Organocatalytic Enantioselective Continuous-Flow Cyclopropanation

Article abstract of DOI:10.1021/acs.orglett.6b03156

A set of six solid-supported diarylprolinol catalysts (varying on the anchoring strategy and the type of polymeric support) has been prepared and applied to the enantioselective cyclopropanation reaction. The selected candidate allows implementation of a long flow experiment (48 h) and generates a library of 12 cyclopropanes by sequential flow experiments. The mildness and utility of the method have enabled a telescoped process in which the outstream is directly used in a Wittig flow reaction.

Full text of DOI:10.1021/acs.orglett.6b03156

Letter
pubs.acs.org/OrgLett
Organocatalytic Enantioselective Continuous-Flow Cyclopropanation
Patricia Llanes,‡ Carles Rodríguez-Escrich,*,‡ Sonia Sayalero,‡ and Miquel A. Pericas*,‡,§
̀
‡Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Av. Països Catalans, 16,
43007 Tarragona, Spain
§Departament de Química Inorgan
̀ ̀
ica i Organica, Universitat de Barcelona (UB), 08028 Barcelona, Spain
S
* Supporting Information
ABSTRACT: A set of six solid-supported diarylprolinol catalysts
(varying on the anchoring strategy and the type of polymeric
support) has been prepared and applied to the enantioselective
cyclopropanation reaction. The selected candidate allows implemen-
tation of a long flow experiment (48 h) and generates a library of 12
cyclopropanes by sequential flow experiments. The mildness and
utility of the method have enabled a telescoped process in which the
outstream is directly used in a Wittig flow reaction.
yclopropanes, the smallest all-carbon cyclic systems, are
Scheme 1. Aminocatalytic Cyclopropanation of Enals with
Dimethyl Bromomalonate
C
widespread in natural products,1 and their structure can be
found in myriad pharmaceutically active compounds.2 Their
strained nature endows them with special features both
chemically (where they can serve as spring-loaded alkyl units
or radical clocks3) and biologically (where they are considered
bioisosters of alkyl chains4 with improved in vivo stability).
However, cyclopropane itself is of little use (its early application
in anesthesia was abandoned in the 1980s5), and substituted
analogues are usually required. Indeed, the preparation of
compounds bearing cyclopropane rings has been a matter of
study for many years, giving rise to several methodologies like the
classical Simmons−Smith6 or Corey−Chaykovsky7 reactions.
Given the interest in obtaining optically pure cyclopropanes for
biological or pharmaceutical applications, several catalytic
enantioselective protocols have been developed8 involving
mainly Cu-9 and Rh-mediated10 [2 + 1] cycloadditions.
Nevertheless, carbene or carbenoid intermediates are not easy
to tame, so metal-free cyclopropanations have been considered
as an alternative. Indeed, successful organocatalytic approaches
toward these targets include the condensation of α-chloroke-
tones with electron-poor olefins through the intermediacy of
ammonium ylides11 or an iminium ion-mediated cyclopropana-
tion with sulfonium ylides12 among others.13 In 2007, Wang14
and co-workers developed a particularly appealing aminocatalytic
strategy that exploited the dual reactivity of bromomalonates as
both nucleophiles and electrophiles (Scheme 1). This perfectly
matched with the iminium ion−enamine manifold, giving rise to
a Michael initiated cascade reaction that produced highly
enantioenriched cyclopropanes15 even in water.16 Among all
aminocatalysts tested, silylated diarylprolinols (Jørgensen−
Hayashi-type catalysts17) proved to be the best choice in terms
of reactivity and selectivity. As shown in Scheme 1, however, this
approach is not devoid of limitations, since the presence of the
gem-diester group on the cyclopropane adducts triggers a base-
mediated ring opening process. We reasoned that this problem
could be mitigated by minimizing the contact time between the
cyclopropane and the base required for the cycloaddition. This
goal could be conveniently achieved by replacing batch operation
with a continuous process involving a suitable immobilized
catalyst.
