Modular Synthesis of Triazole-Based Chiral Iodoarenes for Enantioselective Spirocyclizations

Article abstract of DOI:10.1002/adsc.201700246

A new triazole-based C₁-symmetrical chiral iodoarene was synthesized in a highly modular route. Based on enzymatic kinetic resolution of an easily accessible propargylic alcohol both enantiomers were accessible in enantiopure form. By Huisgen-type azide-alkyne cycloaddtion a series of differently substituted iodoarenes was synthesized in high overall yields. Finally this novel iodoarene was successfully applied in the oxidative Kita cyclization of naphthol derivatives. Good yields and high ee values were obtained in the asymmetric spirocyclization via in situ generation of the hypervalent iodine species using mCPBA as the terminal oxidant. (Figure presented.).

Full text of DOI:10.1002/adsc.201700246

Title: Modular Synthesis of Triazole-based Chiral Iodoarenes for
Enantioselective Spirocyclizations
Authors: Christian Hempel, caecilia maichle-moessmer, Miquel Àngel
Pericàs, and Boris Johannes Nachtsheim
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700246
Link to VoR: http://dx.doi.org/10.1002/adsc.201700246

Advanced Synthesis & Catalysis
10.1002/adsc.201700246
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Modular Synthesis of Triazole-based Chiral Iodoarenes
for Enantioselective Spirocyclizations
a
b
c
Christian Hempel, Caeciliea Maichle-Mössmer, Miquel A. Pericàs * and
a*
Boris J. Nachtsheim
a
Universität Bremen, Institut für Organische und Analytische Chemie, Leobener Straße NW2C, 28359
Bremen, Germany; Fax: + 49 421 218 63120; phone: + 49 421 218 63120; nachtsheim@uni-bremen.de
Universität Tübingen, Institut für Anorganische Chemie
Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology;
b
c
mapericas@iciq.es
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201######.((Please delete if not appropriate))
Abstract.
A new triazole-based C1-symmetric chiral Keywords: Hypervalent compounds; Iodine; Spiro
iodoarene was synthesized in a highly modular route. Based compounds; Cyclization; C-O-coupling
on enzymatic kinetic resolution of an easy accessible
propargylic alcohol both enantiomers were accessible in
enantiopure
form. By Huisgen-type
azide-alkyne
cycloaddtion a series of differently substituted iodoarenes
were synthesized in high overall yields. Finally this novel
iodoarene was successfully applied in the oxidative Kita
cyclization of naphthol derivatives. Good yields and high ee
values were obtained in the asymmetric spirocyclization via
in situ generation of the hypervalent iodine species using
mCPBA as the terminal oxidant.
as chiral iodoarene.[5] Quideau and co-workers
developed Binaphthyl-derived chiral iodoarenes and
successfully used these compounds for the ortho-
hydroxylation of naphthols. While these mostly C1-
symmetric structures could be efficiently used for
intermolecular oxygenation reactions, they usually
fail to give good selectivities in intramolecular
enantioselective dearomatizations. In 2008 Kita and
Introduction
[6]
Hypervalent iodine compounds, in particular aryl-
3
λ -iodanes, have become commonly used reagents in
organic synthetic chemistry due to their low toxicity,
easy handling and good availability.[1] The potential
of these reagents is demonstrated by the diverse
reactivities they offer in oxidative transformations
such as the functionalization of alkynes and alkenes,
α-functionalizations of ketones or dearomatization
reactions.[ A variety of these transformations create
at least one stereogenic center offering the possibility
co-workers reported
spirolactonization of
the
1-naphtol
asymmetric
derivatives.
Unprecedented high ee values were observed
utilizing the structural rigid C2-symmetric 1,1’-
2]
[7d]
bisindane based iodoarene 1 (Figure 1). Recently,
for asymmetric induction by using an optical active
Ishihara and co-workers presented the lactate derived
reagent.[
3]
Seminal works on the successful
C
-symmetric iodoarene
2
for the same
2
3
[8]
application of chiral aryl-λ -iodanes were based on
the principle of optical active ligands derived from
the chiral pool.[ However, these reagents were
limited to the asymmetric oxidation of sulfides. In an
alternative approach the stereogenic center is part of
the iodoarene. The first successful application of this
strategy was described by Wirth and co-workers in
the asymmetric α-oxytosylation of ketones using a
C1-symmetric (R)-2-(1-methoxyethyl)-phenyl iodide
transformation. A similar C1-symmetric catalyst, as
described by Fujita and coworkers, was initially
investigated in tetrahydrofuranylation of but-3-enyl
4]
[9]
carboxylates. However, this catalyst gave poor
[8]
yields and poor selectivities in spirocyclizations.
Catalysts of type 2 were also successfully applied in a
3
plethora of other aryl-λ -iodane-mediated oxidative
transformations
such
as
oxylactonizations,
oxygenations, (oxy)aminations, aminofluorinations
1
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
and rearrangements.[10] Very recently, Ibrahim and
furthermore, by using kinetic enzymatic resolution,
both enantiomers of the final iodoarene should be
easily accessible in an enantiopure form.
co-workers developed the chiral iodoarene 3 based on
a
rigid
all-carbon
anti-dimethanoanthracene
[11]
framework.
So far C2-symmetric iodoarenes
and/or their hypervalent iodine derivatives 1-3 were
the most successful reagents for intramolecular
oxidative spirolactonizations.
Scheme 1. Retrosynthetic analysis of target structure.
For our initial synthetic studies, we selected the
commercially available 2-iodobenzaldehyde (6) and
ethynylmagnesium
bromide
(Scheme
2).
Figure 1. Structures of common chiral iodoarenes for
enantioselective oxidative transformations.
Nucleophilic addition of this reagent gave the alcohol
rac-7 in 98% yield. We were pleased to find that
Novozyme 435 (Candida antarctica lipase B, CALB)
tolerated the sterically demanding iodine atom and
selectively acetylated the (R)-enantiomer to give its
acylated derivative (R)-8 in 49% yield and the free
C1-symmetric chiral iodoarenes are not common
for this important reaction. To the best of our
knowledge there was only one very recent report by
Masson and co-workers who introduced a novel
binaphthylamine-based iodoarene 4 for oxidative
spirocyclizations, however with only moderate
enantioselectivties.[
[14]
alcohol (S)-7 in 47% yield and >99.9% ee. (R)-8
could be efficiently transformed into the free alcohol
(
R)-7 by mild base treatment. However, (S)-7 was
further submitted to the copper catalyzed azide-
alkyne cycloaddition using commercially available
12]
Hereby we would like to report our recent results
in the design of a new C1-symmetric triazole-
functionalized chiral iodoarene which can be easily
synthesized in a modular fashion and is therefore
easily adaptable to a variety of enantioselective
synthetic tasks, in particular the Kita-type
spirolactonization.
[15]
benzyl azide to afford triazole (R)-9a in 96% yield.
Methylation or benzylation of the free hydroxy group
led to the desired iodoarenes (R)-5a and (R)-5b in
9
9
4% yield (42% overall yield). Other triazoles (R)-
b-e bearing different sterically demanding aryl and
alkyl groups at N1 were synthesized accordingly by
treatment of (S)-7 with different aryl and alkyl azides.
Benzyl substituted 1,5-triazole (R)-9f was obtained in
9
3% yield by changing reaction conditions of the
Results and Discussion
Huisgen-type cycloaddition. Changing the typical
Cu-catalyst to a Ru-catalyst resulted in an inversion
of the regioselectivity. Finally, a variety of silyl-
based protecting groups were installed onto structures
In the course of our investigations on new ligands
for asymmetric transition metal catalyzed reactions
we identified a new class of C1-symmetric triazole-
based chiral iodoarenes 5 as potential catalysts in
(
R)-9b-f using the corresponding silyl chlorides or
triflates. The desired C1-symmetric iodoarenes (R)-
c-i were obtained in good to very high yields.
[13]
asymmetric oxidative transformations (Scheme 1).
5
These iodoarenes potentially offer a wide range of
possible modifications due to their modular structure
consistent of the iodoarene, the chiral linker and the
triazole moiety. Our retrosynthetic strategy towards
these novel iodoarenes involves the nucleophilic
addition of an alkyne to the appropriate
iodobenzaldehyde followed by a copper-catalyzed
azide-alkyne cycloaddition and final protection of the
alcohol. This approach would exponentially generate
a number of different substituted iodoarenes and
2
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
loading which resulted in continuously improved
yields of 11a but only a moderate improvement in
enantioselectivities. A maximum ee of 52% was
observed when stoichiometric amounts of 5b were
used (entries 3-5).
Next, we focused our attention on the structure of the
iodoarene.
Table 1. Optimization of the reaction conditions for the
enantioselective spirocyclization of 10a.
Entrya) Iodoarene
mol%)
Time Yieldb
eec
[%]
(
[h]
[%]
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
(R)-5a (15)
(R)-5b (15)
(R)-5b (25)
(R)-5b (50)
(R)-5b (100)
(R)-5c (15)
(R)-5d (15)
(R)-5e (15)
(R)-5f (15)
(R)-5g (15)
(R)-5h (15)
(R)-5i (15)
(R)-5j (15)
(R)-5e (25)
(R)-5e (50)
(R)-5e (100)
(R)-5e (100)
(S)-5e (100)
72
36
24
16
8
36
24
24
36
60
48
60
72
18
12
6
no conv.
29
34
46
62
26
24
25
28
21
28
28
no conv.
32
45
64
61
62
-
38
40
42
52
64
78
80
80
74
72
76
-
80
80
80
86((99)
84
0
1
2
3
4
5
6
7
8
d
e
24
30
1
a)
General reaction conditions: 0.1 mmol substrate in 5 mL
b)
c)
DCM. Isolated yield after column chromatography.
Determined by chiral HPLC. Reaction carried out
at -20 °C. After a single recrystallization.
d)
e)
Scheme 2. Modular synthesis of triazole-containing chiral
iodoarenes.
We hypothesized that sterically more demanding
protecting groups should be favorable in terms of
asymmetric induction and therefore tested the
trialkylsilyl-protected iodoarenes 5c-5e. The absolute
configuration of these novel iodoarenes could be
With these 10 novel chiral iodoarenes in hand, we
investigated the oxidative dearomatization of
[16]
[7, 8]
verified by X-Ray analysis of 5e (Figure 2). Under
catalytic conditions using 15 mol% of the
corresponding iodoarene yields were still low (entries
hydroxynapthalene propionic acid 10a (Table 1).
In this reaction especially Ishihara’s lactate-derived
catalysts 2 gave access to high ee values of up to
7-9).
92%. However, C1-symmetric derivatives carrying
only one sidechain were much less efficient (32%
ee).[ While the methyl protected iodoarene 5a did
not show any reactivity in this transformation, we
were happy to find, that 15 mol% of the benzyl-
protected derivative 5b at 0 °C gave the desired
product 11a in 29% yield and 38% ee (Table 1,
entries 1 and 2). Further attempts to improve the yield
and enantioselectivity by changing the solvent or the
concentration of the reaction were unsuccessful.
Therefore, we decided to stepwise raise the catalyst
9]
3
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
However, we could show that with only one
recrystallization step enantioselectivity of product
1
1c can be increased to 94%. Under catalytic
conditions (Method C), both yields and selectivities
remained constant. Next, we investigated 4-acyl-
substituted 1-naphthols 10d and 10e. Applying
Method A, again an improved yield was observed for
both substrates with an overall maximum of 89% for
lactone 11d however accompanied by a loss of
enantioselectivity (76 and 68% ee; entries 3 and 4).
Using benzoyl- and acyl -substituted naphthols 10d
and 10e enantiomeric ratios slightly improved when
running the reaction at -20 °C (Method B), however a
significant drop in reactivity was observed. In both
cases selectivities did not further improve using
catalytic amounts of the iodoarene (Table 2, entries 3
and 4). 4-Phenyl-substituted naphthol 10f resulted in
formation of spirolactone 11f in good yield and
enantioselectivity using method A (72%, 80% ee). No
significant improvements were observed using lower
temperatures or catalytic amounts of the iodane
(Table 2, entry 5, Methods B and C). However, with
a single recrystallization step enantioselectivities
could be increased to >99% ee. Finally, we focused
on the influence of slightly electron donating
aliphatic substituents (Table 2, entries 6-8). 4-Methyl,
ethyl- or propyl-substituted naphthols 10g-10i gave
the desired spirolactones 11g-11i in throughout good
yields (60-67%) and good enantioselectivities (72-
76%) using either Method A or B. We investigated
substrate 10g under catalytic conditions. The reaction
was very sluggish and the yield dropped to 26% (data
not shown). As a result of this poor reactivity ethyl
and propyl substituted naphthols 10h and 10i were
Figure 2. X-Ray structure of iodoarene (R)-5e.
However, enantiomeric ratios significantly increased
with a maximum of 80% ee when the TIPS- protected
iodoarene 5e was applied (entry 8). Since the
protecting group had a significant impact on the
selectivity, we further investigated iodoarenes 5g-5j
to study the influence of the substituent on the
triazole nitrogen. However, in contrast to the
protecting group, the triazole moiety seemed to have
little influence on the outcome of the reaction and no
further improvement in reaction yields and
enantioselectivity could be achieved (entries 9-13). In
all cases the best yield of 11a was obtained when 1
equivalent of the iodoarene 5e was applied (entry
1
6).[
17]
Lowering the temperature to -20 °C a
maximum of 86% ee was observed with similar yield
entry 17). One single recrystallization step further
(
improved the enantiomeric excess to 99%. It is
interesting to note, that iodoarene 5j, in which the 2-
iodophenyl)(methoxy)methyl group is attached at C5
of the triazole ring and not at C4, shows no reactivity
in the spirocyclization at all. This observation might
imply a significant nitrogen-iodine interaction in the
reactive hypervalent state. Finally, we could show
that under these conditions using the enantiomeric
iodoarene (S)-5e resulted in the complete inversion of
the enantioselectivity (entry 18).
[18]
not tested using Method C.
Table 2. Scope of the reaction.
We next investigated the scope of this transformation
applying a series of 1-napthol derivatives bearing a
substituent in position C4 (Table 2). Since we
observed a significant inverse correlation between
product yields and a positive correlation between
enantioselectivities
and
decreasing
reaction
temperatures (0°C and -20 °C), we investigated
various substrates under those distinct conditions
Entrya)
1
R
Method
T
[h]
Yield
[%]
ee
[%]
b)
c)
(
Method A and Method B). Additionally, substrates
0b-10g were transformed under catalytic conditions
15 mol% of 5e, Method C). Carrying out the reaction
under the previously optimized conditions at 0 °C
Method A) we were pleased to find that halogenated
(mol%)
1
(
Cl
11b)
A
B
C
A
B
C
A
B
C
A
B
C
11
82
77
72
85
72
73
89
60
76
76
40
77
64
80
58
62
(
72
48
9
(
2
3
4
Br
11c)
substrates 10b and 10c gave access to the
corresponding spirolactones 11b and 11c in high
yields of 82 and 85% but only moderate
enantioselectivities (64 and 62% ee; entries 1 and 2).
Using the same substrates with Method B (-20 °C)
confirmed our initial findings of slightly lower
reactivity and significantly higher enantioselectivities
at lower reaction temperatures (80 and 78% ee).
d)
(
48
24
24
55
72
35
96
80
78 (94)
64
COPh
11d)
76
80
72
68
70
64
(
COMe
11e)
(
4
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
1
d)
d)
H NMR spectra were recorded on an Avance 400 MHz or
5
Ph
11f)
A
B
C
A
B
A
B
A
B
13
50
72
10
24
10
24
12
24
72
63
39
62
67
66
62
65
60
80 (99)
82 (99)
70
AMX 600 MHz instrument in deuterated chloroform
(
(
3 4 6
CDCl ), methanol (Methanol-d ), acetone (acetone-d ) or
dimethyl sulfoxide (DMSO-d ). Chemical shifts (δ) are
6
1
6
7
8
Me
11g)
Et
11h)
Pr
11i)
74
76
76
76
72
72
given in parts per million (ppm). H NMR spectra were
referenced to the residual hydrogen signal in CDCl at δ =
3
(
7
2
.26 ppm, in methanol-d
4
δ = 3.31 ppm, in acetone-d
6
δ =
at δ
.05 ppm or to the residual hydrogen signal in DMSO
6
13
(
= 2.50 ppm. C NMR spectra were recorded on either 100
MHz or 150 MHz and were fully decoupled by broad band
13
decoupling. C spectra were referenced to the CDCl
3
(
4
triplet signal at δ = 77.0 ppm, to the methanol-d septet
a)
General reaction conditions: 0.1 mmol substrate in 5 mL
6
signal at δ = 49.0 ppm, to the acetone-d septet signal at δ
b)
c)
DCM. Isolated yield after column chromatography.
Determined by chiral HPLC. After a single
= 29.84 ppm or to septet signal at δ = 39.52 ppm in
d)
DMSO-d . The following abbreviations were used to
6
describe splitting patterns: br = broad, s = singlet, d =
doublet, t = triplet, q = quartet, sep = septet, m = multiplet.
Coupling constants J are given in Hz. Mass spectra were
recorded on a Finnigan MAT95 or an Agilent 5977 MSD
by using either EI or ESI ionization. High resolution mass
spectra were recorded by using ESI ionization with a FT-
ICR or TOF mass analyzer. High-performance liquid
chromatography (HPLC) analysis was conducted using
Hewlett Packard Series 1100 coupled diode array-detector
and chiral column of Dr. Maisch OM (4.6 mm x 25 cm),
AM (4.6 mm x 25 cm) and ZM (2.3 mm x 25 cm). Gas
chromatography (GC) analysis was conducted using
Shimadzu GC-2010 coupled with a flame ionisation
detector and chiral -dex 120 (30 m x 250 µm x 0.25 µm)
column. Thin layer chromatography was performed on
fluorescence indicator marked precoated silca gel 60 plates
recrystallization.
Finally, the absolute configuration of the spirolactone
products was determined to be S from X-ray
crystallographic analysis of 11f (>99% ee) (Figure
[16]
3).
(
Macherey-Nagel, ALUGRAM Xtra SIL G/UV254) and
visualization was achieved by UV light (254 nm). Flash
chromatography was performed on silica gel (0.040 –
0
.063 mm). Unless otherwise stated all reactions were
carried out under air. For air or moisture sensitive reactions
standard Schlenk-techniques were applied under an argon
atmosphere. Schlenk-glassware was heated in vacuo and
flushed with argon several times before they were used.
Reagents and solvents were added by syringe/septum
techniques. IR spectra were recorded on JASCO FT/IR-
Figure 3. X-Ray structure of spirolactone (S)-11f.
4
100. A selection of signals is given in reciprocal
-1
centimeters (cm ). Solvents for flash chromatography
were distilled before use. Water free solvents were dried
by a Braun SPS system. Unless stated, all other
commercially available substances and reagents were used
as received from their suppliers (Acros, Alfa Aesar, Sigma
Aldrich) without further purification.
Conclusion
In conclusion, we have developed a novel and robust
chiral iodoarene scaffold bearing a unique triazole-
motif and successfully demonstrated its application in
the asymmetric dearomatization of naphthol
derivatives via in situ generation of the hypervalent
iodine species. The spirolactones were obtained in
moderate to high yields and high ee values which
represent the best results for a C1-symmetric
iodoarene so far. Based on an approach including
enzymatic kinetic resolution both enantiomers of the
chiral iodoarene are available in >99.9% ee and high
overall yields. Our newly developed synthesis
towards these structures is highly modular to allow
easy modifications of the iodoarene scaffold.
