Stoichiometric and Catalytic C?C and C?H Bond Formation with B(C6F5)3 via Cationic Intermediates

Article abstract of DOI:10.1002/anie.201704789

This work showcases a new catalytic cyclization reaction using a highly Lewis acidic borane with concomitant C?H or C?C bond formation. The activation of alkyne-containing substrates with B(C₆F₅)₃ enabled the first catalytic intramolecular cyclizations of carboxylic acid substrates using this Lewis acid. In addition, intramolecular cyclizations of esters enable C?C bond formation as catalytic B(C₆F₅)₃ can be used to effect formal 1,5-alkyl migrations from the ester functional groups to unsaturated carbon–carbon frameworks. This metal-free method was used for the catalytic formation of complex dihydropyrones and isocoumarins in very good yields under relatively mild conditions with excellent atom efficiency.

Full text of DOI:10.1002/anie.201704789

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Accepted Article
Title: B(C6F5)3: Stoichiometric and Catalytic C-C and C-H Bond
Formation via Cationic Intermediates
Authors: Yashar Soltani, Lewis Charles Wilkins, and Rebecca Melen
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201704789
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B(C6F5)3: Stoichiometric and Catalytic C–C and C–H Bond
Formation via Cationic Intermediates
Yashar Soltani,‡[a] Lewis C. Wilkins‡[a] and Rebecca L. Melen*[a]
Dedicated to the memory of Bernd Wrackmeyer.
Abstract: This work showcases a new method of catalytic cyclization
reaction using a highly Lewis acidic borane with concomitant C–H or
C–C bond formation. Activation of alkyne containing substrates using
B(C6F5)3 allows catalytic intramolecular cyclizations of carboxylic acid
substrates to be achieved for the first time using this Lewis acid. In
addition, intramolecular cyclizations of esters enables C–C bond
formation in which catalytic B(C6F5)3 is used to effect formal 1,5-alkyl
migrations from ester functionalities to unsaturated carbon-carbon
frameworks. Using this new methodology, the catalytic formation of
complex dihydropyrones and isocoumarins in extremely good yields
under relatively mild conditions with excellent atom efficiency can be
achieved in a metal-free manner.
extensive uses in anti-inflammatory, antidiabetic, and
antimicrobial agents, amongst others.[13] In addition to their
biological activity, dihydropyrones also serve as synthetically
useful intermediates for the synthesis of oxygen-containing
heterocycles such as pyridones and γ-lactones.[14] The
combination of biological activity and synthetic utility of
dihydropyrones has led to considerable interest in their
preparation. Although many synthetic routes to pyrones exist,[15]
many involve heavy or noble metals in the latter stages of
preparation thus making these syntheses less attractive within the
pharmaceutical and industrial setting.[16]
A major development in the field of main group chemistry over the
last decade is that of frustrated Lewis pairs (FLPs).[1] These act
as cooperative reagents in small molecule activation and metal-
free hydrogenation catalysis. Subsequently, FLP chemistry has
led to new ways of thinking about Lewis acidity and basicity and
now encompass broader applications across synthetic organic
chemistry.[2] Yet, this thriving field is still in its naissance, with
avenues still remaining uncovered and many practical
applications still await development. One Lewis acid which has
come to light through these advancements is B(C6F5)3.[3] This
electron deficient borane has been shown to act as a hard Lewis
acid with particular oxophilic character, but has also displayed the
proclivity to act as a π-Lewis acid through the activation of softer
Lewis basic centers such as alkynes and alkenes[4] which is
reminiscent of soft transition metal catalysts such as gold,[5]
palladium[6] and platinum.[7] Indeed, there has been a great deal
of work by Erker, Oestreich, Paradies, Piers and ourselves inter
alia to establish the wide range of transformations this reagent
can effect such as 1,n-carboborations,[8] benzannulations,[9]
cyclizations,[3a, 10] and hydrosilylations[11] (Scheme 1, top).
Scheme 1. Examples of B(C6F5)3 catalysis.
Initially, a variety of alkynyl carboxylic acids (1a–k) and
esters (2a–u) were synthesized according to literature procedures
(Figure 1).[16a] The reaction of the electron rich alkynyl
functionalized carboxylic acids 1a–c with B(C6F5)3 in a 1:1 molar
ratio in CDCl3 produced the cyclized lactone products 3a–c
quantitatively within 30 minutes when monitored by in situ NMR
spectroscopy with excellent isolated yields above 90%. However,
when functionalizing the backbone with unsaturated moieties (1i-
j), lower isolated yields of 45% for 3d and 52% for 3e were
recorded (Scheme 2). A crop of colorless crystals of 3a and 3d–e
were grown from a saturated CH2Cl2/hexane solution stored at
-40 °C, which were suitable for single-crystal X-ray diffraction
(Figure 2 and SI).