Several research groups,18 including our own,19 have
immobilized Jørgensen−Hayashi-type catalysts on a variety of
solid supports to exploit the inherent advantages derived from
heterogenization such as easy purification of the products, the
possibility of easy recycling and reuse of the catalyst, and the
potential for its use in flow. Bearing in mind the problems
associated with aminocatalytic cyclopropanation in batch as
discussed above, we decided to study whether a solid-supported
diarylprolinol would be competent in promoting flow
enantioselective cyclopropanations. Literature precedents in-
clude the continuous production of cyclopropanes in a racemic
fashion20 or in an enantioselective manner with supported Cu
and Rh21 complexes, but to the best of our knowledge, the
asymmetric organocatalytic cyclopropanation in flow remains
unexplored.
Received: October 21, 2016
© XXXX American Chemical Society
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DOI: 10.1021/acs.orglett.6b03156
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The deployment of immobilized chiral catalysts22 in
enantioselective flow processes23 is an especially challenging
task; although activity and selectivity are still important
parameters, mechanical stability of the support proves crucial
for long-term operation. Thus, herein we decided to establish a
direct comparison between microporous resins (with 1−2%
cross-linking) and monoliths. Typically used in flow, monoliths24
are rodlike, single pieces of porous material prepared by
polymerization inside cylindrical reactors. Their relatively high
cross-linking levels make them macroporous in nature, with
lower swelling ability than microporous resins.
Therefore, at the onset of the project, we envisaged three
different immobilization strategies: grafting hydroxyproline
derivatives onto polystyrene through benzyl- (1 series) or
1,2,3-triazole-based linkers (2 series) and copolymerizing with
styrene diarylprolinol units bearing p-vinylphenyl aryl groups (3
series). For each case, both the formation of a microporous resin
(R) and a monolith (M) were studied, giving rise to the six solid-
supported Jørgensen−Hayashi catalysts depicted in Figure 1 (see
the Supporting Information for synthetic details).
conditions, we were ready to test the behavior of these six
polymeric catalysts in the flow cyclopropanation of enals with
bromomalonates.
The flow setup consisted of two feeding streams (each of them
connected to a pump) that were combined right before an
omnifit column packed with the catalytic monolith or resin.
Downstream of this column, a third inlet with ammonium
chloride and a liquid−liquid separator were placed to remove the
base from the outgoing flow, thus preventing the secondary
reaction involving ring-opening of the cyclopropane. In this
manner, the collected organic phase contained only the final
product, excess bromomalonate, and any unreacted starting
material (Figure 2). Under the conditions described above, all of
the immobilized catalysts were subjected to a 2-h flow process
with a combined flow rate of 100 μL min−1 (Table 1).
a
Table 1. Comparison of Catalyst Behavior in Flow
entry
catalyst
conv (%)
ee (%)
1
2
3
4
5
6
1R
1M
2R
2M
3R
3M
71
34
94
79
50
20
93
96
87
90
94
97
a
See Figure 2 for the setup (R = 4-NO2C6H4). Total flow rate: 100 μL
min−1. Solution A: enal and dimethyl bromomalonate (0.6 M) in
CH2Cl2. Solution B: N-methylimidazole (0.6 M) in CH2Cl2.
Resin 2R proved to give the best conversions, albeit at the cost
of slightly decreased enantioselectivity. Indeed, comparing all the
results, the presence of a triazole-based linker (2 series, entries 3
and 4) appears optimal for catalytic activity but detrimental for
ee. The 3 series, which involves immobilization through the
diaryl moiety,25 gave rise to comparatively less active catalysts,
probably because this immobilization strategy does not ensure
enough distance between the active site and the polymer matrix.
Overall, resin 1R (entry 1) and monolith 2M (entry 3) gave the
best combination of yield and ee.
In order to compare the robustness of both catalysts, we ran
two long-flow experiments (>24 h) with 1R and 2M (setup as in
Figure 2; R = Ph) where conversion and ee were measured
periodically (see the Supporting Information for details).
Notably, monolith 2M remained active for ca. 24 h but then
catalytic activity sharply dropped to practically disappear. We
attribute this behavior to mechanical collapse of the resin under
the rather high working pressure. In turn, 1R was active for more
than 48 h, with the ee’s remaining essentially constant with both
resins for the whole operation time. In addition, the residence
time observed for 1R was lower than that of 2M (12 vs 40 min),
which allows the contact time between reagents and catalyst to be
Figure 1. Polystyrene-supported catalysts tested in this work.
