Desymmetric hydrogenation of a meso-cyclic acid anhydride toward biotin synthesis

Article abstract of DOI:10.1016/j.tet.2011.09.065

Catalytic reactivity in the hydrogenation of a cyclic anhydride to a biotin synthetic intermediate has been investigated on the basis of Lyons' original method using Wilkinson Ru complex, revealing the high performance of DPPF and XANTPHOS diphosphines possessing wide bite angles. The results have shown a new trail for design of the corresponding asymmetric catalysts, and the potential utility of (S,S)-Et-FerroTANE and (S,S)-(R,R)-Ph-TRAP has been demonstrated.

Full text of DOI:10.1016/j.tet.2011.09.065

Tetrahedron 67 (2011) 10006e10010
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Desymmetric hydrogenation of a meso-cyclic acid anhydride toward biotin
synthesis
Masahiro Yoshimura, Kazuomi Tsuda, Hiroshi Nakatsuka, Tomoya Yamamura,
*
Masato Kitamura
Research Center for Materials Science and Department of Chemistry, Nagoya University, Chikusa, Nagoya 464-8602, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 July 2011
Received in revised form 14 September 2011
Accepted 15 September 2011
Available online 22 September 2011
Catalytic reactivity in the hydrogenation of a cyclic anhydride to a biotin synthetic intermediate has been
investigated on the basis of Lyons’ original method using Wilkinson Ru complex, revealing the high
performance of DPPF and XANTPHOS diphosphines possessing wide bite angles. The results have shown
a new trail for design of the corresponding asymmetric catalysts, and the potential utility of (S,S)-Et-
FerroTANE and (S,S)-(R,R)-Ph-TRAP has been demonstrated.
Ó 2011 Elsevier Ltd. All rights reserved.
Dedicated to Professor Gilbert Stork on the
occasion of his 90th birthday
Keywords:
Desymmetrization
Hydrogenation
Ruthenium
Cyclic anhydride
Biotin
1. Introduction
Cyclic anhydrides provide potentially useful hydrogenation
substrates for the lactone synthesis.1 The reaction is environmen-
tally benign. The only coproduct is water, and the transformation
exhibits a high atom economy.2 The asymmetric version, particu-
larly enantiotopos selective or desymmetric hydrogenation of
meso-cyclic anhydrides,3 should add a further value to the process.
The water generated, however, sometimes causes the hydrolysis of
anhydride to diacid, lowering the catalysis efficiency in terms of
chemical yield, reactivity, and selectivity. This may be a reason for
a sluggish development in the field, though over 35 years have
passed since the first report on the homogeneous system in which
Wilkinson Ru complex catalyzes hydrogenation of succinic anhy-
dride to g
-lactone in 50% yield.1a,4 Getting back to the Lyons’ orig-
Fig. 1. Desymmetrization of meso-cyclic anhydride to a key intermediate for biotin
synthesis.
inal report, we have reinvestigated the phosphine structure/
reactivity/selectivity relationship only with the focus on the hy-
drogenation to a biotin synthetic intermediate (Fig. 1).5 This paper
reports the results together with the possibilities to the asymmetric
version.
2. Results and discussion
2.1. Reactivity
First of all, the catalytic reactivity of Ruephosphine complexes in
hydrogenation of meso-cyclic anhydride 1 was investigated under the
fixed standard conditions ([1]¼100 mM; [[RuCl2(C6H6)]2]¼0.25 mM;
[ligand]¼0.5 mM; [t-C4H9OK]¼0.5 mM; 100 atm H2: toluene; 110 ꢀC;
* Corresponding author. Tel.: þ81 52 789 2957; fax: þ81 52 789 2958; e-mail
address: kitamura@os.rcms.nagoya-u.ac.jp (M. Kitamura).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.09.065

M. Yoshimura et al. / Tetrahedron 67 (2011) 10006e10010
10007
12 h) with reference to the Lyons’ report1a and our own results of
ketone hydrogenations.6 Table 1 lists the results in order of the bite
angles (BA) of bidentate ligands used.7 DPPE gave neither the desired
lactone 2 nor hydroxy lactone 3, while DPPP and DPPB gave 2 in ca.
