Oxahelicene NHC ligands in the asymmetric synthesis of nonracemic helicenes

Article abstract of DOI:10.1039/c7cc00781g

A straightforward approach to enantiopure 2H-pyran-modified amino[5]helicenes and amino[6]helicenes was developed. They were converted to 1,3-disubstituted imidazolium salts and used as NHC ligand precursors in the Ni⁰-catalysed enantioselective [2+2+2] cycloisomerisation of aromatic triynes to obtain the model helicene derivatives in up to 86% ee.

Full text of DOI:10.1039/c7cc00781g

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Sánchez, M. Šámal, J. Nejedlý, M. Karras, J. Klívar, J. Rybáek, M. Budšínský, L. Bednárová, B. Seidlerová
and I. G. Stará, Chem. Commun., 2017, DOI: 10.1039/C7CC00781G.
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Oxahelicene NHC ligands in the asymmetric synthesis of
nonracemic helicenes†
Received 00th January 20xx,
Accepted 00th January 20xx
Isabel Gay Sánchez,a Michal Šámal,a Jindřich Nejedlý,a Manfred Karras,a Jiří Klívar,a Jiří Rybáček,a
Miloš Buděšínský,a Lucie Bednárová,a Beata Seidlerová,a Irena G. Stará*a and Ivo Starý*a
DOI: 10.1039/x0xx00000x
www.rsc.org/
A straightforward approach to enantiopure 2H‐pyran‐modified
amino[5]helicenes and amino[6]helicene was developed. They
were converted to 1,3‐disubstituted imidazolium salts and used as
NHC ligand precursors in the Ni0‐catalysed enantioselective
[2+2+2] cycloisomerisation of aromatic triynes to receive the
model helicene derivatives in up to 86% ee.
O
O
N+
-
O
Tol
Tol
Tol
Tol
Mes
N
Tol
Tol
N
N+
ClO4
Cl-
O
O
O
(-)-(M,R,R)-1
(-)-(M,R,R),(M,R,R)-2
N
R
N+
O
O
Tol
Cl-
Helicene‐derived1 1,3‐disubstituted imidazolium salts are rare
in the chemical literature despite the fact that they represent
inherently chiral entities attractive for material science,
chiroscience and catalysis. In fact, only a few related papers
have so far been published. Teplý et al. succeeded in
embedding the imidazolium core into the backbone of racemic
helicene‐like mono‐ or tricationic compounds.2 Storch et al.
synthesised a racemic imidazolium salt bearing a hexahelicen‐
2‐ylmethyl unit and used it for fabrication of a fully reversible
thin‐layer humidity sensor.3 Finally, Crassous, Autschbach et al.
utilised the same hexahelicene motif in the preparation of the
first enantiopure helicene–NHC–iridium complexes whose
stereochemical, electronic and chiroptical properties were
studied both experimentally and computationally.4
Tol
Tol
Tol
R
O
O
(-)-(M,R,R),(M,R,R)-3a-g
t-Bu
a: R = H
b: R =
d: R =
g: R =
Ph
t-Bu
e: R =
Ph
i-Pr
c: R =
f: R =
i-Pr
Fig. 1 Enantiopure oxahelicene 1,3‐disubstituted imidazolium salts
precursors to helically/centrally chiral NHC ligands (Mes: mesityl, Tol: 4‐tolyl).
1‐3 as
synthetic approach to enantiopure oxahelicene amines
represented by the 2H‐pyran‐modified 2‐amino[5]helicene and
2‐amino[6]helicene derivatives and their conversion to 1,3‐
To the best of our knowledge, helicene‐based imidazolium
salts as precursors of helical N‐heterocyclic carbenes (NHC)5
have never been employed in enantioselective catalysis.6
Actually, a reason for that might be the lack of a methodology
for the preparation of key enantiopure aminohelicene building
blocks through asymmetric synthesis. Racemic aminohelicenes
with the amino group attached directly to the helicene
backbone were already described but their number is rather
limited.7
disubstituted imidazolium salts 1‐3 (Fig. 1). Helically/centrally
chiral NHC ligands generated in situ from these salts were then
used in the Ni0‐catalysed enantioselective [2+2+2]
cycloisomerisation of aromatic triynes to receive model
helicene derivatives in up to 86% ee.
