Ni-Catalyzed Regioselective Hydrocarboxylation of Alkynes with CO2 by Using Simple Alcohols as Proton Sources

Article abstract of DOI:10.1021/jacs.5b05513

A mild and user-friendly Ni-catalyzed regioselective hydrocarboxylation of alkynes with CO₂ (1 bar) is described. This protocol is characterized by a wide scope while obviating the need for sensitive organometallic species and by an unprecedented regioselectivity pattern using simple alcohols as proton sources.

Full text of DOI:10.1021/jacs.5b05513

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Communication
Ni-catalyzed Regioselective Hydrocarboxylation of Alkynes
with CO2 by Using Simple Alcohols as Proton Sources
Xueqiang Wang, Masaki Nakajima, and Ruben Martin
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b05513 • Publication Date (Web): 30 Jun 2015
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Ni-catalyzed Regioselective Hydrocarboxylation of Alkynes with CO2
by Using Simple Alcohols as Proton Sources
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Xueqiang Wang†, Masaki Nakajima†, Ruben Martin†§*
†Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007 Tarragona, Spain
§ Catalan Institution for Research and Advanced Studies (ICREA), Passeig Lluïs Companys, 23, 08010, Barcelona, Spain
Supporting Information Placeholder
wellꢀdefined silanes (path b) as hydride sources. A close
inspection into these procedures, however, indicates that
CO2 insertion preferentially occurs adjacent to aromatic
or directing groups;10 furthermore, low selectivity proꢀ
files were found for sterically unbiased combinations.
While we anticipated that altering such selectivity patꢀ
tern would be rather problematic, we were attracted to
the challenge of providing new knowledge in retrosynꢀ
thetic analysis while leading to a priori inaccessible
building blocks. As part of our studies in CO2,11 we reꢀ
port herein an exceedingly practical and userꢀfriendly
hydrocarboxylation of alkynes that obviates the need for
airꢀsensitive or organometallic reagents (path c).12 Imꢀ
portantly, the method is characterized by an exceptional
chemoselectivity profile at atmospheric pressure of CO2.
While counterintuitive, the inclusion of simple alcohols
as proton sources results in an exquisite and predictable
selectivity switch, even for sterically unbiased unsym-
metrical alkynes, exploiting a previously unrecognized
opportunity in reductive carboxylation events.
ABSTRACT: A mild and userꢀfriendly Niꢀcatalyzed reꢀ
gioselective hydrocarboxylation of alkynes with CO2 (1
bar) is described. This protocol is characterized by a
wide scope while obviating the need for sensitive organꢀ
ometallic species and by an unprecedented regioselectivꢀ
ity pattern using simple alcohols as proton sources.
The recent years have witnessed a tremendous progress
within the crossꢀcoupling arena, invariably leading to
new knowledge in catalytic design.1 Unfortunately, siteꢀ
selectivity is oftentimes sacrificed at the expense of disꢀ
covering new reactivity.2 Indeed, the ability to switch the
outcome of catalytic endeavors in a rational and predictꢀ
able manner still remains a formidable challenge.1,2 Unꢀ
doubtedly, such scenario represents a unique opportunity
to increase our everꢀgrowing chemical repertoire and
improve the flexibility in synthetic design.
Scheme 1. Hydrocarboxylation of Alkynes with CO2.
Table 1. Optimization of the Reaction Conditions.a
The utilization of carbon dioxide (CO2) as abundant and
inexpensive C1ꢀsynthon3 has gained considerable moꢀ
mentum in catalytic reductive events,4,5 holding promise
for defining new paradigms en route to carboxylic acids,
privileged motifs in a myriad of pharmaceuticals.6 Intriꢀ
guingly, a limited number of catalytic carboxylation
protocols of alkynes with CO2 have been described.7,8
Among these, hydrocarboxylation events are particularly
appealing, providing rapid access to industrially relevant
acrylic acids.9 In 2011, Tsuji8d and Ma8e independently
reported an elegant hydrocarboxylation of alkynes with
airꢀsensitive and pyrophoric Et2Zn (Scheme 1, path a) or
a 1a (0.25 mmol), 2 (0.375 mmol), NiCl2 glyme (5 mol%),
.
ligand (6 mol%), Mn (0.375 mmol), DMF (1 mL) at 60 oC.
b HPLC yield using naphthalene as internal standard. Isoꢀ
c
lated yield. d NiCl2·glyme (10 mol%), L (20 mol%).
