Fluorohydration of alkynes via I(I)/I(III) catalysis

Article abstract of DOI:10.3762/BJOC.16.135

Substrate specificity is ubiquitous in biological catalysis, but less pervasive in the realm of small-molecule catalysis. Herein, we disclose an intriguing example of substrate specificity that was observed whilst exploring catalysis-based routes to generate α-fluoroketones from terminal and internal alkynes under the auspices of I(I)/I(III) catalysis. Utilising p-TolI as an inexpensive organocatalyst with Selectfluor and amine/HF mixtures, the formation of protected α-fluoroketones from simple alkynes was realised. Whilst the transient p-TolIF₂ species generated in situ productively engaged with pentynyl benzoate scaffolds to generate the desired α-fluoroketone motif, augmentation or contraction of the linker suppressed catalysis. The prerequisite for this substructure was established by molecular editing and was complemented with a physical organic investigation of possible determinants.

Full text of DOI:10.3762/BJOC.16.135

Fluorohydration of alkynes via I(I)/I(III) catalysis
Jessica Neufeld, Constantin G. Daniliuc§ and Ryan Gilmour*¶
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2020, 16, 1627–1635.
Organisch-Chemisches Institut, Westfälische Wilhelms-Universität
Münster, Corrensstraße 40, 48149 Münster, Germany
doi:10.3762/bjoc.16.135
Received: 07 May 2020
Accepted: 30 June 2020
Published: 10 July 2020
Email:
Ryan Gilmour* - ryan.gilmour@uni-muenster.de
* Corresponding author
This article is part of the thematic issue "Organo-fluorine chemistry V".
Guest Editor: D. O'Hagan
§ X-ray crystallographer
¶ https://www.uni-muenster.de/Chemie.oc/Gilmour
Keywords:
© 2020 Neufeld et al.; licensee Beilstein-Institut.
License and terms: see end of document.
α-fluoroketone; alkyne; fluorination; hypervalent iodine;
organocatalysis
Abstract
Substrate specificity is ubiquitous in biological catalysis, but less pervasive in the realm of small-molecule catalysis. Herein, we
disclose an intriguing example of substrate specificity that was observed whilst exploring catalysis-based routes to generate α-fluo-
roketones from terminal and internal alkynes under the auspices of I(I)/I(III) catalysis. Utilising p-TolI as an inexpensive organocat-
alyst with Selectfluor® and amine/HF mixtures, the formation of protected α-fluoroketones from simple alkynes was realised.
Whilst the transient p-TolIF2 species generated in situ productively engaged with pentynyl benzoate scaffolds to generate the
desired α-fluoroketone motif, augmentation or contraction of the linker suppressed catalysis. The prerequisite for this substructure
was established by molecular editing and was complemented with a physical organic investigation of possible determinants.
Introduction
The venerable role of fluorine as a powerful physicochemical render fluorination a valuable strategy in drug discovery [11]
modulator in small-molecule drug discovery is a compelling and agrochemical development [12]. In the conception of
argument for the importance of sustained innovation to facili- enabling fluorination technologies, the α-fluorocarbonyl motif
tate this form of structural editing [1-4]. Routinely employed as has emerged as a prominent target scaffold [13]. Remarkable
a bioisostere of hydrogen or hydroxy [5,6], substitution may advances in the direct fluorination (F2/N2) of carbonyl com-
enable inversion of the local electronic environment, or the pounds by Sandford and co-workers [14,15] are noteworthy in
precise deletion of hydrogen-bond donors, respectively, with this regard, and mitigate the expense and poor atom economy
minimal steric variation [7]. The latter aspect is a crucial deter- associated with stoichiometric approaches. Moreover, this
minant in enabling fluorinated materials to adopt intriguing con- substructure provides a versatile entry point for subsequent
formations which are a manifest representation of stabilising C(sp3)–C(sp3) bond-forming reactions [16,17], and closely
non-covalent interactions [8-10]. These collective attributes resembles one of the very few biological blueprints for the prep-
1627

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
aration of fluorine-containing materials [18-21]. However, in Elegant reports describing the conversion of internal alkynes to
translating the fluoroacetate-like building blocks to a laboratory α-fluoroketones via π-acid catalysis were also disclosed
paradigm, the intrinsic toxicity of these species in inhibiting (Figure 1B). Seminal reports by Nevado [41,42] and
aconitase [22] must be reconciled with synthetic utility. To that Gouverneur [43] enabled the synthesis of α-fluoroketones and
end, catalysis-based strategies to unmask the venerable α-fluo- -enones from terminal and internal alkynes, thereby mitigating
rocarbonyl motif [23] from a terminal alkyne were considered difluoroketone formation: This is commonly observed in
(Figure 1). This general strategy was appealing given the com- the fluorination of alkynes using stoichiometric electrophilic
mercial availability of the substrates and the plenum of methods fluorinating reagents [44,45]. Developments by Hammond
available to activate π-bonds [24,25].
