Catalyst self-adaptation in conjugate addition to nitroalkenes and nitroacrylates: Instant chirality control in diphenylmethane-based phosphoramidite ligands

Article abstract of DOI:10.1021/ja710340n

The tropos diphenylmethane-based phosphoramidite ligand (A) provides high catalytic activity and enantioselectivity in the Cu catalysis of conjugate addition to nitroalkenes and nitroacrylate, by virtue of instant chirality control in A. Copyright

Full text of DOI:10.1021/ja710340n

Published on Web 03/22/2008
Catalyst Self-Adaptation in Conjugate Addition to
Nitroalkenes and Nitroacrylates: Instant Chirality Control in
Diphenylmethane-Based Phosphoramidite Ligands
Kazuki Wakabayashi,† Kohsuke Aikawa,† Susumu Kawauchi,‡ and Koichi Mikami*,†
Departments of Applied Chemistry and Organic and Polymeric Materials, Tokyo Institute of
Technology, O-okayama, Meguro-ku, Tokyo 152-8552, Japan
Received November 15, 2007; E-mail: mikami.k.ab@m.titech.ac.jp
Asymmetric catalysis1 has long relied on the design of chirally
Scheme 1. Instant Chirality Control in Ligands (A)
rigid, particularly atropisomeric (atropos in Greek),2 ligands to
attain high enantioselectivity. However, even higher enantiose-
lectivity has recently been attained by chirally flexible (tropos)2
achiral benzophenone-derived diphosphine ligands, of which the
chirality is instantaneously controlled by a chiral activator
(A*-A) (Scheme 1a, M ) Ru, Rh, Pd, and Pt).3
Recently, binaphthol (BINOL)-derived phosphoramidite ligands
were developed for asymmetric conjugate additions.4 The
addition to nitroalkenes5 is one of the most synthetically
important methods to provide chiral amino (acid) derivatives6
but requires the matched combination of BINOL and amine
chiralities (Scheme 2, ligand B). We report here tropos
benzophenone-like phosphoramidite ligands (A) in which the
chirality can be instantaneously controlled7 by a chiral amine
built therein (Scheme 1b). Higher enantioselectivity and catalytic
activity can be attained in the Cu catalysis, by virtue of instant
chirality control in the ligands A; the ligands A fit well and
instantly with substrates and reagents (Scheme 2).
Scheme 2. Conjugate Additions to Nitroalkenes and Nitroacrylates
Complexation of phosphoramidite ligands A (A1: X ) H2, R
) 4-Me; A2: X ) H2, R ) H) and PdCl2(cod) was found to
give single PdCl2A2 enantiomers within minutes. Single PdCl2A2
enantiomers with C2-symmetry were instantaneously observed
1
in H NMR to show two singlets of four 4-Me groups in 2A
(see Supporting Information).
The advantage of the phosphoramidite ligand A can be seen
in the conjugate addition of diethylzinc to ꢀ-nitrostyrene (Table
1). Even at -78 °C within 3 h, the ligand A showed remarkably
high catalytic activity and enantioselectivity in the Cu catalysis
(>99%, 98% ee, entries 2 and 3).8
In order to differentiate from the biphenol (BIPOL) coun-
terpart C, the conformation of the Cu2+ precatalyst with the
ligand A2 was deduced with DFT calculation. Figure 1 shows
the most stable conformation localized in the Cu2+ precatalyst
with the phosphoramidite ligand A2. The side view of the A2
complex shows the more effective shielding of phenyl rings to
give higher enantioselectivity than the BIPOL or BINOL
counterparts (C, B) as observed in Table 1. The ethane-bridged
phosphoramidite A′ shows a similarly (or more) effective
shielding of phenyl rings.9
By contrast, enantioselectivity obtained even by an excellent
atropos biphenyl phosphoramidite ligand D sharply decreased
from p- to o-methoxyphenyl substrates (99 to 68% ee, entries
5, 7, and 9). The high enantioselectivity with ligand A1 (97 to
91% ee, entries 4, 6, and 8) exemplifies the advantage of instant
chirality control to fit well with the substrate change.
With the success in dialkylzinc reagent, the conjugate addition
of trimethylaluminum reagent to nitroacrylate substrate was then
Conjugate additions to other nitroalkene substrates were also
examined with the ligand A1 to give constantly high enanti-
oselectivities (Table 2). The p-, m-, and o-methoxyphenyl,
p-methylphenyl, and furyl substrates were also shown to give
high enantiomeric excesses (up to 99% ee).10
† Department of Applied Chemistry.
‡ Department of Organic and Polymeric Materials.
Figure 1. DFT calculations of Cu2+ precatalysts.
9
5012 J. AM. CHEM. SOC. 2008, 130, 5012–5013
10.1021/ja710340n CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Asymmetric Conjugate Additions of Et2Zn to ꢀ-Nitrostyrene
In summary, we have developed the ligands A to give higher
enantioselectivity and catalytic activity in the Cu-catalyzed
conjugate additions to nitroalkenes, by virtue of their instant
chirality control. The highly tropos phosphoramidite ligands A
outperform the analogous rigid (atropos) BINOL- and even
BIPOL-derived phosphoramidite ligands. These results represent
emblematic cases of catalyst self-adaptation and tuning.
Acknowledgment. This work was supported by a Grant-in-
Aid for Scientific Research on Priority Areas “Advanced Molecular
Transformations of Carbon Resources” from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
entry
ligand
temp (°C)
conv. (%)
ee (%)
1
2
3
A1 (R ) Me)
A1 (R ) Me)
A2 (R ) H)
(R)/(S,S)-B
(R)/(S,S)-B
(R)/(S,S)-B
(S)/(S,S)-B
(S)/(S,S)-B
C
-45
-78
-78
-45
-30
-78
-45d
-78
-45
-30
-65
>99
>99
>99
>99
>99
90
>99
80
>99
>99
>99
94 (S)
98 (S)
98 (S)
59
48 (R)
48 (S)
32
39 (S)
77
8 (R)
94 (R)
Supporting Information Available: Experimental procedures
for the preparation of ligand A and for the conjugative addition to
nitroalkenes; DFT calculation data of the Cu(II) precatalyst of ligand
A2 and C (PDF). This material is available free of charge via the
Internet at http://pubs.acs.org.
4a
5b
6c
7a
8c
9a
10b
11e
References
C
D
(1) (a) Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH: New York, 1993,
2000; Vols. I and II. (b) Brunner, H.; Zettlmeier, W. Handbook of
EnantioselectiVe Catalysis; VCH: Weinheim, Germany, 1993. (c) Noyori,
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M., Eds; Wiley: New York, 2007.
a See ref 5d. b See ref 5c. c See ref 5a. d Lower temperature (-78 °C)
led to a lower reaction rate. e Cu(OTf)2 (1 mol %), ligand (2 mol %),
reaction time (6 h) (ref 5g).
Table 2. Asymmetric Conjugate Additions of Et2Zn to Nitroalkenes
(2) The word atropos consists of “a” meaning “not” and “tropos” meaning
“turn” in Greek. Therefore, the chirally rigid or flexible nature of a ligand
can be called atropos or tropos, respectively. (a) Mikami, K.; Aikawa, K.;
Yusa, Y.; Jodry, J. J.; Yamanaka, M. Synlett 2002, 1561–1578. Also see:
(b) Kuhn, W. In Stereochemie; Freudenberg, K., Ed.; Franz Deuticke:
Leipzig, 1933; pp 803–824.
entry
Ar
ligand
temp (°C)
conv. (%)
ee (%)
(3) Review: (a) Mikami, K.; Yamanaka, M. Chem. ReV. 2003, 103, 3369–
3400. (b) Mikami, K.; Wakabayashi, K.; Aikawa, K. Org. Lett. 2006, 8,
1517–1519. (c) Mikami, K.; Wakabayashi, K.; Yusa, Y.; Aikawa, K. Chem.
Commun. 2006, 2365–2367. (d) Jing, Q.; Sandoval, C. A.; Wang, Z.; Ding,
K. Eur. J. Org. Chem. 2006, 3606–3616. (e) Mikami, K.; Sayo, N. PCT
Int. Appl. 2005, 107.
(4) Reviews: (a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346–353. (b) Alexakis,
A.; Benhaim, C. Eur. J. Org. Chem. 2002, 3221–3236. (c) Feringa, B. L.;
Naasz, R.; Imbos, R.; Arnold, L. A. In Modern Organocopper Chemistry;
Krause, N., Ed.; Wiley-VCH: Weinhiem, Germany, 2002; pp 224–258.
(d) Feringa, B. L.; Pineschi, M.; Arnold, L. A.; Imbos, R.; de Vries, A. H. M.
Angew. Chem., Int. Ed. Engl. 1997, 36, 2620–2623. Tropos biphenol ligand
C: (e) Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.; Benhaim,
C. Synlett 2001, 1375–1378. (f) Hua, Z.; Vassar, V. C.; Choi, H.; Ojima, I.
Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5411–5416. (g) Monti, C.; Gennari,
C.; Piarulli, U. Chem. Eur. J. 2007, 13, 1547–1558.
1
p-MePh
p-MePh
p-MePh
p-MeOPh
p-MeOPh
m-MeOPh
m-MeOPh
o-MeOPh
o-MeOPh
p-CF3Ph
p-CF3Ph
furyl
A1
-78
-30
-65
-78
-65
-78
-65
-78
-65
-78
-65
-78
-30
-65
>99
>99
>99
>99
>99
>99
>99
99
>99
>99
>99
>99
>99
>99
96
25
98
97
99
93
84
91
67
91
77
99
8
2a
3b
4
(R)/(S,S)-B
D
A1
5b
6
D
A1
7b
8
D
A1
9b
10
11b
12
13a
14b
D
A1
D
A1
furyl
furyl
(R)/(S,S)-B
D
(5) Conjugate additions to nitroalkenes: (a) Sewald, N.; Wendisch, V. Tetra-
hedron: Asymmetry 1998, 9, 1341–1344. (b) Alexakis, A.; Benhaim, C.
Org. Lett. 2000, 2, 2579–2581. (c) Alexakis, A.; Benhaim, C.; Rosset, S.;
Humam, M. J. Am. Chem. Soc. 2002, 124, 5262–5263. (d) Duursma, A.;
Minnaard, A. J.; Feringa, B. L. Tetrahedron 2002, 58, 5773–5778. (e)
Luchaco-Cullis, C. A.; Hoveyda, A. H. J. Am. Chem. Soc. 2002, 124, 8192–
8193. (f) Duursma, A.; Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc.
2003, 125, 3700–3701. (g) Choi, H.; Hua, Z.; Ojima, I. Org. Lett. 2004, 6,
2689–2691. (h) Cote, A.; Lindsay, V.N. G.; Charette, A. B. Org. Lett. 2007,
9, 85–87.
92
a See ref 5b. b Cu(OTf)2 (1 mol %), ligand (2 mol %), reaction time
(6 h) (ref 5g).
Table 3. Conjugate Additions of Me3Al to Nitroacrylate
(6) Broen, B. R. The Organic Chemistry of Aliphatic Nitrogen Compounds;
Oxford University: Oxford, 1994; pp 443–469..
(7) Compared to one single bond rotation of a biphenyl compound, two single
bond rotations of a benzophenone-like compound are more facile and the
chirality in A can be instantaneously controlled. Also see: Lunazzi, L.;
Mazzanti, A.; Minzoni, M. J. Org. Chem. 2005, 70, 456–462.
entry
ligand
temp (°C)
yield (%)
ee (%)
1
2
3
a
A1
-78
-78
-78
-50
>99
74
72
93 (S)
93 (R)
60 (R)
92 (R)
(8) After submission of our paper, ligand A2 has been reported to give, however,
only low enantioselectivity (35% ee). Palais, L.; Mikhel, I. S.; Bournaud,
C.; Falciola, C. A.; Vuagnoux-d’Augustin, M.; Rosset, S.; Bernardinelli,
G.; Alexakis, A. Angew. Chem., Int. Ed. 2007, 46, 7462–7465.
(9) The ethane-bridged phosphoramidites are now under investigation.
(10) Conjugate additions to other nitroalkene substrates are shown in Supporting
Information. The reaction with diphenylzinc did not take place.
(11) Conjugate additions to nitroacrylates: (a) Versleijen, J. P. G.; van Leusen, A. M.;
Feringa, B. L. Tetrahedron Lett. 1999, 40, 5803–5806. (b) Rimkus, A.;
Sewald, N. Org. Lett. 2003, 5, 79–80. (c) Eilitz, U.; Leßmann, F.; Seidelmann,
O.; Wendisch, V. Tetrahedron: Asymmetry 2003, 14, 3095–3097.
(12) (a) Cheng, R. P.; Gellman, S. H.; DeGrado, W. F. Chem. ReV. 2001, 101,
3219–3232. (b) Hagiwara, H.; Anthony, N. J.; Stout, T. J.; Clardy, J.;
Schreiber, S. L. J. Am. Chem. Soc. 1992, 114, 6568–6570.
(S)/(R,R)-B
(R)/(R,R)-B
(S)/(R,R)-B
85
a See ref 11c.
examined11 to give synthetically useful ꢀ-amino acid derivative,
ꢀ2-alanine12 (Table 3). Phosphoramidite ligand A1 afforded high
yield and enantioselectivity (>99%, 93% ee). The product can
be easily transformed to ꢀ2-alanine ethyl ester by hydrogenation
with palladium on charcoal.11c
JA710340N
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J. AM. CHEM. SOC. VOL. 130, NO. 15, 2008 5013