In all cases, the tert-butyldimethylsilyl group was chosen to
protect the tertiary hydroxy group due to its superior stability
compared to its trimethylsilyl analogue.19d It is also worth
mentioning that in most cases we decided to prepare the
polymers ourselves rather than starting from commercial
Merrifield-type resins. This strategy allows complete regiochem-
ical control in the functional polymers as well as fine-tuning in
terms of functionalization and cross-linking. Commercial
Merrifield resins that could be used as alternative starting
materials involve mixtures in variable proportions of m- and p-
chloromethyl substituted aryl groups and lack the possibility of
fine-tuning in functionality and cross-linking.
A preliminary study of the cyclopropanation reaction in batch
allowed to establish the optimal reaction conditions. These
involve CH2Cl2 as solvent, the use of the α,β-unsaturated
aldehyde as the limiting reagent (1.3:1 molar ratio of
bromomalonate to aldehyde), performing the reaction at room
temperature and using N-methylimidazole15c as the base (see the
Supporting Information for details). After finding suitable
Figure 2. Continuous flow setup for the enantioselective cyclopropanation.
B
DOI: 10.1021/acs.orglett.6b03156
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Letter
minimized. These facts, together with the versatility of
microporous resins (monoliths are prepared and used as a
whole batch whereas resins can be accurately weighed),
convinced us that 1R was a better choice to study the scope of
the reaction in flow.
To this end, a family of α,β-unsaturated aldehydes was
submitted to the 1R-catalyzed flow process with dimethyl
bromomalonate as the reaction partner. Each flow experiment
was allowed to run for 6 h at 100 μL min−1 under the conditions
previously optimized for 6b. After every example, the column was
simply rinsed with CH2Cl2 to be used with the next combination
of substrates. With this sequential approach, up to 12 different
analogues were prepared (Scheme 2) with excellent ee’s and
diastereoselectivities (a single diastereomer was detected in all
cases by NMR; dr >95:5).
conditions can be adjusted to optimize the production of any
particular cyclopropane product 6. Moreover, it is worth
mentioning that the lower productivities of 6e, 6f, and 6k can
be attributed to the low solubility of the corresponding
aldehydes, which hampers the flow process.
In order to assess the benefits of the continuous process,
comparative experiments were run in batch (with 1R) and in
homogeneous medium (with TBS-protected diphenylprolinol).
Whereas with electron-poor enals the results were comparable,
with electron-rich ones the limitation of contact time between
the final product and the catalyst/base (inherent to the flow
process) allowed minimization of the byproduct formation
described in Scheme 1 (see the Supporting Information for
details). This illustrates the potential of flow with respect to batch
when the formation of byproducts arising from consecutive
reactions can occur.
Remarkably, all of the flow experiments summarized in
Scheme 2 have been carried out with the same sample of catalyst
over a period of 12 months, which further proves the robustness
of the system; during this time frame, 1R could be stored and
reused without apparent loss of activity. Encouraged by these
results, we decided to test the possibility of increasing the
molecular complexity generated by the flow process by using the
cyclopropanecarboxaldehyde product as the starting material for
a consecutive Wittig reaction. Using the same catalytic cartridge,
a third feed solution with a Wittig ylide was added to the flow
device, connecting it to the outstream of the reactor packed with
1R (Figure 3).
Scheme 2. Library of Analogues Prepared in Flow with 1R
Figure 3. Telescoped cyclopropanation−Wittig reaction in flow.
To our delight, the telescoped flow process took place
uneventfully, giving rise to 1.08 g of the α,β-unsaturated ester 7d
(94% ee, 1.08 mmol h−1 gresin−1). This last experiment served to
prove two points: on the one hand, it showcases the mildness of
the reaction conditions, as the solution obtained after the
cyclopropanation requires no further purification to be
derivatized. On the other hand, the enantioselectivity obtained
with cinnamaldehyde during the previous experiments (see
Scheme 2, product 6d) was exactly replicated in the two-step
process with the same resin sample after completion of the
generation of the library of cyclopropanes 6a−i. This is a clear
demonstration of the robustness of the catalytic resin 1R.
