Double-Carboxylation of Two C-H Bonds in 2-Alkylheteroarenes Using LiO- t-Bu/CsF

Article abstract of DOI:10.1021/acs.orglett.9b01386

We describe the double-carboxylation of two C-H bonds (i.e., at the benzylic and the β-positions) in 2-alkylheteroarenes using a combination of LiO-t-Bu and CsF. A diverse range of substrates, namely benzothiophene, thiophene, benzofuran, furan, and indole derivatives, are efficiently converted into the doubly carboxylated products. A variety of functionalities (i.e., methyl, methoxy, halogen, cyano, ester, ketone, and amide moieties) are well tolerated.

Full text of DOI:10.1021/acs.orglett.9b01386

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Double-Carboxylation of Two C−H Bonds in 2‑Alkylheteroarenes
Using LiO‑t‑Bu/CsF
Masanori Shigeno,* Keita Sasaki, Kanako Nozawa-Kumada, and Yoshinori Kondo*
Department of Biophysical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578,
Japan
S
* Supporting Information
ABSTRACT: We describe the double-carboxylation of two C−H bonds
(i.e., at the benzylic and the β-positions) in 2-alkylheteroarenes using a
combination of LiO-t-Bu and CsF. A diverse range of substrates, namely
benzothiophene, thiophene, benzofuran, furan, and indole derivatives,
are efficiently converted into the doubly carboxylated products. A variety
of functionalities (i.e., methyl, methoxy, halogen, cyano, ester, ketone,
and amide moieties) are well tolerated.
he development of carboxylation reactions using CO2 to
Tform C−C bonds has long received significant interest
due to the abundance, nontoxicity, and low cost of CO2 as a
C1 source since the pioneering works using organolithium,1
organomagnesium,2 and sodium phenoxide3 were reported.
Indeed, the development of monocarboxylation reactions of a
variety of functionalized σ-bonds (i.e., C−Sn, C−B, C−Si, C−
Zn, C−Al, and C−halogen), unfunctionalized C−H bonds,
and unsaturated bonds has been reported in which one CO2
molecule couples with one substance.4 In contrast, the studies
of the corresponding double-carboxylation reactions, wherein
two CO2 molecules are captured by one substance, have not
been advanced, despite the fact that they can efficiently provide
dicarboxylic acids.5 So far, the double-carboxylation reactions
of unsaturated bonds, such as those present in acetylenes,
allenes, alkenes, and dienes, have been achieved using either a
catalytic or a stoichiometric amount of transition metals with a
reducing reagent or Brønsted base or upon electrochemical
reduction.6 The direct double-carboxylation of two C−H
bonds is also of great interest due to the abundance of C−H
bonds in organic substances (Figure 1a). Although several
examples have been demonstrated by employing transition-
metal catalysts and Brønsted bases,7−13 these examples are
limited to specific substrates, such as acetonitrile,7 acetylene,8
benzene,9 phenol,10 phenylpyrazole,11 and 1,2,4,5-tetrafluoro-
and -chlorobenzenes.12,13 This is due to a drop in the
nucleophilicity of the molecule following the first carbox-
ylation, in addition to the increased steric hindrance, both of
Figure 1. Double carboxylation of two C−H bonds.
which significantly affect the reactivities of C−H bonds close
substrate scope and functional group tolerance.14 As such, no
to the introduced carboxylic moiety. The stepwise operation,
system applicable to a diverse range of substrates has been
involving the deprotonation of two C−H bonds followed by
established.15 We recently reported that the carboxylation of
subsequent coupling with CO2, also results in double-
electron-rich heteroarenes proceeds smoothly using the
carboxylation (Figure 1b). This protocol, however, requires
the use of very strong Brønsted bases, such as n-BuLi, s-BuLi, t-
BuLi, or 2,2,6,6-tetramethylpiperidide base, to generate
Received: April 20, 2019
unstable dicarbanionic species, which significantly limits the
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01386
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Brønsted base system LiO-t-Bu/CsF/18-crown-6.16,17 Thus,
we herein report the use of LiO-t-Bu and CsF to promote the
double-carboxylation of 2-alkylheteroarenes (i.e., benzothio-
phene, thiophene, benzofuran, furan, and indole derivatives) at
the benzylic C(sp3)−H and the β-C(sp2)−H bonds (Figure
1c). The tolerance of this system to a wide range of functional
groups will also be examined.
