A highly enantioselective access to tetrahydroisoquinoline and β-carboline alkaloids with simple noyori-type catalysts in aqueous media

Article abstract of DOI:10.1002/chem.200902289

Silver enhancement: A very convenient modified protocol for the enantioselective transfer hydrogenation of dihydroisoquinoline skeletons under aqueous conditions is reported. Unmodified Noyori ligands can be used and the activity of the catalyst is greatly enhanced with silver additives (see scheme). The protocol was used in a very short synthesis of the alkaloids (S)-harmicine and (S)-crispine.

Full text of DOI:10.1002/chem.200902289

COMMUNICATION
DOI: 10.1002/chem.200902289
A Highly Enantioselective Access to Tetrahydroisoquinoline and b-Carboline
Alkaloids with Simple Noyori-Type Catalysts in Aqueous Media
[
b]
[b]
[a]
Laurent Evanno, Joel Ormala, and Petri M. Pihko*
The asymmetric synthesis of enantiomerically pure tetra-
hydroisoquinolines and tetrahydro-b-carbolines remains a
challenge in organic synthesis. This skeleton is shared by a
need for an excess of triethylamine and the possibility of
formation of carbon monoxide in this system renders it
less attractive for scale up.
[4]
[1]
number of biologically active compounds, such as reticu-
Since the seminal publication by the Noyori group on
line (1), (R)-harmicine (2), yohimbine (3) and reserpine
asymmetric transfer hydrogenation with the HCOOH–Et N
3
[3]
(
not depicted) (Scheme 1). Currently, the state-of-the-art
azeotropic mixture, a number of variants of the original
monotosylated diamine ligand and the ruthenium catalyst
have been reported. The modifications have addressed the
[2]
method for accessing this skeleton is asymmetric reduction
by using the Ru catalysts described by the Noyori group
[3]
[5,6,7]
[8]
(
Scheme 2). Typically, an azeotropic mixture of Et N and
role of the metal (Ru, Ir, Rh),
the diamine ligand, and
3
[3,9,10,11]
HCOOH (ca. 5:2 ratio) is used as a source of hydrogen. The
the p-complexed aromatic ring.
The hydride-transfer
catalyst system has generally been very tolerant to all of
those modifications, affording typically good to excellent
enantioselectivities. However, the use of alternative condi-
tions that might allow water soluble or otherwise recalci-
trant substrates to be reduced has received relatively little
attention. For reactions in aqueous solution, Sꢀss-Fink and
co-workers reported the use of a catalyst based on trans-1,2-
[8a]
[8b]
diaminocyclohexane
and (aminomethyl)pyrrolidine
Scheme 1. Alkaloids containing the tetrahydroisoquinoline system.
chiral ligands. Zhu and co-workers have also described a
highly interesting sulfonated variant 6 (Scheme 2) of the
original Noyori ligand.
[12]
Herein, we report a very convenient protocol for asym-
metric hydrogen-transfer reductions of dihydroisoquinoline
skeletons with simple unmodified, commercially available
diamine ligands under aqueous conditions using sodium for-
[13]
mate as the hydride source. In addition, for substrates re-
sistant to the standard conditions, we also present an experi-
mentally simple solution in which the reaction is accelerated
by increasing the activity of the catalyst with silver salts as
well as activation of the substrate with lanthanide triflates.
Initially, we focused on the reduction of simple alkyl-sub-
stituted dihydroisoquinolines and b-carbolines (8a,b and
10a,b, Scheme 3 and Table 1) using aqueous sodium formate
Scheme 2. The Noyori catalyst and selected variants.
[
a] Prof. P. M. Pihko
Department of Chemistry, University of Jyvꢁskylꢁ
P.O. Box 35, 40014 JYU (Finland)
Fax : (+358)14-260-2501
as the hydride source and cetyltrimethylammonium bromide
[5a,14]
(
CTAB) as a cationic surfactant.
To our delight, using
E-mail: Petri.Pihko@jyu.fi
the simple Noyori-type catalyst 4, we obtained the products
in excellent yields (87% or higher) and enantiomeric excess
[
b] Dr. L. Evanno, J. Ormala
Department of Chemistry, Helsinki University of Technology
P. O. Box 6100, 02015 TKK (Finland)
(
99% ee or higher).
The aqueous conditions might be highly useful for the re-
duction of fused iminium ions of the type 12 and 13
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.200902289.
