C?C Bond Formation of Benzyl Alcohols and Alkynes Using a Catalytic Amount of KOtBu: Unusual Regioselectivity through a Radical Mechanism

Article abstract of DOI:10.1002/anie.201812687

We report a C?C bond-forming reaction between benzyl alcohols and alkynes in the presence of a catalytic amount of KO^tBu to form α-alkylated ketones in which the C=O group is located on the side derived from the alcohol. The reaction proceeds under thermal conditions (125 °C) and produces no waste, making the reaction highly atom efficient, environmentally benign, and sustainable. Based on our mechanistic investigations, we propose that the reaction proceeds through radical pathways.

Full text of DOI:10.1002/anie.201812687

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Accepted Article
Title: C ̶ C Bond Formation of Benzyl Alcohols and Alkynes using
Catalytic Amount of KOtBu: Unusual Regioselectivity via a
Radical Mechanism
Authors: David Milstein, Amit Kumar, Trevor Janes, Subrata
Chakraborty, Prosenjit Daw, Raanan Carmieli, and Yael
Diskin-Posner
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201812687
Angew. Chem. 10.1002/ange.201812687
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10.1002/anie.201812687
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C ̶ C Bond Formation of Benzyl Alcohols and Alkynes using
Catalytic Amount of KOtBu: Unusual Regioselectivity via a
Radical Mechanism
Amit Kumar,† Trevor Janes,† Subrata Chakraborty,† Prosenjit Daw,† Niklas von Wolff,† Raanan
Carmieli,‡ Yael Diskin-Posner‡ and David Milstein.†*
significant progress, this reaction is limited to ketones as the
starting materials. For wide synthetic application, it would be
attractive to use other substrates instead of ketones for the
production of α-alkylated ketones using alcohol as the alkylating
agent.
Abstract: We report the C-C bond-forming reaction of benzyl alcohols
and alkynes using a catalytic amount of KOtBu to form α-alkylated
ketones in which the C=O group is located on the side derived from
the alcohol. The reaction proceeds under thermal condition (125 oC)
and produces no waste, making the reaction highly atom-efficient,
environmentally benign and sustainable. Based on our mechanistic
investigations we propose that the reaction proceeds through radical
pathways.
Recently, the C-C bond-forming reaction of alkynes with
alcohols using a combination of transition-metal-catalysts and
water (or without water) to form α-alkylated ketones has been
reported (Scheme 1c).[7] The reaction proceeds via the
Markovnikov hydration of alkynes to form methyl ketones followed
by the C-alkylation of methyl ketones using alcohols. The
obtained product contains the C=O group on the side derived from
the alkyne. Herein, we present the C-C bond forming reaction of
benzyl alcohols with alkynes using a catalytic amount KOtBu
(Scheme 1d). The obtained products, α-alkylated ketones, in
particular dihydrochalcones, uniquely contain the C=O group on
the side derived from the alcohol; a reaction exhibiting such
unusual regioselectivity has not been reported in the peer-
reviewed literature.
Transition-metal-catalyzed C-C bond formation is one of the
most powerful tools for the synthesis of organic compounds.[1]
There has been a tremendous amount of development made in
this area offering efficient catalysts for challenging
transformations and enriching our mechanistic understanding.
Nevertheless, transition-metal catalysts have several limitations
such as toxicity, complex handling techniques low abundance and
high cost of noble transition-metals. Therefore, the replacement
of transition-metal catalysts with transition-metal-free catalysts is
of much interest. In fact, significant progress has been made
towards the development of C-C bond forming reactions free from
transition metals.[2] Several C-C coupling reactions have also
been reported using stoichiometric amounts (or more) of KOtBu.[2]
Recently Stoltz and Grubbs have reported a transition-metal-free
silylation of C-H bonds of aromatic heterocycles catalyzed by
KOtBu.[3]
Among several C-C bond forming reactions, formation of α-
alkylated ketones is important because of their interesting
pharmacological and physiological properties.[4] In particular,
dihydrochalcones (a category of α-alkylated ketones) are found in
natural products such as Naringin dihydrochalcone and
Aspalathin and are used as artificial sweeteners and
4g]
antioxidants.[4f,
A conventional route to the synthesis of α-
alkylated ketones involves the reaction of an enolate with an alkyl
halide in presence of at least a stoichiometric amount of base,
Scheme 1. (a) Synthesis of dihydrochalcones by the transition-metal-catalysed
hydrogenation of chalcones (b) Transition-metal catalyzed C-alkylation of
ketones; (c) transition-metal catalyzed reaction of alcohols and alkynes and (d)
the reaction reported in this work.
thus generating
a
stoichiometric amount of waste.