50% yield. With DPPF, a remarkable enhancement of reactivity was
recognized. The anhydride substrate 1 was completely converted to
a >99:1 mixture of 2 and 3 without formation of diacid 4 via hydro-
lysis of 1. Increase in the BA value to 112ꢀ by changing the ligand to
XANTPHOS gave rise to quantitative hydrogenation to lactone 2 even
with the substrate/catalyst (S/C) ratio of 2000.
reactivity of the original achiral XANTPHOS, giving 2 and 3 in 10%
and 60% yields, respectively, together with ca. 20% of diacid 4
(entry 1). The enantiomer ratio (er) of (3aS)- and (3aR)-3 was
65:35.9 Lowering the hydrogen pressure to 8 atm exerted little
effect on the er of 3 and increase the degree of hydrolysis of 1
(entry 2). With the DPPF-based chiral ligand (S,S)-Et-FerroTANE,
however, the desired lactone 2 became predominant (entries 3e7,
9, and 10). When the Ru precursor was changed to Ru(h3
-
C4H7)2(cod) at 100 atm, 2 was obtained in 97% yield as a 19:81 3aS/
3aR mixture. Low-pressure hydrogenation increased the amount
of hydroxy lactone 3 to 40%. Use of RuCl2(nbd)py2 improved both
the reactivity and selectivity, giving 2 with a 14:86 er and in
quantitative yield under either high or low pressure (entries 6 and
7). The reactivity without base was decreased in one-fifth (entry
8). Addition of 1e10 equiv of base relative to RuCl2(nbd)py2
completed the reaction (entries 9 and 10). (S,S)-(R,R)-Ph-TRAP
having the largest BA and the trans chelating ability gave 2 with
a 27:73 3aS/3aR ratio in 70% yield and 3 in 30% yield (entry 11).
Decrease in the temperature to 25 ꢀC stopped the reaction mainly
at the first stage to give 3 in 85% yield as a 12:88 3aS/3aR mixture
and 2 in 10% yield (entry 12). The side product 4 was obtained in
ca. 5% yield. With an isolated complex, [RuCl(p-cymene)((S,S)-
(R,R)-ph-trap)]Cl afforded a similar result (entry 15). At low
pressure, however, the reactivity was lost even at 110 ꢀC in con-
trary to Et-FerroTANE case (entries 7 and 13). In addition, a DPPE-
based chiral ligand (S,S)-CHIRAPHOS8 gave 2 with a 49:51 er in
40% yield, while a DPPB-based chiral ligand (S,S)-DIOP8 with larger
BA increased the yield to >99% but without significant increase in
the er (38:62).
Table 1
Acceleration effect of diphosphine in hydrogenation of a meso-cyclic acid anhydride
1 using [RuCl2(C6H6)]2 as a catalyst precursora
Entry
Ligandb
Bite anglec
S/C
% Yieldd
2
3
4
1
2
3
4
DPPE
DPPP
DPPB
DPPF
Xantphos
Xantphos
85
91
98
96
112
112
200
200
200
200
200
7
52
51
>99
>99
>99
5
48
49
<1
<1
<1
3
<1
<1
<1
<1
<1
5
6e
2000
a
All reactions were carried out under 100 atm of H2 atmosphere in 0.2 mmol
scale with the concentrations of [1]¼100 mM, [RuCl2(C6H6)]2¼0.25 mM, [ligand]¼
0.5 mM, and [t-C4H9OK]¼0.5 mM in toluene at 110 ꢀC for 12 h unless otherwise
specified.
b
See Ref. 7.
c
The values are for the Ru complexes.
d
Determined by 1H NMR analysis with the S/N ratio of ca. 1000.
e
[RuCl2(C6H6)]2¼0.025 mM; [ligand]¼0.05 mM; [t-C4H9OK]¼0.05 mM; 48 h.
