Asymmetric Alkynylation of β-Ketoesters and Naphthols Promoted by New Chiral Biphenylic Iodanes

Article abstract of DOI:10.1002/chem.201703238

The preparation of new chiral biphenylic λ³-iodane reagents bearing transferable alkynyl ligands is described. These reagents transfer their carbon-based ligands onto β-ketoesters with an enantiomeric excess (ee) up to 68 %, and most remarkably, enable the dearomative alkynylation of naphthols in good to high yields up to 84 % ee.

Full text of DOI:10.1002/chem.201703238

A Journal of
Accepted Article
Title: Asymmetric Alkynylation of β-Ketoesters and Naphthols
Promoted by New Chiral Biphenylic Iodanes
Authors: Simon Companys, Philippe Peixoto, Cyril Bosset, Stefan
Chassaing, Karinne Miqueu, Jean-Marc Sotiropoulos, Laurent
Pouységu, and Stephane Quideau
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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to this Accepted Article as a result of editing. Readers should obtain
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201703238
Link to VoR: http://dx.doi.org/10.1002/chem.201703238
Supported by

10.1002/chem.201703238
Chemistry - A European Journal
COMMUNICATION
Asymmetric Alkynylation of -Ketoesters and Naphthols
Promoted by New Chiral Biphenylic Iodanes
Simon Companys, Philippe A. Peixoto, Cyril Bosset, Stefan Chassaing, Karinne Miqueu, Jean-Marc
Sotiropoulos, Laurent Pouységu,* and Stéphane Quideau*
O
A (1.0 equiv)
Abstract: The preparation of new chiral biphenylic
reagents bearing transferable alkynyl ligands is described.
These reagents transfer their carbon-based ligands onto

3-iodane
Previous works
KOtBu (1.0 equiv)
tBuOH, rt, 20 h
Ochiai
30% yield
53% ee
CO2Me
Ph
R

-
O
O
TMS-EBX (1.3 equiv)
B (3 mol%)
ketoesters with an enantiomeric excess (ee) up to 68%, and
most remarkably, enable the dearomative alkynylation of
naphthols in good to high yields up to 84% ee.
CO2CMe2Ph
Waser
CO2R
*
sat. KF, xylene, 0 °C to rt
83% yield
79% ee
O
b-ketoesters
R = alkyl group
C (1.2 equiv), B (3 mol%)
t
K2CO3 (1.2 equiv)
CO2 Bu
S
Maruoka
76% yield
94% ee
toluene, 0 °C, 72 h
Hypervalent organoiodine compounds, also referred to as
iodanes, are increasingly used in organic synthesis because
they offer metal-free alternatives for a wide range of selective
chemical transformations, many of which can be performed
asymmetrically by use of chiral variants of these iodanes.[1,2]
Beyond the recent progress made in asymmetric oxygenation,
amination and halogenation of alkenes, ketones or phenols,[3]
iodanes have also shown efficacy in carbon-based ligand
transfer events, such as trifluoromethylation, cyanation,
phenylation and alkynylation reactions.[4] However, successful
asymmetric versions of these carbon–carbon bond-forming
transformations relying on the use of chiral iodanes are rare. In
fact, the only example we are aware of is the use of the
binaphthylic 3-iodane A reported by Ochiai and co-workers to
promote the -phenylation of -ketoesters, albeit in moderate
yields and enantioselectivities (Scheme 1).[5] Other related
approaches to asymmetric -cyanation or -alkynylation of -
ketoesters are based on the use of achiral 3-iodanes of the
Ph
Ar
Br
Bu
Bu
FBF3
I
S
S
N
Ph
Bn
O
I
SiMe3
O
I
Ph
F3C
F3C
O
Ar
A
C
TMS-EBX
B, Ar = 3,4,5-F3C6H2
This work
O
O
asymmetric alkynylation using
chiral biphenylic iodanes
CO2R1
CO2R1
*
CO2Me
X
n
n
R5
Z
Z
b-ketoesters
R1 = alkyl, n = 1 or 2
Z = various substituents
I
R5
R5
*
O
I
R3
R2
X
D
R5
R2
R3
*
CO2Me
R5
R5 = alkyl or silyl group,
X = heteroatomic ligand
R4
R4
a-naphthols
or
O
R2 = silyloxy, R3 = alkyl or alkoxy, R4 = Br or aromatic
*
or
b-naphthols, R2 = alkoxy, R3 = silyloxy, R4 = H
benziodoxol(on)e type in the presence of
a
chiral
Scheme 1. Asymmetric phenylation and alkynylation reactions using iodanes.