Initially, the reaction of 2-methylbenzothiophene (1a) was
carried out using the various Brønsted bases in 1,3-dimethyl-2-
imidazolidinone (DMI) at 130 °C under ambient CO2
pressure (Table 1). The reaction of LiO-t-Bu provided the
Table 1. Effects of the Alkoxide Bases and Additives on the
a
Reaction
yield of 2a-
yield of
yield of
b
b
b
entry
base
additive(s)
LiF
RbF
CsF
CsCl
CsI
CsF
H
(%)
3
(%)
4
(%)
1
2
3
4
5
6
7
8
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
LiO-t-Bu
12
0
0
0
0
0
0
0
0
6
24
83
14
5
0
5
2
0
1
0
6
Figure 2. Substrate scope: 2-alkylbenzothiophenes. (a) Reactions
were conducted on a 0.3 mmol scale. (b) Isolated yields. (c) Reaction
was conducted on a 1.2 mmol scale. (d) Reaction was conducted at
160 °C. (e) Reaction was conducted at 140 °C. (f) Reaction was
conducted at 100 °C.
0
77
LiO-t-Bu
CsF +
18-crown-6
10
9
NaO-t-Bu
NaO-t-Bu CsF
KO-t-Bu
KO-t-Bu
LiOMe
LiO-t-Bu
27
77
53
57
0
7
3
5
7
0
1
2
3
2
2
0
3
10
11
12
13
CsF
CsF
CsF
1b and 1c, bearing electron-donating methyl and methoxy
groups at the 5-position, afforded the desired products 2b and
2c in yields of 84% and 75%, respectively. The reactions of 1d
and 1e, which contained methoxy substituents at the 6- and 7-
positions, respectively, formed 2d and 2e in yields of 71% and
82%. In addition, halogen atoms (i.e., F, Cl, and Br) were
tolerated to give the corresponding products 2f−h in yields of
87%, 83%, and 82%, respectively. The tolerance of the
relatively weak C(sp2)−Br bond is due to the in situ generation
of the relatively weak tert-butyl carbonate base from tert-
butoxide and CO2, which can prevent the one-electron transfer
reaction of the tert-butoxide to cleave the bond, as noted in our
previous study.16a Actually, we confirmed that the combination
of [t-BuOCO2Li] with CsF resulted in the double-carbox-
ylation of 1h under an argon atmosphere (Scheme S1). The
dimethyl ester structure of the benzothiophene derivative was
confirmed by X-ray crystal analysis of 2h (see the Supporting
Information). Furthermore, 1i and 1j, which contain electron-
withdrawing cyano and ester moieties, were also suitable
substrates, giving 2i and 2j in yields of 82% and 74%,
respectively. 2-Ethylbenzothiophene (1k) and 2-propylbenzo-
thiophene (1l) were also efficiently converted to the desired
products 2k and 2l in 81% and 76% yields, respectively.
Finally, the reaction of substrate 1m bearing two benzothio-
phene moieties was examined; the triple-carboxylated product
2m was obtained in 31% yield along with the double-
carboxylated product 2m′ in 26% yield.
c
14
94
a
Conditions: 1a (0.30 mmol), CO2 (1 atm), alkoxide base (1.50
mmol), additive(s) (1.50 mmol), DMI (1.5 mL), 130 °C, 13 h.
b
Yields were determined by 1H NMR spectroscopy using 1,1,2-
c
trichloroethane as an internal standard. Reaction was conducted at
150 °C.
desired product 2a-H in 12% yield (entry 1). The effects of
additives were then evaluated based on our previous studies
into the monocarboxylation of heteroarenes.16a Among the
examined alkali-metal salts, CsF was the most effective,
furnishing 2a-H in 83% yield (entries 2−6). In the absence
of LiO-t-Bu, 2a-H was not obtained (entry 7). The addition of
18-crown-6 did not increase the yield of 2a-H, and 3 and 4
were also formed in yields of 6% and 10%, respectively (entry
8). In addition, NaO-t-Bu/CsF and KO-t-Bu/CsF gave yields
of 77% and 57%, respectively, while LiOMe/CsF was
ineffective (entries 9−13). When the reaction of LiO-t-Bu
and CsF was carried out at 150 °C, 2a-H was obtained in 94%
yield (entry 14).18,19 Finally, the product obtained using these
conditions was isolated as the dimethyl ester form of 2a in 83%
yield following treatment with TMSCH2N2 (Figure 2).