Furthermore, varying the organic azide in the
cycloaddition step as well as installing different
protecting groups, the properties of the iodoarene
could be selectively adjusted. Further investigations
towards the influence of substituents on the iodoarene
moiety as well as the C5 atom of the triazole are
underway.
Experimental Details
Synthesis of Chiral Iodoarenes
(R)-1-(2-Iodophenyl)prop-2-yn-1-yl acetate (R-(8)) and
(
S)-1-(2-iodophenyl)prop-2-yn-1-ol (S-(7)): A solution of
ethynylmagnesium
bromide
(2.23 g,
25.0 mmol,
1
.25 equiv.) in THF (50 mL) was cooled to 0 °C.
Subsequently, 2-iodobenzaldehyde (4.64 g, 20.0 mmol, 1.0
equiv.) dissolved in dry THF (20 mL) was added for 0.5 h.
The resulting reaction mixture was stirred for an additional
2
4
h at 0 °C. Saturated NH Cl (100 mL) was added, phases
were separated and the aqueous layer was extracted with
EtOAc (3 x 40 mL). The combined organic layers were
2 4
washed with brine (100 ml), dried over Na SO and the
solvent was removed under reduced pressure. The crude
rac-(6) (5.07 g, 19.6 mmol, 98%) was used without further
purification in the following kinetic resolution. rac-(6)
(4.75 g, 18.4 mmol, 1.0 equiv) was dissolved in dry
toluene (35 mL) and CALB (110 mg, 6 mg∙mmol-1),
isopropenyl acetate (3.04 mL, 27.6 mmol, 1.5 equiv) and
Na
2
CO
3
(1.84 g, 18.4 mmol, 1.0 equiv.) were added
successively. The resulting mixture was stirred at room
temperature and the progress was monitored by chiral GC.
After 3 days full conversion of one enantiomer was
observed. The reaction mixture was filtered off, washed
with toluene and the solvent was removed under reduced
pressure. The crude reaction mixture was purified by
column chromatography on silica gel using cyclohexane
and EtOAc (10:1 to 2:1) to obtain the acetate R-(8) as well
Experimental Section
General Informations
5
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
as the free propargyl alcohol S-(8). Spectroscopic data: R-
(s, 1H), 3.36 (br s, 1H). 13C-NMR (100 MHz, CDCl
)
3
(
8): off white solid (2.68 g, 8.92 mmol, 49%). Melting
 = 143.8, 139.7, 130.0, 129.8, 129.0, 129.0, 128.2, 120.8,
2
1
1
•+
point: 36 °C. []
D
-17.5 (c 1.0 in CHCl
3
). H-NMR
97.8, 72.5. MS (EI): m/z = 377 [M] . HR-MS (ESI): m/z
+
(
(
400 MHz, CDCl
3
)  = 7.87 (dd, J = 7.9, 1.1 Hz, 1H), 7.77
calculated for C15
H
12IN
3
NaO [M+Na] : 399.99173, found
-
1
dd, J = 7.8, 1.6 Hz, 1H), 7.42 (m, 1H), 7.07 (m, 1H), 6.52
399.99168. IR νmax/cm 3734, 3627, 1748, 1715, 1499,
(
d, J = 2.2 Hz, 1H), 2.69 (d, J = 2.2 Hz, 1H), 2.14 (s, 3H).
1364, 1226, 1047, 760, 658.
1
3
C-NMR (100 MHz, CDCl )  = 169.5, 140.0, 138.8,
3
1
30.9, 129.4, 128.8, 98.6, 79.6, 76.2, 69.5, 21.0. MS (EI):
(
R)-(1-(2,6-Diisopropylphenyl)-1H-1,2,3-triazol-4-yl)(2-
+
m/z = 300 [M] . HR-MS (ESI): m/z calculated for
iodophenyl)methanol ((R)-9c) was prepared following a
+
C H INaO [M+Na] : 322.95395, found 322.95399. IR
9 7
slightly modified method reported by Moses and
-1
ν
max/cm 3254, 1738, 1467, 1371, 1221, 1194, 1011, 950,
54, 717.
[19]
coworkers: 2,6-diisopropyl aniline (126 l, 0.667 mmol,
7
1
.0 equiv.) was dissolved in acetonitrile (500 l) and tert-
Butyl nitrate (119 l, 1.0 mmol, 1.5 equiv.) was added at
0 °C. The reaction mixture was stirred for 5 minutes.
Trimethylsilyl azide (177 l, 1.33 mmol, 2.0 equiv.) was
added dropwise and the resulting reaction mixture was
allowed to warm to room temperature slowly. After stirring
at room temperature for 1 h the reaction mixture was
transferred to a suspension of (S)-7 (258 mg, 1.0 mmol, 1.5
S-(7): Brownish solid (2.23 g, 8.64 mmol, 47%). Melting
2
1
1
point: <25 °C. []
D
-24.6 (c 1.0 in CHCl
)  = 7.85 (dd, J = 7.9, 1.1 Hz, 1H), 7.78
dd, J = 7.8, 1.6 Hz, 1H), 7.41 (dt, J = 7.6, 1.1 Hz, 1H),
3
). H-NMR
(
(
400 MHz, CDCl
3
7
1

6
.04 (m, 1H), 5.67 (d, J = 2.2 Hz, 1H), 2.68 (d, J = 2.2 Hz,
13
3
H), 2.43 (br s, 1H). C-NMR (100 MHz, CDCl )
= 142.1, 139.9, 130.5, 129.0, 128.2, 98.3, 82.7, 75.5,
equiv),
Tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol
+
8.5. MS (EI): m/z = 258 [M] . HR-MS (EI): m/z
copper chloride (2.0 mg, 3.33 µmol, 0.005 equiv.) and
distilled water (1 mL). The solution was stirred for 24 h at
+
calculated for C
9
H
7
IO [M] : 257.95416, found 257.95581.
-
1
IR νmax/cm 3284, 3271, 1461, 1190, 1119, 1040, 1010,
2
70 °C. EtOAc (3 mL) and H O (3 mL) were added and the
9
3
>
39, 750, 639. GC, inlet 220 °C, 150 °C isothermal and
50 mL/min of Helium as carrier gas, t = 45.37 min, for
99.99% ee.
phases were separated. The aqueous layer was extracted
with EtOAc (3 x 4 mL) and the combined organic layers
2 4
were washed with brine, dried over Na SO and the solvent
removed under reduced pressure. The crude product was
further purified by column chromatography on silica gel
using cyclohexane and EtOAc (8:1 to 4:1) to obtain
(
R)-1-(2-Iodophenyl)prop-2-yn-1-ol ((R)-7): Compound
R)-8 (300 mg, 1.0 mmol, 1 equiv.) was dissolved in a 1:1
(
unreacted iodoarene (S)-8 and (R)-9c as white solid
mixture of MeOH (10 mL) and water (10 mL). K
2
CO
3
1
(
(
(
170 mg, 0.368 mmol, 55%). Mp: 130 °C. H-NMR
(
138 mg, 1.0 mmol, 1 equiv.) was added and the reaction
400 MHz, CDCl )  = 7.84 (dd, J = 7.9, 1.1 Hz, 1H), 7.77
3
mixture was stirred 6 h at room temperature. EtOAC (5 ml)
and water (5 mL) were added, the phases separated and the
aqueous layer extracted with EtOAc (3 x 5 mL). The
combined organic layers were washed with brine, dried
dd, J = 7.8, 1.6 Hz, 1H), 7.47-7.42 (m, 2H), 7.26-7.24 (m,
4
1
H), 7.03 (dt, J = 7.6, 1.7 Hz, 1H), 6.31 (s, 1H), 3.20 (br s,
H), 2.28-2.18 (m, 2H), 1.14 (d, J = 6.8 Hz, 3H), 1.13 (d, J
=
6.8 Hz, 3H), 1.07 (d, J = 6.7 Hz, 3H), 1.05 (d, J = 6.9
2 4
over Na SO and the solvent removed under reduced
13
Hz, 3H). C-NMR (100 MHz, CDCl
146.1, 143.7, 139.7, 133.1, 131.0, 129.9, 128.9, 128.1,
25.5, 123.9, 123.9, 97.5, 72.2, 28.5, 28.5, 24.4, 24.3, 24.2.
One signal is missing due to signal overlapping. MS (EI):
3
)  = 149.3, 146.2,
pressure. Colorless solid (257 mg, 0.996 mmol, 99%).
2
1
1
[
]
D
+20.2 (c 1.0 in CHCl
3 3
). H-NMR (400 MHz, CDCl )
1

= 7.85 (dd, J = 7.9, 1.1 Hz, 1H), 7.78 (dd, J = 7.8, 1.6
Hz, 1H), 7.41 (dt, J = 7.6, 1.1 Hz, 1H), 7.04 (m, 1H), 5.67
•+
m/z = 461 [M] . HR-MS (EI): m/z calculated for
(
1
1
d, J = 2.2 Hz, 1H), 2.68 (d, J = 2.2 Hz, 1H), 2.43 (br s,
•+
1
3
21 3
C H24IN O [M] : 461.09641, found 461.09801. IR
-1
H). C-NMR (100 MHz, CDCl
3
)  = 142.1, 139.9, 130.5,
ν
1
max/cm 3296 (br), 2964, 2872, 1459, 1363, 1220, 1053,
009, 747, 665.
29.0, 128.2, 98.3, 82.7, 75.5, 68.5.
General procedure for the synthesis of 1,4-triazoles
GP1): To a suspension of (S)-7 (1.0 equiv.) in distilled
(
R)-(2-Iodophenyl)(1-(naphthalen-1-yl)-1H-1,2,3-
(
triazol-4-yl)methanol ((R)-9d) was prepared according to
GP1 at room temperature using azidonaphthalene and
water (1 M) were added the corresponding azide (1.3
equiv.) and tris(1-benzyl-1H-1,2,3-triazol-4-yl)methanol
copper chloride (0.005 equiv.). The reaction mixture was
vigorously stirred for 17 h at the temperature specified
below. The precipitate formed was dissolved in EtOAc, the
phases separated and the aqueous layer was extracted with
EtOAc (three times). The combined organic layers were
obtained as off white solid (310 mg, 0.725 mmol, 73%).
1
Melting point: 132 °C. H-NMR (400 MHz, CDCl
3
)

= 8.01-7.97 (m, 1H), 7.94-7.92 (m, 1H), 7.85 (dd, J =
.8, 1.1 Hz, 1H), 7.81 (dd, J = 7.8, 1.7 Hz, 1H), 7.60-7.49
7
(
m, 6H), 7.44 (dt, J = 7.5 , 1.1 Hz, 1H), 7.03 (dt, J = 7.6,
13
1
.7 Hz, 1H), 6.40 (s, 1H), 3.34 (br s, 1H). C-NMR
2 4
washed with brine, dried over Na SO and the solvent was
removed under reduced pressure. The crude product was
purified by recrystallization from toluene.
(
100 MHz, CDCl
3
)  = 149.6, 143.8, 139.7, 134.2, 133.6,
1
1
30.6, 130.0, 129.0, 128.6, 128.4, 128.2, 128.1, 127.2,
25.0, 125.0, 123.8, 122.4, 97.7, 72.4. MS (EI): m/z = 427
•+
[
[
(
M] . HR-MS (EI): m/z calculated for C19H14IN O
3
(
R)-(1-Benzyl-1H-1,2,3-triazol-4-yl)(2-iodophenyl)-
•
+
-
1
M+Na] : 427.01816, found 427.01653. IR νmax/cm 3156
methanol ((R)-9a) was prepared according to GP1 at room
br), 1709, 1438, 1359, 1222, 1193, 1117, 1041, 759, 667.
temperature using benzyl azide and obtained as a white
solid (374 mg, 0.956 mmol, 96%). Melting point: 132 °C.
1
(R)-(1-Benzhydryl-1H-1,2,3-triazol-4-yl)(2-iodophenyl)-
methanol ((R)-9e)was prepared according to GP1 at 70 °C
using diphenylmehtyl azide and obtained as white solid
H-NMR (400 MHz, CDCl )  = 7.82 (dd, J = 7.9, 1.1 Hz,
3
1
7
1
H), 7.63 (dd, J = 7.8, 1.6 Hz, 1H), 7.40-7.33 (m, 4H),
.23-7.20 (m, 2H), 7.18 (s, 1H), 7.00 (dt, J = 7.7, 1,7 Hz,
13
(461 mg, 1.30 mmol, 99%). Melting point: 147-148 °C.
H), 6.20 (s, 1H), 5.48 (s, 2H), 3.24 (br s, 1H). C-NMR
1
H-NMR (400 MHz, CDCl )  = 7.81 (d, J = 7.80 Hz, 1H),
3
(
100 MHz, CDCl
3
)  = 150.0, 143.9, 139.6, 134.6, 129.9,
7
.63 (d, J = 7.8 Hz, 1H), 7.39-7.34 (m, 7H), 7.15-6.98 (m,
1
29.2, 128.9, 128.8, 128.2, 128.0, 122.0, 97.8, 72.5, 54.4.
13
•+
7H), 6.2 (s, 1H), 3.32 (br s, 1H). C-NMR (100 MHz,
CDCl )  = 149.3, 143.7, 139.6, 138.0, 138.0, 129.8, 129.1,
129.0, 128.3, 128.1, 122.2, 97.8, 72.4, 68.4. MS (EI):
MS (EI): m/z = 391 [M] . HR-MS (ESI): m/z calculated
+
3
for C16
IR νmax/cm 3471 (br), 3105, 3054, 1432, 1225, 1123,
055, 1003, 751, 713.
H14IN NaO [M+Na] : 414.00738, found 414.00697.
3
-1
•+
m/z = 467 [M] . HR-MS (ESI): m/z calculated for
1
+
C H18IN NaO [M+Na] : 490.03868, found 490.03851. IR
22 3
-1
ν
max/cm 3293 (br), 1712, 1454, 1225, 1126, 1051, 1003,
49, 694, 666.
(
R)-(2-Iodophenyl)(1-phenyl-1H-1,2,3-triazol-4-
yl)methanol ((R)-9b) was prepared according to GP1 at
0 °C using azidobenzene and obtained as white solid
305 mg, 0.808 mmol, 81%). Melting point: 129-130 °C.
7
7
(
R)-(1-Benzyl-1H-1,2,3-triazol-5-yl)(2-iodophenyl)-
(
1
methanol ((R)-9f): (S)-7 (50 mg, 0.193 mmol, 1.0 equiv.)
H-NMR (400 MHz, CDCl
3
)  = 7.86-7.84 (m, 1H), 7.74-
was dissolved in dry THF (1 mL). Subsequently, benzyl
azide
7
.66 (m, 4H), 7.50-7.39 (m, 4H), 7.06-7.02 (m, 1H), 6.32
(29.1 l,
0.232 mmol,
1.2 equiv.)
and
6
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201700246
Cp*Ru(C10
H
8
)BF
4
(0.87 mg, 1.93 µmol, 0.01 equiv.) were
(R)-1-Benzyl-4-(((tert-butyldiphenylsilyl)oxy)(2-
iodophenyl)methyl)-1H-1,2,3-triazole ((R)-5c): To
added. The resulting mixture was stirred for 17 h at 45 °C.
a
EtOAc (2 mL) and H
2
O (3 mL) were added and phases
solution of (R)-9a (70.0 mg, 0.179 mmol, 1.0 equiv.) in dry
DCM (1.5 mL) imidazole (24.3 mg, 0.358 mmol, 2.0
equiv.) and tert-butyldiphenylsilyl chloride (55.8 l,
0.215 mmol, 1.2 equiv.) were added consecutively. The
resulting mixture was stirred at room temperature for 16 h.
were separated. The aqueous layer was extracted with
EtOAc (3 x 2 mL) and the combined organic layers were
2 4
washed with brine, dried over Na SO and the solvent was
removed under reduced pressure. The crude product was
purified by column chromatography on silica gel using
cyclohexane and EtOAc (2:1 to 1:1) to obtain (R)-9f as
2
Subsequently DCM (3 mL) and H O (3 mL) were added
and the phases were separated. The aqueous layer was
extracted with DCM (3 x 3mL) and the combined organic
1
light brown oil (70 mg, 0.179 mmol, 93%). H-NMR
(
(
400 MHz, CDCl
3
)  = 7.75 (dd, J = 7.9, 1.1 Hz, 1H), 7.48
2 4
layers were washed with brine, dried over Na SO and the
dd, J = 7.8, 1.6 Hz, 1H), 7.35 (td, J = 7.6, 1.0 Hz, 1H),
solvent was removed under reduced pressure. The crude
product was purified by column chromatography on silica
gel using cyclohexane and EtOAc (15:1 to 7:1) to obtain
7
1
1
.32-7.23 (m, 5H), 7.01 (td, J = 7.7, 1.7 Hz, 1H), 6.95 (s,
H), 5.83 (s, 1H), 5.66 (d, J = 15.2 Hz, 1H), 5.61 (d, J =
1
3
1
5.2 Hz, 1H), 3.81 (br s, 1H). C-NMR (100 MHz,
(R)-5c as a colorless oil (98.0 mg, 0.155 mmol, 87%). H-
CDCl
3
)  = 142.3, 139.7, 138.3, 134.5, 134.1, 130.3, 129.1,
3
NMR (400 MHz, CDCl )  = 8.01 (dd, J = 7.8, 1.6 Hz,
1
28.9, 128.6, 128.1, 128.0, 97.7, 70.2, 52.8. MS (EI):
1H), 7.66 (dd, J = 7.9, 1.1 Hz), 7.56-7.54 (m, 2H), 7.49-
7.46 (m, 2H), 7.41 (dt, J = 7.5, 1.0 Hz, 1H), 7.39-7.33 (m,
5H), 7.27-7.21 (m, 5H), 7.12-7.08 (m, 2H), 6.94 (dt, J =
7.7, 1.7 Hz, 1H), 6.87 (s, 1H), 6.07 (s, 1H), 5.40 (d, J =
•+
m/z = 391 [M] . HR-MS (EI): m/z calculated for
•
+
16 3
C H14IN O [M] : 391.01816, found 391.02008. IR
-1
ν
8
max/cm 3159 (br), 1712, 1461, 1438, 1234, 1056, 1009,
33, 749, 693.
1
3
15.0, 1H), 5.35 (d, J = 15.0 Hz, 1H), 1.04 (s, 9H). C-
NMR (100 MHz, CDCl
3
)  = 149.7, 144.5, 139.0, 136.0,
1
1
5
36.0, 135.0, 133.3, 133.0, 129.9, 129.7, 129.3, 129.1,
(
R)-1-Benzyl-4-((2-iodophenyl)(methoxy)methyl)-1H-
,2,3-triazole ((R)-5a): (R)-9a (200 mg, 0.512 mmol, 1.0
equiv.) was dissolved in dry THF (2 mL) and cooled to
°C. NaH (60% in mineral oil, 26.6 mg, 0.665 mmol, 1.3
equiv.) was added and the resulting mixture was stirred for
0 minutes at room temperature. The reaction mixture was
cooled to 0 °C and iodomethane (38,2 µL, 0.614 mmol,
.2 equiv.) was added. After stirring for an additional 2 h
at room temperature EtOAc (3 mL) and saturated NaHCO
29.0, 128.6, 128.6, 128.0, 127.7, 127.6, 122.3, 97.3, 73.8,
1
3.9, 27.0, 19.5. HR-MS (ESI): m/z calculated for
+
C
32
H
33IN
3
OSi [M+H] : 630.14321, found 630.14293. IR
0
-
1
ν
max/cm 2932, 2856, 1712, 1427, 1362, 1225, 1111, 1043,
22, 699.