organocatalyst.[4a,6] For example, alkynylations were reported to
occur with good to excellent enantioselectivities using Waser’s
TMS-EBX 3-iodane, or its analogue C, and Maruoka’s catalyst
B (Scheme 1).[4a,6b-d]
This investigation began with our atropisomerically pure
bis(iodoarenes) (R)- and (S)-1 as starting materials (Scheme
2).[3e] Application of the m-CPBA/p-TsOH-based one-pot
procedure reported by Olofsson for the synthesis of achiral
alkynyliodonium salts[9a] unfortunately led to quick degradation of
1 into intractable mixtures. However, the use of Selectfluor® in
acetonitrile/acetic acid (4:1)[9b,c] pleasingly led to a clean and
efficient conversion of 1 into the -oxo-bridged[9c,d] diiodosyl
diacetate 2a, which was engaged without further purification in
the first ligand exchange step by reaction with p-TsOH•H2O in
CH2Cl2/TFE (1:1) to give the ditosylate 2b (see the Supporting
Information). Next, addition of the alkynylboronic ester 3a or 3b
promoted the second ligand exchange step, thus affording the
desired bis(alkynyl-3-iodanes)[8] 4a and 4b as stable
amorphous beige powders in overall isolated yields of 80-85%
from 1 (Scheme 2). 13C NMR analysis was used to confirm the
oxidation state of the iodine centres on the basis of the chemical
shift of the aromatic ipso-carbon atom (Cipso-IIII) at 119.7 and
120.4 ppm for 4a and 4b, respectively (see the Supporting
Information).[9a,10] Moreover, the distinctive signal of the ethynylic
-carbon, which was assigned by a 2D HMBC experiment,
resonated at 114.8 and 113.7 ppm for 4a and 4b, respectively,
in agreement with literature data.[9a,10] Each pure atropisomer of
4a and 4b was also characterized by circular dichroism
measurements (see the Supporting Information). Attempts to get
The efficient stereoinduction shown by our axially chiral
biarylic bis(iodyl) reagents in hydroxylative dearomatization of
phenols (up to 94% ee)[3e] led us to investigate the possibility of
mounting transferable carbon-based ligands onto the iodine
centres of their C2-symmetrical bis(iodoarene) precursors.[3e,7]
Herein, we describe the synthesis of novel axially chiral 3-
iodanes bearing alkynyl ligands,[8] and the evaluation of their
performance in asymmetric alkynylations of -ketoesters and, for
the first time, of naphthol derivatives (Scheme 1).
[*]
Dr. S. Companys, Dr. P. A Peixoto, Dr. C. Bosset,
Prof. L. Pouységu, Prof. S. Quideau
Univ. Bordeaux, ISM (CNRS-UMR 5255)
351 cours de la Libération, 33405 Talence Cedex (France)
E-mail: laurent.pouysegu@u-bordeaux.fr,
stephane.quideau@u-bordeaux.fr
Dr. S. Chassaing
ITAV, Univ. Toulouse, CNRS, UPS, 31106 Toulouse (France)
Dr. K. Miqueu, Dr. J.-M. Sotiropoulos
Univ. Pau et Pays de l’Adour, IPREM (CNRS-UMR 5254)
Hélioparc, 2 avenue Pierre Angot, 64053 Pau Cedex 09 (France)
Supporting information of this article can be found under:
http://dx.doi.org/…
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10.1002/chem.201703238
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COMMUNICATION
tBu
B(OiPr)2
3a (2.0 equiv)
CO2Me
CO2Me
OAc
CO2Me
OTs
or
O
O
CO2Me
SelectFluor®
p-TsOH•H2O
(1.65 equiv)
TBS
B
OTs
3b (2.0 equiv)
(7.0 equiv)
I
I
I
I
I
I
R
R
O
O
*
*
*
*
I
I
MeCN/AcOH (4:1)
rt, 18 h
CH2Cl2/TFE (1:1)
rt, 30 min
CH2Cl2/TFE (1:1)
rt, 30 min
(R)-4a: R = tBu (80%)
(S)-4a: R = tBu (81%)
(R)-4b: R = TBS (83%)
(S)-4b: R = TBS (85%)
OAc
OTs
OTs
CO2Me
(R)-1 or (S)-1
CO2Me
CO2Me
CO2Me
(R)-2a or (S)-2a
(R)-2b or (S)-2b
Scheme 2. Synthesis of axially chiral biphenylic bis(alkynyl-3-iodanes) 4a and 4b. Selectfluor® = 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane
bis(tetrafluoroborate), p-TsOH = para-toluenesulfonic acid, TFE = 2,2,2-trifluoroethanol, Ts = tosyl.
