Phosphathiahelicenes: Synthesis and Uses in Enantioselective Gold Catalysis

Article abstract of DOI:10.1002/chem.201402822

Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine–Au^Icomplex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee).

Full text of DOI:10.1002/chem.201402822

DOI: 10.1002/chem.201402822
Communication
&
Gold Catalysis
Phosphathiahelicenes: Synthesis and Uses in Enantioselective
Gold Catalysis
[
a]
[a]
[b]
[b]
Paul Aillard, Arnaud Voituriez,* Davide Dova, Silvia Cauteruccio,
[b]
[a]
Emanuela Licandro,* and Angela Marinetti*
Dedicated to Professor Max Malacria on the occasion of his 65th birthday
Abstract: Enantiomerically pure thiahelicenes displaying
a terminal phosphole unit and a stereogenic phosphorus
center have been prepared by oxidative photocyclization
of a diaryl-olefin precursor. Starting from one of these
phosphathiahelicene oxides, the corresponding trivalent
I
phosphine–Au complex is obtained with complete diaste-
reoselectivity. It affords a new, excellent precatalyst for the
enantioselective cycloisomerization of N-tethered enynes
(up to 96% ee).
[
8]
Figure 1. HelPhos gold complexes from previous studies and targeted
ligands.
Helically chiral structures are known to display peculiar proper-
ties with applications in many fields including asymmetric cat-
A brief analysis of the structural features of complex 1 and
comparison of its catalytic behavior with other phosphaheli-
cenes, suggest that a key for high enantioinduction from these
ligands specifically relates to the positioning of the phospho-
[
1]
alysis. However, both the synthesis of helical phosphorus
[
2]
ligands and their uses in enantioselective organometallic cat-
alysis have been underdeveloped so far. Catalytic screenings in
enantioselective reactions mainly include Rh-promoted hydro-
[10]
rus function in the internal rim of the helical scaffold. Thus,
as the next step of our work, we intend to expand the same
design to phosphahelicenes combining phosphole units with
different helical scaffolds, so as to finely tune their structural
features and catalytic behaviors.
[
2e,3]
genations or hydroformylations of olefins,
palladium-pro-
[
4]
moted allylic substitutions and Ir-promoted allylic aminations
[
3c]
of cinnamyl-type substrates. The phosphines used in these
processes display phosphorus functions grafted on helical scaf-
[5]
folds. Following to the pioneering work of Tanaka and
In this work we demonstrate that thiophene-containing heli-
cal scaffolds can be adapted suitably to the synthesis of phos-
phahelicenes of this class, as well as that the corresponding
gold complexes afford unprecedented enantioselectivity levels
in enyne cycloisomerization reactions.
[
6]
Nozaki, we have introduced recently a new design for helical
phosphorus ligands where a trivalent phosphorus function is
[7]
embedded in the helical structure itself, as a phosphole unit.
In these series, the so-called HelPhos ligands (Figure 1) afford-
ed excellent catalysts for gold-promoted enantioselective cy-
cloisomerizations with ee values up to 86% for the conversion
Helicenes based on alternating thiophene and benzene
units have been extensively developed by Licandro et al. by
using the photochemical oxidative cyclization of dithienyl ole-
[8]
of N-tethered 1,6-enynes into 3-azabicyclo[4.1.0]heptenes.
[11]
These promising results are especially rewarding as enantiose-
lectivity in gold-catalyzed processes remains to date a highly
fins as the preferred synthetic approach. Inspired by this
work and considering that heterohelicenes can be functional-
[
9]
[12]
challenging target.
ized and tuned more easily than the carbon analogues, joint
studies have been set up with the aim of preparing thiaheli-
cene mimics of the HelPhos ligand in 1 (Figure 1).
[
a] P. Aillard, Dr. A. Voituriez, Dr. A. Marinetti
Institut de Chimie des Substances Naturelles, CNRS UPR 2301
The synthesis of the targeted helicene (HelPhos-S), involves
preparation of the diaryl olefin 7, which combines a [5]-thiahe-
licene and a 1H-phosphindole fragments (Scheme 1), followed
by a photochemical oxidative cyclization step (Scheme 2).