and Xu validated N-pyridine oxides as terminal oxidants
to substitute Selectfluor® for the cationic Au(I)/Au(III) cycle,
Confidence in this approach stemmed from our recent vicinal thereby enabling high functional group tolerance [46-49].
and geminal difluorination of alkenes [26-30], and contempora- Inspired by these and other selected advances [50,51], in metal-
neous studies from the Jacobsen laboratory [31-34], under the based fluorination, a complementary organocatalytic variant
auspices of I(I)/I(III) catalysis [35-37]. Moreover, elegant [52], based on an I(I)/I(III) catalysis platform was explored
studies by Hara and co-workers have demonstrated that α-fluo- (Figure 1C). It was envisaged that the in situ generation of
roketones could be prepared by exposing silyl enol ethers to p-TolIF2 via oxidation of p-TolI with Selectfluor® in the pres-
stoichiometric p-ToIIF2, in the presence of BF3·OEt2 and ence of an amine/HF complex might enable the title transfor-
NEt3/HF 1:2 [38]. A report by Kitamura and co-workers in mation [53].
which the direct fluorination of acetophenone derivatives was
achieved using iodosylarenes and commercially available Results and Discussion
NEt3/HF 1:5 to generate the ArIF2 species in situ is also highly To explore the feasibility of generating α-fluoroketones from
pertinent [39,40] (Figure 1A).
terminal alkynes via I(I)/I(III) catalysis, 4-pentynyl benzoate (1)
Figure 1: (A) Synthetic routes to α-fluoroketones from silyl enol ethers or acetophenone derivatives. (B) Selected Au-catalysed syntheses of α-fluo-
roketones from alkynes. (C) This work: synthesis of α-fluoroketones from pentynyl benzoates via I(I)/I(III) catalysis.
1628

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
was selected as the substrate for optimisation studies (Table 1). 56% yield, respectively, Table 1, entries 2 and 4). Fluorinated
The inexpensive, commercially available p-TolI was used as an solvents such as hexafluoroisopropanol (HFIP) or ethyl tri-
organocatalyst, Selectfluor® was employed as the terminal fluoroacetate (ETFA) led to similar results (52% and 50% yield,
oxidant, and an amine/HF complex enlisted as the fluoride respectively, Table 1, entries 5 and 6). Switching to non-halo-
source (please see Supporting Information File 1 for full genated solvents such as acetonitrile or toluene proved to be
details). The reaction was performed in CHCl3 at ambient tem- detrimental (19% and 10%, respectively, Table 1, entries 7 and
perature and the crude reaction mixtures were analysed by 8). A screen of common oxidants for I(I)/I(III) catalysis con-
19F NMR spectroscopy using ethyl fluoroacetate as the internal firmed Selectfluor® as being ideally suited, in line with our
standard. Initially, the effect of Brønsted acidity was explored previous observations [26-30]. Whereas m-CPBA generated the
by varying the amine/HF ratio with mixtures of commercially desired α-fluoroketone 2 (50% yield), ground Oxone® or
available NEt3/HF 1:3 and Olah’s reagent (pyr/HF 1:9.23). N-pyridine oxide proved to be ineffective (Table 1, entries
Lower amine/HF ratios (1:4.5) resulted in poor conversion (9% 9–11). Increasing the reaction temperature to 50 °C led to the
yield, Table 1, entry 1), whereas increasing the Brønsted acidity same outcome as at ambient temperature (64% yield, Table 1,
to 1:7.5 furnished the desired α-fluoroketone 2 in 64% yield entry 12). Finally, the control reactions in the absence of cata-
(Table 1, entry 2). However, employing Olah’s reagent (1:9.23) lyst, oxidant and HF source were performed and supported the
had a negative impact on the efficiency (45% yield, Table 1, involvement of the postulated I(I)/I(III) cycle (Table 1, entries
entry 3) thereby allowing a plateau to be established (vide 13–15).