In this paper, we demonstrate that this Lewis acid can
catalyze the rearrangement of alkynyl carboxylic acids and esters
to give 3,4-dihydropyrones and isocoumarins in high yields under
relatively mild conditions (Scheme 1, bottom). Naturally occurring
or synthetic dihydropyrones are omnipresent motifs in numerous
biologically active compounds[12] with derivatives having
[a]
Mr. Y. Soltani, Mr. L.C. Wilkins, Dr. R.L. Melen
‡ These authors contributed equally
School of Chemistry, Cardiff University
Main Building, Park Place, Cardiff, CF10 3AT, Cymru/Wales, U.K.
E-mail: MelenR@cardiff.ac.uk
Supporting information for this article is given via a link at the end of
the document.
Figure 1. Substrates 1 and 2 used in this study.
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These results were surprising since carboxylic acids are not
usually tolerated in B(C6F5)3 related chemistry, other than the few
reports of coordinative structural investigations as well as
B(C6F5)3 catalyzed deoxygenations, amongst a small number of
others.[17] Electron poor, or more sterically demanding ortho-
substituted alkynes 1d–1h, exhibited reduced reactivity. In these
cases, multinuclear NMR spectroscopy showed a mixture of
products, with the expected target molecule presenting only as a
minor component.
3d
3a
The limited scope and the propensity of carboxylic acids to
interfere with B(C6F5)3 chemistry encouraged us to undertake the
related ester chemistry which also led to an increase in complexity
of the subsequent lactone product (Scheme 2). Reactions of
isopropyl or allyl esters (2a–b) resulted in no discernible formation
of the target dihydropyrone, however, exposing benzyl or
benzhydrol derivatives (2c–u) to the same reaction conditions
triggered the analogous rearrangement as the carboxylic acids to
give γ-functionalized 3,4-dihydropyrones and isocoumarins 3 as
the borane adduct through a C–C bond forming reaction.
Notably, compounds 3g–j and 3l–x could be formed in
excellent yields (>90% conversion; 81%–97% isolated) in as little
as 30 minutes at room temperature, whereas formation of 3f and
3k exhibited slightly longer reaction times (24 h) to give the
corresponding rearrangement product in very high yields (91%
and 92% respectively). The crystal structures of 3h–i, 3m and 3v
were determined by X-ray diffraction and confirmed atomic
connectivity (Figure 2 and SI).
3v
4c
Figure 2. Solid-state structure of compound 3a, 3d, 3v and 4c. Disordered F
atom modelled over two sites (3v and 4c). Thermal ellipsoids shown at 50%
probability.
Since the resulting lactone products 3 sequester the borane
as the O–B adduct, it was posited that if the boron-oxygen bond
could be thermally cleaved, catalytic turnover should be permitted
to give compounds 4 (Scheme 3). Indeed, using 2d as the model
system, the catalytic reaction in CDCl3 at ambient temperature
using 10 mol% B(C6F5)3 resulted in >95% conversion to the
product after 6 h at 70 °C. The catalytic system was subsequently
established through optimization of the reaction conditions viz.
borane catalyst, solvent, and catalytic loading (Table 1).
Less Lewis acidic boranes such as BPh3, and other
fluorinated aryl boranes BR3 [R = (2,6-F2C6H3) or (2,4,6-
F3C6H2)][18] resulted in no detectable product after 24 h at 70 °C
(entries 1–3, Table 1). In addition, less sterically hindered boranes
such as BF3∙OEt2 also showed no appreciable conversion even
though the Lewis acidity is only deemed slightly less than that of
B(C6F5)3 (entry 4, Table 1).[19] Further reduction of the catalyst
loading did not negatively affect the catalytic efficiency, giving
excellent conversion using as little as 1 mol% (entry 7, Table 1).
However, for the interests of tandem catalytic processes, a
catalyst loading of 5 mol% was used in subsequent reactions
(entries 5–7, Table 1).
Table 1. Optimization for the catalytic cyclization.
Loading
(mol%)
Conv.