In summary, a solid-supported organocatalyst has been applied
to the enantioselective cyclopropanation of α,β-unsaturated
aldehydes in flow. Several immobilization strategies, as well as
different types of polystyrene (microporous resin vs monolith)
have been tested. Among the six supported catalysts prepared,
1R has afforded excellent results while proving remarkably robust
under the reaction conditions, as demonstrated by an experiment
spanning more than 48 h. A similar setup was used to prepare a
small library of 12 analogues by sequential 6 h experiments with
different α,β-unsaturated aldehydes. Finally, an experiment
where two consecutive reactions were performed in flow
We provide for every example the production (in mmol of
cyclopropane product under identical conditions: 6 h experi-
ment, 100 μL min−1 combined flow) and a productivity value
referred to the converted substrate. While the productivity values
reflect the reactivity of the different aldehyde substrates, the
production values correlate with the yield parameter in batch and
reflect both the reactivity of the starting aldehyde and the
intensity of the base-mediated ring opening process of the
cyclopropane products.
As it can be seen, both electron-rich and electron-poor
cinnamaldehydes are well tolerated in this process, and even
heteroaromatic enals conveniently produced the desired cyclo-
propanes (6g, 6k, 6l) with high enantiomeric purity. Indeed, 1R
proved extremely robust, with productivities up to 2.1 mmol h−1
gresin−1, which amounts to a total TON of 94.0 (up to 76 h
running). As indicated above, the discrepancies observed in
Scheme 2 between productivities and productions are mostly due
to the base-promoted cyclopropane ring-opening leading to α,β-
unsaturated aldehyde byproducts. In any case, it is important to
keep in mind that the scope study summarized in Scheme 2 was
performed for comparison purposes under experimental
conditions optimized for substrate 4b. In the same way,
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(12) Kunz, R. K.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127,
3240.
(cyclopropanation and Wittig with the resulting aldehyde) was
carried out to further demonstrate the synthetic potential of this
methodology. Most remarkably, a small catalytic reactor packed
with 1R was used in an intermittent manner over a one year
period without showing any sign of deactivation or decrease in
performance.
(13) (a) Xuan, Y.-n.; Nie, S.-z.; Dong, L.-t.; Zhang, J.-m.; Yan, M. Org.
Lett. 2009, 11, 1583. (b) Cheng, Y.; An, J.; Lu, L.-Q.; Luo, L.; Wang, Z.-
Y.; Chen, J.-R.; Xiao, W.-J. J. Org. Chem. 2011, 76, 281. (c) Biswas, A.; De
Sarkar, S.; Tebben, L.; Studer, A. Chem. Commun. 2012, 48, 5190.
(14) Xie, H.; Zu, L.; Li, H.; Wang, J.; Wang, W. J. Am. Chem. Soc. 2007,
129, 10886.
ASSOCIATED CONTENT
* Supporting Information
(15) (a) Rios, R.; Sunden
Cordova, A. Adv. Synth. Catal. 2007, 349, 1028. (b) Ibrahem, I.; Zhao,
G.-L.; Rios, R.; Vesely, J.; Sunden, H.; Dziedzic, P.; Cordova, A. Chem. -
́
, H.; Vesely, J.; Zhao, G.-L.; Dziedzic, P.;
■
S
́
́
́
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b03156.
Eur. J. 2008, 14, 7867. (c) Terrasson, V.; vanderLee, A.; Marcia de
Figueiredo, R.; Campagne, J. M. Chem. - Eur. J. 2010, 16, 7875.
(16) Uria, U.; Vicario, J. L.; Badía, D.; Carrillo, L.; Reyes, E.; Pesquera,
A. Synthesis 2010, 2010, 701.
Experimental procedures and product characterization
(PDF)
́
(17) (a) Franzen, J.; Marigo, M.; Fielenbach, D.; Wabnitz, T. C.;
Kjærsgaard, A.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 18296.
(b) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem., Int. Ed.
2005, 44, 4212. (c) Marigo, M.; Wabnitz, T. C.; Fielenbach, D.;
Jørgensen, K. A. Angew. Chem., Int. Ed. 2005, 44, 794. (d) Mielgo, A.;
Palomo, C. Chem. - Asian J. 2008, 3, 922. (e) Jensen, K. L.; Dickmeiss,
G.; Jiang, H.; Albrecht, Ł.; Jørgensen, K. A. Acc. Chem. Res. 2012, 45, 248.