Dihydrochalcones are also synthesized by the transiton-metal
catalyzed hydrogenation of chalcones (Scheme 1a).[5] Much
attention has been paid to the C-alkylation of ketones using
alcohols as alkylating agents and several catalysts based on
transition metals such as iridium, ruthenium, palladium,
manganese, cobalt, iron and copper have been reported for this
transformation (Scheme 1b).[6] In most of the cases at least a
stoichiometric amount of base is used as additive. Despite
We discovered that refluxing a toluene solution of benzyl
alcohol (0.5 mmol) and phenyl acetylene (0.5 mmol) at 125 oC for
24 h in the presence of KOtBu (5 mol%) results in the formation
of 1,3-diphenylpropan-1-one (1) in 80% yield. The reaction also
proceeds, although with relatively lower yields, with other strong
potassium bases such as KH, KOH and KHMDS (Table 1, entries
2-4). We also observed that use of non-polar solvents such as
toluene or methyl cyclohexane resulted in better product yield
compared to polar solvents such as THF, 1,4-dioxane or
acetonitrile (entries 10-13). Using DMF as a solvent also resulted
in lower yield of 1 (entry 14); styryl ether (I, vide infra, 55% yield)
was observed as the major product. DMF in presence of KOtBu
can be deprotonated to form CONMe2 anion that can be involved
in the electron transfer reactions.[8] Finally, no conversion of
reactants was observed when the reaction was performed in the
absence of base (entry 15).
[*]
Dr. A. Kumar, Dr. T. Janes, Dr. S. Chakraborty, Dr. P. Daw, Dr. N.
von Wolff, Prof. D. Milstein
Department of Organic Chemistry, Weizmann Institute of Institution
Rehovot, Israel, 76100
E-mail: david.milstein@weizmann.ac.il
Dr. R. Carmieli, Dr. Y. Diskin-Posner
Chemical Research Support, Weizmann Institute of Science
Rehovot, Israel, 76100
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201812687
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benzyl alcohols and substituted phenyl acetylenes. Electron-
donating substituents on the benzyl alcohol such as methoxy and
t-Bu groups (3 and 4) gave better yields relative to the electron
withdrawing substituents fluoride and CF3 (8 and 9). Product 2
was also isolated on a gram scale (1.45 g, 65% yield). The
structure of product 4 was confirmed by single crystal X-ray
diffraction, proving that the carbonyl group is on the side derived
from the alcohol (SI, Figure S11). It is worth noting that the only
transformation with the regioselectivity of this type was reported
in a recent patent[9] using an iridium catalyst, and to the best of
our knowledge it is unknown in the peer-reviewed literature. Using
an internal alkyne, diphenyl acetylene in place of phenyl
acetylene, also did not result in any product formation, benzyl
alcohol and diphenyl acetylene were recovered after the reaction
(see Table S2, in SI). In case of an aliphatic alcohol such as
hexanol, no ketone product formed. Instead, a vinyl ether was
produced (see SI), as also reported earlier by Kondo.[10]
Table 1: Optimization of the reaction of benzyl alcohol and phenyl acetylene.a
We, then attempted to understand the mechanism of this
reaction. The influence of light or trace transition metals was ruled
out by control experiments and ICP-MS analysis (see SI). As
demonstrated earlier, potassium ion is important for the product
formation as lower yields are obtained using the corresponding
sodium bases (Table 1). Moreover, addition of 18-Crown-6 (10
mol%) to the reaction mixture decreased the product yield to 40%,
confirming the important role of the potassium ion, as also
11]
previously observed by Stoltz and Houk, and Wilden.[3c,
A possible mechanism for this transformation could
proceed via
a
hydrogenation/dehydrogenation pathway;
dehydrogenation of the alcohol to aldehyde followed by its
coupling with the alkyne and then hydrogenation and
rearrangement. However, formation of hydrogen during the
aConditions: KOtBu (0.025 mmol), benzyl alcohol (0.5 mmol), phenyl acetylene
(0.5 mmol), solvent (1 mL), 24 h (reaction time), temperature: 125oC. The yield
of the product (1) was determined by 1H NMR spectroscopy using mesitylene
as an internal standard.
1
reaction was not detected by GC or H NMR spectroscopy. We
also did not observe the formation of any aldehyde or styrene that
might be formed via the transfer hydrogenation mechanism.