The synthesis of the imidazolium salts 1‐3 relied on the
general methodology for the preparation of 2H‐pyran‐
modified helicenes in an enantio‐ and diastereomerically pure
form that we developed recently.8 The starting enantiopure
diyne (+)‐(R)‐4a8 was subjected to Sonogashira coupling with
In this communication, we report on a straightforward
aryl iodide
(Scheme 1). The free phenolic group in (‐)‐(R)‐6a was
propargylated by the enantiopure alcohol (‐)‐(S)‐ under
5 bearing OH and Boc‐protected NH2 groups
a. Institute of Organic Chemistry and Biochemistry, Czech Academy of
Sciences, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic. E‐
mail: stara@uochb.cas.cz, stary@uochb.cas.cz
7
† I. G. Sánchez and M. Šámal contributed equally to this work.
Electronic Supplementary Information (ESI) available: Experimental
procedures and spectroscopic data of all new compounds. See
DOI: 10.1039/x0xx00000x
Mitsunobu reaction conditions (with an inversion of the
configuration at the stereogenic centre) to provide triyne
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
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(‐)‐(R,R)‐8a
.
It underwent microwave‐assistVeiedw Art[ic2le+O2n+li2ne]
9
DOI: 10.1039/C7CC00781G
cyclotrimerisation in the presence of CpCoCO(fum) that
resulted in the diastereo‐ and enantiomerically pure
oxa[5]helicene (‐)‐(M,R,R)‐9a (for the discussion about efficient
stereocontrol by the 1,3‐allylic‐type strain, see refs 8 and 10).
After the removal of the Boc protecting group, the free helical
amine (‐)‐(M,R,R)‐10a was transformed either into the
unsymmetrical 1‐oxahelicenyl‐3‐mesityl imidazolium salt (‐)‐
BocHN
BocHN
BocHN
OH
Tol
I
Tol
HO(-)-(S)-
7
OH
O
O
O
O
5
Tol
Tol
Tol
R1
a
b
(+)-(R)-4a R=H
(+)-(R)-4b R=Cl
R1
R1
(-)-(R)-6a R = H
(-)-(R)-6b R = C l
(-)-(R,R)-8a R = H
(-)-(R,R)-8b R=Cl
(M,R,R)‐1 (employing the N‐(2‐oxoethyl)formamide derivative
O
R2HN
11 according to the stepwise procedure by Fürstner et al.)11 or
the symmetrical 1,3‐bisoxahelicenyl imidazolium salt (‐)‐
(M,R,R),(M,R,R)‐3a (on reaction with aqueous glyoxal and
formaldehyde according to Baslé, Mauduit et al.).12
Tol
Tol
c
R1
O
O
(-)-(M,R,R)-9a R1=H, R2=Boc
(-)-(M,R,R)-9b R1=Cl, R2=Boc
(-)-(M,R,R)-10a R 1=H, R2=H
N
d
O
11
The versatility of this synthetic methodology was further
underlined by the preparation of the homologous diastereo‐
and enantiomerically pure oxa[6]helicene amine (‐)‐(M,R,R)‐16
starting from the enantiopure naphthalene building block (‐)‐
(R)‐128 (Scheme 2). The amine was finally converted to the
symmetrical 1,3‐bisoxahelicenyl imidazolium chloride (‐)‐
e
O
O
O
f
Mes
N
N+
-
N
N+
Cl-
O
O
CH
O
2
Tol
Tol
Tol
Tol
Tol
ClO 4
Tol
O
O
O
(-)-(M,R,R)-
1
(-)-(M,R,R),(M,R,R)-3a
(M,R,R),(M,R,R)‐
2 on reaction with aqueous glyoxal and
formaldehyde as described above.