8
3
1
General procedure for the synthesis of O-trialkylsilyl
protected iodoarenes (GP2): The corresponding
iodoarene (R)-9a – (R)-9e (1.0 equiv.) was dissolved in dry
DCM (0.15m) and cooled to 0°C. Then 2,6-lutidine (2
3
(
5 mL) were added. The phases were separated and the
aqueous layer was extracted with EtOAc (3 x 5 mL). The
combined organic layers were washed with brine, dried
equiv.)
and
the
corresponding
trialkylsilyl
over Na
2
SO
4
and the solvent was removed under reduced
trifluoromethanesulfonate (1.2 equiv.) were added
consecutively and the reaction mixture was stirred for 6 h
pressure. The crude product was purified by column
chromatography on silica gel using cyclohexane and
2
at room temperature. Distilled H O was added, the phases
EtOAc (10:1 to 5:1) to obtain (R)-5a as a white solid
separated and the aqueous phase was extracted with DCM
(three times). The combined organic layers were washed
1
(
196 mg, 0.484 mmol, 94%). Melting point: 69-70 °C. H-
NMR (400 MHz, CDCl
3
)  = 7.84 (dd, J = 7.9, 1.1 Hz,
2 4
with brine, dried over Na SO and the solvent was
1
7
1
3
1
1
H), 7.58 (dd, J = 7.8, 1.6 Hz, 1H), 7.42-7.33 (m, 4H),
removed under reduced pressure. The crude product was
purified by column chromatography on silica gel using
cyclohexane and EtOAc (20:1 to 7:1).
.24-7.22 (m, 2H), 7.20 (s, 1H), 7.04-7.00 (m, 1H), 5.73 (s,
H), 5.53 (d, J = 15.0 Hz, 1H), 5.47 (d, J = 15.0 Hz, 1H),
1
3
.44 (s, 3H). C-NMR (100 MHz, CDCl )  = 148.4,
3
42.1, .139.7, 134.7, 129.9, 129.2, 128.8, 128.2, 128.0,
(
R)-1-Benzyl-4-(((tert-butyldimethylsilyl)oxy)(2-iodoph
22.4, 98.9, 81.3, 57.4, 54.2. HR-MS (ESI): m/z calculated
enyl)methyl)-1H-1,2,3-triazole ((R)-5d) was prepared
following GP2 from (R)-9a (250 mg, 0.64 mmol) and tert-
butyldimethylsilyl trifluoromethanesulfonate (176 µL,
+
for C17
H
16IN
3
NaO [M+Na] : 428.02303, found 428.02288.
-
1
IR νmax/cm 3111, 2942, 2824, 1712, 1432, 1339, 1190,
085, 834, 746.
1
0
0
.766 mmol) and obtained as a white solid (304 mg,
1
.601 mmol, 94%). Melting point: 94-95 °C. H-NMR
(
R)-1-Benzyl-4-((benzyloxy)(2-iodophenyl)methyl)-1H-
,2,3-triazole ((R)-5b): (R)-9a (200 mg, 0.512 mmol, 1.0
equiv.) was dissolved in dry DMF (2 mL) and cooled to
°C. NaH (60% in mineral oil, 26.6 mg, 0.665 mmol, 1.3
equiv.) was added and the resulting mixture was stirred for
0 minutes at room temperature. The reaction mixture was
cooled to 0 °C and benzyl bromide (72.9 µL, 0.614 mmol,
.2 equiv.) was added. After stirring for additional 2 h at
room temperature EtOAc (3 mL) and saturated NaHCO
(400 MHz, CDCl
3
)  = 7.77 (dd, J = 7.9, 1.1 Hz, 1H), 7.69
1
(dd, J = 7.8, 1.6 Hz, 1H), 7.38-7.31 (m, 4H), 7.20-7.18 (m,
2H), 7.10 (s, 1H), 6.96 (td, J = 7.7, 1.7 Hz, 1H), 6.15 (s,
1H), 5.50 (d, J = 15.1 Hz, 1H), 5.44 (d, J = 15.1 Hz, 1H),
0
13
0.87 (s, 9H), 0.07 (s, 3H), 0.05 (s, 3H). C-NMR
3
3
(100 MHz, CDCl )  = 151.3, 145.2, 139.4, 135.0, 129.4,
129.1, 128.7, 128.5, 128.4, 127.9, 121.8, 97.3, 73.6, 54.1,
26.0, 18.4, -4.60. One signal is missing due to signal
1
3
overlapping. HR-MS (ESI): m/z calculated for
+
(
5 mL) were added. The phases were separated and the
C
ν
22
H
29IN
3
OSi [M+H] : 506.11191, found 506.11225. IR
-
1
aqueous layer was extracted with EtOAc (3 x 5 mL). The
combined organic layers were washed with brine, dried
max/cm 3137, 2926, 2849, 1715, 1461, 1362, 1250, 1089,
834, 742.
2 4
over Na SO and the solvent was removed under reduced
pressure. The crude product was purified by column
chromatography on silica gel using cyclohexane and
(
R)-1-Benzyl-4-((2-iodophenyl)((triisopropylsilyl)oxy)-
methyl)-1H-1,2,3-triazole ((R)-5e) was prepared
following GP2 from (R)-9a (250 mg, 0.64 mmol) using
EtOAc (10:1 to 5:1) to obtain (R)-5b as a white solid
1
(
232 mg, 0.482 mmol, 94%). Melting point: 83 °C. H-
triisopropylsilyl
trifluoromethanesulfonate
(206 µL,
NMR (400 MHz, CDCl
3
)  = 7.83 (dd, J = 7.9, 1.0 Hz,
0
0
1
.766 mmol) and obtained as white solid (337 mg,
1
7
1
4
H), 7.67 (dd, J = 7.8, 1.6 Hz, 1H), 7.42-7.25 (m, 9H),
21
.617 mmol, 96%). Melting point: 60 °C. []
D
+17.4 (c
.23-7.21 (m, 3H), 7.01 (dt, J = 7.7, 1.7 Hz, 1H), 5.93 (s,
H), 5.51 (d, J = 15.0 Hz, 1H), 5.44 (d, J = 15.0 Hz, 1H),
1
3 3
.0 in CHCl ). H-NMR (400 MHz, CDCl )  = 7.79-7.74
(
(
m, 2H), 7.38-7.31 (m, 4H), 7.20-7.16 (m, 3H), 6.97-6.93
13
.64 (d, J = 11.6 Hz, 1H), 4.58 (d, J = 11.6 Hz, 1H). C-
m, 1H), 6.25 (s, 1H), 5.51 (d, J = 15.1 Hz, 1H), 5.43 (d, J
NMR (100 MHz, CDCl
3
)  = 148.6, 142.3, .139.7, 137.8,
34.7, 129.9, 129.2, 128.8, 128.5, 128.1, 128.1, 127.9,
22.5, 119.7, 98.4, 79.2, 71.3, 54.2. HR-MS (ESI): m/z
=
15.1 Hz, 1H), 1.89-1.10 (m, 3H), 0.99-0.96 (m, 18H).
1
1
13
C-NMR (100 MHz, CDCl )  = 151.5, 145.7, 139.2,
3
1
9
35.1, 129.3, 129.1, 128.6, 128.6, 128.3, 127.8, 121.7,
7.2, 73.5, 54.1, 18.0, 12.4. One signal is missing due to
+
calculated for C23
H
20IN
3
NaO [M+Na] : 504.05433, found
-
1
5
1
04.05415. IR νmax/cm 3134, 2853, 1715, 1457, 1327,
222, 1095, 1049, 749, 714.
overlapping. HR-MS (ESI): m/z calculated for
+
C H35IN OSi [M+H] : 548.15941, found 548.15866. IR
ν
25 3
-1
max/cm 3134, 2942, 2863, 1712, 1461, 1368, 1091, 885,
7
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201700246
8
23, 690. HPLC (OM column), Hexane–i-PrOH = 98:2 as
triisopropylsilyl
trifluoromethanesulfonate
(58.0 µL,
[
20]
eluent, 1.0 mL/min, t = 17.5 min, for >99.99% ee.
0.215 mmol) and obtained as a colorless oil (14.5 mg,
1
0
.027 mmol, 15%). H-NMR (400 MHz, CDCl )  = 7.93
3
(
s, 1H), 7.71 (dd, J = 7.9, 1.1 Hz, 1H), 7.50 (dd, J = 7.9,
(
R)-4-((2-Iodophenyl)((triisopropylsilyl)oxy)methyl)-1-
1
6
.7 Hz, 1H), 7.23-7.17 (m, 4H), 6.90-6.86 (m, 1H), 6.85-
.82 (m, 2H), 6.21 (s, 1H), 5.57 (d, J = 15.9 Hz, 1H), 5.52
phenyl-1H-1,2,3-triazole ((R)-5f) was prepared following
GP2 from (R)-9b (250 mg, 0.64 mmol) using
(
d, J = 15.9 Hz, 1H), 1.14-1.04 (m, 3H), 0.95-0.90 (m,
triisopropylsilyl
trifluoromethanesulfonate
(214 µL,
13
1
3
8H). C-NMR (100 MHz, CDCl )  = 142.5, 139.8,
0
0
.795 mmol) and obtained as white solid (331 mg,
1
139.5, 135.2, 134.5, 130.2, 129.4, 128.8, 128.6, 127.8,
.620 mmol, 94%). Melting point: 60 °C. H-NMR
)  = 7.85 (dd, J = 7.8, 1.7 Hz, 1H), 7.80
dd, J = 7.9, 1.1 Hz, 1H), 7.70-7.67 (m, 3H), 7.50-7.37 (m,
H), 7.00 (dt, J = 7.7, 1.7 Hz, 1H), 6.36 (s, 1H), 1.27-1.16
1
26.6, 97.6, 72.5, 52.6, 18.0, 18.0, 12.5. HR-MS (ESI): m/z
(
(
400 MHz, CDCl
3
+
calculated for C25
48.15867.
3
H35IN OSi [M+H] : 548.15886, found
5
4
1
3
(
3
m, 3H), 1.06-1.02 (m, 18H). C-NMR (100 MHz, CDCl )

= 151.9, 145.6, 139.3, 137.3, 129.8, 129.5, 128.7, 128.4,
20.6, 119.6, 97.4, 73.5, 18.1, 18.1, 12.4. One signal is
Enantioselective oxidative spirocyclization
1
missing due to overlapping. HR-MS (ESI): m/z calculated
General procedure for the asymmetric oxidative
spirocyclization
+
for C24
IR νmax/cm 3127, 3060, 2942, 2866, 1712, 1461, 1234,
042, 881, 678.
H33IN OSi [M+H] : 534.14321, found 534.14296.
3
-1
1
Yields and enantioselectivities of the corresponding
spirolactones 11 vary depending on the following
methods and are given in table 2.
(
R)-1-(2,6-Diisopropylphenyl)-4-((2-iodophenyl)((triisop
ropylsilyl)oxy)methyl)-1H-1,2,3-triazole ((R)-5g) was
prepared following GP2 from (R)-9c (100 mg,
Method A: The appropriate naphthol derivative 10
0
.216 mmol)
using
triisopropylsilyl
(
1.0 equiv.) was dissolved in dichloromethane (0.02M) and
trifluoromethanesulfonate (70.0 µL, 0.260 mmol) and
cooled to 0 °C. Then the chiral iodoarene (1.0 equiv.) and
mCPBA (1.3 equiv.) were added consecutively. The
reaction mixture was stirred at 0 °C until full conversion of
the starting material (indicated by TLC). Saturated
obtained as a white solid (109 mg, 0.180 mmol, 82%).
Melting point: 77-78 °C. H-NMR (400 MHz, CDCl
1
3
)

= 7.87 (dd, J = 7.9, 1.7 Hz, 1H), 7.80 (dd, J = 7.9, 1.1
Hz, 1H), 7.46-7.39 (m, 3H), 7.25-7.23 (m, 2H), 6.98 (dt, J
7.7, 1.7 Hz 1H), 6.35 (s, 1H), 2.32-2.13 (m, 2H), 1.26-
2 2 3 2 3
Na S O and 1M Na CO were added and the phases were
=
1
1
3
separated. The aqueous layer was extracted with EtOAc
three times) and the combined organic layers were washed
.17 (m, 3H), 1.13-1.02 (m, 30H). C-NMR (100 MHz,
)  = 150.6, 146.3, 146.2, 145.4, 139.4, 133.5, 130.7,
29.4, 128.6, 128.5, 125.1, 123.9, 123.8, 97.2, 73.3, 28.4,
8.4, 24.4, 24.4, 24.3, 24.1, 24.1, 18.1, 12.4. One signal is
(
CDCl
3
2 4
with brine and dried over Na SO . The solvent was
1
2
removed under reduced pressure and the crude product was
purified by column chromatography on silica gel using
cyclohexane and EtOAc (4:1 to 2:1).
missing due to overlapping. HR-MS (ESI): m/z calculated
+
for C30
IR νmax/cm 2971, 2946, 2866, 1712, 1461, 1362, 1086,
032, 834, 665.
H45IN OSi [M+H] : 618.23711, found 618.23676.
3
-1
1
Method B: The appropriate naphthol derivative 10
(
1 equiv.) was dissolved in dichloromethane (0.02m) and
cooled to -20 °C. Then the chiral iodoarene (1 equiv.) and
mCPBA (1.3 equiv.) were added consecutively. The
reaction mixture was stirred at this temperature until full
conversion of the starting material as indicated by TLC.
(
(
R)-4-((2-Iodophenyl)((triisopropylsilyl)oxy)methyl)-1-
naphthalen-1-yl)-1H-1,2,3-triazole ((R)-5h) was
prepared following GP2 from (R)-9d (100 mg,
0
.234 mmol)
using
triisopropylsilyl
2 2 3 2 3
Saturated Na S O and 1m Na CO were added and the
trifluoromethanesulfonate (75.0 µL, 0.281 mmol) and
phases were separated. The aqueous layer was extracted
with EtOAc (three times) and the combined organic layers
obtained as a white solid (123 mg, 0.211 mmol, 90%).
1
Melting point: 125 °C. H-NMR (400 MHz, CDCl
3
)
2 4
were washed with brine and dried over Na SO . The

= 8.00-7.96 (m, 1H), 7.95-7.92 (m, 1H), 7.91 (dd, J =
.8, 1.7 Hz, 1H), 7.82 (dd, J = 7.9, 1.1 Hz, 1H), 7.67 (d, J
0.4 Hz, 1H), 7.59-7.49 (m, 5H), 7.45-7.41 (m, 1H), 7.00
solvent was removed under reduced pressure and the crude
product was purified by column chromatography on silica
gel using cyclohexane and EtOAc (4:1 to 2:1).
7
=
(
dt, J = 7.7, 1.7 Hz, 1H), 6.43 (s, 1H), 1.31-1.20 (m, 3H),
13
1

1
1
.10-1.05 (m, 18H).
3
C-NMR (100 MHz, CDCl )
= 151.0, 145.6, 139.4, 134.2, 134.0, 130.4, 129.5, 128.8,
28.7, 128.5, 128.3, 127.9, 127.1, 125.1, 124.5, 123.7,
Method C: The appropriate naphthol derivative 10
(1 equiv.) was dissolved in dichloromethane (0.02m) and
cooled to 0 °C. Then the chiral iodoarene (0.15 equiv.) and
mCPBA (1.3 equiv.) were added consecutively. The
reaction mixture was stirred at this temperature until full
conversion of the starting material as indicated by TLC.
22.6, 97.4, 73.5, 18.1, 18.1, 12.4. HR-MS (ESI): m/z
+
calculated for C28
H
35IN
3
OSi [M+H] :584.15886, found
-
1
5
84.15874. IR νmax/cm 2946, 2863, 1712, 1461, 1364,
222, 1034, 835, 770, 658.
1
2 2 3 2 3
Saturated Na S O and 1m Na CO were added and the
phases were separated. The aqueous layer was extracted
with EtOAc (three times) and the combined organic layers
(
R)-1-Benzhydryl-4-((2-iodophenyl)((triisopropylsilyl)o
xy)methyl)-1H-1,2,3-triazole ((R)-5i) was prepared
following GP2 from (R)-9e (100 mg, 0.234 mmol) using
2 4
were washed with brine and dried over Na SO . The
solvent was removed under reduced pressure and the crude
product was purified by column chromatography on silica
gel using cyclohexane and EtOAc (4:1 to 2:1).
triisopropylsilyl
trifluoromethanesulfonate
(69.0 µL,
0
0
7
(
(
(
.256 mmol) and obtained as a colorless oil (128 mg,
1
.205 mmol, 96%). H-NMR (400 MHz, CDCl
3
)  = 7.79-
.75 (m, 2H), 7.38-7.32 (m, 7H), 7.21 (s, 1H), 7.10-7.05
m, 4H), 7.04 (s, 1H), 6.95 (dt, J = 7.7, 1.7 Hz, 1H), 6.24
s, 1H), 1.18-1.09 (m, 3H), 0.98-.095 (m, 18H). C-NMR
100 MHz, CDCl
4'-Dihydro-1'H,5H-spiro[furan-2,2'-naphthalene]-1',5-
13
dione (11a): White solid (13.1 mg, 0.061 mmol, 61%).
[
13]
1
3
)  = 150.8, 145.4, 139.3, 138.4, 138.4,
29.3, 128.9, 128.6, 128.5, 128.5, 128.4, 128.3, 128.2,
21.9, 97.2, 73.4, 68.1, 18.0, 12.3. Several signals are
Melting point: 100 °C (lit.: 104-105 °C).
H-NMR
1
1
3
(400 MHz, CDCl )  = 8.00 (d, J = 7.7 Hz, 1H), 7.64-7.60
(m, 1H), 7.41-7.38 (m, 1H), 7.26 (d, J = 8.2 Hz, 1H), 6.65
(d, J = 9.0 Hz, 1H), 6.19 (d, J = 9.9 Hz, 1H), 2.94-2.85 (m,
missing due to overlapping. HR-MS (ESI): m/z calculated
+
for C31
IR νmax/cm 2942, 2866, 1713, 1457, 1362, 1222, 1085,
009, 882, 691.
H
39IN
3
OSi [M+H] : 624.19016, found 624.18990.
1H), 2.62-2.55 (m, 1H), 2.44-2.38 (m, 1H), 2.22-2.14 (m,
-
1
13
1H). C-NMR (100 MHz, CDCl
3
)  = 196.7, 176.6, 136.9,
1
135.8, 132.4, 129.1, 128.1, 128.1, 127.9, 127.5, 83.5, 31.4,
+
-1
2
2
6.7. MS (ESI): m/z = 237 [M+Na] . IR νmax/cm 2362,
343, 1772, 1683, 1450, 1291, 1175, 930, 779, 690. HPLC
(
R)-1-Benzyl-5-((2-iodophenyl)((triisopropylsilyl)oxy)-
(
OM column), Hexane–i-PrOH = 85:15 as eluent, 1.0
methyl)-1H-1,2,3-triazole (5j) was prepared following
GP2 from (R)-9f (70 mg, 0.179 mmol) using
mL/min, t
S
= 27.0 min (major), t
R
= 22.8 min (minor), for
8
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
8
6% ee (>99.9% ee after a single recrystallization from
4'-Methyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
isopropanol).
naphthalene]-1',5-dione (11g): White solid (15.4 mg,
1
0
.067 mmol, 67%). Melting point: 94 °C. H-NMR
(
(
400 MHz, CDCl
3
)  = 8.02 (dd, J = 7.7, 1.4 Hz, 1H), 7.67
4
'-Chloro-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
td, J = 7.6, 1.5 Hz, 1H), 7.44–7.38 (m, 2H), 6.01 (d, J =
naphthalene]-1',5-dione (11b): White solid (19.2 mg,
1
1.5 Hz, 1H), 2.94–2.81 (m, 1H), 2.62–2.52 (m, 1H), 2.44–
0
.077 mmol, 77%). Melting point: 148 °C. H-NMR
13
2
.33 (m, 1H), 2.24–2.09 (m, 4H). C-NMR (100 MHz,
CDCl )  = 196.9,.176.7, 138.1, 135.7, 133.3, 129.1, 128.8,
28.0, 127.5, 125.0, 83.7, 31.6, 27.0, 19.4. MS (ESI):
(
400 MHz, CDCl
3
)  = 8.07-8.05 (m, 1H), 7.79-7.73 (m,
3
2
2
H), 7.54-7.50 (m, 1H), 6.4 (s, 1H), 2.95-2.85 (m, 1H),
.66-2.58 (m, 1H), 2.49-2.42 (m, 1H), 2.28-2.20 (m, 1H).
1
+
-1
13
m/z = 251 [M+Na] . IR νmax/cm 2359, 1779, 1684, 1594,
450, 1170, 1137, 930, 761, 645. HPLC (ZM column),
Hexane–i-PrOH = 90:10 as eluent, 0.3 mL/min, t
0.9 min (minor), t = 58.3 min (major), for 76% ee.
C-NMR (100 MHz, CDCl )  = 194.8, 175.9, 136.0,
3
1
1
2
1
34.7, 132.0, 130.3, 129.3, 128.2, 127.5, 126.3, 83.6, 31.6,
+ -1
R
=
6.7. MS (ESI): m/z = 271 [M+Na] . IR νmax/cm 2359,
5
S
779, 1690, 1594, 1291, 1188, 1161, 1025, 927, 763.
HPLC (ZM column), Hexane–i-PrOH = 80:20 as eluent,
0
.3 mL/min, t
R
= 19.6 min (minor), t
S
= 26.9 min (major),
4'-Ethyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
naphthalene]-1',5-dione (11h): White solid (16.1 mg,
for 80% ee.
0
9
7
.066 mmol, 66%). Melting point: 94-95 °C (lit.: 96-
[13] 1
7 °C).
3
H-NMR (400 MHz, CDCl )  = 8.03 (dd, J =
4
'-Bromo-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
.7, 1.4 Hz, 1H), 7.66 (td, J = 7.7, 1.5 Hz, 1H), 7.48–7.43
naphthalene]-1',5-dione (11c): White solid (21.6 mg,
1
(m, 1H), 7.41 (td, J = 7.5, 1.1 Hz, 1H), 6.00-6.00 (m, 1H),
0
.072 mmol, 72%). Melting point: 160 °C. H-NMR
2
2
.95–2.81 (m, 1H), 2.62–2.53 (m, 3H), 2.44–2.34 (m, 1H),
(
400 MHz, CDCl
3
)  = 8.04-8.02 (m, 1H), 7.76-7.71 (m,
13
.23–2.08 (m, 1H), 1.24 (t, J = 7.4 Hz, 4H). C-NMR
)  = 197.0, 176.7, 138.4, 137.6, 135.6,
2
2
H), 7.53-7.47 (m, 1H), 6.67 (s, 1H), 2.93-2.84 (m, 1H),
.65-2.58 (m, 1H), 2.49-2.43 (m, 1H), 2.29-2.20 (m, 1H).
(
100 MHz, CDCl
3
13
128.6, 128.2, 127.7, 127.3, 124.5, 83.9, 31.7, 27.0, 25.2,
C-NMR (100 MHz, CDCl )  = 194.9, 175.8, 136.0,
3
+ -1
1
2.5. MS (ESI): m/z = 265 [M+Na] . IR νmax/cm 2957,
1
2
1
35.3, 133.6, 130.3, 129.0, 128.1, 127.5, 122.7, 84.4, 31.3,
+ -1
2871, 2359, 1782, 1714, 1364, 1217, 1170,1030, 933.
6.6. MS (ESI): m/z = 315 [M+Na] . IR νmax/cm 2359,
HPLC (ZM column), Hexane–i-PrOH = 90:10 as eluent,
0
775, 1690, 1587, 1291, 1186, 1033, 911, 764, 668. HPLC
R S
.3 mL/min, t = 39.4 min (minor), t = 50.4 min (major),
(
OM column), Hexane–i-PrOH = 90:10 as eluent, 1.0
for 76% ee.
mL/min, t
8% ee (94% ee after a single recrystallization from
isopropanol).
R S
= 29.6 min (minor), t = 32.1 min (major), for
7
4'-Propyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
naphthalene]-1',5-dione (11i): White solid (16.8 mg,
1
0
.065 mmol, 65%). Melting point: 92-93 °C. H-NMR
4
'-Benzoyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
(
(
400 MHz, CDCl
td, J = 7.7, 1.5 Hz, 1H), 7.46–7.37 (m, 2H), 5.98 (s, 1H),
3
)  = 8.03 (dd, J = 7.7, 1.4 Hz, 1H), 7.66
naphthalene]-1',5-dione (11d): White solid (13.1 mg,
0
1
7
7
2
2
1
1
.060 mmol, 60%). Melting point: 147 °C (lit.: 153-
[10] 1
2.93–2.81 (m, 1H), 2.62–2.56 (m, 1H), 2.55–2.47 (m, 2H),
54 °C).
3
H-NMR (400 MHz, CDCl )  = 8.11 (dd, J =
2
1

.44–2.36 (m, 1H), 2.21–2.10 (m, 1H), 1.69–1.59 (m, 2H),
.7, 1.1 Hz, 1H), 7.97-7.95 (m, 2H), 7.66-7.58 (m, 2H),
.51-7.45 (m, 3H), 7.41-7.39 (m, 1H), 6.38 (s, 1H), 2.95-
.85 (m, 1H), 2.65-2.57 (m, 1H), 2.55-2.49 (m, 1H), 2.32-
13
.02 (t, J = 7.3 Hz, 3H). C-NMR (100 MHz, CDCl
3
)
= 197.0, 176.7, 137.5, 136.9, 135.6, 128.6, 128.4, 128.2,
1
3
127.8, 124.7, 83.8, 34.5, 31.7, 27.0, 21.3, 14.0. HR-MS
.24 (m, 1H). C-NMR (100 MHz, CDCl )  = 195.4,
3
+
(ESI): m/z calculated for
2
C
16
H
16NaO
3
[M+Na] :
94.6, 176.0, 137.6, 136.1, 135.9, 134.5, 134.3, 134.2,
30.2, 129.9, 129.1, 128.6, 127.5 127.1, 82.8. 31.3, 26.4.
-
1
79.09917, found 279.09931. IR νmax/cm 2967, 2359,
+
-1
1780, 1714, 1597, 1364, 1171, 1030, 930, 748. HPLC (ZM
MS (ESI): m/z = 357 [M+Na] . IR νmax/cm 2362, 2343,
column), Hexane–i-PrOH = 85:15 as eluent, 0.3 mL/min,
1
768, 1660, 1594, 1447, 1197, 1040, 941, 687. HPLC (OM
column), Hexane–i-PrOH = 80:20 as eluent, 1.0 mL/min,
= 32.4 min (minor), t = 37.4 min (major), for 80% ee.
R S
t = 22.8 min (minor), t = 29.4 min (major), for 72% ee.
t
R
S
4
'-Acetyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
Acknowledgements
naphthalene]-1',5-dione (11e): White solid (19.4 mg,
1
0
.076 mmol, 76%). Melting point: 161 °C. H-NMR
We gratefully acknowledge Prof. Miquel A. Pericàs for the
chance to initiate this project in his lab and fruitful discussions as
well as the financial support by the DAAD (short term PhD
scholarship). CH also thanks EU-ITN network Mag(net)icFun
(
3
400 MHz, CDCl )  = 8.06 (dd, J = 7.7, 1.4 Hz, 1H),
7
6
3
.95–7.90 (m, 1H), 7.70-7.65 (m, 1H), 7.50-7.45 (m, 1H),
.80 (s, 1H), 2.91-2.81 (m, 1H), 2.65-2.58 (m, 1H), 2.55 (s,
1
3
H), 2.49-2.41 (m, 1H), 2.31-2.22 (m, 1H). C-NMR
(PITN-GA-2012-290248) for a secondment.
(
100 MHz, CDCl
3
)  = 199.0, 195.1, 175.7, 137.5, 136.9,
35.8, 133.2, 129.8, 128.6, 127.7, 127.5, 83.2, 31.2, 29.1,
6.2. HR-MS (ESI): m/z calculated for C15
1
2
[
H
12NaO
4
+
-1
M+H] : 279.06278, found 279.06283. IR νmax/cm 2355,
339, 1781, 1714, 1364, 1220, 1172, 1030, 931, 769.
HPLC (OM column), Hexane–i-PrOH = 75:25 as eluent,
.0 mL/min, t = 24.5 min (major), t = 31.2 min (minor),
for 68% ee.
References
2
1
S
R
[1]
a) T. Wirth, Angew. Chem. Int. Ed. 2005, 44,
656-3665; b) V. V. Zhdankin, P. J. Stang, Chem.
3
Rev. 2008, 108, 5299-5358; c) S. Quideau, L.
