Ruthenium-catalyzed reduction of racemic tricarbonyl(η6-aryl ketone)chromium complexes using transfer hydrogenation: A simple alternative to the resolution of planar chiral organometallics

Article abstract of DOI:10.1016/j.jorganchem.2005.03.048

Racemic planar chiral (η⁶-aryl ketone)Cr(CO)₃ complexes (aryl ketone = 1-indanone, 1-tetralone, 4-chromanone and thiochroman-4-one) were prepared by refluxing the aryl ketone with Cr(CO) ₆ in a 10:1 mixture of dibutyl ether and THF. The reductions of the organometallic ketones by transfer hydrogenation in 2-propanol containing KOH and the catalyst precursor, generated from [RuCl₂(η⁶- benzene)]₂ and (-)-ephedrine, resulted in optically active syn-(R,S)-(η⁶-aryl alcohol)Cr(CO)₃ and (R)-(η⁶-aryl ketone)Cr(CO)₃ compounds in 31-97% ee. Reduction of racemic (η⁶-thiochroman-4-one)Cr(CO)₃ with the catalyst precursor generated from (+)-norephedrine, instead of (-)-ephedrine, inverted the configuration of the products obtained. Syn-(S,R)-(η⁶-thiochroman-4-ol)Cr(CO)₃ and (S)-(η⁶-thiochroman-4-one)-Cr(CO)₃ were isolated in 49% and >95% ee, respectively. The free aryl ketones were reduced using the same conditions as their respective chromium complexes, giving aryl alcohols in high ee (>95%). Reactions of non-rigid acetophenone, propriophenone and their tricarbonylchromium complexes resulted in moderate to low ee.

Full text of DOI:10.1016/j.jorganchem.2005.03.048

Journal of Organometallic Chemistry 690 (2005) 3176–3186
www.elsevier.com/locate/jorganchem
Ruthenium-catalyzed reduction of racemic
tricarbonyl(g6-aryl ketone)chromium complexes
using transfer hydrogenation: A simple alternative
to the resolution of planar chiral organometallics
*
Cleber V. Ursini, Gilson H.M. Dias, J. Augusto R. Rodrigues
State University of Campinas, Institute of Chemistry, UNICAMP – Instituto de Quimica, CP 6154, 13084-971 Campinas SP, Brazil
Received 27 January 2005; revised 28 March 2005; accepted 28 March 2005
Available online 12 May 2005
Abstract
Racemic planar chiral (g6-aryl ketone)Cr(CO)3 complexes (aryl ketone = 1-indanone, 1-tetralone, 4-chromanone and thiochro-
man-4-one) were prepared by refluxing the aryl ketone with Cr(CO)6 in a 10:1 mixture of dibutyl ether and THF. The reductions of
the organometallic ketones by transfer hydrogenation in 2-propanol containing KOH and the catalyst precursor, generated from
[RuCl2(g6-benzene)]2 and (ꢀ)-ephedrine, resulted in optically active syn-(R,S)-(g6-aryl alcohol)Cr(CO)3 and (R)-(g6-aryl keto-
ne)Cr(CO)3 compounds in 31–97% ee. Reduction of racemic (g6-thiochroman-4-one)Cr(CO)3 with the catalyst precursor generated
from (+)-norephedrine, instead of (ꢀ)-ephedrine, inverted the configuration of the products obtained. Syn-(S,R)-(g6-thiochroman-
4-ol)Cr(CO)3 and (S)-(g6-thiochroman-4-one)-Cr(CO)3 were isolated in 49% and >95% ee, respectively. The free aryl ketones were
reduced using the same conditions as their respective chromium complexes, giving aryl alcohols in high ee (>95%). Reactions of non-
rigid acetophenone, propriophenone and their tricarbonylchromium complexes resulted in moderate to low ee.
ꢀ 2005 Elsevier B.V. All rights reserved.
Keywords: Arene complexes; Chromium; Transfer hydrogenation; Resolution; Planar chirality; Ruthenium
1. Introduction
solvents 2-propanol and a formic acid–triethylamine
mixture have been used almost exclusively as hydrogen
donor in conjunction with Ru(II), amino alcohols and
diamines as chiral ligands in asymmetric reductions [2].
Chiral diamine-based RuII complexes are particularly
efficient catalysts for the enantioselective reduction
of prochiral ketones under mild conditions using 2-
propanol and formic acid as hydrogen source [1g]. This
kind of ligand is expensive and employs several steps in
its synthesis, in contrast to the large variety and ready
availability of chiral amino alcohols which allow optimi-
zation of the performance of [Ru(g6-arene)(2-amino
alcohol)] systems in terms of activity and enantioselec-
tivity by varying the structure [1c,3] and the functional
groups [4].
Transfer hydrogenation of ketones by ruthenium(II)
catalysts has recently emerged as a good alternative to
the widely used catalytic hydrogenation for the produc-
tion of achiral and chiral alcohols. Its operational sim-
plicity, the easy availability of reductants and the
possibility in obtaining products in high yields under
mild conditions, avoiding the use of hydrogen gas and
reactive metal hydrides, are responsible for the increas-
ing interest in catalytic transfer hydrogenation [1]. The
*
Corresponding author. Tel.: +55 1937883141; fax: +55 1937883023.
E-mail address: jaugusto@iqm.unicamp.br (J.A.R. Rodrigues).
0022-328X/$ - see front matter ꢀ 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2005.03.048

C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
3177
A flaw of transfer hydrogenation using 2-propanol is
the reversibility of the reaction and its efficiency is highly
dependent on the redox properties of the alcohols
formed [1g,5]. However, this tendency can be utilized
for kinetic resolution of racemic alcohols using acetone
as a hydrogen acceptor [6].
Because of the increasing interest in transfer hydroge-
nation and its reversibility, preventing complete conver-
sion, we decided to verify the possibility to resolve
racemic planar chiral tricarbonyl(g6-aryl ketone)chro-
mium complexes and the effect caused by the organome-
tallic fragment on the stereochemistry of the products
using this method.
organometallics is normally employed to generate chiral
(g6-aryl ketone)Cr(CO)3 compounds [12,13].
In this work, we investigated a practical system for
the direct resolution of racemic mixtures of tricar-
bonyl(g6-aryl ketone)chromium. Our strategy consisted
in the synthesis of racemic tricarbonylchromium com-
plexes of the bicyclic aryl ketones 1-indanone (1a), 1-
tetralone (1b), 4-chromanone (1c) and thiochroman-
4-one (1d), using the accessible reagent Cr(CO)6 and
later reduction of preferentially one enantiomer to the
respective alcohol by transfer hydrogenation in 2-
propanol catalyzed with chiral 2-amino alcohol-RuII-
(g6-benzene).
Planar chiral transition-metal complexes, such as
ferrocenyl derivatives and tricarbonyl(g6-arene)chro-
mium compounds, have applications as chiral building
blocks for the synthesis of complex organic molecules
[7] and as ligands in catalytic reactions [8], including
transfer hydrogenation [9]. In the specific case of the tri-
carbonylchromium fragment on complexation to arenes,
modification of steric and eletronic factors and of the
symmetry of the substrate ligand can thus be explored
in the synthesis of benzene derivatives and dearomatiza-
tion reactions difficult or impossible to obtain by other
methods [7e,7f,10]. Among the various procedures for
the preparation of enantiopure planar chiral tricar-
bonyl(g6-arene)chromium complexes [11], organometal-
lic aryl alcohols are obtained usually by complexation of
racemic alcohols followed by fractionalization of their
derivatives [12] or enzymatic resolution [8f,12b]. An effi-
cient method to prepare such complexes of 1-tetralol
derivatives consists of the direct diastereoselective coor-
dination of the respective optically active alcohols to the
2. Results and discussion
The arene-chromium complexes rac-2a–d and 2e–f
were synthesized using the standard procedure of
refluxing Cr(CO)6 in dibutyl ether:THF (10:1) [14] in
the presence of the respective arenes 1a–f (Schemes 1
and 2). The two faces of the employed cyclic aryl ke-
tones: 1-indanone (1a), 1-tetralone (1b), 4-chromanone
(1c) and thiochroman-4-one (1d) are enantiotopic and
enantiomeric complexes arise from the coordination
of the Cr(CO)3 fragment to one of these two faces.
We carried out the catalytic transfer hydrogenation
of rac-2a–d, 2e–f and of their respective free arenes,
1a–f, in parallel, for comparison (Schemes 1 and 2).