X-ray quality crystals of 4a and 4b were all fruitless, but DFT
calculations (WB97XD/6-31G** for C,H,O,N and SDD for I)
carried out on (S)-4a and (S)-4b supported the proposed
bis(iodosyl) structures by showing the expected T-shaped
geometry of the two iodine(III) centres (T angle values ranging
between 166 and 177°) for all calculated isomers (see the
Supporting Information). Attempts to change the heteroatomic
Most of these substrates were cleanly converted into the
alkynylated compounds 6b-i in good to excellent isolated yields
(64-98%), but the asymmetric induction became more erratic.
The 5-methoxy substituted 1-indanone 5b was converted into 6b
with 62% ee, while its 5-bromo analogue 6c was obtained with a
slightly lower enantioselectivity (52% ee). The lowest selectivity
(27% ee) was observed for the 4,7-dimethoxy-1-indanone 5d.
Smaller and more flexible substrates, such as the
cyclopentanone- and cyclohexanone-derived -ketoesters 5e
and 5f, as well as the propiophenone-derived ester 5h, gave rise
to the corresponding alkynylated products with moderate
enantioselectivities (39-52% ee). Higher selectivities around the
60% ee value were again observed starting from the -tetralone
5g or the bulky ester-bearing 1-indanone 5i (Table 1). These
results underline the substrate-dependent efficacy of this chiral
iodane-mediated asymmetric alkynylation reaction, as in the
case of TMS-EBX use in the presence of a chiral catalyst.[6c]
However, it is interesting to note that enantioinduction from our
bis(alkynyl-3-iodane) atropisomers (up to 68% ee) does not
necessitate the presence of a bulky ester alkyl group onto the
substrates (i.e., Me vs tBu or CMe2Ph, see Scheme 1).[6c]
ligand of iodanes
4 by generating bis(trifluoroacetate) or
bis(tetrafluoroborate) derivatives according to the same
procedure, as well as by direct treatment of 2a with 3a, gave
mixtures of degradation materials, together with some starting
bis(iodoarene) 1. Only the bis(triflate) analogue of 4a could be
isolated (61% yield), but this iodane turned out to be unstable in
solution and inefficient for alkynyl-transfer reaction (see the
Supporting Information).
We then evaluated the capacity of these novel chiral 3-
iodanes 4a and 4b to transfer their alkynyl ligand(s) in an
asymmetric fashion to a series of -ketoesters 5. Appropriate
reaction conditions were identified using 1.0 equiv of iodane (S)-
4a (R = tBu) and KOtBu (3 equiv) to promote the desired alkynyl
group transfer onto the 1-indanone 5a (R1 = Me, Z = H, n = 1) in
dry THF (33 mM, in the presence of 4Å MS) at –40 °C (for
optimization studies, see Table S1 in the Supporting
Information). The -alkynylated product (–)-6a[11,12] was thus
obtained in 90% isolated yield with a promising 67% ee (Table
1). To the best of our knowledge, this is the first example of
enantioselective alkynylation reaction promoted by a chiral
iodane. Of particular note is that (i) no reaction was observed at
–78 °C, (ii) the use of 3.0 equiv of KOtBu turned out to be crucial
to guarantee the efficient in situ formation of the 5a-derived
enolate intermediate (see Table S1), and (iii) the use of
inorganic bases, such as potassium, sodium or cesium
carbonate, or Hünig’s base (iPr2NEt) improved neither the
chemical yield nor the ee of 6a (see Table S2). The -
alkynylation of 5a was then also achieved with the synthetically
more valuable iodane 4b (R = TBS) to afford 6a’ in high to
nearly quantitative yields with 58% ee using (R)-4b, and with
68% ee in favour of the other enantiomer using the (S)-
atropisomer of 4b (Table 1, and see Table S2 in the Supporting
Information). Again, reactions run at lower temperature (–60 or –
78 °C) did not lead to any improvement of selectivity (64% ee),
but required longer reaction times (48 h) at the expense of yields
(80 and 74%) (see Table S2). Interestingly, the use of only 0.6
equiv of 4b afforded 6a’ with 51% ee, but with a lower yield
(41%), suggesting that only one alkynyl ligand was transferred
onto the substrate (see Table S2).
Table 1. Asymmetric alkynylation of -ketoesters 5 using chiral iodanes 4a
and 4b.[a-c]
O
O
1. KOtBu (3.0 equiv),
THF, 4Å MS, rt, 1 h
CO2R1
CO2R1
*
n
2. Chiral iodane 4a or 4b (1.0 equiv),
THF, 4Å MS, –40 °C, 24 h
n
R2
Z
Z
6a-i
(±)-5a-i
R1 = Me, Et or CMe2Ph, R2 = tBu or TBS, Z = various substituents, n = 1 or 2
O
*
ORTEP view
of (R)-6a
ORTEP view
of (S)-6a
CO2Me
tBu
6a: 90% yield, 67% ee[d]
O
*
O
O
CO2Me
TBS
CO2Me
CO2Me
TBS
*
*
5
5
MeO
Br
TBS
6a’: 99% yield, 68% ee
6b: 97% yield, 62% ee
6c: 80% yield, 52% ee
OMe
O
O
7
O
CO2Et
CO2Me
*
CO2Me
*
*
TBS
TBS
4
TBS
OMe
6d: 64% yield, 27% ee
6e: 98% yield, 52% ee
6f: 87% yield, 39% ee
O
O
O
O
CO2Me
*
CO2Me
O
Ph
TBS
6i: 67% yield, 61% ee
*
*
TBS
TBS
6h: 81% yield, 42% ee[e]
6g: 83% yield, 59% ee
[a] Reactions run using [5] = 33 mM. [b] Isolated yield. [c] Enantiomeric excess
determined by chiral HPLC analysis. [d] X-ray structure of each
enantiomer.[11,12] [e] Determined on the desilylated derivative of 6h.
The selection of -ketoesters 5b-i served to evaluate the
scope of this asymmetric alkynyl-transfer reaction (Table 1).
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We next turned our attention to the dearomative alkynylation
of 2-substituted -naphthols, a transformation that, to the best of
our knowledge, has never been achieved in a stereocontrolled
fashion using chiral iodanes.[13] 2-Methoxy--naphthol (not
shown) was selected to set up the experimental conditions, but
para-brominated analog 7f into 8f (Table 2). In other cases,
para-bromination had a rather positive effect, since it led to an
increase of enantioselectivity by about 10% for the 2-methoxy
naphthol derivative (7g8g: 81% ee) and even also for the 2-
methylnaphthol derivative (7h8h: 56% ee). Finally, the
the use of KOtBu (3 equiv) in THF, followed by addition of (S)-4b, presence of para-aryl groups had no significant impact, as both
afforded the alkynylated compound 8a in disappointing isolated
yield (33%) and selectivity (20% ee) (for optimization studies,
see Table S3 in the Supporting Information). However, we found
out that a TBAF-mediated release of the naphtholate anion from
its silyl ether precursor 7a, in the presence of Hünig’s base (3
equiv) in THF at –78 °C (see Table S3), allowed a clean and
efficient conversion into 8a, which was obtained in 78% yield
with an encouraging 71% ee (Table 2). A series of 2-substituted
O-silyl -naphthols 7b-j was then similarly alkynylated in good to
excellent yields, but the enantioselectivity has again proven to
be highly substrate-dependent (Table 2). Alkynylations of the O-
silyl 2-methyl- and 2-allylnaphthols 7b and 7d were performed
both in lower yields and with ee’s lower than 50%, thus
alkynylated products 8i and 8j were obtained in good yields with
70% ee.