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a As for Table 1 (entry 1) but at 0.5 mmol scale. b Isolated
We initiated our investigations with 1a as the model subꢀ
strate and CO2 (1 bar). After scrupulous evaluation of all
reaction parameters,13 we found that a cocktail consistꢀ
ing of NiCl2·glyme (5 mol%), L5 (6 mol%), Mn as reꢀ
ducing agent, i-PrOH (2a) as hydrogen donor in DMF
delivered 3a in 94% isolated yield (Table 1, entry 1). It
is worth noting that 4a was not detected in the crude
mixtures. As anticipated, the efficiency was found to be
strongly dependent on the nature of the ligand backbone
(entries 6ꢀ9). Among all ligands analyzed, we found that
nitrogenꢀcontaining motifs possessing orthoꢀsubstituents
exclusively promoted the targeted transformation, with
L5 providing the best results. Interestingly, inferior reꢀ
sults were found with other solvents, catalysts or reducꢀ
ing agent combinations, thus showing the subtleties of
our protocol (entries 2ꢀ5). Strikingly, the inclusion of
HFIP (2b) or t-BuOH (2c) had a deleterious effect, thus
revealing a nonꢀinnocent behavior of the alcohol strucꢀ
ture and suggesting an intimate interplay between elecꢀ
tronic and steric effects (entries 11 and 12).13,14 As exꢀ
pected, control experiments indicated that all reaction
parameters were essential for the reaction to occur.15
c
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yields, average of at least two independent runs. 1a (1.10
e
g). d tꢀBuOH (2c) was used instead of 2a. With 2a: 74%
f
g
yield (3d:3d’=4:1). With 2a: 85% yield (3e:3e’=4:1).
h
With 2a: 84% yield (3g:3g’=4:1). With 2a: 81% yield
(3h:3h’=3:1). With 2a: 77% yield (3j:3j’=5:1). With 2a:
82% yield (3l:3l’=4:1). NiCl2·glyme (10 mol%) at rt.
i
j
k
l
The corresponding 1,3ꢀdioxolane was used as coupling
partner. m NiCl2·glyme (15 mol%) at 80 ºC. n E:Z = 15:1.
9
Encouraged by these findings, we set out to explore the
preparative scope of our Niꢀcatalyzed regioselective hyꢀ
drocarboxylation event (Table 2). As expected, the couꢀ
pling of symmetrical alkynes posed no problems (3a-
3c). Notably, the reaction could be executed on a gram
scale, delivering 3a in 87% isolated yield. As shown in
Table 2, our protocol exhibited a remarkable chemoseꢀ
lectivity profile, as a host of substrates containing alꢀ
kenes (3i), carbamates (3m), esters (3n, 3v, 3x), ketones
(3o), amides (3q), acetals (3r), nitrogenꢀcontaining hetꢀ
erocycles (3m) and nitriles (3s) were perfectly accomꢀ
modated.16 Importantly, an exquisite regioselectivity pro-
file was found for a wide variety of unsymmetrical alꢀ
kynes, even without significant steric bias (3d-3x). As
evident from careful NMR spectroscopic analysis,13 CO2
insertion took place predominantly distal to the aromatic
site. Such observation was univocally confirmed by Xꢀ
ray crystallography of 3u. These results are in contrast
with the opposite selectivity pattern or the significant
erosion in regioselectivity observed in previous hydroꢀ
carboxylation events for sterically unbiased alkynes,8d,8e
thus showing the genuine potential of our protocol.
Strikingly, the nature of the alcohol motif exerted a proꢀ
found influence on siteꢀselectivity for unsymmetrical
substrates. While a regime based on i-PrOH (2a) resultꢀ
ed in low regioselectivity profiles, the utilization of t-
BuOH (2c) dramatically improved the selectivity patꢀ
tern, delivering single regioisomers in virtually all cases
analyzed, albeit with some exceptions (3h and 3o). At
present, we do not have an explanation for such distincꢀ
tive selectivity pattern depending on the substrate utiꢀ
lized. Care, however, must be taken when generalizing
this since single regioisomers were found for 3q and 3s
by using i-PrOH (2a), thus showing the subtleties of our
system. Although tentative, we believe these results reꢀ
inforce the notion that the alcohol utilized is not a mere
spectator and that interacts with the putative reaction
intermediates. Interestingly, no carboxylation occurred
at electrophilic sites amenable to Niꢀcatalyzed coupling
reactions such as aryl chlorides5f (3p) or aryl pivalates
(3v),10c thus providing a handle for further manipulation.
Notably, the reaction could be extended to internal alꢀ
kynes possessing aliphatic motifs at both ends (3y).17
Taken together, we believe these results clearly demonꢀ
strate that our exceedingly practical Niꢀcatalyzed regiꢀ
oselective hydrocarboxylation protocol might pave the
way for future reductive CO2 fixation techniques into
organic matter.
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Table 2. Scope of the Hydrocarboxylation Event.a,b
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on the alkyne terminus of III.29 Subsequently, a protoꢀ
Although an inꢀdepth mechanistic discussion should
1
await further investigations, the utilization of alcohols as
hydrogen donors exhibits features reminiscent of a numꢀ
ber of elegant hydrogen borrowing strategies reported in
the literature.18 In order to shed light on the mechanism,
we decided to gather indirect evidence by studying the
reactivity of 2a-D1 and 2a-D2 (Scheme 2). While 2a-D1
reacted at a significantly lower rate than 2a-D2, 3a-D1
was exclusively observed with a protocol based on 2a-
D1 (Scheme 2, top right).19 Interestingly, we observed a
kH/kD = 1.1 when comparing the initial rates of 1a with
2a or 2a-D1.13 Importantly, 2d was fully recovered en
route to 3a with not even traces of benzophenone detectꢀ
ed in the crude mixtures (Scheme 2, top left).20 Overall,
the results depicted in Scheme 2 reinforce the notion that
a hydrogen borrowing strategy does not come into play21
and suggests that alcohols might be acting with dual
roles, both as proton sources and as reagents that interact
with reaction intermediates within the catalytic cycle.
This interpretation gains credence by the markedly disꢀ
tinct selectivity pattern observed in Table 2 under a 2c or
2a regime.22 Next, we set out to explore the reactivity of
523 or Ni(COD)2/L5 with 1a and 2a in a stoichiometric
fashion followed by DCl quench (Scheme 2, bot-
tom).24,25 As shown, we found that 3a was invariably
formed regardless of whether Mn was present or not.26
nolysis might occur at the C–Ni(II) bond, generating IV
that precedes a reduction event to afford manganese carꢀ
boxylate V while regenerating the propagating Ni(0)L5n
species.30 A final hydrolytic workup would deliver the
targeted acrylic acid and the corresponding alcohol.
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Scheme 3. Mechanistic Rationale.
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In summary, we have described a novel, mild and userꢀ
friendly Niꢀcatalyzed hydrocarboxylation of alkynes at
atmospheric pressure of CO2 that occurs with an exquisꢀ
ite regioselectivity profile using commercially available
alcohols as proton sources. We anticipate this study will
find widespread use, leading to new knowledge in cataꢀ
lytic reductive carboxylation reactions. Further mechaꢀ
nistic investigations and the extension to a wide variety
of πꢀsystems are currently ongoing in our laboratories.
Scheme 2. Isotope-labeling and Stoichiometric Studies.
ASSOCIATED CONTENT
Supporting Information. Experimental procedures and
spectral data. This material is available free of charge via
the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* rmartinromo@iciq.es
Funding Sources
No competing financial interests have been declared.
ACKNOWLEDGMENT
We thank ICIQ, the European Research Council (ERCꢀ
277883), MINECO (CTQ2012ꢀ34054 & Severo Ochoa
Excellence Accreditation 2014ꢀ2018, SEVꢀ2013ꢀ0319) and
Cellex Foundation for support. Johnson Matthey, Umicore
and Nippon Chemical Industrial are acknowledged for a
gift of metal & ligand sources. We sincerely thank Eddy
and Eduardo Escudero for all XꢀRay data. This paper is
dedicated to Stephen L. Buchwald on his 60th birthday.
The regioselectivity profile shown in Table 2 does not
match the inherent propensity of metal hydride comꢀ
plexes to undergo cisꢀaddition across the alkyne motif
with the incoming hydride located at the most sterically
hindered position (3d’-x’).27 Although tentative, we
support a mechanistic scenario consisting of the interꢀ
mediacy of nickelalactones (II and III)28 that are likely
in equilibrium upon CO2 extrusion via I (Scheme 3). We
propose that II reacts preferentially with the alcohol doꢀ
nor in order to avoid the clash with the alkyl substituent
REFERENCES
(1) Diederich, F.; de Meijere, A., Eds. Metal-Catalyzed Cross-
Coupling Reactions; WileyꢀVCH: Weinheim, 2004
(2) For selected reviews: (a) Mahatthananchai, J.; Dumas, A. M.;
Bode, J. W. Angew. Chem. Int. Ed. 2012, 51, 10954. (b) Afagh,
ACS Paragon Plus Environment

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Page 4 of 5
N. A.; Yudin, A. K. Angew. Chem. Int. Ed. 2010, 49, 262. (c)
(15) Under the limits of detection, we did not observe even traces of
Neufeldt, S. R.; Sanford, M. S. Acc. Chem. Res. 2012, 45, 936.
(3) For selected reviews: (a) Zhang, L.; Hou, Z. Chem. Sci. 2013, 4,
3395. (b) Tsuji, Y.; Fujihara, T. Chem. Commun. 2012, 48,
9956. (c) Cokoja, M.; Bruckmeier, C.; Rieger, B.; Herrmann,
W. A.; Kühn, F. E. Angew. Chem. Int. Ed. 2011, 50, 8510. (d)
Martin, R.; Kleij, A. W. ChemSusChem 2011, 4, 1259. (e)
Huang, K.; Sun, C.; Shi, Z. Chem. Soc. Rev. 2011, 40, 2435.
(4) For selected reviews on metalꢀcatalyzed reductive couplings: (a)
Moragas, T.; Correa, A.; Martin, R. Chem. Eur. –J. 2014, 20,
8242. (b) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Nature
2014, 509, 299. (c) Everson, D. A.; Weix, D. J. J. Org. Chem.
2014, 79, 4793. (d) Knappe, C. E. I.; Grupe, S.; Gärtner, D.;
Corpet, M.; Gosmini, C.; Jacobi von Wangelin, A. Chem. Eur.
–J. 2014, 20, 6828. (e) Montgomery, J. Organonickel Chemis-
try. Organometallics in Synthesis; Ed. John Wiley & Sons, Inc.;
Hoboken, 2013.
(5) Selected references: (a) Nogi, K.; Fujihara, T.; Terao, J.; Tsuji,
Y. Chem. Commun. 2014, 50, 13052. (b) Hendriksen, C.;
Pidko, E. A.; Yang, G.; Schäffner, B.; Vogt, D. Chem. Eur. –J.
2014, 20, 12037. (c) Huguet, N.; Jevtovikj, I.; Gordillo, A.; Leꢀ
jkowski, M. L.; Linder, R.; Bru, M.; Khalimon, A. Y.; Rominꢀ
ger, F.; Schunk, S. A.; Hofmann, P.; Limbach, M. Chem. Eur. –
J. 2014, 20, 1. (d) TranꢀVu, H.; Daugulis, O. ACS Catal. 2013,
3, 2417. (e) Greenhalgh, M. D.; Thomas, S. P. J. Am. Chem.
Soc. 2012, 134, 11900. (f) Fujihara, T.; Nogi, K.; Xu, T.; Terao,
J.; Tsuji, Y. J. Am. Chem. Soc. 2012, 134, 9106. (g) Williams,
C. M.; Johnson, J. B.; Rovis, T. J. Am. Chem. Soc. 2008, 130,
14936.
the corresponding cyclic anhydride via double carboxylation,
see: Fujihara, T.; Horimoto, Y.; Mizoe, T.; Sayyed, F. B.; Tani,
Y.; Terao, J.; Sakaki, S.; Tsuji, Y. Org. Lett. 2014, 16, 4960.
(16) While terminal acetylenes resulted in competitive trimerization
pathways, diarylacetylenes bearing a p-CF3ꢀC6H4 and p-OMeꢀ
C6H4 groups resulted in 15% yield in a 1:1 regioisomeric ratio.
The utilization of trimethylsilyl phenyl acetylene resulted in
cinnamyl acid in 33% yield via competitive desilylation.
1
2
3
4
5
6
7
8
(17) Although not fully optimized, the Niꢀcatalyzed carboxylation of
4,4ꢀdimethylpentꢀ2ꢀyne (1z) with CO2 and 2c exclusively reꢀ
sulted in (E)ꢀ2,4,4ꢀtrimethylpentꢀ2ꢀenoic acid (3z; 21% yield).
(18) For selected reviews: (a) Ketcham, J. M.; Shin, I.; Montgomery,
T. P.; Krische, M. J. Angew. Chem. Int. Ed. 2014, 53, 9142. (b)
Moran, J.; Krische, M. J. Pure Appl. Chem. 2012, 84, 1729. (c)
Obora, Y.; Ishii, Y. Synlett 2011, 30. (d) Bower, J. F.; Krische,
M. J. Top. Organomet. Chem. 2011, 43, 107. (e) Dobereiner, G.
E.; Crabtree, R. H. Chem. Rev. 2010, 110, 681. (f) Guillena, G.;
Ramón, D. J.; Yus, M. Chem. Rev. 2010, 110, 1611. (g) Hamid,
M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth.
Catal. 2007, 349, 1555.
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24
25
26
27
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(19) The carboxylation of 1a with 2a as proton source in DMFꢀd7
resulted in the exclusive formation of 3a.
(20) N reductive coupling of 1a with in situ generated benzophenone
was observed in the crude reaction mixtures.
(21) These results are in sharp contrast with a recent elegant work
reported by Matsubara in which i-PrOH (2a) was utilized in Niꢀ
catalyzed reductive couplings via a hydrogen borrowing strateꢀ
gy en route to allylic alcohols: Nakai, K.; Yoshida, Y.; Kuꢀ
rahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2014, 136, 7797.
(22) A rather illustrative correlation between regioselectivity pattern
and the size of the alcohol utilized was found for the reaction of
1d with CO2: MeOH (76% yield, 3d:3d’=1.5:1); EtOH (73%
yield, 3d:3d’=2:1); BnOH (81% yield, 3d:3d’=2:1); iPrOHꢀ2a
(3d:3d’=4:1); tBuOHꢀ2b (85% yield 3d, single regioisomer).
(23) (a) ref. 11a. (b) Powers, D. C.; Anderson, B. L.; Nocera, D. G.
J. Am. Chem. Soc. 2013, 135, 18876.
(24) At present, we do not have a rationale for the lower yield of 3a
when using 5 as compared to the Ni(COD)2/L5 regime.
(25) The reaction of 1a with 5 using 2d as proton source followed
by DCl quench resulted in 3a in 50% yield (not even traces of
3a-D1 in the crude mixtures) while recovering back 2d.
(26) While these results might support a scenario based on Ni(II)
species, we cannot completely rule out the intermediacy of
Ni(I) intermediates generated upon single electron transfer reꢀ
duction. See, for example: (a) see ref. 5f, 15, (b) Duñach, E.;
Esteves, A. P.; Medeiros, M. J.; Olivero, S. New J. Chem. 2005,
29, 633. (c) Nadal, M. L.; Bosch, J.; Vila, J. M.; Klein, G.; Riꢀ
cart, S.; Moretó, J. M. J. Am. Chem. Soc. 2005, 127, 10476.
(27) (a) Trost, B. M.; Ball, Z. T. Synthesis 2005, 6, 853. (b) Andersꢀ
son, P. G.; Munslow, I. J. Modern Reduction Methods; Ed.
WileyꢀVCH, 2008. (c) See also ref. 8d or ref. 10 for examples
dealing with CO2 or CO as coupling partner.
(28) (a) Fischer, R.; Langer, J.; Malassa, A.; Walther, D.; Görls, H.;
Vaughan, G. Chem. Commun. 2006, 2510. (b) Hoberg, H.; Perꢀ
es, Y.; Krüger, C.; Tsay, Y. H. Angew. Chem. Int. Ed. 1987, 26,
771. (c) Hoberg, H.; Schäfer, H.; Burkhardt, G.; Krüger, C.;
Rmao, M. J. J. Organomet. Chem. 1984, 266, 203. (d) Hoberg,
H.; Schäfer, D. J. Organomet. Chem. 1983, 251, C51. (d)
Burkhardt, G.; Hoberg, H. Angew. Chem. Int. Ed. 1982, 21, 76.
(29) Care must be taken when invoking that the regioselectivity
pattern is merely attributed to a steric model since the observed
outcome for 3i or 3o, among others, might indicate that other
factors come into play.
(6) For selected examples: (a) Patai, S. The Chemistry of Acid De-
rivatives; Wiley: New York, 1992. (b) Gooßen, L. J.;
Rodríguez, N.; Gooßen, K. Angew. Chem. Int. Ed. 2008, 47,
3100. (c) Maag, H. Prodrugs of Carboxylic Acids; Springer:
New York, 2007.
(7) For selected carboxylation events of ꢀsystems using stoichioꢀ
metric amounts of metal complexes: (a) Shimizu, K.; Takimoto,
M.; Sato, Y.; Mori, M. Org. Lett. 2005, 7, 195. (b) Aoki, M.;
Kaneko, M.; Izumi, S.; Ukai, K.; Iwasawa, N. Chem. Commun.
2004, 2568. (c) Saito, S.; Nakagawa, S.; Koizumi, T.; Hirayaꢀ
ma, K.; Yamamoto, Y. J. Org. Chem. 1999, 64, 3975. (d)
Hoberg, H.; Ballesteros, A.; Signan, A.; Jegat, C.; Milchereit,
A. Synthesis 1991, 395. (e) Hoberg, H.; Peres, Y.; Michereit, A.
J. Organomet. Chem. 1986, 307, C38, and citations therein.
(8) (a) Takimoto, M.; Hou, Z. Chem. Eur. –J. 2013, 19, 11439. (b)
Zhang, L.; Cheng, J.; Carry, B.; Hou, Z. J. Am. Chem. Soc.
2012, 134, 14314. (c) Fujihara, T.; Tani, Y.; Semba, K.; Terao,
J.; Tsuji, Y. Angew. Chem. Int. Ed. 2012, 51, 11487. (d) Fujihaꢀ
ra, T.; Xu, T.; Semba, K.; Terao, J.; Tsuji Y. Angew. Chem. Int.
Ed. 2011, 50, 523. (e) Li, S.; Yuan, W.; Ma, S. Angew. Chem.
Int. Ed. 2011, 50, 2578.
(9) Wittcoff, H. A.; Reuben, B. G.; Plotkin, J. S. Industrial Organic
Chemicals; Ed.; John Wiley & Sons, Inc.; Hoboken, 2012.
(10) For selected metalꢀcatalyzed hydrocarboxylation reactions of
alkynes using CO or CO surrogates occurring with C1ꢀ
selectivity: (a) Hou, J.; Xie, J.; Zhou, Q. Angew. Chem. Int. Ed.
2015, 54, 6302. (b) Trotus, I. –T.; Zimmermann, T.; Schüth, F.
Chem. Rev. 2014, 114, 1761. (c) Brennführer, A.; Neumann,
H.; Beller, M. ChemCatChem 2009, 1, 28. (c) El Ali, B.;
Vasapollo, G.; Alper, H. J. Org. Chem. 1993, 58, 4739.
(11) (a) Wang, X.; Liu, Y.; Martin, R. J. Am. Chem. Soc. 2015, 137,
6476. (b) Moragas, T.; Cornella, J.; Martin, R. J. Am. Chem.
Soc. 2014, 136, 17702. (c) Liu, L.; Cornella, J.; Martin, R. J.
Am. Chem. Soc. 2014, 136, 11212. (d) Correa, A.; León, T.;
Martin, R. J. Am. Chem. Soc. 2014, 136, 1062. (e) León, T.;
Correa, A.; Martin, R. J. Am. Chem. Soc. 2013, 135, 1221. (f)
Correa, A.; Martin, R. J. Am. Chem. Soc. 2009, 131, 15974.
(12) Correa, A.; Martin, R. Angew. Chem. Int. Ed. 2009, 48, 6201.
(13) See Supporting information for details
(30) Although radical intermediates might also account for the obꢀ
served reactivity, we found no significant inhibition in the presꢀ
ence of BHT or related radical scavengers.
(14) The utilization of TFA, triflic acid or benzoic acid as proton
sources resulted in no conversion to products.
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