(%)a
Entry
Catalyst
Solvent
Product
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
BPh3
(2,6-F2C6H3)3B
(2,4,6-F3C6H2)3B
BF3∙OEt2
B(C6F5)3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
THF
1,4-Dioxane
Toluene
Et2O
CH2Cl2
CDCl3
CDCl3
CDCl3
10
10
10
10
10
5
<5
<5
<5
4c
4c
4c
4c
4c
4c
4c
4c
4c
4c
4c
4c
4a
4a
4a
7
>95
>95
>95
52
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
B(C6F5)3
1
10
10
10
10
10
5
54
>95
>95
>95
>95
0
In situ NMR conversion (isolated yield). a 24 h reaction time.
CF3CO2H
CF3SO3H
5
5
Tracesb
a In situ NMR conversion after 6 hours at 70 °C. b Multiple products observed.
Scheme 2. Substrate scope for the cyclization reaction of 1 with B(C6F5)3.
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Once the optimal borane and catalyst loading had been
elucidated, various solvents were screened with the observation
that the catalytic reactions proceeded rapidly in high yields (over
95%) in a variety of solvents (CDCl3, CH2Cl2, Et2O and toluene)
but less well in more coordinating solvents such as THF and 1,4-
dioxane (entries 5, 8–12, Table 1) which likely leads to catalyst
deactivation processes through formation of solvent-borane
adducts. When applying these conditions to the electron rich
carboxylic acid 1c, clean quantitative formation of 4a was also
observed (entry 13, Table 1). Additionally, trifluoroacetic acid was
trialled in the synthesis of 4a using 5 mol% loading at 70 °C for 6
h to interrogate whether the cyclisation is proton mediated as a
result of borane coordination to the carbonyl of the carboxylic acid
fragment, or whether it is indeed the borane that activates the
alkynyl fragment. Using these conditions, in situ monitoring of the
reaction showed no conversion (entry 14, Table 1). Using a
stronger acid, trifluoromethylsulfonic acid (entry 15, Table 1), in 5
mol% loading garnered a mixture of products with little indication
of the target molecule (see SI).
case of 4a, 4c and 4f, storing the saturated hexane/CH2Cl2
solutions at -40 °C yielded colorless crystals that were
characterized by single-crystal X-ray diffraction (Figure 2 and SI).
Further functionalization of these products was evidenced
through a subsequent Suzuki-Miyaura coupling reaction of the
para-bromo substituted derivative 4e showcasing its candidacy as
an excellent building block for further derivatizations and uses in
organic synthesis (see SI, compound 5).
Supplementary investigations sought to conduct tandem
catalytic rearrangements/reduction reactions using a one-pot
synthesis from 2 to give γ-functionalized cyclic silylacetals
(Scheme 4). Initially we hoped to effect a one-pot catalytic
cyclization followed by an FLP hydrogenation of the lactone
functionality using B(C6F5)3 as the catalyst. Unfortunately, these
reactions proved unsuccessful at 5 atm of H2 using 2d as a
substrate and 10 mol% borane. However, we subsequently
turned our attention to the hydrosilylation reaction for the second
step which is well-documented using B(C6F5)3 to much greater
success.[11] Indeed, the simple addition of either HSiPh3 or HSiEt3
after the initial cyclization reaction resulted in the quantitative
formation of the hydrosilylated products 6a–f after a further 6 h at
70 °C with excellent isolated yields from the tandem reaction (90–
95%). Single crystals of 6a could be grown from a saturated
CH2Cl2/hexane solution stored at -40 °C and whose structure was
confirmed by X-ray diffraction (see SI).
Scheme 4. Tandem catalytic one-pot cyclization/hydrosilylation to yield 6.
The method by which the benzylic fragment undergoes the
1,5-migration in these rearrangements was hence probed via a
set of crossover reactions. Using a 1:1 mixture of 2f and 2h, the
presence (or absence) of any mixing of the [Ar1C(H)Ar2]+ moiety
upon reaction with 2 equivalents of B(C6F5)3 was studied
(Crossover A, Scheme 5). Similarly, the analogous reaction was
also carried out using 2d and 2j in a bid to clarify further whether
the reaction proceeds via an inter- or intra-molecular pathway
(Crossover B, Scheme 5). It was observed that in both cases
scrambling of the migratory group does indeed occur giving
mixtures of 3h, 3j, 3l and 3n, lending credence to a proposed
intermolecular pathway with generation of a carbenium ion in
solution. When probing this further, it was seen that in crossover
experiment A, very little variance was seen in the generation of all
four products, however, when looking at crossover B, the
formation of 3h was preferential over 3j, 3l and 3n.
In situ NMR conversion (isolated yield). a Isolated yield after 120 h. b 10 mol%
catalyst. c 16 h reaction time. d 24 h reaction time. e 48 h reaction time.
Scheme 3. Catalytic formation of 4 using B(C6F5)3.
The alkynyl carboxylic acids and esters were then tested in
the borane catalyzed rearrangement reactions using these
optimized conditions. Whilst the most electron rich alkynyl
carboxylic acid generated the corresponding dihydropyrone 4a in
excellent yields, less activated substrates (1a–b, 1d–e) showed
little reactivity under the established conditions. Conversely,
favorable returns were observed for the vast majority of the
lactone products with many being isolated in yields over 90% (4c–
e, 4l–m, Scheme 3). Lower conversions were noted for products
4b and 4f with isolated yields of 33% and 27% respectively.
Additionally, to generate 4h–j in good yields (71–78%), 10 mol%
catalyst was used with a reaction time of 24 h (Scheme 3). In the
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This was also repeated with substrate 1a using 5 mol% and
stoichiometric amounts of triflic acid, however no change was
1
noted via the in situ H NMR spectrum. This leads us to believe
that pathway II is perhaps more plausible, due to the rapid
reaction with B(C6F5)3 and distinct lack thereof when utilising a
direct proton source however, further mechanistic investigations
are ongoing in the group.
Scheme 5. Crossover reactions.
This is presumably due to the substrate containing a more
activated alkyne (more electron rich) than the CF3 substituted
phenyl acetylene. This also explains the reduced reactivity of the
CF3 substituted precursors 2h–j in the catalytic experiments
described earlier. In addition, the p-F substituted benzhydrol
starting material results in the formation of a more stable
carbenium ion than the p-Br substituted benzhydrol starting
material (the σp Hammett constant for p-F>p-Br).
Mechanistically, two possible cyclization pathways are
possible; borane activation of the carbonyl resulting in elimination
of a carbenium ion, followed by a 6-endo-dig cyclization reaction
(pathway I, Scheme 6). Alternatively, borane activation of the
Scheme 6. Proposed mechanistic pathways.
In conclusion, this work has shown how the strong Lewis acid
B(C6F5)3 can be utilized to great effect in the catalytic cyclization
reactions, showcasing a powerful new metal-free pathway to C–
H and C–C bonds in the formation of structurally complex pyrones
and isocoumarins. Indeed, the reactions are quantitative in most
stoichiometric examples after just 30 minutes at ambient
temperature with the catalytic systems requiring mild heating to
give generally good to excellent yields. Further functionalization
of these systems has also been displayed through tandem
cyclization/hydrosilylation reactions afford complex cyclic
silylacetals in excellent yields, with exceptional atom efficiency.
Further studies into catalytic C–C bond forming processes as well
as tandem B(C6F5)3 catalysis is ongoing in our group.
alkyne followed by
a 1,2-trans oxyboration reaction with
subsequent proto- or carbodeboration could occur (pathway II,
Scheme 6). Both pathways have been observed previously in
other reactions with B(C6F5)3. For example, we have previously
noted the deprotection of Boc groups using catalytic amounts of
B(C6F5)3 reminiscent of pathway I,[20] while the oxyboration
pathway II has also been observed in work by ourselves[20,21] and
others[10b,22] in the synthesis of oxazoles, dioxaborinines, pyrylium
and lactone systems.
It could be argued that the hard Lewis acidic B(C6F5)3
coordinates preferentially to the harder carbonyl oxygen over the
softer π-bond of the alkyne, lending credence to pathway I which
may also detected in the 11B NMR spectrum (ca. 40 ppm).
However, a transient sharp singlet at ca. -15 ppm is observed in
the 11B NMR spectrum, indicative of a vinyl borate suggesting that
pathway II is indeed witnessed. This may be further reinforced by
the lack of selectivity and reactivity when using ortho-substituted
alkynyl carboxylic acids (1f and 1g). Although these groups, or
derivatives thereof, have been shown to activate the alkyne
fragment, the increased steric bulk may obstruct the approach of
the bulky Lewis acid. Both proposed mechanisms proceed
through carbenium intermediates which explains the lack of
reactivity with substrates 3a and 3b and the lower
reactivity/activity with 3c, which are less able to stabilize a
carbocation intermediate than the diaryl or ethylphenyl substituted
benzhydrol units. In addition to these observations, when
conducting the control reaction of substrate 1c with catalytic
amounts of trifluoroacetic acid at elevated temperatures, no
reaction occurred after 6 h (see SI). When 1c was subjected to 5
mol% of the stronger triflic acid, some reactivity was seen
however, conversion to the target molecule was not observed.