infra).
Since the conditions described in Table 1, entry 2 furnished the
Having established that an amine/HF ratio of 1:7.5 provides the desired α-fluoroketone 2 in a respectable yield without the addi-
optimal Brønsted acidity for catalysis, a solvent screen was con- tion of H2O, efforts to establish the influence of rigorous exclu-
ducted to assess the effect of the reaction medium. Chlorinated sion and excess addition were conducted (Table 2). In both
solvents proved to be most effective, with reactions performed scenarios, comparable results were observed (without H2O
in CHCl3 slightly outperforming those in CH2Cl2 (64% and 64%, with addition of 1.0 equiv 64% yield, Table 2, entries 1
Table 1: Reaction optimisation for the synthesis of α-fluoroketone 2 from alkyne 1.a
entry
oxidant
amine/HFb
solvent
yieldc
1
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
Selectfluor®
m-CPBA
1:4.5
1:7.5
1:9.23
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
1:7.5
–
CHCl3
CHCl3
CHCl3
CH2Cl2
HFIP
9%
2
64%
45%
56%
52%
50%
19%
10%
50%
<5%
<5%
64%
<5%
<5%
<5%
3
4
5
6
ETFA
7
CH3CN
toluene
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
8
9
10
11
12d
13e
14
15
gr. Oxone®
N-pyridine oxide
Selectfluor®
Selectfluor®
–
Selectfluor®
aStandard reaction conditions: alkyne 1 (0.2 mmol), p-TolI (20 mol %), oxidant (1.5 equiv), solvent (0.5 mL), amine/HF source (0.5 mL), ambient tem-
perature, 24 h. bSee Supporting Information File 1 for the exact calculation of the amine/HF mixtures. cDetermined by 19F NMR analysis of the crude
reaction mixture using ethyl fluoroacetate as the internal standard. dReaction was performed at 50 °C. eControl reaction without catalyst.
1629

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
Table 2: Investigating the role of H2O during the reaction.a
entry
equiv of H2O
yieldb
correlation of equiv H2O versus yieldc
1
2
3
4
5
–
64%
64%
56%
48%
29%
1.0
2.0
5.0
10
aStandard reaction conditions: alkyne 1 (0.2 mmol), p-TolI (20 mol %), Selectfluor® (1.5 equiv), H2O (0–10 equiv), CHCl3 (0.5 mL), amine/HF 1:7.5
(0.5 mL), ambient temperature, 24 h. See Supporting Information File 1 for the exact calculation of the amine/HF mixtures. bDetermined by 19F NMR
analysis of the crude reaction mixture using ethyl fluoroacetate as internal standard. cLinear correlation of the equivalent of H2O and the correspond-
ing yield of 2.
and 2). Further increasing the amount of H2O from 2.0 equiv to the solid state, a dihedral angle of φ = −3.7° was observed
10 equiv suppressed reactivity (to 29% yield, Table 2, entries thereby placing the C–F bond in the same plane as the carbonyl
3–5). In addition, a nearly linear correlation between the equiv- group.
alents of added H2O and the product yield was observed
(Table 2 insert). Cognisant that H2O is likely being introduced To establish the limitations of the title transformation, a process
to the reaction via the HF source, and to prevent reproducibility of substrate editing was initiated (Figure 3). However, efforts to
issues due to variation of the H2O content, 1.0 equiv was added contract or expand the alkynyl chain to four or six carbons,
in the general procedure to enable comparison.
respectively, had a negative impact on the yield of the
α-fluoroketone (16%, <5% for 8 and 9, respectively,
With the optimised reaction conditions in hand (Table 2, entry Figure 3A). Deletion of the ester carbonyl (10) and replace-
2), the scope and limitations of the title transformation were ment of the phenyl group by methyl (11) was also detrimental.
explored. Initially, the influence of modifying the aryl fragment From these data it is tempting to speculate upon the involve-
of the 4-pentynyl benzoate motif was established (Scheme 1). ment of a chair-like transition state in which the intramolecular
Exposing the standard substrate 1 to the general reaction condi- interaction of the phenyl π-system, carbonyl and alkynyl group
tions furnished the desired product 2 in a synthetically useful are optimally preorganised with a C5 linker. With this in mind,
isolated yield of 60%. Introduction of para-substituents was the amide derivatives 12 and 13 were exposed to the standard
tolerated enabling formation of the chloro, methoxy, and nitro reaction conditions. Curiously, the reactions were extremely
derivatives 3–5 with up to 54% yield. The exposure of a model ineffective yielding the respective α-fluoroketones in only 15%
internal alkyne to the standard conditions proved also success- yield as determined by 19F NMR spectroscopy. This contrasts
ful affording 6 in 46% yield. Finally, replacement of the sharply with the phthalimide derivative 7 (64%). Doping a rep-
benzoate unit by a phthalimide moiety was possible and led to resentative reaction (14 → 9) with methyl benzoate (15)
the protected amine derivative 7 (64% yield).
(Figure 3B) to explore for potential activator effects also proved
unsuccessful.
The structure of α-fluoroketone 2 was unequivocally estab-
lished by single crystal X-ray diffraction (Figure 2). Interest- Finally, a stoichiometric reaction of alkynyl phthalimide 16
ingly, a study by Pattison has established that α-fluoroketones with freshly prepared p-TolIF2 17 demonstrated the importance
preferentially adopt a cis-conformation in polar solvents [54]. In of the exogenous amine·HF as a Brønsted acid activator
1630

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
Scheme 1: Substrate scope with standard reaction conditions: alkyne (0.2 mmol), p-TolI (20 mol %), Selectfluor® (1.5 equiv), H2O (1.0 equiv), CHCl3
(0.5 mL), amine/HF 1:7.5 (0.5 mL), ambient temperature, 24 h. Yields refer to isolated products while 19F NMR yields are given in parentheses (deter-
mined by 19F NMR analysis of the crude reaction mixture using ethyl fluoroacetate as internal standard). See Supporting Information File 1 for the
exact calculation of the amine/HF mixtures.
Figure 2: X-ray molecular structure of compound 2. Conformation of the carbonyl group and the fluoride with a torsion angle of φO=C-C-F = −3.7°.
CCDC number 2000136.
(Figure 3C). Similar yields were observed when comparing the Hammett plot was essentially zero (ρ ≈ 0). In contrast, a second
stoichiometric reaction and the catalytic process using an Hammett analysis in which the substitution of the iodoarene
amine/HF ratio of 1:7.5.
catalyst was explored (R = Me, H, Cl, and Br) revealed a build-
up of positive charge (ρ < 0) during the rate-determining step
To interrogate the importance of the benzoate group in the sub- (Figure 4B).
strate, a Hammett analysis was conducted. To that end,
log(kR/kH) was plotted against the Hammett σ−p parameter for From a methodological perspective, this study provides a
the para-substituted pentynyl benzoates with R = OMe, H, Cl, conceptual platform to unmask the valuable α-fluoroketone
and NO2 (Figure 4A). However, the resulting slope of the motif from alkynes. Selectfluor®-mediated oxidation of p-TolI
1631

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
Figure 3: (A) Structure activity relationship of the core scaffold. (B) Exploring the effect of methyl benzoate as an activator. (C) Stoichiometric reac-
tion with p-TolIF2 17 and alkyne 16. Yields refer to spectroscopical yields determined by 19F NMR analysis of the crude reaction mixtures using ethyl
fluoroacetate as an internal standard.
Figure 4: (A) Hammett plot varying the para-substitution on the alkyne (ρ ≈ 0). (B) Hammett plot varying the para-substitution on the catalyst (ρ < 0).
1632

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
in the presence of an amine/HF source, which plays a dual func- Preliminary mechanistic experiments, supported by Hammett
tion as fluoride source and Brønsted acid activator, enables in analyses, have identified key determinants that are essential for
situ generation of p-TolIF2 (Figure 5). From these preliminary reaction efficiency. X-ray crystal structure analysis of ketone 2
mechanistic investigations, conclusions regarding the extreme reveals a dihedral angle of φO=C-C-F = −3.7°. Although the
sensitivity of the fluorohydration towards changes in the sub- origin of this specificity requires clarification, this fluorohydra-
strate must be drawn with caution. The importance of the tion reaction constitutes a rare case of substrate specificity in
pentynyl linker, together with the requirement for the benzoyl small-molecule catalysis. It is envisaged that this organocata-
ester, suggest a highly preorganised structure [55] in which the lytic variant of the venerable Kucherov reaction will find appli-
carbonyl group functions as a tempered Lewis base upon ligand cation in contemporary organofluorine chemistry [61] and con-
exchange (Figure 5) [56]. This working hypothesis may also tributes to the current interest in alkyne functionalisation via
rationalise the deletion experiment (10), the recalcitrance of I(I)/I(III) catalysis [62,63].
acetyl derivatives, and the striking reactivity disparity between
amides (12/13) and the phthalimide derivative 16. Finally, to in-
vestigate the fate of water in the transformation, the catalytic
process was repeated in the presence of H218O. Through
isotope-shift experiments (please see Supporting Information
File 1), it was possible to establish that the aryl ketone of the
product contains the 18O atom (ΔδC = 4.42 Hz) [57-59]. Forma-
tion of the corresponding enol [60], tautomerisation and dis-
placement liberates the α-fluoroketone and regenerates the ArI
catalyst.
Supporting Information
Supporting Information File 1
Experimental details, characterization data and copies of
spectra.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-16-135-S1.pdf]
Conclusion Acknowledgements
In conclusion, the synthesis of α-fluoroketones from 4-pentynyl We thank the analytical department of our institute for excel-
benzoates based on an I(I)/I(III) catalysis manifold is disclosed. lent support.
Figure 5: An overview of the I(I)/I(III)-catalysed fluorohydration of alkynes.
1633

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
23.Rozen, S.; Filler, R. Tetrahedron 1985, 41, 1111–1153.
Funding
doi:10.1016/s0040-4020(01)96514-7
We acknowledge generous financial support from the WWU
Münster and the Deutsche Forschungsgemeinschaft (SFB 858,
fellowship to J.N.).
24.Yamamoto, Y.; Gridnev, I. D.; Patil, N. T.; Jin, T. Chem. Commun.
2009, 5075–5087. doi:10.1039/b909978f
25.Kohlhepp, S. V.; Gulder, T. Chem. Soc. Rev. 2016, 45, 6270–6288.
doi:10.1039/c6cs00361c
26.Molnár, I. G.; Gilmour, R. J. Am. Chem. Soc. 2016, 138, 5004–5007.
doi:10.1021/jacs.6b01183
ORCID® iDs
Constantin G. Daniliuc - https://orcid.org/0000-0002-6709-3673
27.Scheidt, F.; Neufeld, J.; Schäfer, M.; Thiehoff, C.; Gilmour, R. Org. Lett.
2018, 20, 8073–8076. doi:10.1021/acs.orglett.8b03794
28.Scheidt, F.; Schäfer, M.; Sarie, J. C.; Daniliuc, C. G.; Molloy, J. J.;
Gilmour, R. Angew. Chem., Int. Ed. 2018, 57, 16431–16435.
doi:10.1002/anie.201810328
Ryan Gilmour - https://orcid.org/0000-0002-3153-6065
References
1. Böhm, H.-J.; Banner, D.; Bendels, S.; Kansy, M.; Kuhn, B.; Müller, K.;
Obst-Sander, U.; Stahl, M. ChemBioChem 2004, 5, 637–643.
doi:10.1002/cbic.200301023
29.Molnár, I. G.; Thiehoff, C.; Holland, M. C.; Gilmour, R. ACS Catal.
2016, 6, 7167–7173. doi:10.1021/acscatal.6b02155
30.Scheidt, F.; Thiehoff, C.; Yilmaz, G.; Meyer, S.; Daniliuc, C. G.;
Kehr, G.; Gilmour, R. Beilstein J. Org. Chem. 2018, 14, 1021–1027.
doi:10.3762/bjoc.14.88
2. Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881–1886.
doi:10.1126/science.1131943
3. Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev.
2008, 37, 320–330. doi:10.1039/b610213c
31.Banik, S. M.; Medley, J. W.; Jacobsen, E. N. J. Am. Chem. Soc. 2016,
138, 5000–5003. doi:10.1021/jacs.6b02391
4. Liang, T.; Neumann, C. N.; Ritter, T. Angew. Chem., Int. Ed. 2013, 52,
8214–8264. doi:10.1002/anie.201206566
32.Banik, S. M.; Medley, J. W.; Jacobsen, E. N. Science 2016, 353,
51–54. doi:10.1126/science.aaf8078
5. Gillis, E. P.; Eastman, K. J.; Hill, M. D.; Donnelly, D. J.; Meanwell, N. A.
J. Med. Chem. 2015, 58, 8315–8359.
33.Mennie, K. M.; Banik, S. M.; Reichert, E. C.; Jacobsen, E. N.
J. Am. Chem. Soc. 2018, 140, 4797–4802. doi:10.1021/jacs.8b02143
34.Haj, M. K.; Banik, S. M.; Jacobsen, E. N. Org. Lett. 2019, 21,
4919–4923. doi:10.1021/acs.orglett.9b00938
doi:10.1021/acs.jmedchem.5b00258
6. Meanwell, N. A. J. Med. Chem. 2018, 61, 5822–5880.
doi:10.1021/acs.jmedchem.7b01788
35.Arnold, A. M.; Ulmer, A.; Gulder, T. Chem. – Eur. J. 2016, 22,
8728–8739. doi:10.1002/chem.201600449
7. O'Hagan, D. Chem. Soc. Rev. 2008, 37, 308–319.
doi:10.1039/b711844a
36.Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328–3435.
doi:10.1021/acs.chemrev.5b00547
8. Zimmer, L. E.; Sparr, C.; Gilmour, R. Angew. Chem., Int. Ed. 2011, 50,
11860–11871. doi:10.1002/anie.201102027
37.Lee, J. H.; Choi, S.; Hong, K. B. Molecules 2019, 24, 2634.
doi:10.3390/molecules24142634
9. Aufiero, M.; Gilmour, R. Acc. Chem. Res. 2018, 51, 1701–1710.
doi:10.1021/acs.accounts.8b00192
38.Sato, S.; Yoshida, M.; Hara, S. Synthesis 2005, 2602–2605.
doi:10.1055/s-2005-872105
10.Thiehoff, C.; Rey, Y. P.; Gilmour, R. Isr. J. Chem. 2017, 57, 92–100.
doi:10.1002/ijch.201600038
39.Kitamura, T.; Muta, K.; Muta, K. J. Org. Chem. 2014, 79, 5842–5846.
doi:10.1021/jo500691b
11.O’Hagan, D. J. Fluorine Chem. 2010, 131, 1071–1081.
doi:10.1016/j.jfluchem.2010.03.003
40.Nash, T. J.; Pattison, G. Eur. J. Org. Chem. 2015, 3779–3786.
doi:10.1002/ejoc.201500370
12.Fujiwara, T.; O’Hagan, D. J. Fluorine Chem. 2014, 167, 16–29.
doi:10.1016/j.jfluchem.2014.06.014
41.de Haro, T.; Nevado, C. Adv. Synth. Catal. 2010, 352, 2767–2772.
doi:10.1002/adsc.201000559
13.Harsanyi, A.; Sandford, G. Green Chem. 2015, 17, 3000–3009.
doi:10.1039/c5gc00402k
42.de Haro, T.; Nevado, C. Chem. Commun. 2011, 47, 248–249.
doi:10.1039/c002679d
14.Sandford, G. J. Fluorine Chem. 2007, 128, 90–104.
doi:10.1016/j.jfluchem.2006.10.019
43.Hopkinson, M. N.; Giuffredi, G. T.; Gee, A. D.; Gouverneur, V. Synlett
2010, 2737–2742. doi:10.1055/s-0030-1258992
44.Zupan, M.; Iskra, J.; Stavber, S. J. Org. Chem. 1995, 60, 259–260.
doi:10.1021/jo00106a045
15.Breen, J. R.; Sandford, G.; Yufit, D. S.; Howard, J. A. K.; Fray, J.;
Patel, B. Beilstein J. Org. Chem. 2011, 7, 1048–1054.
doi:10.3762/bjoc.7.120
16.Erian, A. W.; Sherif, S. M.; Gaber, H. M. Molecules 2003, 8, 793–865.
doi:10.3390/81100793
45.Stavber, S.; Zupan, M. Synlett 1996, 693–694.
doi:10.1055/s-1996-5544
17.Dobson, L. S.; Pattison, G. Chem. Commun. 2016, 52, 11116–11119.
doi:10.1039/c6cc05775f
46.Wang, W.; Jasinski, J.; Hammond, G. B.; Xu, B.
Angew. Chem., Int. Ed. 2010, 49, 7247–7252.
18.O'Hagan, D.; Schaffrath, C.; Cobb, S. L.; Hamilton, J. T. G.;
Murphy, C. D. Nature 2002, 416, 279. doi:10.1038/416279a
19.Dong, C.; Huang, F.; Deng, H.; Schaffrath, C.; Spencer, J. B.;
O'Hagan, D.; Naismith, J. H. Nature 2004, 427, 561–565.
doi:10.1038/nature02280
doi:10.1002/anie.201003593
47.Xu, B.; Wang, W.; Hammond, G. B. J. Fluorine Chem. 2011, 132,
804–810. doi:10.1016/j.jfluchem.2011.05.006
48.Zeng, X.; Liu, S.; Shi, Z.; Liu, G.; Xu, B. Angew. Chem., Int. Ed. 2016,
55, 10032–10036. doi:10.1002/anie.201603914
20.Zhu, X.; Robinson, D. A.; McEwan, A. R.; O'Hagan, D.; Naismith, J. H.
J. Am. Chem. Soc. 2007, 129, 14597–14604. doi:10.1021/ja0731569
21.Chan, K. K. J.; O'Hagan, D. Methods Enzymol. 2012, 516, 219–235.
doi:10.1016/b978-0-12-394291-3.00003-4
49.Zeng, X.; Lu, Z.; Liu, S.; Hammond, G. B.; Xu, B. Adv. Synth. Catal.
2017, 359, 4062–4066. doi:10.1002/adsc.201701179
50.Li, F.-H.; Cai, Z.-J.; Yin, L.; Li, J.; Wang, S.-Y.; Ji, S.-J. Org. Lett. 2017,
19, 1662–1665. doi:10.1021/acs.orglett.7b00453
22.Murphy, C. D.; Schaffrath, C.; O’Hagan, D. Chemosphere 2003, 52,
455–461. doi:10.1016/s0045-6535(03)00191-7
1634

Beilstein J. Org. Chem. 2020, 16, 1627–1635.
51.Chen, X.; Martini, S.; Michelet, V. Adv. Synth. Catal. 2019, 361,
3612–3618. doi:10.1002/adsc.201900268
52.Hummel, S.; Kirsch, S. F. Beilstein J. Org. Chem. 2011, 7, 847–859.
doi:10.3762/bjoc.7.97
53.Sarie, J. C.; Thiehoff, C.; Mudd, R. J.; Daniliuc, C. G.; Kehr, G.;
Gilmour, R. J. Org. Chem. 2017, 82, 11792–11798.
doi:10.1021/acs.joc.7b01671
54.Pattison, G. Beilstein J. Org. Chem. 2017, 13, 2915–2921.
doi:10.3762/bjoc.13.284
55.Boaventura, M. A.; Drouin, J.; Conia, J. M. Synthesis 1983, 801–804.
doi:10.1055/s-1983-30519
See for the cyclisation of ε-acetylenic carbonyl compounds.
56.Heinen, F.; Engelage, E.; Cramer, C. J.; Huber, S. M.
J. Am. Chem. Soc. 2020, 142, 8633–8640. doi:10.1021/jacs.9b13309
57.Coplen, T. B.; Böhlke, J. K.; De Bièvre, P.; Ding, T.; Holden, N. E.;
Hopple, J. A.; Krouse, H. R.; Lamberty, A.; Peiser, H. S.; Révész, K.;
Rieder, S. E.; Rosman, K. J. R.; Roth, E.; Taylor, P. D. P.;
Vocke, R. D.; Xiao, Y. K. Pure Appl. Chem. 2002, 74, 1987–2017.
doi:10.1351/pac200274101987
58.Diakur, J.; Nakashima, T. T.; Vederas, J. C. Can. J. Chem. 1980, 58,
1311–1315. doi:10.1139/v80-204
59.Vederas, J. C. Can. J. Chem. 1982, 60, 1637–1642.
doi:10.1139/v82-223
60.Ding, W.; Chai, J.; Wang, C.; Wu, J.; Yoshikai, N. J. Am. Chem. Soc.
2020, 142, 8619–8624. doi:10.1021/jacs.0c04140
See for the synthesis of β-λ3-iodanyl vinyl ethers.
61.Kutscheroff, M. Ber. Dtsch. Chem. Ges. 1881, 14, 1540–1542.
doi:10.1002/cber.188101401320
62.Asari, N.; Takemoto, Y.; Shinomoto, Y.; Yagyu, T.; Yoshimura, A.;
Zhdankin, V. V.; Saito, A. Asian J. Org. Chem. 2016, 5, 1314–1317.
doi:10.1002/ajoc.201600383
63.Takahashi, S.; Umakoshi, Y.; Nakayama, K.; Okada, Y.;
Zhdankin, V. V.; Yoshimura, A.; Saito, A. Adv. Synth. Catal. 2020.
doi:10.1002/adsc.202000381
See for a study on the fluorocyclization of N-propargyl carboxamides
which appeared whilst this manuscript was under review.
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0). Please note
that the reuse, redistribution and reproduction in particular
requires that the authors and source are credited.
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
(https://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.16.135
1635