Moreover, further variations of the reaction conditions using
our best substrate 7g showed that i) no improvement was
observed at –95 °C (8g: 97% yield, 80% ee) and, most
importantly, ii) no significant loss of yield and selectivity (8g:
86% yield, 78% ee) was observed using only 0.6 equivalent of
(S)-4b at –78 °C, thus indicating, in contrast to -ketoester
alkynylations, that its two iodine(III) centres successfully
transferred their alkynyl ligand onto the naphtholic substrate
(see the Supporting Information). A three-fold scale-up of this
reaction confirmed both the excellent yield (95%) and very good
enantioselectivity [84% ee in favour of (R)-8g],[12,14] while
allowing recovery of the bis(iodoarene) (S)-1 in 98% yield.
suggesting that
a more electron-donating 2-alkoxy group
positively influences the reaction outcomes. This was supported
by the conversion of the O-silyl 2-methoxymethoxynaphthol 7c
into the alkyne 8c in 81% yield with an enantioselectivity back to
the 71% ee value. However, a bulkier alkoxy group, such as an
isopropoxy group, while maintaining a high level of chemical
yield, had a detrimental effect on the enantioinduction (< 50%
ee) for the alkynylation of 7e into 8e, as well as for that of its
As a final point in this work, we tested this dearomative
asymmetric alkynylation on a couple of 1-substituted -naphthol
silyl ethers (Scheme 3). Compared to their -analogues, the
alkoxylated derivatives 9a (R = OMe) and 9b (R = OMOM) were
alkynylated in much lower yields and enantioselectivities (< 50%
ee). The replacement of these alkoxy groups by electron-
withdrawing formyl or ester groups (R = CHO, CO2CH3) was
found prejudicial as no reaction took place. Nevertheless, the
presence of an acetyl group (R = COCH3) led to the isolation,
albeit in only 26% yield, of a new product, which was identified
by X-ray analysis as the alkynyl aryl ether 11 (Scheme 3).
Table 2. Asymmetric dearomative alkynylation of 2-substituted O-silyl -
naphthols 7 using chiral iodane (S)-4b.[a-c]
1. TBAF (1.1 equiv), iPr2NEt (3.0 equiv),
THF, 4Å MS, –78 °C (1 min),
rt (1-5 min), then –78 °C (15 min)
OTBS
R1
O
R1
*
TBS
2. (S)-4b (1.0 equiv), THF, 4Å MS,
–78 °C (1.5 h), then 0 °C (2 h)
7a-j
8a-j
R
R3 R2
R3 R2
OTBS
R1 = alkoxy or alkyl group, R2 = H or Br, R3 = H or OMe
+
Iodane (S)-4b
O
O
O
9
OMe
Me
OMOM
TBS
R = alkoxy
R = COCH3
*
*
*
O
TBS
TBS
TBS
R
see Table 2
for conditions
ORTEP view of 11
TBS
O
O
*
8a: 78% yield, 71% ee
8b: 68% yield, 44% ee
8c: 81% yield, 71% ee
O
O
O
OiPr
OiPr
10a: R = OMe, 67% yield, 49% ee
10b: R = OMOM, 40% yield, 46% ee
11: 26% yield
*
*
*
TBS
TBS
TBS
Scheme 3. Synthesis of alkynyl compounds 10a/b and alkynyl aryl ether 11[12] from
1-substituted O-silyl -naphthols 9 using iodane (S)-4b.
OMe
Br
8d: 63% yield,[d] 47% ee
8e: 99% yield, 47% ee
8f: 78% yield, 46% ee[e]
O
The non-dearomative process leading to 11 is
mechanistically unveiling, as it could result from a direct C–O
ipso-ipso ligand coupling (LC)[15] between the alkynyl and O--
naphtholate moieties both mounted onto the iodine(III) centres of
4b via path a (i.e., a ligand exchange step), such as in
intermediate E (Scheme 4). Similarly, alkynes 8 could also result
from a direct nucleophilic attack (path a) of O--naphtholate
anions onto 4b to give intermediates of type F, followed by C–C
ipso-allyl ligand coupling (LC’) events.[15] However, the -
alkynylation of -ketoesters has been shown to proceed through
a conjugate nucleophilic attack of ketoester-derived and softer
C-enolates onto the alkyne moiety of the 3-iodane reagent.[6d,16]
This process, exemplified in Scheme 4 for the conversion of 5a
into 6a’ using the iodane 4b, would give rise to intermediates of
type G (path b). As indicated by 13C-labeling studies,[6d,16] such
OMe
*
TBS
ORTEP view
of (R)-8g
8g: 99% yield, 81% ee[f]
95% yield, 84% ee[g]
Br
O
O
O
Me
OMe
OMe
*
*
*
TBS
TBS
TBS
Br
8h: 67% yield, 56% ee
8j: 81% yield,
71% ee[e]
CF3
8i: 69% yield,
70% ee
F3C
[a] Reactions run using [7] = 33 mM. [b] Isolated yield. [c] Enantiomeric excess
determined by chiral HPLC analysis. [d] Quick evolution in solution to a by-
product resulting from a Cope rearrangement/rearomatization process. [e]
Determined on the desilylated derivatives of 8f or 8j. [f] X-ray structure of the
R enantiomer.[12,14] [g] Three-fold scale-up. TBS = tert-butyldimethylsilyl.
