An efficient and recyclable hybrid nanocatalyst to promote enantioselective radical cascade rearrangements of enediynes

Article abstract of DOI:10.1039/c1cc10551e

Mesoporous silica grafted with a tertiary amine was used as a basic nanocatalyst to promote in confined medium the enantioselective cascade rearrangement of enediynes based on the phenomenon of memory of chirality; the multi-substrates recyclable catalyti

Full text of DOI:10.1039/c1cc10551e

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COMMUNICATION
An efficient and recyclable hybrid nanocatalyst to promote
enantioselective radical cascade rearrangements of enediynesw
Malek Nechab,*a Eric Besson,*a Damien Campolo,a Patricia Perfetti,a Nicolas Vanthuyne,b
Emily Bloch,a Renaud Denoyela and Michele P. Bertrand*a
Received 27th January 2011, Accepted 11th March 2011
DOI: 10.1039/c1cc10551e
Mesoporous silica grafted with a tertiary amine was used as a basic
nanocatalyst to promote in confined medium the enantioselective
cascade rearrangement of enediynes based on the phenomenon of
memory of chirality; the multi-substrates recyclable catalytic
reagent could easily be recovered by simple filtration, and reused
without any decrease in activity even when changing the solvent.
i.e., hybrid materials bearing a tertiary amino group prepared
from mesoporous silica according to grafting protocols. In our
previous procedure, we used 5 to 10 equivalents of basic Al2O3
to induce the formation of the allene moiety from an aryl
propargyl sulfone. Alumina could not be recycled; moreover,
it was shown to retain part of the reaction products, and, as a
consequence, to be responsible for a loss in yield. We disclose
herein a new protocol based on mesoporous silicas grafted
with a tertiary amine which allowed the generalisation of the
rearrangement to alkyl propargyl sulfone based substrates. As
exemplified in Scheme 1 with the rearrangement of 1a–b, the
cascade involves a 1,3-proton shift leading to A. The latter
undergoes a spontaneous Saito–Myers13 cyclisation to give
biradical B. Subsequent 1,5-hydrogen atom transfer14 leads to
biradical (C) which, owing to the conformational requirements
imposed by the atom transfer step, is generated in a chiral
conformation at the capto-dative reactive center. This chirality
is preserved during the intramolecular coupling of biradical
(C), which affords diastereomeric mixtures of 2a–b and 3a–b in
good yields, together with side-products 4a–b (Fig. 1) resulting
from a dismutation process.
One of the most important goals nowadays is the development
of environmentally friendly processes. Cascade reactions are
continuously growing in popularity and many new sequences
have been published.1 The benefits of cascade reactions are well
established, they include atom and time economy, and low waste
generation.2 Therefore, cascade reactions can be considered to
fall under the banner of ‘‘green chemistry’’. We have recently
reported the enantioselective cascade rearrangement of enediynes
leading to heterocycles bearing a quaternary stereogenic center.3
These reactions proceed with memory of chirality.4
Over the recent past years, there has been a dramatic rise in the
number of reports dealing with the preparation, characterisation
and use of hybrid materials based on mesoporous silica of a
tunable pore size.5 Supported heterogeneous catalysts with
chemically designed surfaces have received much attention,6
not only as recoverable reagents, immobilized in mesoporous
silicas,7 but also as multifunctional surface materials. Many
examples dealing with enantioselective catalysis with chiral
ligands have been reported.8 The improvements compared to
homogeneous processes were ascribed to confinement effects.
There are very few examples dealing with cascade reactions
in confined media,9 as well as very few reports dealing with the
influence of confinement on radical processes (most examples
are concerned with photochemical processes).10,11
Mesoporous silicas with different pore diameters were
prepared from tetraethyl orthosilicate (TEOS) in the presence
We describe herein a polar/radical crossover cascade
rearrangement of enediynes bearing
a sulfone moiety
as a precursor of an intermediate enyne-allene.12 These
rearrangements were promoted by recyclable nanocatalysts,
a
´
´
´ ˆ
LCP UMR 6264, Aix-Marseille Universite, Faculte de St Jerome,
Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20,
France. E-mail: malek.nechab@univ-provence.fr,
eric.besson@univ-provence.fr, michele.bertrand@univ-cezanne.fr
b
´
´
´ ˆ
ISM2, UMR 6263, Aix-Marseille Universite, Faculte de St Jerome,
Avenue Normandie-Niemen, 13397 Marseille Cedex 20, France
w Electronic supplementary information (ESI) available: Experimental
procedures, characterisation of hybrid materials and new compounds,
and analysis by chiral HPLC. See DOI: 10.1039/c1cc10551e
Scheme 1
c
5286 Chem. Commun., 2011, 47, 5286–5288
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The high surface area of the materials concentrates a great density
of functional groups. The smaller the pore size, the higher the
probability of efficient collisions between the catalyst and the
substrate is. A confinement effect explains the lower activity of
GA-Si2000 compared to that of GA-MCM41 and GA-SBA15.
GA-SBA15 was selected to continue our study by screening
different substrates. Under these conditions, 2a (72% ee) and 3a
(68% ee) were isolated in 29% and 45% yields, respectively, from
1a (88% ee). The dismutation product 4a was isolated in 20%
yield (entry 7). Whereas the influence of the catalyst on the rate of
the reaction was obvious, no significant effect of confinement was
observed on the diastereoselectivity or on the enantioselectivity.15
The recycling of the catalyst is of prime importance in a
heterogeneous reaction. Therefore, we have investigated the
reusability of GA-SBA15 nanocatalyst. As shown in Table 2,
the grafted silica could be reused at least five times in benzene
in the rearrangement of 1b with no loss of activity. The
cyclisation of 1b (97% ee) afforded 30% of 2b (81% ee); and
39% of 3b (79% ee); again the dismutation product 4b was
isolated (entry 7). Thus the consecutive uses of the same
catalyst allowed the complete conversion of this substrate with
enantiomeric excesses very close to those observed in the first
run. An additional cycle carried out after changing the solvent
from benzene to acetonitrile did not affect either the activity,
or the diastereomeric ratio, and the ee’s.
Fig. 1 Structures of substrates and catalysts.
of cetyl-ammonium bromide (CTAB) or pluronic P123 as
templates. They were then submitted to post synthesis-grafting
with diethylaminopropyltrimethoxysilane (DEAP) (Fig. 1). These
materials were analysed by N2 adsorption/desorption (average
pore diameters of 2, and 5 nm were determined for GA-MCM41
and GA-SBA15, respectively). GA-Si2000 was prepared by
grafting commercially available Si2000 (200 nm pore diameter).
The presence of the organic moiety was confirmed by 13C and 29Si
solid-state NMR spectroscopy. The small-angle X-ray diffraction
(XRD) indicated highly ordered structures with d100 values of
3.9 nm and 10.7 nm for GA-MCM41 and GA-SBA15,
respectively. Thermogravimetric analysis showed a ratio close to
1.5 mmol of amine per gram of silica.
The multi-substrates recycling of the same catalyst was
extended to other substrates. It was first carried out with
oxazolidinone 5a (Scheme 2) to afford (R,S)-6a (21%) and
(S,S)-7a (62%) with 93% and 84% ee’s, respectively (entry 1,
Table 3).
We next examined the ability of these mesoporous silicas to
promote the cycloaromatisation reaction. The results obtained
from the rearrangements of 1a and 1b in benzene at 80 1C are
summarized in Table 1. Basic alumina gave a poor conversion in
the cyclization of 1a even when increasing the time of reaction up
to 20 h. As expected, ungrafted silica (control reaction) did not
afford any rearranged product. In the presence of GA-Si2000
(entry 3), the rearrangement of 1a (88% ee) proceeded with 67%
conversion to afford (3S,4S)-2a and (3S,4R)-3a with 68% and
72% ee’s, respectively. This means that the reaction proceeded
with a high degree of memory of chirality. Product 4a was also
isolated. Under the same conditions, GA-MCM41 afforded 2a
and 3a (93% conversion) with the same ee’s, and identical
products ratio (entry 4). Similar results were obtained when using
GA-SBA15 used as prepared, or after passivation, (entries 5
and 6). Mesoporous silica has a regular cylindrical shape.
Because of the acidity of the proton in position a relative to
the ethylsulfonyl group, the stereogenic center linked to sulfur
undergoes epimerisation into the thermodynamically most
stable product, i.e., (S,S)-7a as the major diastereoisomer, as
already evidenced in previous work.3
When submitted to the same conditions, 5b afforded (R,S)-
6b (58%) and (S,S)-7b (29%) with 96% and 72% ee’s,
respectively (entry 2, Table 3). These results are comparable
to those observed in the procedure using alumina,3 except that
the yield was higher under the new conditions. Pyroglutamic
derivative 5c (entry 3, Table 3) led to a mixture of (S,S)-6c and
(R,S)-7c that were isolated in 35% and 53% yields, with 94%
and 87% ee’s, respectively. The tosylated analogue 5d (entry 4)
gave very similar results.
Table 1 Cyclisation of 1a (88% ee) leading to 2a and 3a with various
basesa
Table 2 Recycling of the grafted catalyst in the cascade rearrangement
of 1b (97% ee)a
Time/
h
Entry Base (2 eq.)
Convc (%) %2d (ee%)b %3d (ee%)b %4d
Cycle Solvent
1st Benzene
2nd Benzene
Time/h Convb (%) ee of 2bc (%) ee of 3bc (%)
1
2
3
4
5
6
7
Al2O3
Silica
GA-Si2000
GA-MCM41
GA-SBA15
GA-SBA15e
20
6
6
6
6
20
0
6
—
9
—
4
—
16
20
20
19
20f
3
3
3
3
3
100
100
100
100
100
100
100
82
81
82
82
82
81
81
80.5
80.5
80
80
79
67
93
94
93
100
20 (72)
28 (71)
29 (72)
29 (73)
29f (72)
31 (68)
45 (69)
45 (68)
45 (70)
45f (68)
3rd
4th
5th
6th
7th
Benzene
Benzene
Benzene
Acetonitrile 3
Benzene
6
3
81 (30%)d
79 (39%)d
GA-SBA15 10
a
a
Reaction conditions: 1a (0.02 mmol), Benzene (1 mL), base
b
Reaction conditions: 1b (0.035 mmol), Benzene (2 mL), GA-SBA15
b
c
(0.04 mmol), 80 1C. Determined by chiral HPLC. Conversion
determined by NMR based on consumed substrate. NMR ratio.
(0.07 mmol), 80 1C. Conversion determined by NMR based on
consumed substrate. Determined by chiral HPLC. Number in
parentheses give the isolated yield on 0.2 mmol scale.
d
c
d
e
f
Passivated before grafting. Isolated yield on 0.26 mmol scale.
c
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catalytic or in stoichiometric amount. This nanoreactor is easy
to recover by simple filtration and washing. It can be reused,
with no loss in yield or enantioselectivity. Current efforts to
induce additional confinement effects will be reported in due
course.
We are grateful for the financial support from the
ANR-10-JCJC-0710-MOCER2.
Notes and references
1 (a) L. F. Tietze, G. Brasche and K. Gericke, in Domino Reactions in
Organic Synthesis, Wiley-VCH, Weinheim, 2006; (b) M. Albert,
L. Fensterbank, E. Lacote and M. Malacria, Top. Curr. Chem.,
2006, 264, 1; (c) D. P. Curran, Aldrichimica Acta, 2000, 33, 105.
2 (a) B. M. Trost, Science, 1991, 254, 1471; (b) B. M. Trost, Angew.
Chem., Int. Ed. Engl., 1995, 34, 259.
Scheme 2
Table 3 Multi-substrates recycling in the rearrangement of enediynes
5a–da
3 M. Nechab, D. Campolo, J. Maury, P. Perfetti, N. Vanthuyne,
D. Siri and M. P. Bertrand, J. Am. Chem. Soc., 2010, 132, 14742.
4 (a) T. Kawabata and K. Fuji, in Topics in Stereochemistry, ed.
S. E. Denmark, Wiley, New York, 2003, vol. 23, pp. 175–205;
(b) H. Zhao, D. C. Hsu and P. R. Carlier, Synthesis, 2005, 1;
(c) For seminal examples in radical chemistry, see: (d) B. Giese,
P. Wettstein, C. Stahelin, F. Barbosa, M. Neuburger, M. Zehnder
and P. Wessig, Angew. Chem., Int. Ed., 1999, 38, 2586;
(e) A. J. Buckmelter, A. I. Kim and S. D. Rychnovsky, J. Am.
Chem. Soc., 2000, 122, 9386.
Entry
Substrate (ee)b
Time/h
%6c (ee%)b
%7c (ee%)b
1
2
3
4
5a (99)
5b (99)
5c (97)
5d (99)
4
2
2.5
2
21 (93)
58 (96)
35 (94)
36 (93)
62 (84)
29 (72)
53 (87)
50 (88)
a
Reaction conditions: 5 (0.34 mmol), Benzene (10 mL), GA-SBA15
b
c
(0.7 mmol), 80 1C. Determined by chiral HPLC. Isolated yield.
5 F. Hoffmann and M. Froba, Chem. Soc. Rev., 2011, 40, 608
¨
(special issue dedicated to hybrid materials).
Finally, the cascade rearrangement was achieved using
20 mol% loading of GA-SBA15. Under these conditions, only
the reaction time was changed, neither the diastereoselectivity
nor the enantioselectivity were affected (Table 4). Time needed
for completion was 13.5 h instead of 10 h for the cyclo-
aromatisation of 1a (entry 1), which indicated that the procedure
was still very efficient. Substrate 1b afforded 2b (33%, 81% ee),
3b (42%, 80% ee) and 4b (21%) after 8 h (entry 2).
6 M. Tada and Y. Iwasawa, Coord. Chem. Rev., 2007, 251,
2702.
7 (a) Q. Wang and D. F. Shantz, J. Catal., 2010, 271, 170;
(b) H.-T. Chen, S. Huh, J. W. Wiench, M. Pruski and
V. S.-Y. Lin, J. Am. Chem. Soc., 2005, 127, 13305;
(c) D.-H. Lee, J.-Y. Jung and M.-J. Jin, Green Chem., 2010,
12, 2024; (d) C. M. Crudden, M. Sateesh and R. Lewis, J. Am.
Chem. Soc., 2005, 127, 10045; (e) Y. Huang, S. Xu and S.-Y. Lin,
Angew. Chem., Int. Ed., 2011, 50, 661.
In contrast to the stoichiometric reaction, in the case of 5a,
the catalytic procedure led to 6a as the major diastereomer
(60%) and 7a was isolated in 30% yield as the minor diastereo-
isomer (entry 3). This could be explained by the slowing down
of the rate of epimerisation under catalytic conditions (entry 1,
Table 3). Due to the faster epimerisation of the product, the
cyclization of 5b gave almost the same results as the stoichio-
metric process (entry 4). Similar observations apply to the
rearrangement of pyroglutamic derivatives 5c and 5d. By the
way, we did succeed in performing a catalytic process with
yields as high as those obtained with 2 equivalents of base
without any loss of the enantioselectivity.
8 (a) J. M. Thomas and R. Raja, Acc. Chem. Res., 2008, 41, 708;
(b) J. M. Fraile, J. I. Garcıa, C. I. Herrerıas, J. A. Mayoral and
´ ´
E. Pires, Chem. Soc. Rev., 2009, 38, 695; (c) C. Li, H. Zhang,
D. Jiang and Q. Yang, Chem. Commun., 2007, 223; (d) R. de
´
Miguel, E. Brule and R. G. Margue, J. Chem. Soc., Perkin Trans.
1, 2001, 3085; (e) H. Yang, L. Zhang, P. Wang, Q. Yang and C. Li,
Green Chem., 2009, 11, 257; (f) A. Fuerte, A. Corma and
´
F. Sanchez, Catal. Today, 2005, 107–108, 404.
9 Y. Huang, B. G. Trewyn, H.-T. Chen and V. S.-Y. Lin, New J.
Chem., 2008, 32, 1311.
10 (a) J. P. Da Silva, S. Jockusch, J. M. G. Martinho, M. F. Ottaviani
and N. J. Turro, Org. Lett., 2010, 12, 3062; (b) A. Moscatelli,
Z. Liu, X. Lei, J. Dyer, L. Abrams, M. F. Ottaviani and
N. J. Turro, J. Am. Chem. Soc., 2008, 130, 11344 and previous
references cited therein; (c) M. K. Kidder, P. F. Britt,
A. L. Chaffee and A. C. Buchanan, Chem. Commun., 2007, 52;
(d) A. K. Sundaresan and V. Ramamurthy, Photochem. Photobiol.
Sci., 2008, 7, 1555.
In conclusion, mesoporous silica grafted with a tertiary
amino group is very efficient to promote in confined medium
the enantioselective cascade rearrangement of enediynes, in
11 For the unique example of Bergman cyclisation, see: X. Yang,
Z. Li, J. Zhi, J. Ma and A. Hu, Langmuir, 2010, 26, 11244.
12 (a) M. Kar and A. Basak, Chem. Rev., 2007, 107, 2861;
(b) D. S. Rawat and J. M. Zaleski, Synlett, 2004, 393;
(c) K. K. Wang, Chem. Rev., 1996, 96, 207; (d) J. W. Grissom,
G. U. Gunawardena, D. Klingberg and D. Huang, Tetrahedron,
1996, 52, 6453.
Table 4 Rearrangement of enediynes 1 and 5 using 20 mol % of
GA-SBA15a
Entry Substrate (ee)b Time/h 6c or 2 % (ee%)b 7c or 3% (ee%)b
1
2
3
4
5
6
1ad (88)
1bd (97)
5a (99)
5b (99)
5c (97)
5d (99)
13.5
8
13
5
13
5
30 (73)
33 (81)
60 (92)
61 (95)
34 (94)
40e (92)
44 (70)
42 (80)
30 (63)
31 (70)
56 (86)
60e (90)
13 (a) A. G. Myers and P. S. Dragovich, J. Am. Chem. Soc., 1989,
111, 9130; (b) R. Nagata, H. Yamanaka, E. Okazaki and I. Saito,
Tetrahedron Lett., 1989, 30, 4995.
14 For elegant examples of biradicals rearrangements, see:
K. K. Wang, in Modern Allene Chemistry, ed. N. Krause and
A. S. K. Hashmi, Wiley-VCH, Weinheim, 2004, p. 1091, vol. 2, and
references cited therein.
a
Reaction conditions:
1 or 5 (0.184 mmol), benzene (4 mL),
b
15 Similar results were obtained with Et3N (pKa = 11), but other
substrates like 5b led to faster epimerisation (pKaGA-SBA15 =
8.5). In addition, under homogeneous conditions, in CH3CN,
1b led to a significant amount of side-products.
GA-SBA15 (0.037 mmol, 20%), 80 1C. Determined by chiral
HPLC. Isolated yield. 21% of 4 was also isolated after cyclization.
c
d
e
NMR ratio, completed reaction was performed on 0.033 mmol.
c
5288 Chem. Commun., 2011, 47, 5286–5288
This journal is The Royal Society of Chemistry 2011