Enantioselective NHC-Catalyzed Redox [2+2] Cycloadditions with Perfluoroketones: A Route to Fluorinated Oxetanes

Article abstract of DOI:10.1002/chem.201504256

The N-heterocyclic carbene (NHC) catalyzed redox formal [2+2] cycloaddition between α-aroyloxyaldehydes and perfluoroketones, followed by ring-opening in situ delivers a variety of perfluorinated β-hydroxycarbonyl compounds in good yield, and excellent diastereo- and enantioselectivity. Through a reductive work-up and subsequent cyclization, this protocol offers access to highly substituted fluorinated oxetanes in two steps and in high ee.

Full text of DOI:10.1002/chem.201504256

DOI: 10.1002/chem.201504256
Communication
&
Organocatalysis
Enantioselective NHC-Catalyzed Redox [2+2] Cycloadditions with
Perfluoroketones: A Route to Fluorinated Oxetanes
Alyn T. Davies, Alexandra M. Z. Slawin, and Andrew D. Smith*[a]
Perfluorinated heterocycles are of great industrial relevance,
Abstract: The N-heterocyclic carbene (NHC) catalyzed
with a number of biologically active molecules, such as Lonap-
redox formal [2+2] cycloaddition between a-aroyloxyalde-
risan (Bayer), currently under development containing such
hydes and perfluoroketones, followed by ring-opening in
functionality (Scheme 1).[12] However, methods for the introduc-
situ delivers a variety of perfluorinated b-hydroxycarbonyl
tion of perfluorinated groups are currently limited,[13] and
compounds in good yield, and excellent diastereo- and
enantioselectivity. Through a reductive work-up and sub-
sequent cyclization, this protocol offers access to highly
substituted fluorinated oxetanes in two steps and in high
ee.
Organocatalysis has grown to become one of the most impor-
tant sub-classes of organic chemistry, responsible for the devel-
opment of a vast array of novel processes and catalytic
modes.[1] Within this field, the use of N-heterocyclic carbenes
Scheme 1. Lonaprisan, a pentafluoroethyl-substituted progesterone receptor
antagonist from Bayer,[12] and recent work on the synthesis of fluorinated ox-
(NHCs) has become popularized due to the variety of unusual
etanes from the group of Miller.[18a]
catalytic intermediates that can be accessed from simple start-
ing materials.[2] NHC-catalyzed redox processes can be used to
generate a number of these useful catalytic intermediates, key
among which is azolium enolates.[3] Mono-substituted azolium
these often consist of direct perfluorination, as opposed to uti-
enolates can be accessed directly from starting materials such
as a-haloaldehydes,[4] enals,[5] and p-nitrophenol esters.[6] Alter-
natively, Rovis and co-workers[7] and Chi and co-workers[8] have
used aldehydes in conjunction with a stoichiometric oxidant to
generate azolium enolates. Our previous work has shown the
ability of bench-stable a-aroyloxyaldehydes to access azolium
intermediates through an NHC-redox mechanism.[9] These stud-
ies and numerous others have shown the ability of azolium
enolates to undergo a range of [4+2] cycloaddition reac-
tions.[4–8] To date di-substituted azolium enolates derived from
the reaction of NHCs with alkylarylketenes undergo [2+2] cy-
cloadditions with aryl aldehydes and imines to form b-lactones
and b-lactams respectively,[10] while [2+2] cycloadditions of
mono-substituted azolium enolates have received little atten-
tion.[8,11] In this area, Chi and co-workers have reported two iso-
lated examples of oxidative [2+2] cycloadditions between hy-
drocinnamaldehyde and trifluoroacetophenones, which re-
quires superstoichiometric quantities of quinone as an oxidant
(see Scheme 2a).[8]
lizing perfluoro-containing building blocks such as ketones.
Similarly, the oxetane motif has received considerable attention
within medicinal chemistry due to the physicochemical proper-
ties it can impart onto molecules,[14] as well as its potential to
be used as a bioisostere for the ketone functional group or
a more lipophilic replacement for the gem-dimethyl moiety.[14]
As such, novel approaches to oxetane scaffolds are of great in-
terest, and in recent times a number of methods have been
developed (Scheme 1).[15] Perfluorinated oxetanes have shown
numerous applications in the literature, ranging from building
blocks for inkjet polymers,[16] to inhibitors for numerous biolog-
ical targets.[17] Despite this popularity, only limited studies on
the synthesis of such compounds have been reported, often
utilizing an allenoate [2+2] cycloaddition, as developed by
Miller.[18a]
In this manuscript, the enantioselective NHC-catalyzed redox
formal [2+2] cycloaddition between a-aroyloxyaldehydes and
fluorinated ketones, followed by in situ ring-opening to form
a variety of fluorinated quaternary b-hydroxycarbonyl com-
pounds with excellent diastereo- and enantioselectivity is de-
scribed. Through a reductive work-up and subsequent cycliza-
tion, this protocol allows access to highly functionalized ster-
eodefined fluorinated oxetanes (Scheme 2b).
[a] A. T. Davies, Prof. A. M. Z. Slawin, Prof. A. D. Smith
EaStCHEM, School of Chemistry University of St Andrews
North Haugh, St Andrews, Fife KY16 9ST (UK)
E-mail: ads10@st-andrews.ac.uk
Initial studies into the NHC-catalyzed redox formal [2+2] cy-
cloaddition investigated potential reaction conditions with per-
fluorinated ketones (Table 1). Consideration of both organic
Homepage: http://ch-www.st-andrews.ac.uk/staff/ads/group/
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201504256.
Chem. Eur. J. 2015, 21, 18944 – 18948
18944
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
isolated as a single diastereomer in 57% yield and 99% ee
(entry 7). Variation of the perfluorinated group showed that
the pentafluoroethyl derivative provided a dramatic increase in
diastereoselectivity, giving 5 in 74% yield and 96% ee (entry 8).
Similarly impressive diastereo- and enantioselectivity was ob-
tained by using a perfluorobutyl ketone (entry 9).
Next, b-lactone ring-opening with a series of nucleophiles
was screened under the optimised reaction conditions
(Table 2). Using the p-BrC6H4 pentafluoroethyl ketone,
Table 2. Formal [2+2] cycloadditions with perfluorinated ketones and a-
aroyloxyaldehydes; ring-opening with
a
variety of nucleophiles.
Scheme 2. a) Oxidative NHC-catalyzed [2+2] cycloaddition from the group
of Chi.[8] b) An asymmetric NHC-catalyzed formal [2+2] cycloaddition leading
to fluorinated oxetanes.
Table 1. Formal [2+2] cycloaddition optimization.
Product
yield [%][a]
d.r.,[b] ee[c]
Product
yield [%][a]
d.r.,[b] ee[c]
Product
yield [%][a]
d.r.,[b] ee[c]
7, 80% yield
94:6 d.r., 96% ee
8, 75% yield
92:8 d.r., 89% ee
9, 70% yield
92:8 d.r., 94% ee
Entry Rf
Solvent Base
d.r.[a]
3
Amide Amide
NMR
yield
ee
[%][d]
yield [%][b] [%][c]
1
2
3
4
5
6
7
8
9
CF3
THF
THF
THF
CH2Cl2
Et2O
Et3N
71:29
48
50
88
61
58
55
–
–
–
–
–
–
–
57
74
45
–
–
–
–
–
–
99
96
96
CF3
CF3
CF3
CF3
CF3
CF3
iPr2NEt 70:30
Cs2CO3 73:27
Cs2CO3 80:20
Cs2CO3 72:28
10, 81% yield
90:10 d.r., 99% ee
11, 50% yield[d]
88:12 d.r., 97% ee
12, 75% yield
>95:5 d.r., 89% ee
toluene Cs2CO3 68:32
THF
[a] Isolated yield of major diastereomer (>95:5 d.r.). [b] d.r. determined
by analysis of the crude H NMR spectra. [c] ee determined by chiral HPLC
or chiral GC analysis. [d] 15 equivalents of N,O-dimethylhydroxylamine
were used.