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10.1002/chem.201703238
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[3]
a) K. Muñiz, L. Barreiro, R. Martín Romero, C. Martínez, J. Am. Chem.
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an iodo-allene would then evolve into the alkylidene carbene H,
which could rapidly rearrange via a 1,2-silyl shift into the -
alkynylated product 6a’. The ligand exchange/coupling
sequence through the iodosyl intermediate I (path a) thus
appears less likely for the formation of -alkynylated -
ketoesters such as 6a’, but further mechanistic scrutinization
should not totally disregard the LC/LC’ pathways when using
harder nucleophiles such as O-naphtholate anions.
Nu
Nu = O-naphtholate or
b-ketoester-derived C-enolate
a
b
TBS
TsO
I
Ar = C2-symmetrical biphenylic moiety
Ar 4b
9-derived
O-naphtholate
O
O
[4]
a) Y. Li, D. P. Hari, M. V. Vita, J. Waser, Angew. Chem. Int. Ed. 2016,
55, 4436; b) K. Aradi, B. L. Tóth, G. L. Tolnai, Z. Novák, Synlett
2016, 27, 1456; c) J. Charpentier, N. Früh, A. Togni, Chem. Rev. 2015,
ipso-ipso
LC
Ar
O
O
a
I
TBS
– ArI
– TsO
E
11
TBS
115, 650
.
TBS
[5]
[6]
M. Ochiai, Y. Kitagawa, N. Takayama, Y. Takaoka, M. Shiro, J. Am.
Chem. Soc. 1999, 121, 9233.
Ar
7-derived
O-naphtholate
I
O
O
ipso-allyl
LC’
OR
a) M. Chen, Z.-T. Huang, Q.-Y. Zheng, Org. Biomol. Chem. 2015, 13,
8812; b) X. Wu, S. Shirakawa, K. Maruoka, Org. Biomol. Chem. 2014,
OR
a
TBS
– ArI
– TsO
12, 5388; c) D. Fernández González, J. P. Brand, R. Mondière, J.
F
8
O
O
Waser, Adv. Synth. Catal. 2013, 355, 1631; d) D. Fernández González,
CO2Me
CO2Me
TBS
b
J. P. Brand, J. Waser, Chem. Eur. J. 2010, 16, 9457.
– ArI
TBS
[7]
[8]
[9]
S. Quideau, G. Lyvinec, M. Marguerit, K. Bathany, A. Ozanne-
Beaudenon, T. Buffeteau, D. Cavagnat, A. Chénedé Angew. Chem. Int.
Ed. 2009, 48, 4605.
–TsO
•
G
H
•
•
5a-derived
C-enolate
I
1,2-shift
Ar
O
O

3-iodanes are also commonly referred to as
ipso-ipso
LC
a) These T-shaped
a
CO2Me
CO2Me
TBS
alkynyliodonium salts, their ionic analogues; b) V. V. Zhdankin, P. J.
Stang, Tetrahedron 1998, 54, 10927.
I
– ArI
–TsO
Ar
I
6a’
a) M. J. Bouma, B. Olofsson, Chem. Eur. J. 2012, 18, 14242; b) C. Ye,
B. Twamley, J. M. Shreeve, Org. Lett. 2005, 7, 3961; c) T. Dohi, A.
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Ochiai, Y. Takaoka, Y. Masaki, Y. Nagao, M. Shiro, J. Am. Chem. Soc.
1990, 112, 5677.
TBS
Scheme 4. Possible mechanisms for iodane-mediated alkynylation reactions.