NHC ligands are known to form with Ni0 efficient catalytic
Scheme 1 Asymmetric synthesis of the enantiopure 2H‐pyran‐modified 2‐
amino[5]helicenes 10a and 9b and conversion of the former to the
systems for
a plethora of intra‐ and intermolecular
corresponding 1,3‐disubstituted imidazolium salts
Pd(PPh3)2Cl2 (2 mol%), CuI (3 mol%), i‐Pr2NH (1.6 equiv. for 4a, 1.0 equiv. for 4b),
toluene, room temperature, 3 h, 66% for 6a or 67% for 6b; (b) (1.2 equiv.),
1 and 3a. (a) 5 (0.8 equiv.),
cycloaddition reactions to construct carbo‐ and heterocycles.13
Having the enantiopure oxahelicene imidazolium salts (‐)‐
7
PPh3 (1.2 equiv.), DIAD (1.2 equiv.), benzene, room temperature, 3‐4 h, 90% for
8a or 77% for 8b; (c) CpCo(CO)(fum) (30 mol% for 8a, 50 mol% for 8b), THF,
microwave reactor, [bdmim]BF4 (25 μl/ml of the reaction solution), 140 oC, 15
min, 82% for 9a or 74% for 9b; (d) TFA (15 equiv.), CH2Cl2, room temperature,
overnight, 78%; (e) 11 (1.9 equiv.), acetic anhydride (excess), HClO4 (70% in
water, 3.6 equiv.), room temperature, 12 h, then 10a (1.0 equiv.), room
(M,R,R)‐
1, (‐)‐(M,R,R),(M,R,R)‐2 and (‐)‐(M,R,R),(M,R,R)‐3a in
hand, we could explore their efficiency in the benchmark
enantioselective
Ni0‐catalysed
alkyne
[2+2+2]
cycloisomerisation.14 Instead of using the capriciously unstable
Ni(cod)2 (necessary to handle in a drybox), we generated a Ni0
o
temperature, 4 h, then HClO4 (70% in water, 3.6 equiv.), 80 C, overnight, 38%;
(f) glyoxal (40% in water, 0.5 equiv.), formaldehyde (37% in water, 0.7 equiv.),
glacial acetic acid, 40 oC, 25 min, work‐up with saturated aq. NaCl, 66%. species in situ by reducing dry Ni(acac)2 with EtMgCl in excess,
[bdmim]BF4
= 1‐butyl‐2,3‐dimethylimidazolium tetrafluoroborate; DIAD =
which mediated also the release of the NHC ligands from the
corresponding imidazolium salts. EtMgCl was found superior to
other reducing agents such as n‐BuLi, DIBAH, L‐Selectride or
Super‐Hydride with respect to the yields of the alkyne [2+2+2]
cycloisomerisation reaction (on 0.025 mmol scale), stability
under dilution and ease of determination of its concentration
(by titration with iodine). We focused first on cyclisation of the
aromatic triyne 17 to helical dibenzo[6]helicene 18 (Table 1).
The Ni0‐catalysed [2+2+2] cycloisomerisation in the presence
diisopropyl azodicarboxylate; fum = dimethyl fumarate; TFA = trifluoroacetic
acid.
BocHN
BocHN
BocHN
Tol
OH
I
HO
Tol
OH
O
O
(-)-(S)-
7
O
5
Tol
Tol
Tol
a
b
O
(-)-(R)-12
[]D -43 (in CH2Cl2)
[]D +23 (in CHCl3)
of the helical NHC ligands generated from (‐)‐(M,R,R)‐
(M,R,R),(M,R,R)‐ or (‐)‐(M,R,R),(M,R,R)‐3a delivered uniformly
(+)‐(P)‐18 in high yield but with different enantiomeric
excesses. Due to the poor performance of (Table 1, entry 1)
the unsymmetrical imidazolium salt (and possible analogues)
was excluded from further study. Instead, attention was
focused on the symmetrical 1,3‐bisoxahelicenyl imidazolium
1, (‐)‐
(-)-(R)-13
(-)-(R,R)-14
2
c
O
O
O
Tol
1
Tol
Tol
Tol
N
N+
Tol
RHN
Tol
O
O
O
(-)-(M,R,R),(M,R,R)-
2
(-)-(M,R,R)-15 R=Boc
(-)-(M,R,R)-16 R=H
salts
2 and 3a that provided promising enantiomeric excesses
d
O
O
CH
O
(Table 1, entries 2 and 3).
2
e
Obviously, the design of the helical NHC ligands required
modifications to improve enantioselectivity of the Ni0‐
Scheme 2 Asymmetric synthesis of the enantiopure 2H‐pyran‐modified 2‐
amino[6]helicene 16 and its conversion to the corresponding 1,3‐disubstituted catalysed alkyne [2+2+2] cycloisomerisation. We reasoned that
imidazolium salt
2
. (a)
5
(0.8 equiv.), Pd(PPh3)2Cl2 (2 mol%), CuI (4 mol%), i‐Pr2NH
(1.2 equiv.), PPh3 (1.2 equiv.), DIAD
diversifying the structure of the 1,3‐bisoxahelicenyl
imidazolium salts in the late stage of their synthesis would
facilitate the access to a small library of ligands.15 Accordingly,
we turned our attention to the readily accessible enantiopure
(1.7 equiv.), benzene, 45 oC, 4.5 h, 70%; (b)
7
(1.2 equiv.), benzene, room temperature, 2.5 h, 88%; (c) CpCo(CO)(fum) (40
mol%), THF, microwave reactor, [bdmim]BF4 (25 μl/ml of the reaction solution),
140 oC, 15 min, 63%; (d) TFA (15 equiv.), CH2Cl2, room temperature, overnight,
77%; (e) glyoxal (40% in water, 0.5 equiv.), formaldehyde (37% in water, 0.6
equiv.), glacial acetic acid, 55 oC, 35 min, 78%.