Additionally, reaction of benzaldehyde with either styrene or
Table 2: Substrate scope for the formation of α-alkylated ketones.a
o
phenyl acetylene in presence of 10 mol% KOtBu (125 C, 24 h)
resulted in the formation of benzyl benzoate as the major product,
most likely through the Tischenko mechanism,[12] while styrene or
phenyl acetylene were found to be mostly unreacted. This
suggests that the reaction does not proceed through
hydrogenation/dehydrogenation pathways.
We also ruled out the possibility of a mechanism where
the coupling of alcohol and alkyne proceeds via the Markovnikov
addition of water to the alkyne since the presence of molecular
sieves in the reaction mixture did not affect the product yield. Also,
the reaction proceeding via the Markovnikov addition of water to
alkyne would result in a product where the C=O group is located
on the side of the alkyne derivative as previously reported.[7]
However in this case, as confirmed by the X-ray diffraction, the
product contains the C=O group on the side of alcohol (SI, Figure
S11).
Another pathway we considered involves reaction of
benzyl alcohol and phenyl acetylene to give styryl ether I that
undergoes a 1,2-Wittig type rearrangement[13] to give an allylic
alcohol (II) which can isomerize to the ketone product 1 (Scheme
2). However, this possibility was ruled out since no conversion of
the styryl ether (I) was obtained when refluxed in toluene in
presence of 10 mol% KOtBu.
aConditions: KOtBu (0.05 mmol), alcohol (1 mmol), alkyne (1 mmol), toluene (2
mL), 24 h, 125oC. bKOtBu (0.2 mmol). cKOtBu (0.05 mmol), benzyl alcohol (1
mmol), 1,4-diethynylbenzene (0.5 mmol), Products were confirmed by GC-MS.
The yields of the products were determined by 1H NMR spectroscopy using
mesitylene as an internal standard. Numbers in parentheses represent the
isolated yields.
Scheme 2. Ruling out of the mechanism involving styryl ether intermediate.
Furthermore, we explored the possibility of a radical
mechanism. Interestingly, addition of one equivalent of the radical
scavengers TEMPO or galvinoxyl to the reaction mixture under
the conditions of Table 1, entry 1, decreased the yield of the
We next explored the substrate scope of this reaction. As
shown in Table 2, the reaction works well with various substituted
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product to 40% and 0%, respectively. Unfortunately, attempts to
characterize any trapped radical were not successful.
Interestingly, an EPR spectrum taken after 5 minutes of heating
(125 oC) of benzyl alcohol and phenyl acetylene in the presence
of KOtBu (10 mol%) showed a signal suggesting a carbon-based
radical (Figure 1). No EPR signal was detected by heating a
toluene solution of benzyl alcohol and phenyl acetylene in the
absence of KOtBu or by reacting benzyl alcohol, phenyl acetylene
and KOtBu (10 mol% in toluene) at room temperature. Control
EPR experiments performed by reacting KOtBu (10 mol%) and
benzyl alcohol or KOtBu (10 mol%) and phenyl acetylene in
possibility, and has been suggested by Houk and Stoltz based on
DFT calculations.[3c] To explore this possibility, we carried out an
experiment in presence of 200 or 2000 ppm of oxygen gas using
the reaction conditions as described in Table 1, entry 1. After
completion of the reaction, similar conversion of reactants and the
similar product yield was observed as that observed without
adding any external oxygen gas (see SI). However, when a
reaction was performed using 1 bar of oxygen, no formation of 1
and almost no conversion of benzyl alcohol was observed. Based
on these experimental evidences, it seems unlikely that molecular
oxygen is involved in the reaction, and more detailed mechanistic
investigation will be pursued in future communications.
o
toluene (125 C) also did not show the presence of any radical.
This suggests that perhaps the role of KOtBu is to deprotonate the
alcohol and that the radical is generated by interaction of the
alkoxide with the alkyne. This is consistent with the observation
of product formation, albeit in lower yields, with bases such as
KOH and KH that are not known for exhibiting electron transfer
reactivity under the reaction conditions used here. Mechanisms
where KOtBu or KH are not the radical source itself but assist in
the generation of a radical source by reacting with an additive or
substrate were proposed before.[2b, 14]
Scheme 3. Proposed mechanism for the reaction of benzyl alcohols and phenyl
acetylene using a catalytic amount of base.
Figure 1. EPR spectrum upon heating a toluene solution of benzyl alcohol,
phenyl acetylene and KOtBu.