In summary, we have prepared new axially chiral biphenylic
iodine(III) reagents equipped with alkynyl ligands. Even though it
would be premature at this stage to propose a full mechanistic
rationale for their stereoselective bond-forming aptitude, we
have demonstrated the capacity of these bis(3-iodanes) to
promote asymmetric alkynylation of -ketoesters and, for the first
time, -naphthol silyl ethers in high yields with very good
enantioselectivity up to 84% ee.
[10] A. R. Katritzky, J. K. Gallos, H. Dupont Durst, Magn. Reson. Chem.
1989, 27, 815; Although 13C NMR chemical shifts enable the
assignment of the oxidation state of the iodine atom, the structures of
iodanes 4a/b, for which we could not obtain X-ray quality crystals,
remain hypothetical.
[11] Under similar conditions, conversion of 5a using racemic iodane (±)-4a
furnished (±)-6a, whose enantiomers were separated by HPLC and
unambiguously characterized by NMR and X-ray analyses (see the SI).
[12] CCDC 1424985 ((R)-6a), 1424986 ((S)-6a), 1477527 ((R)-8g), 1495372
((±)-10a) and 1495370 (11) contain the supplementary crystallographic
data for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre.
Acknowledgements
Financial support from the Ministère de la Recherche, the CNRS,
and the Conseil Régional d’Aquitaine, including doctoral
fellowships for S.C. and C.B., is gratefully acknowledged.
[13] Examples of enantioselective C–C bond-forming dearomatization of -
naphthols using chiral phosphoric acids or ligand•metal complexes: a)
X.-Q. Li, H. Yang, J.-J. Wang, B.-B. Gou, J. Chen, L. Zhou, Chem. Eur.
J. 2017, 23, 5381; b) H.-F. Tu, C. Zheng, R.-Q. Xu, X.-J. Liu, S.-L. You,
Angew. Chem. Int. Ed. 2017, 56, 3237; c) D. Yang, L. Wang, M. Kai, D.
Li, X. Yao, R. Wang, Angew. Chem. Int. Ed. 2015, 54, 9523; d) C.-X.
Zhuo, S.-L. You, Angew. Chem. Int. Ed. 2013, 52, 10056; e) T. Oguma,
T. Katsuki, J. Am. Chem. Soc. 2012, 134, 20017.
Conflict of interest
The authors delclare no conflict of interest.
Keywords: alkynylation • asymmetric synthesis • hypervalent
compounds • iodanes • metal-free reactions
[14] HPLC separation of an enantioenriched mixture of 8g, followed by
crystallization of the major optical isomer, led to the identification of the
R-enantiomer (see the SI).
[1]
a) Hypervalent Iodine Chemistry, in Topics Curr. Chem., Vol. 373 (Ed.:
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Zhdankin, Chem. Rev. 2016, 116, 3328.
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Compounds, Vol. 18, Pergamon, Oxford, 1998; b) A. Ozanne-
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a) F. Berthiol, Synthesis 2015, 47, 587; b) A. Parra, S. Reboredo,
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Chem. Int. Ed. 2011, 50, 11849.
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10.1002/chem.201703238
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COMMUNICATION
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COMMUNICATION
The preparation of new axially chiral
biphenylic iodine(III) reagents
Dr. Simon Companys, Dr. Philippe A.
Peixoto, Dr. Cyril Bosset, Dr. Stefan
Chassaing, Dr. Karinne Miqueu, Dr.
Jean-Marc Sotiropoulos, Prof. Laurent
Pouységu,* and Prof. Stéphane
Quideau*
new chiral bis(l3-iodanes)
CO2Me
OTs
equipped with alkynyl ligands is
described. These bis(3-iodane)
reagents demonstrate their capacity to
promote the asymmetric alkynylation
of -ketoesters with enantiomeric
excesses up to 68%, and most
remarkably, to enable the dearomative
alkynylation of naphthols with
R1
R1
I
I
S
OTs
CO2Me
b-ketoesters
a-naphthols
asymmetric
alkynylation
Page No. – Page No.
O
O
R2
CO2R2
Asymmetric Alkynylation of -
Ketoesters and Naphthols Promoted
by New Chiral Biphenylic Iodanes
*
R1
*
n
R1
Z
enantiomeric excesses up to 84%.
R4 R3
10 examples
10 examples
up to 68% ee
up to 84% ee
This article is protected by copyright. All rights reserved.