Development of new thiazole-based iridium catalysts and their applications in the asymmetric hydrogenation of trisubstituted olefins

Article abstract of DOI:10.1039/b714744a

New thiazole-based chiral N,P-ligands that are open-chain analogues of known cyclic thiazole ligands have been synthesized and evaluated in the iridium-catalyzed asymmetric hydrogenation of trisubstituted olefins. Chirality was introduced into the ligands through a highly diastereoselective alkylation using Oppolzer's camphorsultam as chiral auxiliary. In general, the new catalysts are as reactive and selective as their cyclic counterparts for the asymmetric hydrogenation of various trisubstituted olefins. This journal is The Royal Society of Chemistry.

Full text of DOI:10.1039/b714744a

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Development of new thiazole-based iridium catalysts and their applications in
the asymmetric hydrogenation of trisubstituted olefins†
Pradeep Cheruku,‡ Alexander Paptchikhine,‡ Muhammad Ali,‡ Jo¨rg-M. Neudo¨rfl and Pher G. Andersson*
Received 25th September 2007, Accepted 9th November 2007
First published as an Advance Article on the web 4th December 2007
DOI: 10.1039/b714744a
New thiazole-based chiral N,P-ligands that are open-chain analogues of known cyclic thiazole ligands
have been synthesized and evaluated in the iridium-catalyzed asymmetric hydrogenation of
trisubstituted olefins. Chirality was introduced into the ligands through a highly diastereoselective
alkylation using Oppolzer’s camphorsultam as chiral auxiliary. In general, the new catalysts are as
reactive and selective as their cyclic counterparts for the asymmetric hydrogenation of various
trisubstituted olefins.
diop3 and Ru-binap4 catalysts for this reaction, many phosphine
ligands have been developed and evaluated for the hydrogenation
of functionalized olefins.5
Introduction
Asymmetric catalysis is a powerful tool for generating enantiomer-
ically pure materials.1 Asymmetric hydrogenation, the atom-
economical addition of H2 to a carbon–carbon or carbon–
heteroatom double bond to obtain a single enantiomeric product,
is the most versatile reaction in this family.2
Because of its simplicity, cost-effectiveness and environmental
affability, transition-metal-catalyzed asymmetric hydrogenation
has become a widely used method in organic synthesis. There
are many examples of optically active compounds that contain a
hydrogen atom at the stereocentre, and asymmetric hydrogenation
is of particular importance to access these compounds in highly
enantiomerically pure form.
In preliminary studies with Ir complexes,6 Crabtree’s achiral
version [(COD)Ir(py)(PCy3)]+ [PF6]− served as a conceptual tem-
plate for modifications. Replacing the monodentate pyridine and
phosphine ligands provided the foundation for chiral bidentate
N,P-ligands. The new Ir complexes emerged as powerful tools
in asymmetric hydrogenations of mainly unfunctionalized olefins
with good enantiofacial recognition, and are essentially com-
plementary to Rh- and Ru-diphosphine catalysts.7 Since then,
development of new N,P-ligands8 for Ir-catalysts has been an
important and challenging area of research.
Lately, we have demonstrated that the substrate scope for these
catalysts is not limited to unfunctionalized olefins; they can also
selectively hydrogenate various functionalized olefinic substrates.9
However, Ir-catalyzed asymmetric hydrogenation is still highly
substrate-dependent, and the development of new efficient chi-
ral ligands that can tolerate broader range of substrates is a
requisite.
Recently, we reported a new class of iridium–phosphine-thiazole
complexes 1–310 (Fig. 1) that are highly enantioselective for a wide
range of olefin substrates.
There has been especially intense interest in the asymmetric
hydrogenation of prochiral olefins. Since the first reports of Rh-
Department of Biochemistry and Organic Chemistry, Box 576, 75123, Up-
psala University, Sweden. E-mail: Pher.Andersson@biorg.uu.se; Fax: +46-
18-471 3820; Tel: +46-18-471 3816
† CCDC reference number 664206. For crystallographic data in CIF or
other electronic format see DOI: 10.1039/b714744a
‡ All authors have contributed equally to this work.
Fig. 1 Iridium complexes having thiazole-phosphine ligands with varying backbone structures.
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We also investigated the effect of structural variations of the
ligand on the stereochemical outcome of hydrogenation reactions.
In our previous studies we evaluated the effect of the cyclic
backbone by altering the size of the cycloalkane ring of the ligand,
which significantly affected the stereochemical outcome of the
hydrogenation of olefins.10 Based on these findings, we decided to
further alter the ligand structure by replacing the cycloalkane with
an open-chain backbone having various substituents. We expected
the open-chain ligands to be more flexible than the cyclic ones,
and we hoped this would allow them to selectively reduce olefins
that were challenging for catalysts with cycloalkane-based thiazole
ligands.
Here we report the synthesis of open-chain-backbone thiazole-
phosphine ligands and their application in the asymmetric hydro-
genation of olefins.
Scheme 1 Introduction of the isopropyl group.
the monoalkylated ethyl acetoacetate 5.12 Terminal bromination,
followed by condensation with the thiobenzamide, afforded
compound 6, which was then reduced by LiAlH4 to obtain a
racemic primary alcohol 7 (Scheme 1). Unfortunately, we could
not separate the enantiomers of the racemic ester 6 or of the
corresponding alcohol 7 by any means.
As the separation of enantiomers of 6 or 7 was difficult to
achieve, we envisaged an alternative strategy which involved a
highly diastereoselective alkylation (initially isopropylation was
studied) mediated by chiral auxiliaries. Preliminary screening of
chiral auxiliaries revealed that the Oppolzer camphorsultam,13
which is commonly used and demonstrates a great deal of
versatility in asymmetric synthesis,14 proved to be efficient.
In the alternative route (Scheme 2), ethyl acetoacetate 4 was
brominated regioselectively at the c-carbon in chloroform followed
by the condensation of the resulting brominated ester with
thiobenzamide, to give ethyl 2-(2-phenylthiazol-4-yl)acetate 8.
The coupling reaction of (2R)-(−)-bornane-2,10-sultam and ethyl
Results and discussion
The synthesis of new complexes (14a–c) starts with an inexpensive
b-ketoester. Methyl acetoacetate 4a was brominated in chloro-
form, and a stream of air was bubbled through the solution for
2 hours. This removed the HBr and introduced moisture to create
the best conditions for the migration of bromine from the a-carbon
to the c-carbon.11 Condensation of the resulting bromoketone with
thiobenzamide gave ethyl 2-(2-phenylthiazol-4-yl)acetate 8a.