(18) (a) Li, Y.; Liu, X.-Y.; Zhao, G. Tetrahedron: Asymmetry 2006, 17,
2034. (b) Varela, M. C.; Dixon, S. M.; Lam, K. S.; Schore, N. E.
Tetrahedron 2008, 64, 10087. (c) Maltsev, O. V.; Kucherenko, A. S.;
Zlotin, S. G. Eur. J. Org. Chem. 2009, 2009, 5134. (d) Kristensen, T. E.;
Vestli, K.; Jakobsen, M. G.; Hansen, F. K.; Hansen, T. J. Org. Chem.
2010, 75, 1620. (e) Wang, B. G.; Ma, B. C.; Wang, Q.; Wang, W. Adv.
Synth. Catal. 2010, 352, 2923. (f) Mager, I.; Zeitler, K. Org. Lett. 2010,
12, 1480. (g) Wang, C. A.; Zhang, Z. K.; Yue, T.; Sun, Y. L.; Wang, L.;
Wang, W. D.; Zhang, Y.; Liu, C.; Wang, W. Chem. - Eur. J. 2012, 18,
6718. (h) Keller, M.; Perrier, A.; Linhardt, R.; Travers, L.; Wittmann, S.;
Caminade, A.-M.; Majoral, J.-P.; Reiser, O.; Ouali, A. Adv. Synth. Catal.
2013, 355, 1748. (i) Zheng, W.; Lu, C.; Yang, G.; Chen, Z.; Nie, J. Catal.
Commun. 2015, 62, 34.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: crodriguez@iciq.es.
*E-mail: mapericas@iciq.es.
ORCID
Carles Rodríguez-Escrich: 0000-0001-8159-416X
Miquel A. Pericas: 0000-0003-0195-8846
̀
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was funded by the ICIQ Foundation, MINECO/
FEDER (Grant CTQ2015-69136-R), and DEC Generalitat de
Catalunya (Grant 2014SGR827). We also thank MINECO for a
Severo Ochoa Excellence Accreditation 2014−2018 (SEV-2013-
0319).
(19) (a) Alza, E.; Pericas
(b) Alza, E.; Sayalero, S.; Kasaplar, P.; Almasi
Eur. J. 2011, 17, 11585. (c) Riente, P.; Mendoza, C.; Pericas, M. A. J.
Mater. Chem. 2011, 21, 7350. (d) Fan, X.; Sayalero, S.; Pericas, M. A.
Adv. Synth. Catal. 2012, 354, 2971. (e) Fan, X.; Rodríguez-Escrich, C.;
Sayalero, S.; Pericas, M. A. Chem. - Eur. J. 2013, 19, 10814. (f) Fan, X.;
Rodríguez-Escrich, C.; Wang, S.; Sayalero, S.; Pericas, M. A. Chem. - Eur.
J. 2014, 20, 13089.
̀
, M. A. Adv. Synth. Catal. 2009, 351, 3051.
̧
, D.; Pericas, M. A. Chem. -
̀
DEDICATION
Dedicated to the memory of Prof. Jose
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Barluenga.
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REFERENCES
■
̀
(1) For a recent review, see: Chen, D. Y. K.; Pouwer, R. H.; Richard, J.-
A. Chem. Soc. Rev. 2012, 41, 4631.
(2) (a) Reichelt, A.; Martin, S. F. Acc. Chem. Res. 2006, 39, 433.
(b) Brackmann, F.; de Meijere, A. Chem. Rev. 2007, 107, 4493.
(c) Brackmann, F.; de Meijere, A. Chem. Rev. 2007, 107, 4538.
(3) (a) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1980, 13, 317.
(b) Nonhebel, D. C. Chem. Soc. Rev. 1993, 22, 347.
(4) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529.
(5) (a) Johnstone, M. Heart 1950, 12, 239. (b) MacDonald, A. G. Br. J.
Anaesth. 1994, 72, 710.
(6) (a) Simmons, H. E.; Smith, R. D. J. Am. Chem. Soc. 1958, 80, 5323.
(7) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353.
(8) (a) Li, A.-H.; Dai, L.-X.; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341.
(b) Lebel, H.; Marcoux, J.-F.; Molinaro, C.; Charette, A. B. Chem. Rev.
