 as the solvent, the decarboxylative
Different N-(acyloxy)phthalimides could be used as
substrates to react with 1,1-disubstituted olefins (Table 2).
These thermally induced radical reactions could be compatible
with a wide range of functional groups, including halogens (F
(
32
piperidines (42
36 40), amides (42
,
41), Cl
(
,
35), Br
43 and 50), indole (68)), esters (48), alkenes
44 50), hydroxyl (52), ketone (73),
(33)), heterocycles (pyridine (35),
alkylation product 3 could be obtained in 79% yield (see Eq. 1).
The use of 1,3,5-trimethyl-1,4-cyclohexadiene is crucial to
suppress the disproportionation of the diaryl radical
(
,
-
,
suggesting that this protocol can serve as a versatile platform
for further modification. The primary (Table 2a), secondary
carboxylic acids (Table 2b) are good alkyl radical precursors to
form the 1,1-diarylalkane derivatives in good to excellent
yields. The use of tertiary carboxylic acids (Table 2c) could
offer the 1,1-diarylalkane compounds with quaternary carbon
intermediate (
After identifying the optimal conditions, the substrate scope
of alkenes was investigated with as the substrate (Table 1). A
F
).7c
1
broad variety of α-methylstyrenes, with withdrawing groups
and electron-donating group at the para-position of arene
moiety, could be used as radical acceptors to form the
center with high levels of efficiency (46-52) in 48-91% yield.
Since 1,1-diaryl motif is an important moiety in medicinal
chemistry,12 our method could provide a straightforward way
for the generation of a library of drug relevant molecules
containing 1,1-diarylalkanes. More importantly, some electron
deficient aromatic carboxylic acid reactive esters (derived from
pyridine, isoquinoline or benzene carboxylic acids) could also
be used as coupling partners to generate the radical adducts
corresponding adducts
trifluoromethyl styrenes, α-ester styrenes and 2-
vinylsubstituted naphthalene could also be used with similar
efficiency, as shown by the formation of 10-13. Good to
excellent yields of decarboxylative adducts (4-6, 11) were
generally obtained for styrenes bearing withdrawing groups.
Heterocyclic structure is an important class of structural unit
found in drugs and other bioactive molecules, and the
synthesis of diverse functionalized heterocycle containing
compounds in a metal-free manner is attractive. Notably, our
method tolerates a wide range of 1,1-disubstituted olefins
4
-
7
and
8
-
9
.
Additionally, α-
(
53-67) in moderate yields (Table 2d). In contrast, the aromatic
carboxylic acids or their reactive eaters have not been used in
photoredox- or Ni-catalyzed decarboxylative alkylation
reaction with alkenes.2d, 3, 4c In addition, this method is also
applicable in the late-stage structural modification of drug
molecules (Table 2e). N-(acyloxy)phthalimides derived from
containing heterocyclic moiety, including 2-pyridine (14-16), 4-
2 | J. Name., 2012, 00, 1-3
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some drug molecules (indometacin, fenofibric acid and step is the hydrogen abstraction from 1,3,5-trimethyl-1,4-
gemfibrozil), were all converted to the corresponding cyclohexadiene to afford the radical species via TSF-3, with a
decarboxylative adducts 58 74 in 51-84% yield. barrier of 24.8 kcal/mol (relative to the radical ). The whole
F
(
-
)
F
Decarboxylative alkylation of the NHPI ester derived from reaction is strongly exothermic by 50.5 kcal/mol. These results
indometacin to form 68 was successfully scaled up to 2.4 are in qualitative accord with the experimental condition (120
mmol, with the product 68 in 61% yield.
oC is used). In addition, our DFT calculations suggest that the
direct SET process from the pyridine-boryl radical to the NHPI
ester is highly endergonic by 55.8 kcal/mol (see Figure S3).
Thus, the SET pathway for the activation of the NHPI ester to
form a carboxylate radical can be excluded.
Table 2. Substrate scope of NHPI esters.a
Figure 2. Gibbs free energy profile of the proposed pathway
Furthermore, we performed several control experiments to
verify the proposed pathway (Fig. 3 and Fig. S4). First, the
intermediacy of the pyridine-boryl radical can be confirmed by
the detection of EPR signal from the mixture of 4-
carboethoxypyridine/B2(pin)2 (g = 2.0031, 298 K) (see Fig. S4).