Initially, we planned to introduce a bulky group, such as tert-
butyl, into the backbone of the N,P-ligand by alkylation of b-
ketoester 4. All the efforts for this transformation proved to be
futile, so an isopropyl group was introduced instead, using a much
simpler route (Scheme 1).
The alkylation of b-ketoester 4 using isopropyl iodide in the
presence of freshly distilled DBU proceeded smoothly to yield
Scheme 2 Synthesis of the new iridium complexes. Reagents and conditions: i) Br2, CHCl3, 0 ◦C, 16 h; ii) thiobenzamide, ethanol, pyridine, reflux, 4 h;
iii) MeSO3H, methanol, reflux, 2 h; iv) Oppolzer sultam, Me3Al, dichloromethane, reflux, 24 h; v) LiHMDS, THF, −78 ◦C, RBr, DMPU, 4 h; vi) LiAlH4,
THF, −10 ◦C to r.t., 4 h; vii) TsCl, pyridine, dichloromethane, 0 ◦C to r.t, 16 h; viii) HP(BH3)Ph2, n-BuLi, −78 ◦C to 0 ◦C, 40 min, then 12, DMF, −78 ◦C
to r.t, 16 h; ix) Et2NH (excess), r.t, 16 h; x) [Ir(COD)Cl]2, dichloromethane, reflux, 40 min; xi) H2O, NaBArF, r.t, 2 h.
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2-(2-phenylthiazol-4-yl)acetate was carried out by adding Me3Al15
to (2R)-(−)-bornane-2,10-sultam, then reacting the resulting alu-
minium amide with the ethyl ester 8. Ethyl ester 8 was found
to be a very resilient substrate under the coupling conditions,
yielding only 23% of product even after 7 days of reflux. In
contrast, methyl ester 8a was smoothly converted to the desired
acyl camphorsultam 9 after 24 hours of reflux, yielding more than
85% of the product. Ethyl ester 8 was converted to the methyl
ester analogue 8a by refluxing in an excess of methanol with a
catalytic amount of methanesulfonic acid. Alternatively, 8a could
be obtained from methyl acetoacetate 4 in the same manner.
The coupling product, acyl camphorsultam 9, was treated
with lithium hexamethyldisilazide (LHMDS), the lithium enolate
generated being quenched with an excess of isopropyl iodide in the
presence of 10% DMPU in THF. The overall yield of the reaction
was <10%, but the diastereomeric excess was >99%. However, the
same method was then applied to introduce benzyl, methyl and
allyl groups, which gave the best outcome in terms of reaction
yield and also diastereoselectivity (>95%). Though only reactive
alkyl halides could be used as electrophiles in this methodology,
intermediate 9 was alkylated with several different electrophiles to
obtain chiral ligand precursors with high diastereomeric purities.
The alkylated acyl sultams 10a–c were reduced to corresponding
enantiomerically pure alcohols with LiAlH4. The enantiopuri-
ties of these alcohols 11a–c were determined by chiral HPLC
using Chiralcel OB-H in 10% isopropanol–hexane before being
converted to the corresponding tosylates 12a–c in good yields.
Treatment of the tosylates with lithiated diphenylphosphine–
borane adduct at −78 ◦C (then warming to room temperature)
in THF–DMF yielded the borane-protected chiral phosphines in
high yields.
result in polymerization of the complex. Upon decomposition,
this complex changes colour from bright orange to dark brown.
Due to its instability, complex 14c was evaluated for hydrogenation
activity immediately after it was synthesized.
Hydrogenation of various tri-substituted olefins (Entries 1–10,
Table 1) using the newly synthesized complexes (14a–c) revealed
that complexes 14a and 14b have equal reactivity and selectivity
when compared to their cyclic analogue 2 (up to and above 99%
ee). Complex 14c is clearly less selective in general, although its
activity is comparable with that of the other catalysts shown in
Table 1. The lower selectivity of 14c may be due to its instability.
An increase in ee was observed for substrates 22 (51%) and 24
(56%) (Entries 8 and 10, Table 1) with complex 14a; the same
substrates gave a product with 40% ee and racemic product,
respectively, when complex 2 was used.
Complexes 14a and 14b also gave good enantioselectivities for
imine substrate 25 (51% and 49%) (Entry 11, Table 1), whereas the
closed-chain analogue 2 showed only 16% ee.
Conclusions
We have developed open-chain-backbone analogues of previously
reported thiazole-phosphine ligands in order to study the effect
of ligand backbone structure on the stereochemical outcome
of iridium-catalyzed olefin hydrogenation. We have developed
a route to synthesize these new ligands via diastereoselective
alkylation. The new catalysts reduced several prochiral olefins in
excellent yield and stereoselectivity, and reduced a prochiral imine
in moderate ee. Comparing these catalysts to the closed-chain
analogue 2, we find that these new catalysts behaved similarly to
the original catalysts in asymmetric hydrogenations for most of
the substrates.
Removal of the borane protecting group was achieved by
treating it with an excess of freshly distilled diethylamine. The
borane-free phosphines (13a–c) were eventually transformed into
corresponding iridium complexes (14a–c) in moderate yields using
the previously employed protocol.10
Experimental
The absolute configuration of the alkylated compound 10a was
found by X-ray crystallography to be R (Fig. 2).
General methods
All solvents were dried according to the reported procedures.16
The chromatographic separations were performed on Kieselgel
60 H silica gel (particle size: 0.063–0.100 mm). Thin layer
chromatography (TLC) was performed on aluminium-backed
plates coated with Kieselgel 60 0.20 mm (UV254), and visualized
under ultra-violet light (at 254 nm), or by staining with ethanolic
phosphomolybdic acid followed by heating. 1H-NMR spectra
were recorded at 500, 400 or 300 MHz in CDCl3, and referenced
to the residual CHCl3 peak (7.26 ppm). 13C-NMR spectra were
recorded with at 100 or 75 MHz in CDCl3 and referenced to
the central peak of CDCl3 (77.0 ppm). 31P-NMR spectra were
recorded at 121.47 MHz in CDCl3, using 85% phosphoric acid
as an external standard. Chemical shifts are reported in ppm
(d scale). IR spectra were recorded on Perkin-Elmer 100 FT/IR
spectrometer. Enantiomeric excesses were determined using chiral
HPLC or GC. HPLC was performed at 254 nm UV detector, using
a chiral column (Chiralcel OB-H), and GC analysis was performed
using a chiral column (Chiral DexG-TA). Optical rotations
were recorded on a thermostatted polarimeter using a 1.0 dm
cell. Absolute configurations were determined by comparing the
retention times of the products to the literature data.