With the optimized reaction conditions in hand, they were
then applied to the double carboxylation of a variety of 2-
alkylbenzothiophenes (Figure 2). 2-Methylbenzothiophenes
B
DOI: 10.1021/acs.orglett.9b01386
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
To broaden the substrate scope, the current system was then
applied to the double carboxylation of 2-methylheteroarenes
other than 2-methylbenzothiophenes (Figure 3). Thus, the
Scheme 1. Proposed Mechanism
Figure 3. Substrate scope: 2-methylheteroarenes with the exception
of 2-methylbenzothiophenes. (a) Reactions were conducted on a 0.3
mmol scale. (b) Isolated yields. (c) Reaction was conducted at 130
°C. (d) Reaction was conducted at 180 °C. (e) DMI (2.0 mL) was
used.
To gain insight into the reaction pathway of the proposed
double-carboxylation, additional experiments were carried out
(Figures 4 and 5). Initially, monocarboxylated substrates 3 and
reactions of 2-methylthiophenes 5a and 5b, bearing phenyl and
p-cyanophenyl moieties at the 5-position, proceeded to form
6a and 6b in yields of 80% and 88%, respectively. The
regioselectivity of the double-carboxylation in the thiophene
derivative was confirmed by X-ray crystal analysis of 6b (see
the Supporting Information). It was found that electrophilic
keto and amide substituents were well tolerated on the
thiophene ring to provide the desired products 6c and 6d in
67% and 82% yields, respectively. In addition, 2-methylbenzo-
furan (5e) and 2-methyl-5-phenylfuran (5f) were also
smoothly converted to their corresponding products in yields
of 92% and 77%, respectively, while 2-methylindoles 5g−i,
bearing methyl, phenyl, and pyridyl groups on their nitrogen
atom, gave diesters 6g−i in yields of 77%, 90%, and 70%,
respectively.
On the basis of the above results, a mechanism for the
double-carboxylation process was proposed (Scheme 1). In
this mechanism, an equilibrium exists between the tert-
butoxide base, [t-BuOM] (M = Li or Cs), and the carbonate,
[t-BuOCO2M], under a CO2 atmosphere.20,21 The increased
reactivity obtained by the combined Brønsted bases of LiO-t-
Bu and CsF is considered to be due to the generation of the
cesium base, a stronger base than the corresponding lithium
base, with the formation of stable LiF salt.22 The base initially
deprotonates the benzylic C(sp3)−H bond of 1a to generate
the anionic species 7,23 which then reacts with CO2 at the
benzylic position to form 8. Subsequently, deprotonation of
the benzylic position and coupling with CO2 at the β-position
occur to form 10, which is further deprotonated to give 11
(path a). Alternatively, 7 undergoes the first carboxylation at
the β-position and the second at the benzylic position (path b).
Figure 4. Conversion of monocarboxylated substrates 3 and 4 to 2a.
(a) Reactions were conducted on a 0.3 mmol scale. (b) Isolated
yields.
4 were subjected to the carboxylation reaction, and both
provided dicarboxylated product 2a. This result suggests that
both types of monocarboxylated intermediate may be involved
in the present system and that both paths a and b can be
involved. The reaction of 2-isopropylbenzothiophene (15) was
then carried out to give the monocarboxylated product 16 at
Figure 5. Monocarboxylation of 15 and 17 at the benzylic C(sp3)−H
bonds. (a) Reactions were conducted on a 0.3 mmol scale. (b)
Isolated yields.
C
DOI: 10.1021/acs.orglett.9b01386
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the benzylic position and not at the β-position.24 The benzylic
carboxylation of 2,3-dimethylbenzothiophene (17) also
occurred, thereby indicating that the carboxylation reaction
takes place at the benzylic position prior to the β-position. This
result appeared to favor pathway a.25
In summary, we successfully demonstrated that the Brønsted
base system LiO-t-Bu/CsF opened the door for the efficient
direct double-carboxylation of two C−H bonds in 2-
alkylheteroarenes. Indeed, this system facilitated the double-
carboxylation of various substrates, namely benzothiophene,
thiophene, benzofuran, furan, and indole derivatives. The
reaction was also found to be compatible with a wide range of
functional groups, such as methyl, methoxy, halogen, cyano,
ester, ketone, amide, and pyridyl moieties.
