Synthesis of anti-l,3-Diols through RuCl3/PPh3-Mediated Hydrogenation of β-Hydroxy Ketones: An alternative to organoboron reagents

Article abstract of DOI:10.1002/ejoc.200900316

Hydrogenation of enantioenriched β-hydroxy ketones promoted by the catalyst generated in situ from commercially available and inexpensive RuCl ₃ and PPh₃ under hydrogen pressure allowed the efficient preparation of a variety of anti1

Full text of DOI:10.1002/ejoc.200900316

FULL PAPER
DOI: 10.1002/ejoc.200900316
Synthesis of anti-1,3-Diols through RuCl3/PPh3-Mediated Hydrogenation of
β-Hydroxy Ketones: An Alternative to Organoboron Reagents
Christophe Roche,[a] Olivier Labeeuw,[a] Mansour Haddad,[a] Tahar Ayad,[a]
Jean-Pierre Genet,[a] Virginie Ratovelomanana-Vidal,*[a] and Phannarath Phansavath*[a]
Keywords: Homogeneous catalysis / Hydrogenation / Phosphane ligands / Ruthenium
Hydrogenation of enantioenriched β-hydroxy ketones pro- selectivity. This method should be an interesting alternative
moted by the catalyst generated in situ from commercially
available and inexpensive RuCl3 and PPh3 under hydrogen
pressure allowed the efficient preparation of a variety of anti-
1,3-diols in good yields and with a high level of diastereo-
to organoboron reagents for the diastereoselective reduction
of β-hydroxy ketones.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
action proceeded with full conversion and high dia-
stereomeric excess for the anti-1,3-diol 2 (91% de, entry 1,
Table 1).
Introduction
Because 1,3-diol units are present in a large variety of
polyketide-derived natural products,[1] the development of
new methods for their preparation in either a syn or anti
relationship is of great interest.[2] Among the numerous pro-
cedures developed for the formation of acyclic 1,3-diols,
metal hydride reduction of β-hydroxy ketones has been par-
ticularly investigated and allows the stereocontrolled prepa-
ration of both syn and anti compounds.[3,4] In this area,
borohydride reagents are commonly used, and the develop-
ment of selective but less expensive and environmentally
more benign procedures is desirable. Towards this end, we
published recently an operationally simple and waste-free
method for diastereoselective catalytic hydrogenation[5] of
β-hydroxy ketones into anti-1,3-diols by using an inexpen-
sive RuCl3/phosphane combination.[6,7] Herein, we report
an expanded substrate scope as well as additional experi-
ments including the study of various ruthenium sources and
other transition-metal complexes. Complementary results
obtained with achiral diphosphanes are also described.
Table 1. Catalyst survey.[a]
Entry Precatalyst
Conv. [%][b] de [%][c]
1
2
3
4
5
RuCl3 + PPh3
[RuCl2(p-cymene)PPh3]
[RuCl2(PPh3)3]
100
100
100
91
82
90
91
89
[Ru(COD)(2-methylallyl)2] + PPh3 + HBr 100
[RuCl2(η6-benzene)]2 + PPh3 +
Et2NH.HCl
100
6
7
8
9
10
11
12
13
[Ir(COD)Cl]2+ PPh3
[Ir(COD)2Cl]2 + PPh3
IrCl3·xH2O + PPh3
RhCl3·xH2O + PPh3
[Rh(COD)Cl]2 + PPh3
[AuCl4][Na] + PPh3
[AuHCl] + PPh3
0
0
0
0
0
0
0
0
–
–
–
–
–
–
–
–
[PdCl2(PPh3)2]
Results and Discussion
[a] All reactions were performed with 0.5 mmol of substrate 1 in
2 mL of MeOH by using 10 µmol of the metal complex in the pres-
As a starting point, hydrogenation of β-hydroxy ketone 1
was examined by using various transition-metal complexes termined by H NMR spectroscopy of the crude product. [c] The
associated with PPh3 as a ligand (Table 1). The reaction was
conducted in methanol at 50 °C with 2 mol-% of the metal
source and 4 mol-% of PPh3 under 10 bar of hydrogen for
24 h. With anhydrous RuCl3 under these conditions, the re-
ence of 20 µmol of PPh3 when necessary. [b] Conversions were de-
1
de values were determined by HPLC analysis. For the determi-
nation of the diastereomeric excess, an authentic sample of the anti-
1,3-diol 2 was obtained by reduction of 1 with Me4NBH(OAc)3,[4b]
while an authentic sample of the syn-1,3-diol was prepared by re-
duction with Et2BOMe/NaBH4.[3b] The identities of the dia-
stereomers were established on the corresponding acetonides by
using the protocol reported by Rychnovsky.[10]
[a] Laboratoire Charles Friedel, UMR CNRS 7223, ENSCP Chi-
mie ParisTech,
11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France
Fax: +33-1-44071062
A comparative study with other ruthenium sources was
then carried out. The hydrogenation reaction catalyzed by
commercially available ruthenium(II) complexes [RuCl2(p-
E-mail: phannarath-phansavath@enscp.fr
virginie-vidal@enscp.fr
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V. Ratovelomanana-Vidal, P. Phansavath et al.
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cymene)PPh3] and [RuCl2(PPh3)3] afforded results compar-
The catalytic species involved in the reduction process is
able to those obtained with RuCl3/PPh3 in terms of both most likely the ruthenium hydride complex [RuHCl-
conversion and selectivity (entries 2–3, Table 1). Likewise, (PPh3)2] previously reported in the literature. Indeed, it is
with the ruthenium complex prepared by addition of PPh3 well established that reaction of PPh3 with a methanol solu-
and hydrobromic acid to commercially available [Ru- tion of RuCl3 leads to the formation of the mononuclear
(COD)(2-methylallyl)2],[8] complete conversion and high de complex [RuCl2(PPh3)3].[11] Upon exposure to hydrogen,
were obtained (entry 4, Table 1). Similar results were again this complex loses chloride to afford the species
observed with the ruthenium complex prepared by treat- [RuHCl(PPh3)3][12] (Figure 1). The latter in turn forms com-
ment of [RuCl2(η6-benzene)]2 with PPh3 and Et2NH.HCl[9] plex I, in which hydroxy ketone 1 is coordinated to the ru-
(entry 5, Table 1). Next, other transition-metal complexes thenium center through the keto and hydroxy functions, as
were investigated in the model reaction. However, under the in the most commonly considered mechanism for (diphos-
standard reaction conditions, the tested iridium, rhodium, phane)Ru-catalyzed hydrogenation of functionalized
gold, and palladium complexes proved to be inefficient, ketone.[13] Further hydride transfer from the ruthenium cen-
since no conversion was obtained with any of those (entries ter to the coordinated ketone function provides ruthenium
6–13, Table 1).
alkoxide II. The 1,3-diol 2 is then released by protonolysis,
An optimization of the reaction parameters with ruthe- yielding ruthenium complex III, which reacts with hydrogen
nium complexes was then undertaken, and the RuCl3/PPh3 to complete the catalytic cycle.
combination was preferred, as RuCl3 is the least expensive
of the ruthenium sources (Table 2).
Table 2. Hydrogenation of 1 in the presence of RuCl3/PPh3.[a]
Entry Solvent
P [bar] T [°C] t [h][b] Conv. [%][c] de [%][d]
[e]
1
2
3
4
5
6
7
8
MeOH
MeOH
MeOH
MeOH
CH2Cl2
hexane
toluene
10
100
10
4
10
10
10
25
25
50
50
50
50
50
50
72
72
24
48
24
24
24
48
30
88
100
35
61
16
10
75
–
83
91
[e]
–
44
59
62
83
CH2Cl2/MeOH (10:1) 10
[a] Conditions: 1 (0.5 mmol), solvent (2 mL), RuCl3 (10 µmol),
PPh3 (20 µmol). [b] Reaction times were not optimized. [c] Conver-
sions were determined by 1H NMR spectroscopy of the crude prod-
uct. [d] The de values were determined by HPLC analysis. [e] Not
determined.
Figure 1. Proposed mechanism for the diastereoselective hydrogen-
ation of 1 in the presence of RuCl3/PPh3.
The hydrogenation of 1 was carried out in methanol at
room temperature for 72 h, under either low or high pres-
sure of hydrogen (10 or 100 bar, respectively, entries 1 and
2, Table 2). However, under these conditions, incomplete
The anti selectivity observed in the hydrogenation reac-
conversions were observed. Actually, full conversion was tion would result from the intramolecular hydride delivery
achieved under the previously established standard condi- step I Ǟ II. Two chelation modes of hydroxy ketone 1 are
tions at a temperature of 50 °C under 10 bar hydrogen pres- possible, via the re- or si-faces, affording two diastereomers,
sure (entry 3, Table 2). At a slightly lower hydrogen pressure I and II, respectively (Figure 2). Energy minimization by
(4 bar), only 35% conversion was attained after 48 h (entry using molecular mechanics calculations (CAChe MM2 pro-
4, Table 2). With the above optimized reaction parameters, gram) was performed on both structures I and II and
other solvents were then used. The results in Table 2 indi- showed that structure I displayed a lower relative energy
cate that methanol was the solvent of choice for the model than that of its diastereomer II (∆E = 1.7 kcalmol–1). This
reaction, since low conversions and unsatisfactory dia- difference in relative energy between the two transition
stereomeric excesses were obtained in CH2Cl2, hexane, and states of step I Ǟ II would explain the formation of anti-
toluene (entries 5–7, Table 2). On the other hand, when the 1,3-diol 2 as the major product.
reaction was conducted in dichloromethane, addition of a
In an attempt to increase the selectivity of the reaction,
small amount of methanol allowed a significant increase in we next focused our attention on the influence of the mono-
diastereoselectivity (from 44% to 83% de, entries 5 and 8, phosphane ligands on the hydrogenation of 1 by using vari-
Table 2).
ous phosphanes under the optimized conditions (Table 3).