Fig. 2 The X-ray crystallographic structure of 10a provides evidence for
the R absolute configuration of the ligand.
Complexes 14a and 14b were stable at ambient temperature for
months, whereas complex 14c decomposed after several days even
at lower temperatures (−20 ◦C). The reason for the instability of
complex 14c is not known, but it might be due to the displacement
of COD by an allyl group from another complex, which would
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Table 1 Iridium-catalyzed asymmetric hydrogenation of substrates 15–25a
14a
14b
Conv.b (%) eec (%)
14c
210
Conv.b (%) eec (%)
Entry
1
Substrate
Conv.b (%) eec (%)
Conv.b (%) eec (%)
>99
96 (R)
94 (R)
>99
>99 (R)
>99
87(R)
>99
>99 (S)
2
3
>99
>99
99 (R)
>99
85(R)
>99
99 (S)
>99
80 (S)
>99
57 (S)
>99
>99
88(S)
87(R)
>99
93 (R)
4
5
>99
>99
98 (R)
78 (R)
>99
>99
94 (R)
78 (R)
>99
>99
>98 (S)
98 (R)
d
—
d
d
6
>99
90 (R)
>99
97 (R)
—
—
7
8
>99
>99
79 (R)
51 (R)
>99
>99
91 (R)
32 (R)
90
70(R)
40(R)
>99
>99
99 (S)
40 (S)
>99
9
>99
97 (R)
56 (S)
>99
98 (R)
23 (S)
>99
90(R)
>99
>99
98 (S)
d
10
75
75
—
—
Racemic
d
11
70e
51 (S)
27e
49 (S)
65e
16 (R)
a Reagents and conditions: 50 bar H2, rt, dichloromethane, 0.5 mol% catalyst. b Determined by 1H NMR spectroscopy. c Determined by chiral HPLC or
chiral GC and compared to the literature data. Absolute configuration is given in parentheses. d Not attempted. e 1 mol% catalyst loading.
Methyl 4-bromo-3-oxobutanoate
via a bubbler for the last 2 hours. This removed the HBr and
introduced moisture to create the best conditions for the migration
of bromine from the a-carbon to the c-carbon. The reaction
mixture was washed once with cold water, and then extracted
with dichloromethane. The organic layer was dried over MgSO4,
filtered, and the solvent was removed in vacuo to obtain the crude
bromoketoester as light yellow oil in a quantitative yield. The
A solution of bromine (14.8 g, 92.66 mmol) in 20 mL of chloroform
was added to a stirred solution of methyl acetoacetate (10.76 g,
92.66 mmol) in 30 mL of chloroform at 0 ◦C under an inert
atmosphere over a period of 1.5 hours. The reaction mixture
was stirred for 16 hours at room temperature; air was blown in
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crude product was utilized for the next step without further puri-
fication.
with 10% NaHCO3 solution, extracted with dichloromethane (4 ×
20 mL) and washed with brine. The combined organic extracts
were dried over MgSO4 and evaporated to dryness.
Synthesis of methyl 2-(2-phenylthiazol-4-yl)acetate (8a)
(2R)-(−)-Benzylated acyl sultam (10a). The crude product was
subjected to column chromatography using 10% ethyl acetate
in pentane as eluent. The purified product was then recrystal-
lized from diethyl ether to afford 10a as white needle-shaped
crystals. The crystals had >99% diastereomeric purity by 1H-
NMR. Yield = 85%; [a]D24.5 = −95.0 (c 1, CHCl3); Rf = 0.48 (20%
To a stirred solution of methyl 4-bromo-3-oxobutanoate (10.0 g,
51.3 mmol) in dry methanol was added thiobenzamide (7.03 g,
51.3 mmol), and then pyridine (4.14 mL, 51.3 mmol). The reaction
mixture was stirred for one hour at room temperature and then
refluxed for 4 hours. After the completion of reaction (TLC
analysis), the reaction mixture was washed with water (2 × 20 mL)
and the aqueous phase was extracted with dichloromethane (3 ×
30 mL) followed by washing with brine. The combined organic
phases were dried over MgSO4 and the solvent was removed
in vacuo to obtain the crude product. Flash chromatography
eluting with dichloromethane–pentane (30 : 70) yielded 8a as light
yellow oil in 64% yield. Analytical data of compound 8a was found
to be consistent with earlier reported data.
1
ethyl acetate in pentane); H-NMR (400 MHz, CDCl3): d 8.03–
7.97 (m, 2H, ArH), 7.48–7.38 (m, 3H, ArH), 7.35–7.30 (m, 2H,
ArH), 7.27–7.22 (m, 3H, ArH), 7.19 (s, 1H, het.), 4.99 (t, J =
7.58 Hz, 1H), 3.82 (dd, J = 7.71, 4.73 Hz, 1H), 3.49 (d, J =
7.58 Hz, 2H), 3.42 (d, J = 14.4 Hz, 1H), 3.36 (d, J = 14.4 Hz, 1H),
2.05–1.95 (m, 2H), 1.91–1.72 (m, 3H), 1.36–1.20 (m, 2H), 0.89 (s,
3H), 0.65 (s, 3H); 13C-NMR (100 MHz, CDCl3): d 171.5, 167.7,
153.4, 139.0, 138.8, 130.0, 129.82, 129.0, 128.5, 126.92, 126.85,
65.6, 53.4, 49.95, 48.4, 48.0, 45.0, 41.0, 38.8, 33.2, 26.7, 20.8, 20.2;
IR (CHCl3): 3019, 2961, 2885, 1690, 1333, 1215 cm−1; MS (GC)
m/z: 506 (M+, 1%), 476 (1), 448 (1), 334 (5), 264 (8), 202 (12), 138
(11), 125 (21), 91 (3).