The combinations [RuCl2(g6-benzene)] and (ꢀ)(1R,2S)-
ephedrine (or (+)-(1S,2R)-norephedrine) were used as
catalyst precursor in 2-propanol containing KOH. The
reactions were conducted at room temperature (except
for the reduction of rac-2c, carried out at 50 ꢁC, Table
1, entry 4) either overnight or until conversion
stabilization.
tricarbonylchromium via KundigÕs reagent, tricar-
¨
bonyl(g6-naphthalene)chromium [13]. The oxidation of
enantiomerically enriched (g6-aryl alcohol)Cr(CO)3
O
OH
R
O
R
S
(b)
(CH2)n
X
(CH2)n
+
(CH2)n
X
X
(OC)3Cr
O
(OC)3Cr
(OC)3Cr
(a)
rac-2a-d
(-)-(R)-2a-d
(+)-syn-(R,S)-3a,c,d
(-)-syn-(R,S)-3b
(CH2)n
(d)
X
OH
(c)
(b)
1a-d
(CH2)n
OH
OH
X
R
S
(d)
n
X
(-)-(R)-4a,b
(+)-(R)-4c,d
(CH2)n
X
(CH2)n
X
a
1
CH2
(OC)3Cr
b
c
d
2
2
2
CH2
O
S
(+)-(S)-4a,b
(-)-(S)-4c,d
(-)-syn (S,R)-3a,c,d
(+)-syn (S,R)-3b
Scheme 1. (a) Cr(CO)6, Bu2O:THF (10:1), reflux 24–48 h; (b) 2-PrOH, (ꢀ)-ephedrine, [RuCl2(benzene)]2, KOH; (c) NaBH4, EtOH; (d) sunlight, air.

3178
C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
O
The results of the experiments are summarized in
Table 1 (for organochromium complexes) and Table 2
(for free aryl ketones), including conversions, yields,
enantiomeric excesses of the alcohols produced and of
the remaining organometallic ketones, with optical
rotations.
R
(b)
(a)
OH
(OC)3Cr
O
2e
2f
R
Reduction of the racemic mixture of (g6-1-inda-
none)Cr(CO)3 (rac-2a) showed a conversion of 84%
to (+)-syn-(1R,7aS)-(g6-1-indanol)Cr(CO)3, (R,S)-3a
(Table 1, entry 1). This product and the optically active
unchanged (ꢀ)-(7aR)-(g6-1-indanone)Cr(CO)3, (R)-2a,
were separated by silica gel column chromatography
to give yellow and orange solids, respectively (Scheme
R
(OC)3Cr
(b)
(d)
1e R = Me
1f R = Et
OH
(-)-(R)-3e
(-)-(R)-3f
R
(+)-(R)-4e
(+)-(R)-4f
1
1). The H NMR of (R,S)-3a confirmed the syn config-
uration and the positive signal of optical rotation
identified the predominant enantiomer [8f,12]. The
enantiomeric excess of 31% was determined by GC on
Scheme 2. (a) Cr(CO)6, Bu2O:THF (10:1), reflux 24–48 h; (b) 2-PrOH,
(ꢀ)-ephedrine, [RuCl2(benzene)]2, KOH; (c) NaBH4, EtOH;
(d) sunlight, air.
Table 1
Transfer hydrogenation of tricarbonyl(g6-aryl ketone)chromium compounds in 2-propanol:KOH catalyzed by rutheniumII(g6 benzene)-(ꢀ)-
ephedrine complex
Entry
Substrate
Conversion (%)a
Alcohol produced
ee (%)a
Ketone recovered
ee (%)c
b
b
[a]D
[a]D
Yield (%)
Yield (%)
1
2
Rac-2a
Rac-2b
Rac-2c
Rac-2c
Rac-2c
Rac-2d
Rac-2d
Rac-2d
2e
84
45
(R,S)-3a
(R,S)-3b
(R,S)-3c
(R,S)-3c
–
31d
+10(0.42)
ꢀ17 (0.36)
–
56
20
–
(R)-2a
(R)-2b
–
82d
48d
ꢀ262(0.29)
13
26
–
77d
ꢀ507(1.45)
3
7
15
96e
97e
–
–
–
4f
5g
6
+243 (0.66)
–
11
–
(R)-2c
–
25e
95e
>95e
>95e
–
ꢀ241(1.45)
40
–
Not observed
–
–
50
63
69
95
96
(R,S)-3d
(R,S)-3d
(S,R)-3d
(R)-3e
85e (95)e,h
+295h (0.27)
+290h (0.95)
ꢀ162(0.29)
ꢀ6.1(2.3)
ꢀ3(0.80)
37
40
61
44
75
(R)-2d
(R)-2d
(S)-2d
–
ꢀ1320(1.63)
20
19
20
–
7
70e (83)e,h
ꢀ1388(1.43)
8g
9
49
33
4
+1298(1.00)
–
–
10
a
2f
(R)-3f
-
–
–
Determined by GC analysis of the free arene ligands after decomplexation under sunlight/air.
Concentrations of solutions in CHCl3 (g/100 mL) in parenthesis.
Determined after reduction of the ketone complex with borohydride to the respective syn-(g6-aryl alcohol)tricarbonylchromium and GC analysis
b
c
on chiral phase of the free aryl alcohol obtained after decomplexation under sunlight/air.
d
Macherey Hydrodex-b 3P capillary column.
Supelco b-dextrin-120 capillary column.
Carried out at 50 ꢁC.
e
f
g
(+)-Norephedrine was used instead of (ꢀ)-ephedrine to generate the catalyst.
h
After recrystallization.
Table 2
Transfer hydrogenation of free aryl ketones in 2-propanol:KOH catalyzed by rutheniumII(g6benzene)-(ꢀ)-ephedrine complex
Conversion (%)a
Alcohol
ee (%)a
[a]D
Yield (%)
b
Entry
Substrate
1
1a
1b
1c
1c
1d
1d
1e
1f
18
54
(R)-4a
(R)-4b
(R)-4c
(S)-4c
(R)-4d
(S)-4d
(R)-4e
(R)-4f
96c
96c
ꢀ29 (0.41)
ꢀ37.0 (2.12)
+66.0 (3.03)
ꢀ61 (0.50)
+141 (2.11)
ꢀ136 (1.00)
–
11
37
76
39
75
80
74
73
2
3
91
54
97c
4d
5
>97c
>97c
97c
62e
41e
92
6d
7
>99
97
8
93
+10 (2.02)
a
Determined by GC analysis.
Concentrations of solutions in CHCl3 (g/100 mL) in parenthesis.
b
c
Supelco b-dextrin-120 capillary column.
d
e
(+)-Norephedrine was used instead of (ꢀ)-ephedrine to generate the catalyst.
Macherey dydrodex-b 3P capillary column.

C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
3179
a chiral column after photochemical oxidation in air to
release the ligand (R)-4a. The recovered and resolved ke-
tone (R)-2a showed 82% ee, determined after reduction
with sodium borohydride to (ꢀ)-syn-(S,R)-3a [13,15]
followed by decomplexation and GC analysis on a chiral
phase of the resultant (S)-4a (Scheme 1).
A lower conversion (18%) was observed for the
reduction of free 1-indanone (1a) to 1-indanol (R)-4a,
with 96% ee (Table 2, entry 1). Higher conversions and
(rac-2c) to sulfur (rac-2d), resulted in a significant gain
of conversion at room temperature: from 7% for rac-
2c (Table 1, entry 3) to 50–63% for rac-2d (Table 1, en-
tries 6 and 7). The parallel transfer hydrogenation of
free thiochroman-4-one (1d) gave (R)-thiochroman-4-
ol, (R)-4d, in 75% yield (92% conversion) and >97% ee
(Table 2, entry 5). This result was similar to that
achieved for the reduction of 4-chromanone (1c) (Table
2, entry 3), in contrast to the different behaviors ob-
served for the respective organometallic rac-2c and
rac-2d (Table 1, entries 3, 4, 6 and 7).
Two experiments were carried out with rac-2d at room
temperature (Table 1, entries 6 and 7). In the first, the
enantiomeric excess remained practically unchanged
duringthereaction(85%ee). Theproduct(+)-tricarbonyl-
(g6-thiochroman-4-ol)chromium, (+)-3d, and the opti-
cally active unchanged (ꢀ)-2d were separated by silica
gel column chromatography and crystallized with
CH2Cl2:hexane to give yellow and red crystals of (+)-3d
(37% yield) and (ꢀ)-2d (20% yield), respectively. The 1H
and 13C NMR spectra of (+)-3d displayed only the syn
diastereoisomer resonances, confirmed after comparison
with the respective spectra of (ꢀ)-syn-3d (see below).
Decomplexation of (+)-3d furnished (+)-(R)-thiochro-
man-4-ol, (R)-4d, with 95% ee (Scheme 1). Consequently,
the ee of (+)-syn-3d was the same (95% ee) and its config-
uration was attributed as (4R,4aS)-3d, simplified here to
(R,S)-3d (Table 1, entry 6).
similar ee were reported with
a diamine (S,S)-
TsDPEN and [RuCl2(g6-mesitylene)]2 combination in
2-propanol (conversion of45% with 91% ee) [16] orformic
acid–triethylamine (conversion >99% and 99% ee) [17].
Hydrogen-transfer reactions of the free 1-tetralone
(1b) and of the rac-(g6-1-tetralone)Cr(CO)3 (rac-2b) in
2-PrOH, using a (ꢀ)-ephedrine and [RuCl2(g6-ben-
zene)]2 combination, were accompanied by GC on a chi-
ral phase. After 30 min of reaction, the organometallic
rac-2b was reduced to syn-(1R,8aS)-(g6-1-tetra-
lol)Cr(CO)3, (R,S)-3b, with 41% conversion and 84%
ee. After 210 min, the conversion was 45% with 78%
ee. No gain in conversion was observed after this period.
1
The H and 13C NMR of the crude product displayed
signals of syn-3b and unreacted (g6-tetralone)Cr(CO)3
(2b). Separation by silica gel column chromatography
gave (ꢀ)-(R,S)-3b (20%) and (ꢀ)-(R)-2b (26%) with
77% and 48% ee [18], respectively (Scheme 1, Table 1).
The reaction of the free ligand 1b to give (ꢀ)-(R)-1-tetra-
lol, (R)-4b, showed conversion of 60% after 150 min,
with excellent enantiomeric excess (98% ee). Additional
reaction time was prejudicial. After 24 h of reaction,
GC analysis showed 54% of conversion and (R)-4b was
isolated in 37% yield with 96% ee (Table 2, entry 2). Sim-
ilar results were reported on the reduction of 1-tetralone
to 1-tetralol using the more expensive catalytic combina-
tions of [Ru(g6-cymene)Cl2]2 and cis-(1R,2S)-1-aminoin-
dan-2-ol (40% yield of (S)-1-tetralol in 98% ee) [2a] or
[Ru(g6-cymene)Cl2]2 and NH-benzyl (1R,2S)-norephe-
drine (68% conversion to (R)-1-tetralol in 96% ee) [19].
Reductions of the free 4-chromanone (1c) and of the
respective racemic tricarbonyl chromium complex (rac-
2c) at room temperature, showed drastically different
conversions. To our surprise, only 7% of the organome-
tallic rac-2c was converted to (+)-(R,S)-3c in 96% ee
(Table 1, entry 3), while 91% of the free ligand 1c was
converted to (R)-4-chromanol, (R)-4c, in 76% yield with
97% ee (Table 2, entry 3). At 50 ꢁC, the conversion of
rac-2c to (+)-(R,S)-3c rose to 15% after 6 h of reaction.
Extending the reaction time was not effective in increas-
ing the conversion. The product (+)-(R,S)-3c was iso-
lated in 11% yield with high enantioselectivity (97%
ee). The unchanged ketone (ꢀ)-(R)-2c was recovered in
40% yield with 25% ee, determined after reduction with
borohydride to give (ꢀ)-(S,R)-3c [20].
The reduction of the isolated (ꢀ)-2d with sodium
borohydride gave exclusively the syn product (ꢀ)-
(4S,4aR)-3d [20] in 95% ee, determined for the decom-
plexed ligand (S)-4 (Scheme 1). This result allowed to
determine the R configuration for the stereogenic centers
on carbons 4a of (ꢀ)-2d and (ꢀ)-3d.
A second experiment carried out with rac-2d showed
an increase in the conversion, 63%, (Table 1, entry 7),
but with loss of ee for the alcohol obtained (R,S)-3d
(70% ee for the crude product and 83% ee after recrystal-
lization) in comparison to the previous experiment,
which gave (+)-(R,S)-3d in 95% ee. We believe that small
variations of the temperature and concentrations of the
substrate and catalyst components of medium, affected
the conversion and the stereoselectivity of the reaction.
Reductions of the non-rigid aryl ketones acetophe-
none (1e) and propiophenone (1f) and their respective
achiral complexes 2e and 2f, with the catalytic system
RuII(benzene)-(ꢀ)-ephedrine, resulted in high conver-
sions (93–97%) to their respective alcohols 4e–f and
3e–f (Scheme 2). The reasonable enantiomeric excesses
of (R)-4e (62% ee) and (R)-4f (41% ee) obtained on the
reduction of the free ligands 1e and 1f were not surpris-
ing with this simple catalytic system (Table 2, entries 7
and 8) [2a]. High ee for the alcohols 4e and 4f may be
obtained from the free ketones 1e and 1f with appropri-
ate catalytic combinations of arene ligand and chiral
amino alcohol or diamine auxiliaries on ruthenium
The changing of the heteroatom on the aryl ketone li-
gand of the organochromium compound, from oxygen

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C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
[1g]. The fragment Cr(CO)3 coordinated to the acetoph-
enone and to the propiophenone (complexes 2e and 2f)
caused a loss in the ee of the aryl alcohols produced:
33% ee for 3e and 4% ee for 3f (Table 1, entries 9 and
10).
To verify the influence of the catalyst stereochemistry
on the stereoselectivity of the transfer hydrogenation
reductions of the racemic tricarbonyl(g6-aryl
ketone)chromium complexes, we carried out the repre-
sentative reductions of rac-2d and of the free ligand 1d
with the combination (+)-(1S,2R)-norephedrine/[RuCl2
(g6-benzene)]2 in 2-propanol. (+)-(1S,2R)-Norephedrine
and (ꢀ)-(1R,2S)-ephedrine are similar molecules with
opposite configurations at the stereogenic centers
(Scheme 3).
HO
NH2
HO
NHMe
The reduction of rac-2d by transfer hydrogenation
with the combination (+)-(1S,2R)-norephedrine/
[RuCl2(g6-benzene)]2 in 2-propanol (Scheme 4) showed
a conversion of 69% to (S,R)-3d (Table 1, entry 8).
The starting material was recovered (20%) as (+)-(S)-
2d (>95% ee) and the alcohol produced, (ꢀ)-(S,R)-3d,
was isolated in 61% yield (49% ee) after separation by
column chromatography. With the same conditions, to-
tal conversion was observed for the reduction of the free
ligand 1d to give (ꢀ)-(S)-4d in 80% yield with 97% ee
(Table 2, entry 6). These results demonstrated that
similar chiral auxiliaries (ꢀ)-(1R,2S)-ephedrine and
(+)-(1S,2R)-norephedrine with rutheniumII catalysts
(+)-(1S,2R)-norephedrine
Scheme 3.
(-)-(1R,2S)-ephedrine
O
S
OH
O
S
R
S
RT
2-PrOH
S
+
(+)-norephedrine/
[RuCl2(benzene)]2
S
(OC)3Cr
(OC)3Cr
(OC)3Cr
KOH
(+)-(S)-2d
rac-2d
(-)-syn-(S,R)-3d
Scheme 4.
Ru
[RuCl2(benzene)]2
base
O
Cl
H
+
N
Ph
- HCl
(-)-ephedrine
CH3
H3C
base
- HCl
O
OH
S
Ru
Ru
hydride
intermediate
O
H
H
H
N
O
N
Ph
OH
CH3
CH3
S
H3C
R
X
Ph
CH3
(CH2)n
O
(OC)3Cr
(CH2)n
syn-(R,S)-3a-d
X
(OC)3Cr
or
rac-2a-d
OH
R
S
(CH2)n
X
X
(CO)
Cr
X
3
(OC)3Cr
(S)
S
Ru
(CH2)n
Ru
N
S
syn-(S,R)-3a-d
O
O
H
H
or
(CH2)n
Cr
(CO)3
R
Ph
N
Ph
H
O
H
O
CH3
CH3
CH3
CH3
A
B
Scheme 5.