Radical chain cycle: The alkoxide radical A can insert into
phenyl acetylene to form B, ΔG for which was found to be 10.8
kcal mol-1. B can undergo a 1,2-hydrogen shift to form C (ΔG =
6.8 kcal mol-1). B and C can convert to D via 1,3 and 1,2-hydrogen
shifts, respectively, which is related to the radical E via resonance
(ΔG, B to D = -57.7 kcal mol-1 & ΔG, C to D = -64.5 kcal mol-1). E
can then be protonated by PhCH2OH to form the radical F and
PhCH2O- anion (ΔG = 38.6 kcal mol-1).[19] PhCH2O- anion can
transfer a hydrogen radical (HAT) to F to form G and regenerate
A (ΔG = -22.7 kcal mol-1). Upon tautomerization, G transforms to
product 1 (ΔG = -5.5 kcal mol-1). It is very likely that the reaction
is driven by the highly favorable thermodynamics of the product
formation as the ΔG of the overall reaction was found to be -36.5
kcal mol-1. It is worth noting that the values of ΔG presented here
are only for the purpose of comparing the relative energy of the
intermediates as potassium is excluded from the calculation for
the sake of simplicity. We believe that the stability of radical
intermediates such as A and B is critical for the formation of α-
alkylated ketones since the reaction scope is limited to benzylic
alcohols where the radicals are stabilized by resonance with the
phenyl ring. Similarly, higher yields are obtained with phenyl
acetylene compared to aliphatic alkynes where self-coupling of
the alkyne is observed as the major product (18, Table 2, also see
Table S1 in SI).
Additionally, cyclic voltammetry experiments (SI,
Figures S3-S4) exhibited a high potential gap ΔE = 1.83 V
between the first oxidation peak potential of a mixture of
PhCH2OH/KOtBu (+0.58 V) and the first reduction peak potential
of phenyl acetylene (-1.25 V) excluding a fast outer sphere
electron transfer, as also suggested by Jutand and Lei for the
electron transfer between KOtBu and 1,10-phenanthroline.[15]
Based on these experiments we propose the following
mechanism for the C-C bond forming reaction of benzyl alcohols
and alkynes (Scheme 3).
Initiation: We suggest that the first step is the deprotonation of
benzyl alcohol by KOtBu to form PhCH2OK. The reaction can get
initiated by a Hydrogen Atom Transfer (HAT) from PhCH2O- to
phenyl acetylene resulting in the formation of the radicals A and
A’.[16] The transfer of a hydrogen radical from the benzylic position
of the corresponding alkoxides has previously been proposed.[16a,
17] The transfer of a hydrogen radical to phenyl acetylene was also
documented before.[16b] Additionally, based on our DFT
calculations at the M062X/6-31+G(d,p) level, ΔG for the HAT from
PhCH2O- to phenyl acetylene was found to be 8.3 kcal mol-1
suggesting that the process might be feasible under the reaction
conditions used here.[18] We suggest that the radical A’ generated
in the initiation process gets consumed by its reaction with phenyl
acetylene as the conversion of alkynes are greater than the
conversion of benzyl alcohols (Table S1, SI). Additionally, ESI-
MS experiment of the reaction mixture showed signals with a
mass difference of 102 in the region of m/z 491 to 799 indicative
of the formation of poly(phenyl acetylene), presumably from the
reaction of A’ with phenyl acetylene (see SI, Figure S10).
Although all the reactions were performed using deoxygenated
solvents and reagents in a nitrogen glove box, radical initiation via
reaction of KOtBu with adventitious molecular oxygen is a
To lend support for the hydrogen shifts as proposed in the
mechanism, we performed experiments with deuterated
substrates. Indeed, the reaction of PhCCD with PhCH2OH, or
PhCCH with the PhCH2OD under the conditions described in
Table 2 resulted in deuterium scrambling at the α and β carbons
of the product 1 as detected by the 1H and 2H NMR spectroscopy
and GC-MS (Scheme 4). Deuterium scrambling also suggests the
possibility of proton exchange between benzyl alcohol and phenyl
acetylene, possibly via an alkoxide intermediate.
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[10] T. Imahori, C. Hori, Y. Kondo Adv. Synth. Catal. 2004, 346, 1090-1092.
[11] J. Cuthbertson, J. D. Wilden, Tetrahedron 2015, 71, 4385-4392.
[12] (a) S. Tsunetake, N. Tetsuo, O. Makoto, Chem. Lett. 2006, 35, 824-829;(b)
M. K. Barman, A. Baishya, S. Nembenna, J. Organomet. Chem. 2015, 785, 52-
60.