The EPR parameters obtained from simulations of the
experiment spectra are listed in Table S2. The SOMO picture
from our calculations shows that the unpaired electron of this
radical (A) is mainly delocalized over the pyridine ring (Fig. S4).
Then, the formation of the alkyl radical via the decarboxylation
of N-(acyloxy)phthalimides was verified by a radical-clock
experiment using 75 as the substrate (Fig. 3a). The isolation of
5-exo cyclization related product (76) in 65% yield indicates
that the direct addition of the alkyl radical to alkenes is much
slower than the intramolecular radical addition step within the
alkyl radical (see Fig. S5).14 The direct hydrogen abstraction
reaction of the decarboxylative carbon radical from 1,3,5-
trimethylcycylohexandiene is also possible. As expected, when
the substrate 77 was subjected to the standard condition in
the absence of alkenes, the decaboxylative reduction product
78 was isolated in 79% yield, and only trace amount of the C-B
coupling product 79 was detected by GC-MS analysis (Fig. 2b,
see Fig. S6 for details). In contrast, when the 1,1-
aReaction conditions: NHPI ester (0.2 mmol), B2(pin)2 (0.2 mmol), 4-
carboethoxypyridine (0.04 mmol), alkenes (0.4 mmol), PhCF3 (1.0 ml), 1,3,5-
trimethyl-1,4-cyclohexadiene (0.3 mmol), 18 hours. bPerformed at 2.4 mmol
scale for 18 hours.
diphenylethylene was added, the decarboxylative adduct (80
)
With 1,3,5-trimethyl-1,4-cyclohexadiene as
a hydrogen
was formed in 76% yield (Fig. 2b). These results suggest that
the addition of the carbon radical to 1,1-disubstituted ethylene
is more favorable than the hydrogen abstraction from 1,3,5-
trimethyl-1,4-cyclohexadiene in the reaction. In addition, the
source, we have computationally investigated the free energy
profile of the reaction between 1,1-diphenylethylene, NHPI
ester 1 and the pyridine-boryl radical (A) along the pathway
proposed in Figure 1b with DFT calculations (with the M06-2X
functional).13 Our calculations suggest that the formation of
the pyridine-boryl radical A from 4-carboethoxypyridine and
formation of the key intermediate, phthalimide-B(pin) (D),
could be detected by crude HRMS analysis of the reaction
mixture of 77 and 1,1-diphenylethylene (see Fig. S7). Finally,
we also found that the pyridine/B2pin2 system was even
compatible with some classical electron acceptors (which are
easily reduced via a SET pathway). For example, with N-
tosylindole 81, Weinreb amide 82 or aryl iodides 83a-b as
additives, the decarboxylative radical addition related product
B2(pin)2 is exothermic by 14.9 kcal/mol, with a free energy
barrier of 24.6 kcal/mol (see Fig. S1 for computational details).
For the reaction among 1,1-diphenylethylene, NHPI ester
A
1
and the pyridine-boryl radical , the calculated free energy
profile is shown in Fig. 2. It can be seen that the six steps
proposed above are supported by our calculations. Among six
steps, two steps have relatively large activation barriers. The
(3 and 3’) could be formed as expected, leaving these electron
acceptors untouched (see Table S3).10b,15 These control
experiments also revealed that this decarboxylative alkylation
is likely to proceed via a pyridine-boryl radical association-
homolytic cleavage of the O-N bond in
radical via TSB-C involves a barrier of 21.8 kcal/mol (relative
to the reactants and ). Nevertheless, the rate-determining
B to form a carboxylate
C
1
A
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4
T. Qin, L. R. Malins, J. T. Edwards, R. R. Merchant, A. J. E.
Novak, J. Z. Zhong, R. B. Mills, M. Yan, C. Yuan, M. D.
Eastgate and P. S. Baran, Angew. Chem. Int. Ed. 2017, 56, 260.
(a) C. Cassani, G. Bergonzini and C.-J. Wallentin, Org. Lett.
2014, 16, 4228. (b) J. D. Griffin, M. A. Zeller and D. A.
Nicewicz, J. Am. Chem. Soc. 2015, 137, 11340. (c) G. L.
Lackner, K. W. Quasdorf, G. Pratsch and L. E. Overman, J.
Org. Chem. 2015, 80, 6012. (d) Y. Slutskyy and L. E. Overman,
Org. Lett. 2016, 18, 2564. (e) C. C. Nawrat, C. R. Jamison, Y.
Slutskyy, D. W. C. MacMillan and L. E. Overman, J. Am. Chem.
Soc. 2015, 137, 11270. (f) D. Wang, N. Zhu, P. Chen, Z. Lin
and G. Liu, J. Am. Chem. Soc. 2017, 139, 15632. (g) H. Huang,
C. Yu, Y. Zhang, Y. Zhang, P. S. Mariano and W. Wang, J. Am.
Chem. Soc. 2017, 139, 9799. (h) C. Wang, Y. Lei, M. Guo, Q.
Shang, H. Liu, Z. Xu and R. Wang, Org. Lett. 2017, 19, 6412. (i)
M. J. Schnermann and L. E. Overman, Angew. Chem., Int. Ed.
2012, 51, 9576. (j) K. Okada, K. Okamoto, K. Okubo and M.
Oda, J. Am. Chem. Soc. 1988, 110, 8736. (k) L. Candish, M.
Teders and F. Glorius, J. Am. Chem. Soc. 2017, 139, 7440. (l)
L. Ren and H. Cong, Org. Lett. 2018, 20, 3225. (m) A. C. Sun,
E. J. McClain, J. W. Beatty and C. R. J. Stephenson, Org. Lett.
2018, 20, 3487.
triggered NHPI ester fragmentation pathway rather than a SET
process.
Figure 3. Mechanistic investigations.
In summary, we have established an organocatalytic
decarboxylative alkylation of N-hydroxyphthalimide based
reactive esters with olefins using 4-carboethoxypyridine as the
catalyst. DFT calculations and control experiments suggest that
the formation of alkyl or aryl radicals in this decarboxylation
alkylation process is induced by the association of the pyridine-
boryl radicals with NHPI esters. This metal-free strategy offers
an alternative decarboxylative alkylation protocol, different
from existing photoredox or transition-metal catalyzed
decarboxylative alkylation protocols. This pyridine-boryl radical
promoted decarboxylation protocol provides a facile access to
a variety of alkyl and aryl radicals from readily available N-
hydroxyphthalimide based reactive esters. Moreover, this
protocol exhibits broad substrate scope and good functional
group compatibility. The potential of this protocol in late-stage
modifications of drug molecules has been demonstrated. We
hope that our present work might stimulate more studies on
radical chemistry.
5
6
A. Fawcett, J. Pradeilles, Y. Wang, T. Mutsuga, E. L. Myers
and V. K. Aggarwal, Science, 2017, 357, 283.
(a) G. Li, T. Wang, F. Fei, Y.-M. Su, Y. Li, Q. Lan and X.-S.
Wang, Angew. Chem. Int. Ed. 2016, 55, 3491. (b) M. O. Konev
and E. R. Jarvo, Angew. Chem. Int. Ed. 2016, 55, 11340. (c) G.
J. P. Perry, J. M. Quibell, A. Panigrahi and I. Larrosa, J. Am.
Chem. Soc. 2017, 139, 11527. (d) X. Tan, Z. Liu, H. Shen, P.
Zhang, Z. Zhang and C. Li, J. Am. Chem. Soc. 2017, 139
,
12430. (e) W. Xue and M. Oestreich, Angew. Chem. Int. Ed.
2017, 56, 11649. (f) J. M. Smith, T. Qin, R. R. Merchant, J. T.
Edwards, L. R. Malins, Z. Liu, G. Che, Z. Shen, S. A. Shaw, M.
D. Eastgate and P. S. Baran, Angew. Chem. Int. Ed. 2017, 56
,
11906. (g) F. Sandfort, M. J. O'Neill, J. Cornella, L. Wimmer
and P. S. Baran, Angew. Chem. Int. Ed. 2017, 56, 3319. (h) F.
Toriyama, J. Cornella, L. Wimmer, T.-G. Chen, D. D. Dixon, G.
Creech and P. S. Baran, J. Am. Chem. Soc. 2016, 138, 11132.
(a) G. Wang, H. Zhang, J. Zhao, W. Li, J. Cao, C. Zhu and S. Li,
Angew. Chem. Int. Ed. 2016, 55, 5985. (b) G. Wang, J. Cao, L.
Gao, W. Chen, W. Huang, X. Cheng and S. Li, J. Am. Chem.
Soc. 2017, 139, 3904-3910. (c) J. Cao, G. Wang, L. Gao, X.
Cheng and S. Li, Chem. Sci., 2018, 9, 3664.
W.-M. Cheng, R. Shang, B. Zhao, W.-L. Xing and Y. Fu, Org.
Lett. 2017, 19, 4291.
(a) E. C. Neeve, S. J. Geier, I. A. I. Mkhalid, S. A. Westcott and
T. B. Marder, Chem. Rev. 2016, 116, 9091. (b) A. B. Cuenca,
R. Shishido, H. Ito and E. Fernandez, Chem. Soc. Rev. 2017,
46, 415.
7
This work was supported by the National Natural Science
Foundation of China (21333004, 21361140376 and 21572099),
and China Postdoctoral Science Foundation (2017M620198).
We also thank Dr. Gengwen Tan (Nanjing University) for his
help in the simulation of EPR spectra.
8
9
Conflicts of interest
10 (a) L. Zhang and L. Jiao, J. Am. Chem. Soc. 2017, 139, 607. (b)
L. Zhang and L. Jiao, Chem. Sci. 2018, 9, 2711.
There are no conflicts to declare.
11 For reviews on the persistent radical, see: (a) A. Studer,
Chem. Soc. Rev. 2004, 33, 267. (b) A. Studer and D. P. Curran,
Angew. Chem, Int. Ed. 2016, 55, 58.
12 (a) G. Jones, R. F. Maisey, A. R. Somerville and B. A. Whittle,
J. Med. Chem. 1971, 14, 161. (b) A. Vasilopoulos, S. L.
Zultanski and S. S. Stahl, J. Am. Chem. Soc. 2017, 139, 7705.
13 (a) Y. Zhao, N. E. Schultz and D. G. Truhlar, J. Chem. Theory.
Notes and references
1
2
(a) D. W. Manley, R. T. McBurney, P. Miller, R. F. Howe, S.
Rhydderch and J. C. Walton, J. Am. Chem. Soc. 2012, 134
13580. (b) L. Chu, C. Ohta, Z. Zuo and D. W. C. MacMillan, J.
Am. Chem. Soc. 2014, 136, 10886. (c) G. H. Lovett and B. A.
Sparling, Org. Lett. 2016, 18, 3494.
(a) K. Okada, K. Okamoto, N. Morita, K. Okubo and M. Oda, J.
Am. Chem. Soc. 1991, 113, 9401. (b) J. W. Tucker and C. R. J.
Stephenson, J. Org. Chem. 2012, 77, 1617. (c) C. R. Jamison
and L. E. Overman, Acc. Chem. Res. 2016, 49, 1578. (d) J.
Schwarz and B. Konig, Green Chem. 2016, 18, 4743. (e) A.
Tlahuext-Aca, R. A. Garza-Sanchez and F. Glorius, Angew.
Chem. Int. Ed. 2017, 56, 3708. (f) M. Sandip, Adv. Synth.
Catal. 2018, 360, 1735. (g) Y. Li, L. Ge, M. T. Muhammad and
H. Bao, Synthesis. 2017, 49, 5263.
,
Comput. 2006, 2, 364. (b) Y. Zhao and D. G. Truhlar, J. Chem.
Phys. 2006, 125, 194101. (c) Y. Zhao and D. G. Truhlar, J.
Phys. Chem. A. 2006, 110, 13126.
14 (a) M. Yan, J. C. Lo, J. T. Edwards and P. S. Baran, J. Am. Chem.
Soc. 2016, 138, 12692. (b) D. Griller and K. U. Ingold, Acc.
Chem. Res. 1980, 13, 317.
15 K. D. Collins and F. Glorius, Nat. Chem. 2013, 5, 597.
4 | J. Name., 2012, 00, 1-3
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