Cs2CO3 76:24
Cs2CO3 >95:5
Cs2CO3 >95:5
1
C2F5 THF
C4F9 THF
–
–
1
[a] d.r. determined by analysis of the crude H NMR spectra. [b] Combined
NMR yield of both diastereomers determined by analysis of the crude
1H NMR spectra with reference to 2,5-dimethylfuran as an internal stan-
dard. [c] Isolated yield of major diastereomer (>95:5 d.r.). [d] ee deter-
mined by chiral HPLC or chiral GC analysis.
a number of different amine nucleophiles proved amenable,
including ammonia, benzylamine and secondary amines such
as pyrrolidine forming products 8–10 in high yield and excel-
lent diastereo- and enantioselectivity.[20] N,O-dimethylhydroxyl-
amine could also be used allowing access to Weinreb amide
11. The p-BrC6H4-substituted allyl amide 7 provided unambigu-
ous determination of the relative and absolute configuration
of this molecular class through X-ray crystallographic analy-
sis.[21] The p-BrC6H4 perfluorobutyl ketone also proved reactive
with secondary amines, with the corresponding morpholine
amide 12 accessed in excellent yield and selectivity (Table 2).
To further expand the versatility of this methodology, varia-
tion of the aromatic group within the pentafluoroethyl ketone
was examined, with some interesting reactivity patterns noted
(Table 3). Substitution of the aromatic ring with functional
groups with a negative Hammett s constant[22] led to a dramat-
and inorganic bases showed that caesium carbonate was opti-
mal in the system (entries 1–3), and variation of the solvent
showed that THF provided the best yield of the desired prod-
uct (entries 3–6), with similar diastereoselectivity (approximate-
ly 75:25) observed in all cases. While b-lactone 3 was stable to
work-up and could be directly isolated in moderate purity it
was unstable to further purification by chromatography. To
provide stable, isolable products numerous ring-opening pro-
cedures were investigated,[19] and ring-opening with allylamine
provided the chromatographically stable b-hydroxyamide
product. Under these conditions the desired product 4 was
Chem. Eur. J. 2015, 21, 18944 – 18948
www.chemeurj.org
18945
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
hydes, heteroaromatic groups and aromatic ring substitution
were all tolerated, with the products synthesized in good yield
with excellent enantioselectivity (22–24).
Table 3. Formal [2+2] cycloadditions with perfluorinated ketones and
variety of a-aroyloxyaldehydes; ring-opening with allylamine.
a
Having explored the scope of this process, derivatization of
the b-lactone intermediates into perfluorinated oxetanes was
investigated. NHC-catalyzed formal [2+2] cycloaddition, fol-
lowed by reduction with lithium borohydride gave isolable
diols 25, 27, 29, 31 and 33 as single diastereoisomers after pu-
rification (Table 4). Treatment of these diols with sodium hy-
Product
yield [%][a]
d.r.,[b] ee[c]
Product
yield [%][a]
d.r.,[b] ee[c]
Product
yield [%][a]
d.r.,[b] ee[c]
Table 4. Oxetane synthesis via a formal [2+2] cycloaddition, reduction
and subsequent ring closure.
13, 63% yield
14, 64% yield
15, 86% yield
92:8 d.r., 98% ee
93:7 d.r., 96% ee
94:6 d.r., 97% ee
Alcohol
yield%[a]
d.r.,[b] ee[c]
Oxetane
yield%[a]
d.r.[b]
16, 58% yield
17, 79% yield
18, 56% yield
92:8 d.r., 95% ee
>95:5 d.r., 98% ee
90:10 d.r., 95% ee
25, 63% yield
91:9 d.r., 88% ee
26, 89% yield
>95:5 d.r.
19, 51% yield
93:7 d.r., 94% ee
20, 50% yield
93:7 d.r., 98% ee
21, 63% yield
92:8 d.r.[d]
27, 53% yield
91:9 d.r., 94% ee
28, 99% yield
>95:5 d.r.
22, 86% yield
23, 81% yield
24, 55% yield
>95:5 d.r., 96% ee
>95:5 d.r., 97% ee
>95:5 d.r., 95% ee
29, 63% yield
92:8 d.r., 97% ee
30, 96% yield
>95:5 d.r.
[a] Isolated yield of major diastereomer (>95:5 d.r.) [b] d.r. determined by
analysis of the crude H NMR spectra. [c] ee determined by chiral HPLC or
1
chiral GC analysis. [d] ee could not be determined by chiral HPLC or chiral
GC.
31, 51% yield
89:11 d.r., 94% ee
32, 78% yield
>95:5 d.r.
ic decrease in conversion (60% with p-MeC6H4, no observed re-
activity with p-MeOC6H4 and p-Me2NC6H4). However, the incor-
poration of substituents with a positive Hammett s value (p-
BrC6H4, p-FC6H4, p-F3CC6H4 and m-MeOC6H4) were all tolerated,
giving the corresponding b-hydroxyamides in good yield, with
excellent diastereo- and enantioselectivity. 2-Pyridyl pentafluor-
oethyl ketones also proved reactive in this system, allowing
the introduction of heterocyclic structures into the products
(13–16).[23] A variety of different a-aroyloxyaldehydes could be
utilized in this process, introducing functionality such as pro-
tected oxygen substitutents, allyl groups and p-methoxybenzyl
(PMB) groups, with all of the desired products produced in
good yield with excellent diastereo- and enantioselectivity
(17–21). Furthermore, selected examples with perfluorobutyl-
substituted ketones showed this methodology could be ex-
panded to this class of ketones. Functionalized a-aroyloxyalde-
33, 64% yield
>95:5 d.r., 94% ee
34, 91% yield
>95:5 d.r.
[a] Isolated yield of major diastereomer (>95:5 d.r.). [b] d.r. determined
by analysis of the crude H NMR spectra. [c] ee determined by chiral HPLC
or chiral GC analysis.
1
dride and trisyl chloride subsequently allowed access to the
corresponding oxetanes in excellent yield as a single diastereo-
mer (26, 28, 30, 32, 34). This procedure tolerates p-BrC6H4, p-
F3CC6H4, p-FC6H4 and m-MeOC6H4 substituents, with the prod-
ucts isolated in good yield, and excellent diastereoselectivity
Chem. Eur. J. 2015, 21, 18944 – 18948
www.chemeurj.org
18946
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
2013, 42, 4906–4917; e) D. M. Flanigan, F. Romavov-Michailidis, N. A.
White, T. Rovis, Chem. Rev. 2015, 115, 9307–9387.
[3] For reviews on NHC-redox catalysis, see: a) H. U. Vora, P. Wheeler, T.
Rovis, Adv. Synth. Catal. 2012, 354, 1617–1639; b) J. Douglas, G. Church-
ill, A. D. Smith, Synthesis 2012, 2295–2309.
(>95:5 d.r.). Variation of the a-aroyloxyaldehyde was also toler-
ated as well as a perfluorobutyl-substituted ketone, with oxe-
tanes 32 and 34 produced in good yield as a single diastereo-
mer (Table 4).[24]
[4] a) N. T. Reynolds, J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc. 2004, 126,
9518–9519; b) M. He, G. J. Uc, J. W. Bode, J. Am. Chem. Soc. 2006, 128,
15088–15089.
The highly functionalized nature of the oxetane products
offers many possible opportunities for further manipulation. To
confirm the ability of these products to undergo such transfor-
mations oxetane 34 (derived from diol 33, 94% ee) was sub-
jected to Suzuki–Miyaura coupling conditions using [Pd(PPh3)4]
(10 mol%) and boronic acid 35, giving 36 in 81% yield and
94% ee (Scheme 3). This derivatization also confirms the enan-
tiointegrity of the oxetane products generated within this pro-
cess.
[5] a) M. He, J. R. Struble, J. W. Bode, J. Am. Chem. Soc. 2006, 128, 8418–
8420; b) M. Wadamoto, E. M. Phillips, T. E. Reynolds, K. A. Schedit, J. Am.
Chem. Soc. 2007, 129, 10098–10099; c) J. Kaeobamrung, M. C. Kozlow-
ski, J. W. Bode, Proc. Natl. Acad. Sci. USA 2010, 107, 20661–20665; d) X.
Fang, X. Chen, Y. R. Chi, Org. Lett. 2011, 13, 4708–4711; e) Z. Fu, H. Sun,
S. Chen, B. Tiwari, G. Li, Y. R. Chi, Chem. Commun. 2013, 49, 261–263;
f) E. O’Bryan McCusker, K. A. Scheidt, Angew. Chem. Int. Ed. 2013, 52,
13616–13620; Angew. Chem. 2013, 125, 13861–13865.
[6] a) L. Hao, Y. Du, H. Lv, X. Chen, H. Jiang, Y. Shao, Y. R. Chi, Org. Lett.
2012, 14, 2154–2157; b) L. Hao, S. Chen, J. Xu, B. Tiwari, Z. Fu, T. Li, J.
Lim, Y. R. Chi, Org. Lett. 2013, 15, 4956–4959; c) S. Chen, L. Hao, Y.
Zhang, B. Tiwari, Y. R. Chi, Org. Lett. 2013, 15, 5822–5825; d) L. Hao,
C. W. Chuen, R. Ganguly, Y. R. Chi, Synlett 2013, 1197–1200.
[7] X. Zhao, K. E. Ruhl, T. Rovis, Angew. Chem. Int. Ed. 2012, 51, 12330–
12333; Angew. Chem. 2012, 124, 12496–12499.
[8] J. Mo, R. Yang, X. Chen, B. Tiwari, Y. R. Chi, Org. Lett. 2013, 15, 50–53.
[9] a) K. B. Ling, A. D. Smith, Chem. Commun. 2011, 47, 373–375; b) A. T.
Davies, J. E. Taylor, J. Douglas, C. J. Collett, L. C. Morrill, C. Fallan, A. M. Z.
Slawin, G. Churchill, A. D. Smith, J. Org. Chem. 2013, 78, 9243–9257;
c) J. E. Taylor, D. S. B. Daniels, A. D. Smith, Org. Lett. 2013, 15, 6058–
6061; d) A. T. Davies, P. M. Pickett, A. M. Z. Slawin, A. D. Smith, ACS Catal.
2014, 4, 2696–2700.
Scheme 3. Derivatization of oxetane 34 under Suzuki–Miyaura conditions.
[10] a) N. Duguet, C. D. Campbell, A. M. Z. Slawin, A. D. Smith, Org. Biomol.
Chem. 2008, 6, 1108–1113; b) Y.-R. Zhang, L. He, X. Wu, P.-L. Shao, S. Ye,
Org. Lett. 2008, 10, 277–280; c) X.-H. Wang, P.-L. Shao, H. Lv, S. Ye, Org.
Lett. 2009, 11, 4029–4031; d) J. Douglas, J. E. Taylor, G. Churchill,
A. M. Z. Slawin, A. D. Smith, J. Org. Chem. 2013, 78, 3925–3938.
[11] C. Burstein, S. Tschan, X. Xie, F. Glorius, Synthesis 2006, 2418–2439.
[12] a) W. Jonat, T. Bachelot, T. Ruhstaller, I. Kuss, U. Reimann, J. F. Robertson,
Ann. Oncol. 2013, 24, 2543–2548; b) J. D. Croxtall, K. McKeage, Drugs
2011, 71, 363–380.
[13] a) J.-A. Ma, D. Cahard, Chem. Rev. 2004, 104, 6119–6146; b) Y. MacØ, E.
Magnier, Eur. J. Org. Chem. 2012, 2479–2494.
[14] a) G. Wuitschik, E. M. Carreira, B. Wagner, H. Fischer, I. Parrilla, F. Schuler,
M. Rogers-Evans, K. Müller, J. Med. Chem. 2010, 53, 3227–3246; b) C. A.
Malapit, A. R. Howell, J. Org. Chem. 2015, 80, 8489–8495.
In summary, the first NHC-catalyzed redox formal [2+2] cy-
cloaddition from a-aroyloxyaldehydes has been developed.
This methodology allows access to b-hydroxycarbonyl com-
pounds following ring-opening in excellent yield, diastereo-
and enantioselectivity. Through a reductive ring-opening and
subsequent cyclization, a number of fluorinated oxetanes can
be accessed in good yield as a single diastereomer over two
steps. Derivatization of one of these oxetanes has confirmed
no erosion of ee in the cyclization process. Current research
within this laboratory is focused on developing alternative
novel asymmetric processes using a-aroyloxyaldehydes in NHC
redox catalysis and other methodologies.
[15] a) T. Sone, G. Lu, S. Matsunaga, M. Shibasaki, Angew. Chem. Int. Ed.
2009, 48, 1677–1680; Angew. Chem. 2009, 121, 1705–1708; b) O. A.
Davis, J. A. Bull, Angew. Chem. Int. Ed. 2014, 53, 14230–14234; Angew.
Chem. 2014, 126, 14454–14458.
Acknowledgements
[16] A. E. Feiring, F. L. Schadt III, V. A. Petrov, B. E. Smart, W. B. Farnham (Du
Pont), WO 2004/014960A2, 2004.
[17] a) M. Lehmann, K. Schçllkopf, P. Strehlke, N. Heinrich, K.-H. Fritzemeier,
H.-P. Muhn, R. Krattenmacher (Schering AG), WO 98/54159, 1998;
b) C. W. Am Ende, B. A. Fish, M. E. Green, D. S. Johnson, P. B. Mullins,
C. J. O’Donnell, M. Y. Pettersson, C. M. Stiff, C. Subramanyam, T. P. Tran,
T. Navaratnam (Pfizer Inc.), WO 2012/131539A1, 2012; c) M. Curtis, B. A.
Duclos, R. A. Ewin, P. D. Johnson, T. A. Johnson, R. Vairagoundar, D.
Billen, R. M. Goodwin, A. K. Haber-Stuk, G. M. Kyne, S. M. K. Sheehan
(Zoetis), WO 2013/134061A1, 2013.
We thank the Royal Society for a University Research Fellow-
ship (A.D.S.), and the European Research Council under the Eu-
ropean Union’s Seventh Framework Programme (FP7/2007–
2013) ERC grant agreement no. 279850 (A.T.D.). We also thank
the EPSRC UK National Mass Spectrometry Facility at Swansea
University.
[18] a) L. B. Saunders, S. J. Miller, ACS Catal. 2011, 1, 1347–1350; b) Q.-Y.
Zhao, L. Huang, Y. Wei, M. Shi, Adv. Synth. Catal. 2012, 354, 1926–1932;
Keywords: Lewis
organocatalysis · oxetane · pentafluoroethyl
base
·
N-heterocyclic
carbene
·
ˇ
c) P. Selig, A. Turockin, W. Raven, Chem. Commun. 2013, 49, 2930–2932;
d) K. Aikawa, Y. Hioki, N. Shimizu, K. Mikami, J. Am. Chem. Soc. 2011,
133, 20092–20095; e) K. Mikami, K. Aikawa, J. Aida, Synlett 2011, 2719–
2724.
[1] P. I. Dalko, L. Moisan, Angew. Chem. Int. Ed. 2004, 43, 5138–5175;
Angew. Chem. 2004, 116, 5248–5286.
[19] DMAP-catalyzed ring-opening to the corresponding methyl or benzyl
ester was successful, however the esters proved unstable to purifica-
tion.
[20] The d.r. and ee of the amides 7–11 varied with amine nucleophile. This
unexpected variation cannot be easily accounted for and may be due
to experimental error or crystallisation effects upon purification. Varia-
[2] For reviews on NHC catalysis, see: a) N. Marion, S. Díez-Gonzµlez, S. P.
Nolan, Angew. Chem. Int. Ed. 2007, 46, 2988–3000; Angew. Chem. 2007,
119, 3046–3058; b) D. Enders, O. Niemeier, A. Henseler, Chem. Rev.
2007, 107, 5606–5655; c) J. L. Moore, T. Rovis, Top. Curr. Chem. 2010,
291, 77–144; d) S. J. Ryan, L. Candish, D. W. Lupton, Chem. Soc. Rev.
Chem. Eur. J. 2015, 21, 18944 – 18948
www.chemeurj.org
18947
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
tion in ee and d.r. through epimerisation or retro-cycloaddition/cycload-
dition process cannot be ruled out.
[21] CCDC 1420970 (7) contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre.
[24] The ee of oxetanes 26, 28, 30, 32 and 34 could not be directly estab-
lished by either chiral HPLC or GC analysis. However, the ee of 34 was
confirmed by derivatization (Scheme 3), confirming the enantiointegrity
of the oxetanes generated in this protocol.
[22] D. H. McDaniel, H. C. Brown, J. Org. Chem. 1958, 23, 420–427.
[23] The corresponding 2-furyl and 2-thiophenyl pentafluoroethyl ketones
show excellent reactivity in the catalytic system, however the products,
when using allylamine as the nucleophile, proved unstable to isolation
and purification.
Received: October 22, 2015
Published online on November 23, 2015
Chem. Eur. J. 2015, 21, 18944 – 18948
www.chemeurj.org
18948
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim