Atroposelective [2+2+2] cycloadditions catalyzed by a rhodium(i)-chiral phosphate system

Article abstract of DOI:10.1039/c3cc43188f

Enantioselective cationic Rh(i)-catalyzed [2+2+2] cycloaddition reactions between diynes and isocyanates relying on the chiral anion strategy have been devised. In the presence of [Rh(cod)Cl]₂, 1,4-bis(diphenylphosphino) butane, and the silver phosphate salt Ag(S)-TRIP as the unique source of chirality, axially chiral pyridones were isolated with ees up to 82%. This approach is novel in the field of chiral anion-mediated asymmetric catalysis since atroposelective transformations have so far remained unprecedented. It also proves to be complementary to the classical strategy based on chiral L-type ligands.

Full text of DOI:10.1039/c3cc43188f

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Atroposelective [2+2+2] cycloadditions catalyzed
by a rhodium(I)–chiral phosphate system†
Cite this: DOI: 10.1039/c3cc43188f
a
a
a
a
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Mylene Auge, Marion Barbazanges, Anh Tuan Tran, Antoine Simonneau,
Paulin Elley,a Hani Amouri,a Corinne Aubert,*a Louis Fensterbank,*a
Vincent Gandon,b Max Malacria,a Jamal Moussaa and Cyril Ollivier*a
Received 30th April 2013,
Accepted 26th June 2013
DOI: 10.1039/c3cc43188f
www.rsc.org/chemcomm
Enantioselective cationic Rh(I)-catalyzed [2+2+2] cycloaddition the case of asymmetric allenol or allenamide cycloisomerization.5m
reactions between diynes and isocyanates relying on the chiral To the best of our knowledge, there is no example of asymmetric
anion strategy have been devised. In the presence of [Rh(cod)Cl]2, [2+2+2] cycloaddition relying on this strategy and the use of chiral
1,4-bis(diphenylphosphino)butane, and the silver phosphate salt anions to control the axial chirality remains unprecedented.
Ag(S)–TRIP as the unique source of chirality, axially chiral pyridones Besides, to the best of our knowledge, rhodium ACDC has been
were isolated with ees up to 82%. This approach is novel in the field of reported only once, by Leitner, Klankermayer and co-workers,
chiral anion-mediated asymmetric catalysis since atroposelective trans- in the enantioselective hydrogenation of dimethyl itaconate
formations have so far remained unprecedented. It also proves to be based on a large excess of chiral borate anions.5ee,6
complementary to the classical strategy based on chiral L-type ligands.
We describe herein our efforts to construct a carbon–nitrogen
axis in an asymmetric fashion from diynes and isocyanates7
Metal-catalyzed cyclizations of unsaturated substrates represent an using chiral [Rh(I)][phosphate] ion pairs.
active area of research in organic synthesis.1 Within this family,
As reported by Tanaka and coll. the cycloaddition of diynes 1
transition metal-catalyzed [2+2+2] cycloaddition reactions figure with isocyanates 2 in the presence of a pre-stirred solution of
among the most expedient routes to synthesise complex polycyclic [Rh(cod)2][BF4] and (R)-BINAP under H2 leads to pyridones 3 in good
scaffolds.1b,2 A very attractive feature of such transformations is that yields and modest to good enantiomeric excesses (Scheme 1).7c
they can lead to optically active compounds of high synthetic Alternatively, the catalytic species can be generated in situ from
potential. In particular, cationic Rh(I)+/BINAP-type bisphosphine [Rh(cod)Cl]2, AgBF4 and (R)-BINAP under H2 at room temperature.
complexes proved to be versatile catalysts which control axial,
We sought to implement the chiral anion strategy in this reaction
planar, central, and helical chirality.1b,2,3 In this approach, the by altering the conditions and promoting anion metathesis between
metal is bound to a strongly coordinating chiral L2-type ligand. [Rh(cod)Cl]2 and the chiral silver phosphate Ag(S)–TRIP (Ag-4a) to
Although chemo-, regio-, and diastereoselectivities are generally provide a [Rh(I)][phosphate] chiral complex. By means of compar-
well-controlled, enantioselective approaches are highly dependent ison, the classical approach was also performed (Table 1). Use of
on the substrates, and create a real need for new catalytic systems. [Rh(cod)Cl]2, AgBF4 as chloride scavenger, and no additional ligand,
An alternative way to achieve cationic Rh(I)-catalyzed enantio- gave no conversion (entry 1). On the other hand, with (R)-BINAP,
selective [2+2+2] cycloadditions would be to locate the stereo- compound (+)-3aa was isolated in 84% yield and 67% ee (entry 2),
chemical information at the weakly coordinating X-type ligand which is consistent with Tanaka’s results when using the preformed
which can be easily displaced by the substrate. Asymmetric [Rh(cod)2][BF4] (72%, 68% ee).7c Likewise, no reaction took place
counteranion-directed catalysis (ACDC), as coined by List, is an with Ag-4a and no bisphosphine (entry 3). The presence of rac-BINAP
emerging strategy in enantioselective synthesis.4,5 Importantly, it unlocked the situation but pyridone (ꢀ)-3aa was formed in low yield
has allowed to bypass some physical and chemical barriers such as
the gold(I) linear coordination, as shown by Toste and co-workers in
a
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UPMC Univ Paris 06, UMR 7201 CNRS, Institut Parisien de Chimie Moleculaire,
F-75005, Paris, France. E-mail: corinne.aubert@upmc.fr,
louis.fensterbank@upmc.fr, cyril.ollivier@upmc.fr; Fax: +33 1-44-27-73-60
b Univ Paris-Sud 11, ICMMO, UMR CNRS 8182, 91405 Orsay, France
† Electronic supplementary information (ESI) available: Representative proce-
dures, chiral HPLC chromatogram, characterization and spectra of new pyridones
synthesized. See DOI: 10.1039/c3cc43188f
Scheme 1 [2+2+2] Cycloaddition of diynes 1 with isocyanates 2.7c
c
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Table 1 Ligand screening
Table 3 Scope and limitations
Substrate
Entry R1
Product Yield (%) eea (%) eea (%)
Entry
La
AgX
Yield (%)
eeb (%)
1
2
3
4
5
6
7
OMe 3aa
77
73
69
87
88
18
18
71 (ꢀ)
81 (ꢀ)
29 (ꢀ)
32 (ꢀ)
26 (+)
36 (ꢀ)
8 (ꢀ)
67 (+)c
59 (+)c
OEt
Me
Et
i-Pr
Cl
3ab
3ac
3ad
3ae
3af
1
2c
3
4
5
6
None
(R)-BINAP
None
rac-BINAP
DppL
Dppb
AgBF4
AgBF4
Ag-4a
Ag-4a
Ag-4a
Ag-4a
0
84
0
30
0
—
67 (+)
—
79 (+)c
60 (+)c
9 (ꢀ)
—
Br
3ag
39
18 (ꢀ)
8
9
10
11
12
OMe 3ba
84
80
84
75
51
77 (ꢀ)
79 (ꢀ)
34 (ꢀ)
4 (+)
58 (+)b
46 (+)c
30 (+)b
67 (+)b
56 (+)b
a
BINAP: 2,20-bis(diphenylphosphino)-1,10-binaphthyl; dppL: PPh2–
OEt
Me
i-Pr
Cl
3bb
3bc
3be
3bf
[CH2]n–PPh2 (n = 1, 2, 3, 5, 6); dppb: 1,4-bis(diphenylphosphino)butane.
b
c
Chiral HPLC: AD-H, 90/10 n-hex/i-PrOH, 1 mL minꢀ1
. So-called
classical approach.
34 (ꢀ)
13
14
15
OMe 3ca
68
64
85
74 (ꢀ)
82 (ꢀ)
41 (ꢀ)
39 (+)c
25 (+)c
OEt
Me
3cb
3cc
and poor enantiomeric excess (entry 4). Diyne 1a remained
intact when using achiral 1,n-bis(diphenylphosphino)alkanes
(entry 5), except with 1,4-bis(diphenylphosphino)butane (entry
6), but again the selectivity was low. Thus, with rac-BINAP and
dppb, pyridone (ꢀ)-3aa could be isolated in modest yield and ee
compared to the classical approach. Nevertheless, the concept
was validated and it encouraged us to explore further this
intriguing case of asymmetric chiral anion-directed [2+2+2]
cycloaddition.
16
17
OMe 3da
OMe 3ea
38
65
72 (ꢀ)
58 (ꢀ)
34 (+)b
52 (ꢀ)c
Chiral HPLC. b Ref. 7c ([Rh(cod)2][BF4]/(R)-BINAP, 5 mol%). c [Rh(cod)Cl]2/
(R)-BINAP/AgBF4 (5 mol%), H2 pre-stirring, rt. Ts: 4-p-toluenesulfonyl.
a
When the reactions were carried out without H2 premix (or
after an extended argon premix), less than 5% conversion was further increased to 71% using a slight excess of Ag-4a in a
reached. Since the role of H2 is to eliminate the cyclooctadiene sealed vessel (entry 3).8 Good to excellent yields were obtained
(cod) ligand from the coordination sphere of the metal, we with the other tested silver salts, however the ee dropped
reasoned that higher temperature might also be beneficial. In dramatically (entries 4–7). Although the enantioselectivities
fact, carrying out the reaction in dichloroethane at 80 1C were lower with Ag-4b–e, it is nonetheless interesting to note
significantly improved the selectivity (Table 2). Even without that the substitution at the 3,30 positions of the biaryl frame-
H2 pre-stirring, the desired pyridone was isolated in 95% yield work influences the absolute configuration.
and 52% ee (entry 1). An additional 15 min argon pre-stirring
Using the optimized conditions (Table 2, entry 3), the scope
improves the enantiomeric excess to 67%. The ee could be and limitations of the title reaction were investigated next
(Table 3). With diyne 1a, various isocyanates proved compatible
with the chiral anion approach (entries 1–7). However, those
exhibiting at R1 an ortho alkoxy group gave rise to the best ees
Table 2 Conditions and chiral phosphate screening
(entries 1 and 2, 71% and 81% ee respectively). With R1 = alkyl
groups, although the yields are good to excellent, the steric
demand seems to play a negative role in the enantioselectivity
(entries 3–5). The presence of chlorine or bromine substituents
proved detrimental in terms of yield and enantioselectivity
(entries 6 and 7). The same conclusions could be reached with
the other diynes. Starting from alkoxylated isocyanates, the ee
could be improved to 77–79% by changing the nature of the
diyne tether to the gem-diester 1b (entry 8 and 9). The cyclic
acetal substituted diyne 1c was also converted in appreciable
yield and ee when reacted with the same isocyanates (entries 13
and 14, 74% and 82% ee respectively). Diyne 1d exhibiting an
NTs group in the tether gave rise to the expected pyridone 3da in
moderate yield, but in a significantly enantioenriched fashion
(entry 16, 72% ee). Lastly, when testing diyne 1e possessing a
Entry
AgX
x
Yield (%)
eea (%)
1b
2
3
4
5
Ag-4a
Ag-4a
Ag-4a
Ag-4b
Ag-4c
Ag-4d
Ag-4e
5
5
7.5
7.5
7.5
7.5
7.5
95
83
77
87
86
95
69
52 (ꢀ)
67 (ꢀ)
71 (ꢀ)
20 (ꢀ)
20 (+)
16 (+)
0
6
7
a
b
Chiral HPLC: AD-H, 90/10 n-hex/i-PrOH, 1 mL minꢀ1
.
No pre-stirring. 3-carbon unsubstituted tether, both yield and ee decreased,
c
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52, 518; (e) E. P. Avila and G. W. Amarante, ChemCatChem, 2012,
indicating the underlying positive gem-dialkyl effect on the
reaction (entry 17).9
´
´
4, 1713; ( f ) A. Parra, S. Reboredo, A. M. Martın Castro and J. Aleman,
Org. Biomol. Chem., 2012, 10, 5001; (g) K. Brak and E. N. Jacobsen,
Angew. Chem., Int. Ed., 2013, 52, 534.
Overall, the trends deduced from Table 3 are opposite to those of
the classical approach. An important learning coming from this 5 Copper: (a) D. B. Llewellyn, D. Adamson and B. A. Arndtsen, Org. Lett.,
2000, 2, 4165; (b) D. B. Llewellyn and B. A. Arndtsen, Organometallics,
2004, 23, 2838; (c) D. B. Llewellyn and B. A. Arndtsen, Tetrahedron:
Asymmetry, 2005, 16, 1789; (d) B. Zhao, H. Du and Y. Shi, J. Org.
study is that the chiral counterion strategy can outperform the
classical one sometimes. The examples displayed in entries 1, 2,
8–10, 13, 14, 16 and 17 show that better enantioselectivities can be
reached mainly with alkoxylated isocyanates. In contrast, chlorinated
and sterically demanding alkyl isocyanate derivatives are relevant
choices when the classical method is implemented, as shown in
entries 5, 6, 11 and 12. The two methods are thus complementary.
In conclusion, we have performed the first asymmetric chiral
anion-directed transition metal-catalyzed [2+2+2] cycloaddition
reactions through the use of [Rh(I)][phosphate] system. This
transformation involves an axial (chiral anion) to axial (pyridone)
chirality transfer. Of particular interest, the chiral counterion
strategy proved complementary to the classical one involving
chiral bisphosphines, which emphasizes its relevance as an
alternative to chiral L-type ligands to induce enantioselectivity
in metal-catalyzed reactions. Studies aimed at characterizing the
intermediates involved and to gain insights into the mechanism
of this reaction are underway in our laboratory.
Chem., 2009, 74, 8392; (e) R. Yazaki, N. Kumagai and M. Shibasaki,
J. Am. Chem. Soc., 2010, 132, 10275. Palladium: ( f ) S. Mukherjee and
B. List, J. Am. Chem. Soc., 2007, 129, 11336; (g) G. Jiang and B. List,
Angew. Chem., Int. Ed., 2011, 50, 9471; (h) G. Jiang, R. Halder, Y. Fang
and B. List, Angew. Chem., Int. Ed., 2011, 50, 9752; (i) Z. Chai and
T. J. Rainey, J. Am. Chem. Soc., 2012, 134, 3615; ( j) M. Arthuis,
R. Beaud, V. Gandon and E. Roulland, Angew. Chem., Int. Ed., 2012,
51, 10510; (k) K. Ohmatsu, M. Ito, T. Kunieda and T. Ooi, Nat. Chem.,
2012, 4, 473; (l) K. Ohmatsu, M. Ito, T. Kunieda and T. Ooi, J. Am.
Chem. Soc., 2013, 135, 590. Gold: (m) G. L. Hamilton, E. J. Kang,
M. Mba and F. D. Toste, Science, 2007, 317, 496; (n) K. Aikawa,
M. Kojima and K. Mikami, Angew. Chem., Int. Ed., 2009, 48, 6073;
(o) R. L. Lalonde, Z. J. Wang, M. Mba, A. D. Lackner and F. D. Toste,
Angew. Chem., Int. Ed., 2010, 49, 598; (p) K. Aikawa, M. Kojima and
K. Mikami, Adv. Synth. Catal., 2010, 352, 3131; (q) A. K. Mourad,
J. Leutzow and C. Czekelius, Angew. Chem., Int. Ed., 2012, 51, 11149;
(r) M. Kojima and K. Mikami, Synlett, 2012, 57; (s) S. Gaillard, D. Rix,
A. M. Z. Slawin, J. Lacour and S. P. Nolan, Dalton Trans., 2012,
41, 8235. Ruthenium: (t) G. Jiang and B. List, Chem. Commun.,
2011, 47, 10022; (u) J. R. Zbieg, E. Yamaguchi, E. L. McInturff and
M. J. Krische, Science, 2012, 336, 324. Manganese: (v) S. Liao and
B. List, Angew. Chem., Int. Ed., 2010, 49, 628. Indium: (w) Y.-Y. Huang,
A. Chakrabarti, N. Morita, U. Schneider and S. Kobayashi, Angew.
Chem., Int. Ed., 2011, 50, 11121. Yttrium: (x) Y. Deng, L. Liu,
R. G. Sarkisian, K. Wheeler, H. Wang and Z. Xu, Angew. Chem., Int.
Ed., 2013, 52, 3663. Iron: (y) S. Liao and B. List, Adv. Synth. Catal.,
2012, 354, 2363. Iridium: (z) C. Li, C. Wang, B. Villa-Marcos and
J. Xiao, J. Am. Chem. Soc., 2008, 130, 14450; (aa) C. Li, B. Villa-Marcos
and J. Xiao, J. Am. Chem. Soc., 2009, 131, 6967; (bb) M. Barbazanges,
This work was supported by the CNRS, UPMC, IUF and
Agence Nationale de la Recherche (ANR-09-BLAN-108 SACCAOR)
which we gratefully acknowledge. We warmly thank Prof. Ken
Tanaka for a fruitful discussion about the generation of the
catalytic species.
Notes and references
´
M. Auge, J. Moussa, H. Amouri, C. Aubert, C. Desmarets, L. Fensterbank,
V. Gandon, M. Malacria and C. Ollivier, Chem.–Eur. J., 2011, 17, 13789;
(cc) M. Rueping and R. M. Koenigs, Chem. Commun., 2011, 47, 304;
(dd) W. Chen and J. F. Hartwig, J. Am. Chem. Soc., 2013, 135, 2068.
Rhodium: (ee) D. Chen, B. Sundararaju, R. Krause, J. Klankermayer,
P. H. Dixneuf and W. Leitner, ChemCatChem, 2010, 2, 55.
1 (a) Handbook of Cyclization Reactions, ed. S. Ma, Wiley-VCH, Wein-
heim, 2009, vol. 1; (b) [m+n+2] Carbocyclization Reactions C. Aubert,
M. Malacria and C. Ollivier, in Science of Synthesis: Stereoselective
Synthesis, ed. J. G. De Vries, G. Molander and P. A. Evans, 2011,
ch. 3.4, vol. 3, p. 145.
6 The use of a rhodium catalyst in the presence of chiral phosphoric
acid has also been reported by Krische and co-workers, see:
V. Komanduri and M. J. Krische, J. Am. Chem. Soc., 2006, 128, 16448.
7 (a) K. Tanaka, A. Wada and K. Noguchi, Org. Lett., 2005, 7, 4737;
(b) R. T. Yu and T. Rovis, J. Am. Chem. Soc., 2006, 128, 12370;
(c) K. Tanaka, Y. Takahashi, T. Suda and M. Hirano, Synlett, 2008,
1724; (d) E. E. Lee and T. Rovis, Org. Lett., 2008, 10, 1231; (e) R. T. Yu,
E. E. Lee, G. Malik and T. Rovis, Angew. Chem., Int. Ed., 2009, 48, 2379;
( f ) M. E. Oinen, R. T. Yu and T. Rovis, Org. Lett., 2009, 11, 4934;
(g) R. K. Friedman and T. Rovis, J. Am. Chem. Soc., 2009, 131, 10775;
(h) D. M. Dalton, K. M. Oberg, R. T. Yu, E. E. Lee, S. Perreault,
M. E. Oinen, M. L. Pease, G. Malik and T. Rovis, J. Am. Chem. Soc.,
2009, 131, 15717.
2 (a) V. Gandon, C. Aubert and M. Malacria, Chem. Commun., 2006, 2209;
(b) B. Heller and M. Hapke, Chem. Soc. Rev., 2007, 36, 1085; (c) N. Agenet,
O. Buisine, F. Slowinski, V. Gandon, C. Aubert and M. Malacria, Org.
React., 2007, 68, 1; (d) W. Hess, J. Treutwein and G. Hilt, Synthesis, 2008,
´
3537; (e) J. A. Varela and C. Saa, Synlett, 2008, 2571; ( f ) D. Leboeuf,
V. Gandon and M. Malacria, in Handbook of Cyclization Reactions, ed.
S. Ma, Wiley-VCH, Weinheim, 2009, vol. 1, p. 367; (g) K. Tanaka,
Chem.–Asian J., 2009, 4, 508; (h) B. R. Galan and T. Rovis, Angew. Chem.,
Int. Ed., 2009, 48, 2830; (i) P. A. Inglesby and P. A. Evans, Chem. Soc. Rev.,
´
´
2010, 39, 2791; ( j) G. Domınguez and J. Perez-Castells, Chem. Soc. Rev.,
2011, 40, 3430; (k) N. Weding and M. Hapke, Chem. Soc. Rev., 2011,
40, 4525; (l) Y. Shibata and K. Tanaka, Synthesis, 2012, 323; (m) D. L. J.
Broere and E. Ruijter, Synthesis, 2012, 2639.
8 The same reaction performed under double stereodifferentiating
conditions, in the presence of enantiomerically pure (R)-BINAP and
(S)-BINAP as the ligand, afforded pyridone 3aa in similar but opposite
62% (+) and 61% (ꢀ) ee, respectively.
3 K. Tanaka, Synlett, 2007, 1977.
4 For recent reviews, see: (a) J. Lacour and D. Moraleda, Chem. Com-
mun., 2009, 7073; (b) R. J. Phipps, G. L. Hamilton and F. D. Toste, Nat.
Chem., 2012, 4, 603; (c) M. Mahlau and B. List, Isr. J. Chem., 2012,
52, 630; (d) M. Mahlau and B. List, Angew. Chem., Int. Ed., 2013, 9 M. E. Jung and G. Piizi, Chem. Rev., 2005, 105, 1735.
c
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Chem. Commun.