(2) Gilman, H.; St. John, N. B.; Schulze, F. Org. Synth. 1931, 11, 80.
(3) (a) Kolbe, H.; Lautemann, E. Liebigs Ann. Chem. 1860, 113, 125.
(b) Schmitt, R. J. Prakt. Chem. 1885, 31, 397.
(4) For examples of reviews, see: (a) Liu, Q.; Wu, L.; Jackstell, R.;
Beller, M. Nat. Commun. 2015, 6, 5933. (b) Huang, K.; Sun, C.-L.;
́
Shi, Z.-J. Chem. Soc. Rev. 2011, 40, 2435. (c) Tortajada, A.; Julia-
́
̈
Hernandez, F.; Borjesson, M.; Moragas, T.; Martin, R. Angew. Chem.,
Int. Ed. 2018, 57, 15948. (d) Zhang, L.; Hou, Z. Chem. Sci. 2013, 4,
3395. (e) Fujihara, T.; Tsuji, Y. Beilstein J. Org. Chem. 2018, 14, 2435.
(f) Brill, M.; Lazreg, F.; Cazin, C. S. J.; Nolan, S. P. Top. Organomet.
Chem. 2015, 53, 225. (g) Manjolinho, F.; Arndt, M.; Gooßen, K.;
Gooßen, L. J. ACS Catal. 2012, 2, 2014. (h) Yeung, C. S.; Dong, V.
M. Top. Catal. 2014, 57, 1342. (i) Janes, T.; Yang, Y.; Song, D. Chem.
Commun. 2017, 53, 11390. (j) Gui, Y.-Y.; Zhou, W.-J.; Ye, J.-H.; Yu,
D.-G. ChemSusChem 2017, 10, 1337. (k) Luo, J.; Larrosa, I.
ChemSusChem 2017, 10, 3317. (l) Hong, J.; Li, M.; Zhang, J.; Sun,
B.; Mo, F. ChemSusChem 2019, 12, 6. (m) Zhang, Z.; Ju, T.; Ye, J.-H.;
Yu, D.-G. Synlett 2017, 28, 741.
ASSOCIATED CONTENT
* Supporting Information
■
S
(5) Dicaroboxylic acid derived compounds are widely found in
biologically active materials; see: (a) Li, J. J. Heterocyclic Chemistry in
Drug Discovery; Wiley, 2013. (b) Li, J. J.; Corey, E. J. Drug Discovery:
Practices, Processes, and Perspectives; Wiley, 2013.
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01386.
(6) For examples, see: (a) Fujihara, T.; Horimoto, Y.; Mizoe, T.;
Sayyed, F. B.; Tani, Y.; Terao, J.; Sakaki, S.; Tsuji, Y. Org. Lett. 2014,
16, 4960. (b) Tortajada, A.; Ninokata, R.; Martin, R. J. Am. Chem. Soc.
2018, 140, 2050. (c) Takimoto, M.; Kawamura, M.; Mori, M.; Sato,
Y. Synlett 2005, 2019. (d) Zhang, W.-Z.; Yang, M.-W.; Yang, X.-T.;
Shi, L.-L.; Wang, H.-B.; Lu, X.-B. Org. Chem. Front. 2016, 3, 217.
Experimental details of synthetic procedures, effects of
amounts of reagents and solvents (Table S1), double
carboxylation of 1h with [t-BuOCO2Li] and CsF under
an Ar atmosphere (Scheme S1), spectra data for
obtained products, and X-ray crystallographic data for
2h and 6b (PDF)
́
́
(e) Derien, S.; Clinet, J.-C.; Dunach, E.; Perichon, J. Tetrahedron
1992, 48, 5235.
̃
Accession Codes
(7) Van Ausdall, B. R.; Poth, N. F.; Kincaid, V. A.; Arif, A. M.; Louie,
CCDC 1898070−1898071 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
J. J. Org. Chem. 2011, 76, 8413.
(8) Wang, X.; Lim, Y. N.; Lee, C.; Jang, H.-Y.; Lee, B. Y. Eur. J. Org.
Chem. 2013, 2013, 1867.
(9) Banerjee, A.; Dick, G. R.; Yoshino, T.; Kanan, M. W. Nature
2016, 531, 215.
(10) Kito, T.; Hirao, I. Bull. Chem. Soc. Jpn. 1971, 44, 3123.
(11) Mizuno, H.; Takaya, J.; Iwasawa, N. J. Am. Chem. Soc. 2011,
133, 1251.
(12) Boogaerts, I. I. F.; Fortman, G. C.; Furst, M. R. L.; Cazin, C. S.
J.; Nolan, S. P. Angew. Chem., Int. Ed. 2010, 49, 8674.
(13) Boogaerts, I. I. F.; Nolan, S. P. J. Am. Chem. Soc. 2010, 132,
8858.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: mshigeno@m.tohoku.ac.jp.
*E-mail: ykondo@m.tohoku.ac.jp.
(14) For examples, see: (a) Martínez-Martínez, A. J.; Kennedy, A.
R.; Mulvey, R. E.; O’Hara, C. T. Science 2014, 346, 834. (b) Schlosser,
M.; Guio, L.; Leroux, F. J. Am. Chem. Soc. 2001, 123, 3822.
(c) Kitajima, H.; Ito, K.; Aoki, Y.; Katsuki, T. Bull. Chem. Soc. Jpn.
1997, 70, 207. (d) Bedworth, P. V.; Tour, J. M. Macromolecules 1994,
27, 622. (e) Eaton, P. E.; Lee, C.-H.; Xiong, Y. J. Am. Chem. Soc.
1989, 111, 8016.
ORCID
Masanori Shigeno: 0000-0002-9640-8283
Kanako Nozawa-Kumada: 0000-0001-8054-5323
Notes
The authors declare no competing financial interest.
(15) For double-carboxylation reactions using one or two function-
alized σ-bonds, see: (a) Juhl, M.; Laursen, S. L. R.; Huang, Y.;
Nielsen, D. U.; Daasbjerg, K.; Skrydstrup, T. ACS Catal. 2017, 7,
1392. (b) Mita, T.; Ishii, S.; Higuchi, Y.; Sato, Y. Org. Lett. 2018, 20,
7603. (c) Mita, T.; Masutani, H.; Ishii, S.; Sato, Y. Synlett 2019, 30,
841.
(16) For our previous work into the monocarboxylation reaction,
see: (a) Shigeno, M.; Hanasaka, K.; Sasaki, K.; Nozawa-Kumada, K.;
Kondo, Y. Chem. - Eur. J. 2019, 25, 3235. For our related studies of
deprotonative functionalizations of C−H bonds by using an in situ
generated amide base, see: (b) Inamoto, K.; Okawa, H.; Taneda, H.;
Sato, M.; Hirono, Y.; Yonemoto, M.; Kikkawa, S.; Kondo, Y. Chem.
Commun. 2012, 48, 9771. (c) Inamoto, K.; Okawa, H.; Kikkawa, S.;
Kondo, Y. Tetrahedron 2014, 70, 7917. (d) Taneda, H.; Inamoto, K.;
Kondo, Y. Chem. Commun. 2014, 50, 6523. (e) Shigeno, M.; Fujii, Y.;
Kajima, A.; Nozawa-Kumada, K.; Kondo, Y. Org. Process Res. Dev.
2019, 23, 443. (f) Shigeno, M.; Nakaji, K.; Nozawa-Kumada, K.;
Kondo, Y. Org. Lett. 2019, 21, 2588. Also see: (g) Shigeno, M.; Kai,
ACKNOWLEDGMENTS
■
This work was financially supported by JSPS KAKENHI Grant
No. 16H00997 in Precisely Designed Catalysts with Custom-
ized Scaffolding (Y.K.), JSPS KAKENHI Grant No. 17K15419
(M.S.), JSPS KAKENHI Grant No. 19K06967 (M.S.), Grand
for Basic Science Research Projects from The Sumitomo
Foundation (M.S.), Yamaguchi Educational and Scholarship
Foundation (M.S.), NIPPON SHOKUBAI Award in Synthetic
Organic Chemistry, Japan (M.S.), and also the Platform
Project for Supporting Drug Discovery and Life Science
Research funded by Japan Agency for Medical Research and
Development (AMED) (M.S., K.N.K., and Y.K.).
REFERENCES
■
̈
(1) Wittig, G.; Pockels, U.; Droge, H. Ber. Dtsch. Chem. Ges. B 1938,
71, 1903.
D
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Letter
Y.; Yamada, T.; Hayashi, K.; Nozawa-Kumada, K.; Denneval, C.;
Kondo, Y. Asian J. Org. Chem. 2018, 7, 2082.
(17) For other examples of carboxylations of (hetero)arenes using
Brønsted bases, see: (a) Luo, J.; Preciado, S.; Xie, P.; Larrosa, I. Chem.
- Eur. J. 2016, 22, 6798. (b) Yoo, W.-J.; Nguyen, T. V. Q.; Capdevila,
M. G.; Kobayashi, S. Heterocycles 2015, 90, 1196. (c) Vechorkin, O.;
Hirt, N.; Hu, X. Org. Lett. 2010, 12, 3567. (d) Fenner, S.; Ackermann,
L. Green Chem. 2016, 18, 3804. (e) Zhang, Z.; Ju, T.; Miao, M.; Han,
J.-L.; Zhang, Y.-H.; Zhu, X.-Y.; Ye, J.-H.; Yu, D.-G.; Zhi, Y.-G. Org.
Lett. 2017, 19, 396. (f) Zhang, Z.; Liao, L.-L.; Yan, S.-S.; Wang, L.;
He, Y.-Q.; Ye, J.-H.; Li, J.; Zhi, Y.-G.; Yu, D.- G. Angew. Chem., Int. Ed.
2016, 55, 7068. Also see ref 9.
(18) For more details regarding the reaction optimization (quantities
of reagents and solvents), see Table S1.
(19) The reaction under high-pressure conditions was also examined
as follows, but it did not improve the yield of 2a-H. 2a-H was
obtained in the same yield of 11% when the reaction of 1a with LiO-t-
Bu (5 equiv) and CsF (5 equiv) in DMI at 110 °C was conducted
under either 1.0 or 6.0 atm of CO2 (results not shown).
(20) See Scheme S1 for the double carboxylation using the
combination of [t-BuOCO2Li] with CsF.
(21) Lan, Yu, and co-workers showed that the equilibrium is mainly
shifted to the carbonate side. See: Song, L.; Zhu, L.; Zhang, Z.; Ye, J.-
H.; Yan, S.-S.; Han, J.-L.; Yin, Z.-B.; Lan, Y.; Yu, D.-G. Org. Lett. 2018,
20, 3776.
(22) The Wang, Zhang, and Uchiyama group reported that use of
both LiO-t-Bu and CsF efficiently leads to tert-butyl ether formation
of an aryl ammonium salt as compared with the case of using only
LiO-t-Bu. See: (a) Wang, D.-Y.; Yang, Z.-K.; Wang, C.; Zhang, A.;
Uchiyama, M. Angew. Chem., Int. Ed. 2018, 57, 3641. Also see:
(b) Oparina, L. A.; Shaikhudinova, S. I.; Parshina, L. N.; Vysotskaya,
O. V.; Preiss, Th.; Henkelmann, J.; Trofimov, B. A. Russ. J. Org. Chem.
2005, 41, 656.
(23) Krenske, O’Brien, and co-workers used [t-BuOCO2Na] for the
catalytic Wittig reaction as a weak base and proposed that [t-
BuOCO2Na] slowly releases t-BuONa. See: Coyle, E. E.; Doonan, B.
J.; Holohan, A. J.; Walsh, K. A.; Lavigne, F.; Krenske, E. H.; O’Brien,
C. J. Angew. Chem., Int. Ed. 2014, 53, 12907.
(24) In this reaction, 41% of starting material 15 remained
1
unreacted, which was determined by the H NMR analysis of the
crude material.
(25) In a related study, we recently found that the deprotonative
coupling reaction of 1a with carbonyl compounds takes place at the
benzylic position using an in situ generated amide base; see ref 16f.
E
DOI: 10.1021/acs.orglett.9b01386
Org. Lett. XXXX, XXX, XXX−XXX