C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
3181
exhibited opposite effects on the stereoselectivity of the
hydrogen-transfer reduction of rac-2d and 1d.
try of the resulting organometallic products. The ee of
the recovered organometallic ketones and the organo-
metallic alcohols produced depended of the reaction
conversion. Low conversions (<50%) gave alcohols in
high to reasonable ee and recovered ketones with low
ee (Table 1, entries 2, 3 and 4). High conversions
(>50%) showed the contrary effect: alcohols in low to
moderate ees and ketones with high and reasonable ee
(Table 1, entries 1, 7 and 8). Reduction with 50% of con-
version gave more efficient resolutions as observed for
the reaction of rac-2d (Table 1, entry 6). In that experi-
ment, we observed 50% conversion (Table 1, entry 6) to
the alcohol (R,S)-3d, crystallized in good ee (95%). The
recovered ketone (R)-2d was also isolated in 95% ee after
crystallization. These results open new perspectives in
the search for a suitable molecular architecture for chiral
metal complexes, coupled with appropriate selection of
reaction conditions, which allows an efficient and prac-
tical resolution of racemic (g6-aryl ketone)Cr(CO)3.
To our knowledge, this is the first report on the use of
hydrogen transfer on the ruthenium-catalyzed reduction
of racemic tricarbonyl(g6-aryl ketone)chromium
complexes.
Rac-2c was tentatively reduced with the (+)-(1S,2R)-
norephedrine/[RuCl2(g6-benzene)]2 system, but no con-
version was observed. In parallel, the free ligand 1c
was reduced to (S)-4c (54% conversion) in >97% ee
(Table 2, entry 4).
According to NoyoriÕs mechanism for hydrogen
transfer reactions catalyzed by RuII-arene complexes
containing 1,2-diamines or 2-amino alcohols as chiral
modifiers [2b], the configuration at the Ru stereogenic
center is defined by the chiral auxiliary and experimental
data and theoretical calculations show that Ru hydride
intermediates exist as a single diastereoisomer [21]. In
our specific case, the (ꢀ)-(1R,2S)-ephedrine ligand prob-
ably leads to the hydride intermediate with S configura-
tion at the Ru atom and the (+)-(1S,2R)-norephedrine
leads to the respective intermediate with R configuration,
since (1S,2R)-norephedrine derivatives are invoked to
generate (R)-Ru hydrides, based on NMR and X-ray dif-
fraction studies [22]. According to this proposal, the chi-
ral organometallic ketones (S)-2a–d interact with the Ru
hydride catalytic intermediate via the transition state A
(TS A) and the complexes (R)-2a–d interact via TS B
(Scheme 5). The possibility of TS with the fragment
Cr(CO)3 in an internal position was discarded because
only syn-(g6-aryl alcohol)Cr(CO)3 diastereoisomers were
produced. The ee of the alcohols (R,S)-3a–d produced by
the reductions of rac-2a–d with the (ꢀ)-ephedrine-RuII
catalytic system suggest a preference for TS A over
TS B. The more favorable TS A is explained by the
CH/p attraction between the g6-arene-Ru and the aryl
substituents in the ketone [23], however, the electron-
withdrawing effect of the fragment Cr(CO)3 [7e] proba-
bly reduces this attraction, resulting in the lower ee
obtained for the complexes (R,S)-3a–d and (R)-3e–f
(Table 1), in comparison to those observed for the free
aryl alcohols (R)-4a–f (Table 2).
4. Experimental
All reagents and solvents were obtained from com-
mercial sources. Ethyl acetate, hexane and chloroform
were distilled under argon before use. The solvents
dichloromethane and methanol were distilled under ar-
gon from suspensions over calcium hydride and calcium
oxide, respectively. Hexane, THF and dibutyl ether were
distilled under argon from a mixture containing sodium.
Thin layer chromatography (TLC) analyses was per-
formed with precoated aluminium sheets (silica gel 60
Merck) and flash column chromatography was carried
out on silica (200–400 mesh, Merck). IR spectra were re-
corded on a FT-IR BOMEM MB-100 from Hartmann
& Braun. 1H NMR spectra were determined at 300
(Varian Gemini 300) or 500 MHz (INOVA-500), and
13C NMR spectra were determined at 75.5 MHz (Varian
Gemini 300) or 125.7 MHz (INOVA 500). Chemical
shifts are reported in ppm relative to tetramethylsilane
(TMS) in CDCl3. Gas chromatographic analyses and
mass spectra were obtained on a QP 5000-SHIMADZU
or an AGILENT CG 6890/HEWLETT PACKARD
5973 equipped with J. & W. Scientific HP-5 (5%
phenylmethylpolysiloxane, 30.0 m · 250 lm · 0.25 lm),
Supelco 10710-01B b-dextrin-120 (25.0 m · 250 lm ·
0.25 lm) or Macherey 212117/91 Hydrodex-b 3P
(25.0 m · 250 lm · 0.25 lm) capillary columns. For tri-
carbonyl(g6-arene)chromium compounds, decomplex-
ation under sunlight/air and filtration through a short
column of silica and celite was necessary before GC
analyses. Gas chromatographic analyses of reaction
3. Conclusions
Our studies using a simple combination of [RuCl2(g6-
benzene)]2 and (ꢀ)-(1R,2S)-ephedrine demonstrated
that Ru-catalyzed hydrogen transfer in 2-propanol is a
practical method for the direct resolution of racemic
chiral planar (g6-arene)Cr(CO)3 with rigid aryl ketones
as arene ligands, such as 1-indanone, 1-tetralone, 4-
chromanone and thiochroman-4-one. In all cases, the
syn-(R,S)-(g6-aryl alcohol)Cr(CO)3 and (R)-(g6-aryl
ketone)Cr(CO)3 complexeswereobtainedin enantiomeric
excess. The use of the chiral auxiliary (+)-(1S,2R)-
norephedrine instead of (ꢀ)-(1R,2S)-ephedrine for the
reduction of rac-2d led to the opposite enantiomers
(S,R)-3d and (S)-2d, demonstrating that the nature of
the chiral auxiliary is crucial to define the stereochemis-

3182
C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
mixture samples were made after evaporation, dilution
with ethyl acetate, decomplexation under sunlight/air
(for chromium complexes) and filtration through a short
column of silica and celite. Elemental analyses were per-
formed on a Perkin–Elmer 2400 CHN microanalyser.
High-resolution mass spectrum was determined on a
VG AUTO SPEC Micromass. Optical rotations were
measured with a Perkin–Elmer Polarimeter 341. Melting
points were measured on a Microquimica MQ APF-301.
J = 17.2 Hz, J = 6.2 Hz, J = 4.7 Hz, 1H, OCH2CHH-
C(O)], 2.77 [ddd, 1H, J = 17.2 Hz, J = 9.1 Hz,
J = 5.1 Hz, OCH2CHHC(O)]. 13C1H NMR (CDCl3,
75.5 MHz): d 230.19 (C„O), 189.29 (C@O), 144.13
(Ph), 95.23 (Ph), 90.04 (Ph), 85.12 (Ph), 82.03 (Ph),
79.28 (Ph), 66.99 (OCH2), 36.79 [C(O)CH2]. Anal. Calc.
for C12H8CrO5 (284.19 g molꢀ1): C, 50.72; H, 2.84.
Found: C, 50.59; H, 2.71%.
4.1.4. Rac-tricarbonyl(g6-thiochroman-4-one)chromium
(rac-2d)
4.1. Synthesis of tricarbonyl(g6-aryl ketone)chromium
complexes rac-2a–d, 2e–f
Yield: 38% of a red solid; m.p. 137.5–138.5 ꢁC. IR
(Nujol, cmꢀ1): 1975 (vs), 1898 (vs), 1876 (vs), 1679
(sh), 1660 (s). 1H NMR (CDCl3, 300 MHz): d 6.32
(dd, J = 6.6 Hz, J = 1.1 Hz, 1H, Ph), 5.73 (td,
J = 6.2 Hz, J = 1.1 Hz, 1H, Ph), 5.29 (dd, J = 6.6 Hz,
J = 0.7 Hz, 1H, Ph), 5.15 (td, J = 6.4 Hz, J = 1.1 Hz,
1H, Ph), 3.50–3.34 (m, 1H, CH2), 3.15–3.04 (m, 2H,
CH2), 2.92–2.78 (m, 1H, CH2). 13C{1H} NMR (CDCl3,
75.5 MHz): d 230.32 (C„O), 192.22 (C@O), 118.86
(Ph), 94.66 (Ph), 91.67 (Ph), 88.81 (Ph), 88.36 (Ph),
86.90 (Ph), 38.79 [C(O)CH2], 26.20 (SCH2). Anal. Calc.
for C12H8CrO4S (300.24 g molꢀ1): C, 48.00; H, 2.69.
Found: C, 48.16; H, 2.66%.
The complexes were prepared according to the meth-
od of Pauson and co-workers [14].
4.1.1. Rac-tricarbonyl(g6-1-indanone)chromium (rac-2a)
Yield: 25% of an orange solid; m.p. 122.5–123.5 ꢁC. IR
(Nujol, cmꢀ1): 1969 (vs), 1900 (sh), 1889 (vs), 1713 (s). 1H
NMR (CDCl3, 500 MHz): d 6.02 (d, J = 6.4 Hz, 1H, Ph),
5.71 (t, J = 6.1 Hz, 1H, Ph), 5.42 (d, J = 6.1 Hz, 1H, Ph),
5.19 (t, J = 6.1 Hz, 1H, Ph), 3.13 [ddd, 1H, J = 16.8 Hz,
J = 8.9 Hz, J = 5.5 Hz, CHHC(O)], 3.02 [ddd, 1H,
J = 16.5 Hz, J = 8.2 Hz, J = 2.1 Hz, CHHC(O)], 2.73
(ddd, 1H, J = 19.2 Hz, J = 8.2 Hz, J = 5.2 Hz,
CHHCH2), 2.63 (ddd, 1H, J = 18.9 Hz, J = 8.9 Hz,
J = 2.1 Hz, CHHCH2CH2). 13C{1H} NMR (CDCl3,
125.7 MHz): d 230.03 (C„O), 202.40 (C@O), 123.15
(Ph), 96.00 (Ph), 95.44 (Ph), 89.76 (Ph), 88.25 (Ph),
86.89 (Ph), 34.53 [C(O)CH2], 24.95 (CH2). Anal. Calc.
for C12H8CrO4 (268.18 g molꢀ1): C, 53.74; H, 3.01.
Found: C, 53.80; H, 2.82%.
4.1.5. Tricarbonyl(g6-acetophenone)chromium (2e)
Yield: 19% of an orange solid (via its dioxolane deriv-
ative); m.p. 85–86 ꢁC; lit. [25]: 84–85 ꢁC. IR (Nujol,
cmꢀ1): 1964 (vs), 1904 (vs), 1887 (vs),1687 (s). 1H
NMR (CDCl3, 300 MHz): d 6.06 (br d, J = 6.2 Hz,
2H, Ph), 5.65 (br t, J = 6.2 Hz, 1H, Ph), 5.29 (br t,
J = 6.2 Hz, 2H, Ph), 2.46 (s, 3H, CH3). Anal. Calc. for
C11H8CrO4 (256.17 g molꢀ1): C, 51.57; H, 3.15. Found:
C, 51.70; H, 2.86%.
4.1.2. Rac-tricarbonyl(g6-1-tetralone)chromium (rac-2b)
Yield: 30% of an orange solid; m.p. 125–126 ꢁC; lit.
[24]: 125–127 ꢁC. IR (Nujol, cmꢀ1): 1970 (vs), 1878
4.1.6. Tricarbonyl(g6-propiophenone)chromium (2f)
Yield: 20% of an orange solid; m.p. 96–97 ꢁC. IR
(Nujol, cmꢀ1): 1979 (vs), 1965 (vs), 1904 (vs), 1880
(vs), 1681 (s). 1H NMR (CDCl3, 300 MHz): d 6.08
(dd, J = 6.8 Hz, J = 0.9 Hz, 2H, Ph), 5.64 (br t,
J = 6.6 Hz, 1H, Ph), 5.30 (t, J = 6.6 Hz, 2H, Ph), 2.80
(q, J = 7.3 Hz, 2H, CH2) 1.23 (t, J = 7.3 Hz, 3H, CH3).
13C{1H} NMR (CDCl3, 75.5 MHz): d 230.65 (C„O),
197.82 (C@O), 144.13 (Ph), 95.57 (Ph), 95.01 (Ph),
93.83 (Ph), 89.38 (Ph), 30.51 (CH2), 8.07 (CH3). Anal.
Calc. for C12H10CrO4 (270.20 g molꢀ1): C, 53.34; H,
3.73. Found: C, 53.25; H, 3.51%.
1
(vs), 1671 (s). H NMR (CDCl3, 300 MHz): d 6.17 (d,
J = 6.7 Hz, 1H, Ph), 5.63 (t, J = 6.1 Hz, 1H, Ph), 5.29
(t, J = 6.4 Hz, 1H, Ph), 5.15 (d, J = 6.2 Hz, 1H, Ph),
2.97 [m, 1H, CH2], 2.77 [br s, 1H, CH2], 2.72 [br t,
1H, CH2], 2.45 [m, 1H, CH2], 2.25–2.08 [m, 2H, CH2].
13C{1H} NMR (CDCl3, 75.5 MHz): d 230.18 (C„O),
195.54 (C@O), 115.13 (Ph), 94.63 (Ph), 92.62 (Ph),
91.18 (Ph), 89.70 (Ph), 89.10 (Ph), 37.87 [C(O)CH2],
28.51 (CH2), 21.84 (CH2). Anal. Calc. for C13H10CrO4
(282.22 g molꢀ1): C, 55.33; H, 3.57. Found: C, 55.34;
H, 3.53%.
4.1.3. Rac-tricarbonyl(g6-4-chromanone)chromium
(rac-2c)
4.2. General procedure for the hydrogen-transfer
reduction of the ketones 1a–f, rac-2a–d, 2e–f
Yield: 40% of an orange solid; m.p. 121–122 ꢁC. IR
(Nujol, cmꢀ1): 1972 (vs), 1913 (vs), 1880 (vs), 1852
A solution of [RuCl2(g6-benzene)]2 (6 lmol) and (ꢀ)-
(1R,S)-ephedrine hemi-sulfate (24 lmol) in dry 2-propa-
nol (3 mL) was heated at 80 ꢁC for 30 min under argon.
It was cooled to room temperature and transferred to a
flask containing a solution of the ketone (0.6 mmol) and
1
(m), 1692 (s). H NMR (CDCl3, 300 MHz): d 6.19 (d,
J = 6.2 Hz, 1H, Ph), 5.76 (t, J = 6.2 Hz, 1H, Ph), 5.22
(d, J = 6.0 Hz, 1H, Ph), 5.03 (t, J = 6.2 Hz, 1H, Ph),
4.59–4.41 (m, 2H, OCH2CH2C(O)], 2.88 [ddd,

C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
3183
KOH (60 lmol) in 2-propanol (3 mL). The resulting
mixture was then stirred at room temperature under ar-
gon. After evaporation of volatiles under vacuum the
products were purified by flash column chromatography
on silica gel.
(EI): m/z (rel intensity) 151 (9), 150 (M+, 82), 133 (18),
132 (15), 131 (41), 122 (59), 121 (100), 120 (8), 107 (22),
105 (27), 104 (19), 103 (15), 94 (13), 93 (13), 92 (8), 91
(11), 79 (15), 78 (10), 77 (45), 76 (20), 75 (8), 74 (9), 66
(20), 65 (47), 64 (12), 63 (23), 55 (19), 53 (15), 52 (13),
51 (62), 50 (32), 43 (14), 40 (17).
4.2.1. Hydrogen-transfer reduction of 1-indanone (1a)
(Table 2, entry 1)
(R)-1-indanol [(R)-4a] was isolated as a white solid in
4.2.4. Hydrogen-transfer reduction of thiochroman-
4-one (1d) (Table 2, entry 5)
11% yield after flash chromatography on silica gel (ethyl
(R)-thiochroman-4-ol [(R)-4d] was isolated as a
white solid in 75% yield after flash chromatography
on silica gel (ethyl acetate:hexane: 1:9); m.p. 79.5–
23
D
acetate:hexane: 1:9); m.p. 66.5–68.0 ꢁC, ½aꢁ ¼ ꢀ29ꢂ (c
22
0.41, CHCl3), 96% ee. Lit. [12]; m.p. 72 ꢁC, ½aꢁ ¼ þ34ꢂ
D
22
1
(c 1.895, CHCl3) for S enantiomer. H NMR (CDCl3,
80.5 ꢁC. ½aꢁ ¼ þ141ꢂ (c 2.11, CHCl3), >97% ee. Lit.
D
1
300 MHz): d 7.46–7.42 (m, 1H, Ph), 7.24–7.20 (m, 2H,
Ph), 7.14–7.10 (m, 1H, Ph), 5.27 (br t, J = 5.9 Hz, 1H,
CHOH), 3.07 [ddd, J = 16.2 Hz, J = 8.4 Hz, J = 4.8 Hz,
1H, CHHCH2CH(OH)], 2.84 (br dd, J = 16.2 Hz,
J = 7.0 Hz, 1H, CHHCH2C(OH)H), 2.51 (m, 1H,
CHHC(OH)H), 1.97 (m, 1H, CHHC(OH)H), 1.75 (br
s, 1H, OH). MS (EI): m/z (rel intensity) 134 (M+, 51),
133 (100), 117 (12), 116 (14), 115 (28), 105 (30), 103
(12), 91 (32), 89 (9), 79 (25), 78 (15), 77 (45), 74 (2), 66
(16), 65 (22), 63 (25), 57 (25), 55 (32), 53 (9), 52 (13), 51
(57), 50 (29).
[27]: m.p. 77–79 ꢁC, [a]D = + 129ꢁ (c 1.3, MeOH). H
NMR (CDCl3, 300 MHz): d 7.33 (br d, J = 7.0 Hz,
1H, Ph), 7.20–7.13 (m, 2H, Ph), 7.11–7.05 (m, 1H,
Ph), 4.83 (dd, J = 4.4 Hz, J = 2.9 Hz, 1H, CHOH),
3.34 (dt, J = 12.4 Hz, J = 2.9 Hz, 1H, SCHH), 2.88
(ddd, J = 12.8 Hz, J = 5.7 Hz, J = 3.7 Hz, 1H, SCHH),
2.37 (m, 1H, CH(OH)CHH), 2.07 (m, 1H,
CH(OH)CHH), 1.82 (br d, J = 4.4 Hz, 1H, OH). MS
(EI): m/z (rel intensity) 168 (3), 167 (6), 166 (M+,
56), 165 (4), 150 (5), 149 (13), 148 (57), 147 (100),
138 (47), 137 (67), 136 (6), 135 (5), 134 (9), 133 (8),
132 (5), 123 (5), 121 (5), 116 (8), 115 (13), 110 (20),
109 (32), 108 (9), 105 (33), 104 (68), 91 (12), 77 (40),
76 (27), 74 (13), 73 (13), 69 (31), 66 (25), 65 (35), 63
(18), 55 (27), 51 (49), 50 (30), 45 (55).
Recovered 1a: 45%.
4.2.2. Hydrogen-transfer reduction of 1-tetralone (1b)
(Table 2, entry 2)
(R)-1-tetralol [(R)-4b] was isolated as a colorless oil in
37% yield after flash chromatography on silica gel (ethyl
4.2.5. Hydrogen-transfer reduction of acetophenone
(1e) (Table 2, entry 7)
22
D
acetate:hexane: 1:9). ½aꢁ ¼ ꢀ37.0ꢂ (c 2.12, CHCl3), 96%
ee. Lit. [2a]: [a]D =+34.4ꢁ (c 1.01, CHCl3) for S enantio-
(R)-1-phenylethanol [(R)-4e] was isolated as colorless
oil in 74% yield after flash chromatography on silica gel
(ethyl acetate:hexane: 1:9) in 62% ee. MS (EI): m/z (rel
intensity) 122 (M+, 22), 108 (8), 105 (13), 103 (5), 91 (4),
80 (8), 79 (100), 78 (28), 77 (70), 76(4), 74 (5), 63 (8), 53
(30), 52 (15), 51 (54), 50 (23), 45 (14), 44 (13), 43 (98).
1
mer. H NMR (CDCl3, 300 MHz): d 7.46–7.42 (m, 1H,
Ph), 7.24–7.20 (m, 2H, Ph), 7.14–7.10 (m, 1H, Ph), 4.79
(apparent t, J = 4.4 Hz, 1H, CHOH), 2.85–2.65 (m, 2H,
CH2), 2.05–1.75 (m, 5H, CH2, CH2, OH). MS (EI): m/z
(rel intensity) 148 (M+, 18), 147 (25), 131 (18), 129 (43),
128 (20), 127 (13), 121 (8), 120 (80), 119 (67), 115 (28),
105 (47), 104 (15), 92 (20), 91 (100), 90 (15), 89 (15),
79 (10), 78 (30), 77 (34), 66 (10), 65 (47), 64 (30), 63
(41), 62 (10), 60 (10), 57 (11), 55 (10), 53 (14), 52 (16),
51 (69), 50 (28), 43 (23), 41 (31), 40 (12).
4.2.6. Hydrogen-transfer reduction of propiophenone
(1f) (Table 2, entry 8)
(R)-1-phenylpropanol [(R)-4f] was isolated as a color-
less oil in 73% yield after flash chromatography on silica
22
D
Recovered 1b: 39%.
gel (ethyl acetate:hexane: 1:9). ½aꢁ ¼ þ10ꢂ (c 2.02,
CHCl3), 41% ee. Lit. [17]: [a]D ꢀ 34.0ꢁ (c 5.03, EtOH),
for S enantiomer in 97% ee. MS (EI): m/z (rel intensity)
136 (M+, 8), 117 (3), 108 (7), 107 (100), 105 (9), 91 (4), 80
(6), 79 (97), 78 (12), 77 (58), 74 (2), 63 (5), 57 (8), 53 (6),
52 (8), 51 (35), 50 (13), 43 (8), 41 (4).
4.2.3. Hydrogen-transfer reduction of 4-chromanone
(1c) (Table 2, entry 3)
(R)-4-chromanol [(R)-4c] was isolated as a white solid
in 76% yield after flash chromatography on silica gel
22
D
(ethyl acetate:hexane: 1:9); m.p. 73–74 ꢁC. ½aꢁ
¼
þ66.0ꢂ (c 3.03, CHCl3), 97% ee. Lit. [26]: m.p. 77–
78 ꢁC, [a]D = + 68.7ꢁ (c 0.49, CHCl3). 1H NMR (CDCl3,
300 MHz): d 7.33 (dd, J = 7.3 Hz, J = 1.2 Hz, 1H, Ph),
7.22 (m, 1H, J = 7.9 Hz, J = 1.5 Hz, 1H, Ph), 6.93 (br t,
J = 7.3 Hz, 1H, Ph), 6.86 (br d, J = 8.4 Hz, 1H, Ph),
4.81 (bt, 1H, CHOH), 4.31–4.26 (m, 2H, OCH2), 2.20–
2.00 (m, 2H, CH(OH)CH2), 1.86 (br s, 1H, OH). MS
4.2.7. Hydrogen-transfer reduction of rac-2a (Table 1,
entry 1)
(R)-2a and (R,S)-3a were isolated as orange and yel-
low solids in 13% and 56% yields, respectively, after
flash chromatography on silica gel (ethyl acetate:dichlo-
romethane:hexane: 1:10:10) and crystallization from
dichloromethane:hexane.

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C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
4.2.7.1. (ꢀ)-(7aR)-tricarbonyl(g6-1-indanone)chromium
(c 1.45, CHCl3), 25% ee. 1H and 13C{1H} NMR analyses
were in good agreement with rac-2c (Section 4.1.3).
23
[(R)-2a]. M.p. 138.5–140.0 ꢁC; ½aꢁ ¼ ꢀ262ꢂ (c 0.29,
D
22
D
CHCl3), 82% ee. Lit. [12]: m.p. 143 ꢁC; ½aꢁ ¼ ꢀ334ꢂ
1
(c 1.165, CHCl3). H NMR analysis was in good agree-
ment with rac-2a (Section 4.1.1).
4.2.9.2. (+)-(4R,4aS)-tricarbonyl(g6-4-chromanol)chro-
22
D
mium [(R,S)-3c]. ½aꢁ ¼ þ243ꢂ (c 0.66, CHCl3), 97%
ee. IR (Nujol, cmꢀ1): 3581 (m), 3557 (m), 1953 (vs), 1932
1
(s), 1880 (sh), 1859 (vs), 1826 (sh). H NMR (CDCl3,
4.2.7.2.
(+)-(1R,7aS)-tricarbonyl(g6-1-indanol)chro-
22
D
mium [(R,S)-3a]. ½aꢁ ¼ þ10ꢂ (c 0.42, CHCl3), 31%
300 MHz): d 5.83 (dd, J = 6.2 Hz, J = 1.1 Hz, 1H, Ph),
5.63 (dt, J = 6.4 Hz, J = 1.1 Hz, 1H, Ph), 5.02 (br d,
J = 6.9 Hz, 1H, Ph), 4.82 (dt, J = 6.3 Hz, J = 0.7 Hz, 1H,
Ph), 4.59 (ddd, J4,–OH = 9.1 Hz, J = 6.6 Hz, J = 5.1 Hz,
1H, CHOH), 4.31 (ddd, J = 11.7 Hz, J = 6.9 Hz, J =
3.3 Hz, 1H, OCHH), 4.16 (ddd, J = 11.7 Hz, J = 6.9 Hz,
J = 3.3 Hz, 1H, OCHH), 2.24–2.04 (m, 2H, CH(OH)CH2],
1.64 (d, J4,–OH = 9.1 Hz, OH). 13C{1H} NMR (CDCl3,
75.5 MHz): d 232.66 (C„O), 99.02 (Ph), 96.50 (Ph),
94.49 (Ph), 83.39 (Ph), 77.89 (Ph), 64.25 (CHOH), 61.53
(OCH2), 31.31 (CH(OH)CH2). EIHRMS Found:
285.99265. Calc. for C12H10CrO5: 285.99333.
22
22
ee. Lit.: ½aꢁ ¼ þ61ꢂ (c 1.0, CHCl3) [8f], ½aꢁ ¼ þ60.9ꢂ
D
D
1
(c 2.07, CHCl3) [12]. H NMR (CDCl3, 500 MHz): d
5.69 (d, J = 6.4 Hz, 1H, Ph), 5.45 (t, J = 6.4 Hz, 1H,
Ph), 5.27 (d, J = 6.4 Hz, 1H, Ph), 5.16 (t, J = 6.1 Hz,
1H, Ph), 5.05 (ddd, J1,–OH = 10.7 Hz, J1,2 = 8.9 Hz,
J1;20 ¼ 7.6 Hz, 1H, CHOH), 2.75–2.71 (m, 2H), 2.54
(m, 1H, CH(OH)CHH], 1.79 (dq, J = 12.5 Hz,
J = 9.5 Hz, 1H), 1.68 (d, J1,–OH = 10.7 Hz, OH). The
1H NMR analysis was in good agreement with the liter-
ature [8f].
4.2.8. Hydrogen-transfer reduction of rac-2b (Table 1,
entry 2)
4.2.10. Hydrogen-transfer reduction of rac-2d (Table 1,
entry 6)
(R)-2d and (R,S)-3d were isolated as red and yellow
solids in 20% and 37% yields, respectively, after flash
chromatography on silica gel (ethyl acetate:hexane:
4:6) and recrystallization from dichloromethane/hexane.
(R)-2b and (R,S)-3b were isolated as orange and yel-
low solids in 26% and 20% yields, respectively, after
flash chromatography on silica gel (ethyl acetate:dichlo-
romethane:hexane: 1:10:10) and crystallization from
dichloromethane:hexane.
4.2.8.1. (ꢀ)-(8aR)-tricarbonyl(g6-1-tetralone)chromium
4.2.10.1. (ꢀ)-(4aR)-tricarbonyl(g6-thiochroman-4-one)
(c 1.63, CHCl3), 95% ee. IR, 1H and 13C{1H} NMR anal-
yses were in good agreement with rac-2d (Section 4.1.4).
23
[(R)-2b]. M.p. 113.5–116 ꢁC; ½aꢁ ¼ ꢀ507ꢂ (c 1.45,
20
20
chromium[(R)-2d]. M.p. 151.5–153 ꢁC. ½aꢁ ¼ ꢀ1320ꢂ
D
CHCl3), 48% ee. Lit.: m.p. 119 ꢁDC, [a]D = ꢀ864ꢁ (c
1.55, CHCl3) [12]; ½aꢁ ¼ ꢀ802ꢂ (CHCl3), 92% ee [13].
D
1H NMR analysis is in good agreement with rac-2b (Sec-
tion 4.1.2).
4.2.10.2.
(+)-(4R,4aS)-tricarbonyl(g6-thiochroman-4-
20
ol)chromium[(R,S)-3d]. ½aꢁ ¼ þ295ꢂ (c0.27,CHCl3),
D
4.2.8.2.
(ꢀ)-(1R,8aS)-tricarbonyl(g6-1-tetralol)chro-
95% ee. IR (Nujol, cmꢀ1): 3371 (br m), 1943 (vs), 1881 (vs),
1868 (vs), 1859 (vs), 1831 (m). 1H NMR (CDCl3,
300 MHz): d 5.93 (br d, J = 6.6 Hz, 1H, Ph), 5.58 (br t,
J = 6.6 Hz, 1H, Ph), 5.14 (br d, J = 6.6 Hz, 1H, Ph), 4.97
(br t, J = 6.6 Hz, 1H, Ph), 4.58 (dt, J4,–OH = 8.8 Hz,
J = 8.4 Hz, J = 4.4 Hz, 1H, CHOH), 3.15–3.01 (m, 2H,
SCH2), 2.43–2.33 (m, 1H, CH(OH)CHH], 2.30–2.17 (m,
1H, CH(OH)CHH), 1.74 (d, J4,–OH = 8.8 Hz, OH). 13C
{1H} NMR (CDCl3, 75.5 MHz): d 232.80 (C„O),
107.93 (Ph), 95.13 (Ph), 94.09 (Ph), 86.01 (Ph), 85.90
(Ph), 65.27 (CHOH), 31.93 (CH(OH)CH2), 23.98
(SCH2). Anal. Calc. for C12H10CrO4S (302.26 g molꢀ1):
C, 47.68; H, 3.33. Found: C, 47.35; H, 3.23%.
23
mium [(R,S)-3b]. M.p. 130–133 ꢁC (dec.); ½aꢁ
¼
D
ꢀ17ꢂ (c 0.36, CHCl3), 77% ee. Lit. [8f]: m.p. 140 ꢁC;
[a]D = ꢀ20ꢁ (c 1.45, CHCl3). 1H NMR (CDCl3,
500 MHz): d 5.84 (d, J = 6.4 Hz, 1H, Ph), 5.52
(t, J = 6.4 Hz, 1H, Ph), 5.15 (t, J = 6.4 Hz, 1H, Ph),
5.10 (d, J = 6.4 Hz, 1H, Ph), 4.55–4.49 (m, 1H,
CH(OH)], 2.79–2.72 (m, 1H), 2.61 (apparent dt,
J = 16.8 Hz, J = 4.8 Hz, 1H), 2.14–2.09 (m, 1H), 2.02–
1.94 (m, 1H), 1.75–1.68 (m, 2H), 1.62 (d, J1,–
OH = 10.1 Hz, OH). 1H NMR analysis was in good
agreement with the literature [28].
4.2.9. Hydrogen-transfer reduction of rac-2c at 50 ꢁC
(Table 1, entry 4)
4.2.11. Hydrogen-transfer reduction of 2e (Table 1,
entry 9)
(R)-2c and (R,S)-3c were isolated as orange and yel-
low solids in 40% and 11% yields, respectively, after
flash chromatography on silica gel (ethyl acetate:hexane:
4:6) and crystallization from dichloromethane:hexane.
(ꢀ)-(1R)-tricarbonyl(g6-1-phenylethanol)chromium
[(R)-3e] was isolated as a yellow oil in 44% yield after
flash chromatography on silica gel (ethyl acetate:hexane:
24
D
4:6). ½aꢁ ¼ ꢀ6.1 ꢂC (c 2.3, CHCl3), 33% ee. Lit. [29]:
22
½aꢁ ¼ þ18ꢂ (c 2.1, CHCl3) for S enantiomer in 89%
4.2.9.1. (ꢀ)-(4aR)-tricarbonyl(g6-4-chromanone)chro-
D
20
mium [(R)-2c]. M.p. 120–122 ꢁC. ½aꢁ ¼ ꢀ241ꢂ
ee. IR (Nujol, cmꢀ1): 3412 (br m), 1960 (vs), 1871 (vs).
D

C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
3185
1H NMR (CDCl3, 300 MHz): d 5.58 (br d, J = 6.2 Hz,
1H, Ph), 5.45–5.28 (m, 4H, Ph), 4.58 (m, J1,2 = 6.2 Hz,
4.3.3.1. (+)-(4aS)-tricarbonyl(g6-thiochroman-4-one)
22
D
chromium [(S)-2d]. M.p. 150–152.5 ꢁC. ½aꢁ ¼ þ1298ꢂ
1
(c 1.00, CHCl3), >95% ee. H NMR analysis was in
good agreement with rac-2d (Section 4.1.4).
J1,–OH = 4.0 Hz, 1H, CHOH), 2.03 (br d, J1,–OH
=
4.0 Hz, 1H, OH), 1.50 (d, J1,2 = 6.6 Hz, 3H, CH3). 13C
{1H} NMR (CDCl3, 75.5 MHz): d 232.35 (C„O),
117.14 (Ph), 92.77 (Ph), 92.53 (Ph), 92.14 (Ph), 90.80
(Ph), 89.46 (Ph), 68.31 (CHOH), 25.33 (CH3).
4.3.3.2. (ꢀ)-(4S,4aR)-tricarbonyl(g6-thiochroman-4-ol)
22
chromium [(S,R)-3d]. ½aꢁ ¼ ꢀ162ꢂ (c 0.27, CHCl3),
D
1
49% ee. H NMR analysis was in good agreement with
(+)-(R,S)-3d (Section 4.2.10.2).
4.2.12. Hydrogen-transfer reduction of 2f (Table 1,
entry 10)
(ꢀ)-(1R)-tricarbonyl(g6-1-phenylpropanol)chromium
4.4. General procedure for the reduction of (R)-2a–d
and (S)-2d with sodium borohydride
[(R)-3f] was isolated as an yellow oil in 75% yield after
flash chromatography on silica gel (ethyl acetate:hexane:
24
D
4/6). ½aꢁ ¼ ꢀ3ꢂ (c 0.80, CHCl3), 4% ee. 1H NMR
To a solution of the (R)-2a–d or (S)-2d (0.10 mmol) in
EtOH (5 mL) was added sodium borohydride (0.15–
0.20 mmol) and the mixture was stirred (1–2 h) under ar-
gon. It was then acidified with aqueous HCl (1 mol/L)
and evaporated. The crude product was extracted with
dichloromethane, washed with water, dried over MgSO4
and filtered through a short column of silica gel. The
solution was evaporated under reduced pressure to give
the respective yellow solids of syn-3a–d.
(CDCl3, 300 MHz): d 5.59 (br d, J = 6.6 Hz, 1H, Ph),
5.45–5.23 (m, 4H, Ph), 4.30 (dt, J1,2 = 6.2 Hz, J1,–OH
=
3.6 Hz, 1H, CHOH), 1.99 (br d, J1,–OH = 3.6 Hz, 1H,
OH), 1.75 (quint., J = 7.2 Hz, 2H, CH2), 1.03
(t, J2,3 = 7.3 Hz, 3H, CH3). 13C{1H} NMR (CDCl3,
75.5 MHz): d 232.66 (C„O), 116.49 (Ph), 92.86 (Ph),
92.52 (Ph), 92.14 (Ph), 91.34 (Ph), 89.39 (Ph), 73.41
(CHOH), 32.39 (CH2), 10.10 (CH3).
4.3. Hydrogen-transfer reduction of 1c, 1d and rac-2d
using (+)-(1S,2R)-norephedrine as chiral ligand
4.4.1. (ꢀ)-(1S,7aR)-tricarbonyl(g6-1-indanol)
chromium [(S,R)-3a]
Obtained from (R)-2a and isolated as a yellow solid
23
1
The general procedure for the hydrogen-transfer
reduction (Section 4.2) was used with (+)-(1S,2R)-nor-
ephedrine instead of the (ꢀ)-(1R,2S)-ephedrine hemi-
sulfate.
in 62% yield. ½aꢁ ¼ ꢀ24ꢂ (c 0.25, CHCl3), 82% ee. H
D
NMR analysis is in good agreement with (R,S)-3a iso-
lated from the hydrogen-transfer reduction of rac-2a.
4.4.2. (+)-(1S,8aR)-tricarbonyl(g6-1-tetralol)
chromium [(S,R)-3b]
Obtained from (ꢀ)-(R)-2b and isolated as a yellow so-
lid in 90% yield (48% ee). 1H NMR analysis was in good
agreement with (ꢀ)-(R,S)-3b isolated from the hydro-
gen-transfer reduction of rac-2b.
4.3.1. Hydrogen-transfer reduction of 1c (Table 2,
entry 4)
(ꢀ)-(S)-4-chromanol [(S)-4c] was isolated as a white
solid in 39% yield after flash chromatography on silica
gel (ethyl acetate:hexane: 1:9); m.p. 73.5–75.0 ꢁC;
22
D
½aꢁ ¼ ꢀ61ꢂ (c 0.50, CHCl3), >97% ee. Lit. [26]: m.p.
77–78 ꢁC; [a]D = +68.7ꢁ (c 0.49, CHCl3) for R enantio-
mer. 1H NMR analysis was in good agreement with
(R)-4c (Section 4.2.3).
4.4.3. (ꢀ)-(4S,4aR)-tricarbonyl(g6-4-chromanol)
chromium[(S,R)-3c]
Obtained from (ꢀ)-(R)-2c and isolated as a yellow so-
20
lid in 60% yield. ½aꢁ ¼ ꢀ54ꢂ (c 0.46, CHCl3), 25% ee. 1H
Recovered 1c: 37%.
D
NMR analysis was in good agreement with (R,S)-3c iso-
lated from the hydrogen-transfer reduction of rac-2c.
4.3.2. Hydrogen-transfer reduction of 1d (Table 2,
entry 6)
(ꢀ)-(S)-thiochroman-4-ol [(S)-4d] was isolated as a
white solid in 80% yield after flash chromatography on
silica gel (ethyl acetate:hexane: 1:9); m.p. 77.5–79.5 ꢁC.
4.4.4. (ꢀ)-(4S,4aR)-tricarbonyl(g6-thiochroman-4-ol)
chromium [(S,R)-3d]
Obtained from (ꢀ)-(R)-2d and isolated as a yellow so-
22
D
20
1
½aꢁ ¼ ꢀ136ꢂ (c 1.00, CHCl3), 97 % ee. H NMR and
lid in 70% yield. ½aꢁ ¼ ꢀ304ꢂ (c 0.37, CHCl3), >95% ee.
D
MS (EI) analyses were in good agreement with (R)-4d
(Section 4.2.4).
IR and 1H NMR analyses were in good agreement with
(R,S)-3d isolated from the hydrogen-transfer reduction
of rac-2d.
4.3.3. Hydrogen-transfer reduction of rac-2d (Table 1,
entry 8)
4.4.5. (+)-(4R,4aS)-tricarbonyl(g6-thiochroman-4-ol)
chromium [(R,S)-3d]
Obtained from (+)-(S)-2d and isolated as a yellow so-
(S)-2d and (S,R)-3d were isolated as red and yellow
solids in 20% and 61% yields, respectively, after flash
chromatography on silica gel (ethyl acetate:hexane: 4:6).
23
lid in 71% yield. ½aꢁ ¼ þ358ꢂ (c 0.28, CHCl3), >95% ee.
D

3186
C.V. Ursini et al. / Journal of Organometallic Chemistry 690 (2005) 3176–3186
1H NMR analysis was in good agreement with (+)-
(R,S)-3d isolated from the hydrogen-transfer reduction
of rac-2d.
[9] T. Sammakia, E.L. Stangeland, J. Org. Chem. 62 (1997) 6104.
´
[10] A. Soladie-Cavallo, in: L.S. Liebeskind (Ed.), Advances in Metal-
organic Chemistry, vol. 1, JAI Press, Greenwich, 1989, p. 99.
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Bernardinelli, Chem. Commun. (2004) 1548;
(b) A. Bo¨ttcher, H.-G. Schmalz, Synlett (2003) 1595;
(c) S.E. Gibson, E.G. Reddington, Chem. Commun. (2000) 989;
(d) L.A. Bromley, S.G. Davies, C.L. Goodfellow, Tetrahedron:
Asymm. 2 (1991) 139;
Acknowledgments
We thank FAPESP for financial support and for a
fellowship to C.V. Ursini.
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147;
´
(f) B. Malezieux, G. Jaouen, J. Salaun, J.A.S. Howell, M.G.
¨
Palin, P. McArdle, M. OÕGara, D. Cunningham, Tetrahedron:
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