2 | J. Name., 2012, 00, 1‐3
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Table 1 Enantioselective [2+2+2] cycloisomerisation of triyne 17 to dibenzo[6]helicene
18 in the presence of enantiopure NHC ligands generated from 1, 2 or 3a
Table 3 The conversion of the 2‐aminooxa[5]helicenes 10b‐g to the symmetrical 1,3‐
View Article Online
disubstituted imidazolium salts 3b‐g
DOI: 10.1039/C7CC00781G
O
O
(-)-(M,R,R)-
-
(-)-(M,R,R),(M,R,R)-
-
3b g
10b g
CH
O
2
Ni(acac)2, EtMgCl
Entry
Educt
Producta
3b
3c
3d
3e
3f
Yield (%)b
57
NHC ligand precursor
1
2
3
4
5
6
10b
10c
10d
10e
10f
64
82
83
82
61
17
(+)-(P)-18
Entry
NHC ligand precursor
(‐)‐(M,R,R)‐1
Conv. (%)a,b
ee (%)c of 18
17 (+)
1
2
3
>90
>90
>90
10g
3g
(‐)‐(M,R,R),(M,R,R)‐3a
(‐)‐(M,R,R),(M,R,R)‐2
41 (+)
59 (+)
a
Glyoxal (40% in water, 0.5‐0.6 equiv.), formaldehyde (37% in water, 0.6‐0.8
equiv.), glacial acetic acid, 45‐55 oC, 0.7‐3.7 h, work‐up with saturated aq. NaCl. b
Preparative yield.
a Ni(acac)2 (20 mol%), EtMgCl (0.4 M in THF, 0.9 equiv.), NHC ligand precursor 1, 2
or 3a (44 mol%), THF, room temperature, 2 h. b Estimated by HPLC. c Determined
by HPLC on a Chiralpak IA column.
noticeable improvement in enantiomeric excess of (+)‐(P)‐18
:
From 41% ee (for nonarylated 3a; Table 1, entry 2) to 61% ee
(for 3,5‐diphenylphenyl‐substituted 3b), 64% ee (for 3,5‐
diisopropylphenyl‐substituted 3c) or 66% ee (for 3,5‐di‐tert‐
Boc‐protected 2‐aminooxa[5]helicene (‐)‐(M,R,R)‐9b bearing
the chlorine atom (Scheme 1). The following Suzuki‐Miyaura
coupling of (‐)‐(M,R,R)‐9b with diverse arylboronic acids or
esters proceeded smoothly allowing the variable extension of
butylphenyl‐substituted 3d
) (Table 4, entries 1‐3). The
presence of a less bulky aryl group such as (1,1'‐biphenyl)‐4‐yl
in 3e or those exhibiting conformational ambiguity such as
phenanthren‐9‐yl in 3f or pyren‐1‐yl in 3g resulted in a small
increase in enantiomeric excess of (+)‐(P)‐18 (Table 4, entries
4‐6).
the oxa[5]helicene backbone in (‐)‐(M,R,R)‐19b
After removal of the Boc protecting group, the free amines (‐)‐
(M,R,R)‐10b were converted to the desired symmetrical
bisoxahelicenyl imidazolium salts (‐)‐(M,R,R),(M,R,R)‐3b‐g on
reaction with aqueous glyoxal and formaldehyde (Table 3).
Indeed, the installation of a bulky aryl group at the
opposite terminus of the oxa[5]helicene backbone with
respect to the position of the imidazolium unit led to a
‐g (Table 2).