Pouységu, D. Deffieux, Synlett 2008, 467–495; d)
L. Pouységu, D. Deffieux, S. Quideau,
Tetrahedron 2010, 66, 2235-2261; e) L. F. Silva,
Jr., B. Olofsson, Nat. Prod. Rep. 2011, 28, 1722-
1754; f) A. Yoshimura, V. V. Zhdankin, Chem.
Rev. 2016, 116, 3328-3435.
4
'-Phenyl-3,4-dihydro-1'H,5H-spiro[furan-2,2'-
naphthalene]-1',5-dione (11f): White solid (21.0 mg,
1
0
.072 mmol, 72%). Melting point: 194 °C. H-NMR
(
3
400 MHz, CDCl )  = 8.09 (dd, J = 7., 1.2 Hz, 1H), 7.60-
7
7
1
.53 (m, 1H), 7.49-7.41 (m, 4H), 7.36-7.34 (m, 2H), 7.17-
.15 (m, 1H), 6.12 (s, 1H), 2.97 (m, 1H), 2.66-2.59 (m,
1
3
H), 2.56-2.50 (m, 1H), 2.32-2.34 (m, 1H). C-NMR
(
100 MHz, CDCl
3
)  = 196.6, 176.5, 140.0, 137.8, 137.5,
1
1
35.5, 130.7, 129.0, 128.9, 128.8, 128.6, 128.3, 127.8,
[2]
a) Iodine Chemistry and Applications (Ed.
T.Kaiho), Wiley-VCH, Weinheim, 2015, pp. 103-
+
27.5, 83.8, 31.6, 26.9. MS (ESI): m/z = 313 [M+Na] . IR
-1
ν
max/cm 2359, 1780, 1695, 1441, 1361, 1186, 1032, 930,
1
59; b) Topics in Current Chemistry, Hypervalent
7
72, 702. HPLC (OM column), Hexane–i-PrOH = 85:15 as
eluent, 1.0 mL/min, t = 22.6 min (major), t = 31.6 min
minor), for 80% ee (>99.9% ee after single
Iodine Chemistry (Ed. T. Wirth), Springer
International Publishing Switzerland, 2016.
S
R
(
a
[
21]
recrystallization from isopropanol).
9
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.201700246
[
[
3]
4]
For recent reviews on chiral hypervalent iodine
chemistry see: a) H. Liang, M. A. Ciufolini,
Angew. Chem. Int. Ed. 2011, 50, 11849-11851; b)
A. Parra, S. Reboredo, Chem. – Eur. J. 2013, 19,
Gong, Chem. - Eur. J. 2015, 21, 10314-10317; k)
M. Brown, R. Kumar, J. Rehbein, T. Wirth,
Chem. Eur. J. 2016, 22, 4030-4035; l) S.
Haubenreisser, T. H. Woste, C. Martinez, K.
Ishihara, K. Muniz, Angew. Chem. Int. Ed. 2016,
55, 413-417.
a) S. J. Murray, H. Muller-Bunz, H. Ibrahim,
Chem. Commun. 2012, 48, 6268-6270; b) S. J.
Murray, H. Ibrahim, Chem. Commun. 2015, 51,
2376-2379;.
1
2
2
7244-17260; c) A. M. Harned, Tetrahedron Lett.
014, 55, 4681-4689; d) F. Berthiol, Synthesis
015, 47, 587-603.
[11]
a) R. Pribram, Liebigs Ann. Chem., 1907, 351,
4
1
81-485; b) T. Imamoto, H. Koto, Chem. Lett.
986, 967-968; c) D. G. Ray, G. F. Koser, J. Am.
Chem. Soc. 1990, 112, 5672-5673; d) D. G. Ray,
G. F. Koser, J. Org. Chem. 1992, 57, 1607-1610;
e) M. Xia, Z.-C. Chen, Synth. Commun. 1997, 27,
[12]
[13]
M. Bekkaye, G. Masson, Synthesis 2016, 48, 302-
312.
Recently, Wirth and co-workers reported an
optical active iodoarene carrying a pyridine motif:
a) P. Mizar, A. Laverny, M. El-Sherbini, U. Farid,
M. Brown, F. Malmedy, T. Wirth, Chem. – Eur.
J. 2014, 20, 9910-9913. For application of a
triazol-based ligand in transition metal catalysis
see: b) V. de la Fuente, R. Marcos, X. C.
Cambeiro, S. Castillón, C. Claver, M. A. Pericàs,
Adv. Synth. Catal. 2011, 353, 3255-3261.
a) D. Xu, Z. Li, S. Ma, Tetrahedron Lett. 2003,
44, 6343-6346; b) C. Raminelli, J. V. Comasseto,
L. H. Andrade, A. L. M. Porto, Tetrahedron:
Asymmetry 2004, 15, 3117-3122.
a) S. Özçubukçu, E. Ozkal, C. Jimeno, M. A.
Pericàs, Org. Lett. 2009, 11, 4680-4683; b) E.
Ozkal, P. Llanes, F. Bravo, A. Ferrali, M. A.
Pericàs, Adv. Synth. Catal. 2014, 356, 857-869.
For details, see Supporting Informations.
The chiral iodoarene was reisolated in >95%. No
epimerization of the iodoarene was observed.
The significant drop in reactivity might be the
result of decreased catalyst solubility. The
development of modified catalysts with a good
solubility at even low temperatures is part of our
ongoing research.
1
321-1326; f) A. Y. Koposov, V. V. Boyarskikh,
V. V. Zhdankin, Org. Lett. 2004, 6, 3613-3615.
U. H. Hirt, B. Spingler, T. Wirth, J. Org. Chem.
[
[
5]
6]
1
998, 63, 7674-7679.
S. Quideau, G. Lyvinec, M. Marguerit, K.
Bathany, A. Ozanne-Beaudenon, T. Buffeteau, D.
Cavagnat, A. Chénedé, Angew. Chem. Int. Ed.
2
009, 48, 4605-4609.
[
7]
For recent reviews on oxidative spirocyclizations
see: a) W. T. Wu, L. M. Zhang, S. L. You, Chem.
Soc. Rev. 2016, 45, 1570-1580; b) L. Pantaine, X.
Moreau, V. Coeffard, C. Greck, Tetrahedron Lett.
[14]
[15]
2
016, 57, 2567-2574; c) W. S. Sun, G. F. Li, L.
Hong, R. Wang, Org. Biomol. Chem. 2016, 14,
164-2176. In the first example of an oxidative
2
spirocyclization using the C2-symmetric 1,1’-
bisindane 1, Wirth’s C1-symmetric (R)-2-(1-
methoxyethyl)-phenyl iodide gave only 1% ee: d)
T. Dohi, A. Maruyama, N. Takenaga, K. Senami,
Y. Minamitsuji, H. Fujioka, S. B. Caemmerer, Y.
Kita, Angew. Chem. Int. Ed. 2008, 47, 3787-3790.
e) T. Dohi, N. Takenaga, T. Nakae, Y. Toyoda,
M. Yamasaki, M. Shiro, H. Fujioka, A.
Maruyama, Y. Kita, J. Am. Chem. Soc. 2013, 135,
[16]
[17]
[18]
4
558-4566.
[19]
[20]
K. Barral, A. D. Moorhouse, J. E. Moses, Org.
Lett. 2007, 9, 1809-1811.
CCDC 1495386 contains the supplementary
crystallographic data for compound 2e. This
material is free of charge from the Cambridge
[
8]
a) M. Uyanik, T. Yasui, K. Ishihara, Angew.
Chem. Int. Ed. 2010, 49, 2175-2177; b) M.
Uyanik, T. Yasui, K. Ishihara, Tetrahedron 2010,
6
6, 5841-5851.
[
[
9]
M. Fujita, S. Okuno, H. J. Lee, T. Sugimura, T.
Okuyama, Tetrahedron Lett. 2007, 48, 8691-
Crystallographic
Data
Centre
via
www.ccdc.cam.uk/data_request/cif was deposited
CCDC 1495387 contains the supplementary
crystallographic data for compound 11f. This
material is free of charge from the Cambridge
8
694.
[21]
10]
a) M. Fujita, Y. Yoshida, K. Miyata, A.
Wakisaka, T. Sugimura, Angew. Chem. Int. Ed.
2
010, 49, 7068-7071; b) M. Fujita, M. Wakita, T.
Crystallographic
Data
Centre
via
Sugimura, Chem. Commun. 2011, 47, 3983-3985;
c) C. Röben, J. A. Souto, Y. González, A.
Lishchynskyi, K. Muñiz, Angew. Chem. Int. Ed.
www.ccdc.cam.uk/data_request/cif was deposited
2
011, 50, 9478-9482; d) U. Farid, T. Wirth,
Angew. Chem. Int. Ed. 2012, 51, 3462-3465; e) U.
Farid, F. Malmedy, R. Claveau, L. Albers, T.
Wirth, Angew. Chem. Int. Ed. 2013, 52, 7018-
7
022; f) W. Kong, P. Feige, T. de Haro, C.
Nevado, Angew. Chem. Int. Ed. 2013, 52, 2469-
473; g) M. Uyanik, T. Yasui, K. Ishihara,
2
Angew. Chem. Int. Ed. 2013, 52, 9215-9218; h) P.
Mizar, T. Wirth, Angew. Chem. Int. Ed. 2014, 53,
5
993-5997; i) B. Basdevant, C. Y. Legault, Org.
Lett. 2015. j) D.-Y. Zhang, L. Xu, H. Wu, L.-Z.
1
0
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
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Advanced Synthesis & Catalysis
10.1002/adsc.201700246
FULL PAPER
Modular Synthesis of Triazole-based Chiral
Iodoarenes for Enantioselective Spirocyclizations
Adv. Synth. Catal. Year, Volume, Page – Page
a
b
Christian Hempel, Caeciliea Maichle-Mössmer,
c
a*
Miquel A. Pericàs * and Boris J. Nachtsheim
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