Chem. Eur. J. 2009, 15, 12963 – 12967
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
12963

responding benzene complex 5. The silver-modified method
was particularly suitable for the hydrogenation of the imini-
um salts 13a and 13b, which are only sparingly soluble in or-
ganic solvents. Their reduction allows a very short synthesis
of the indoloquinolizidine alkaloid (À)-(S)-harmicine 15a
and its homologue 15b (Table 2, entries 7 and 8). It is worth
Table 2. Asymmetric transfer hydrogenation of polycyclic iminium salts.
[
a]
Entry Substrate Cat. Additive Yield [%] ee [%] Configuration
Scheme 3. Asymmetric transfer hydrogenation of alkyl imines.
[
b]
1
2
3
4
6
7
8
12a
12a
12a
12a
12b
13a
13b
4
4
5
7
5
4
4
–
<5
37
45
85
65
94
85
ND
87
94
58
96
98
98
–
S
S
S
S
S
S
[
[
c]
c]
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF6
AgSbF
6
6
6
6
Table 1. Asymmetric transfer hydrogenation of alkyl-substituted imines
in aqueous media.
[c]
[
a]
[b]
[c]
Entry
Substrate
T
Yield [%]
ee [%]
Configuration
6
1
2
3
4
8a
8b
10a
10b
RT
408C
RT
90
87
90
92
99
99.5
>99
>99
S
S
S
S
[a] The ee value was determined by HPLC (Daicel-OD column).
[b] ND=not determined. [c] Isolated as a hydrochloride salt.
408C
[
a] Isolated yields. Reaction time: 16 h. See the Experimental Section for
conditions (0.25 mmol scale, 0.6 mol% catalyst). [b] The ee value was de-
termined by HPLC (Daicel-OD column).
noting that hydrogenation-transfer methods provide the
shortest enantioselective routes published so far for crisp-
[17]
[18]
ine
and harmicine;
furthermore, our protocol also
(
Scheme 4). Their reduction affords a direct route to indole
allows a significant improvement to the enantioselectivity
compared with previous reports.
[19]
alkaloid skeletons. As an alternative, the acyl-Pictet–Spen-
gler reaction also allows the catalytic asymmetric synthesis
To shed light on the mechanism of the activation with
silver, we attempted to isolate the active catalyst by a two-
[8a]
step process (Scheme 5). Although only a very low yield
of the catalyst was obtained (mainly due to the low solubili-
ty of 4 in water), the isolated complex exhibited NMR spec-
troscopy and HRMS data that were consistent with structure
1
6. To test the activity of this catalyst, we selected benzyl-
substituted substrate 18 (Scheme 6), which gave only 40%
conversion with the original Noyori catalyst 4 (Table 3, en-
tries 1–3). The isolated complex turned out to be just as
active in the reduction of 18 as our original catalyst system
(
compare Table 4, entry 1), affording the reduction product
in 88% yield. Taken together, these two experiments strong-
Scheme 4. Asymmetric transfer hydrogenation of polycyclic iminium
salts.
[15]
of similar ring systems.
Unfortunately, the acyl-Pictet–
Spengler approach appears to be limited to b-carbolines
with an indole ring system, and all attempts to expand the
scope to the enantioselective synthesis of isoquinolines have
failed.
Our first experiments with polycyclic iminium systems
were not very encouraging and less than 5% conversions
were observed after 24 h under the initial conditions. Fortu-
nately, a solution was easily found by the addition of
Scheme 5. Isolation of the active catalyst.
[16]
AgSbF to generate an in situ modification of the catalyst
6
to increase the turnover of the catalyst. With complex 4,
polycyclic iminiums 12a and 12b were reduced with fair se-
lectivity, although in modest yields (37 and 50% respective-
ly), thus creating compounds 14a and 14b. However, a sig-
nificant improvement was obtained by switching to the cor-
Scheme 6. Substrates bearing aromatic or benzylic substituents.
12964
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 12963 – 12967

Noyori-Type Catalysts in Aqueous Media
COMMUNICATION
Table 3. Optimization experiments for substrates 17 and 18, resistant to
standard conditions.
thanide and bismuth
reactions with imines.
when silver and Lewis acid activation were used together
Table 3, entries 7–12). Increasing the size of the cation in
ACHTUNGTRENUNNG( III) triflates are known to accelerate
[
a]
[21]
The best results were obtained
[
b]
[c]
[d]
Entry Substrate Additive
Conv.
