Synthesis of non-symmetric bis(oxazoline)-containing ligands and their application in the catalytic enantioselective Nozaki-Hiyama-Kishi allylation of benzaldehyde

Article abstract of DOI:10.1039/b715834c

We report the good to high-yielding three-step synthesis of non-symmetrical bis(oxazoline)-containing ligands possessing an N-thienylaniline unit. The convergent synthesis employed a palladium-catalysed aryl amination of 2-(2′-bromothiophene)nitrile as th

Full text of DOI:10.1039/b715834c

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www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of non-symmetric bis(oxazoline)-containing ligands and their
application in the catalytic enantioselective Nozaki–Hiyama–Kishi allylation
of benzaldehyde†
Gra´inne C. Hargaden, Timothy P. O’Sullivan and Patrick J. Guiry*
Received 15th October 2007, Accepted 20th November 2007
First published as an Advance Article on the web 20th December 2007
DOI: 10.1039/b715834c
We report the good to high-yielding three-step synthesis of non-symmetrical bis(oxazoline)-containing
ligands possessing an N-thienylaniline unit. The convergent synthesis employed a palladium-catalysed
aryl amination of 2-(2ꢀ-bromothiophene)nitrile as the key step, with sixteen ligands prepared in total.
These ligands were subsequently applied in the chromium-catalysed enantioselective
Nozaki–Hiyama–Kishi allylation of benzaldehyde with an optimal enantioselectivity of 73%.
We have previously reported the synthesis of ligand class 4 in
Introduction
which an N-phenylaniline unit links the two oxazoline rings, and
Because of their ready availability, modular nature, and ap-
their application in the enantioselective Nozaki–Hiyama–Kishi
plicability in a wide range of metal-catalysed transformations,
(NHK) allylation, crotylation and methallylation of a range of
aromatic and aliphatic aldehydes.5 The highest enantioselectivities
in all three NHK processes were obtained utilising the non-C2-
symmetric ligand with t-Bu/Bn-substituted oxazolines, which, for
example, afforded 99.5% ee in the methallylation of benzaldehyde.
We wished to investigate further non-C2-symmetric bis(oxazoline)
ligands and thus designed ligand class 5 in which one of the arene
rings is replaced by a thiophene in order to study the effect of this
desymmetrisation of the ligand.
compounds containing a chiral oxazoline ring have become one
of the most successful, versatile and commonly used classes of
ligands for asymmetric catalysis.1 The majority of these ligands
are synthesised from commercially available chiral amino alcohols
in a few high-yielding steps. Tridentate bis(oxazoline) ligands have
been designed by incorporating a donor atom which links the two
chiral oxazoline rings. Of particular interest to us are tridentate
[NNN] bis(oxazoline) ligands (Fig. 1). Nishiyama’s “pybox”
ligand 1 has been used in various asymmetric reactions including
Ru-catalysed cyclopropanation of olefins, Rh-catalysed hydrosi-
lylation of ketones and Cu-catalysed allylic oxidation of olefins.2
Zhang’s “ambox” ligand 2 has resulted in excellent conversions
and enantioselectivities in the Ru-catalysed transfer hydrogenation
of aromatic ketones.3 Nakada’s bis(oxazolinyl)carbazole ligand 3b
provided enantioselectivities of up to 93% ee in the asymmetric
allylation of benzaldehyde.4
Results and discussion
Ligand synthesis
We envisaged using a similar synthetic strategy to that employed
in the synthesis of ligand class 4. Accordingly, we proposed that
ligand class 5 could be synthesised by a three-step convergent
synthesis with the key step being a palladium-catalysed aryl
amination between 2-(2ꢀ-aminophenyl)oxazolines 8 and 2-(2ꢀ-
bromothiophene)oxazolines 10.
Accordingly, both 8 and 10 were prepared from the correspond-
ing commercially available nitriles 6 and 9 by the reaction with
the appropriate chiral amino alcohol in the presence of ZnCl2 in
yields of 65–80% (Scheme 1).6
We then attempted the palladium-catalysed aryl amination
using 8a (R = Bn) and 10 as the test coupling partners. The
formation of an aryl–amine bond by the Pd-catalysed reaction
of an aryl halide with an aryl/alkyl amine has been extensively
studied by the groups of Buchwald and Hartwig and is a
rapidly expanding area of research.7 A range of Pd precursors,
ligands, bases and solvents have been used in an attempt to
increase yields, decrease reaction times, reduce diarylation and
b-hydride elimination products and widen the substrate scope.
Although functionalised thiophenes are useful precursors for
pharmaceuticals and natural products, there are few reports of
halothiophenes being applied as substrates in palladium-catalysed
aryl aminations.8
Fig. 1
Centre for Synthesis and Chemical Biology, UCD School of Chemistry
and Chemical Biology, UCD Conway Institute, University College Dublin,
Belfield, Dublin 4, Ireland. E-mail: p.guiry@ucd.ie
† Electronic supplementary information (ESI) available: Characterisation
data for compounds 5a–p and 11a–d. See DOI: 10.1039/b715834c
562 | Org. Biomol. Chem., 2008, 6, 562–566
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Scheme 3
would allow us to investigate the effect on enantioselectivity of
having a particular substituent on the arylamine or thienylamine
oxazoline ring (e.g. comparing 5e versus 5f, 5g versus 5h, etc.).
Scheme 1
Application in catalysis: the asymmetric Nozaki–Hiyama–Kishi
reaction
We screened a range of Pd complexes of diphosphines and
monophosphines, including the bulky, electron-rich biaryl ligands
recently successfully applied in the aryl amination of chlorothio-
phene by Buchwald et al.9 However, in each case the attempted
coupling of 8a and 10 failed to afford any of the desired product.
We then proposed removing the oxazoline from 10 and instead
attempting the aryl amination with its nitrile precursor 9 as we
were encouraged by the recent report by Luker et al. who reported
the aryl amination of 9 with BuNH2 using BINAP and Pd(OAc)2
with an isolated yield of 89% after 20 hours.10 We thus coupled
8 and 9 under similar conditions and were pleased to find the
reaction proceeded in high to excellent yields after 36 hours at
110 ◦C (Scheme 2).
The Nozaki–Hiyama–Kishi reaction was first reported in the late
1970’s and has proven to be a highly versatile procedure for
the formation of C–C bonds involving the nucleophilic addition
to carbonyl compounds of intermediate organochromium(III)
reagents. These reagents are typically generated in situ from
the insertion of chromium(II) species into allyl, alkenyl, alkynyl,
propargyl and aryl halides or sulfonates.11 A number of unique
and important features, including pronounced chemoselectivity
for reactions with aldehydes in the presence of ketones and an
unprecedented compatibility with numerous functional groups in
both reaction partners, has led to the reaction being utilised in the
synthesis of many complex natural products. Two such examples
are the total synthesis of palytoxin and halichondrin B which both
involve extensive use of chromium additions.12
The development of the asymmetric Nozaki–Hiyama-–Kishi
reaction has recently been reviewed13 and to date a limited range
of ligand classes have been tested in this reaction, with the most
promising examples emerging from the groups of Yamamoto,14
Sigman,15 Cozzi and Umani-Ronchi,16 Nakada,4 Berkessel,17
Kishi18 and ourselves.5,19 Our new ligand class 5 was applied in the
chromium-catalysed reaction of allyl bromide with benzaldehyde
(Table 2).
Scheme 2
Our previous studies have shown that the optimal reaction
conditions for allylation require THF–acetonitrile (7 : 1) as
the solvent and N,N-diisopropylethylamine as the base. The
reactions proceeded cleanly under these conditions with high
conversions after 16 hours at room temperature. Of the ligands
possessing identical oxazoline substituents (5a–d), the highest
enantioselectivity of 63% (S) was obtained with the bis(isopropyl)
oxazolines 5b (entry 2). This substitution also provided the highest
enantioselectivities in our original ligand class 4.5b Of the ligands
Conversion of the aryl amination products 11a–d to the required
bis(oxazoline)-containing ligands 5a–p was carried out using
ZnCl2 and the appropriate amino alcohol (Scheme 3). These
reactions proceeded in good to high yields (Table 1). This approach
allows for the synthesis of non-symmetric ligands as with ligand
class 4 and, in addition, offers the opportunity for the selective
placement of different substituents on both oxazoline rings. This
Table 1 Conversion of 11a–d to 5a–p
Entry
Ligand
R1
R2
Yield (%)
Entry
Ligand
R1
R2
Yield (%)
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
Bn
i-Pr
Ph
t-Bu
Ph
Bn
t-Bu
Bn
Bn
i-Pr
Ph
t-Bu
Bn
Ph
Bn
t-Bu
70
74
78
56
71
70
69
75
9
10
11
12
13
14
15
16
5i
t-Bu
i-Pr
i-Pr
Ph
t-Bu
Ph
i-Pr
t-Bu
Ph
i-Pr
Ph
t-Bu
i-Pr
Bn
68
69
72
71
65
67
73
76
5j
5k
5l
5m
5n
5o
5p
5g
5h
Bn
i-Pr
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Table 2 Application of ligands 5 in NHK allylation of benzaldehyde
Entry
Ligand
R1
R2
Conv.a (%)
Yieldb (%)
Eec (%) (Conf.)d
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
Bn
i-Pr
Ph
t-Bu
Ph
Bn
t-Bu
Bn
t-Bu
i-Pr
i-Pr
Ph
t-Bu
Ph
Bn
i-Pr
Ph
t-Bu
Bn
Ph
Bn
t-Bu
i-Pr
t-Bu
Ph
i-Pr
Ph
t-Bu
i-Pr
Bn
80
82
80
83
75
88
88
85
84
78
90
82
85
82
100
91
78
78
72
79
73
75
83
82
76
70
87
79
78
78
90
84
8 (S)
63 (S)
38 (S)
22 (R)
12 (R)
13 (S)
73 (R)
62 (R)
48 (R)
35 (S)
43 (R)
32 (R)
49 (R)
13 (S)
33 (S)
15 (R)
Bn
i-Pr
a Determined from the 300 MHz 1H NMR spectrum of the crude silylated product. b Isolated yields of the allylic alcohol 14. c Determined by chiral HPLC
analysis of the alcohol product 14 using a Daicel Chiralcel OD column. d Determined by comparison of the chiral HPLC retention times with literature
values.12
with different oxazoline substituents (5e-p) the best enantioselec-
tivities of 73% (R) and 62% (R) (entries 7,8) were achieved with
the ligands containing the benzyl/tert-butyl substituted oxazolines
(5g, 5h), again following the trend observed in allylation studies
employing ligand class 4. It is clear from the results obtained
herein that the magnitude of stereoinduction changes when R1
and R2 are reversed, reflecting both the steric and electronic effects
of the aromatic rings. Interestingly, the sense of stereoinduction
is maintained only when the oxazoline substituents are tert-
butyl/benzyl- and isopropyl/phenyl-containing.
Ideally a proposal to explain the asymmetric induction observed
would be strengthened by obtaining an X-ray structure of a
chromium–ligand 5 complex. However, despite many attempts we
have not yet obtained such a structure although we have obtained
an X-ray structure of a zinc complex of the related bis{2-[(4S)-
4-tert-butyl-4,5-dihydrooxazol-2-yl]phenyl}methylamine ligand 4
(R1, R2 = t-Bu).20 That complex shows that only the oxazoline
nitrogen atoms were coordinated and we propose a similar
binding mode of chromium to ligand 5g. In the absence of
coordination through the secondary amine unit, the role of DIPEA
is important as results obtained in its absence show lowered
levels of enantioselectivities. In addition we believe that only one
ligand is coordinated in the active complex as a two-fold excess of
ligand was found to lead to a diminution of enantiomeric excesses.
However, an accurate picture of the precise coordination sphere
around chromium is still unavailable for the ligands reported
herein and related bis(oxazoline)-containing ligand systems.
bromothiophene)oxazoline 10 was unsuccessful, the ligand class
was accessed in an alternative synthetic strategy by coupling 2-(2ꢀ-
aminophenyl)oxazolines 8a–d and 2-(2ꢀ-bromothiophene)nitrile
9. This is one of the few examples reported to date where
a substituted thiophene has been successfully employed as a
substrate in aryl aminations. Subsequent ZnCl2-mediated reaction
of intermediates 11a–d furnished ligand class 5 in good to high
yields. The synthetic route allowed for the synthesis of non-
symmetric bis(oxazoline)-containing ligands possessing either
identical or different oxazoline substituents and the option for
selective placement of substituents on each oxazoline ring. The
ligands were applied in the chromium-catalysed enantioselective
allylation of benzaldehyde with excellent conversions and good
enantioselectivities of up to 73% being observed. Our results
again highlight the significant effect that the substituents on
the oxazoline rings have on both the magnitude and sense of
asymmetric induction. The application of these ligands in other
chromium-catalysed processes will be reported in due course from
these laboratories.
Experimental
General experimental
1H NMR (300 and 400 MHz) and 13C (75 and 100 MHz) spectra
were recorded on Varian Oxford 300 or 400 spectrometers at
room temperature in CDCl3 using tetramethylsilane as an internal
standard. Chemical shifts (d) are given in parts per million
and coupling constants are given as absolute values expressed
in Hertz. HRMS were obtained using a Micromass/Waters
LCT instrument. Infra-red spectra were recorded on a Perkin-
Elmer infra-red FT spectrometer. Optical rotation values were
measured on a Perkin-Elmer 343 polarimeter at room temperature.
Conclusion
A new class of bis(oxazoline)-containing ligands 5 has been
prepared in good yield. Although Pd-catalysed aryl ami-
nation between 2-(2ꢀ-aminophenyl)oxazolines 8a–d and 2-(2ꢀ-
564 | Org. Biomol. Chem., 2008, 6, 562–566
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Melting points were determined in open capillary tubes in a
Gallenkamp melting point apparatus and are uncorrected. Thin
layer chromatography (TLC) was carried out on plastic sheets pre-
coated with silica gel 60 F254 (Merck). Column chromatography
separations were performed using Merck Kieselgel 60 (0.040–
0.063 mm). HPLC analysis was performed on an LC 2010A
HC(phenyl)), 7.70 (dd, J = 7.9, 1.5 Hz, 1H, Ar-HC(1)), 11.43
(br s, 1H, NH); 13C NMR (75 MHz, CDCl3): d = 41.9 (CH2Ph),
68.0 (CHN), 70.7 (CH2O), 91.6 (Ar-C(2ꢀ)), 112.0 (C≡N), 114.5
(Ar-C(5)), 114.8 (Ar-HC(3), Ar-HC(4), Ar-HC(4ꢀ), Ar-HC(5ꢀ),
Ar-HC(phenyl), 119.6 (Ar-HC(2)), 121.0, 126.7, 128.8, 129.5 (Ar-
HC(3), Ar-HC(4), Ar-HC(4ꢀ), Ar-HC(5ꢀ), Ar-HC(phenyl), 130.2
(Ar-HC(1)), 132.0, 132.4 (Ar-HC(3), Ar-HC(4), Ar-HC(4ꢀ), Ar-
R
machine equipped with a UV–vis detector employing a Chiracelꢀ
OD column from Daicel Chemical Industries. All reagents were
purchased from Sigma-Aldrich and used as received. Solvents
were dried before use by distillation from standard drying agents.
Anhydrous chlorobenzene was purchased from Sigma-Aldrich
and used without further purification. ZnCl2 (Sigma-Aldrich) and
CrCl3 were flame-dried under vacuum immediately prior to use.
General procedures for the two key steps of ligand syntheses will
be described and physical data of a typical product per step (11a
and 5a) are given. Physical data for all other products (11a–d and
5b–p) are available in the electronic supplementary information†.
The general procedure employed for the Nozaki–Hiyama–Kishi
allylation of benzaldehyde is described below.
HC(5ꢀ), Ar-HC(phenyl), 138.0 (ipso-Ph), 143.6 (Ar-C(6)), 150.6
ꢀ
=
(Ar-C(3 ), 163.9 (C N); IR (CHCl3 film): m = 1420, 1466, 1554,
1633, 2105, 2204, 3027, 3115 cm−1; HRMS (ES+) calculated for
C21H18N3OS [M + H]+: 360.1171, found: 360.1161.
General procedure for the synthesis of ligands 5a–p
To a flame-dried Schlenk tube was added 11a–d (0.40 mmol), the
required amino alcohol (0.80 mmol, 2 equiv.) and flame-dried
ZnCl2 (163 mg, 1.20 mmol, 3 equiv.) under an atmosphere of
nitrogen. Anhydrous chlorobenzene (5 mL) was added via syringe
and the resulting mixture was stirred at 145 ◦C for 12 hours.
The reaction was cooled to room temperature and solvent was
removed in vacuo. The crude product was purified by column
chromatography on silica gel to yield pure product.
General procedure for the screening of conditions for
palladium-catalysed aryl aminations
R
To an oven-dried Radleysꢀ tube was added 2-(o-aminophenyl)-
{2-[(4S)-4-Benzyl-4,5-dihydrooxazol-2-yl]-phenyl}{2-[(4S)-4-
benzyl-4,5-dihydrooxazol-2-yl]-thiophene-3-yl}amine 5a
oxazoline 8a (0.60 mmol), 3-(bromo-thiophene)oxazoline 10
(0.50 mmol), base (0.60 mmol), ligand (0.05 mmol) and palladium
precursor (0.025 mmol Pd). Dry degassed solvent (1.5 mL) was
added and the reaction was stirred under an atmosphere of
nitrogen at the required temperature for 7 days. The reaction
mixture was cooled to room temperature, solvent was removed
in vacuo and the resulting brown oil was passed through a short
pad of silica using pentane–ethyl acetate as eluent. The solvent was
removed in vacuo and a 1H NMR spectrum obtained to determine
if any aryl–amine product had formed.
Yield: 61% (0.21 g), pale yellow solid; mp: 50–54 ◦C; TLC: Rf =
0.50 (pentane–ethyl acetate 5 : 1); [a]D = +87.7 (c = 0.80 in
1
CHCl3); H NMR (300 MHz, CDCl3): d = 2.60–2.73 (m, 2H,
CH2Ph), 3.08–3.19 (m, 2H, CH2Ph), 3.88–3.98 (m, 2H, CH2O),
4.16 (dd, J = 18.3, 9.2 Hz, 2H, CH2O), 4.38 (t, J = 6.3 Hz, 1H,
CHN), 4.47 (t, J = 7.1 Hz, 1H, CHN), 6.79 (t, J = 6.7 Hz, 1H,
Ar-HC(2)), 7.14–7.32 (m, 14H, Ar-HC(3), Ar-HC(4), Ar-HC(4ꢀ),
Ar-HC(5ꢀ), Ar-HC(phenyl)), 7.72 (d, J = 7.6 Hz, 1H, Ar-HC(1)),
10.87 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d = 40.8
(CH2Ph), 40.9 (CH2Ph), 66.8 (CHN), 67.0 (CHN), 69.3 (CH2O),
70.5 (CH2O), 107.4 (Ar-C(2ꢀ)), 112.0 (Ar-C(5)), 115.2 (Ar-HC(3),
Ar-HC(4), Ar-HC(4ꢀ), Ar-HC(5ꢀ), Ar-HC(phenyl)), 118.0 (Ar-
HC(3), Ar-HC(4), Ar-HC(4ꢀ), Ar-HC(5ꢀ), Ar-HC(phenyl)), 120.1
(Ar-HC(2)), 124.2, 125.3, 125.4, 127.0, 127.2, 127.4, 128.0, 128.2,
128.3, 129.0 (Ar-HC(3), Ar-HC(4), Ar-HC(4ꢀ), Ar-HC(5ꢀ)), 130.7
(Ar-HC(1)), 136.9 (ipso-Ph), 137.2 (ipso-Ph), 142.7 (Ar-C(6), Ar-
General procedure for the palladium-catalysed aryl amination of
2-(2-aminophenyl)oxazoline 8a–d and
3-bromothiophene-2-carbonitrile 9
R
An oven-dried Radleysꢀ tube was charged with 3-bromothio-
phene-2-carbonitrile 9 (188 mg, 1.00 mmol), 2-(o-aminophenyl)-
oxazoline 8a–d (1.20 mmol), 2,2ꢀ-bis(diphenylphosphino)-1,1ꢀ-
binaphthyl (BINAP) (62.3 mg 0.10 mmol), Pd(OAc)2 (22.4 mg,
0.10 mmol) and cesium carbonate (456 mg, 1.4 mmol). After the
addition of dry, degassed toluene (10 mL) via syringe, the tube was
capped under an atmosphere of nitrogen and the reaction mixture
was heated at 120 ◦C for 36–48 hours, with monitoring by TLC. On
completion, the dark orange–brown reaction mixture was cooled
to room temperature and concentrated in vacuo to give a brown
oil which was purified by column chromatography on silica gel.
ꢀ
ꢀ
=
=
C(3 )), 142.9 (Ar-C(6), Ar-C(3 )), 158.7 (C N), 162.0 (C N); IR
(CHCl3 film): m = 1412, 1557, 1584, 1633, 2360, 2924, 3026 cm−1;
HRMS (ES+) calculated for C30H27N3O2S [M + H]+: 494.1884,
found: 494.1878.
General procedure for the Nozaki–Hiyama–Kishi allylation of
benzaldehyde
A flame-dried Schlenk tube was charged with dry THF (1 mL)
and dry acetonitrile (150 lL). Anhydrous chromium(III) chloride
(4.0 mg, 25.3 lmol) and manganese (41.7 mg, 0.76 mmol)
were added simultaneously to the solvent mixture. The resulting
suspension was allowed to stand at room temperature for approx-
imately 30 minutes until the characteristic purple colour of the
chromium(III) salt disappeared. The mixture was stirred vigorously
under an atmosphere of nitrogen for 1 h resulting in a green
reaction mixture. DIPEA (13 lL, 75.9 lmol) was added followed
by the ligand 5 (30.4 lmol) resulting in an immediate green catalyst
{2[(4S)-4-Benzyl-4,5-dihydrooxazol-2-yl]phenyl}(thiophene-2-
carbonitrile)amine 11a
Yield: 96% (0.35 g), pale orange oil; TLC: Rf = 0.60 (CH2Cl2);
[a]D = +55.2 (c = 0.90 in CHCl3); 1H NMR (300 MHz, CDCl3):
d = 2.72 (dd, J = 13.8, 8.1 Hz, 1H, CH2Ph), 3.14 (dd, J =
13.8, 5.6 Hz, 1H, CH2Ph), 3.99 (m, 1H, CH2O), 4.22 (m, 1H,
CH2O), 4.59 (m, 1H, CHN), 6.80 (m, 1H, Ar-HC(2)), 7.09–7.36
(2 × m, 9H, Ar-HC(3), Ar-HC(4), Ar-HC(4ꢀ), Ar-HC(5ꢀ), Ar-
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mixture. This was stirred at room temperature for 1 hour prior to
the addition of the allyl bromide (0.51 mmol) with the resulting
chromium(III) allyl solution being stirred for a further 1 hour. The
reaction was initiated by the addition of aldehyde (0.25 mmol)
and chlorotrimethylsilane (64 lL, 0.51 mmol) and stirred under
an atmosphere of nitrogen at room temperature for 16 hours. The
resulting green–brown suspension was quenched with saturated
aqueous NaHCO3 (1 mL) and extracted with Et2O (3 × 1 mL).
The combined organic layers were concentrated in vacuo to give a
green residue. This was flushed through a small silica gel column
(1.5 × 5 cm, pentane–AcOEt 9 : 1) to remove the catalyst and, after
evaporation of the solvent, the reaction products were isolated as
a yellow oil. The % conversion of the reaction was determined
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1
at this stage from the H NMR spectrum of the crude product
(generally a mixture of silylated and free alcohol) by measuring
the ratio of aldehyde to product and assuming that all aldehyde
consumed went to product. Peaks consistent with the product of
pinacol coupling were not observed in any of the catalytic studies
employing ligands 5. The yellow oil was dissolved in THF (1 mL),
a few drops of aqueous 1 M HCl were added, and the resulting
solution was stirred for 10 min when TLC (pentane–AcOEt 9 : 1)
showed complete desilylation. The solvent was removed in vacuo
and the resulting aqueous phase was extracted with Et2O (3 ×
2 mL). The organic layers were combined, dried over anhydrous
Na2SO4 and concentrated in vacuo to give a yellow oil. This was
purified by flash column chromatography on silica gel (1 × 15 cm)
using cyclohexane–AcOEt 5 : 1 as the eluent to give the required
product as a pale yellow oil. Enantioselectivity was determined
by HPLC: Chiralcel OD, hexane–isopropanol 98 : 2, flow rate
0.3 mL min−1: (R) 35.1 min, (S) 41.7 min.
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Acknowledgements
We thank the Irish Research Council for Science, Engineering
and Technology for the award of a postgraduate scholarship to
GH (RS/2003/36). TPO’S acknowledges financial support from
the Centre for Synthesis and Chemical Biology (CSCB), which
was funded by the Higher Education Authority’s Programme
for Research in Third-Level Institutions (PRTLI). We thank our
colleague Professor Declan Gilheany for helpful discussions on
chromium chemistry.
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