‐
g
The highest level of chirality transfer from a helical NHC
ligand to a helical product
was achieved in [2+2+2]
cycloisomerisation of the aromatic triyne 20 to
dibenzo[7]helicene (+)‐(P)‐21 (Table 5). Although the reactivity
of 20 was slightly lower than that of 17, employing the
Table 2 Suzuki‐Miyaura coupling of the chloro derivative 9b with arylboronic acids or
esters followed by the Boc removal to provide the 2‐aminooxa[5]helicenes 10b‐g
oxa[6]helicene imidazolium salt
2 (Table 5, entry 1) or
oxa[5]helicene imidazolium salt 3a (Table 5, entry 2) resulted
in (+)‐(P)‐21 with 74% or 72% ee, respectively. Finally, 3,5‐
diisopropylphenyl‐substituted oxa[5]helicene imidazolium salt
3c outperformed the other NHC ligand precursors by providing
(+)‐(P)‐21 with 86% ee (Table 5, entry 3).
O
O
O
BocHN
ArB(OR)2
H2N
BocHN
Tol
Tol
Tol
Tol
Tol
Tol
TFA
R
R
Cl
O
O
O
(-)-(M,R,R)-9b
(-)-(M,R,R)-19b-g
(-)-(M,R,R)-10b-g
Entry
ArB(OR)2
19b‐g (%)a,b
10b‐g (%)b,c
Ph
Ph
Table 4 Enantioselective [2+2+2] cycloisomerisation of triyne 17 to dibenzo[6]helicene
18 in the presence of enantiopure NHC ligands generated from 3b‐g
O
B
O
1
19b (79)
19c (89)
19d (82)
10b (97)
i-Pr
O
B
O
2
3
4
5
6
10c (98)
10d (85)
10e (78)
10f (76)
10g (86)
i-Pr
Ni(acac)2, EtMgCl
t-Bu
t-Bu
B(OH)2
NHC ligand precursor
B(OH)2
19e (87)
17
(+)-(P)-18
Entry
NHC ligand precursor
(‐)‐(M,R,R),(M,R,R)‐3b
(‐)‐(M,R,R),(M,R,R)‐3c
(‐)‐(M,R,R),(M,R,R)‐3d
(‐)‐(M,R,R),(M,R,R)‐3e
(‐)‐(M,R,R),(M,R,R)‐3f
(‐)‐(M,R,R),(M,R,R)‐3g
Conv. (%)a,b
ee (%)c of 18
B(OH)
2
19f (89)
19g (82)
1
2
3
4
5
6
90
90
81
89
73
90
61 (+)
64 (+)
66 (+)
44 (+)
56 (+)
47 (+)
B(OH)2
a Arylboronic acid or ester (2.1‐3.3 equiv.), XPhos Pd G2 (5‐8 mol%), K3PO4 (0.5M
in water, 1.1‐2.5 equiv.), THF, 100 oC, 1‐6 h. Preparative yield. TFA (15‐33
b
c
a Ni(acac)2 (20 mol%), EtMgCl (0.4 M in THF, 0.9 equiv.), NHC ligand precursor 3b‐
g (44 mol%), THF, room temperature, 2 h. b Estimated by HPLC. c Determined by
HPLC on a Chiralpak IA column.
equiv.), CH2Cl2, room temperature, 3‐16 h.
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Table 5 Enantioselective [2+2+2] cycloisomerisation of triyne 20 to dibenzo[7]helicene
21 in the presence of enantiopure NHC ligands generated from 2, 3a or 3c
Synthesis, Vol. 45b (Eds.: J. S. Siegel, Y. Tobe), Thieme,
View Article Online
Stuttgart, 2010, pp. 885−953.
DOI: 10.1039/C7CC00781G
2
3
M. Čížková, D. Šaman, D. Koval, V. Kašička, B. Klepetářová, I.
Císařová and F. Teplý, Eur. J. Org. Chem., 2014, 5681–5685.
J. Storch, J. Zadny, T. Strasak, M. Kubala, J. Sykora, M. Dusek,
V. Cirkva, P. Matejka, M. Krbal and J. Vacek, Chem. Eur. J.,
2015, 21, 2343–2347.
N. Hellou, C. Jahier‐Diallo, O. Baslé, M. Srebro‐Hooper, L.
Toupet, T. Roisnel, E. Caytan, C. Roussel, N. Vanthuyne, J.
Autschbach, M. Mauduit and J. Crassous, Chem. Commun.,
2016, 52, 9243–9246.
M. N. Hopkinson, C. Richter, M. Schedler and F. Glorius,
Nature, 2014, 510, 485–496 and references cited therein.