Introduction of (2R)-(−)-bornane-2,10-sultam to the ester 8a (9)
To a stirred solution of (2R)-(−)-bornane-2,10-sultam (2.76 g,
12.9 mmol) in 20 mL of dry dichloromethane was added Me3Al
(2 M in heptane, 8.35 mL, 16.7 mmol, 1.3 eq.) dropwise at room
temperature under N2. The reaction mixture was stirred at room
temperature for 30 min. Methyl 2-(2-phenylthiazol-4-yl)acetate
(8a) (3.0 g, 12.9 mmol) in 5 mL dichloromethane was added to the
reaction mixture and refluxed for 24 hours. HCl (1 M, 20 mL) was
added slowly (addition of HCl causes methane gas to evolve) and
the reaction mixture was then extracted with ethyl acetate (3 ×
20 mL). The combined organic phases were washed with brine
and dried over MgSO4. Purification by flash chromatography (1%
methanol in toluene) yielded compound 9 as a white solid. The
purified product was recrystallized from diethyl ether to obtain
white crystals. Yield = 4.24 g (86%); [a]2D4.5 = −143.0 (c 1, CHCl3);
Rf = 0.26 (1% methanol in toluene); 1H-NMR (400 MHz, CDCl3):
d 7.97–7.92 (m, 2H, ArH), 7.46–7.40 (m, 3H, ArH), 7.22 (s, 1H,
het.), 4.39 (d, J = 17.7 Hz, 1H), 4.28 (d, J = 17.7 Hz, 1H), 3.95
(dd, J = 7.71, 4.72 Hz, 1H), 3.56 (d, J = 13.91 Hz, 1H), 3.50 (d,
J = 13.91 Hz, 1H), 2.24–2.05 (m, 2H), 2.0–1.85 (m, 3H), 1.48–
1.32 (m, 2H), 1.20 (s, 3H), 0.98 (s, 3H); 13C-NMR (100 MHz,
CDCl3): d 168.8, 168.0, 149.2, 134.0, 130.0, 129.0, 127.0, 117.0,
65.8, 53.2, 49.0, 48.2, 45.0, 38.8, 38.3, 33.2, 26.8, 21.2, 20.2; IR
(CHCl3): 3013, 2961, 2884, 1698, 1327, 1213 cm−1; MS (GC) m/z:
416.48 (M+, 1%), 352 (3), 203 (10), 164 (13), 151 (38), 138 (81),
125 (100).
(2R)-(−)-Methylated acyl sultam (10b). The crude product
was dissolved in toluene and washed with water to remove
DMPU. Flash chromatography using toluene–methanol (99 : 1
1
gradient to 75 : 25) afforded 10b as a colourless oil. H-NMR
showed 95% diastereomeric excess. Yield = 91%; [a]2D3.8 = −58.3
1
(c 1, CHCl3); Rf = 0.3 (dichloromethane); H-NMR (400 MHz,
CDCl3): 7.98–7.92 (m, 2H, ArH), 7.43–7.34 (m, 3H, ArH), 7.21
(d, J = 0.8 Hz, 1H, ArH), 4.72 (dq, J = 7.1, 0.8 Hz, 1H), 3.94
(dd, J = 7.8, 4.9 Hz, 1H), 3,53 (d, J = 13.8 Hz, 1H), 3,45 (d,
J = 13.8 Hz, 1H), 2.16 (m, 1H), 2.07 (dd, J = 13.9, 7.8 Hz, 1H),
1.95–1.82 (m, 3H), 1,71 (d, J = 7.0 Hz, 3H, Me), 1.45–1.26 (m,
2H), 1.21 (s, 3H, Me), d 0.98 (s, 3H, Me); 13C-NMR (100 MHz,
CDCl3): d 19.2, 20.1, 21.1, 26.7, 33.1, 38.7, 42.9, 45.0, 48.0, 48.7,
53.4, 65.6, 115.3, 126.9, 128.9, 129.9, 134.2, 155.2, 167.5, 173.1; IR
(CDCl3): 2960, 1693, 1329, 1209, 908, 725 cm−1; MS (GC) m/z:
431 (M+, 12%), 251 (100), 188 (47), 150 (10), 86 (34), 84 (46).
(2R)-(−)-Allylated acyl sultam (10c). Flash chromatography
eluting with toluene–methanol (99 : 1 gradient to 75 : 25) afforded
10c as a pale yellow solid. 1H-NMR showed 93% diastereomeric
excess. Yield = 87%; [a]2D4.5 = −33.4 (c 0.8, CHCl3); Rf = 0.3
(dichloromethane); 1H-NMR (500 MHz, CDCl3): d 7.97–7.94 (m,
2H, ArH), 7.43–7.35 (m, 3H, ArH), 7.24 (s, 1H, het.), 5.89 (m,
1H), 5.16 (dq, J = 17.0, 3.24, 1.62 Hz, 1H), 5.03 (dm, 1H) 4.76
(dd, J = 8.5, 5.7 Hz, 1H), 3.93 (dd, J = 7.7, 5.2 Hz, 1H), 3.57 (d,
J = 13.9 Hz, 1H) 3.48 (d, J = 13.9 Hz, 1H), 3.0–2.86 (m, 2H),
2.16–2.04 (m, 3H), 1.95–1.85 (m, 4H), 1.42–1.25 (m, 3H), 1.21 (s,
3H), 0.98 (s, 3H); 13C-NMR (100 MHz, CDCl3): d 171.5, 167.3,
153.1, 134.6, 133.7, 129.7, 128.7, 126.6, 117.9,115.8, 65.5, 53.2,
48.3, 47.7, 47.3, 44.7, 40.95, 38.8, 38.4, 32.9, 26.4, 20.9, 19.9; IR
(CHCl3): 3076, 2960, 2883, 1693, 1641, 1363, 1208 cm−1; MS (GC)
m/z: 457.25 (M+, 1, 18%), 456.26 (M+, 40), 455.28 (100), 241.11
(17), 239.27 (12), 214.23 (18), 213.21 (12), 121.16 (14), 91.1 (4),
77.14 (11).
General procedure for diastereoselective alkylation of acyl sultam 9
Lithium hexamethyldisilazide (LiHMDS, 1 M in THF, 5.04 mmol,
1.2 eq.) was added dropwise over a period of 10 min to a stirred
solution of (2R)-(−)-acyl sultam 9 (4.2 mmol) in 15 mL of dry
THF at −78 ◦C under inert atmosphere. The reaction mixture was
stirred at this temperature for an additional 45 min. The lithium
enolate of 9 was then quenched with an excess of freshly distilled
alkyl halide (37 mmol) in 5 mL of THF, after which 2 mL of freshly
distilled DMPU was added. The reaction mixture was brought up
to room temperature and stirred for 4 hours until all the starting
materials disappeared (TLC). The reaction mixture was quenched
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General procedure for reduction of alkylated acyl sultam to the
corresponding primary alcohols
After completion of the reaction (TLC), the reaction mixture was
diluted with dichloromethane, and then washed with cold 10%
NaHCO3 (aq.) and brine. The organic phase was dried over MgSO4
and the solvent was removed in vacuo to yield the tosylates 12a–c.
LiAlH4 (2.0 mmol) was added to a stirred solution of (2R)-
(−)-alkylated acyl sultam (10a–c) (1.5 g, 1.0 mmol) in 10 mL
of dry THF at −10 ◦C. The reaction mixture was brought up
to room temperature and stirred for 4 hours. The reaction was
then quenched by adding a mixture of H2O (0.22 mL), NaOH
(2 M, 0.44 mL) and H2O (0.22 mL). The cake formed was filtered
through a pad of Celite and washed several times with ethyl acetate.
The filtrate was dried over Na2SO4 and the solvent was evaporated
to obtain crude alcohol (11a–c).
(R)-3-Phenyl-2-(2-phenylthiazol-4-yl)propyl 4-methylbenzene-
sulfonate (12a). The crude reaction mixture was purified by
chromatography (5% ethyl acetate in pentane) to afford 12a.
Yield = 90%; [a]2D4.5 = −2.45 (c 1, CHCl3); Rf = 0.56 (20% ethyl
acetate in pentane); 1H-NMR (400 MHz, CDCl3): d 7.87–80 (m,
2H, ArH), 7.60 (d, 2H, J = 8.3 Hz, ArH), 7.47–7.41 m, 3H, ArH),
7.26–7.17(m, 3H, ArH), 7.15 (d, 2H, J = 8.3 Hz, ArH), 7.05 (d,
2H, J = 7.93 Hz, ArH), 6.82 (s, 1H, het.), 4.25 (m, 2H, SO3-CH2),
3.50–3.40 (m, 1H, CH), 3.07 (d, 2H, J = 7.43 Hz, Ph-CH2),
2.22 (s, 1H, CH3); 13C-NMR (100 MHz, CDCl3): d 167.9 (het.),
156.0 (het.), 144.9, 138.8, 133.9, 132.7, 130.2, 129.9, 129.3, 129.1,
128.7, 128.0, 126.7, 126.6 (arom.), 115.7 (het.), 71.8, 43.8, 37.1,
21.7; IR (CHCl3): 3028, 1598, 1516, 1496, 1456, 1359, 1216, 1189,
1175 cm−1; MS (GC) m/z: 450 (M + 1, 2), 449 (M+, 5), 419 (2),
388 (14), 295 (5), 264 (39), 202 (62), 92 (100), 91 (93).
(R)-(−)-3-Phenyl-2-(2-phenylthiazol-4-yl)propan-1-ol
(11a).
The crude product was purified by silica gel column
chromatography using 1% methanol in toluene as eluent to
afford the pure alcohol as a colourless oil. Yield = 75%; [a]D24.5
=
−17.8 (c 1, CHCl3); Rf = 0.61 (5% methanol in toluene); 1H-NMR
(400 MHz, CDCl3): d 8.03–7.95 (m, 2H, ArH), 7.53–7.44 (m, 3H,
ArH), 7.35–7.29 (m, 2H, ArH), 7.27–7.19 (m, 3H, ArH), 6.81 (s,
1H, het.), 4.05–3.88 (m, 2H), 3.84 (br, 1H), 3.35–3.26 (m, 1H),
3.16 (d, J = 7.0 Hz, 2H); 13C-NMR (100 MHz, CDCl3): d 168.4,
159.2, 140.2, 133.6, 130.4, 129.4, 129.3, 128.6, 126.8, 126.4, 114.5,
65.2, 45.8, 38.0; IR (CHCl3): 3386, 3024, 2924, 2864, 1514, 1495,
1454 cm−1; MS (GC) m/z: 296 (M + 1, 23%), 295 (M+, 19), 266
(18), 265 (75), 264 (100), 176 (24), 128 (32), 92 (6), 66 (4).
(R)-2-(2-Phenylthiazol-4-yl)propyl
4-methylbenzenesulfonate
(12b). The crude tosylate was precipitated twice from hot
methanol–water (8 : 1) to afford 12b as white powder. Yield =
71%; [a]2D4.5 = −0.72 (c 1.38, CHCl3); Rf = 0.42 (dichloromethane);
HPLC on OD-H (heptane–isopropanol 97 : 3, 0.4 mL min−1)
42.5 min (major) and 49.0 min (minor), >99% ee; 1H-NMR
(400 MHz, CDCl3): 7.85–7.80 (m, 2H, ArH), 7.67–7.62 (m, 2H,
ArH), 7.43–7.37 (m, 3H, ArH), 7.20–7.14 (m, 2H, ArH), 6.94 (d,
J = 0.7 Hz, 1H, ArH), 4.36 (dd, J = 9.4, 6.4 Hz), 4.26 (dd, J =
9.4, 6.0 Hz), 3.34 (m, 1H), 2.26 (s, 3H, Me), d 1.37 (d, J = 7.1 Hz,
3H, Me); 13C-NMR (100 MHz, CDCl3): d 16.3, 21.4, 36.1, 73.6,
114.0, 126.4, 127.7, 128.8, 129.6, 129.9, 133.0, 133.7, 144.4, 157.8,
167.7; IR (solid): 2972, 1598, 1518, 1461, 1352, 1172, 949, 844,
765, 667 cm−1; MS (GC) m/z: 374 (M + 1, 22%), 201 (100), 188
(15), 121 (15), 98 (11), 97 (17).
(R)-2-(2-Phenylthiazol-4-yl) propan-1-ol (11b). The crude
product was purified by column chromatography using
dichloromethane–methanol (100 : 0 gradient to 95 : 5) to afford
the alcohol as a colourless oil. Yield = 69%; [a]2D4.5 = −19.1 (c 1.6,
CHCl3); Rf = 0.57 (5% methanol in dichloromethane); 1H-NMR
(400 MHz, CDCl3): 7.95–7.88 (m, ArH), 7.46–7.36 (m, 3H, ArH),
6.96 (d, J = 1.0 Hz, 1H, ArH), 3.90–3.75 (m, 2H), 3.60 (br, 1H),
3.19 (m, 1H), d 1.36 (d, J = 7.1 Hz, 3H, Me); 13C-NMR (100 MHz,
CDCl3): d 16.2, 38.1, 67.7, 112.7, 126.5, 128.9, 130.0, 133.5, 161.1,
168.1; IR (CDCl3): 3353 (br.), 2965, 2928, 2872, 1513, 1455, 1435,
1240, 1027, 987, 918, 761 cm−1; MS (GC) m/z: 220 (M + 1, 100%),
189 (13), 188 (12), 104 (2), 85 (4).
(R)-2-(2-Phenylthiazol-4-yl)pent-4-enyl 4-methylbenzenesulfo-
nate (12c). The crude mixture was purified by silica gel column
chromatography using dichloromethane–methanol (100 : 0 gradi-
ent to 99.5 : 0.5) to afford 12c as a white crystalline solid. Yield =
80%; [a]2D3.5 = −4.8 (c 1, CHCl3); Rf = 0.52 (0.5% methanol in
dichloromethane); 1H-NMR (500 MHz, CDCl3): d 7.83–7.78 (m,
2H, ArH), 7.62–7.58 (m, 2H, ArH), 7.43–7.39 (m, 3H, ArH), 7.14
(dm, 2H, ArH), 6.94 (s, 1H, het.), 5.73–5.64 (m, 1H), 5.05-4.98
(m, 2H) 4.33 (ddd, J = 14.5, 9.5, 5.4 Hz, 2H), 3.26 (dddd, J =
12.8. 7.0, 5.4 Hz, 1H), 2.57–2.46 (m, 2H), 2.2 (s, 3H); 13C-NMR
(125 MHz, CDCl3): d 167.9, 156.2, 144.8, 135.1, 133.8, 132.8,
130.1, 129.9, 129.1, 128.0, 126.7, 117.8, 115.3, 72.1, 41.5, 35.1,
21.6.; IR (CHCl3): 3115.25, 2976.63, 1641.80, 1597.24, 1457.00,
1354.79, 1190.07, 1175.36, 1097.69, 973.08, 927.06, 830.00, 814.56,
701.21, 691.24, 650.00 cm−1; MS (GC) m/z: 400.17 (M + 1, 19%),
399.16 (M+, 36), 398.20 (100), 244.19 (36), 226.24 (35), 222.21 (12),
121.13 (15), 91.13 (20).
(R)-2-(2-Phenylthiazol-4-yl) pent-4-en-1-ol (11c). The crude
product was purified by column chromatography using
dichloromethane–methanol (100 : 0 gradient to 95 : 3) to afford
the alcohol as a colourless oil. Yield = 72%; [a]2D4.5 = −18.3 (c
1
1, CHCl3); Rf = 0.4 (20% ethyl acetate in pentane); H-NMR
(500 MHz, CDCl3): d 7.94–7.90 (m, 2H, ArH), 7.45–7.38 (m, 3H,
ArH), 6.98 (s, 1H, het.), 5.82 (m, 1H), 5.09 (dq, J = 17.1, 3.4,
1.6 Hz, 1H), 5.04 (dm, 1H), 3.92 (ddd, J = 14.6, 10.7, 3.9 Hz, 2H),
3.63 (br, 1H), 3.09 (m, 2H), 2.54 (m, 2H); 13C-NMR (125 MHz,
CDCl3): d 168.1, 159.0, 144.8, 136.1, 133.3, 130.0, 128.9, 126.4,
116.7, 113.7, 65.3, 43.2, 35.5; IR (CHCl3): 3389, 3021, 2920, 2859,
1514, 1495, 1454 cm−1; MS (GC) m/z: 246.03 (M + 1, 14%), 245.06
(M+, 23), 244.16 (100), 228.3 (22), 215.2 (14), 176 (21), 121.2 (15),
104.4 (10), 77.0 (8).
General procedure for tosylation of alcohols
General procedure for the preparation of borane-protected
phosphines (13a–c)
To a solution of alcohol (0.35 g, 1.18 mmol) in 10 mL of dry
dichloromethane was added p-toluenesulfonyl chloride (0.45 g,
2.36 mmol) and pyridine (0.24 mL, 2.36 mmol) at 0 ◦C. The reac-
tion mixture was allowed to stir at room temperature overnight.
n-BuLi (1.6 M, 1.2 eq.) was added dropwise to a solution of
diphenylphosphine–borane adduct (1.16 mmol) in 5 mL of dry
THF at −78 ◦C under inert atmosphere. The reaction mixture
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was warmed to 0 ◦C and stirred for 40 min. The lithiated
diphenylphosphine–borane adduct was transferred dropwise via
a cannula to a pre-stirred solution of tosylate (0.77 mmol) in
1 mL of dry DMF at −78 ◦C. The reaction mixture was then
warmed to room temperature and stirred for 16 hours. After
completion (NMR), the reaction mixture was poured into 10%
ice-cold NaHCO3 solution and extracted with dichloromethane
(15 mL × 3). The combined organic extracts were washed with
brine and dried over MgSO4. The solvent was removed in vacuo
and the crude product was purified by column chromatography to
obtain 13a–c.
(d, J = 3.4 Hz), 135.7, 133.8, 132.4, 132.3, 131.6, 131.5, 131.4,
131.0, 130.7 (d, J = 2.5 Hz), 130.5 (d, J = 2.5 Hz), 129.6, 129.0,
128.7, 128.6, 128.1, 128.0, 127.9, 127.6, 126.4, 117.2, 115.6, 41.4
(d, J = 11.6 Hz), 37.1, (d, J = 1.4 Hz), 30.0, 29.7; 31P-NMR
(121 MHz, CDCl3): d 14.7 (m); IR (CHCl3): 3058.80, 2911.34,
2379.17, 1970.73, 1889.38, 1824.91, 1640.13, 1436.98, 1106.71,
1061.17, 985.29, 917.05, 838.63, 765.27, 736.22 cm−1; MS (GC)
m/z: 428.38 (M + 1, 3%), 427.29 (M+, 5), 426.32 (17), 387.31 (28),
386.25 (100), 385.28 (28), 296.24 (15), 225.30 (16), 198.22 (13),
185.24 (14), 183.26 (26), 121.16 (8), 77.13 (4).
General procedure for preparation of Ir complexes 14a–c
(R)-4-(1-(Diphenylphosphino)-3-phenylpropan-2-yl)-2-phenylthi-
azole–borane adduct (13a). Chromatography on silica gel using
toluene as an eluent afforded 13a as colourless oil. Yield = 92%;
[a]D24.5 = −194.0 (c 1, CHCl3); Rf = 0.66 (toluene); 1H-NMR
(400 MHz, CDCl3): d 7.90–7.83 (m, 2H, ArH), 7.67–7.58 (m,
2H, ArH), 7.55–7.34 (m, 8H, ArH), 7.26–7.08 (m, 6H, ArH),
7.05 (d, J = 7.71 Hz, 2H, ArH), 6.54 (s, 1H, het.), 3.78–3.65
(m, 1H), 3.28–3.04 (m, 3H), 2.60–2.48 (m, 1H), 1.62–0.60 (br,
3H, BH3); 13C-NMR (100 MHz, CDCl3): d 167.8, 157.6, 139.7,
134.2, 132.6 (d, JC,P = 9.64 Hz), 131.9 (d, JC,P = 9.6 Hz), 131.1
(d, JC,P = 2.7 Hz), 130.8 (d, JC,P = 2.7 Hz), 130.0, 129.4, 129.3,
129.0, 128.9, 128.5, 128.4, 128.3, 126.8, 126.4, 116.3, 43.8 (d,
JC,P = 11.4 Hz), 39.8 (d, JC,P = 1.6 Hz), 30.4 (d, JC,P = 37.2 Hz);
31P-NMR (121 MHz, CDCl3): d 15.8 (br); IR (CHCl3): 3726,
3060, 3007, 2382, 1518, 1494, 1461, 1436, 1216 cm−1; MS (GC)
m/z: 477 (M+, 1%), 386 (15), 264 (16), 219 (45), 214 (100), 202
(49), 183 (16), 91 (7).
Borane adduct 13a–c (0.6 mmol) was stirred with an excess
of freshly distilled diethylamine under N2 overnight. Excess
diethylamine was then removed in vacuo and the product was
filtered through a short pad of silica using toluene as the eluent.
The borane-free N,P-ligand was employed in the next step without
further characterization.
To the solution of borane-free N,P-ligand (0.6 mmol) in 15 mL
of dry dichloromethane was added [Ir(COD)Cl]2 (0.3 mmol), and
the mixture was refluxed under an inert atmosphere for 40 min.
The reaction mixture was cooled to room temperature and the
−
replacement of chloride ion with BArF anion was carried out by
adding first 20 mL of distilled water, then NaBArF (1.5 eq.), to the
reaction mixture. The resultant mixture was stirred vigorously at
room temperature for 2 hours and extracted with dichloromethane
(20 mL × 3). Combined organic extracts were dried over MgSO4
and the solvent was removed in vacuo to obtain crude complex
14a–c.
(R)-4-(1-(Diphenylphosphino)propan-2-yl)-2-phenylthiazole–
borane adduct (13b). Chromatography on silica gel with pentane–
dichloromethane (90 : 10 gradient to 40 : 60) afforded 13b as a
colourless oil. Yield = 91%; [a]2D4.6 = +94.9 (c 1, CHCl3); Rf = 0.52
(dichloromethane); 1H-NMR (400 MHz, CDCl3): d 0.54–1.60 (m,
3H, BH3), 1.44 (dd, J = 6.7, 1.1 Hz, 3H), 2.40 (ddd, J = 14.0, 8.4,
5.5 Hz, 1H), 3.15 (td, J = 14.1, 7.9 Hz, 1H), 3.59 (m, 1H), 6.78
(m, 1H, ArH), 7.16–7.27 (m, 3H, ArH), 7.35–7.45 (m, 6H, ArH),
7.54–7.62 (m, 2H, ArH), 7.63–7.70 (m, 2H, ArH), 7.81–7.86 (m,
2H, ArH); 13C-NMR (75 MHz, CDCl3): d 23.0 (d, 9.9 Hz), 32.1
(d, J = 4.2 Hz), 32.3 (d, J = 41.6 Hz), 113.9, 126.4, 127.9, 128.2
(d, J = 9.9 Hz), 128.6–128.8 (m), 129.7, 130.6–130.9 (m), 131.5–
131.8 (m), 132.3–132.6 (m), 133.8, 160.3 (d, J = 5.5 Hz), 167.7;
31P-NMR (121 MHz, CDCl3): 15.1 (br. d, 15.4 Hz); IR (CHCl3):
3057, 2966, 2375, 1960, 1888, 1812, 1436, 1106, 1061, 909, 764,
730 cm−1; MS (GC) m/z: 401 (M+, 44%), 400 (100), 387 (21), 386
(26), 359 (9), 310 (25), 297 (11), 265 (16), 264 (11), 200 (11), 183
(14), 121 (6).
Complex 14a. The iridium complex was purified by column
chromatography using pentane–dichloromethane 50 : 50 as the
eluent to afford 14a as an orange solid. Yield = 54%; [a]D24.5
=
−124.0 (c 1, CHCl3); Rf = 0.66 (dichloromethane); 1H-NMR
(400 MHz, CDCl3): d 8.04–7.98 (m, 2H), 7.78–7.76 (m, 2H),
7.73–7.68 (m, 8H, BArF), 7.67–7.65 (m, 2H), 7.63–7.59 (m, 2H),
7.53-7.49 (m, 4H, BArF), 7.48–7.43 (m, 6H), 7.31–7.27 (m, 2H),
7.19–7.15 (m, 2H), 7.02 (s, 1H), 6.64 (dd, J = 7.79, 3.65 Hz, 2H),
4.53–4.49 (m, 1H, COD), 4.34–4.30 (m, 1H, COD), 3.62 (dt, J =
13.06, 4.13 Hz, 1H), 3.33–3.20 (m, 1H, COD), 3.10-2.98 (m, 2H),
2.72–2.62 (m, 1H, COD), 2.56–2.40 (m, 2H, COD-H), 2.36–2.22
(m, 2H), 2.20–2.10 (m, 1H, COD-H), 1.80–1.75 (m, 1H, COD-
H), 1.42–1.20 (m, 4H, COD-H); 13C-NMR (100 MHz, CDCl3): d
173.0, 162.7, 162.2, 161.7, 161.2 (4C, BArF), 160.1, 137.6, 135.0
(m, 8C, BArF), 133.7, 133.6, 133.3, 132.6 (d, JC,P = 2.9 Hz), 131.8,
131.3 (d, JC,P = 2.9 Hz), 131.0, 130.5 (d, JC,P = 9.6 Hz), 129.8 (d,
JC,P = 9.6 Hz), 129.7, 129.5, 129.3, 129.2, 129.0, 128.0, 126.1, 118.0
(m, 4C, BArF), 115.5, 67.7, 64.6, 39.6 (d, JC,P = 14.6 Hz), 37.3 (d,
JC,P = 4.3 Hz), 34.0 (4C, COD), 30.1 (d, JC,P = 35.4 Hz), 28.4
(4C, COD-C); 31P-NMR (121 MHz, CDCl3): d 10.0 (s); 19F-NMR
(282 MHz, CDCl3): d −62.4 (s); IR (CHCl3): 3065, 3031, 2997,
1610, 1353, 1273 cm−1.
(R)-4-(1-(Diphenylphosphino)pent-4-en-2-yl)-2-phenylthiazole–
borane adduct (13c). Chromatography using toluene as an eluent
afforded 13c as a colourless oil. Yield = 89%; [a]2D4.5 = −94.5 (c 1.1,
CHCl3); Rf = 0.5 (0.5% methanol in dichloromethane); 1H-NMR
(500 MHz, CDCl3): d 7.83–7.78 (m, 2H, ArH), 7.65–7.59 (m, 2H,
ArH), 7.51–7.35 (m, 8H, ArH), 7.20–7.06 (m, 3H, ArH), 6.74
(s, 1H, ArH), 5.75–5.64 (m, 1H), 5.04 (dd, J = 3.4, 1.46 Hz, 1H),
5.02–4.98 (m, 1H) 3.57–3.48 (m, 1H), 3.12 (ddd, J = 15.1, 10.2 Hz,
1H), 2.68–2.52 (m, 2H), 2.46 (dddd, J = 14.5, 8.16, 3.5 Hz, 1H),
1.6–0.7 (br, 3H); 13C-NMR (125 MHz, CDCl3): d 167.6, 157.8
Complex 14b. The iridium complex was purified by column
chromatography using pentane–dichloromethane (75 : 25 gradient
to 20 : 80), affording 14b as an orange solid. Yield = 60%; [a]D23.8
=
−35.2 (c 1.21, CHCl3); Rf = 0.29 (dichloromethane–pentane 50 :
50); 1H-NMR (400 MHz, CDCl3): d 1.51–1.27 (m, 3H), 1.73 (br.
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dd, J = 6.8, 1.6 Hz, 3H), 1.93 (m, 1H), 2.10 (dd, J = 14.9, 7.6 Hz,
1H), 2.35–2.22 (m, 2H), 2.55-2.39 (m, 2H), 2.98 (ddd, J = 14.8,
10.6, 3.2 Hz, 1H), 3.08 (m, 1H), 3.32 (m, 1H), 4.48–4.34 (m, 2H),
4.60 (m, 1H), 7.32–7.19 (m, 3H, ArH), 7.61–7.38 (m, 14H, ArH),
7.83–7.64 (m, 9H, ArH), 8.07–7.99 (m, 2H); 13C-NMR (100 MHz,
CDCl3): d 19.8 (d, J = 15.6 Hz), 25.6, 28.3, 33.3, 33.6 (d, J =
34.3 Hz), 37.0 (m), 65.8 (d, J = 179.8 Hz), 88.3 (d, J = 15.0 Hz),
96.0 (d, J = 8.7 Hz), 115.3, 117.5 (m), 120.6, 123.3, 126.0, 128.3–
129.7 (m), 130.8, 130.9, 131.4 (m), 132.1, 132.8, 132.9, 134.9 (m),
160.8 (m), 161.1, 161.5, 162.0, 162.5, 172.4; 31P-NMR (121 MHz,
CDCl3): d 10.9; IR (solid): 1610, 1353, 1274, 1163, 1126, 887, 716,
682, 669 cm−1.
Acknowledgements
This work was supported by grants from AstraZeneca, the
Swedish Research Council (VR) and Ligbank, and M.A. gratefully
acknowledges the financial support from the Pakistan Higher
Education Commission. We are also grateful to Mr Tobias Robert
and Dr Jo¨rg-M. Neudo¨rfl for helping with X-ray crystal structure
determination.
References
1 (a) J. M. Brown, in Comprehensive Asymmetric Catalysis, ed. E. N.
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Complex 14c. The iridium complex was purified by column
chromatography using pentane–dichloromethane (50 : 50) as
eluent to afford 14c as an orange solid. Yield = 70%; [a]D23.8
=
−23.7 (c 0.7, CHCl3); Rf = 0.38 (dichloromethane–pentane 50 :
50); 1H-NMR (400 MHz, CDCl3): d 8.03–7.99 (m, 2H), 7.80–7.71
(m, 8H), 7.60–7.45 (m, 14H, BArF), 7.30–7.21 (m, 3H), 7.25–7.22
(m, 2H), 6.20–5.90 (m, 1H), 5.20–5.09 (m, 1H), 5.06–5.02 (m, 1H),
4.51–4.20 (m, 2H), 4.53–4.49 (m, 1H, COD), 4.34–4.30 (m, 1H,
COD), 3.62 (dt, J = 13.06, 4.13 Hz, 1H), 3.33–3.20 (m, 1H, COD),
3.10–2.98 (m, 2H), 2.72–2.62 (m, 1H, COD), 2.56–2.40 (m, 2H,
COD-H), 2.36–2.22 (m, 2H), 2.20–2.10 (m, 1H, COD-H), 1.80–
1.75 (m, 1H, COD-H), 1.42–1.20 (m, 4H, COD-H); 13C-NMR
(100 MHz, CDCl3): d 173.0, 162.7, 162.2, 161.7, 161.2 (4C, BArF),
160.1, 137.6, 135.0 (m, 8C, BArF), 133.7, 133.6, 133.3, 132.6 (d,
JC,P = 2.9 Hz), 131.8, 131.3 (d, JC,P = 2.9 Hz), 131.0, 130.5 (d,
JC,P = 9.6 Hz), 129.8 (d, JC,P = 9.6 Hz), 129.7, 129.5, 129.3, 129.2,
129.0, 128.0, 126.1, 118.0 (m, 4C, BArF), 115.5, 67.7, 64.6, 39.6 (d,
JC,P = 14.6 Hz), 37.3 (d, JC,P = 4.3 Hz), 34.0 (4C, COD), 30.1 (d,
JC,P = 35.4 Hz), 28.4 (4C, COD-C); 31P-NMR (121 MHz, CDCl3):
d 10.0 (s); 19F-NMR (282 MHz, CDCl3): d −62.4 (s); IR (CHCl3):
3065, 3031, 2997, 1610, 1353, 1273 cm−1
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General procedure for hydrogenation reactions
The substrate (0.5 mmol) and catalyst (0.5–1 mol%) were weighed
into a glass vial and 2.0 mL of anhydrous dichloromethane
was added. The vial was placed in high-pressure hydrogenation
equipment, which was purged three times with nitrogen before
being pressurized to 50 bar with hydrogen gas. The pressure
was held overnight, then vented. The solvent was removed
in vacuo. The crude product was redissolved in ether, filtered
through a short plug of silica and the solvent was evaporated.
Enantiomeric excesses were determined by HPLC and GC analysis
and comparison of the retention times with previously reported
data.10
16 D. D. Perrin, W. L. F. Armarego and D. R. Perrin, Purification of
Laboratory Chemicals, Pergamon Press, Oxford, 1985.
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