%]
ee
[%]
Configuration
[
(
[
e]
3+
3+
3+
1
2
3
4
5
6
7
8
9
1
1
1
18
18
18
17
17
17
17
17
17
17
17
17
none
AgSbF
none, cat. 16
none
40
90
88
5
27
20
31
60
80
72
54
87
ND
S
S
S
–
S
–
S
S
S
S
S
S
the series Sc <Y <La
afforded better conversions
[
[
f]
f]
6
98.5
99
[.22]
(
compare Table 3, entries 7–9);
the use of bismuth also
[
e]
gave good results (Table 3, entry 12) and good enantioselec-
tivities.
ND
97
ND
90
92
94
AgSbF
La(OTf)
6
[
e]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
3
The results of the application of the double activation
method to the reduction of other aromatic/benzylic sub-
strates are presented in Table 4 (entries 1–13). To summarize
the results (compare Tables 1, 2, and 3), imines with alkyl
substituents could be reduced without any additive, but for
aromatic substituents both Lewis acid activation and catalyst
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
AgSbF
6
6
6
6
6
6
/Sc ACHTUNGTRENNUNG( OTf)
3
/Y
/La
/Ce
/Yb
/Bi(OTf)
A
H
U
G
R
N
U
G
3
A
H
U
G
R
N
U
G
3
3
0
1
2
A
H
U
G
R
N
U
G
93.5
94.5
94
A
T
N
T
E
N
N
3
A
T
N
T
E
N
N
3
[
(
a] Reaction time: 16 h. See the Experimental Section for conditions.
0.125 mmol scale, 1.3 mol% catalyst, 2.4 mol% AgSbF ) [b] Conv.=con-
activation (AgSbF ) were indispensable. The benzyl-substi-
6
6
tuted substrates and the fused iminium salts represent inter-
mediate cases in which only the catalyst needs to be activat-
ed with silver salts.
version, as determined by crude NMR spectroscopy. [c] The ee value was
determined by HPLC (Daicel-OD column). [d] Hydrogenation products
are levorotary. [e] ND=not determined. [f] Isolated yield.
Although the conversions with the surfactant method
were typically excellent, purification of the products from
the surfactant residues was more problematic with aromatic
substrates (especially 17 and 20a). In addition, thiophenyl-
substituted 20b was surprisingly unreactive (Table 4, en-
tries 7 and 8). For these cases, we found that aqueous meth-
Table 4. Optimization of the Ag-Lewis acid activated transfer hydrogen-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ations in aqueous conditions and comparison with H
2
O/MeOH condi-
[
a]
At ions.
C
H
T
U
N
G
T
R
E
N
N
U
N
G
[
d,e]
Entry Substrate Conditions
Additive
Yield
ee
[
b]
A
H
U
G
R
N
U
G
anol (2:1 H O/MeOH) could be used (Table 4, entries 9–13)
2
[23]
as a simple alternative to the surfactant conditions. Of the
solvent mixtures tested (mixtures of water with methanol,
ethanol, acetonitrile, and THF), aqueous methanol (2:1
1
2
3
4
5
6
7
8
9
1
1
1
1
18
19
19
20a
20a
20a
20b
20b
8a
H
H
H
H
H
H
H
H
H
H
H
H
H
2
2
2
2
2
2
2
2
2
2
2
2
2
O/CTAB AgSbF
O/CTAB AgSbF
O/CTAB AgSbF
O/CTAB AgSbF
O/CTAB AgSbF
O/CTAB AgSbF
O/CTAB AgSbF
O/CTAB AgSbF
O/MeOH AgSbF
O/MeOH AgSbF
O/MeOH AgSbF
O/MeOH AgSbF
O/MeOH AgSbF
6
6
6
6
6
6
6
6
6
6
6
6
6
90 (99)
98
99
99
87
70
60
90
94
99
95
93
98
94
[
[
f]
f]
[c]
/La
A
T
N
R
N
U
G
3
(94)
[c]
/Bi(OTf)
A
H
N
T
E
N
N
(99)
[
[
[
b]
c]
c]
(40)
(99)
(99)
(27)
(22)
H O/MeOH) afforded the highest rates. This protocol was
2
/La
/Bi(OTf)
/La(OTf)
/Bi(OTf)
A
H
U
G
R
N
U
G
especially useful for lipophilic substrates with aromatic sub-
stituents, such as 17, 19, and 20b. The optimized procedures
A
H
U
T
E
U
A
H
U
T
E
U
G
A
H
U
T
E
U
are summarized in Table 4. The H O/MeOH system allows
2
59 (99)
90 (99)
80 (99)
78 (99)
50 (54)
for easier purification and this procedure is more convenient
to scale up. However, for the alkyl-substituted imines, such
as 8a (Table 4, entry 9) and most polycyclic iminium salts
(see Table 2), the CTAB method afforded better results
(only the reduction of 13b proceeded with a higher yield in
0
1
2
3
13b
17
19
/La
/La
/La
A
H
U
G
R
N
N
ACHTUNGTRENNUNG
20b
ACHTUNGTRENNUNG
[
[
a] Reaction time: 16 h. See the Experimental Section for conditions.
b] Conv.=conversion, as determined by NMR spectroscopy. [c] The iso-
[24]
aqueous methanol).
lated yields in these cases were generally 20–30% lower due to difficul-
ties in removing the CTAB residues. [d] The ee value was determined by
HPLC (Daicel-OD column). [e] All hydrogenation products are levorota-
ry and are likely to have the same configuration. [f] Reaction time 40 h.
Although it has been established that the reductions pro-
ceed through protonated substrates, it is interesting to note
that the reductions of alkyl-substituted imines do proceed
under our (slightly basic) aqueous conditions. Blackmond
et al. have suggested that reductions of imines with Rh–di-
ly suggest the in situ generation of cationic intermediate 16.
Interestingly, the less bulky BF4 and PF6 salts were not ef-
fective and even decreased the catalytic activity.
Although benzyl-substituted substrate 18 (Scheme 6) was
readily reduced under the micelle conditions, substrates with
aryl substituents conjugated to the imine system (e.g., 17,
ACHTUNGTRENNUaGN mine catalysts might proceed via the unprotonated
À
À
[25]
imine.
However, to explain the observed rate enhance-
ment effect of metal triflates, we suggest that these reduc-
tions proceed by the ionic “anti” mechanism proposed by
[25b]
Wills et al.
Although the NÀH bond of the catalyst al-
ready activates the imine, the Lewis acid may provide addi-
tional activation (Scheme 7). In most cases this extra activa-
tion does not appear to disturb the enantioselectivity of the
catalyst; however, in the case of furan 20a, the enantioselec-
tivity was clearly eroded (compare entries 4–6, Table 4), pos-
sibly due to complexation of the furan ring with lanthanum.
In summary, we have developed two alternative modifica-
tions to the original Noyori reduction procedure by per-
forming the reaction under aqueous conditions and using
19, 20a, and 20b; Scheme 6) turned out to be more chal-
lenging. For the asymmetric reduction of 17, a work-around
based on the reduction of N-benzyl iminium derivatives has
[12b]
been proposed.
It has previously been established that under the original
Noyori conditions the reduction proceeds via a protonated
[20]
iminium species. We hypothesized that activation of the
imine with water-soluble Lewis acids might be possible. Lan-
Chem. Eur. J. 2009, 15, 12963 – 12967
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12965

P. M. Pihko et al.
[
[
1] a) J. R. F. Allen, B. R. Holmstedt, Phytochemistry 1980, 19, 1573–
1
582; b) V. G. Kartsev, Med. Chem. Res. 2004, 13, 325–336.
2] For review on asymmetric transfer hydrogenation of C=O and C=N
bonds, see: a) M. J. Palmer, M. Wills, Tetrahedron: Asymmetry 1999,
1
0, 2045–2061; b) S. E. Clapham, A. Hadzovic, R. H. Morris, Coord.
Chem. Rev. 2004, 248, 2201–2237.
[
3] N. Uematsu, A. Fujii, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1996, 118, 4916–4917.
Scheme 7. The Willsꢄ anti ionic mechanism allows dual activation of the
substrate by the catalyst and lanthanum.
[4] a) C. Fellay, P. J. Dyson, G. Laurenczy, Angew. Chem. 2008, 120,
4030–4032; Angew. Chem. Int. Ed. 2008, 47, 3966–3968; b) S. Ogo,
H. Nishida, H. Hayashi, Y. Murata, S. Fukuzumi, Organometallics
2
005, 24, 4816–4823.
[
5] a) F. Wang, H. Liu, L. Cun, J. Zhu, J. Deng, Y. Jiang, J. Org. Chem.
2
8
005, 70, 9424–9429; b) J. Mao, D. C. Baker, Org. Lett. 1999, 1,
41–843.
sodium formate as the hydrogen donor. The use of AgSbF6
to boost the activity of the ruthenium catalyst, as well as the
optional use of lanthanide Lewis acids and aqueous metha-
nol, allowed the reactions to proceed at good rates and
good-to-excellent enantioselectivities, and substrates nor-
mally resistant to hydrogenation could also be used. The
method is also applicable to the reduction of polycyclic imi-
nium salts, allowing for a very short synthesis of the alka-
loids crispine and harmicine. Applications of the method to
the total synthesis of more complex targets will be reported
in due course.
[
6] K. Murata, T. Ikariya, R. Noyori, Org. Chem. 1999, 64, 2186–2187.
[7] X. H. Li, J. Blacker, I. Houson, X. F. Wu, J. L. Xiao, Synlett 2006,
1155–1160.
[
8] a) J. Canivet, G. Labat, H. Stoeckli-Evans, G. Sꢀss-Fink, Eur. J.
Inorg. Chem. 2005, 4493–4500; b) J. Canivet, G. Sꢀss-Fink, Green
Chem. 2007, 9, 391–397; c) K. Murata, H. Konishi, M. Ito, T. Ikar-
iya, Organometallics 2002, 21, 253–255; d) M. Yamakawa, H. Ito, R.
Noyori, J. Am. Chem. Soc. 2000, 122, 1466–1478; e) L. Cai, Y. Han,
H. Mahmoud, B. M. Segal, J. Organomet. Chem. 1997, 568, 77–86.
9] F. K. Cheung, A. M. Hayes, J. Hannedouche, A. S. Y. Yim, M. Wills,
Org. Chem. 2005, 70, 3188–3197.
[
[
[
10] T. Koike, T. Ikariya, J. Organomet. Chem. 2007, 692, 408–419.
11] J. Hannedouche, G. J. Clarkson, M. Wills, J. Am. Chem. Soc. 2004,
1
26, 986–987.
[12] a) Y. P. Ma, H. Liu, L. Chen, X. Cui, J. Zhu, J. E. Deng, Org. Lett.
003, 5, 2103–2106; b) J. Wu, F. Wang, Y. Ma, X. Cun, J. Zhu, J.
Experimental Section
2
Deng, Chem. Commun. 2006, 1766–1768.
Typical procedure for asymmetric transfer hydrogenation of imines in
aqueous media by yusing Lewis acids and CTAB: In a GC vial, imine
[13] a) F. Wang, H. Liu, L. Cun, J. Zhu, J. Deng, Y. Jiang, J. Org. Chem.
2005, 70, 9425–9429; b) X. Wu, X. Li, W. Hems, F. King, J. Xiao,
Org. Biomol. Chem. 2004, 2, 1818–1821.
[14] The choice of the surfactant was based on the excellent study of
Zhu and Deng (see ref. [5a]); for an additional example, see: H. Y.
Rhyoo, H. J. Park, W. H. Suh, Y. K. Chung, Tetrahedron Lett. 2002,
43, 269–272.
[15] a) D. J. Mergott, S. J. Zuend, E. N. Jacobsen, Org. Lett. 2008, 10,
745–748; b) I. T. Raheem, P. V. Thiara, E. A. Peterson, E. N. Jacob-
sen, J. Am. Chem. Soc. 2007, 129, 13404–13405; c) M. S. Taylor,
E. N. Jacobsen, J. Am. Chem. Soc. 2004, 126, 10558–10559.
[16] a) C. Li, J. Xiao, J. Am. Chem. Soc. 2008, 130, 13208–13209; b) C. L.
Li, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc. 2009, 131, 6967–
6969.
[17] a) F. D. King, Tetrahedron 2007, 63, 2053–2056; b) S. M. Allin, S. N.
Gaskell, J. M. R. Towler, P. C. Bulman Page, B. Saha, M. J. McKen-
zie, W. P. Martin, J. Org. Chem. 2007, 72, 8972–8975.
(
0.125 mmol, 100 mol%), (R,R)-Noyori catalyst, (1.0 mg, 0.0016 mmol,
.3 mol%), AgSbF (1.0 mg, 0.0030 mmol, 2.4 mol%), Lewis acid
(OTf) (0.041 mmol, 33 mol%), CTAB (46 mg, 0.13 mmol, 100 mol%)
and sodium formate (130 mg, 1.9 mmol, 1500 mol%) were mixed with
.75 mL of degassed water and vigorously stirred for 16 h at 408C under
inert atmosphere. The reaction mixture was allowed to cool to RT and
then extracted with CH Cl (2ꢃ2 mL). The combined extracts were dried
Na SO ) and concentrated. Purification of the residue by flash chroma-
tography (1–10% MeOH in CH Cl ) afforded the desired products.
Typical procedure for asymmetric transfer hydrogenation of imines in
water/methanol mixture using lanthanum(III) triflate: In a small vial,
imine (0.125 mmol, 100 mol%), (R,R)-Noyori catalyst, (1.0 mg,
.0016 mmol, 1.3 mol%), AgSbF (3.0 mg, 0.009 mmol, 2.4 mol%),
sodium formate (130 mg, 1.9 mmol, 1500 mol%), lanthanum triflate
1
6
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
M
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
3
0
2
2
(
2
4
2
2
AHCTUNGTRENNUNG
0
6
(
(
24 mg, 0.041 mmol, 33 mol%) were dissolved in water-methanol mixture
2:1 v/v, 0.75 mL) and vigorously stirred for 16 h at 408C under inert at-
mosphere. The mixture was allowed to cool to RT and extracted by
CH Cl (2ꢃ3 mL). The combined extracts were dried (Na SO ) and con-
centrated. Purification of the residue by flash chromatography (silica gel,
–10% MeOH in CH Cl ) afforded the desired products.
[18] W. A. da Silva, M. T. Rodrigues, Jr., N. Shankaraiah, R. B. Ferreira,
C. Kleber, Z. Andrade, R. A. Pilli, L. S. Santos, Org. Lett. 2009, 11,
2
2
2
4
3
238–3241.
1
2
2
[
19] J. Szawkało, S. J. Czarnocki, A Zawadzka, K. Wojtasiewicz, A. Leni-
ewski, J. K. Maurin, Z. Czarnocki, J. Drabowicz, Tetrahedron: Asym-
metry 2007, 18, 406–413.
[
20] a) J. S. M. Samec, J. E. Bꢁckvall, P. G. Andersson, P. Brandt, Chem.
Rev. 2006, 106, 237–248; b) R. Noyori, M. Yamakawa, S. Hashigu-
chi, J. Org. Chem. 2001, 66, 7931–7934; c) M. Yamakawa, I.
Yamada, R. Noyori, Angew. Chem. 2001, 113, 2900–2903; Angew.
Chem. Int. Ed. 2001, 40, 2818–2821.
Acknowledgements
Financial support from PCAS Finland is gratefully acknowledged. We
thank Dr. Jari Koivisto (TKK) for help with NMR spectra and Drs. Oili
Kallatsa and Satu Ahvas (PCAS Finland) for insightful comments.
[
21] a) S. Kobayashi, K. Manabe, Pure Appl. Chem. 2000, 72, 1373–
1
380; b) T. Itoh, K. Nagata, A. Kurihara, M. Miyazaki, A. Ohsawa,
Tetrahedron Lett. 2002, 43, 3105–3108.
[
22] a) R. D. Shannon, C. T. Prewitt, Acta Crystallogr. Sect. B 1969, 25,
9
25–945; b) R. D. Shannon, C. T. Prewitt, Acta Crystallogr. Sect. B
Keywords: alkaloids · asymmetric synthesis · catalysis ·
imines · lanthanides · transfer hydrogenation
1
970, 26, 1046–1048.
12966
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Chem. Eur. J. 2009, 15, 12963 – 12967

Noyori-Type Catalysts in Aqueous Media
COMMUNICATION
[
[
23] For a related system, see: H. F. Zhou, Q. H. Fana, Y. Y. Huana, L.
[25] a) D. G. Blackmond, M. Ropic, M. Stefinvic, Org. Process Res. Dev.
2006, 10, 457–4563; b) J. E. D. Martins, G. J. Clarkson, M. Wills,
Org. Lett. 2009, 11, 847–850.
Wu, Y. M. He, W. J. Tang, L. Q. Gu, A. S. C. Chan, J. Mol. Catal. A
2
007, 275, 47–53.
24] The polycyclic iminium salts 12a, 12b, and 13a afforded only poor-
to-moderate results under these conditions; see the Supporting In-
formation for details.
Received: August 18, 2009
Published online: October 26, 2009
Chem. Eur. J. 2009, 15, 12963 – 12967
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12967