For applications of small helical molecules to asymmetric
catalysis, see: (a) M. J. Narcis and N. Takenaka, Eur. J. Org.
Chem., 2014, 21–34; (b) P. Aillard, A. Voituriez and A.
Marinetti, Dalton Trans., 2014, 43, 15263–15278.
Ni(acac)2, EtMgCl
NHC ligand precursor
4
20
(+)-(P)-21
Entry
NHC ligand precursor
(‐)‐(M,R,R),(M,R,R)‐2
(‐)‐(M,R,R),(M,R,R)‐3a
(‐)‐(M,R,R),(M,R,R)‐3c
Conv. (%)a,b
ee (%)c of 18
5
6
1
2
3
76
64
86
74 (+)
72 (+)
86 (+)
a Ni(acac)2 (20 mol%), EtMgCl (0.4 M in THF, 0.9 equiv.), NHC ligand precursor 2,
3a or 3c (44 mol%), THF, room temperature, 2 h. Estimated by HPLC.
Determined by HPLC on a Chiralpak IA column.
b
c
7
(a) 5‐amino[6]helicene: P. M. op den Brouw and W. H.
Laarhoven, Recl. Trav. Chim. Pays‐Bas, 1978, 97, 265–268;
(b) 3‐amino[5]helicene derivative: Z. Y. Wang, Y. Qi, T. P.
Bender and J. P. Gao, Macromolecules, 1997, 30, 764–769;
(c) 3‐amino[6]helicene derivatives: F. Teplý, I. G. Stará, I.
Starý, A. Kollárovič, D. Šaman, Š. Vyskočil and P. Fiedler, J.
Org. Chem., 2003, 68, 5193–5197; (d) tetrahydro derivative
of 5‐amino[6]helicene: A. Perzyna, C. D. Zotto, J.‐O. Durand,
M. Granier, M. Smietana, O. Melnyk, I. G. Stará, I. Starý, B.
Klepetářová and D. Šaman, Eur. J. Org. Chem., 2007, 4032–
4037; (e) 6,11‐diamino[6]helicene derivatives: G. Pieters, A.
In summary, we developed a straightforward access to
optically pure 2‐aminooxa[5]helicenes (‐)‐(M,R,R)‐10a and 2‐
aminooxa[6]helicene (‐)‐(M,R,R)‐16 employing the key [2+2+2]
cycloisomerisation of chiral functionalised triynes (‐)‐(R,R)‐8a
and (‐)‐(R,R)‐14 featuring ultimate stereocontrol. We showed
that the structure of the chloro‐substituted helical Boc‐
protected amine (‐)‐(M,R,R)‐9b could further be diversified by
attaching aryl substituents through Suzuki‐Miyaura coupling
with arylboronic acids or esters. The 2‐aminooxa[5]helicenes (‐
‐
g
,
b
Gaucher, D. Prim and J. Marrot, Chem. Commun., 2009
,
4827–4828; (f) amino[5]oxa‐ and thiahelicene derivatives: G.
Pieters, A. Gaucher, S. Marque, F. Maurel, P. Lesot and D.
Prim, J. Org. Chem., 2010, 75, 2096–2098; (g) [6]helicene‐
derived 2‐aminopyridinium ions: N. Takenaka, J. Chen, B.
Captain, R. S. Sarangthem and A. Chandrakumar, J. Am.
Chem. Soc., 2010, 132, 4536–4537; (h) 5‐amino cationic
[6]helicene derivative: F. Torricelli, J. Bosson, C. Besnard, M.
Chekini, T. Bürgi and J. Lacour, Angew. Chem. Int. Ed., 2013,
52, 1796–1800; (i) 9‐amino[7]helicene: J. Žádný, P. Velíšek,
M. Jakubec, J. Sýkora, V. Církva and J. Storch, Tetrahedron,
2013, 69, 6213–6218; (j) 5‐amino[6]helicene: M. W. van der
Meijden, E. Gelens, N. M. Quirós, J. D. Fuhr, J. E. Gayone, H.
Ascolani, K. Wurst, M. Lingenfelder and R. M. Kellogg, Chem.
Eur. J., 2016, 22, 1484–1492.