2003, 103, 977. (c) Pellissier, H. Tetrahedron 2008, 64, 7041. (d) Bartoli,
G.; Bencivenni, G.; Dalpozzo, R. Synthesis 2014, 46, 979.
(9) (a) Evans, D. A.; Woerpel, K. A.; Hinman, M. M.; Faul, M. M. J. Am.
Chem. Soc. 1991, 113, 726. (b) Evans, D. A.; Woerpel, K. A.; Scott, M. J.
Angew. Chem., Int. Ed. Engl. 1992, 31, 430.
(20) Roda, N. M.; Tran, D. N.; Battilocchio, C.; Labes, R.; Ingham, R.
J.; Hawkins, J. M.; Ley, S. V. Org. Biomol. Chem. 2015, 13, 2550.
(21) Burguete, M. I.; Cornejo, A.; Garcia-Verdugo, E.; Garcia, J.; Gil,
M. J.; Luis, S. V.; Martinez-Merino, V.; Mayoral, J. A.; Sokolova, M.
Green Chem. 2007, 9, 1091.
(22) (a) Trindade, A. F.; Gois, P. M. P.; Afonso, C. A. M. Chem. Rev.
2009, 109, 418. (b) Kristensen, T. E.; Hansen, T. Eur. J. Org. Chem.
2010, 2010, 3179.
(23) (a) Mak, X. Y.; Laurino, P.; Seeberger, P. H. Beilstein J. Org. Chem.
2009, DOI: 10.3762/bjoc.5.19. (b) Kirschning, A.; Solodenko, W.;
Mennecke, K. Chem. - Eur. J. 2006, 12, 5972. (c) Tsubogo, T.; Ishiwata,
T.; Kobayashi, S. Angew. Chem., Int. Ed. 2013, 52, 6590. (d) Zhao, D.;
Ding, K. ACS Catal. 2013, 3, 928. (e) Atodiresei, I.; Vila, C.; Rueping, M.
̀
ACS Catal. 2015, 5, 1972. (f) Rodríguez-Escrich, C.; Pericas, M. A. Eur. J.
Org. Chem. 2015, 2015, 1173. (g) Porta, R.; Benaglia, M.; Puglisi, A. Org.
Process Res. Dev. 2016, 20, 2.
(24) (a) Heck, R. M.; Gulati, S.; Farrauto, R. J. Chem. Eng. J. 2001, 82,
̌
149. (b) Svec, F.; Tennikova, T. B.; Deyl, Z. Monolithic Materials,
(10) (a) Aggarwal, V. K.; Alonso, E.; Fang, G.; Ferrara, M.; Hynd, G.;
Porcelloni, M. Angew. Chem., Int. Ed. 2001, 40, 1433. (b) Lou, Y.;
Horikawa, M.; Kloster, R. A.; Hawryluk, N. A.; Corey, E. J. J. Am. Chem.
Preparation, Properties and Applications; Elsevier: Amsterdam, 2003.
(c) Kunz, U.; Kirschning, A.; Wen, H. L.; Solodenko, W.; Cecilia, R.;
Kappe, C. O.; Turek, T. Catal. Today 2005, 105, 318. (d) Chiroli, V.;
Benaglia, M.; Puglisi, A.; Porta, R.; Jumde, R. P.; Mandoli, A. Green
Chem. 2014, 16, 2798.
Soc. 2004, 126, 8916. (c) Muller, P.; Bernardinelli, G.; Allenbach, Y. F.;
̈
Ferri, M.; Flack, H. D. Org. Lett. 2004, 6, 1725.
(11) (a) Papageorgiou, C. D.; Ley, S. V.; Gaunt, M. J. Angew. Chem., Int.
Ed. 2003, 42, 828. (b) Johansson, C. C. C.; Bremeyer, N.; Ley, S. V.;
Owen, D. R.; Smith, S. C.; Gaunt, M. J. Angew. Chem., Int. Ed. 2006, 45,
6024.
(25) (a) Itsuno, S.; Watanabe, K.; Koizumi, T.; Ito, K. React. Polym.
1995, 24, 219. (b) Sagamanova, I.; Rodríguez-Escrich, C.; Molnar
́
, I. G.;
Sayalero, S.; Gilmour, R.; Pericas, M. A. ACS Catal. 2015, 5, 6241.
̀
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