2.2. Asymmetric hydrogenation
With the acceleration effect of wide BA diphosphines in hand,
i
three chiral ligands Pr-XANTANE (5), Et-FerroTANE (6), and Ph-
TRAP (7)8 were adopted for the further examination on the
desymmetrization of 1 under the standard conditions above. The
results are shown in Table 2. (R,R)-iPr-XANTANE lost the high
Table 2
Desymmetrization of meso-cyclic acid anhydride 1 using chiraldiphosphineeRu complexesa
Entry
Ligand
Ru precursor
2
3
4
% Yieldb
3aS/3aR
% Yieldb
3aS/3aR
% Yieldb
1c
5
5
6
6
6
6
6
6
6
6
7
7
7
7
7
[RuCl2(C6H6)]2
[RuCl2(C6H6)]2
[RuCl2(C6H6)]2
10
20
80
97
60
>99
>99
20
>99
>99
70
10
<1
0
d
60
40
20
<3
40
0
0
40
0
65:35
64:36
d
20
30
0
0
0
0
0
<5
0
0
2c,e
3d
d
23.5:76.5
19:81
16:84
14:86
14:86
d
4d
Ru(
Ru(
h
h
3-C4H7)2(cod)
3-C4H7)2(cod)
d
5d,e
6d
d
RuCl2 (nbd) py2
RuCl2 (nbd) py2
RuCl2 (nbd) py2
RuCl2 (nbd) py2
RuCl2 (nbd) py2
[RuCl2(C6H6)]2
[RuCl2(C6H6)]2
[RuCl2(C6H6)]2
[RuCl2(C6H6)]2
[RuCl2(p-cymene)]2
d
7d,e
8e,f
9e,g
10e,h
11
d
d
14:86
14:86
27:73
12:88
d
d
0
d
30
85
<5
0
d
0
12i
13e
14e,i
15d,i,j
12:88
d
<5
<5
0
d
d
<5
d
80
15:85
10
a
All reactions were carried out under 100 atm of H2 atmosphere in 0.2e1 mmol scale with the concentrations of [1]¼100 mM, [RuCl2(C6H6)]2¼0.25 mM, [ligand]¼0.5 mM,
and [t-C4H9OK]¼0.5 mM in toluene at 110 ꢀC for 12 h unless otherwise specified.
b
Determined by 1H NMR analysis.
32 h.
c
d
[t-C4H9OK]¼1.0 mM.
e
8 atm H2.
f
[t-C4H9OK]¼0 mM.
g
[t-C4H9OK]¼0.5 mM.
h
[t-C4H9OK]¼5 mM.
i
25 ꢀC.
j
[RuCl (p-cymene)((S,S)-(R,R)-ph-trap)] Cl was used.

10008
M. Yoshimura et al. / Tetrahedron 67 (2011) 10006e10010
2.3. Supposed mechanisms of enantiotopos selection
4. Experimental section
Mechanism is not clear at the present stage. Possible reaction
pathways from 1 to 2 are not simple,3,10 but we assume that the
most plausible route is the first hydrogenation of the anhydride
carbonyl group of 1 followed by the second hydrogenation of al-
dehyde carbonyl group liberated from hydroxy lactone 3. A route
via acyl oxonium intermediate but not aldehyde carboxylic acid is
also possible.11 The reaction may proceed via RueH/C]O [2þ2]
metathesis.12 Supposed mechanism of enantiotopos selection of
4.1. General
Nuclear magnetic resonance (NMR) spectra were recorded on
a
JEOL JNM-ECA-600 spectrometer. The chemical shifts are
expressed in parts per million (ppm) downfield from tetrame-
thylsilane or in ppm relative to CHCl3, CHD2C(O)CD3 ( 7.26, 2.05 in
1H NMR; 77.0, 29.8 in 13C NMR, respectively). Signal patterns of 1H
d
d
NMR are indicated as follows: s, singlet; d, doublet; t, triplet; q,
quartet; m, multiplet; and br, broad signal. High performance liquid
chromatography (HPLC) analyses were performed on a Shimadzu
LC-10AD instrument equipped with an SCL-10A system controller,
a DGU-4A degasser, an SIL-10AXL autosampler, and a Shimadzu
SPD-10A UV detector. Hydrogenation was conducted in an 80-mL
glass autoclave for the 8-atm condition. The high-pressure re-
action was carried out in a 50-mL glass vessel placed in a stainless
steel autoclave.