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RuCl3/PPh3-Mediated Hydrogenation of β-Hydroxy Ketones
cases, only moderate conversions were observed (30–75%)
because of the steric hindrance brought by the cyclohexyl
group.
With PPh2Cy, the formal exchange of a phenyl ring by a
cyclohexyl group led to a decrease in diastereoselectivity
(from 91% de for PPh3 to 83% de for PPh2Cy, anti isomer,
Figure 2. Structures of I and II minimized by molecular mechanics
calculations.
A comparison of various triarylphosphanes was first made
(entries 1–7, Table 3). High anti diastereoselectivities were
obtained by using P(p-MeC6H4)3, P(p-MeOC6H4)3, or P(m-
MeC6H4)3, although lower conversions were achieved rela-
tive to PPh3 (77–80% conversion and 89–90% de, entries 2,
3, and 5 vs. 100% conversion and 91% de, entry 1, Table 3).
Presumably because of the higher steric hindrance of P(o-
MeC6H4)3, very poor conversion was obtained in this case
(entry 6, Table 3). On the other hand, the less electron-rich
phosphanes P(p-ClC6H4)3 and P(m-NaO3S-C6H4)3 yielded
complete conversions, albeit with lower diastereomeric ex-
cesses (respectively 74 and 77% de, entries 4 and 7, Table 3).
The hydrogenation reaction was also performed with mono-
phosphanes bearing one or more alkyl substituents, namely,
PPh2Cy, PPhCy2, and PCy3 (entries 8–10, Table 3). In these
Figure 3. Correlation between the cone angles and the diastereo-
selectivity of the catalytic hydrogenation of compounds 1, 18, and
20 with PPh3, PPh2Cy, PPhCy2 and PCy3.
Table 4. Hydrogenation of 1 in the presence of [Ru(PP)Br2].
Table 3. Hydrogenation of 1 in the presence of RuCl3/PR3.
[b]
Entry Phosphane[a]
θ [°][b]
pKa
Conversion [%][c] de[%][d]
1
2
3
4
5
6
7
8
PPh3
145
145
145
145
148
178
2.73
3.84
4.59
1.03
3.30
100
80
77
100
78
10
100
50
30
75
0
91 (anti)
90 (anti)
89 (anti)
74 (anti)
90 (anti)
P(p-MeC6H4)3
P(p-MeOC6H4)3
P(p-ClC6H4)3
P(m-MeC6H4)3
P(o-MeC6H4)3
[e]
[f]
–
–
[e]
P(m-NaO3SC6H4)3 166
–
77 (anti)
83 (anti)
23 (anti)
27 (syn)
–
PPh2Cy
PPhCy2
PCy3
153
162
170
182
5.05
[e]
9
10
11
–
9.70
11.40
P(tBu)3
[a] In the absence of phosphane, no reduction was observed. [b]
Values of cone angles (θ) and pKa were taken from the literature.[14]
[c] Conversions were determined by H NMR spectroscopy of the
1
1
[a] Conversions were determined by H NMR spectroscopy of the
crude product. [d] The de values were determined by HPLC analy-
sis. [e] Unknown. [f] Not determined.
crude product. [b] The de values were determined by HPLC analy-
sis.
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V. Ratovelomanana-Vidal, P. Phansavath et al.
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entries 1 and 8, Table 3). An even stronger decrease in dia- case, the syn-1,3-diol was obtained as the major product
stereoselectivity was observed upon switching from PPh2Cy (27% de for the syn-1,3-diol, entry 10, Table 3). It appears
to PPhCy2 (from 83% to 23% de, anti isomer, entries 8 and from these data that an increase in the cone angle values
9, Table 3). Moreover, a reversal of diastereoselectivity was results in a decrease in the diastereoselectivity. With a phos-
observed in the hydrogenation of 1 with PCy3, since in this phane bearing a higher cone angle value (θ = 182°) such as
Table 5. Synthesis of variously substituted β-hydroxy ketones from enantiomerically enriched β-hydroxy esters.
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RuCl3/PPh3-Mediated Hydrogenation of β-Hydroxy Ketones
P(tBu)3, the hydrogenation failed to afford any conversion tivities (91–93% de, entries 2, 4–5, Table 4), except for dppp
because the related steric hindrance was the highest (entry (78% de, entry 3, Table 4).
11, Table 3). A correlation between the cone angles and the
However, hydrogenation of 1 with dppm [bis(diphenyl-
stereochemical issues of the hydrogenation reaction of com- phosphanyl)methane] and 1,6-bis(diphenylphosphanyl)hex-
pound 1 with PPh3, PPh2Cy, PPhCy2, and PCy3 can be vis- ane afforded the anti-diol 2 with lower conversions and
ualized in Figure 3. We have also observed this significant moderate to high diastereoselectivities (75–92% de, entries
decrease in selectivity upon moving from PPh3 to PCy3 in 1 and 6, Table 4). Full conversion was obtained with 1,1Ј-
the hydrogenation reactions of β-hydroxy ketones 18 and bis(diphenylphosphanyl)ferrocene, although a lower de was
20.
observed (72% de, entry 7, Table 4). Finally, with the 1,2-
Achiral diphosphanes were also tested in the hydrogena- bis(diphenylphosphanyl)benzene and 1,2-bis(dicyclohexyl-
tion reaction of compound 1. However, the RuCl3/diphos- phosphanyl)ethane ligands, diol 2 was obtained with good
phane combination failed to afford complete conversion be- de albeit with low conversions (89–92% de, entries 8–9,
cause of the lower activity of the relevant ruthenium com- Table 4).
plex. The hydrogenation reactions of 1 were therefore con-
In order to establish the generality of the RuCl3/PPh3-
ducted under the standard conditions by using the [Ru(PP)- promoted hydrogenation, the reaction was applied to a
Br2] complexes,[8] prepared in situ from commercially avail- series of β-hydroxy ketones 1, 17–28 bearing various substi-
able [Ru(COD)(2-methylallyl)2] and the diphosphane by ad- tution patterns. These compounds were first synthesized by
dition of hydrobromic acid (Table 4). Thus, with dppe [1,2- starting from enantiomerically pure or enriched β-hydroxy
bis(diphenylphosphanyl)ethane], dppp [1,3-bis(diphenyl- esters 3–9 (Table 5).
phosphanyl)propane], dppb [1,4-bis(diphenylphosphanyl)-
These readily accessible compounds were first converted
butane], or 1,5-bis(diphenylphosphanyl)pentane as diphos- into their corresponding Weinreb amides[15] 10–16 in yields
phanes, the reaction proceeded quantitatively and delivered of 70–97% by reaction with N,O-dimethylhydroxylamine
the corresponding anti-1,3-diol 2 with good diastereoselec- hydrochloride and n-butyllithium.[16] Subsequent addition
Table 6. Substrate scope of the RuCl3/PPh3 mediated diastereoselective hydrogenation of β-hydroxy ketones.[a]
[a] All reactions were performed with 0.5 mmol of substrate in 2 mL of MeOH. [b] Isolated yield after column chromatography. [c] The de
values were determined by HPLC analysis. [d] The de values were obtained after reduction of the β-hydroxy ketones with Me4NBH(OAc)3.
[e] The de values were determined by GC analysis of the corresponding Mosher diesters. [f] Together with 38% of recovered starting
material. [g] Together with 58% of recovered starting material.
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CH2Cl2 was dried and then distilled from calcium hydride. THF
and Et2O were distilled from sodium-benzophenone. n-Butyllith-
ium was purchased as 2.5  solutions in hexanes and titrated before
use. Other commercially available reagents were used without fur-
of various alkyllithium reagents to these compounds then
afforded the corresponding β-hydroxy ketones 1, 17–28 in
essentially good yields.
Applying the optimized conditions, these compounds
were reduced with good to excellent diastereoselectivities
into the corresponding anti-1,3-diols 2, 29–39 (Table 6). By
using the RuCl3/PPh3-catalyzed hydrogenation procedure, a
series of variously substituted diols bearing phenyl or ben-
zyloxy groups as well as linear and branched alkyl chains
1
ther purification. Nuclear magnetic resonance: H and 13C NMR
spectra were recorded at room temperature either at 200 MHz and
50 MHz, respectively, with an AC200 Bruker spectrometer, or at
300 MHz and 75 MHz, respectively, with an Avance 300 Bruker
spectrometer. The chemical shifts (δ) for 1H and 13C NMR spectra
are given in ppm; the signals of residual CHCl3 (δ = 7.26 ppm) and
were prepared in good yields (entries 1–13, Table 6). Start- CDCl3 (δ = 77.0 ppm) are used as internal standards. Coupling
constants (J) are given in Hertz (Hz). The abbreviations m, s, d, t,
q, quint, sext, and sept stand for multiplet, singlet, doublet, triplet,
quartet, quintet, sextet, and septet, respectively. Infrared spectra
(IR) were recorded with either a Perkin–Elmer 783G spectrometer
or an IRFT Nicolet 205 spectrometer. Mass spectra (MS) were
measured with a Nermag R10–10C mass spectrometer (DCI/NH3)
and a PE Sciex API 3000 mass spectrometer (ESI). Flash column
chromatography was performed with Merck silica gel (0.040–
0.063 mesh). TLC analysis was performed with Merck silica gel 60
PF 254 and revealed either by UV light at 254 nm or by a potas-
ing from β-hydroxy ketone 26, which is the antipode of 1,
the corresponding diol 37 was obtained in high yield and
with comparable diastereoselectivity (89% de, entry 11 vs.
91% de, entry 1, Table 6). α-Substituted β-hydroxy ketones
were also examined. RuCl3/PPh3-promoted hydrogenation
of compound 27 bearing a methyl substituent in the α posi-
tion afforded 38 in excellent yield and with high anti dia-
stereoselectivity (99% yield, 94% de, entry 12, Table 6). Fi-
nally, hydrogenation of substrate 28, bearing a tert-butyldi-
phenylsilyl ether function, under the standard conditions sium permanganate solution. Optical rotation values were recorded
with a Perkin–Elmer 241 polarimeter at 589 nm (sodium lamp).
High-performance liquid chromatography analyses (HPLC) were
performed with a Waters instrument (Waters 486 detector, 717 au-
tosampler equipped with Daicel Chiralcel OA, OB, OD, OD-H,
OJ, and Chiralpack AD and AS-H). Elemental analysis was per-
formed by the Service Régional de Microanalyse de l’Université
Pierre et Marie Curie.
failed to afford the corresponding diol in reasonable yield.
In this case, only 18% of diol 39 was obtained together with
58% of recovered starting material and 24% of the triol
resulting from deprotection of the silyl ether (entry 13,
Table 6). For this compound, the use of the ruthenium com-
plex prepared by treatment of [RuCl2(η6-benzene)]2 with
PPh3 and Et2NH.HCl[9] at a higher hydrogen pressure
(80 bar) allowed the formation of the expected diol in a
more reasonable yield of 50%, with no deprotection of the
silyl ether observed. For comparison, a number of β-hy-
droxy ketones were reduced with Me4NBH(OAc)3. In all
cases, the RuCl3/PPh3-mediated hydrogenation afforded the
anti-1,3-diols with either comparable selectivities (entries 1,
3, and 5, Table 6) or significantly higher diastereomeric ex-
cess (97% vs. 80%, entry 4, Table 6).
Synthesis of the β-Hydroxy Esters 3–9: Compounds 3, 4, 5, 6, 7,
and 9 were prepared by ruthenium-mediated asymmetric hydrogen-
ation of the corresponding β-keto esters according to reported pro-
cedures.[17,18] The preparation of β-hydroxy ester 8 is described be-
low.
Ethyl (2R,3S)-4-Benzyloxy-3-hydroxy-2-methylbutyrate (8): A solu-
tion of β-hydroxy ester 7 (5.0 g, 21.0 mmol) in THF (40 mL) was
added dropwise to a solution (–78 °C) of LDA (50.4 mmol) in THF
(30 mL). After stirring at –78 °C for 1 h, HMPA (4.4 mL,
25.2 mmol) and methyl iodide (11.8 mL, 189 mmol) were added.
The reaction mixture was gradually warmed to –5 °C over 3.5 h,
then cooled to –50 °C and quenched with saturated aqueous
NH4Cl. After extraction with Et2O, the combined organic layers
were washed with brine, dried with MgSO4, and concentrated in
vacuo. Purification of the residue by flash chromatography on silica
gel (elution with cyclohexane/AcOEt: 75:25) afforded 8 (3.6 g,
Conclusions
In summary, we have shown that the inexpensive RuCl3/
PPh3 combination can be used efficiently for the ruthenium-
catalyzed diastereoselective hydrogenation of β-hydroxy
ketones. On the basis of the simplicity of the procedure, we
think this should be a valuable alternative to well-estab-
lished methods involving boron reagents for the preparation
of anti-1,3-diols. Moreover, this catalytic procedure gener-
ates no waste, avoids the need for aqueous work-up and is
particularly suitable for large-scale reactions. On the other
hand, achiral diphosphanes can also be used for the dia-
stereoselective reduction of β-hydroxy ketones by using the
related [Ru(PP)Br2] complexes.
1
68%) as a colorless oil. Rf = 0.25 (cyclohexane/AcOEt, 75:25). H
NMR (300 MHz, CDCl3): δ = 1.19 (d, J = 7.1 Hz, 3 H, 5-H), 1.26
(t, J = 7.2 Hz, 3 H, 7-H), 2.73 (approx. quint, J = 7.1 Hz, 1 H, 2-
H), 3.52 (dd, J = 3.9 and 9.9 Hz, 1 H, 4-H), 3.58 (dd, J = 5.4 and
9.9 Hz, 1 H, 4Ј-H), 3.88–3.93 (m, 1 H, 3-H), 4.13 (q, J = 7.2 Hz, 2
H, 6-H), 4.53 (d, J = 12.0 Hz, 1 H, CH2Ph), 4.59 (d, J = 12.0 Hz,
1 H, CH2Ph), 7.28–7.39 (m, 5 H, Ph) ppm. 13C NMR (75 MHz,
CDCl3): δ = 13.9, 14.1, 42.4, 60.5, 71.8, 72.3, 73.4, 127.7 (2 C),
128.4, 137.9, 175.4 ppm. [α]2D5 = +26.7 (c = 1.4, MeOH), lit.:[19]
[α]2D1 = +24.6 (c = 1.3, MeOH).
General Procedure for the Preparation of Weinreb Amides from the
Corresponding β-Hydroxy Esters: To a solution of N,O-dimethylhy-
droxylamine hydrochloride (6.69 g, 67.2 mmol) in THF (120 mL)
was added nBuLi (134 mmol) at –78 °C. After stirring at room tem-
perature for 10 min, the mixture was cooled to –78 °C, and a solu-
tion of the β-hydroxy ester (22.4 mmol) in THF (35 mL) was
added. The reaction mixture was stirred at –78 °C for 2 h, then
Experimental Section
General: Unless specially mentioned, all reactions were carried out
under an argon atmosphere. All solvents were reagent grade and
were distilled under a positive pressure of argon prior to use.
Amines were dried and then distilled from potassium hydroxide.
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RuCl3/PPh3-Mediated Hydrogenation of β-Hydroxy Ketones
quenched with saturated aqueous NH4Cl and warmed to room
temperature. After extraction with Et2O, the combined organic lay-
ers were dried with MgSO4 and concentrated. Purification of the
residue by flash chromatography on silica gel (elution with cyclo-
hexane/AcOEt) afforded the corresponding pure Weinreb amide
(4.5 g, 21.7 mmol, 97%).
7.2 Hz, 3 H, MeCH), 3.17 (s, 3 H, NMe), 3.14–3.23 (m, 1 H, 2-H),
3.47 (dd, J = 5.7 and 9.6 Hz, 1 H, 4-H), 3.53 (dd, J = 5.9 and
9.6 Hz, 1 H, 4Ј-H), 3.67 (s, 3 H, OMe), 3.88 (q, J = 5.4 Hz, 1 H,
3-H), 4.46 (d, J = 12.0 Hz, 1 H, 5-H), 4.52 (d, J = 12.0 Hz, 1 H,
5Ј-H), 7.26–7.34 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3):
δ = 14.7, 31.8, 36.5, 61.5, 72.6, 73.0, 73.4, 127.7 (2 C), 128.3, 138.1,
177.5 ppm.
(3S)-4-(Benzyloxy)-3-hydroxy-N-methoxy-N-methylbutanamide
(10): 4.6 g, 87 % yield, pale yellow oil. Rf = 0.63 (cyclohexane/
AcOEt, 1:1). 1H NMR (400 MHz, CDCl3): δ = 2.66 (m, 2 H, 2-
H), 3.19 (s, 3 H, OMe), 3.54 (d, J = 5.4 Hz, 2 H, 4-H), 3.68 (s, 3
H, NMe), 4.26 (m, 1 H, 3-H), 4.58 (s, 2 H, 5-H), 7.25–7.37 (m, 5
H, Ph) ppm. 13C NMR (50 MHz, CDCl3): δ = 31.8, 35.2, 61.2,
67.2, 73.2, 73.4, 127.6 (2 C), 128.4, 138.1, 173.1 ppm. MS (DCI/
(3R)-7-(tert-Butyldiphenylsilyloxy)-3-hydroxy-N-methoxy-N-methyl-
heptanamide (16): 1.2 g, 82% yield, colorless oil. Rf = 0.20 (cyclo-
hexane/AcOEt, 7:3). 1H NMR (300 MHz, CDCl3): δ = 1.05 (s, 9
H, tBu), 1.35–1.70 (m, 6 H, 4-H, 5-H and 6-H), 2.43 (dd, J = 16.8
and 9.6 Hz, 1 H, 2-H), 2.65 (d, J = 16.8 Hz, 1 H, 2Ј-H), 3.20 (s, 3
H, NMe), 3.67 (s, 3 H, OMe), 3.67 (t, J = 6.3 Hz, 2 H, 7-H), 3.95–
4.05 (m, 1 H, 3-H), 7.34–7.46 (m, 6 H, Ph), 7.64–7.70 (m, 4 H, Ph)
ppm. 13C NMR (75 MHz, CDCl3): δ = 19.2, 21.8, 26.8, 31.8, 32.4,
36.2, 38.1, 61.2, 63.8, 67.8, 127.5, 129.5, 134.0, 135.5, 173.9 ppm.
NH ): m/z = 254 [M + H]+, 271 [M + NH ]+. IR (neat): ν = 3431,
˜
3
4
3063, 3027, 2940, 2858, 1650 cm–1. [α]2D5 = –31.3 (c = 1.12, CHCl3),
lit.:[20] [α]1D8 = –25.7 (c = 3.0, CHCl3). C13H19NO4 (253.29): calcd.
C 61.64, H 7.56, N 5.53; found C 61.31, H 7.85, N 5.54.
IR (neat): ν = 3452, 1648 cm–1. [α]25 = –20.2 (c = 1.25, CHCl3).
˜
D
(3S)-3-Hydroxy-N-methoxy-N-methyl-3-phenylpropanamide (11):
4.5 g, 97% yield, pale yellow oil. Rf = 0.14 (cyclohexane/AcOEt,
6:4). 1H NMR (300 MHz, CDCl3): δ = 2.78 (dd, J = 16.6 and
9.2 Hz, 1 H, 2-H), 2.88 (dd, J = 16.6 and 2.5 Hz, 1 H, 2Ј-H), 3.21
(s, 3 H, NMe), 3.63 (s, 3 H, OMe), 5.15 (dt, J = 2.5 and 9.2 Hz, 1
H, 3-H), 7.25–7.42 (m, 5 H, Ph) ppm. 13C NMR (50 MHz, CDCl3):
δ = 32.0, 40.6, 61.4, 70.3, 125.8, 127.6, 128.5, 143.1, 173.3 ppm. IR
General Procedure for the Preparation of β-Hydroxy Ketones from
the Corresponding Weinreb Amides: To a solution of the Weinreb
amide (9.6 mmol) in THF (20 mL) at –78 °C was added dropwise
a solution of the corresponding alkyllithium (28.7 mmol). After
stirring at –78 °C for 0.5–2 h, the reaction mixture was quenched
with methanol and saturated aqueous NH4Cl, then warmed to
room temperature and extracted with Et2O. The combined organic
layers were dried with MgSO4 and concentrated. Purification of
the residue by flash chromatography on silica gel (elution with cy-
clohexane/AcOEt) afforded the pure β-hydroxy ketone.
(neat): ν = 3420, 3070, 3040, 2980, 2940, 1700, 755, 700 cm–1
.
˜
[α]2D5 = –76.7 (c = 1.00, CHCl3), lit.:[21] [α]2D3 = –36.6 (c = 1.0,
CHCl3), 47% ee.
(3R)-3-Hydroxy-N-methoxy-N-methylhexanamide (12): 4.2 g, 91%
yield, pale yellow oil. Rf = 0.19 (cyclohexane/AcOEt, 1:1). 1H
NMR (200 MHz, CDCl3): δ = 0.93 (t, J = 6.9 Hz, 3 H, 6-H), 1.50
(m, 4 H, 4-H and 5-H), 2.44 (dd, J = 16.9 and 9.3 Hz, 1 H, 2-H),
2.68 (d, J = 16.9 and 2.0 Hz, 1 H, 2Ј-H), 3.21 (s, 3 H, NMe), 3.70
(s, 3 H, OMe), 4.04 (m, 1 H, 3-H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 14.1, 18.8, 31.9, 38.3, 38.7, 61.3, 67.7, 174.0 ppm. MS
(2S)-1-(Benzyloxy)-2-hydroxyoctan-4-one (1):[17] 2.4 g, 85% yield,
colorless oil. Rf = 0.47 (cyclohexane/AcOEt, 6:4). 1H NMR
(CDCl3, 400 MHz): δ = 0.90 (t, J = 7.4 Hz, 3 H, 8-H), 1.30 (sext,
J = 7.4 Hz, 2 H, 7-H), 1.55 (m, 2 H, 6-H), 2.44 (t, J = 7.4 Hz, 2
H, 5-H), 2.63 (m, 2 H, 3-H), 3.44 (dd, J = 9.6 and 5.8 Hz, 1 H, 1-
H), 3.49 (dd, J = 9.6 and 4.8 Hz, 1 H, 1Ј-H), 4.26 (m, 1 H, 2-H),
4.54 (d, J = 12.4 Hz, 1 H, 9-H), 4.58 (d, J = 12.4 Hz, 1 H, 9Ј-H),
7.25–7.38 (m, 5 H, Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ =
13.9, 22.3, 25.7, 43.5, 45.8, 67.0, 73.3, 73.5, 127.8 (2 C), 128.5,
138.0, 211.2 ppm. MS (DCI/NH3): m/z = 251 [M + H]+, 268 [M +
(DCI/NH ): m/z = 176 [M + H]+, 193 [M + NH ]+. IR (neat): ν =
˜
3
4
3546, 2959, 2935, 2873, 1654 cm–1. [α]2D5 = –53.3 (c = 1.2, CHCl3),
lit.:[21] [α]2D3 = –2.7 (c = 0.8, CHCl3), 23% ee.
NH ]+. IR (thin film): ν = 3467, 3058, 3027, 2966, 2930, 2868, 1706
˜
4
(3S)-3-Hydroxy-N-methoxy-N,4-dimethylpentanamide (13): 3.5 g,
77% yield, pale yellow oil. Rf = 0.27 (cyclohexane/AcOEt, 1:1). 1H
NMR (300 MHz, CDCl3): δ = 0.91 (d, J = 6.7 Hz, 3 H, MeCH),
0.94 (d, J = 6.7 Hz, 3 H, MeCH), 1.70 (sept, J = 6.7 Hz, 1 H, 4-
H), 2.41 (dd, J = 16.5 and 9.9 Hz, 1 H, 2-H), 2.62 (d, J = 16.5 Hz,
1 H, 2Ј-H), 3.17 (s, 3 H, NMe), 3.67 (s, 3 H, OMe), 3.75 (m, 1 H,
3-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 18.0, 18.5, 32.0, 33.2,
35.2, 61.3, 72.7, 174.4 ppm. MS (DCI/NH3): m/z = 176 [M + H]+.
cm–1. [α]2D5 = –15.2 (c = 0.91, CHCl3).
(4S)-5-(Benzyloxy)-4-hydroxypentan-2-one (17): 1.0 g, 75% yield,
colorless oil. Rf = 0.64 (cyclohexane/AcOEt, 6:4). 1H NMR
(200 MHz, CDCl3): δ = 2.18 (s, 3 H, 1-H), 2.61 (dd, J = 17.4 and
5.2 Hz, 1 H, 3-H), 2.71 (dd, J = 17.4 and 6.6 Hz, 1 H, 3Ј-H), 3.43
(dd, J = 9.7 and 5.8 Hz, 1 H, 5-H), 3.49 (dd, J = 9.7 and 4.7 Hz,
1 H, 5Ј-H), 4.26 (m, 1 H, 4-H), 4.52 (d, J = 12.0 Hz, 1 H, 6-H),
4.58 (d, J = 12.0 Hz, 1 H, 6Ј-H), 7.25–7.3 (m, 5 H, Ph) ppm. 13C
NMR (50 MHz, CDCl3): δ = 30.9, 46.7, 66.9, 73.3, 73.5, 127.8,
127.9, 128.5, 138.0, 209.7 ppm. MS (DCI/NH3): m/z = 209 [M +
IR (neat): ν = 3470, 2960, 2940, 2875, 1650 cm–1. [α]25 = –63.3 (c
˜
D
= 1.0, CHCl3), lit.:[21] [α]2D3 = –27.8 (c = 0.8, CHCl3), 47% ee.
(3R)-4-(Benzyloxy)-3-hydroxy-N-methoxy-N-methylbutanamide
(14): 3.7 g, 70% yield, pale yellow oil. Rf = 0.63 (cyclohexane/Ac-
OEt, 1:1). 1H NMR (400 MHz, CDCl3): δ = 2.66 (m, 2 H, 2-H),
3.19 (s, 3 H, NMe), 3.54 (d, J = 5.4 Hz, 2 H, 4-H), 3.68 (s, 3 H,
OMe), 4.26 (m, 1 H, 3-H), 4.58 (s, 2 H, 5-H), 7.25–7.37 (m, 5 H,
Ph) ppm. 13C NMR (50 MHz, CDCl3): δ = 31.8, 35.2, 61.2, 67.2,
73.2, 73.4, 127.6 (2 C), 128.4, 138.1, 173.1 ppm. MS (DCI/NH3):
H]+, 226 [M + NH ]+. IR (neat): ν = 3452, 3063, 3032, 2909, 2863,
˜
4
1721 cm–1. [α]2D5 = –15.5 (c = 1.36, CHCl3), lit.:[22] [α]2D5 = –13.8 (c
= 0.58, CH2Cl2), 98% ee.
(1S)-1-Hydroxy-1-phenylheptan-3-one (18): 1.9 g, 98% yield, pale
yellow oil. Rf
=
0.31 (cyclohexane/AcOEt, 7:3). 1H NMR
(300 MHz, CDCl3): δ = 0.90 (t, J = 7.2 Hz, 3 H, 7-H), 1.31 (sext,
J = 7.4 Hz, 2 H, 6-H), 1.57 (quint, J = 7.5 Hz, 2 H, 5-H), 2.44 (t,
J = 7.3 Hz, 2 H, 4-H), 2.78 (dd, J = 17.2 and 4.1 Hz, 1 H, 2-H),
2.86 (dd, J = 17.2 and 8.3 Hz, 1 H, 2Ј-H), 5.16 (dt, J = 8.3 and
3.6 Hz, 1 H, 1-H), 7.25–7.40 (m, 5 H, Ph) ppm. 13C NMR
(75 MHz, CDCl3): δ = 13.8, 22.2, 25.6, 43.4, 51.0, 69.9, 125.6,
127.6, 128.5, 142.9, 211.6 ppm. MS (DCI/NH3): m/z = 189 [M –
m/z = 254 [M + H]+, 271 [M + NH ]+. IR (neat): ν = 3431, 3063,
˜
4
3027, 2940, 2858, 1650 cm–1. [α]2D5 = +31.0 (c = 1.10, CHCl3).
C13H19NO4 (253.29): calcd. C 61.64, H 7.56, N 5.53; found C
61.31, H 7.85, N 5.54.
(2S,3R)-4-Benzyloxy-3-hydroxy-N-methoxy-2,N-dimethylbutan-
amide (15): 2.5 g, 91% yield, pale yellow oil. Rf = 0.18 (cyclohex-
ane/AcOEt, 1:1). 1H NMR (300 MHz, CDCl3): δ = 1.23 (d, J =
H O + H]+, 206 [M + H]+, 224 [M + NH ]+. IR (neat): ν = 3430,
˜
2
4
Eur. J. Org. Chem. 2009, 3977–3986
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3983

V. Ratovelomanana-Vidal, P. Phansavath et al.
FULL PAPER
3070, 3040, 2970, 2940, 1730, 760, 700 cm–1. [α]2D5 = –61.6 (c = 1.00,
3440, 2970, 2940, 2880, 1715 cm–1. [α]2D5 = –61.7 (c = 1.60, CHCl3).
CHCl3), lit.:[21] [α]2D3 = –30.8 (c = 0.6, CHCl3), 46% ee.
(3S)-3-Hydroxy-4-methyl-1-phenylpentan-1-one (25): 0.6 g, 80%
yield, pale yellow oil. Rf = 0.55 (cyclohexane/AcOEt, 6:4). 1H
NMR (300 MHz, CDCl3): δ = 0.99 (d, J = 6.8 Hz, 3 H, 5-H), 1.02
(d, J = 6.8 Hz, 3 H, 5Ј-H), 1.81 (m, 1 H, 4-H), 3.03 (dd, J = 17.5
and 9.4 Hz, 1 H, 2-H), 3.18 (dd, J = 17.5 and 2.5 Hz, 1 H, 2Ј-H),
4.00 (ddd, J = 9.4, 5.6 and 2.5 Hz, 1 H, 3-H), 7.40 (m, 2 H, Ph),
7.56 (m, 1 H, Ph), 7.95 (m, Ph) ppm. 13C NMR (75 MHz, CDCl3):
δ = 18.0, 18.6, 33.2, 42.1, 72.5, 128.2, 128.7, 133.5, 137.1,
201.4 ppm. MS (DCI/NH3): m/z = 193 [M + H]+, 210 [M + NH4]
(4S)-4-Hydroxy-4-phenylbutan-2-one (19): 0.7 g, 89% yield, pale
yellow oil. Rf = 0.21 (cyclohexane/AcOEt, 7:3). H NMR (CDCl3,
1
300 MHz): δ = 2.20 (s, 3 H, 1-H), 2.81 (dd, J = 17.7 and 3.8 Hz, 1
H, 3-H), 2.90 (dd, J = 17.7 and 8.7 Hz, 1 H, 3Ј-H), 5.16 (dd, J =
3.8 and 8.7 Hz, 1 H, 4-H), 7.25–7.40 (m, 5 H, Ph) ppm. 13C NMR
(CDCl3, 75 MHz): δ = 30.8, 52.0, 69.9, 125.6, 127.7, 128.6, 142.8,
209.1 ppm. MS (DCI/NH3): = m/z 147 [M – H2O + H]+, 164 [M –
H O + NH ]+, 182 [M + NH ]+. IR (thin film): ν = 3460, 3065,
˜
2
4
4
2980, 2940, 1720, 760, 705 cm–1. [α]2D5 = –76.1 (c = 0.50, CHCl3),
+. IR (neat): ν = 3470, 3070, 2970, 2940, 2880, 1680, 755, 690 cm–1.
˜
lit.:[23] [α]2D0 = –51.3 (c = 1.0, CHCl3), 79% ee.
[α]2D5 = –83.0 (c = 0.50, CHCl3), lit.:[27] [α]2D3 = –67.7 (c = 1.43,
CHCl3), 98% ee.
(7R)-7-Hydroxydecan-5-one (20):[24] 3.1 g, 80% yield, pale yellow
oil. Rf = 0.65 (cyclohexane/AcOEt, 1:1). 1H NMR (200 MHz,
CDCl3): δ = 0.90 (t, J = 7.2 Hz, 3 H, 1-H or 10-H), 0.92 (t, J =
7.2 Hz, 3 H, 1-H or 10-H), 1.43 (m, 8 H, 2-H, 3-H, 8-H and 9-H),
2.36 (t, J = 7.6 Hz, 2 H, 4-H), 2.52 (dd, J = 17.6 and 8.6 Hz, 1 H,
6-H), 2.60 (dd, J = 17.6 and 3.4 Hz, 1 H, 6Ј-H), 4.03 (m, 1 H, 7-
H) ppm. 13C NMR (50 MHz, CDCl3): δ = 13.8, 14.0, 18.7, 22.3,
25.7, 38.7, 43.4, 49.1, 67.4, 212.5 ppm. MS (DCI/NH3): m/z = 173
(2R)-1-(Benzyloxy)-2-hydroxyoctan-4-one (26):[6] 2.0 g, 70% yield,
colorless oil. Rf = 0.47 (cyclohexane/AcOEt, 6:4). 1H NMR
(CDCl3, 400 MHz): δ = 0.90 (t, J = 7.4 Hz, 3 H, 8-H), 1.30 (sext,
J = 7.4 Hz, 2 H, 7-H), 1.55 (m, 2 H, 6-H), 2.44 (t, J = 7.4 Hz, 2
H, 5-H), 2.63 (m, 2 H, 3-H), 3.44 (dd, J = 9.6 and 5.8 Hz, 1 H, 1-
H), 3.49 (dd, J = 9.6 and 4.8 Hz, 1 H, 1Ј-H), 4.26 (m, 1 H, 2-H),
4.54 (d, J = 12.4 Hz, 1 H, 9-H), 4.58 (d, J = 12.4 Hz, 1 H, 9Ј-H),
7.25–7.38 (m, 5 H, Ph) ppm. 13C NMR (CDCl3, 75 MHz): δ =
13.9, 22.3, 25.7, 43.5, 45.8, 67.0, 73.3, 73.5, 127.8 (2 C), 128.5,
138.0, 211.2 ppm. MS (DCI/NH3): m/z = 251 [M + H]+, 268 [M +
[M + H]+, 190 [M + NH ]+. IR (neat): ν = 3452, 2966, 2930, 2870,
˜
4
1711 cm–1. [α]2D5 = –38.4 (c = 1.26, CHCl3).
(4R)-4-Hydroxyheptan-2-one (21): 0.48 g, 64% yield, pale yellow
oil. Rf = 0.10 (cyclohexane/AcOEt, 7:3). 1H NMR (200 MHz,
CDCl3): δ = 0.92 (t, J = 6.6 Hz, 3 H, 7-H), 1.36 (m, 4 H, 5-H and
6-H), 2.18 (s, 3 H, 1-H), 2.50 (dd, J = 16.4 and 8.4 Hz, 1 H, 3-H),
2.64 (dd, J = 16.4 and 3.5 Hz, 1 H, 3Ј-H), 4.04 (m, 1 H, 4-H) ppm.
13C NMR (50 MHz, CDCl3): δ = 14.0, 18.7, 30.8, 38.6, 50.1, 67.3,
210.1 ppm. MS (DCI/NH3): m/z = 132 [M + H]+, 148 [M +
NH ]+. IR (thin film): ν = 3467, 3058, 3027, 2966, 2930, 2868, 1706
˜
4
cm–1. [α]2D5 = +15.2 (c = 0.9, CHCl3).
(2R,3S)-1-Benzyloxy-2-hydroxy-3-methyloctan-4-one (27):[6] 0.9 g,
77% yield, colorless oil. Rf = 0.25 (cyclohexane/AcOEt, 8:2). 1H
NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 7.4 Hz, 3 H, 8-H), 1.07
(d, J = 7.3 Hz, 3 H, MeCH), 1.27–1.35 (m, 2 H, 7-H), 1.49–1.57
(m, 2 H, 6-H), 2.37–2.57 (m, 2 H, 5-H), 2.82 (quint, J = 7.2 Hz, 1
H, 3-H), 3.45–3.56 (m, 2 H, 1-H), 3.87–3.90 (m, 1 H, 2-H), 4.48
(d, J = 12.0 Hz, 1 H, 9-H), 4.54 (d, J = 12.0 Hz, 1 H, 9Ј-H), 7.26–
7.37 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.7,
13.8, 22.3, 25.3, 42.6, 47.7, 72.2, 72.7, 73.5, 127.7, 127.8, 128.4,
137.8, 215.3 ppm. [α]2D5 = +37.1 (c = 1.1, MeOH).
NH ]+. IR (neat): ν = 3426, 2960, 2925, 2873, 1701 cm–1. [α]25
=
˜
4
D
–49.6 (c = 0.23, CHCl3), lit.:[25] [α]2D5 = –48.0 (c = 0.38, CHCl3).
(5R)-5-Hydroxy-2-methyloctan-3-one (22):[24] 0.8 g, 81% yield, col-
1
orless oil. Rf = 0.52 (cyclohexane/AcOEt, 8:2). H NMR (CDCl3,
300 MHz): δ = 0.92 (t, J = 7.0 Hz, 3 H, 8-H), 1.10 (d, J = 6.6 Hz,
6 H, Me2CH), 1.29–1.45 (m, 4 H, 6-H and 7-H), 2.41–2.61 (m, 3
H, 2-H and 4-H), 3.95–3.98 (m, 1 H, 5-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.0, 18.0 (2 C), 18.7, 38.6, 41.4, 46.5, 67.4,
216.2 ppm. MS (DCI/NH3): m/z = 159 [M + H]+, 176 [M +
(7R)-11-(tert-Butyldiphenylsilyloxy)-7-hydroxyundecan-5-one (28):
0.8 g, 60% yield, colorless oil. Rf = 0.69 (cyclohexane/AcOEt, 7:3).
1H NMR (CDCl3, 300 MHz): δ = 0.91 (t, J = 7.4 Hz, 3 H, 1-H),
1.05 (s, 9 H, tBu), 1.25–1.75 (m, 10 H, 2-H, 3-H, 8-H, 9-H and 10-
H), 2.43 (t, J = 7.4 Hz, 2 H, 4-H), 2.47 (dd, J = 8.8 and 17.5 Hz,
1 H, 6-H), 2.57 (dd, J = 3.1 and 17.5 Hz, 1 H, 6Ј-H), 3.67 (t, J =
6.2 Hz, 2 H, 11-H), 3.95–4.05 (m, 1 H, 7-H), 7.32–7.45 (m, 6 H,
Ph), 7.62–7.69 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ
= 13.8, 19.2, 21.7, 22.3, 25.7, 26.9, 32.4, 36.1, 43.4, 48.8, 63.7, 67.5,
127.6, 129.5, 134.1, 135.5, 212.5 ppm. [α]2D5 = –17.6 (c = 0.9,
CHCl3).
NH ]+. IR (neat): ν = 3430, 2960, 2929, 2873, 1705 cm–1. C H O
˜
4
9
18
2
(158.24): calcd. C 68.31, H 11.47; found C 67.96, H 11.74.
(4R)-4-Hydroxytetradecan-6-one (23):[17] 1.6 g, 80% yield, pale yel-
1
low oil. Rf = 0.63 (cyclohexane/AcOEt, 1:1). H NMR (200 MHz,
CDCl3): δ = 0.90 (t, J = 7.2 Hz, 3 H, 1-H or 14-H), 0.95 (t, J =
7.2 Hz, 3 H, 1-H or 14-H), 1.25 (br. s, 12 H, 8-H, 9-H, 10-H, 11-
H, 12-H and 13-H), 1.50 (m, 4 H, 2-H and 3-H), 2.41 (t, J = 7.4 Hz,
2 H, 7-H), 2.46 (dd, J = 16.4 and 8.4 Hz, 1 H, 5-H), 2.60 (dd, J =
16.4 and 3.7 Hz, 1 H, 5Ј-H), 4.05 (m, 1 H, 4-H) ppm. 13C NMR
(50 MHz, CDCl3): δ = 13.9, 14.0, 18.6, 22.6, 23.6, 29.1, 29.2, 29.3,
31.8, 38.6, 43.7, 48.9, 67.3, 212.6 ppm. MS (DCI/NH3): m/z = 229
Typical Procedure for the Synthesis of 1,3-anti-Diols from the Corre-
sponding β-Hydroxy Ketones: The β-hydroxyketone (0.5 mmol) was
purged by three vacuum/argon cycles, dissolved in degassed meth-
anol (2 mL), and transferred by cannula to a round-bottomed tube
containing a degassed mixture of RuCl3 (2.1 mg, 10 µmol, pur-
[M + H]+, 246 [M + NH ]+. IR (neat): ν = 3518, 2966, 2950, 2827,
˜
4
1705 cm–1. [α]2D5 = –28.7 (c = 1.10, CHCl3).
(6S)-6-Hydroxy-7-methyloctan-4-one (24):[27] 0.95 g, 90% yield, chased from Aldrich Chemicals) and PPh3 (5.2 mg, 20 µmol). The
pale yellow oil. Rf = 0.22 (petroleum ether/Et2O, 7:3). 1H NMR
(300 MHz, CDCl3): δ = 0.91 (d, J = 6.8 Hz, 3 H, MeCH), 0.92 (t,
J = 7.4 Hz, 3 H, 1-H), 0.93 (d, J = 6.8 Hz, 3 H, MeCH), 1.61 (sext,
reaction vessel was placed in a stainless steel autoclave, which was
purged with hydrogen and pressurized to 10 bar. The autoclave was
heated to 50 °C by circulating thermostatted water in the double
J = 7.4 Hz, 2 H, 2-H), 1.68 (m, 1 H, 4-H), 2.42 (t, J = 7.4 Hz, 2 wall, and magnetic stirring was started as soon as the required tem-
H, 3-H), 2.47 (dd, J = 17.3 and 9.3 Hz, 1 H, 5-H), 2.58 (dd, J = perature was reached. After stirring for 24 h, the autoclave was
17.3 and 2.8 Hz, 1 H, 5Ј-H), 3.80 (ddd, J = 9.3, 2.8 and 5.9 Hz, 1
H, 6-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.6, 17.0, 17.7,
18.3, 32.9, 45.5, 45.8, 72.2, 212.7 ppm. MS (DCI/NH3): m/z = 141
cooled to room temperature, hydrogen was vented, and the reaction
mixture was concentrated in vacuo. Purification of the residue by
flash chromatography on silica gel (elution with cyclohexane/Ac-
[M – H O + H]+, 159 [M + H]+, 176 [M + NH ]+. IR (neat): ν = OEt) afforded the corresponding pure 1,3-diol.
˜
2
4
3984
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3977–3986

RuCl3/PPh3-Mediated Hydrogenation of β-Hydroxy Ketones
(2S,4R)-1-(Benzyloxy)octane-2,4-diol (2):[17] Rf = 0.41 (cyclohex-
ane/AcOEt, 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.83 (t, J =
(2R,4R)-Heptane-2,4-diol (33): Rf = 0.43 (cyclohexane/AcOEt, 1:1).
1H NMR (200 MHz, CDCl3): δ = 0.90 (t, J = 6.8 Hz, 3 H, 7-H),
7.1 Hz, 3 H, 8-H), 1.19–1.70 (m, 8 H, 3-H, 5-H, 6-H and 7-H), 1.20 (d, J = 6.4 Hz, 3 H, 1-H), 1.40 (m, 4 H, 5-H and 6-H), 1.56
3.37 (dd, J = 9.5 and 7.3 Hz, 1 H, 1-H), 3.44 (dd, J = 9.5 and (m, 2 H, 3-H), 3.92 (m, 1 H, 4-H), 4.13 (sext, J = 6.0 Hz, 1 H, 2-
4.0 Hz, 1 H, 1Ј-H), 3.80 (m, 1 H, 4-H), 4.06 (m, 1 H, 2-H), 4.48 (s, H) ppm. 13C NMR (50 MHz, CDCl3): δ = 14.0, 18.9, 23.5, 39.5,
2 H, 9-H), 7.31 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ 40.0, 65.4, 69.0 ppm. MS (DCI/NH3): m/z = 133 [M + H]+, 150 [M
= 14.0, 22.7, 27.9, 37.2, 39.1, 67.9, 68.8, 73.3, 74.5, 127.7, 127.8, + NH ]+. IR (neat): ν = 3398, 2969, 2930, 2875 cm–1. [α]25 = –21.7
˜
4
D
128.5, 137.9 ppm. MS (DCI/NH3): m/z = 235 [M – H2O + H]+, (c = 1.15, CHCl3), lit.:[31] [α]2D2 = –8.91 (c = 0.63, CHCl3) for 84%
253 [M + H]+, 270 [M + NH ]+. IR (neat): ν = 3413, 3054, 3034,
ee. GC analysis [diester with (S)-Mosher chloride]: Column, J&W
Scientific DB1701; gas, helium; flow: 1 mL/min; Tinjector: 250 °C;
Tdetector: 260 °C; Toven: 210 °C (1 min) then 10 °C/min to 250 °C;
tR(2R,4R) = 9.94 min, tR(2S,4R) = 11.19 min.
˜
4
2965, 2930, 2860 cm–1. [α]2D5 = –4.2 (c = 1.19, CHCl3). HPLC analy-
sis: Column, Chiralcel OD-H; eluent, hexane/propan-2-ol (95:5);
flow rate: 1.0 mL/min; detection: 254 nm; tR(2S,4R) = 17.85 min,
tR(2S,4S) = 35.42 min.
(3S,5R)-2-Methyloctane-3,5-diol (34):[26] Rf = 0.44 (cyclohexane/
AcOEt, 1:1). 1H NMR (CDCl3, 300 MHz): δ = 0.89 (t, J = 6.9 Hz,
3 H, 8-H), 0.94 (d, J = 6.9 Hz, 6 H, Me2CH), 1.20–1.65 (m, 7 H,
2-H, 4-H, 6-H and 7-H), 3.66 (m, 1 H, 3-H), 3.94 (m, 1 H, 5-H)
ppm. 13C NMR (CDCl3, 75 MHz): δ = 14.0, 18.0, 18.6, 19.0, 33.7,
(2S,4R)-1-(Benzyloxy)pentane-2,4-diol (29):[17] Rf = 0.25 (cyclohex-
ane/AcOEt, 1:1). 1H NMR (200 MHz, CDCl3): δ = 1.19 (d, J =
6.4 Hz, 3 H, 5-H), 1.55 (m, 2 H, 3-H), 3.39 (dd, J = 9.5 and 7.3 Hz,
1 H, 1-H), 3.48 (dd, J = 9.5 and 4.0 Hz, 1 H, 1Ј-H), 4.10 (m, 2 H,
2-H and 4-H), 4.55 (s, 2 H, 6-H), 7.31 (m, 5 H, Ph) ppm. 13C NMR
(50 MHz, CDCl3): δ = 23.6, 40.8, 64.9, 67.9, 73.3, 74.5, 127.7,
127.8, 128.5, 137.8 ppm. MS (DCI/NH3): m/z = 211 [M + H]+, 228
39.4, 39.5, 69.1, 73.8 ppm. IR (neat): ν = 3420, 2970, 2940 cm–1.
˜
[α]2D5 = –22.6 (c = 0.50, CHCl3). GC analysis [diester with (S)-
Mosher chloride]: Column, J&W Scientific DB1701; gas, helium;
flow: 1 mL/min; Tinjector: 250 °C; Tdetector: 260 °C; Toven: 210 °C
[M + NH ]+. IR (neat): ν = 3410, 3055, 3030, 2980, 2930, 2860,
˜
4
(1 min) then 5 °C/min to 250 °C; tR(3S,5R) = 11.55 min, tR(3S,5S)
=
735, 700 cm–1. [α]2D5 = –10.4 (c = 1.17, CHCl3). HPLC analysis:
Column, Chiralcel OD-H; eluent, hexane/propan-2-ol (90:10); flow
rate: 1.0 mL/min; detection: 254 nm; tR(2S,4R) = 12.36 min, tR(2S,4S)
= 19.93 min.
12.21 min.
(4R,6R)-Tetradecane-4,6-diol (35):[17] Rf
= 0.49 (cyclohexane/
AcOEt, 1:1). 1H NMR (200 MHz, CDCl3): δ = 0.87 (t, J = 6.6 Hz,
3 H, 1-H or 14-H), 0.93 (t, J = 6.6 Hz, 3 H, 1-H or 14-H), 1.26
(br. s, 10 H, 9-H, 10-H, 11-H, 12-H and 13-H), 1.43 (m, 8 H, 2-H,
3-H, 7-H and 8-H), 1.58 (dd, J = 6.0 and 5.1 Hz, 2 H, 5-H), 3.92
(m, 2 H, 4-H and 6-H) ppm. 13C NMR (50 MHz, CDCl3): δ = 14.1
(2C), 18.9, 22.6, 25.8, 29.2, 29.5, 29.6, 31.8, 37.5, 39.6, 42.3, 69.1,
69.4 ppm. MS (DCI/NH3): m/z = 231 [M + H]+, 248 [M + NH4]+.
(1S,3R)-1-Phenylheptane-1,3-diol (30): Rf = 0.41 (cyclohexane/
AcOEt, 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz,
3 H, 7-H), 1.31 (m, 4 H, 5-H and 6-H), 1.51 (m, 2 H, 4-H), 1.84
(ddd, J = 3.4, 7.9 and 11.5 Hz, 1 H, 2-H), 1.91 (ddd, J = 3.4, 7.9
and 11.5 Hz, 1 H, 2Ј-H), 3.86 (m, 1 H, 3-H), 5.06 (dd, J = 3.4 and
7.9 Hz, 1 H, 1-H), 7.25–7.35 (m, 5 H, Ph) ppm. 13C NMR
(75 MHz, CDCl3): δ = 14.1, 22.8, 27.9, 37.2, 44.6, 69.4, 71.8, 125.6,
127.4, 128.5, 144.7 ppm. MS (DCI/NH3): m/z = 209 [M + H]+, 226
IR (neat): ν = 3437, 2984, 2954, 2830 cm–1. [α]25 = –12.0 (c = 1.11,
CHCl3). GC analysis [diester with (S)-Mosher chloride]: Column,
J&W Scientific DB1701; gas, helium; flow: 1 mL/min; Tinjector
250 °C; Tdetector: 260 °C; Toven: 210 °C (1 min) then 2 °C/min to
250 °C; tR(4R,6R) = 27.52 min, tR(4R,6S) = 30.22 min.
(1S,3S)-4-Methyl-1-phenylpentane-1,3-diol (36):[32] Rf = 0.19 (cyclo-
hexane/AcOEt, 75:25). H NMR (300 MHz, CDCl3): δ = 0.88 (d,
˜
D
:
[M + NH ]+. IR (neat): ν = 3390, 3070, 3040, 2960, 2935, 2870,
˜
4
750, 700 cm–1. [α]2D5 = –42.9 (c = 0.25, CHCl3), lit.:[28] [α]2D0 = –43.4
(c = 0.15, CHCl3). HPLC analysis: Column, Chiralcel OD-H; elu-
ent, hexane/propan-2-ol (95:5); flow rate: 1.0 mL/min; detection:
215 nm; tR(1S,3R) = 12.21 min, tR(1S,3S) = 16.01 min.
1
J = 6.8 Hz, 3 H, MeCH), 0.91 (d, J = 6.8 Hz, 3 H, MeCH), 1.68
(oct, J = 6.5 Hz, 1 H, 4-H), 1.86 (m, 2 H, 2-H), 3.59 (dt, J = 6.0
and 5.8 Hz, 1 H, 3-H), 5.04 (dd, J = 5.0 and 6.5 Hz, 1 H, 1-H),
7.20–7.36 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ =
17.8, 18.6, 33.8, 41.8, 71.8, 73.9, 125.6, 127.3, 128.5, 144.8 ppm. IR
(1S,3R)-1-Phenylbutane-1,3-diol (31): Rf
= 0.26 (cyclohexane/
AcOEt, 1:1). 1H NMR (300 MHz, CDCl3): δ = 1.25 (d, J = 6.4 Hz,
3 H, 4-H), 1.89 (m, 2 H, 2-H), 4.07 (m, 1 H, 3-H), 5.06 (dd, J =
4.0 and 7.5 Hz, 1 H, 1-H), 7.27–7.40 (m, 5 H, Ph) ppm. 13C NMR
(75 MHz, CDCl3): δ = 23.6, 46.2, 65.5, 71.8, 125.7, 127.4, 128.5,
144.6 ppm. MS (DCI/NH3): m/z = 167 [M + H]+, 184 [M +
(neat): ν = 3450, 3070, 3040, 2970, 2945 cm–1. [α]25 = –73.5 (c =
˜
D
0.50, CHCl3). HPLC analysis: Column, Chiralcel AS-H; eluent,
hexane/propan-2-ol (95:5); flow rate: 1.0 mL/min; detection:
215 nm; tR(1R,3S) = 11.11 min, tR(1S,3S) = 12.14 min.
NH ]+. IR (neat): ν = 3350, 3070, 3040, 2980, 2935, 755, 700 cm–1.
˜
4
[α]2D5 = –67.8 (c = 0.22, CHCl3), lit.:[29] [α]2D5 = –61.6 (c = 0.7,
CHCl3). HPLC analysis: Column, Chiralcel OD-H; eluent, hexane/
propan-2-ol (95:5); flow rate: 1.0 mL/min; detection: 215 nm;
tR(1S,3R) = 15.57 min, tR(1S,3S) = 22.25 min.
(2R,4S)-1-(Benzyloxy)octane-2,4-diol (37):[6] Rf = 0.41 (cyclohex-
ane/AcOEt, 1:1). 1H NMR (300 MHz, CDCl3): δ = 0.83 (t, J =
7.1 Hz, 3 H, 8-H), 1.19–1.70 (m, 8 H, 3-H, 5-H, 6-H and 7-H),
3.37 (dd, J = 9.5 and 7.3 Hz, 1 H, 1-H), 3.44 (dd, J = 9.5 and
4.0 Hz, 1 H, 1Ј-H), 3.80 (m, 1 H, 4-H), 4.06 (m, 1 H, 2-H), 4.48 (s,
2 H, 9-H), 7.31 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ
= 14.0, 22.7, 27.9, 37.2, 39.1, 67.9, 68.8, 73.3, 74.5, 127.7, 127.8,
128.5, 137.9 ppm. MS (DCI/NH3): m/z = 235 [M – H2O + H]+,
(4R,6R)-Decane-4,6-diol (32):[30] Rf = 0.46 (cyclohexane/AcOEt,
1
1:1). H NMR (200 MHz, CDCl3): δ = 0.89 (t, J = 6.5 Hz, 3 H, 1-
H or 10-H), 0.92 (t, J = 6.8 Hz, 3 H, 1-H or 10-H), 1.39 (m, 10 H,
2-H, 3-H, 7-H, 8-H and 9-H), 1.58 (dd, J = 5.3 and 6.2 Hz, 2 H,
5-H), 3.92 (m, 2 H, 4-H and 6-H) ppm. 13C NMR (50 MHz,
CDCl3): δ = 14.0 (2 C), 18.9, 22.7, 28.0, 37.2, 39.6, 42.3, 69.1,
69.4 ppm. MS (DCI/NH3): m/z = 175 [M + H]+, 192 [M + NH4]+.
253 [M + H]+, 270 [M + NH ]+. IR (neat): ν = 3413, 3054, 3034,
˜
4
2965, 2930, 2860 cm–1. [α]2D5 = –10.5 (c = 1.05, CHCl3). HPLC
analysis: Column, Chiralcel OD-H; eluent, hexane/propan-2-ol
IR (neat): ν = 3413, 2959, 2935, 2875 cm–1. [α]25 = –11.5 (c = 0.99,
˜
D
(95:5); flow rate: 1.0 mL/min; detection: 254 nm; tR(2R,4S)
17.26 min, tR(2R,4R) = 23.29 min.
=
CHCl3). GC analysis [diester with (S)-Mosher chloride]: Column,
J&W Scientific DB1701; gas, helium; flow: 1 mL/min; Tinjector
:
250 °C; Tdetector: 260 °C; Toven: 210 °C (1 min) then 10 °C/min to (2R,3R,4S)-1-Benzyloxy-3-methyloctane-2,4-diol (38):[33] Rf = 0.53
1
250 °C; tR(4R,6R) = 13.29 min, tR(4R,6S) = 14.32 min.
(cyclohexane/AcOEt, 1:1). H NMR (300 MHz, CDCl3): δ = 0.91
Eur. J. Org. Chem. 2009, 3977–3986
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3985

V. Ratovelomanana-Vidal, P. Phansavath et al.
FULL PAPER
[9]
The ruthenium complex was prepared according to the pro-
cedure reported for (R)-p-MeO-BINAP by Takaya and Mash-
ima, see: T. Ohta, Y. Tonomura, K. Nozaki, H. Takaya, K.
Mashima, Organometallics 1996, 15, 1521.
S. D. Rychnovsky, B. Rogers, G. Yang, J. Org. Chem. 1993, 58,
3511.
a) T. A. Stephenson, G. Wilkinson, J. Inorg. Nucl. Chem. 1966,
28, 945; b) P. S. Hallman, T. A. Stephenson, G. Wilkinson, In-
org. Synth. 1970, 12, 237.
a) P. S. Hallman, B. R. McGarvey, G. Wilkinson, J. Chem. Soc.
A 1968, 3143; b) R. A. Schunn, E. R. Wonchoba, Inorg. Synth.
1971, 13, 131.
a) R. Noyori, T. Ohkuma, Angew. Chem. Int. Ed. 2001, 40,
40; b) M. Kitamura, M. Yoshimura, N. Kanda, R. Noyori,
Tetrahedron 1999, 55, 8769; c) M. T. Ashby, J. Halpern, J. Am.
Chem. Soc. 1991, 113, 589; d) J. A. Wiles, S. H. Bergens, Orga-
nometallics 1999, 18, 3709; e) C. J. A. Daley, S. H. Bergens, J.
Am. Chem. Soc. 2002, 124, 3680.
a) M. M. Rahman, H.-Y. Liu, K. Eriks, A. Prock, W. P. Gier-
ing, Organometallics 1989, 8, 1; b) D. Woska, A. Prock, W. P.
Gierin, Organometallics 2000, 19, 4629.
S. Nahm, S. M. Weinreb, Tetrahedron Lett. 1981, 22, 3815.
K. Iseki, D. Asada, Y. Kuroki, J. Fluorine Chem. 1999, 97, 85.
Compounds 3, 4, 5, 6 and 7: O. Labeeuw, J.-B. Bourg, P. Phan-
savath, J.-P. Genet, Arkivoc 2007, 10, 94.
(d, J = 6.8 Hz, 3 H, MeCH), 0.91 (t, J = 6.8 Hz, 3 H, 8-H), 1.26–
1.49 (m, 6 H, 5-H, 6-H and 7-H), 1.69–1.72 (m, 1 H, 3-H), 3.48
(dd, J = 9.5 and 7.6 Hz, 1 H, 1-H), 3.58 (dd, J = 9.5 and 3.6 Hz,
1 H, 1Ј-H), 3.81–3.85 (m, 2 H, 2-H and 4-H), 4.56 (s, 2 H,
OCH2Ph), 7.31 (m, 5 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ
= 10.6, 13.8, 22.5, 28.3, 33.2, 38.8, 72.4, 72.7, 73.2, 73.7, 127.5,
[10]
[11]
127.6, 128.2, 137.6 ppm. IR (neat): ν = 3413, 3054, 3034, 2965,
˜
2930, 2860 cm–1. [α]2D5 = –12.0 (c = 0.5, CHCl3). HPLC analysis:
Column, Chiralcel OD-H; eluent, hexane/propan-2-ol (95:5); flow
rate: 1.0 mL/min; detection: 254 nm; tR(2R,3R,4R) = 14.48 min,
tR(2R,3R,4S) = 17.46 min.
[12]
[13]
(5R,7R)-1-(tert-Butyldiphenylsilyloxy)undecane-5,7-diol (39): Rf
=
1
0.30 (cyclohexane/AcOEt, 7:3). H NMR (300 MHz, CDCl3): δ =
0.91 (t, J = 7.0 Hz, 3 H, 11-H), 1.05 (s, 9 H, tBu), 1.20–1.70 (m,
14 H, 2-H, 3-H, 4-H, 6-H, 8-H, 9-H and 10-H), 3.67 (t, J = 6.2 Hz,
2 H, 1-H), 3.85–3.95 (m, 2 H, 5-H and 7-H), 7.33–7.45 (m, 6 H,
Ph), 7.64–7.69 (m, 4 H, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ
= 14.0, 19.2, 22.0, 22.7, 26.9, 27.9, 32.4, 37.1, 37.2, 42.2, 63.8, 69.4,
127.6, 129.9, 134.0, 135.6 ppm. MS (DCI/NH3): m/z = 443 [M +
H]+. [α]2D5 = –5.9 (c = 0.63, CHCl3). HPLC analysis: Column, Chi-
ralpak AD-H; eluent, hexane/propan-2-ol (98:2); flow rate: 1.0 mL/
[14]
[15]
[16]
min; detection: 254 nm; tR(5R,7S) = 14.79 min, tR(5R,7R) = 18.92 min. [17]
[18]
Compound 9: C. Roche, N. Desroy, M. Haddad, P. Phansavath,
J.-P. Genet, Org. Lett. 2008, 10, 3911.
D. Buisson, S. Henrot, M. Larchevêque, R. Azerad, Tetrahe-
dron Lett. 1987, 28, 5033.
Acknowledgments
[19]
We thank the Ministère de l’Education Nationale et de la Recher-
che for grants for C. R. and O. L.
[20]
H. Y. Song, J. M. Joo, J. W. Kang, D.-S. Kim, C.-K. Jung, H. S.
Kwak, J. H. Park, E. Lee, C. Y. Hong, S. Jeong, K. Jeon, J. H.
Park, J. Org. Chem. 2003, 68, 8080.
J. M. Andrés, R. Pedrosa, A. Pérez-Encabo, Tetrahedron 2000,
56, 1217.
D. A. Evans, M. C. Kozlowski, J. A. Murry, C. S. Burgey, K. R.
Campos, B. T. Connell, R. J. Staples, J. Am. Chem. Soc. 1999,
121, 669.
V. D ’Elia, H. Zwicknagl, O. Reiser, J. Org. Chem. 2008, 73,
3262.
K. Körber, P. Risch, R. Brückner, Synlett 2005, 2905.
X. Lu, Y. Liu, B. Sun, B. Cindric, L. Deng, J. Am. Chem. Soc.
2008, 130, 8134.
J. L. Garcia Ruano, A. Tito, R. Culebras, Tetrahedron 1996, 52,
2177.
T. Kochi, T. P. Tang, J. A. Ellman, J. Am. Chem. Soc. 2003,
125, 11276.
T. H. Chan, K. T. Nwe, J. Org. Chem. 1992, 57, 6107.
K. Ahmad, S. Koul, S. C. Taneja, A. P. Singh, M. Kapoor, Ri-
yaz-ul-Hassan, V. Verma, G. N. Qazi, Tetrahedron: Asymmetry
2004, 15, 1685.
[1] a) S. D. Rychnovsky, Chem. Rev. 1995, 95, 2021; b) C. Schnei-
der, Angew. Chem. Int. Ed. 1998, 37, 1375.
[2] For reviews on stereoselective synthesis of 1,3-diols, see: a) S. E.
Bode, M. Wolberg, M. Müller, Synthesis 2006, 557; b) T. Oishi,
T. Nakata, Synthesis 1990, 635.
[3] For syn-reduction, see: a) K. Narasaka, F.-C. Pai, Tetrahedron
1984, 40, 2233; b) F. G. Kathawala, B. Prager, K. Prasad, O.
Repic, M. J. Shapiro, R. S. Stabler, L. Widler, Helv. Chim. Acta
1986, 69, 803; c) A. H. Hoveyda, D. A. Evans, J. Org. Chem.
1990, 55, 5190.
[4] For anti-reduction, see: a) S. Anwar, A. P. Davis, Tetrahedron
1988, 44, 3761; b) A. H. Hoveyda, D. A. Evans, J. Am. Chem.
Soc. 1990, 112, 6447; c) Y. Umekawa, S. Sakaguchi, Y. Nishi-
yama, Y. Ishii, J. Org. Chem. 1997, 62, 3409.
[5] For reviews on asymmetric hydrogenation, see: a) R. Noyori,
T. Ohkuma, Angew. Chem. Int. Ed. 2001, 40, 40; b) T. Ohkuma,
M. Kitamura, R. Noyori, Catalytic Asymmetric Synthesis
(Eds.: I. Ojima); Wiley, VCH, 2000; c) J.-P. Genet, Acc. Chem.
Res. 2003, 36, 908.
[6] For a preliminary report of this work, see: O. Labeeuw, C. Ro-
che, P. Phansavath, J.-P. Genet, Org. Lett. 2007, 9, 105.
[7] For our initial report on asymmetric hydrogenation of β-keto
esters with RuCl3/chiral diphosphanes, see: J. Madec, X. Pfis-
ter, P. Phansavath, V. Ratovelomanana-Vidal, J.-P. Genet, Tet-
rahedron 2001, 57, 2563.
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
K. S. Kirshenbaum, K. B. Sharpless, Chem. Lett. 1987, 11.
M. Nogawa, S. Sugawara, R. Iizuka, M. Shimojo, H. Ohta, M.
Hatanaka, K. Matsumoto, Tetrahedron 2006, 62, 12071.
S.-i. Kiyooka, H. Kuroda, Y. Shimasaki, Tetrahedron Lett.
1986, 27, 3009.
[32]
[33]
T. K. Chakraborty, S. Dutta, J. Chem. Soc. Perkin Trans. 1
1997, 1257.
[8] For the preparation of [Ru(P*P)Br2] complexes by using chiral
diphosphanes, see: J.-P. Genet, C. Pinel, V. Ratovelomanana-
Vidal, S. Mallart, M. C. Cano de Andrade, J. A. Laffite, Tetra-
hedron: Asymmetry 1994, 5, 665.
Received: March 24, 2009
Published Online: July 2, 2009
3986
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 3977–3986