Acknowledgements
We acknowledge Dr. Niklaas Buurma for his assistance with the
crossover experiments. We also thank the EPSRC UK National
Crystallography Service for the collection of crystallographic data.
Keywords: B(C6F5)3 • Boron • Catalysis • Cyclization • Lewis
acid
References:
[1]
a) G. C. Welch, R. R. S. Juan, J. D. Masuda, D. W. Stephan, Science
2006, 314, 1124-1126; b) D. W. Stephan, Science 2016, 354, doi:
10.1126/science.aaf7229.
[2]
a) Y. Liu, H. Du, J. Am. Chem. Soc. 2013, 135, 6810-6813; b) K.
Chernichenko, Á. Madarász, I. Pápai, M. Nieger, M. Leskelä, T. Repo,
Nat. Chem. 2013, 5, 718-723; c) M. A. Legare, M. A. Courtemanche, E.
Rochette, F. G. Fontaine, Science 2015, 349, 513-516.
[3]
a) W. E. Piers, T. Chivers, Chem. Soc. Rev. 1997, 26, 345-354; b) G.
Erker, Dalton Trans. 2005, 1883-1890; c) R. L. Melen, Chem. Commun.
2014, 50, 1161-1174.
This article is protected by copyright. All rights reserved.

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[4]
[5]
[6]
a) Y. Guo, S. Li, Eur. J. Inorg. Chem. 2008, 2008, 2501-2505; b) X. Zhao,
D. W. Stephan, J. Am. Chem. Soc. 2011, 133, 12448-12450.
D. Zuccaccia, L. Belpassi, L. Rocchigiani, F. Tarantelli, A. Macchioni,
Inorg. Chem. 2010, 49, 3080-3082.
P. Maitlis, Metal Complexes: The Organic Chemistry of Palladium, Vol.
1, Elsevier, 2012.
R. Rajeev, R. B. Sunoj, Dalton Trans. 2012, 41, 8430-8440.
G. Kehr, G. Erker, Chem. Sci. 2016, 7, 56-65 and references therein.
a) C. Chen, M. Harhausen, R. Liedtke, K. Bussmann, A. Fukazawa, S.
Yamaguchi, J. L. Petersen, C. G. Daniliuc, R. Fröhlich, G. Kehr, G. Erker,
Angew. Chem. Int. Ed. 2013, 52, 5992-5996; b) R. Liedtke, F. Tenberge,
C. G. Daniliuc, G. Kehr, G. Erker, J. Org. Chem. 2015, 80, 2240-2248.
[15] a) M. He, G. J. Uc, J. W. Bode, J. Am. Chem. Soc. 2006, 128, 15088-
15089; b) X. Zhao, K. E. Ruhl, T. Rovis, Angew. Chem. Int. Ed. 2012, 51,
12330-12333; c) D. Sinha, S. Perera, J. C.-G. Zhao, Chem. Eur. J. 2013,
19, 6976-6979.
[16] a) K. Komeyama, K. Takahashi, K. Takaki, Org. Lett., 2008, 10, 5119–
5122; b) K. Komeyama, K. Takahashi, K. Takaki, Chem. Lett. 2008, 37,
602-603; c) S. Mochida, K. Hirano, T. Satoh, M. Miura, J. Org. Chem.
2009, 74, 6295-6298; d) T. Satoh, M. Miura, Chem. Eur. J. 2010, 16,
11212-11222; e) T. Fujihara, Y. Tsuji, Heterocycles 2014, 89, 1343-1367;
f) M. Al-Amin, J. S. Johnson, S. A. Blum, Organometallics 2014, 33,
5448-5456.
[7]
[8]
[9]
[17] a) V. Gevorgyan, M. Rubin, J.-X. Liu, Y. Yamamoto, J. Org. Chem. 2001,
66, 1672-1675; b) S. Mitu, M. C. Baird; b) S. Mitu, M. C. Baird,
Organometallics 2006, 25, 4888-4896; c) D. Bézier, S. Park, M.
