cis-2,5-diaminobicyclo[2.2.2]octane, a new scaffold for asymmetric catalysis via salen-metal complexes

Article abstract of DOI:10.1021/ol2007378

Chemical equations presented. A new C₂ symmetric salen scaffold based on cis-2,5-diaminobicyclo[2.2.2]octane has been synthesized that forms complexes with a wide range of metals. The chromium(III) complex is shown to catalyze the hetero-Diels-

Full text of DOI:10.1021/ol2007378

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2488–2491
cis-2,5-Diaminobicyclo[2.2.2]octane, a
New Scaffold for Asymmetric Catalysis via
SalenꢀMetal Complexes
James D. White* and Subrata Shaw
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331,
United States
James.white@oregonstate.edu
Received March 18, 2011
ABSTRACT
A new C2 symmetric salen scaffold based on cis-2,5-diaminobicyclo[2.2.2]octane has been synthesized that forms complexes with a wide range of
metals. The chromium(III) complex is shown to catalyze the hetero-DielsꢀAlder reaction and the NozakiꢀHiyamaꢀKishi reaction with high
efficiency and excellent stereoselectivity.
Chiral salen ligands in combination with certain metals
have proven to be highly effective species for catalyzing a
wide range of organic transformations with good to ex-
cellent levelsof asymmetricinduction.1,2 Almostall ligands
ofthistypeare basedona chiral 1,2-diamine, e.g. trans-1,2-
diaminocyclohexane (1), as the core scaffold.3 Exceptions
are Berkessel’s salen ligand “DIANANE”4 derived from
cis-2,5-diaminobicyclo[2.2.1]heptane(2) and a1,4-diamine
derived from isophorone.5 Although diamine 2 has been
prepared in enantiopure form, only the Cr(III) complex of
the salen derivative has been studied as an asymmetric
catalyst. In our search for a chiral template that would
have broad utility as a catalyst in asymmetric synthesis,6
we have examined cis-2,5-diaminobicyclo[2.2.2]octane (3)7
as a scaffold for salenꢀmetal complexes. We have found
that diamine 3 is not only easy to prepare in enantiopure
form but that its salen derivative forms a large number of
stable metal complexes. In this report, we show that the
Cr(III) complex of this salen ligand catalyzes the hetero-
DielsꢀAlder reaction8,9 and the NozakiꢀHiyamaꢀKishi
reaction10,11 in high yield and with excellent levels of
asymmetric induction.
(8) For reviews of the hetero-DielsꢀAlder reaction, see: (a) Jorgen-
sen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558. (b) Lin, L.; Liu., X.;
Feng, X. Synlett 2007, 2147.
(9) For hetero-DielsꢀAlder reactions catalyzed by Cr(salen) com-
plexes, see: (a) Schaus, S. E.; Branal, J.; Jacobsen, E. N. J. Org. Chem.
1998, 63, 403. (b) Aikawa, K.; Irie, R.; Katsuki, T. Tetrahedron 2001, 57,
845. (c) Bandini, M.; Cozzi, P. G.; Umani-Ronchi, A. Chem. Commun.
2002, 919. (d) Mellah, M.; Ansel, F.; Voituriez, A.; Schulz, E. J. Mol.
Catal.: Chem. 2007, 272, 20. (e) Eno, S.; Egami, H.; Uchida, T.; Katsuki,
T. Chem. Lett. 2008, 37, 632.
(10) For NHK reactions catalyzed by Cr(salen) complexes, see: (a)
Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-Ronchi, A. Angew.
Chem., Int. Ed. 1999, 38, 3357. (b) Bandini, M.; Cozzi, P. G.; Umani-
Ronchi, A. Polyhedron 2000, 19, 537. (c) Bandini, M.; Cozzi, P. G.;
Umani-Ronchi, A. Angew Chem. Int. Ed. 2000, 39, 2327. (d) Bandini,
M.; Cozzi, P. G.; Umani-Ronchi, A. Tetrahedron 2001, 57, 835. (e)
Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Morganti, S.; Umani-Ronchi,
A. Org. Lett. 2001, 3, 1153. (f) Berkessel, A.; Menche, D.; Sklorz, C. A.;
Schroder, M.; Paterson, I. Angew. Chem., Int. Ed. 2003, 42, 1032.
(11) For an asymmetric NHK reaction catalyzed by a chiral Cr(III)ꢀ
sulfonamide complex, see: Choi, H.-W.; Nakajima, K.; Demeke,
D.; Kang, F. A.; Jun, H. S.; Wan, Z. K.; Kishi, Y. Org. Lett. 2002, 4, 4435.
(1) Larrow, J. F.; Jacobsen, E. N. Top. Organomet. Chem. 2004, 4,
123.
(2) Canali, L.; Sherrington, D. C. Chem. Soc. Rev. 1999, 28, 85.
(3) Cozzi, P. G. Chem. Soc. Rev. 2004, 33, 410.
€
(4) Berkessel, A.; Schroder, M.; Sklorz, C. A.; Tabanella, S.; Vogl,
€
N.; Lex, J.; Neudorfl, J. M. J. Org. Chem. 2004, 69, 3050.
(5) Berkessel, A.; Roland, K.; Schroder, M.; Neudorfl, J. M.; Lex, J.
J. Org. Chem. 2006, 71, 9312.
(6) A structure meeting this qualification is defined as “privileged”
(Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691).
(7) Aksani, R.; Eichenauer, H.; Kohler, J. Chem. Ber. 1982, 115, 751.
r
10.1021/ol2007378
Published on Web 04/04/2011
2011 American Chemical Society

A structural feature of diamine 3 that is particularly
attractive is the large separation of nitrogen atoms, as
determined by X-ray crystallographic analysis, compared
to 1 and 2 (Figure 1). This gives the salen ligand derived
from 3 a broad “wingspan” that encloses a large volume of
chiral space while preserving a rigid asymmetric environ-
ment. There is also a larger degree of “twist” around the C2
axisof 3, reflectedina HaꢀCꢀCꢀHb dihedral angle of 22°,
than in the bicyclo[2.2.1]heptane frame of 2 where the
corresponding dihedral is calculated to be 14°.
Scheme 1. Synthesis of Diamine (ꢀ)-3 and Its SalenꢀMetal
Complexes
˚
Figure 1. NꢀN distance (A) in chiral diamine scaffolds for 1ꢀ3.
The synthesis of 3 began with the DielsꢀAlder addition
of neat methyl acrylate to 1,3-cyclohexadiene-2-carboxylic
acid (4, Scheme 1).12 The endo adduct was hydrogenated,
and ester 5 was saponified to yield racemic dicarboxylic
acid 6.13 The resolution of 6 was accomplished by treat-
ment with (ꢀ)-brucine which afforded a crystalline salt
amenable to X-ray analysis; acidic hydrolysis of this pure
diastereomer gave (ꢀ)-6 with (1R,2R,4R,5R) absolute
configuration. Diacid (ꢀ)-6 was advanced via the corre-
sponding diacyl chloride 7 to diacyl azide 8 which under-
went in situ double Curtius rearrangement upon heating to
produce bis isocyanate (ꢀ)-9. Hydrolysis of 9 and concomi-
tant decarboxylation of the biscarbamic acid gave diamine
(ꢀ)-3. Condensation of (ꢀ)-3 with 3,5-di-tert-butylsalicylal-
dehyde (10) furnished Schiff base (þ)-11 as a crystalline solid
whose structure was confirmed by X-ray analysis.
Salen ligand (þ)-11 was reacted with the metal salts
shown in Table 1 to give metal complexes 12ꢀ23 in near
quantitative yield. The complexes are high-melting solids
of various colors and crystallinity. The structures of Cu-
(II), Ni(II), and Pd(II) complexes, 13, 14, and 22 respec-
tively, were confirmed by X-ray crystallographic analysis.
The crystal structure including the absolute configuration
of (þ)-22 is shown in Figure 2, confirming the absolute
configuration of (ꢀ)-6. We were unable to prepare metal
complexes of (þ)-11 with Zn(OAc)2 and Rh2(OAc)4.
Our initial studies with metal complexes shown in
Table 1 have focused on Cr(III) salen derivative (þ)-12
as a catalyst for the hetero-DielsꢀAlder cycloaddition of
diene 2414 to aromatic aldehydes 25 (Table 2). Entries 1ꢀ9
in Table 2 establish that (þ)-12 is an efficient catalyst for
this reaction, giving 5,6-dihydro-4- pyranones 26 in good
yield and high enantioselectivity after hydrolysis of inter-
mediate cycloadduct 27. Enantioselectivity was modest for
the reaction of 24 with furfural (entry 9) and with cyclo-
hexanecarboxaldehyde (entry 11) although the yield of the
cycloadduct was high in both cases. The absolute config-
uration of dihydropyranones26 was establishedin all cases
as (6S), except for entries 7 and 10, by comparison of the
observed specific rotation with literature values.
We next examined (þ)-12 as a catalyst for the Nozakiꢀ
HiyamaꢀKishi (NHK) reaction of allyl halides with aro-
matic aldehydes 25 (Table 3). An efficient catalyzed asym-
metric version of the NHK reaction has been a long sought
goal, but a general solution to this problem has remained
elusive.15 The results in Table 3 show that homoallylic
alcohols 28 are produced in high yield and with good
enantioselectivity when allyl bromide reacts with an aryl
aldehyde in the presence of 10 mol % of (þ)-12.
(12) Boger, D. L.; Patel, M.; Takusagawa, F. J. Org. Chem. 1985, 50,
1911.
(13) Tichy, M.; Sicher, J. Collect. Czech. Chem. Commun. 1972, 37,
3106.
(14) Danishefsky, S.; Kitahara, T.; Schuda, P. F. Org. Synth. 1990,
61, 147.
Org. Lett., Vol. 13, No. 9, 2011
2489

Table 1. Complexes Formed by (þ)-11 with Metal Salts
Table 2. Asymmetric Hetero-DielsꢀAlder Reactions Catalyzed
by Chromium(III)ꢀSalen Complex (þ)-12a
reagent
solvent
THF
temp
product
color
brown
CrCl2, Et3N, O2
ambient
(þ)-12, M =
Cr(Cl)a
Cu(OAc)2 H2O
MeOH
MeOH
reflux
reflux
reflux
reflux
reflux
(þ)-13, M =
Cu
(þ)-14, M =
Ni
black
3
Ni(OAc)2 4H2O
red-orange
brown
brown
violet
3
Mn(OAc)2 4H2O, MeOH
(þ)-15, M =
Mn(Cl)a,b
(þ)-16, M =
Fe(Cl)
(þ)-17, M =
Fe(acac)
(þ)-18, M =
V(O)(Cl)
(þ)-19, M =
V(O)(acac)
(þ)-20, M =
Co
3
O2, NaCl
product 26
FeCl3, NaH
Fe(acac)3
THF
temp
t
yield
[%]b
ee
[%]c
MeOH
entry
R
(°C)
(h)
VOCl3, Et3N
VO(acac)2
CoBr2, NaH
AlCl3, NaH
Pd(OAc)2
CH2Cl2 ambient
green
1
C6H5
ꢀ22
ꢀ22
ꢀ22
ꢀ22
ꢀ22
ꢀ22
ꢀ30
ꢀ30
ꢀ22
ꢀ30
ꢀ22
30
24
24
36
24
24
48
40
18
42
36
99
98
99
99
98
99
97
96
99
97
91
97
92
92
96
94
94
94d
94
67
94d
68
2
2-CH3C6H4
3-CH3C6H4
3-CH3OC6H4
4-ClC6H4
MeOH
THF
reflux
reflux
reflux
reflux
green
3
4
orrange
pale yellow
red
5
6
4-O2NC6H4
3,5-(CH3O)2C6H3
1-naphthyl
2-furyl
THF
(þ)-21, M =
Al(Cl)
(þ)-22, M =
Pd
7
8
MeOH
9
TiCl(OiPr)3, Et3N CH2Cl2 ambient
(þ)-23, M =
Ti(Cl)(OiPr)
yellow
10
11
3-furyl
c-C6H11
a The flask was opened to air after the initial reaction. b The reaction
mixture was washed with brine during workup.
a Reactions were carried out on 0.25 mmol scale with 1.2 equiv of 24.
b Yield of isolated product. c Determined by HPLC using a Daicel
Chiralcel OD column. d The absolute configuration was not determined.
Table 3. Asymmetric NozakiꢀHiyamaꢀKishi Reactions Cata-
lyzed by Chromium(III)ꢀSalen Complex (þ)-12a
product 28
cat. load temp
t
yield
[%]b
ee
[%]c
entry
R
(mol %)
(°C)
(h)
1
2
C6H5
C6H5
10
20
10
10
10
10
10
10
10
10
20
8
97
92
92
97
96
96
95
92
97
93
69
89
92
95
89
96
93d
84
97
85
ꢀ10 15
3
2-CH3C6H4
4-CH3C6H4
3-CH3OC6H4
4-ClC6H4
10
10
10
20
10
20
20
10
6.5
4
6.5
6
5
Figure 2. Crystal structure of Pdꢀsalen complex (þ)-22.
6
5
7
3,5-(CH3O)2C6H3
2,6-Cl2C6H3
1-napthyl
3-furyle
8
8
7
The configuration of 28 was found to be (S) in all cases
except entry 7 where it was not determined. Our results
compare favorably with those obtained recently on the
9
4
10
3
a Reactions were carried out on 0.125 mmol scale with 1.5 equiv of
allyl halide. b Yield of isolated product. c Determined by HPLC using a
Daicel Chiralcel OD column. d The absolute configuration was not
determined. e Allyl chloride was used.
(15) For an account of earlier efforts directed towards the NHK
reaction, both stoichiometric and catalytic, see: Furstner, A. Chem. Rev.
1999, 99, 991.
(16) For NHK reactions catalyzed by a Cr(III) complex of other
chiral scaffolds, see: (a) McManus, H. A.; Cozzi, P. G.; Guiry, P. J. Adv.
Synth. Catal. 2006, 348, 551. (b) Hargaden, G. C.; McManus, H. A.;
Cozzi, P. G.; Guiry, P. J. Org. Biomol. Chem. 2007, 5, 763. (c) Inoue, M.;
Suzuki, T.; Nakada, M. J. Am. Chem. Soc. 2003, 125, 1140. (d) Inoue,
M.; Nakada, M. Angew. Chem., Int. Ed. 2006, 45, 252. (e) Lee, J. Y.;
Miller, J. J.; Hamilton, S. S.; Sigman, M. S. Org. Lett. 2005, 7, 1837. (f)
Xia, G.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 2554.
asymmetric NHK reaction using catalysts that employ
both salen10f and other chiral scaffolds.16
A proposed model for coordination of an aryl aldehyde
with chromiumꢀsalen catalyst (þ)-12 is shown in Figure 3.
With the aldehyde positioned in an open quadrant below
2490
Org. Lett., Vol. 13, No. 9, 2011

the bicyclo[2.2.2]octane scaffold and the carbonyl oriented
toavoid a steric interaction between its hydrogen atom and
a neighboring tert-butyl substituent, the re face of the
carbonyl group is blocked by an opposing aryl ring of
the salen residue whereas the si face is accessible. The
addition of diene 24 or allyl bromide to the si face of
aldehyde 25 leads to an (S) configuration of 26 and 28 as
observed. It is likely that a π-stacking interaction contri-
butestostabilization of the coordination complex witharyl
aldehydes, a factor that could explain the lower enantio-
selectivity observed with cyclohexanecarboxaldehyde.
In summary, we have prepared a new salen ligand based
on a chiral diaminobicyclo[2.2.2]octane. The ligand shows
strong affinity for transition metals as well as certain other
metals with which it forms stable well-characterized com-
plexes. The Cr(III) complex of this salen ligand possesses
excellent catalytic activity in the hetero-DielsꢀAlder reac-
tion and the NozakiꢀHiyamaꢀKishi reaction of aromatic
aldehydes, giving products in high enantiomeric excess in
most cases.
Acknowledgment. Wearegrateful toDr. Lev Zakharov,
University of Oregon, for X-ray crystal structure determi-
nation of (þ)-11, (þ)-13, (þ)-14, (þ)-22, and the brucine
salt of (ꢀ)-6. Financial support was provided by the
National Science Foundation (CHE0834862). Support
for the Oregon State University NMR facility through
grants from the Murdock Charitable Trust (Grant
2005265) and from the National Science Foundation
(CHE-0722319) is gratefully acknowledged.
Supporting Information Available. Experimental pro-
cedures and characterization data for new compounds;
X-ray crystallographic data for five compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 3. Proposed model for coordination of an aryl aldehyde
with Crꢀsalen catalyst (þ)-12.
Org. Lett., Vol. 13, No. 9, 2011
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