)‐(M,R,R)‐10a
were converted to the corresponding 1,3‐disubstituted
imidazolium salts (‐)‐(M,R,R)‐ , (‐)‐(M,R,R),(M,R,R)‐ and (‐)‐
(M,R,R),(M,R,R)‐3a (symmetrical or unsymmetrical). These
‐
g
and 2‐aminooxa[6]helicene (‐)‐(M,R,R)‐16
1
2
‐
g
enantiopure precursors to helical NHC ligands were employed
in the enantioselective Ni0‐catalysed triyne [2+2+2]
cycloisomerisation to provide dibenzo[6]helicene (+)‐(P)‐17 or
dibenzo[7]helicene (+)‐(P)‐21 with up to 66% ee or 86% ee,
respectively. It reveals the potential of the oxahelicene NHC
ligands in enantioselective transition metal catalysis. The study
on the conformational flexibility of the oxahelicene NHC
ligands and the mechanism of chirality transfer is in progress.
This work was supported by the Czech Science Foundation
(Reg. No. 14‐29667S) and the Institute of Organic Chemistry
and Biochemistry, Academy of Sciences of the Czech Republic
(RVO: 61388963).
8
9
J. Žádný, A. Jančařík, A. Andronova, M. Šámal, J. Vacek
Chocholoušová, J. Vacek, R. Pohl, D. Šaman, I. Císařová, I. G.
Stará and I. Starý, Angew. Chem. Int. Ed., 2012, 51, 5857–
5861.
A. Geny, N. Agenet, L. Iannazzo, M. Malacria, C. Aubert and
V. Gandon, Angew. Chem. Int. Ed., 2009, 48, 1810–1813.
10 M. Šámal, S. Chercheja, J. Rybáček, J. Vacek Chocholoušová,
J. Vacek, L. Bednárová, D. Šaman, I. G. Stará and I. Starý, J.
Am. Chem. Soc., 2015, 137, 8469–8474.
11 A. Fürstner, M. Alcarazo, V. César and C. W. Lehmann, Chem.
Commun., 2006, 2176–2178.
Notes and references
12 P. Queval, C. Jahier, M. Rouen, I. Artur, J.‐C. Legeay, L.
Falivene, L. Toupet, C. Crévisy, L. Cavallo, O. Baslé and M.
Mauduit, Angew. Chem. Int. Ed., 2013, 52, 14103–14107.
13 (a) G. Domínguez and J. Pérez‐Castells, Chem. Eur. J., 2016,
22, 6720–6739; (b) A. Thakur and J. Louie, Acc. Chem. Res.,
2015, 48, 2354–2365; (c) P. R. Chopadea and J. Louie, Adv.
Synth. Catal., 2006, 348, 2307–2327.
1
For recent reviews, see: (a) Chen, C.‐F.; Shen, Y., Helicene
Chemistry: From Synthesis to Applications; Springer‐Verlag:
Berlin, 2017; (b) N. Saleh, C. Shen and J. Crassous, Chem. Sci.,
2014, 5, 3680–3694; (c) J. Bosson, J. Gouin and J. Lacour,
Chem. Soc. Rev., 2014, 43, 2824–2840; (d) A. Urbano and M.
C. Carreño, Org. Biomol. Chem., 2013, 11, 699−708; (e) K.
Tanaka in Transition‐Metal‐Mediated Aromatic Ring
14 A. Jančařík, J. Rybáček, K. Cocq, J. Vacek Chocholoušová, J.
Vacek, R. Pohl, L. Bednárová, P. Fiedler, I. Císařová, I. G. Stará
and I. Starý, Angew. Chem. Int. Ed., 2013, 52, 9970–9975.
15 P. Aillard, D. Dova, V. Magné, P. Retailleau, S. Cauteruccio, E.
Licandro, A. Voituriez and A. Marinetti, Chem. Commun.,
2016, 52, 10984–10987.
Construction (Ed.: K. Tanaka), Wiley, Hoboken, 2013, pp.
281−298; (f) M. Gingras, Chem. Soc. Rev., 2013, 42, 968–
1006; (g) M. Gingras, G. Félix and R. Peresutti, Chem. Soc.
Rev., 2013, 42, 1007–1050; (h) M. Gingras, Chem. Soc. Rev.,
2013, 42, 1051–1095; (i) Y. Shen and C.‐F. Chen, Chem. Rev.,
2011, 112, 1463–1535; (j) I. G. Stará and I. Starý in Science of
4 | J. Name., 2012, 00, 1‐3
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Table of Contents
Oxahelicene NHC ligands were used in Ni-catalysed enantioselective cycloisomerisation of alkynes to
receive helicenes in up to 86% ee.