two C]O of
1 by (S,S)-Et-FerroTANEe and (S,S)-(R,R)-Ph-
TRAPeRuH complexes was illustrated in Fig. 2. In both cases, the
chiral RueH species would first select one of four lone pairs of two
C]O groups of 1 to give the corresponding substrate/catalyst
complexes. These then move to the transition states (TS) by rotating
the C]O bond in a clockwise or anticlockwise manner so as not to
increase the steric repulsion between the substituents of ligand and
substrate,12a,b,d resulting favorably in a species in which bicyclo
[3.3.0] convex side is faced to the catalyst. Two phosphorous atoms
of (S,S)-Et-FerroTANE should chelate to the central Ru(II) in a cis
manner to open two diastereomeric coordination sites in the
PeRueP plane (XsH). Among four possible TS, 8 would be the
most stable and the hydride is supplied from Re face to give (3aR)-3,
which will be lead to (3aR)-2 via an aldehyde carboxylic in-
termediate.13 The intermediate or the diacid 4 would serve as
a carboxylato ligand to alter the structure of active species during
the course of the hydrogenation. The formation of hydroxy lactone
3 under basic condition may play an important role to prevent the
kind of product inhibition. (S,S)-(R,R)-Ph-TRAPeRuH complex
would prefer trans chelation rather than cis one,15 allowing only
one coordination site for 1. In the same way as above, the TS 9 are
more favorable than the other diastereomeric TS because of the
high degree of stereocomplementarity, giving (3aR)-3 as the major
enantiomer.13
4.2. Materials
Gases: H2 gas of a 99.99999% purity grade was purchased from
Nippon Sanso and used without purification. Argon gas obtained
from Nippon Sanso was purified by being passed through a column
of BASF R3-11 catalyst at 80 ꢀC and then through a column of
granular calcium sulfate.
Solvents: Toluene for hydrogenation was dried and degassed at
reflux temperature in the presence of sodium benzophenone ketyl
under an argon stream for 6 h and distilled into Schlenk flasks. The
solvent was degassed by three freezeethaw cycles before hydro-
genation. Analytical grade solvents (acetone-d6 and acetonitrile-d3)
were purchased from Cambridge Isotope Laboratories and used
without further purification.
Silica gels: Analytical thin-layer chromatography (TLC) was
performed using Merck 5715 indicating plates precoated with silica
gel 60 F254 (layer thickness, 0.25 mm). The product spots were vi-
sualized with a solution of phosphomolybdic acid. Flash column
chromatography was performed using Daiko AP 300 or nacalai
tesque Silica Gel 60 (spherical, neutral).
Catalyst precursors: The following compounds were commercially
available: [RuCl2(C6H6)]2 (Aldrich), Ru(h
3-C4H7)2(cod) (Acros).
RuCl2(nbd)py2 was prepared by the reaction of [RuCl2(nbd)]n and
piperidine followed by reaction with pyridine.16 RuCl2py2[(S,S)-Et-
FerroTANE] was prepared by the reaction of RuCl2(nbd)py2 and (S,S)-
Et-FerroTANE.17
Ligands: The following compounds were commercially available:
DPPE (Tokyo Kasei), DPPP (Tokyo Kasei), DPPB (Tokyo Kasei), DPPF
(Tokyo Kasei), XANTPHOS (Aldrich), (S,S)-Et-FerroTANE (Strem), (S,S)-
CHIRAPHOS (Tokyo Kasei), (S,S)-DIOP (Tokyo Kasei). (S,S)-(R,R)-Ph-
TRAP was prepared according to method previously reported.8c 4,5-Bis
Fig. 2. Supposed transition states in (S,S)-Et-Ferro TANE- and (S,S)-(R,R)-Ph-TRAPeRu-
catalyzed hydrogenation of 1. The backbone of the ligand was omitted for clarity. X¼H,
CI, etc.
[(2R,4R)-2,4-diisopropylphosphetano]-9,9-dimethylxanthene
was
3. Conclusion
prepared by the reaction of 4,5-bisphosphino-9,9-dimethylxan-thene
and cyclic sulfonate.8a
We have revealed that XANTPHOS and DPPF show high re-
activity in Ru-catalyzed hydrogenation of a meso-cyclic acid anhy-
dride 1. On the basis of the ligand structure/reactivity relationship
that the ligands with the larger BA tend to give the higher reactivity,
the potential utility of three chiral ligands iPr-XANTANE, Et-
FerroTANE, and Ph-TRAP have been investigated. Et-FerroTANE di-
rectly produces the lactone 2 with ca. 90:10 er at 8 atm, while Ph-
TRAP affords the hydroxy lactone 3 with ca. 90:10 ratio at 100 atm.
The enantioselectivity has been understood by stereo-
complementary model.12d The performance of the present catalyst
systems are not perfect yet, but the results should increase the
utility of desymmetrization approach to biotin via enantiotopos
hydrogenation of 1 or its related compounds in future.
Substrate and authentic sample: Anhydride (1) was prepared by
dehydration of dicarboxylic acid (4) according to the method pre-
viously reported.5i Lactone ((3aS)-2) of 99% ee is gift from Sumi-
tomo Co. Ltd.
4.3. General procedure for hydrogenation of 1
The procedure is represented with XANTPHOS as diphosphine
ligand. [RuCl2(C6H6)]2 (1.0 mg, 2.0
mmol), XANTPHOS (2.3 mg,
4.0 mol), and toluene (8.0 mL) were placed into a dry, argon-filled
m
20-mL Schlenk tube with a Young’s tap. The solution was degassed
three times by freezeethaw method and was heated at 100 ꢀC for
1 h. After the resulting pale yellow-colored solution was cooled to

M. Yoshimura et al. / Tetrahedron 67 (2011) 10006e10010
10009
25 ꢀC, a 25 mM THF solution of t-C4H9OK (0.16 mL, 4.0
has been degassed by three freezeethaw cycles was added to the
mixture. One-quarter (2 mL, 1.0 mol) of the solution was trans-
mmol), which
precursor were aged at 100 ꢀC for 1 h. Convn, >99%; 2/3/
4¼10:85:<5. The ratio of 3aS/3aR of 3 was 12:88. Absolute config-
uration: 3aR. The enantiomeric excess and absolute configuration
were determined by comparison of the HPLC after converting to
lactone by the reported method.5h To a 1 mL methanol solution of
the hydroxy lactone (15 mg, 0.04 mmol) was added NaBH4 (3 mg,
0.08 mmol) at 0 ꢀC. After the mixture was stirred at 25 ꢀC for
20 min, the mixture was partitioned between CH2Cl2 (5 mL) and
6 M aqueous HCI (2 mL). The aqueous layer was extracted by two
portions of CH2Cl2 (5 mL). The combined organic layers were dried
on Na2SO4, filtered, and concentrated to give an oil (14 mg, 98%
yield), which was subjected to the chiral HPLC analysis. Column,
CHIRALCEL OD-H (4.6 mmꢁ250 mm); eluent, hexane/2-
propanol¼6:4; flow rate, 1 mL/min; detection, 254-nm light; tR of
3aR compound, 9.7 min; tR of 3aS compound, 12.5 min.5i Physical
properties were consistent with those of previously reported.5h,i
m
ferred via stainless cannula to a pre-dried 50-mL stainless autoclave
containing 1 (67.3 mg, 0.2 mmol) under argon pressure. Hydrogen
was initially introduced under 10 atm pressure with several quick
release-fill cycles before being pressurized to 100 atm. The solution
was vigorously stirred for 12 h at 110 ꢀC. After carefully venting the
hydrogen gas, the resulting orange-colored homogeneous solution
was concentrated under reduced pressure to give reddish oil of the
crude product. The 1H NMR analysis (10:1 acetone-d6/acetonitrile-
d3, 25 ꢀC) showed that the conversion was 100% and the product
ratio of lactone (2), hydroxy lactone (3), and dicarboxylic acid (4)
was >99:<1:0. The yield was determined by 1H NMR analysis of
a reaction mixture after addition of a 24 mg (0.2 mmol) of mesi-
tylene. The area of the methyl signal of mesitylene (
d 2.29, factor
1.00) and the following signals of the compounds were compared:
substrate 1,
d
4.63 (s, 2H, 2CH), factor 1.00; lactone 2,
d
4.20 (d, 1H,
4.10 (d, 2H,
4.03 (d, 1H,
Acknowledgements
J¼15.2 Hz, CHHC6H5), factor 1.00; dicarboxylic acid,
d
J¼20.5 Hz, CHHC6H5), factor 1.21; hydroxy lactone 3,
d
This work was aided by the Grant-in-Aid for Scientific Research
(No. 25E07B212) from the Ministry of Education, Science, Sports
and Culture, Japan. We are grateful to Professor M. Sawamura at
Hokkaido University and Mr. I. Kurimoto at Sumitomo Co. Ltd for
the provision of TRAP ligand and biotin synthetic intermediates,
respectively, and to Mrs. T. Noda, Y. Maeda, and Dr. K. Oyama for
their technical support in reaction vessel production and NMR
measurements.
J¼15.0 Hz, CHHC6H5), factor 0.65. Physical properties of 2 and 3
were consistent with those previously reported.5h,i Physical prop-
erties of 4 were consistent with those of the commercially available
sample.
4.4. Asymmetric hydrogenation of 1 using (S,S)-Et-FerroTANE
(6) (Table 2, entry 6)
RuCl2(nbd)py2 (2.1 mg, 5.0
mmol), chiral ligand 6 (2.2 mg,
References and notes
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mmol), and toluene (10 mL) were placed into a dry, argon-filled
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20-mL Schlenk tube with a Young’s tap. The solution was degassed
three times by freezeethaw method and was heated at 100 ꢀC for
1 h. After the resulting pale yellow-colored solution was cooled to
25 ꢀC, the solution (10 mL, 5.0
m
mol) was transferred via stainless
cannula to a pre-dried 50-mL stainless autoclave containing 1
(336 mg, 1.0 mmol) and t-C4H9OK (1.1 mg, 10 mol) under argon
m
pressure. Hydrogen was initially introduced under 10 atm pressure
with several quick release-fill cycles before being pressurized to
100 atm. The solution was vigorously stirred for 12 h at 110 ꢀC. After
carefully venting the hydrogen gas, the resulting orange-colored
homogeneous solution was concentrated under reduced pressure
togive reddish oil of the crude product. The 1H NMR analysis showed
that the conversion was 100% and the product ratio of 2/3/4 was
>99:0:0. The product was purified by flash column chromatography
(silica gel, 10 g; 1:2 hexane/ethyl acetate as eluent) to give (3aR)-2
(319 mg, 99% isolated yield). The ratio of 3aS/3aR of 2 was 14:86. The
enantiomeric excess of the products was determined by chiral HPLC
analysis (Column, CHIRALCEL OD-H (4.6 mmꢁ250 mm); eluent,
hexane/2-propanol¼6:4; flow rate, 1 mL/min; detection, 254-nm
light; tR of 3aR compound, 9.7 min; tR of 3aS compound,
12.5 min).5i The absolute configuration was determined to be 3aR by
comparison of the tR of the authentic (3aS)-2 of 99% ee. Physical
properties were consistent with those of previously reported.5h,i
6. (a) Kitamura, M.; Tokunaga, M.; Noyori, R. J. Org. Chem. 1992, 57, 4053e4054;
(b) Kitamura, M.; Tokunaga, M.; Ohkuma, T.; Noyori, R. Org. Synth. 1993, 71,
1e13; (c) Huang, H.; Okuno, T.; Tsuda, K.; Yoshimura, M.; Kitamura, M. J. Am.
Chem. Soc. 2006, 128, 8716e8717.
4.5. Asymmetric hydrogenation of 1 using (S,S)-(R,R)-Ph-
TRAP (7) (Table 2, entry 12)
7. DPPE¼1,2-bis(diphenylphosphino)ethane. DPPP¼1,3-bis(diphenylphosphino)
The procedure was the same as that for the asymmetric hy-
drogenation of anhydride (1). Listed below are the reaction condi-
tions (amounts of anhydride (1); [RuCl2(C6H6)]2; chiral ligand 7; t-
C4H9OK; amount of toluene; H2, atm; temperature, time), conver-
sion of substrate, product ratio of 2/3/4 estimated by 1H NMR
measurement, the ratio of 3aS/3aR of 3, and the physical property.
propane. DPPB¼1,4-bis(diphenylphosphino)butane. DPPF¼1,1’-bis(diphenyl-
phosphino)ferrocene.
dimethylxanthene Subongkoj, S.; Lange, S.; Chen, W.; Xiao, J. J. Mol. Catal. A:
Chem. 2003, 196, 125e129.
XANTPHOS¼4,5-bis(diphenylphosphino)-9,9-
8. iPr-XANTANE¼4,5-bis[(2R,4R)-2,4-diisopropylphosphetano]-9,9-dimethylxanta-
ne. This was prepared according to the synthesis of 4,5-bis[(2S,5S)-2,5-
dimethylphospholano]-9,9-dimethylxanthene: (a) Dierkes, P.; Ramdeehul, S.;
Barloy, L.; De Cian, A.; Fischer, J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Osborn,
J. A. Angew. Chem., Int. Ed. 1998, 37, 3116e3118 Et-FerroTANE¼1,10-bis[(2S,4S)-2,4-
diethylphosphetano]ferrocene, see; (b) Berens, U.; Burk, M. J.; Gerlach, A.; Hems,
W. Angew. Chem., Int. Ed. 2000, 39, 1981e1984 Ph-TRAP¼(S,S)-(R,R)-2,200-bis[l-
Conditions (Table 2, entry 12): 0.2 mmol of 1; 0.5
[RuCl2(C6H6)]2; 1 mol of chiral ligand 7; 1 mol of t-C4H9OK; 2 mL
of toluene; 100 atm of H2; 25 ꢀC; 12 h. Chiral ligand 7 and Ru
mmol of
m
m

10010
M. Yoshimura et al. / Tetrahedron 67 (2011) 10006e10010
(diphenylphosphinoethyl)-1,100-biferrocene, see: (c) Sawamura, M.; Hamashima,
H.; Sugawara, M.; Kuwano, R.; Ito, Y. Organometallics 1995, 14, 4549e4558 (S,S)-
CHIRAPHOS¼(2S,3S)-2,3-bis(diphenylphosphino)butane. (S,S)-DIOP¼(2S,3S)-2,3-
O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane.
M. Tetrahedron 2006, 62, 5448e5453; (d) Kitamura, M.; Nakatsuka, H. Chem.
Commun. 2011, 842e846 Dihydride mechanism; (e) Sandoval, C. A.; Ohkuma,
T.; Muniz, K.; Noyori, R. J. Am. Chem. Soc. 2003, 125, 13490e13503; (f) Hamilton,
R. J.; Leong, C. G.; Bigam, G.; Miskolzie, M.; Bergens, S. H. J. Am. Chem. Soc. 2005,
127, 4152e4153.
~
9. The stereochemical relationship between C(6a)H and C(6)H of the hydroxy
lactone 3 is supposed to be trans because the J value is 0.5a,b,10a (3aS)-3 rep-
resents (3aS,6aR,6R)-3, while (3aR)-3 does (3aR,6aS,6S)-3.
10. Hydroxy lactone route: (a) Matsuki, K.; Inoue, H.; Ishida, A.; Takeda, M.; Na-
kagawa, M.; Hino, T. Chem. Pharm. Bull. 1994, 42, 9e18 Mechanism of oxidative
addition, hydrogenolysis route; (b) Osakada, K.; Ikariya, T.; Yoshikawa, S. J.
Organomet. Chem. 1982, 231, 79e90; (c) Nagayama, K.; Shimizu, I.; Yamamoto,
A. Bull. Chem. Soc. Jpn. 2001, 74, 1803e1815 Hydrogenation route of aldehy-
deecarboxylic acid; (d) Hara, Y.; Kusaka, H.; Inagaki, H.; Takahashi, K.; Wada, K.
J. Catal. 2000, 194, 188e197.
13. The product in the first hydrogenation using (S,S)-Et-FerroTANE (6) or (S,S)-
(R,R)-Ph-TRAP (7) should be (3aR,6aS,6R)-314 with cis C(6a)H/C(6)H relation. If
the C]O reduction mechanism operates, this would be quickly isomerized to
the more stable (3aR,6aS,6S)-3 via an aldehyde carboxylic acid intermediate.
Under the hydrogenation conditions ([1]¼50 mM, [[RuCl2(C6H6)]2]¼0.25 mM,
[7]¼0.5 mM, [t-C4H9OK]¼0.5 mM, 20 atm H2, toluene-d8, 25 ꢀC), however, the
aldehyde signal was not observed in the 1H NMR spectrum. Kinetic resolution
of 3 is also not likely, because the ers of 2 and 3 in all cases in Table 2 are not
significantly different each other.
11. For acyl oxonium intermediate, see: (a) Terlouw, J. K.; Burgers, P. C.; Schwarz, H.
Org. Mass Spectrom. 1980, 15, 599e605; (b) Costello, J. F.; Draffin, W. N.; Paver, S.
P. Tetrahedron 2005, 61, 6715e6719.
14. The products enantiomeric to the natural biotin are obtained with (S,S)-6 and
(S,S)-(R,R)-7.
15. Kuwano, R.; Kashiwabara, M. Org. Lett. 2006, 8, 2653e2655.
12. Monohydride mechanism: (a) Kitamura, M.; Tsukamoto, M.; Bessho, Y.; Yosh-
imura, M.; Kobs, U.; Widhalm, M.; Noyori, R. J. Am. Chem. Soc. 2002, 124,
6649e6667; (b) Noyori, R.; Kitamura, M.; Ohkuma, T. Proc. Natl. Acad. Sci. U.S.A.
2004, 101, 5356e5362; (c) Tsukamoto, M.; Yoshimura, M.; Tsuda, K.; Kitamura,
16. Leong, C. G.; Akotsi, O. M.; Ferguson, M. J.; Bergens, S. H. Chem. Commun. 2003,
750e751.
ˇ
17. Marinetti, A.; Labrue, F.; Pons, B.; Jus, S.; Ricard, L.; Genet, J.-P. Eur. J. Inorg. Chem.
2003, 2583e2590.