[13] F. Kurosawa, T. Nakano, T. Soeta, K. Endo, Y. Ukaji, J. Org. Chem. 2015,
80, 5696-5703.
[14] J. P. Barham, S. E. Dalton, M. Allison, G. Nocera, A. Young, M. P. John, T.
McGuire, S. Campos, T. Tuttle, J. A. Murphy, J. Am. Chem. Soc. 2018,
140, 11510-11518.
[15] H. Yi, A. Jutand, A. Lei, Chem. Commun. 2015, 51, 545-548.
[16] (a) B. Suchand, G. Satyanarayana, Eur. J. Org. Chem. 2017, 2017, 3886-
3895; (b) D. P. Estes, J. R. Norton, S. Jockusch, W. Sattler, J. Am. Chem. Soc.
2012, 134, 15512-15518.
[17] (a) H.-X. Zheng, Z.-F. Xiao, C.-Z. Yao, Q.-Q. Li, X.-S. Ning, Y.-B. Kang, Y.
Tang, Org. Lett. 2015, 17, 6102-6105; (b) S. Furukawa, Y. Ohno, T. Shishido,
K. Teramura, T. Tanaka, ChemPhysChem 2011, 12, 2823-2830.
[18] ΔG for the HAT from PhCH2O- to diphenyl acetylene was found to be 11.5
kcal mol-1 suggesting that HAT to the terminal alkynes is more favourable
compared to internal alkynes
Scheme 4. Reaction of PhCCD/H and PhCH2OD/H.
In conclusion, we report a transition-metal free C-C
bond-forming reaction of benzyl alcohols and alkynes to form α-
alkylated ketones using a catalytic amount of KOtBu. The reaction
shows unusual regioselectivity and does not produce any waste.
Overall, this is a highly atom-efficient, environmentally benign and
sustainable reaction.
[19] The transition from species D/E to F involves a proton transfer that is
strongly affected by solvation and H-bonding as well as stabilization of the
respective anions by potassium counteraction. We therefore attribute the
unreasonably high barrier of 38.6 kcal.mol-1 to these effects that have not been
accounted for in the computation.
ACKNOWLEDGMENTS
D.M. holds the Israel Matz Professorial Chair of Organic
Chemistry. A.K. and P.D. are thankful to the Israel Planning and
Budgeting Commission (PBC) for a fellowship. T.J. thanks the
Azrieli Foundation for a postdoctoral fellowship. N.v.W. is
supported by the Foreign Postdoctoral Fellowship Program of the
Israel Academy of Sciences and Humanities.
Keywords: Potassium tert-butoxide• α-alkylated ketone • radical•
dihydrochalcone • benzyl alcohol • alkyne•
[1] (a) A. Behr, Organometallic Compounds and Homogeneous Catalysis,
Wiley-VCH: Weinheim, 2002; (b) F. Diederich, Stang, P. J., Metal-Catalyzed
Cross-Coupling Reactions, Wiley-VCH: Weinheim, 1998; (c) G. Dyker, Ed,
Handbook of C-H Transformations: Applications in Organic Synthesis, Wiley-
VCH: Weinheim, 2005; (d) R. Jana, T. P. Pathak, M. S. Sigman, Chem. Rev.
2011, 111, 1417-1492.
[2] (a) C.-L. Sun, Z.-J. Shi, Chem. Rev. 2014, 114, 9219-9280; (b) J. P. Barham,
G. Coulthard, K. J. Emery, E. Doni, F. Cumine, G. Nocera, M. P. John, L. E. A.
Berlouis, T. McGuire, T. Tuttle, J. A. Murphy, J. Am. Chem. Soc. 2016, 138,
7402-7410.
[3] (a) A. A. Toutov, W.-B. Liu, K. N. Betz, A. Fedorov, B. M. Stoltz, R. H. Grubbs,
Nature 2015, 518, 80; (b) S. Banerjee, Y.-F. Yang, I. D. Jenkins, Y. Liang, A. A.
Toutov, W.-B. Liu, D. P. Schuman, R. H. Grubbs, B. M. Stoltz, E. H. Krenske,
K. N. Houk, R. N. Zare, J. Am. Chem. Soc. 2017, 139, 6880-6887; (c) W.-B. Liu,
D. P. Schuman, Y.-F. Yang, A. A. Toutov, Y. Liang, H. F. T. Klare, N. Nesnas,
M. Oestreich, D. G. Blackmond, S. C. Virgil, S. Banerjee, R. N. Zare, R. H.
Grubbs, K. N. Houk, B. M. Stoltz, J. Am. Chem. Soc. 2017, 139, 6867-6879.
[4] (a) D. L. Boger, H. Miyauchi, W. Du, C. Hardouin, R. A. Fecik, H. Cheng, I.
Hwang, M. P. Hedrick, D. Leung, O. Acevedo, C. R. W. Guimarães, W. L.
Jorgensen, B. F. Cravatt, J. Med. Chem. 2005, 48, 1849-1856; (b) J. Y. Hwang,
L. A. Arnold, F. Zhu, A. Kosinski, T. J. Mangano, V. Setola, B. L. Roth, R. K.
Guy, J. Med. Chem. 2009, 52, 3892-3901; (c) K. Biswas, T. A. N. Peterkin, M.
C. Bryan, L. Arik, S. G. Lehto, H. Sun, F.-Y. Hsieh, C. Xu, R. T. Fremeau, J. R.
Allen, J. Med. Chem. 2011, 54, 7232-7246; (d) R. Perrone, F. Berardi, N. A.
Colabufo, E. Lacivita, M. Leopoldo, V. Tortorella, J. Med. Chem. 2003, 46, 646-
649; (e) C. Baskakis, V. Magrioti, N. Cotton, D. Stephens, V. Constantinou-
Kokotou, E. A. Dennis, G. Kokotos, J. Med. Chem. 2008, 51, 8027-8037; (f) G.
H. Robertson, J. P. Clark, R. Lundin, Ind. Eng. Chem. Prod. Res. Develop. 1974,
13, 125-129; (g) M. J. Matos, S. Vazquez-Rodriguez, E. Uriarte, L. Santana,
Expert Opin. Ther. Pat. 2015, 25, 351-366.
[5] (a) L. Krbechek, G. E. Inglett, M. Holik, B. Dowling, R. Wagner, R. Riter, J.
Agric. Food Chem. 1968, 16, 108-112; (b) H. A. B. Linke, D. E. Eveleigh, in Z.
Naturforsch. B, 1975, 30, 606.
[6] (a) F. Huang, Z. Liu, Z. Yu, Angew. Chem. Int. Ed. 2016, 55, 862-875; (b) M.
Pena-Lopez, P. Piehl, S. Elangovan, H. Neumann, M. Beller, Angew. Chem. Int.
Ed. 2016, 55, 14967-14971; (c) S. Elangovan, J.-B. Sortias, M. Beller, C. Darcel,
Angew. Chem. Int. Ed. 2015, 54, 14483-14486; (d) G. Zhang, J. Wu, H. Zeng,
S. Zhang, Z. Yin, S. Zheng, Org. Lett. 2017, 19, 1080-1083; (e) S. Liao, K. Yu,
Q. Li, H. Tian, Z. Zhang, X. Yu, Q. Xu, Org. Biomol. Chem. 2012, 10, 2973-
2978;(f) Y. Yang, A. Qin, K. Zhao, D. Wang, X. Shi, Adv. Synth. Catal. 2016,
358,1433-1439.
[7] (a) J. Ma, N. Wang, F. Li, Asian J. Org. Chem. 2014, 3, 940-947; (b) J.
Umasish, B. Srijit, M. Sukhendu, Eur. J. Org. Chem. 2008, 2008, 5798-5804; (c)
L. R. Jefferies, S. P. Cook, Tetrahedron 2014, 70, 4204-4207.
[8] (a) C. J. Evoniuk, G. dos Passos Gomes, S. P. Hill, S. Fujita, K. Hanson, I.
V. Alabugin, J. Am. Chem. Soc. 2017, 139, 16210–16221; (b) M. Pichette
Drapeau, I. Fabre, L. Grimaud, I. Ciofini, T. Ollevier, M. Taillefer, Angew. Chem.,
Int. Ed. 2015, 54, 10587− 10591.
[9] X. Li, H. Li, C. Xu, X. Hao, Z. Xiao, 2016, CN103242372A.
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A. Kumar, T. Janes, S. Chakraborty, P.
Daw, N. von Wolff, R. Carmieli, Y.
Diskin-Posner, D. Milstein*
Page No. – Page No.
C
̶
Bond Formation of Benzyl
Alcohols and Alkynes Using
Catalytic Amount of KOtBu: Unusual
a
Regioselectivity
Mechanism.
via
a
Radical
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