Brookhart, Org. Lett. 2013, 15, 496-499.
[10] a) T. Mahdi, D. W. Stephan. Chem. Eur. J. 2015, 21, 11134-11142; b) S.
Tamke, Z.-W. Qu, N. A. Sitte, U. Flörke, S. Grimme, J. Paradies, Angew.
Chem. Int. Ed. 2016, 55, 4336-4339; c) D. J. Faizi, A. Issaian, A. J. Davis,
S. A. Blum, J. Am. Chem. Soc. 2016, 138, 2126-2129; d) K. Yuan, S.
Wang. Org. Lett. 2017, 19, 1462-1465; e) S. Tussing, M. Ohland, G.
Wicker, U. Flörkeb, J. Paradies. Dalton Trans., 2017, 46, 1539-1545; f)
A. J. Warner, A. Churn, J. S. McGough, M. J. Ingleson, Angew. Chem.
Int. Ed. 2017, 56, 354-358.
[18] J. A. Nicasio, S. Steinberg, B. Inés, M. Alcarazo, Chem. Eur. J. 2013, 19,
11016-11020.
[19] J. Jacobsen, H. Berke, S. Döring, G. Kehr, G. Erker, R. Fröhlich, O.
Meyer, Organometallics, 1999, 18, 1724-1735.
[20] L.C. Wilkins, P. Wieneke, P. D. Newman, B. M. Kariuki, F. Rominger, A.
S. K. Hashmi, M. M. Hansmann, R. L. Melen, Organometallics 2015, 34,
5298.
[11] For
a comprehensive review on hydrosilylation reactions see: M.
Oestreich, J. Hermeke, J. Mohr, Chem. Soc. Rev. 2015, 44, 2202-2220.
[12] a) Y.-M. Yu, J.-S. Yang, C.-Z. Peng, V. Caer, P.-Z. Cong, Z.-M. Zou, Y.
Lu, S.-Y. Yang, Y.-C. Gu, J. Nat. Prod. 2009, 72, 921-924; b) C.-M. Cui,
X.-M. Li, C.-S. Li, P. Proksch, B.-G. Wang, J. Nat. Prod. 2010, 73, 729-
733.
[13] a) A. Parveen, A. Chakraborty, A. K. Konreddy, H. Chakravarty, A.
Sharon, V. Trivedi, C. Bal, Eur. J. Med. Chem. 2013, 70, 607-612; b) Y.
Kim, H. Ogura, K. Akasaka, T. Oikawa, N. Matsuura, C. Imada, H.
Yasuda, Y. Igarashi, Mar. Drugs 2014, 12, 4110-4125.
[21] a) L. C. Wilkins, H. B. Hamilton, B. M. Kariuki, A. S. K. Hashmi, M. M
Hansmann, R. L. Melen, Dalton Trans. 2016, 45, 5929-5932; b) L. C.
Wilkins, B. A. R. Günther, M. Walther, J. R. Lawson, T. Wirth, R. L. Melen,
Angew. Chem. Int. Ed. 2016, 55, 11292-11295.
[22] K. N. Tu, J. J. Hirner, S. A. Blum, Org. Lett. 2016, 18, 480-483.
[14] a) D. Rosenthal, P. Grabowich, E. F. Sabo, J. Fried, J. Am. Chem. Soc.
1963, 85, 3971-3979; b) A. K. Mandal, D. G. Jawalkar, J. Org. Chem.
1989, 54, 2364-2369; c) F.-Y. Zhang, E. J. Corey, Org. Lett. 2000, 2,
1097-1100.
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Table of Contents
COMMUNICATION
Yashar Soltani,‡[a] Lewis C. Wilkins‡[a]
and Rebecca L. Melen*[a]
B(C6F5)3: Stoichiometric and
Catalytic C–C and C–H Bond
Formation via Cationic Intermediates
The highly Lewis acidic borane, B(C6F5)3, is used in C–H and C–C bond forming reactions.
Activation of alkynyl substrates using the Lewis acid allows catalytic intramolecular
cyclizations of carboxylic acid substrates to be achieved for the first time. Additionally,
intramolecular cyclizations of esters enables C–C bond formation in which catalytic B(C6F5)3
is used to effect 1,5-alkyl migrations from ester functionalities to unsaturated carbon-carbon
frameworks in good to excellent yields and outstanding atom efficiency in a metal-free
manner.
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