1
, av. De la Terrasse - 91198 Gif-sur-Yvette (France)
E-mail: angela.marinetti@cnrs.fr
arnaud.voituriez@cnrs.fr
[11c]
[
b] D. Dova, Dr. S. Cauteruccio, Prof. E. Licandro
Dipartimento di Chimica, Universitꢀ degli Studi di Milano
via Golgi 19, 20133 Milan (Italy)
Olefin 7 has been formed from the olefinic bis-boronate 4
by two subsequent palladium-catalyzed Suzuki couplings in-
[13]
volving the [5]-thiahelicene bromide 3 and the phosphin-
E-mail: emanuela.licandro@unimi.it
[8]
dole triflate (R )-6, respectively. The phosphindole triflate 6 is
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402822.
P
an optically pure compound which displays a chiral l-menthyl
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Communication
The synthesis of gold complexes from (R ,P)-8 was then car-
P
ried out according to Scheme 3. After reduction of the phos-
phine oxide (R ,P)-8 into the corresponding trivalent phos-
P
phine, in situ complexation was performed by reaction with
AuCl·thiodiethanol. This procedure affords the desired gold
complex (S ,P)-10 as a single diastereomer. We could not
P
obtain X-ray data for complex 10, nevertheless, based on NMR
spectroscopy data (see the Supporting Information), we
assume that the gold atom is oriented toward the helical struc-
ture (endo isomer) while the l-menthyl group occupies the ex-
ternal face of the phosphahelicene. The reaction thus involves
overall inversion of the phosphorus configuration, as a result
of the configurational lability of phosphorus in phosphindole-
[15]
type derivatives.
The same reduction-complexation proce-
P
Scheme 1. Synthesis of the olefinic derivative (R )-7 by Suzuki couplings.
dure had been applied before to the analogous all-carbon
phosphahelicenes (Figure 1), but it displayed much lower dia-
stereoselectivity, giving 1:1 mixtures of the exo and endo iso-
group on phosphorus and a stereogenic phosphorus with R
P
[
14]
[8]
configuration ([a] =À150 (c=0.2, CHCl )).
mers of the gold complexes 1.
D
3
The coupling step between the olefinic boronate 4 and the
5]-thiahelicene bromide 3 was performed with Pd(PPh ) as
[
3
4
the catalyst, while the second coupling, which involves (R )-6,
P
requires the use of the Pd(SPhos) Cl precatalyst. It takes place
2
2
in almost quantitative yield, giving olefin (R )-7 as a pale
P
yellow solid ([a] =À187 (c=1, CHCl )).
D
3
Next, the key photocyclization step (Scheme 2) was carried
out in cyclohexane in the presence of iodine and propylene
À1
oxide: irradiation of a diluted solution of (R )-7 (0.3 mgmL )
P
for 1.5 h with a 150 W mercury lamp, afforded a mixture of the
helical compounds (R ,P)-8 and (R ,M)-9 in 66% total yield.
P
P
P
Scheme 3. Synthesis of the gold complex (S ,P)-10.
Structural assignments were made by NMR spectroscopy and
the helical configurations were assigned based on the sign of
optical rotation: [a] = +1358 (c=1, CHCl ) for (R ,P)-8 and
The helical scaffold of (S ,P)-10 differs significantly from that
D
3
P
P
[
a] =À1366 (c=1, CHCl ) for (R ,M)-9.
of the phosphahelicene ligand in (S ,P)-1, as it contains seven
D
3
P
P
ortho-condensed aromatic rings
instead of six and includes five-
membered heterocyclic units.
These structural and geometrical
modifications might result in
deep changes in the catalytic
behavior of the gold complex
(
SP,P)-10, with respect to 1, that
cannot be easily anticipated.
Therefore, the catalytic proper-
ties of (S ,P)-10 were investigated
P
P
Scheme 2. Oxidative photocyclization of (R )-7.
in a systematic way, starting
from its use as precatalyst in
enyne cycloisomerization reac-
The photocyclization reaction gives only very small amounts
of side products and affords the desired [7]-helicene, 8, as the
major product in an 8:2 ratio to 9. Overall this reaction is
therefore much more efficient than the analogous photochem-
ical generation of phosphahelicenes with all-carbon back-
tions. In this field, a benchmark reaction is the cycloisomeriza-
tion of the N-tethered 1,6-enynes 11 into aza-bicyclo-
[4.1.0]heptenes 12 shown in Scheme 4. Starting from 11 a
[16]
(Ar=Ph), the gold complex (S ,P)-10 displayed good catalytic
P
activity at room temperature, after activation with AgBF . It af-
4
[
8]
bones.
forded 12a in 74% enantiomeric excess. Changing the
Both the [7]-helicene 8 and the [8]-helicene 9 were isolated
as single epimers with defined helical configuration, meaning
that the phosphorus configuration dictates the stereochemistry
of the helical structures at this photocyclization step.
activating agent from AgBF to AgNTf2 did not change the
4
enantioselectivity level (ee=75%), while other silver salts such
as AgOTf or AgSbF decreased the enantiomeric excess to 45
6
and 63%, respectively. Significant enantiomeric excesses were
Chem. Eur. J. 2014, 20, 12373 – 12376
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Communication
then up to 93% by carrying out the cycloisomerization reac-
tion at 08C. As far as we know, enantioselective variants of this
reaction have been reported before under platinum catalysis
[16b]
(
92% ee),
never under gold catalysis.
In summary, we have shown that enantiomerically pure
phosphathiahelicenes are easily available by a highly regio-
and diastereoselective photocyclization procedure. Overall the
phosphathiahelicene oxide 8 and the corresponding gold com-
plex 10 are obtained more efficiently than the analogous phos-
phacarbohelicene gold complexes described in our previous
work. The new complex displays especially high enantioselec-
tivity levels in the cycloisomerization of N-tethered dien-ynes.
More extended catalytic screening is currently ongoing in our
group so as to assess the potential of these helical ligands in
enantioselective gold catalysis.
Scheme 4. Enantioselective cycloisomerization of the N-tethered enynes
1a–c.
1
obtained also in the cycloisomerization of enynes with either
electron-rich (11 b) or electron-poor (11 c) aryl substituents on
the alkyne unit (72 and 68% ee, respectively, Scheme 4).
The promising enantioselectivity levels above encouraged us
to extend our investigations to the cycloisomerization of differ-
[
17]
ent classes of enynes. At first, dienynes 13 were considered
that display conjugated enyne moieties (Scheme 5a). Depend-
ing on the nature of the R substituent, the gold-catalyzed cy-
cloisomerization affords either the aza-bicyclo[4.1.0]heptene 15
Acknowledgements
(
for R=H) or the tricyclic derivative 14 (for R=Ph), which re-
We gratefully acknowledge the Paris Sud University, Ecole Doc-
torale 470, for Ph.D. grant to P.A. E.L. acknowledges the Minis-
tero dell’Universitꢁ e della Ricerca (MIUR), Roma, and the Uni-
versity of Milan (UNIMI) within the national project “Nuovi
metodi catalitici stereoselettivi e sintesi stereoselettiva di mo-
lecole funzionali” (PRIN 2009). UNIMI is acknowledged for fel-
lowships to S.C. (Postdoc) and D.D. (Ph.D.).
[18]
sults from a vinylcyclopropane-cyclopentene rearrangement
of the intermediate aza-bicyclo[4.1.0]heptene. In the cycloiso-
merization of 13a (R=Ph), the nature of the silver salt has a re-
markable effect on the enantioselectivity level, going from
a moderate 65% ee for AgX=AgBF to an excellent 96% ee for
4
AgX=AgNTf . The same catalytic system ((S ,P)-10/AgNTf ) af-
fords the aza-bicyclo[4.1.0]heptene 15 in 89% ee. Thus, the
thiaphosphahelicene–Au catalyst (S ,P)-10 gives the highest
2
P
2
I
P
Keywords: enantioselectivity
gold · phosphahelicenes · thiahelicenes
· enyne cycloisomerization ·
enantiomeric excesses attained so far in these cycloisomeriza-
[
19]
tion reactions.
Finally, the same catalyst was used in the cycloisomerization
[
20]
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Scheme 5. Enantioselective cycloisomerizations of dien-ynes promoted by
(
S
P
,P)-10.
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Chem. Eur. J. 2014, 20, 12373 – 12376
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12376
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim