Developing asymmetric iron and ruthenium-based cyclone complexes; Complex factors influence the asymmetric induction in the transfer hydrogenation of ketones

Article abstract of DOI:10.1039/c1ob06010d

The preparation of a range of asymmetric iron and ruthenium-cyclone complexes, and their application to the asymmetric reduction of a ketone, are described. The enantioselectivity of ketone reduction is influenced by a single chiral centre in the catalyst, as well as by the planar chirality in the catalyst. This represents the first example of asymmetric ketone reduction using an iron cyclone catalyst.

Full text of DOI:10.1039/c1ob06010d

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PAPER
Developing asymmetric iron and ruthenium-based cyclone complexes; complex
factors influence the asymmetric induction in the transfer hydrogenation of
ketones†
Jonathan P. Hopewell, Jose´ E. D. Martins, Tarn C. Johnson, Jamie Godfrey and Martin Wills*
Received 24th June 2011, Accepted 1st September 2011
DOI: 10.1039/c1ob06010d
The preparation of a range of asymmetric iron and ruthenium-cyclone complexes, and their application
to the asymmetric reduction of a ketone, are described. The enantioselectivity of ketone reduction is
influenced by a single chiral centre in the catalyst, as well as by the planar chirality in the catalyst. This
represents the first example of asymmetric ketone reduction using an iron cyclone catalyst.
in catalytic reduction reactions of ketones by Casey and Guan.8
The mechanism appears to be analogous to that of the Shvo
catalyst 2 (Fig. 1c). In recent studies, complex 5 has been applied
to the oxidation of alcohols using acetone as an acceptor, and
Introduction
The ruthenium complex 1 (the Shvo catalyst)1–4 reversibly splits to
give hydride 2 and the unsaturated species 3.
a number of its derivatives have been reported and evaluated in
this role.9 In our own studies,10 we reported the synthesis and
applications of racemic complexes 7a–7g in alcohol oxidations.
The complexes were formed by an intramolecular cyclisation
from a linear dialkyne precursor 8, followed by diastereoisomer
By ‘shuttling’ between 2 and 3, the Shvo catalyst transfers pairs
of hydrogen atoms between secondary alcohols and ketones and
has been used to good effect in dynamic kinetic resolution (DKR)
reactions of alcohols and amines.2,3 There is evidence,4 largely
based on kinetic isotope effects, that the hydrogen transfer to
ketones and aldehydes, by the Shvo catalyst, takes place via a
concerted ‘outer sphere’ mechanism (Fig. 1a). This is analogous
to that of ketone reduction by the Noyori catalyst 4 (Fig. 1b).5
separation.7,11
However, given their proposed mechanism for reduction of ke-
tones, we reasoned that asymmetric derivatives of 7b–7g complexes
should be capable of enantioselective ketone reduction reactions.
Asymmetric induction would be predicted to be achieved by the
steric and/or electronic effects of the groups flanking the central
‘C–O’ bond of the cyclone ligand (Fig. 1c).
Since the start of our studies in this area, Yamamoto has
reported the synthesis of the asymmetric Shvo-type catalyst
precursors 9a/9b, which are capable of asymmetric hydrogenation
(35 atm H2) of acetophenone in 14–21% ee and up to 100%
conversion.12a As far as we are aware this is the first example
of an asymmetric Shvo-type catalyst, although Berkessel has very
recently published a closely related system based on chiral-at-Fe
complexes which catalysed pressure hydrogenation (i.e. with H2
gas) of acetophenone in up to 31% ee.12b Despite the difference in
planar chirality, it was found that the same enantiomer of alcohol
product (R) was formed by both 9a and 9b. Herein we disclose
our own results in the area of asymmetric Shvo-type reduction
catalysts using both iron- and ruthenium-based cyclone catalysts
in asymmetric transfer hydrogenation (ATH) reactions (Table 1).
Fig. 1 Comparison of mechanisms of hydrogen transfer by a) ruthenium
hydride 2, b) Noyori catalyst 4 and c) iron hydride 5. In c, the potential for
substituents RL (large) and RS (small) to influence the enantioselectivity is
illustrated.
The Shvo catalyst is also an efficient ketone reducing agent
when using an excess of an alcohol (usually iPrOH) or formic
acid as hydrogen source,1d and can also catalyse hydrogenation
reactions.1b,c,4d,6 The closely related iron complex 5 has recently
been prepared from the tricarbonyl precursor 67 and employed
Department of Chemistry, The University of Warwick, Coventry, UK, CV4
7AL. E-mail: m.wills@warwick.ac.uk; Fax: (+44) 24 7652 3260; Tel: (+44)
24 7652 4112
† Electronic supplementary information (ESI) available: Experimental
details, NMR spectra. See DOI: 10.1039/c1ob06010d
Racemic complex 7a10 was first tested and was found to work
efficiently in a formic acid/triethylamine (FA/TEA) system, as
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Table 1 Asymmetric reduction of acetophenone using iron and ruthe-
nium cyclone complexesa
Complex Conditions
Time/h Conv/%b (alcohol) Ee (R/S)
7a
FA/TEA 28 ◦C 1 M 18
60 (<1 form)
90 (+2 form)
89 (+10 form.)
6.8
52
25
36
10
n/a
n/a
n/a
n/a
7a
FA/TEA 40 ◦C 1 M 18
7a
FA/TEA 60 ◦C 1 M 18
7a
iPrOH 28 ◦C 0.2 M
iPrOH 60 ◦C 0.2 M
18
18
7a
n/a
7b
FA/TEA 28 ◦C 1 M 48
FA/TEA 40 ◦C 1 M 48
FA/TEA 40 ◦C 1 M 96
FA/TEA 28 ◦C 1 M 48
FA/TEA 28 ◦C 1 M 96
FA/TEA 28 ◦C 1 M 48
FA/TEA 40 ◦C 1 M 96
FA/TEA 40 ◦C 1 M 48
FA/TEA 40 ◦C 1 Md 96
FA/TEA 40 ◦C 1 Md 96
FA/TEA 60 ◦C 1.6 M 160
iPrOH 60 ◦C 0.18 M 160
FA/TEA 60 ◦C 1.6 M 160
iPrOH 60 ◦C 0.18 M 160
FA/TEA 60 ◦C 1.6 M 150
iPrOH 60 ◦C 0.18 M 150
FA/TEA 60 ◦C 1.6 M 18
iPrOH 60 ◦C 0.18 M 18
FA/TEA 60 ◦C 1.6 M 150
iPrOH 60 ◦C 0.18 M 150
FA/TEA 60 ◦C 1.6 M 168
iPrOH 60 ◦C 0.18 M 184
FA/TEA 60 ◦C 1.6 M 168
iPrOH 60 ◦C 0.18 M 168
FA/TEA 60 ◦C 1.6 M 168
iPrOH 60 ◦C 0.18 M 168
15 (R)
10 (R)
10 (R)
25 (R)
23 (R)
11 (R)
23 (R)
11 (R)
25 (R)
5 (R)
12 (R)c
11 (R)
3 (R)
4 (R)
5 (R)
3 (R)
17 (R)
11 (R)
15 (S)
5 (S)
n/a
7b
7c
7d
40
69
46
7d
7e
7d
80 (+5 form)
91 (+5 form.)
66 (+10 form.)
17
50
28
61
35
48
58
31
13
19
20
35 (+5 form.)
17
80 (+7 form.)
90
12.5
21
7e
7f
7g
12a
12a
12b
12b
12c
12c
12e
12e
13a/b
13a/b
16
16
n/a
n/a
n/a
n/a
17
Scheme 1 Synthesis of iron catalysts 7b–7g.
17
18
18
n/a
Conversions were in all cases measured by integrating the product
peaks in the GC against the starting material peaks.
a 10 mol% iron catalyst was used, with 10 mol% Me3NO. b form. = formate
byproduct. c ee was 20% (R) at 10 h and decreased with time. d Reactions
at 28 ◦C, 1 M with 7c; 48h, 5% conv, 10% ee (R), 7f; 96h, 2% conv, 29% ee,
7g; 96 h, trace conversion.
The new catalysts were tested in the ATH of acetophenone
(Table 1). In the case of 7b/c, the catalyst proved to be of low
activity and a reduction product of low ee was formed in the
same major enantiomeric form. Each purified, enantiomerically-
pure diastereoisomer of 7d/e was found to be a more effective
catalyst for ketone reduction in 5 : 2 FA/TEA, giving almost
complete transformation within 48–96 h at 40 ◦C. Again, both gave
reduction products of the same absolute configuration, mirroring
the activity of the ruthenium complexes reported by Yamamoto.12
More interestingly, catalysts 7f/g, which bear identical (phenyl)
groups flanking the central C O function in the cyclone, also
gave the same alcohol enantiomers. The chiral centre on the
backbone of the cyclone clearly has a significant effect on the
catalyst enantioselectivity, possibly due to an influence on the
conformation of the phenyl rings. Although the ees are low, the
isomer with the methyl group positioned proximal to the Fe(CO)3
group gave a higher ee in each case (7b,d,f vs. 7c,e,g respectively).
The effect may arise via an influence on the positions of the
CO ligands which subsequently communicates to the reduction
transition state.
commonly used in ATH reactions (Table 1).5 At low temperature
only a trace of formate byproduct was observed. Raising the
temperature to 60 ◦C resulted in essentially complete reduction al-
though some formate co-product was formed. The use of 10 mol%
catalyst was required, along with 10 mol% of trimethylamine N-
oxide to initiate hydride formation.9b,10,13 An inferior result was
observed in iPrOH.5 Enantiopure complexes 7b–7g were prepared
(Scheme 1) from alcohol (R)-11a (made in 96% ee by reduction of
the precursor ketone 10a by ATH using an established catalyst14).
Elaboration of (R)-11a following the reported route10 gave in each
case (i.e. from 8b–d where R1 = TBDMS, TMS and Ph respectively)
two enantiomerically-enriched complexes which were separated
by chromatography on silica gel. In our previous studies on the
racemic series, we had established the relative configuration of
the chiral centres via an X-ray crystallographic solution of 7c; the
other iron complexes are assigned by analogy with 7b/c.10 The
enantiomeric purity of catalyst 7d was established using a shift
reagent and was established to be ca. 92% ee, indicating a small
loss of ee relative to the alcohol but a high enough level to be
meaningful in these investigations (see supporting information†).
Monitoring the reductions over time indicated that the ees did
not change significantly over time, even after several days (e.g.
7d after 48 and 96 h), indicating that product racemisation is
not taking place. Although the conversions appear to level out
over time, it is at present unclear as to whether this may be due to
catalyst deactivation or a solvent effect. Formic acid/triethylamine
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was used in the traditional azeotrope ratio of 5 : 2 throughout. A
ratio of 1 : 1 FA : TEA gave a conversion of 25% in 96 h and 21%
ee when 7d was used as catalyst. A 1 : 2 FA : TEA mixture was
not homogeneous, whilst a 5 : 1 FA : TEA mixture gave only 11%
conversion after 96h, in 26% ee. These results indicate that the
FA : TEA ratio effects the rate but not the ee of the reaction, with
5 : 2 being the best ratio of those tested.
case unexpected (S) configuration (Table 1). Taken together, these
results indicate that asymmetric induction by cyclone catalysts
arises from a combination of control by backbone chiral centres
and planar chirality.
As far as we are aware, this represents the first application of
any iron cyclone complex to the asymmetric reduction of ketones
by transfer hydrogenation,12 and also reveals an unusual effect of
a backbone chiral centre on the observed enantiocontrol.
We also wished to establish whether the analogous ruthenium-
based catalysts would exhibit a similar pattern of enantioselectiv-
ity. To this end, complexes 12a–12f were prepared and evaluated,
using the corresponding diyne precursors.15
The synthesis of catalysts 14a–c was investigated. The TBS-
substituted alcohol (R)-11b was prepared from 10b in quantitative
conversion, 88% isolated yield and over 99% ee using the same
ATH catalyst as was used for 11a.14 Unfortunately, separation of
the diastereomers of these complexes could not be achieved and
these were not evaluated in reductions.
In studies directed at improving the d.e.s of the cyclisation
through the use of a larger group on the chiral centre, we
examined derivatives of 8 where R3 = Ph. Ru/TsDPEN catalysts
are less effective at reduction of aryl/propargylic ketones 10c–
10e,16 therefore these were reduced using (R)-Alpine borane.17
For variation of group R1, we prepared alcohols (R)-11c–11e
however the TMS derivative (R)-11c was prone to loss of the
silyl group in the subsequent alcohol alkylation step. Reaction
of the dialkyne derivatives of (R)-11d (96% ee) and (R)-11e
(97% ee) with Ru3(CO)12 led to the formation of Ru cyclone
complexes 15a–f, all of which were formed as inseparable mixtures
of diastereoisomers and proved to be poor catalysts (see SI†). For
comparison of relative reactivity, symmetrical complexes 16–18
were also prepared and tested in ATH reactions; the TBDMS-
substituted catalyst 17 proved to be the most active (Table 1).
In conclusion, a series of enantiomerically enriched iron and
ruthenium cyclone complexes have been prepared and applied to
the ATH of ketones to alcohols. The iron complexes, in their first
reported role as ATH catalysts, are as effective in terms of asym-
metric induction as the ruthenium complexes, although higher
loadings are required. Other iron-based catalysts have recently
been reported to give higher activities and enantioselectivities.18
The results also indicate that the control of enantioselectivity in
the reductions, whilst modest, appears to rely on a novel means of
asymmetric induction by a remote chiral centre in addition to the
planar symmetry of the catalysts.
Alcohol (R)-11a (96% ee) was converted to the three derivatives
12a–12f following the precedent for the iron complexes10 but with
the use of Ru3(CO)12 in the complexation step.15 Complexes 12a/b,
were formed as a mixture of two separable diastereoisomers of
product in 27 and 12% isolated yields respectively. Although the
relative position of the Me group has not been established, we
have assumed that, in analogy with the iron series, that the major
enantiomer is that in which the Me on the backbone is proximal to
the Ru(CO)3 group. Both 12a and 12b were effective in catalysing
the reduction of acetophenone, again in the same absolute sense
(Table 1). Unlike the Fe series, there was evidence of racemisation
during extended reaction times; for example in the case of 12a, the
ee was 20% after 10 h. For the Ru complexes, in situ formation of
the hydride using NaOH in THF followed by phosphoric acid was
completed prior to the reduction,7a and Me3NO was not required.
The ruthenium catalysts were also used at lower loadings (1 mol%)
than the iron complexes (10 mol%). In the case of 12c/d, only one
isomer was isolated, and in low yield, from the cyclisation, and was
assumed to be of the configuration shown in 12c. This complex
promoted reduction but in poor enantioselectivity.
Complexes 12e/f have two identical groups flanking the central
C
O group, analogous to 7c/d. The cyclisation to form 12e/f was
achieved in low yield, however only one diastereoisomer, assumed
to be 12e, could be isolated. This was capable of reduction of
acetophenone in up to 17% ee (R), which, although low, confirms
that for the Ru catalysts as well as the iron ones, planar asymmetry
is not required for the asymmetric reduction. In order to eliminate
the effect of one backbone chiral centre, complexes 13a/b were
selected for study – in this case containing two methyl groups in
a cis arrangement. This was prepared by reacting alcohol (R)-
11b (see below) with mesylated (R)-11a, resulting in inversion of
configuration. Cyclisation of the resulting diyne with Ru3(CO)12
gave a mixture from which one isomer of 13 was isolated in
pure form. Although the relative positions of the methyl groups
to the Ru(CO)3 centre are not known, this catalyst will rely on
planar chirality alone in the reduction reaction. The result was
that acetophenone was reduced in up to 15% ee, and in this
Experimental section
Procedures for starting material ketones, racemic reductions,
synthesis of 16–18, Tables for reductions using 15a–f and NMR
spectra may be found in the Electronic Supporting Information†.
(R)-4-Phenyl-3-butyne-2-ol 11a14
(R,R)-Tethered Ru(II) catal◦yst (43 mg, 0.07 mmol)14b was dissolved
in iPrOH (135 cm3) at 28 C. KOH (0.1 M in iPrOH, 3.46 cm3,
0.0346 mmol) was added and the solution was observed to initially
turn dark purple and the gradually become lighter in colour. After
stirring for 30 min at 28 ◦C, 4-phenyl-3-butyne-2-one 10a (2.00 g,
13.88 mmol) was added and again the mixture turned dark purple.
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After 15 h the solvent was removed in vacuo to afford a dark oil
which was purified by short path distillation (125 ◦C, 5.8 mbar) to
afford the alcohol as a colourless oil (1.80 g, 12.32 mmol, 89%);
[a]2D8 +32.4 (c 0.966 in CHCl3) (lit.14a [a]D23 -35.0 (c 1.0 in CHCl3)
97% ee (S); m/z (ESI) 169 [M + 23]+; (Found (ESI): M + Na
169.0630, C10H10NaO requires 169.0624); nmax 3298, 2978, 2927,
2870, 2225, 1595 and 1490 cm-1; dH (400 MHz, CDCl3) 7.46–7.41
(2H, m, Ar), 7.34–7.28 (3H, m, Ar), 4.77 (1H, m, CH(OH)CH3),
2.00 (1H, d, J 5.13, OH), 1.57 (3H, d, J 7.03, CH3); dC (100 MHz,
CDCl3) 131.68 (CH, Ar), 128.42(CH, Ar), 128.42(CH, Ar), 122.61
(ipso, Ar), 90.96 (C C), 84.05 (C C), 58.91 (CH(OH)CH3),
24.42 (CH(OH)CH3); The ee was determined using chiral GC
of the acetyl derivative of the alcohol synthesised from reacting a
sample of the alcohol (<10 mg) with acetic anhydride (<50 mL)
and DMAP (<1 mg) in DCM (ca. 1 cm3) overnight; cyclodextrin
CB column; 96% ee, 115 ◦C, H2, 15 psi, 62.72 (S), 64.18 min (R).14b
J 15.6, OCHH), 4.32 (1H, d, J 15.6, OCHH), 1.57 (3H, d, J 6.5,
CH3), 0.20 (9H, s, Si(CH3)3); dC (100 MHz, CDCl3) 131.73 (CH,
Ar), 128.39 (CH, Ar), 128.24 (CH, Ar), 122.55 (ipso, Ar), 101.29
(C C), 91.35 (C C), 88.12 (C C), 85.53 (C C), 64.66 (OCH),
55.61 (OCH2), 22.02 (CHCH3), -0.10 (Si(CH3)3).
(R)-Dipropargylic ether 8 (R1 = (iPr)3Si, R2 = Ph, R3 = Me)
To 8a (8: R1 = H, R2 = Ph, R3 = Me) (0.350 g, 1.9022 mmol,
1 eq.) in THF (12.5 cm3) was added nBuLi (1.6 M in hexanes,
1.3 cm3, 2.092 mmol, 1.1 eq.) at -78 ◦C. After 1 h at -78 ◦C
triisopropylsilylchloride (0.49 cm3, 0.440 g, 2.283 mmol, 1.2 eq.)
was added and the mixture stirred at -78 ◦C for 1 h before being
allowed to warm to room temperature overnight. The reaction
was quenched using saturated NH4Cl(aq) (15 cm3) and extracted
using Et2O (3 ¥ 15 cm3). The combined organics were dried over
MgSO4 and the solvent removed in vacuo to afford the product as
a dark orange oil in quantitative yield and used without further
purification; [a]2D8 +150.35 (c 0.20 in CHCl3); m/z (ESI) 363 [M
+ 23]+; (Found (ESI): M + Na 363.2115 C22H32NaOSi requires
363.2115); nmax 2937, 2890 and 2863 cm-1; dH (400 MHz, CDCl3)
7.47–7.44 (2H, m, Ar), 7.34–7.30 (3H, m, Ar), 4.74 (1H, q, J 6.5,
(OCHCH3)), 4.41 (2H, s, OCH2), 1.57 (3H, d, J 6.5, CHCH3),
1.12–1.08 (21H, m, Si(CH(CH3)2)3); dC (100 MHz, CDCl3) 131.82
(CH, Ar), 128.39 (CH, Ar), 128.27 (CH, Ar), 122.67 (ipso, Ar),
103.14 (C C), 88.30 (C C), 87.73 (C C), 85.34 (C C), 64.01
(OCH), 56.58 (CH2), 22.03, 18.61, 17.72, 12.31, 11.19.
(R)-Dipropargylic ether 8a (8; R1 = H, R2 = Ph, R3 = Me)19
Sodium hydride (0.190 g, 60% on mineral oil, 4.746 mmol, 1.1 eq.)
was added to (R)-4-pheny◦l-3-butyne-2-ol (0.630 g, 4.315 mmol, 1
eq.) in THF (8 cm3) at 0 C. After 30 min, propargylic bromide
(0.55 cm3, 0.7695 g, 80% in toluene, 5.178 mmol, 1.2 eq.) was added
at 0 ◦C and the reaction was left to warm to room temperature over
2.5 h. The mixture was quenched using saturated NH4Cl(aq) (30
cm3) and extracted with ether (3 ¥ 30 cm3). The combined organic
fractions were dried over MgSO4 and the solvent removed in vacuo
to afford a yellow oil. Purification by column chromatography
(EtOAc/pet. ether (40–60) 1 : 20) afforded propargylic ether 8a (8;
R1 = H, R2 = Ph, R3 = Me) as a yellow oil (0.70 g, 3.804 mmol,
88%); [a]2D8 +289.04 (c 0.762 in CHCl3); m/z (ESI) 207 (M+ + 23);
(Found (ESI): M + Na 207.0788, C13H12NaO requires 207.0780);
nmax 3289, 2985, 2932, 2853, 2361, 2223, 2198, 2115, 1958, 1888,
1724, 1671, 1596, 1489, 1439, 1368 and 1325 cm-1; dH (400 MHz,
CDCl3) 7.51–7.45 (2H, m, Ar), 7.38–7.32 (3H, m, Ar), 4.68 (1H, q,
J 6.5, OCHCH3), 4.44 (1H, dd, J 15.6, 2.0, OCHH), 4.36 (1H, dd,
J 15.6, 2.0 OCHH), 2.49 (1H, t, J 2.0, C CH), 1.59 (3H, d, J 6.5,
CH3); dC (100 MHz, CDCl3) 131.73 (CH, Ar), 128.43 (CH, Ar),
128.25 (CH, Ar), 122.45 (ipso, Ar), 87.88 (C C), 85.62 (C C),
79.56 ((C CH), 74.42 (C C), 64.62 (OCH), 55.74 (OCH2), 22.00
(CH3).
(R)-Dipropargylic ether 8b (8: R1 = (tBu)3SiMe2, R2 = Ph,
R3 = Me)10
Compound 8a (8: R1 = H, R2 = Ph, R3 = Me) (0.195 g, 1.06 mmol)
was dissolved in dry THF (15 cm3) and cooled to -78 ◦C. n-
Butyllithium in hexanes (1.6 M, 0.79 cm3, 1.26 mmol) was added
dropwise and the mixture was allowed to stir for 1 h after which
time tert-butyldimethylsilylchloride (0.207 g, 1.37 mmol) in dry
THF (5 cm3) was added. After 17 h the reaction was quenched with
H2O (20 cm3), the THF was removed under reduced pressure and
the product was extracted into Et2O (3 ¥ 20 cm3). The combined
organic phase was dried over Na2SO4, filtered and the solvent was
removed under reduced pressure to give the product as a brown
oil which was purified by column chromatography on silica with a
gradient elution from 100% petroleum ether to 80 : 20 petroleum
ether : ethyl acetate to give the product 8 as a yellow oil (0.206 g,
0.69 mmol, 65%). The measured data is in agreement with that
previously reported for the racemic compound.10 [a]D24 +150.7 (c
1.0 in CHCl3); dH (300 MHz, CDCl3) 7.42–7.46 (2H, m, Ar), 7.28–
7.34 (3H, m, Ar), 4.64 (1H, q, J 6.8, CCH(CH3)O), 4.41 (1H, d,
J 15.8, CCH2O), 4.33 (1H, d, J 15.8, CCH2O), 1.55 (3H, d, J 6.8
Hz, (CCH(CH3)O), 0.95 (9H, s, Si(CH3)2C(CH3)3) 0.12 (6H, s,
Si(CH3)2C(CH3)3.
(R)-Dipropargylic ether 8c (8; R1 = Me3Si, R2 = Ph, R3 = Me)10
To 8a (8; R1 = H, R2 = Ph, R3 = Me) (0.350 g, 1.9022 mmol,
1 eq.) in THF (12.5 cm3) was added nBuLi (1.6 M in hexanes,
1.3 cm3, 2.092 mmol, 1.1 eq.) at -78 ◦C. After 1 h at -78 ◦C,
trimethylsilylchloride (0.29 cm3, 0.248 g, 2.283 mmol, 1.2 eq.) was
added and the mixture stirred at -78 ◦C for 1 h before being
allowed to warm to room temperature overnight. The reaction
was quenched using saturated NH4Cl(aq) (15 cm3) and extracted
using Et2O (3 ¥ 15 cm3). The combined organics were dried over
MgSO4 and the solvent removed in vacuo to afford the product as
a dark yellow oil (0.4800 g, 1.86 mmol, 98%) and used without
further purification; [a]D28 +160.04 (c 0.57 in CHCl3); m/z (ESI)
279 [M + 23]+; (Found (ESI): M + Na 279.1176 C16H20NaOSi
requires 279.1176); nmax 2985, 2954, 2927, 2890, 2843, 2168, 1763,
1595 and 1487 cm-1; dH (400 MHz, CDCl3) 7.48–7.45 (2H, m, Ar),
7.34–7.30 (3H, m, Ar), 4.62 (1H, q, J 6.5, OCHCH3), 4.42 (1H, d,
(R)-Dipropargylic ether 8d (8: R1 = Ph, R2 = Ph, R3 = Me)
To 8a (8: R1 = H, R2 = Ph, R3 = Me) (0.400 g, 2.1739 mmol, 1
eq.), phenyliodide (0.29 cm3, 0.5322 g, 2.6087 mmol, 1.2 eq.) in
triethylamine (7 cm3) at 50 ◦C was added Pd(Cl2)(PPh3) (0.031
g, 0.043 mmol, 0.02 eq.) After stirring for 5 min, CuI (0.04 g,
0.0217 mmol, 0.01 eq.) was added and the mixture kept at 50 ◦C
for 18 h. The mixture was then hot filtered to remove the amide
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salts. Removal of the remaining amine in vacuo afforded a yellow
oil which was purified by column chromatography to afford the
product as a light yellow oil (0.358 g, 1.3769 mmol, 63%); [a]D28
+180.00 (c 0.16 in CHCl3); m/z (ESI) 261 [M + 1]+, 283 [M + 23]+;
(Found (ESI): M + Na 283.1093 C19H16NaO requires 283.1093);
nmax 3052, 2981, 2934, 2843, 2219 and 1716 cm-1; dH (400 MHz,
CDCl3) 7.50–7.46 (4H, m, Ar), 7.35–7.30 (6H, m, Ar), 4.73 (1H,
q, J 6.5, OCHCH3), 4.65 (1H, d, J 15.6, OCHH), (R1 = Ph, R2 =
Ph, R3 = Me).10,19 4.73 (1H, q, J 6.5, OCHCH3), 4.65 (1H, d, J
15.6, OCHH), 4.57 (1H, d, J 15.6, OCHH), 1.61 (3H, d, J 6.5,
OCHCH3); dC (100 MHz, CDCl3) 131.81 (CH, Ar), 131.76 (CH,
Ar), 128.42 (CH, Ar), 128.40 (CH, Ar), 128.25 (CH, Ar), 128.23
(CH, Ar), 122.61 (ipso, Ar), 122.54 (ipso, Ar), 88.18 (C C), 86.22
(C C), 85.61 (C C), 84.92 (C C), 64.66 (OCH), 56.60 (OCH2),
22.08 (OCHCH3).
g, 2.0710 mmol, 1 eq.) was added and the reaction was allowed to
warm to room temperature over 18 h. After quenching the mixture
using saturated aqueous sodium bicarbonate (5 cm3) the mixture
was extracted with Et2O (3 ¥ 7 cm3) and dried over NaSO4, removal
of the solvent in vacuo afforded a yellow oil which was purified by
column chromatography (EtOAc/hexane gradient 1 : 100 to 1 : 10)
yielding the product as a colourless oil (0.1911 g, 0.6125 mmol,
30%); [a]2D8 +0.19 (c 0.78 in CHCl3); m/z (ESI) 335.2 [M + 23]+;
(Found (ESI): M + Na 335.1801 C20H28NaOSi requires 335.1802);
n
max 2983, 2952, 2929, 2880 and 2853 cm-1; dH (400 MHz, CDCl3)
7.48–7.42 (2H, m, Ar), 7.33–7.28 (3H, m, Ar), 4.72 (1H, q, J 6.5,
CH), 4.51 (1H, q, J 6.5, CH), 1.55 (3H, d, J 6.5, CH3), 1.50 (3H,
d, J 6.5, CH3), 0.95 (9H, s, SiC(CH3)3), 0.10 (6H, s, SiCH3); dC
(100 MHz, CDCl3) 131.76 (Ar), 131.70 (Ar), 128.29 (Ar), 128.19
(Ar), 128.14 (Ar), 106.30 (C C), 89.35 (C C), 84.73 (C C),
63.47 (C C), 63.45 (C C), 26.04, 22.10, 21.79. -4.70 (Si(CH3)2).
(R)-Alcohol 11b20
Iron cyclone complexes 7b/c
Tethered-TsDPEN (R,R) Ru(II) catalyst14b (31 mg, 0.005 mmol,
0.5 mol%) was dissolved in anhydrous iPrOH (97 cm3) and warmed
(R)-Dipropargylic ether 8b (8: R1 = (tBu)3SiMe2, R2 = Ph, R3 =
Me, 96% ee) (0.206 g, 0.69 mmol) and Fe(CO)5 (0.27 cm3, 2.05
mmol) were dissolved in dry toluene (3 cm3) and heated at 130 ◦C
for 24 h after which time the solution was allowed to cool to
room temperature and the solvent was removed under reduced
pressure. The brown residue was filtered through celite using a
9 : 1 mixture of hexane : ethyl acetate and subsequent purification
by column chromatography on silica with a gradient elution from
100% petroleum ether to 40 : 60 petroleum ether : ethyl acetate
gave two diastereomers of product, which were separated. The
measured data is in agreement with that previously reported for
the racemic compound.10 Minor diastereomer, yellow solid (0.026
g, 0.056 mmol, 8%); [a]D26 -47.0 (c 0.05 in CHCl3); dH (300 MHz,
CDCl3) 7.99–8.05 (2H, m, Ar), 7.29–7.39 (3H, m, 3H, Ar), 5.56
(1H, q, J 6.8 Hz, CCH(CH3)O), 4.81 (1H, d, J 13.2 Hz, CH2),
4.71 (1H, d, J 13.2 Hz, CH2), 1.53 (3H, d, J 6.8 Hz, CH3), 1.01
(9H, s, SiC(CH3)3) 0.47 (3H, s, Si(CH3)2C(CH3)3), 0.08 (3H, s,
Si(CH3)2C(CH3)3). Major diastereomer, brown oil (0.140 g, 0.300
mmol, 44%); [a]2D8 +20.0 (c 0.05 in CHCl3); dH (300 MHz, CDCl3)
7.47–7.53 (2H, m, Ar), 7.29–7.41 (3H, m, Ar), 5.38 (1H, q, J 6.0
Hz, CCH(CH3)O), 4.79 (1H, d, J 13.2 Hz, CH2), 4.73 (1H, d, J
13.2 Hz, CH2), 1.65 (3H, d, J 6.0 Hz, CH3), 0.97 (9H, s, SiC(CH3)3)
0.51 (3H, s, Si(CH3)2C(CH3)3), 0.06 (3H, s, Si(CH3)2C(CH3)3).
◦
to 28 C. On addition of KOH (in iPrOH, 0.1 M, 2.5 cm3,
0.25 mmol) the colourless solution turned dark purple and was
stirred at 28 ◦C for 30 min before TBDMS-3-butyn-2-one 10b
(1.840 g, 10 mmol) was added. After 18 h at 28 ◦C the solvent was
removed in vacuo and the resulting alcohol was purified by column
chromatography (EtOAc/hexane 5%) to afford a yellow oil (1.630
g, 8.76 mmol, 88%); m/z (ESI) 207 [M + 23]+; [a]D28 +26.29 (c 0.978
in CHCl3); nmax 3315, 2954, 2924, 2887, 2853, 2168, 1470 1358,
1251, 1112, 1072, 1041 and 940 cm-1; dH (300 MHz, CDCl3) 4.52
(1H, dq, J 6.6, 5.3, CH(OH)CH3), 1.77 (1H, d, J 5.3, OH), 1.45
(3H, d, J 6.6, CH(OH)CH3), 0.93 (9H, s, SiC(CH3)3), 0.10 (6H,
s, Si(CH3)2); dC (100 MHz, CDCl3) 108.35 (quat., C C), 86.64
(quat., C C), 58.75 (CH(OH)CH3), 26.00 (CH3), 24.35 (CH3),
16.42 (quat., SiC(CH3)3), -4.71 (CH3, Si(CH3)2). The ee was
determined using the acetyl derivative of the alcohol synthesised
from reacting a trace amount of the alcohol (<10 mg) with acetic
anhydride (<50 mL) and DMAP (<1 mg) in DCM (ca. 1 cm3)
◦
overnight. cyclodextrin CB column; 99% ee, 115 C, H2, 15 psi,
14.19 (S), 14.51 min (R).
(R)-Mesyl derivative of (R)-4-phenyl-3-butyne-2-ol 11a21
To (R)-4-phenyl-3-butyne-2-ol 11a (1.00 g, 1.00 cm3, 6.833 mmol,
1 eq.) and triethylamine (1.90 cm3, 13.46 mmol, 2 eq.) in DCM
(10 cm3) at -78 ◦C was slowly added methanesulfonyl chloride
(0.80 cm3, 10.13 mmol, 1.5 eq.) after 1 h the mixture was allowed
to warm to room temperature and quenched with NaHCO3(aq)
(15 cm3), extracted with DCM (3 ¥ 10 cm3) and dried over
Na2SO4. Removal of the solvent in vacuo afforded the mesylate
as a colourless oil in quantitative yield and was used immediately
without further purification; dH (400 MHz, d6-DMSO) 7.50–7.46
(2H, m, Ar), 7.43–7.34 (3H, m, Ar), 5.55 (1H, q, J 6.5, CHCH3),
3.18 (3H, s, SO2CH3), 1.77 (3H, d, J 6.5, CHCH3).
Iron cyclone complexes 7d/e
These complexes (two diastereomers) were synthesised by the
same procedure as for 7d/e using (R)-dipropargylic ether 8c (8:
R1 = TMS, R2 = Ph, R3 = Me, 96% ee) (0.390 g, 1.53 mmol)
and Fe(CO)5 (0.60 cm3, 4.56 mmol) and were purified by column
chromatography on silica gel with a gradient elution from 100%
petroleum ether to 80 : 20 petroleum ether : ethyl acetate to give two
diastereomers of product which were separated, as brown oils. The
measured data is in agreement with that previously reported for
the racemic material.10 Minor diastereomer (0.111 g, 0.262 mmol,
17%); [a]2D8 -166.0 (c 0.05 in CHCl3); dH (300 MHz, CDCl3) 7.99–
8.03 (2H, m, Ar), 7.29–7.40 (3H, m, Ar), 5.57 (1H, q, J 6.4 Hz,
CCH(CH3)O), 4.81 (1H, d, J 12.8 Hz, CH2), 4.71 (1H, d, J 12.8
Hz, CH2), 1.52 (3H, d, J 6.4 Hz, CH3), 0.33 (9H, s, Si(CH3)3).
Major diastereomer (0.240 g, 0.566 mmol, 37%); [a]2D8 +101.0 (c
(R,S)-Dipropargyl ether precursor of ligand 13a/b
To (R)-4-(t-butyldimethylsilyl)-3-butyne-2-ol 11b (0.3852 g,
2.0710 mmol, 1 eq.) in THF (5 cm3) was added sodium hydride
(0.083 g, 2.0710 mmol, 60% in mineral oil, 1 eq.) at 0 ◦C. After 30
min the mesyl derivative of (R)-4-phenyl-3-butyne-2-ol 11a (0.46
138 | Org. Biomol. Chem., 2012, 10, 134–145
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0.05 in CHCl3); dH (300 MHz, CDCl3) 7.48–7.52 (2H, m, Ar),
7.30–7.40 (3H, m, Ar), 5.36 (1H, q, J 6.4 Hz, CCH(CH3)O), 4.79
(1H, d, J 13.2 Hz, CH2), 4.71 (1H, d, J 13.2 Hz, CH2), 1.65 (3H,
d, J 6.4 Hz, CH3), 0.31 (9H, s, Si(CH3)3).
(100 MHz, CDCl3) 193.94 (C O), 180.55 (C O), 132.74 (ipso,
Ar), 128.72 (CH, Ar), 127.36 (CH, Ar), 126.54 (CH, Ar), 110.96,
109.65, 76.48 (OCHCH3), 75.74, 70.64, 66.33, 63.86, 27.90, 19.06,
-0.40 (Si(CH3)3).
Ruthenium cyclone complex 12c/d
Iron cyclone complexes 7f/g
A sealed tube was charged with 8 (R1 = (iPr)3Si, R2 = Ph,
R3 = Me) (0.5898 g, 1.798 mmol, 3eq.) and Ru3(CO)12 (0.3830
g, 0.5994 mmol, 1 eq.) in acetonitrile (6 cm3) and the reaction
These complexes (two diastereomers) were synthesised by the same
procedure as for 7b/c using (R)-dipropargylic ether 8d (8: R1 = Ph,
R2 = Ph, R3 = Me, 96% ee) (0.165 g, 0.63 mmol) and Fe(CO)5 (0.25
cm3, 1.90 mmol) and were purified by column chromatography
on silica with a gradient elution from 100% petroleum ether to
80 : 20 petroleum ether : ethyl acetate to give two diastereomers of
product, which were separated. The measured data is in agreement
with that previously reported for the racemic material.10 Minor
diastereomer; brown powder (0.026 g, 0.061 mmol, 10%); [a]D28
-75.0 (c 0.01 in CHCl3); dH (300 MHz, CDCl3) 8.06–8.11 (2H, m,
Ar), 7.86–7.93 (2H, m, Ar), 7.32–7.45 (6H, m, Ar), 5.64 (1H, q,
J 6.4 Hz, (CCH(CH3)O), 5.17 (2H, s, CH2), 1.54 (3H, d, J 6.4
Hz, (CCH(CH3)O). A broad resonance exists from 6.5–7.6 ppm
◦
heated to 100 C over 2 days. The solvent was removed in vacuo
and redissolved in DCM and filtered to remove any unreacted
Ru3(CO)12 and purified by column chromatography (EtOAc/pet.
ether (40–60) 1 : 10) to afford only one diastereoisomer cleanly
(0.1197 g, 0.2213 mmol, 12%); [a]2D8 +39.11 (c 0.140, CHCl3);
m/z (ESI) 555 [M + 1]+, 577 [M + 23]+; (Found (ESI): M +
H 555.1148 C22H33O5RuSi requires 555.1142); nmax 2944, 2860,
2077, 2023, 1999 and 1622 cm-1; dH (400 MHz, CDCl3) 7.37–7.32
(2H, m, Ar), 7.29–7.24 (2H, m, Ar), 7.21–7.15 (1H, m, Ar), 5.22
(1H, q, J 6.0, OCHCH3), 4.74 (2H, s, OCH2), 1.53 (3H, d, J
6.0, OCHCH3), 1.32 (3H, sept., J 7.5, Si(CH(CH3)2)3), 1.15–1.08
(18H, m Si(CH(CH3)2)3); dC (100 MHz, CDCl3) 193.83 (C O),
178.95 (C O), 130.38 (ipso, Ar), 129.89 (CH, Ar), 128.37 (CH,
Ar), 127.62 (CH, Ar), 116.19, 111.69, 79.37, 74.72 (OCHCH3),
68.36, 62.42, 23.66, 19.12, 12.32.
1
in the H NMR spectrum that has not been assigned; this may
be due to paramagnetic impurities. Major diastereomer; brown
powder (0.039 g, 0.091 mmol, 14%); [a]2D8 +23.0 (c 0.05 in CHCl3);
dH (300 MHz, CDCl3) 7.90–7.96 (2H, m, Ar), 7.53–7.59 (2H, m,
Ar), 7.32–7.45 (6H, m, Ar), 5.40 (1H, q, J 6.0 Hz, (CCH(CH3)O),
5.25 (1H, d, J 13.2 Hz, CH2), 5.03 (1H, d, J 13.2 Hz, CH2) 1.67
(3H, d, J 6.0 Hz, (CCH(CH3)O). A broad resonance exists from
6.6–7.8 ppm in the 1H NMR spectrum that has not been assigned;
this may be due to paramagnetic impurities.
Ruthenium cyclone complex 12e/f
A sealed tube was charged with 8d (8: R1 = Ph, R2 = Ph, R3 =
Me) (0.3580 g, 1.3769 mmol, 3eq.) and Ru3(CO)12 (0.2933 g,
0.4586 mmol, ◦1 eq.) in acetonitrile (5 cm3) and the reaction was
heated to 100 C over 2 days. The solvent was removed in vacuo
and redissolved in DCM and filtered to remove any unreacted
Ru3(CO)12 and purified by column chromatography (EtOAc/pet.
ether (40–60) 1 : 20) to afford only one diastereoisomer cleanly
(0.1371 g, 0.2898 mmol, 21%); [a]2D8 -61.96 (c 0.092, CHCl3); m/z
(ESI) 475 [M + 1]+, 497 [M + 23]+; (Found (ESI): M + H 475.0123
C23H17O5Ru requires 475.0120); nmax 2074, 1999 and 1622 cm-1;
dH (400 MHz, CDCl3) 7.87 (2H, d, J 7.5, Ar), 7.50 (2H, d, J 7.0,
Ar), 7.43–7.36 (4H, m, Ar), 7.35–7.28 (2H, m, Ar), 5.34 (1H, dq, J
1.5, 6.0, CHCH3), 5.25 (1H, d, J 12.6, CHH), 5.07 (1H, dd, J 2.0,
12.6, CHH), 1.61 (3H, d, J 6.0, CHCH3); dC (100 MHz, CDCl3)
193.80 (C O), 132.39 (ipso, Ar), 130.08 (ipso, Ar), 128.88 (CH,
Ar), 128.47 (CH, Ar), 127.85 (CH, Ar), 127.76 (CH, Ar), 127.00
(CH, Ar), 109.03 (quat.), 107.13 (quat.), 77.98 (quat.), 74.92 (CH),
74.06 (quat.), 67.75 (quat.), 23.74 (CH3).
Ruthenium cyclone complex 12a/b
A sealed tube was charged with 8c (8: R1 = Me3Si, R2 = Ph,
R3 = Me) (0.3813 g, 1.4894 mmol, 3eq.) and Ru3(CO)12 (0.3173
g, 0.4965 mmol, 1 eq.) in acetonitrile (5 cm3) and the reaction
heated to 100 ◦C over 2 days. The solvent was removed in
vacuo and redissolved in DCM then filtered to remove any
unreacted Ru3(CO)12 and purified by column chromatography
(EtOAc/pet. ether (40–60) 1 : 10) to afford the major 12a (0.1787,
0.404 mmol, 27%) and minor 12b (0.0768 g, 0.1738 mmol, 12%)
diastereoisomers. Configurations assigned by analogy with Fe
complexes; Major; m/z (ESI) 471 [M + 1]+, 493 [M + 23]+;
[a]2D8 +79.20 (c 0.11, CHCl3); (Found (ESI): M + H 471.0218
C20H21O5RuSi requires 471.0201); (Found (ESI): M + Na 493.0039
C20H20NaO5RuSi requires 493.0021); nmax 2075, 2006 and 1626
cm-1; dH (400 MHz, CDCl3) 7.43 (2H, d, J 7.0, Ar), 7.35 (2H, t,
J 7.5, Ar), 7.30–7.25 (1H, m, Ar), 5.29 (1H, q, J 6.0, OCHCH3),
4.83–4.73 (2H, m, OCH2), 1.59 (3H, d, J 6.0, OCHCH3), 0.32 (9H,
s, Si(CH3)3); dC (100 MHz, CDCl3) 193.82 (C O), 179.00 (C O),
130.44 (ipso, Ar), 129.80 (CH, Ar), 128.35 (CH, Ar), 127.64 (CH,
Ar), 114.40, 112.85, 80.04, 74.81 (OCHCH3), 67.27, 62.54, 23.73
(OCHCH3), -0.51 (Si(CH3)3); Minor [a]2D8 -8.30 (c 0.112, CHCl3);
m/z (ESI) 471 [M + 1]+, 493 [M + 23]+; (Found (ESI): M + H
471.0200 C20H21O5RuSi requires 471.0201); (Found (ESI): M +
Na 493.0019 C20H20NaO5RuSi requires 493.0021); nmax 2080, 2020
and 1989 cm-1; dH (400 MHz, CDCl3) 7.97 (2H, d, J 7.5, Ar),
7.35 (2H, t, J 7.5, Ar),7.29–7.25 (1H, m, Ar), 5.60 (1H, q, J 6.5,
OCHCH3), 4.89 (1H, dd, J 12.6, 1.0, OCHH), 4.78 (1H, d, J 12.6,
OCHH), 1.43 (3H, d, J 6.5, OCHCH3), 0.33 (9H, s, Si(CH3)3); dC
Ruthenium cyclone complex 13a/b
A sealed tube was charged with the dipropargyl ether precursor
of ligand 13a/b (0.083 g, 0.26 mmol, 3eq.) and Ru3(CO)12
(0.056 g, 0.0.887 mmo◦l, 1 eq.) in acetonitrile (1 cm3) and the
reaction heated to 100 C over 2 days. The solvent was removed
in vacuo and redissolved in DCM and filtered to remove any
unreacted Ru3(CO)12 and purified by column chromatography
(EtOAc/hexane 1 : 20) to afford only one diastereoisomer cleanly
(0.040 g, 0.0805 mmol, 31%); [a]2D8 +38.60 (c 0.020, CHCl3); m/z
(ESI) 527 [M]+; (Found (ESI): M + H 527.0822 C24H29O5RuSi
requires 527.0828); nmax 2075, 1999 and 1638 cm-1; dH (400 MHz,
CDCl3) 7.44–7.40 (2H, m, Ar), 7.37–7.32 (2H, m, Ar), 7.29–7.26
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(1H, m, Ar), 5.22 (1H, qd, J 6.0, 1.5, CHCH3) 5.00 (1H, qd, J
6.0, 1.5, CHCH3), 1.58 (3H, d, J 6.0, CHCH3), 1.55 (3H, d, J 6.0,
CHCH3), 0.99 (9H, s, SiC(CH3)3), 0.51 (3H, s, SiCH3), 0.18 (3H,
s, SiCH3); dC (100 MHz, CDCl3) 193.91 (C O), 180.04 (C O),
130.34 (ipso, Ar), 130.07 (CH, Ar) 128.38 (CH, Ar), 127.70 (CH,
Ar), 119.99, 116.40, 78.22, 74.82, 73.51, 60. 83, 31.56, 28.06, 27.23,
23.76, 22.63, 18.81, -2.04, -3.67.
(R)-Dipropargylic ether 8 (R1 = TMS, R2 = Si(tBu)Me2, R3 = Ph)
A flask was charged with (R)-dipropargylic ether 8 (R1 = H, R2 =
Si(tBu)Me2, R3 = Ph) (0.500 g, 1.7606 mmol) in THF (12 cm3)
◦
and cooled to -78 C. Addition of nBuLi (1.21 cm3, 1.94 mmol,
1.6 M in hexane, 1.1 eq.) afforded a dark green solution. After
1 h TMSCl (0.27 cm3, 2.11 mmol, 1.2 eq.) was added and the
ice bath removed after 5 min. After 30 min the reaction mixture
colour had changed from green to yellow. After 3 h the reaction
was quenched using water (10 cm3) and extracted with Et2O (3 ¥
10 cm3), the organic fractions combined and dried over MgSO4 and
the solvent removed under reduced pressure to afford a yellow oil
which was purified using column chromatography (EtOAc/hexane
0 to 20%) to afford a pale yellow oil (0.4300 g, 1.208 mmol, 69%);
[a]2D8 +27.3 (c 0.68 in CHCl3); m/z (ESI) 379.2 [M + 23]+; (Found
(ESI): M + Na 379.1881. C21H32NaOSi2 requires 379.1884); nmax
2954, 2928, 2898, 2856, 2173, 1249 and 1059 cm-1; dH (400 MHz,
CDCl3) 7.56 (2H, d, J 7.5, Ar), 7.40–7.31 (3H, m, Ar), 5.45
(1H, s, ArCH), 4.40 (1H, d, J 15.8, OCHH), 4.28 (1H, d, J
15.8, OCHH), 0.98 (9H, s, SiC(CH3)3), 0.21 (9H, s, Si(CH3)3),
0.17 (6H, s, Si(CH3)2); dC (100 MHz, CDCl3) 137.77 (ipso, Ar),
128.50 (CH, Ar), 128.41 (CH, Ar), 127.83 (CH, Ar), 102.70 (quat.,
(R)-Alcohol 11d
A flask was charged with (R)-Alpine borane solution (45.08 cm3,
22.54 mmol, 0.5 M in THF) and the solvent was removed in vacuo.
The flask was cooled to 0 ◦C and 3-(t-butyldimethylsilyl)-1-phenyl-
prop-2-ynone 10d (5.00 g, 20.49 mmol) was added dropwise. After
4 days acetylaldehyde (5 cm3) was added. After 1 h, NaOH(aq)
(10 cm3, 5 N), THF (10 cm3) and hydrogen peroxide (11.5
cm3, 30%wt) added. CAUTION: addition of peroxide is very
exothermic. After heating to 40 ◦C for 4 h, in air, the reaction
was extracted using Et2O (3 ¥ 30 cm3) and the combined organic
phases washed using brine (30 cm3), dried over MgSO4 and the
solvent removed in vacuo. Purification by column chromatography
(EtOAc/hexane 0.5%–5%) afforded a colourless oil (Rf 0.13 (10%
EtOAc/hexane), 3.67 g, 14.918 mmol, 73%, 96% ee); [a]2D8 +4.2
(c 1.054 in CHCl3); m/z 269.2 [M + 23]+; (Found (ESI): M +
Na 269.1333. C15H22NaOSi requires 269.1332); nmax 3362 (OH),
2926, 2857, 1671, 1446 and 1003 cm-1; dH (400 MHz, CDCl3) 7.56
(2H, d, J 7.1, Ar), 7.36 (3H, m, Ar), 5.47 (1H, s, Ar), 0.99 (9H, s,
SiC(CH3)3), 0.17 (6H, s, Si(CH3)2); dC (100 MHz, CDCl3) 140.36
(ipso, Ar), 128.49 (CH, Ar), 128.26 (CH, Ar), 126.70 (CH, Ar),
105.69 (quat., C C), 89.81 (quat., C C), 64.90 (CH(OH)), 26.03
(SiC(CH3)3), 16.50 (quat., SiC(CH3)3), -4.71 (Si(CH3)2); dSi (99
MHz, CDCl3) -7.64 (s, Si(CH3)2C(CH3)3). The ee was determined
by chiral GC; cyclodextrin CB column; 96% ee, 100 ◦C, H2, 15 psi,
83.70 min (S), 85.99 min (R).17
C
C
C), 101.11 (quat., C C), 91.81 (quat. C C), 91.60 (quat.
C), 70.39 (ArCH), 56.07 (OCH2), 26.08 (SiC(CH3)3), 16.56
(SiC(CH3)3), -0.16 (Si(CH3)3, -4.70 (Si(CH3)2); dSi (99 MHz,
CDCl3) -7.57 (s, Si(CH3)2C(CH3)3), -17.73 (s, Si(CH3)3).
(R)-Dipropargylic ether 8 (R1 = TIPS, R2 = Si(tBu)Me2, R3 = Ph
A flask was charged with (R)-dipropargylic ether 8 (R1 = H, R2 =
Si(tBu)Me2, R3 = Ph) (0.500 g, 1.7606 mmol) in THF (10 cm3)
◦
and cooled to -78 C. Addition of nBuLi (1.35 cm3, 2.17 mmol,
1.6 M in hexane, 1.2 eq.) afforded a dark green solution. After 30
min TIPSCl (0.50 cm3, 2.36 mmol, 1.3 eq.) was added and the ice
bath removed after 30 min. After 5 h the reaction was quenched
using water (10 cm3) and extracted with Et2O (3 ¥ 10 cm3), the
organic fractions combined and dried over MgSO4 and the solvent
removed under reduced pressure to afford a yellow oil which was
purified using column chromatography (EtOAc/hexane 0 to 5%)
to afford a bright yellow oil (0.219 g, 0.53 mmol, 30%); [a]2D8 +50.1
(c 0.825 in CHCl3); m/z (ESI) 463.3 [M + 23]+; (Found (ESI): M +
Na 463.2821. C27H44NaOSi2 requires 463.2823); nmax 2928, 2889,
2863, 1462, 1249, 1060, 1038,1027 and 1007 cm-1; dH (400 MHz,
CDCl3) 7.56–7.53 (2H, m, Ar), 7.40–7.32 (3H, m, Ar), 5.55 (1H, s,
ArCH), 4.51 (1H, d, J 16.1, OCHH), 4.31 (1H, d, J 16.1, OCHH),
1.08 (21H, m, Si(CH(CH3)2)3) (0.97 (9H, s, SiC(CH3)3), 0.17 (6H,
s, Si(CH3)2); dC (100 MHz, CDCl3) 137.97 (ipso, Ar), 128.49 (CH,
Ar), 128.44 (CH, Ar), 127.87 (CH, Ar), 102.74 (quat., C C),
102.70 (quat., C C), 91.49 (quat. C C), 88.42 (quat., C C),
69.75 (ArCH), 56.22 (OCH2), 26.09 CH3, SiC(CH3)3), 18.61
(Si(CH(CH3)2)3), 16.58 (SiC(CH3)3), 11.18 (CH3, Si(CH(CH3)3)3),
-4.68 (Si(CH3)2); dSi (99 MHz, CDCl3) -1.86 (s, Si(CH(CH3)2)3),
-7.57 (s, Si(CH3)2C(CH3)3).
(R)-Dipropargylic ether 8 (R1 = H, R2 = Si(tBu)Me2, R3 = Ph)
To a solution of (R)-alcohol 11d (1.1606 g, 6.0976 mmol 1 eq.)
in THF (20 cm3) at 0 ◦C was added NaH (0.2881 g, 60% in
mineral oil, 7.2019 mmol, 1.1 eq.). The reaction mixture was
stirred for 30 min at 0 ◦C after which propargylic bromide was
added (0.85 cm3, 80%wt in toluene, 1.17 g, 7.86 mmol, 1.2 eq.)
and the ice bath removed. After 4 h the reaction was quenched
using saturated NaHCO3(aq) solution (20 cm3) and extracted using
Et2O (3 ¥ 10 cm3). The combined organic fractions were dried over
MgSO4 and the solvent removed in vacuo. Purification column
chromatography (EtOAc/hexane 0% to 1%) afforded a colourless
oil (1.121 g, 3.948 mmol, 60%); [a]2D8 +27.3 (c 0.68 in CHCl3); m/z
307.2 [M + 23]+; (Found (ESI): M + Na 307.1483, C18H24NaOSi
requires 307.1489); nmax 2952, 2927, 2884, 2855, 1250 and 1059
cm-1; dH (400 MHz, CDCl3) 7.56 (2H, d, J 7.2, Ar), 7.41-7.34
4
(3H, m, Ar), 5.45 (1H, s, ArCH), 4.41 (1H, dd, J 2.3, J 15.7,
OCHH), 4.29 (1H, dd, 4J 2.3, J 15.7, OCHH), 2.48 (1H, t, 4J 2.3,
C
CH), 0.98 (9H, s, SiC(CH3)3), 0.17 (6H, s, Si(CH3)2); dC (100
(R)-Dipropargylic ether 8 (R1 = Ph, R2 = Si(tBu)Me2, R3 = Ph)
MHz, CDCl3) 137.65 (ipso, Ar), 128.69 (CH, Ar), 128.44 (CH, Ar),
126.75 (CH, Ar), 102.50 (quat., C C), 91.77 (quat., C C), 74.82
(quat. C C), 70.44 (ArCH), 55.26 (OCH2), 26.05 (SiC(CH3)3),
16.55 (SiC(CH3)3), -4.70 (Si(CH3)2); dSi (99 MHz, CDCl3) -7.51
(s, Si(CH3)2C(CH3)3).
A flask was charged with (R)-dipropargylic ether 8 (R1 = H, R2 =
Si(tBu)Me2, R3 = Ph) (0.500 g, 1.7606 mmol), PhI (0.26 cm3,
2.34 mmol, 1.3 eq.) and Et3N (6.3 cm3). To this mixture was added
PdCl2(PPh3)2 (27.4 mg, 0.0391 mmol, 0.02 eq.) and after 5 min
140 | Org. Biomol. Chem., 2012, 10, 134–145
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colourless oil (0.9155 g, 2.8083 mmol, 81%); [a]2D8 +24.25 (c 1.048,
CHCl3); m/z 349.2 [M + 23]+; (Found (ESI): 349.1953 M + Na
C21H30NaOSi requires 349.1958); nmax 2941, 2924, 2864, 2169,
2031 and 1461 cm-1; dH (400 MHz, CDCl3) 7.59–7.56 (2H, m,
Ar) 7.40–7.31 (3H, m, Ar), 5.48 (1H, s, ArCH), 4.44 (1H, dd,
CuI (3.7 mg, ◦0.0195 mmol, 0.01 eq.) was added and the reaction
heated to 50 C for 20 h. The reaction mixture was then filtered
and the remaining amine removed in vacuo. Purification by column
chromatography (EtOAc/hexane 0 to 2%) afforded a light yellow
oil (0.3693 g, 1.03 mmol, 58%); [a]2D8 +58.0 (c 1.02 in CHCl3); m/z
(ESI) 361.2 [M + 1]+; 383.1 [M + 23]+; (Found (ESI): M + Na,
383.1802. C24H28NaOSi requires 383.1802); nmax 2952, 2927, 2884,
2855 and 1057 cm-1; dH (400 MHz, CDCl3) 7.56 (2H, d, J 7.6, Ar),
7.50–7.48 (2H, m, Ar), 7.41–7.31 (6H, m, Ar), 5.53 (1H, s, ArCH),
4.63 (1H, d, J 15.7, OCHH), 4.51 (1H, d, J 15.7, OCHH), 1.05
(9H, s, SiC(CH3)3), 0.18 (6H, s, Si(CH3)2); dC (100 MHz, CDCl3)
137.82 (ipso, Ar), 131.81 (CH, Ar), 128.57 (CH, Ar), 128.53 (CH,
Ar), 128.45 (CH, Ar), 128.25(CH, Ar), 127.81 (CH, Ar), 122.60
(ipso, Ar), 102.83 (quat., C C), 91.70 (quat., C C), 86.62 (quat.,
4
4J 2.4, J 15.6, OCHH), 4.31 (1H, dd, J 2.4, J 15.6, OCHH),
4
2.47 (1H, t, J 2.4, C CH), 1.10 (21H, m, Si(CH(CH3)3); dC
(100 MHz, CDCl3) 137.79 (ipso, Ar), 128.47 (CH, Ar), 128.38
(CH, Ar), 127.75 (CH, Ar), 103.62 (quat., C C), 89.95 (quat.,
C
C), 79.35 (C CH), 74.72 (quat., C C), 70.50 (ArCH), 55.19
(OCH2), 18.58 (Si(CH(CH3)2)3), 11.16 (Si(CH(CH3)2)3); dSi (99
MHz, CDCl3) -1.53 (s, Si(CH(CH3)2)).
(R)-Dipropargylic ether 8 (R1 = Me3Si, R2 = Si(iPr)3, R3 = Ph)
C
C), 84.71 (quat., C C), 70.50 (ArCH), 56.10 (OCH2), 26.08
(SiC(CH3)3), 16.56 (SiC(CH3)3), -4.67 (Si(CH3)2); dSi (99 MHz,
CDCl3) -7.52 (s, Si(CH3)2C(CH3)3).
To a solution of (R)-dipropargylic ether 8 (R1 = H, R2 = Si(iPr)3,
R3 = Ph) (0.190 g, 0.582 mmol) in THF (3 cm3) cooled to -78 ◦C
was added nBuLi (0.4 cm3, 0.6404 mmol, 1.6 M in hexane, 1.1
eq.) affording a dark green solution. After 1 h TMSCl (0.089
cm3, 0.699 mmol, 1.2 eq.) was added and the ice bath removed
after 5 min. After 6 h the reaction was quenched using water (3
cm3) and extracted with Et2O (3 ¥ 4 cm3), the organic fractions
were combined and dried over MgSO4 and the solvent removed
under reduced pressure to afford a yellow oil which was purified
using column chromatography (EtOAc/hexane 0 to 1%) to afford
a yellow oil (0.1362 g, 0.3424 mmol, 59%); [a]2D8 +42.2 (c 1.106,
CHCl3); m/z 421.2 [M + 23]+; (Found (ESI): 421.2354 M + Na
C24H38NaOSi2 requires 421.2353); nmax 2944, 2893, 2865, 1719 and
1250 cm-1; dH (400 MHz, CDCl3) 7.58 (2H, d, J 7.04, Ar), 7.41–
7.31 (3H, m, Ar), 5.49 (1H, s, ArCH), 4.44 (1H, d, J 15.8, OCHH),
4.31 (1H, d, J 15.8, OCHH), 1.10 (21H, m, Si(CH(CH3)3), 0.20
(6H, s, Si(CH3)3); dC (100 MHz, CDCl3) 137.92 (ipso, Ar), 128.44
(CH, Ar), 128.38 (CH, Ar), 127.85 (CH, Ar), 103.78 (quat.,
(R)-Alcohol 11e
(R)-Alpine borane solution (0.5 M, in THF, 22 mmol, 44 cm3)
was introduced to a flask and the solvent removed in vacuo. The
flask was cooled to 0 ◦C and 3-(tri(isopropyl)silyl)-1-phenyl-prop-
2-yn-1-one 10e (5.72 g, 20.0 mmol) was added dropwise. The ice
bath was removed and after 4 days the reaction was quenched using
acetaldehyde (4.5 cm3). After 1 h THF (10 cm3) and NaOH(aq) (5 N,
10 cm3) were added and the reaction mixture put in a water bath
and H2O2 (30 wt%, 11.5 cm3) was added carefully. CAUTION:
very exothermic. After complete addition of the peroxide the
reaction was heated for 4 h in air followed by extraction with
Et2O (3 ¥ 30 cm3). The combined organic fractions were then
washed with brine (30 cm3) and dried over MgSO4. Removal of the
solvent in vacuo afforded a colourless oil which on purification by
column chromatography (hexane/EtOAc) afforded a colourless
oil (2.6031 g, 9.0385 mmol, 45% yield, 97% ee); [a]2D8 +5.81 (c
1.32, CHCl3); m/z 287.2 [M - 1], 309.2 [M + 23]; (Found (ESI):
M - H 287.1816 C18H27OSi requires 287.1826, M + Na 309.1631
C18H26NaOSi requires 309.1645); nmax 3354 (OH), 2941, 2891, 2864
and 2169 cm-1; dH (300 MHz, CDCl3) 7.6–7.56 (2H, m, Ar) 7.42–
7.29 (3H, m, Ar), 5.49 (1H, d, J 6.3, ArCH), 2.17 (1H, d, J 6.3,
OH), 1.09 (21H, m, Si(CH(CH3)3); dC (75 MHz, CDCl3) 128.54
(ipso, Ar), 128.51 (CH, Ar), 128.30 (CH, Ar), 126.77 (CH, Ar),
106.87 (quat., C C), 98.02 (quat., C C), 65.11 (CH(OH)), 18.59
(Si(CH(CH3)2)3), 11.15 (Si(CH(CH3)2)3); The ee was determined
by GC using cyclodextrin CB column; 97% ee, 170 ◦C, H2, 15 psi,
61.96 min (S), 63.68 min (R).17
C
C), 101.17 (quat., C C), 91.77 (C CH), 89.85 (quat., C C)
70.43 (ArCH) 56.02 (OCH2) 18.62 (Si(CH(CH3)2)3), 11.19 (CH,
Si(CH(CH3)2)3), -0.16 (Si(CH3)3).
(R)-Dipropargylic ether 8 (R1 = Si(tBu)Me2, R2 = Si(iPr)3, R3 =
Ph)
To a solution of (R)-dipropargylic ether 8 (R1 = H, R2 = Si(iPr)3,
R3 = Ph) (0.400 g, 1.227 mmol) in THF (7 cm3) cooled to -78 ◦C
was added nBuLi (0.84 cm3, 1.3497 mmol, 1.6 M in hexane, 1.1
eq.) affording a dark green solution. After 1 h TBDMSCl (0.222
g, 1.472 mmol, 1.2 eq.) was added and the ice bath removed
after 5 min. After 16 h the reaction was quenched using water
(10 cm3) and extracted with Et2O (3 ¥ 10 cm3), the organic fractions
were combined and dried over MgSO4 and the solvent removed
under reduced pressure to afford a crude yellow oil (0.4263 g,
0.9689 mmol, 79%); [a]2D8 +65.9 (c 0.50, CHCl3); m/z 463.2 [M
+ 23]+; (Found (ESI): M + Na 463.2819 C27H44NaOSi2 requires
463.2823); nmax 2942, 2927, 2891, 2863, 2173, 1461 and 1063 cm-1;
dH (400 MHz, CDCl3) 7.58 (2H, d, J 7.04, Ar) 7.41–7.31 (3H,
m, Ar), 5.49 (1H, s, ArCH), 4.44 (1H, d, J 15.8, OCHH) 4.31
(1H, d, J 15.8, OCHH) 1.10 (21H, m, Si(CH(CH3)3) 0.20 (6H,
s, Si(CH3)3); dC (100 MHz, CDCl3) 137.92 (ipso, Ar), 128.44
(CH, Ar), 128.38 (CH, Ar), 127.85 (CH, Ar), 103.78 (quat.,
(R)-Dipropargylic ether 8 (R1 = H, R2 = Si(iPr)3, R3 = Ph)
To a solution of (R)-alcohol 11e (1.000 g, 3.472 mmol 1 eq.)
in THF (11 cm3) at 0 ◦C was added NaH (0.1527 g, 60% in
mineral oil, 3.8194 mmol, 1.1 eq.). The reaction mixture was
stirred for 30 min at 0 ◦C after which propargylic bromide was
added (0.45 cm3, 80%wt in toluene, 0.619 g, 4.166 mmol, 1.2 eq.)
and the ice bath removed. After 4 h the reaction was quenched
using saturated NHCO3(aq) solution (20 cm3) and extracted using
Et2O (3 ¥ 10 cm3). The combined organic fractions were dried
over MgSO4 and the solvent removed in vacuo. Purification by
column chromatography (EtOAc/hexane 0 to 1%) afforded a
C
C), 101.17 (quat., C C), 91.77 (CH, C CH), 89.85 (quat.,
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C
C) 70.43 (CH(OH)) 56.02 (OCH2) 18.62 (Si(CH(CH3)2)3),
Ruthenium cyclone complex 15a
11.19 (Si(CH(CH3)2)3), -0.16 (Si(CH3)3).
A pressure tube was charged with (R)-dipropargylic ether 8 (R1 =
TIPS, R2 = Si(tBu)Me2, R3 = Ph) (0.1395 g, 0.3170 mmol 2 eq.),
acetonitrile (1 cm3) and Ru3(CO)12 (0.1013 g, 0.1585 mmol, 1 eq.)
and purged under a steady stream of N2. The tube was then
sealed and heated to 100 ◦C. After 2 d the reaction mixture
was cooled, carefully depressurised and the solvent removed in
vacuo. The resulting black semisolid was dissolved in DCM (2
cm3) and filtered through a cotton wool plug and loaded onto
a short silica column (EtOAc/hexane 0 to 10%) to afford a
yellow solid (0.1404 g, 0.2151 mmol, 68%). The metal complex
was characterised as a mixture of two diastereoisomers in an
approximate ratio of 3 : 1; m/z 655.1 [M + 1]+, 677.1 [M + 23]+;
(Found (ESI): 655.1861 M + H C31H45O5RuSi2 requires 655.1851);
nmax 2946, 2926, 2862, 2077, 2019, 1998 and1629 cm-1; dH (400
MHz, CDCl3) 7.50–7.47 (1.5H, m, Ar), 7.42–7.37 (3H, m, Ar),
7.22–7.20 (0.5H, m, Ar), 5.85 (1H, s, ArCH), 5.00 (1H, d, J 12.8,
OCHH), 4.88 (0.75H, dd, J 2.1, 12.8, OCHH, major), 4.79 (0.25H,
d, J 12.5, OCHH, minor), 1.41 (3H, septet, J 7.2, SiCH(CH3)2),
1.18 (18H, pseudo t, J 7.2, SiCH(CH3)2), 0.98 (9H, s, SitBu),
0.24 (3H, s, Si(CH3)2), -0.71 (3H, s, Si(CH3)2); dC (100 MHz,
CDCl3) 193.76 (quat., C O), 185.60 (quat., C O), 138.53 (ipso,
Ar), 129.62 (CH, Ar), 129.41 (CH, Ar), 129.14 (CH, Ar), 128.95
(CH, Ar), 128.54 (CH, Ar), 128.51 (CH, Ar), 128.32 (CH, Ar),
127.70 (CH, Ar), 121.93 (quat.), 118.11 (quat.), 82.02 (CH), 81.25
(CH), 67.88 (quat./CH2), 64.91 (quat./CH2), 64.01 (quat./CH2),
27.81 (CH/CH3), 27.39 (CH/CH3), 19.67 (CH3), 19.33 (CH3),
19.20 (CH3), 19.15 (CH3), 19.07 (quat.), 15.46 (CH/CH3),
12.37 (CH/CH3), 12.29 (CH/CH3), -3.08 (CH3), -4.40 (CH3);
dSi (99 MHz, CDCl3), 4.22 (s, TBS), 3.31 (s, TBS), 2.51
(s, TIPS).
(R)-Dipropargylic ether 8 (R1 = Ph, R2 = Si(iPr)3, R3 = Ph)
A flask was charged with (R)-dipropargylic ether 8 (R1 = H, R2 =
Si(iPr)3, R3 = Ph) (0.500 g, 1.534 mmol), PhI (0.21 cm3, 1.84 mmol,
1.2 eq.) and Et3N (6 cm3). To this mixture was added PdCl2(PPh3)2
(21.5 mg, 0.0306 mmol, 0.02 eq.) and after 5 min CuI (2.9 mg,
0.0153 mmol, 0.01 eq.) was added and the reaction heated to 50 ◦C
for 20 h. The reaction mixture was then filtered and the remaining
amine removed in vacuo. Purification by column chromatography
(EtOAc/hexane 0 to 0.5%) afforded a light yellow oil (0.5874 g,
1.461 mmol, 95%); [a]2D8 +45.0 (c 1.088, CHCl3); m/z 403.2 [M +
1]+, 425.2 [M + 23]+; nmax 2942, 2890, 2864, 1762, 1644, 1450 and
1240 cm-1; (Found (ESI): 425.2265 M + Na C27H34NaOSi requires
425.2271); dH (400 MHz, CDCl3) 7.50 (2H, d, J 7.50, Ar), 7.49–
7.45 (2H, m, Ar), 7.40–7.31 (6H, m, Ar), 5.56 (1H, s, ArCH), 4.67
(1H, d, J 15.7, OCHH), 4.54 (1H, d, J 15.7, OCHH), 1.12 (21H,
m, Si(CH(CH3)3); dC (100 MHz, CDCl3) 138.00 (ipso, Ar), 131.83
(CH, Ar), 128.47 (CH, Ar), 128.45 (CH, Ar), 128.42(CH, Ar),
128.25 (CH, Ar), 127.84 (CH, Ar), 122.65 (ipso, Ar), 103.87 (quat.,
C
C
C), 90.05 (quat., C C), 86.54 (quat., C C), 84.07 (quat.,
C) 70.57 (CH(OH)) 56.04 (OCH2) 18.63 (Si(CH(CH3)2)3),
11.20 (Si(CH(CH3)2)3); dSi (99 MHz, CDCl3) -1.53 (s).
Ruthenium cyclone complex 15b
A pressure tube was charged with (R)-dipropargylic ether 8 (R1 =
TMS, R2 = Si(tBu)Me2, R3 = Ph), (1.000 g, 2.808 mmol 3 eq.),
acetonitrile (10 cm3) and Ru3(CO)12 (0.5986 g, 0.9363 mmol, 1
eq.) and purged under a steady stream of N2. The tube was then
sealed and heated to 100 ◦C. After 2 d the reaction mixture
was cooled, carefully depressurised and the solvent removed in
vacuo. The resulting black semisolid was dissolved in DCM (4
cm3) and filtered through a cotton wool plug and loaded onto
a short silica column (EtOAc/hexane 0 to 10%) to afford a
yellow solid (0.4522 g, 0.7947 mmol, 28%). The metal complex
was characterised as a mixture of two diastereoisomers in an
approximate ratio of 3 : 1; m/z 571.0 [M + 1]+; (Found (ESI):
571.0918 M + H C25H33O5RuSi2 requires 571.0911); nmax 2951,
2927, 2894, 2881, 2853, 2077, 2019, 1197 and 1632 cm-1; dH
(400 MHz, CDCl3) 7.49–7.44 (1.5H, m, Ar) 7.41–7.36 (3H, m,
Ar), 7.20–7.16 (0.5H, m, Ar), 5.85 (1H, s, ArCH), 4.98 (1H, d,
J 12.1), 4.85 (0.75H, dd, 2.3, 12.8, OCH2, major) 4.90 (0.25H,
d, J 12.5, OCH2, minor), 0.99 (6H, s, SitBu), 0.62 (3H, s,
Si(CH3)2), 0.34 (3H, s, Si(CH3)2), 0.30 (6H, s, Si(CH3)3), 0.22
(3H, s, Si(CH3)2), -0.75 (3H, s, Si(CH3)2); dC (100 MHz, CDCl3)
193.80 (quat., C O), 185.80 (quat., C O), 138.75 (ipso, Ar),
138.48 (ipso, Ar), 129.59 (CH, Ar), 129.41 (CH, Ar), 129.14
(CH, Ar), 128.42 (CH, Ar), 128.32 (CH, Ar), 127.67 (CH, Ar),
119.91 (quat.), 119.29 (quat.), 117.12 (quat.), 82.56 (CH, ArCH),
81.33 (CH, ArCH), 67.13 (quat./CH2), 66.92 (quat./CH2),
64.33 (quat./CH2), 64.20 (quat./CH2), 27.67 (CH/CH3),
27.25 (CH/CH3), 19.00 (quat./CH2), 17.74 (quat./CH2), 14.10
(CH/CH3), -0.28 (CH/CH3), -0.45 (CH/CH3), -3.15 (CH/CH3),
-4.66 (CH3), -4.78 (CH3); dSi (99 MHz, CDCl3), 4.03 (s, TBS), 3.20
(s, TBS), -3.72 (s, TMS).
Ruthenium cyclone complex 15c
A pressure tube was charged with (R)-dipropargylic ether 8 (R1 =
Ph, R2 = Si(tBu)Me2, R3 = Ph), (0.250 g, 0.6944 mmol 2 eq.),
acetonitrile (1.5 cm3) and Ru3(CO)12 (0.2219 g, 0.3472 mmol,
1 eq.) and purged under a steady stream of N2. The tube was
then sealed and heated to 100 ◦C. After 3 d the reaction mixture
was cooled, carefully depressurised and the solvent removed in
vacuo. The resulting black semisolid was dissolved in DCM (2
cm3) and filtered through a cotton wool plug and loaded onto
a short silica column (EtOAc/hexane; 0 to 10%) to afford a
yellow solid (0.1799 g, 0.3139 mmol, 45%). The metal complex
was characterised as a mixture of two diastereoisomers in an
approximate ratio of 4 : 1; m/z 575.0 [M + 1]+; (Found (ESI):
M + H 575.0832 C28H29O5RuSi requires 575.0829); (Found (ESI):
M + Na 597.0654 C28H28NaO5RuSi requires 597.0649); nmax 2952,
2928, 2883, 2854, 2064, 2020 and 2009 cm-1; dH (400 MHz, CDCl3)
7.87 (0.3H, d, J 7.3, Ar), 7.83 (1.6H, d, J 7.3, Ar), 7.54–7.51 (1.5H,
m, Ar), 7.44–7.35(5H, m, Ar), 7.32–7.24 (1.5H, m, Ar) 5.90 (1H, s,
ArCH), 5.40 (0.85H, dd, J 0.9, 12.9, OCHH, major), 5.34 (0.15H,
dd, J 1.4, 12.5, OCHH, minor) 5.23 (0.15H, d, J 12.5, OCHH,
minor), 5.15 (0.85H, dd, J 2.4, 12.9, OCHH, major), 1.03(7.65H,
s, SitBu, major), 0.66 (1.35H, s, SitBu, minor), 0.35 (2.35H, s,
Si(CH3)2, major), 0.33 (0.65H, s, Si(CH3)2, minor), -0.03(0.5H, s,
Si(CH3), minor), -0.74 (2.5H, s, Si(CH3), major); dC (100 MHz,
CDCl3) 193.78 (quat, C O), 193.72 (quat C O), 180.08 (quat,
142 | Org. Biomol. Chem., 2012, 10, 134–145
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C
O), 138.32 (ipso, Ar), 138.08 (ipso, Ar), 132.20 (ipso, Ar),
mixture of two diastereoisomers in an approximate ratio of 7 : 3;
m/z 613.1 [M + 1]+; (Found (ESI): MH+ 613.1375 C28H39O5RuSi2
requires 613.1381); nmax 2943, 2891, 2864, 2047 and 1195 cm-1;
dH (400 MHz, CDCl3) 7.48–7.43 (1.5H, m, Ar), 7.39–7.33 (3H,
m, Ar), 7.19–7.14 (0.5H, m, Ar), 5.92 (0.3H, s, ArCH, minor),
5.86 (0.7H, s, ArCH, major), 5.00 (0.7H, s, J 12.8, OCHH,
major), 4.92 (0.3H, d, J 12.5, OCHH, minor), 4.83 (0.7H, dd,
J 2.1, J 12.8, OCHH, major), 4.78 (0.3H, d, J 12.5, OCHH,
minor), 1.13–1.02 (11H, m, SiiPr), 0.99–0.94 (5H, m, SiiPr), 0.90–
0.86 (5H, m, SiiPr), 0.33 (2.7H, s, TMS, minor), 0.29 (6.3H,
s, TMS, major); dC (100 MHz, CDCl3) 193.85 (quat., C O),
185.98 (quat., C O), 185.91 (quat., C O), 138.44 (quat., Ar),
138.79(quat., Ar), 138.67 (quat., Ar), 129.49 (CH, Ar), 129.38
(CH, Ar), 128.26 (CH, Ar), 128.13 (CH, Ar), 127.43 (CH, Ar),
119.85 (quat.), 118.49 (quat.), 116.93 (quat.), 114.58 (quat.), 82.90
(ArCH), 81.69 (ArCH), 67.12 (quat.), 66.64 (quat.), 66.58 (quat.),
65.77 (quat.), 64.43 (quat.), 64.05 (quat.), 19.69 (CH3/CH), 19.18
(CH3/CH), 19.12 (CH3/CH), 19.00 (CH3/CH), 17.68 (CH3/CH),
12.80 (CH3/CH), 12.76 (CH3/CH) 12.27(CH3/CH), -0.42 (CH3,
TMS), -0.51 (CH3, TMS); dSi (99 MHz, CDCl3), 4.22 (s, TBS),
3.31 (s, TBS), 2.51 (s, TIPS).
132.15 (ipso, Ar), 129.78 (CH, Ar), 129.56 (CH, Ar), 129.19 (CH,
Ar), 128.88 (CH, Ar), 128.86 (CH, Ar), 128.54 (CH, Ar), 128.38
(CH, Ar), 127.79 (CH, Ar), 127.76 (CH, Ar), 127.13 (CH, Ar),
127.11 (CH, Ar), 115.10 (quat.), 113.14 (quat.), 82.62 (CH), 81.46
(CH), 75.53 (quat./CH2), 67.63 (quat./CH2), 67.30 (quat./CH2),
62.34 (quat./CH2), 34.64 (quat./CH2), 31.56 (quat./CH2),
27.72 (CH/CH3), 27.26 (CH/CH3), 25.26 (quat./CH2), 22.63
(quat./CH2), 19.00 (quat./CH2), 14.10 (CH3), -2.96 (CH3), -4.64
(CH3), -4.72 (CH3, SiCH3); dSi (99 MHz, CDCl3), 4.22 (s, TBS),
3.31 (s, TBS), 2.51 (s, TIPS).
Ruthenium cyclone complex 15e
A pressure tube was charged with (R)-dipropargylic ether 8 (R1 =
Ph, R2 = Si(iPr)3, R3 = Ph) (0.3906 g, 0.9716 mmol, 2 eq.),
acetonitrile (3 cm3) and Ru3(CO)12 (0.3104 g, 0.4858 mmol, 1
eq.) and purged under a steady stream of N2. The tube was
then sealed and heated to 100 ◦C. After 2 d the reaction mixture
was cooled, carefully depressurised and the solvent removed in
vacuo. The resulting black semisolid was dissolved in DCM (2
cm3) and filtered through a cotton wool plug and loaded onto a
short silica column (EtOAc/hexane 0 to 5%) to afford a yellow
solid (Rf 0.2, 0.1994 g, 0.3242 mmol, 33%). Found to be a 3 : 2
mixture of diastereoisomers; m/z 617.1 [M + 1]+; (Found (ESI):
M + H 617.1307 C31H35O5RuSi requires 617.1300); (Found (ESI):
M + Na 639.1128 C31H34NaO5RuSi requires 639.1119); nmax 2944,
2864, 2076, 2001 and 1636 cm-1; dH (400 MHz, CDCl3) 7.87–
7.81 (2H, m, Ar), 7.53–7.48 (1.3H, m, Ar), 7.41–7.35 (4.5H, m,
Ar), 7.31–7.23 (2.2H, m, Ar), 5.97 (0.4H, s, ArCH, minor), 5.92
(0.6H, s, ArCH, major), 5.43 (0.6H, d, J 12.8, OCHH, major),
5.27 (0.4H, d, J 12.4, OCHH, minor), 5.21 (0.4H, d, J 12.4,
OCHH, minor), 5.15 (0.6H, dd, J 2 Hz, 12.8, OCHH, major), 1.10
(7.5H, s, SiCH(CH3)2), 1.05 (3.75H, d, J 7.2, SiCH(CH3)2), 1.00
(3.75H, d, J 7.2, SiCH(CH3)2), 0.94 (6H, d, J 6.0, SiCH(CH3)2); dC
(100 MHz, CDCl3) 193.89 (quat., C O), 193.80 (quat., C O),
180.18 (quat., C O), 179.75 (quat., C O), 138.44 (ipso, Ar),
137.96 (ipso, Ar), 132.22 (ipso, Ar), 132.20 (ipso, Ar), 129.67
(CH, Ar), 129.53 (CH, Ar), 129.06 (CH, Ar), 128.87 (CH, Ar),
128.39 (CH, Ar), 128.22 (CH, Ar)127.73 (CH, Ar), 127.54(CH,
Ar), 127.19 (CH, Ar), 127.16 (CH, Ar), 113.27 (quat.), 113.11
(quat.), 107.34 (quat.), 83.00 (ArCH), 81.85(ArCH), 75.36 (quat.),
67.13 (quat.), 67.08 (quat.), 61.88 (quat.), 19.76 (CH3/CH), 19.24
(CH3/CH), 19.18 (CH3/CH), 19.11 (CH3/CH), 12.86 (CH3/CH),
12.78 (CH3/CH); dSi (99 MHz, CDCl3), 4.22 (s, TBS), 3.31 (s,
TBS), 2.51 (s, TIPS).
Ruthenium cyclone complex 15f
A pressure tube was charged with (R)-dipropargylic ether 8 (R1 =
TBDMS, R2 = Si(iPr)3, R3 = Ph) (0.3331 g, 0.7571 mmol 3 eq.),
acetonitrile (3 cm3) and Ru3(CO)12 (0.1613 g, 0.2523 mmol, 1
eq.) and purged under a s◦teady stream of N2. The tube was then
sealed and heated to 100 C. After 3 d the reaction mixture was
cooled, carefully depressurised and the solvent removed in vacuo.
The resulting black semisolid was dissolved in DCM (2 cm3) and
filtered through a cotton wool plug and loaded onto a short silica
column (EtOAc/hexane 0 to 5%) to afford a sticky red solid (0.104
g, 0.1596 mmol, 21%). The metal complex was characterised as a
mixture of two diastereoisomers in an approximate ratio of 3 : 2;
m/z 655.1 [M + 1]+; (Found (ESI): M + H 655.1850 C31H45O5RuSi2
requires 655.1851); nmax 2945, 2927, 2890, 2863, 2079, 2022, 2002
and1620 cm-1; dH (400 MHz, CDCl3) 7.47–7.43 (1 H, m, Ar),
7.39–7.34 (3H, m, Ar), 7.20–7.16 (1H, m, Ar), 5.93 (0.45H, s,
ArCH, minor), 5.86 (0.55H, s, ArCH, major), 5.01 (0.55H, dd, J
0.8, 12.8, OCHH, major), 4.93 (0.45H, dd, J 1.2, 12.5, OCHH,
minor), 4.85 (0.55H, dd, J 2.2, 12.8, OCHH, major), 4.78 (0.45H,
d, J 12.5, OCHH, minor), 1.19–0.6 (30H, m, SiiPr3 and SitBu),
0.43 (1.35H, s, SiCH3, minor), 0.41 (1.65H, s, SiCH3, major),
0.12 (1.35H, s, SiCH3, minor), 0.10 (1.65H, s, SiCH3, major); dC
(100 MHz, CDCl3) 193.84 (quat., C O), 185.43 (quat., C O),
185.34 (quat., C O), 138.68 (ipso, Ar), 138.31 (ipso, Ar), 129.53
(CH, Ar), 129.37 (CH, Ar), 129.00 (CH, Ar), 128.56 (CH, Ar),
128.51 (CH, Ar), 128.34 (CH, Ar), 128.14 (CH, Ar), 127.54
(CH, Ar), 127.39 (CH, Ar), 121.64 (quat.), 117.79 (quat.), 82.74
(ArCH), 81.70 (ArCH), 66.97 (quat./CH2), 66.85 (quat./CH2),
66.82 (quat./CH2), 65.65 (quat./CH2), 63.91 (quat./CH2), 61.87
(quat./CH2), 27.42 (CH3), 27.37 (CH3), 19.67 (CH3/CH), 19.20
(CH3/CH), 19.03 (CH3/CH), 18.84 (quat.), 18.78 (quat.), 18.56
(CH3/CH), 12.76 (CH3/CH), 12.63 (CH3/CH) 11.20 (CH3/CH),
11.12 (CH3/CH), 10.95 (CH3/CH), -4.34 (CH3, TBS), -4.70
(CH3, TBS) -4.81; dSi (99 MHz, CDCl3), 4.22 (s, TBS), 3.31 (s,
TBS), 2.51 (s, TIPS).
Ruthenium cyclone complex 15d
A pressure tube was charged with (R)-dipropargylic ether 8 (R1 =
TMS, R2 = Si(iPr)3, R3 = Ph) (0.400 g, 1.005 mmol 3 eq.),
acetonitrile (3 cm3) and Ru3(CO)12 (0.2141 g, 0.3350 mmol, 1
eq.) and purged under a s◦teady stream of N2. The tube was then
sealed and heated to 100 C. After 3 d the reaction mixture was
cooled, carefully depressurised and the solvent removed in vacuo.
The resulting black semisolid was dissolved in DCM (2 cm3) and
filtered through a cotton wool plug and loaded onto a short silica
column (EtOAc/hexane 0 to 5%) to afford a yellow solid (0.1542
g, 0.2524 mmol, 25%). The metal complex was characterised as a
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Reduction of acetophenone using iron catalysts and FA/TEA
Notes and references
Complex 7a (7.8 mg, 19.1 mmol), trimethylamine-N-oxide (2.1
mg, 18.9 mmol) and acetophenone (23.0 mg, 0.191 mmol) were
dissolved in 5 : 2 formic acid : triethylamine (0.2 cm3) and heated
1 (a) B. L. Conley, M. K. Pennington-Boggio, E. Boz and T. J. Williams,
Chem. Rev., 2010, 110, 2294–2312; (b) Y. Blum and Y. Shvo, J.
Organomet. Chem., 1985, 282, C7–C10; (c) Y. Shvo, D. Czarkie and
Y. Rahamim, J. Am. Chem. Soc., 1986, 108, 7400–7402.
2 (a) O. Pa`mies and J.-E. Ba¨ckvall, Chem. Rev., 2003, 103, 3247–3262;
(b) B. A. Persson, A. I. E. Larsson, M. Le Ray and J.-E. Ba¨ckvall, J. Am.
Chem. Soc., 1999, 121, 1645–1650; (c) O. Pamies and J.-E. Ba¨ckvall, J.
Org. Chem., 2001, 66, 4022–4025.
3 (a) L. K. Thale´n, D. Zhao, J.-B. Sortais, J. Paetzold, C. Hoben and
J.-E. Ba¨ckwall, Angew. Chem., Int. Ed., 2009, 15, 3403–3410; (b) J. S.
M. Samec and J.-E. Ba¨ckvall, Chem.–Eur. J., 2002, 8, 2955–2961; (c) J.
Paetzold and J.-E. Ba¨ckwall, J. Am. Chem. Soc., 2005, 127, 17620–
17621.
4 (a) J. S. M. Samec, J.-E. Ba¨ckvall, P. G. Andersson and P. Brandt, Chem.
Soc. Rev., 2006, 35, 237–248; (b) S. E. Clapham, A Hadzovic and R.
H. Morris, Coord. Chem. Rev., 2004, 248, 2201–2237; (c) C. P. Casey,
S. W. Singer, D. R. Powell, R. K. Hayashi and M. Kavana, J. Am.
Chem. Soc., 2001, 123, 1090–1100; (d) J. B. Johnson and J.-E. Ba¨ckvall,
J. Org. Chem., 2003, 68, 7681–7684; (e) Comas-Vives, G. Ujaque and
A. Lledo´s, Organometallics, 2007, 26, 4135–4144; (f) C. P. Casey, S. E.
Beetner and J. B. Johnson, J. Am. Chem. Soc., 2008, 130, 2285–2295.
5 (a) M. Yamakawa, I. Yamada and R. Noyori, Angew. Chem., Int. Ed.,
2001, 40, 2818–2821; (b) C. P. Casey and J. B. Johnson, J. Org. Chem.,
2003, 68, 1998–2001; (c) S. Hashiguchi, A. Fujii, K. J. Haack, K.
Matsumura, T. Ikariya and R. Noyori, Angew. Chem., Int. Ed. Engl.,
1997, 36, 288–290; (d) F. K. Cheung, C. Lin, F. Minissi, A. Lorente
Criville´, M. A. Graham, D. J. Fox and M. Wills, Org. Lett., 2007, 9,
4659–4662; (e) A. M. Hayes, D. J. Morris, G. J. Clarkson and M. Wills,
J. Am. Chem. Soc., 2005, 127, 7318–7319.
◦
at 28 C for 18 h. The reaction was monitored over time by GC
(Chrompac cyclodextrin-b-236 M 50 M column, T = 130 ◦C,
inj T = 220 ◦C, det T = 220 ◦C, 15 psi He carrier gas). RT:
Acetophenone: 13.4 min. 1-Phenylethyl formate: 15.1 (S), 15.5
(R) min. 1-Phenylethanol: 17.4 (R), 18.0 (S) min.1 The above
procedure was repeated using other complexes, temperatures
and reaction times. The product configurations were assigned
by comparison to previously quoted data1 and use of authentic
reference samples.
Reduction of acetophenone using iron catalysts and iPrOH
Complex 7a (7.8 mg, 19.1 mmol), trimethylamine-N-oxide (2.1
mg, 18.9 mmol) and acetophenone (23.0 mg, 0.◦191 mmol) were
i
dissolved in PrOH (0.96 cm3) and heated at 28 C for 18 h. The
reaction was monitored over time by GC (Chrompac cyclodextrin-
b-236 M 50 M column, T = 130 ◦C, inj T = 220 ◦C, det T =
220 ◦C, 15 psi He carrier gas). RT: Acetophenone: 13.4 min. 1-
Phenylethanol: 17.4 (R), 18.0 (S) min.1 The above procedure was
repeated using other temperatures and concentrations.
6 C. P. Casey, T. E. Vos, S. W. Singer and H. A. Guzel, J. Org. Chem.,
2002, 21, 5038–5046.
7 (a) H.-J. Kno¨lker, E. Baum, H. Goesmann and R. Klauss, Angew.
Chem., Int. Ed., 1999, 38, 2064–2066; (b) H. H. Zhang, D. Z. Chen, Y.
H. Zhang, G. Q. Zhang and J. B. Liu, Dalton Trans., 2010, 39, 1972–
1978; (c) G. N. Schrauzer, J. Am. Chem. Soc., 1959, 81, 5307–5310.
8 (a) C. P. Casey and H. Guan, J. Am. Chem. Soc., 2007, 129, 5816–5817;
(b) C. P. Casey and H. Guan, J. Am. Chem. Soc., 2009, 131, 2499–2507;
(c) H. Zhang, D. Chen, Y. Zhang, G. Zhang and J. Liu, Dalton Trans.,
2010, 39, 1972–1978.
9 (a) M. G. Coleman, A. N. Brown, B. A. Bolton and H. Guan, Adv.
Synth. Catal., 2010, 352, 967–970; (b) S. A. Moyer and T. W. Funk,
Tetrahedron Lett., 2010, 51, 5430–5433; (c) M. K. Thorson, K. L.
Klinkel, J. Wang and T. J. Williams, Eur. J. Inorg. Chem., 2009, 295–302.
10 T. C. Johnson, G. J. Clarkson and M. Wills, Organometallics, 2011, 30,
1859–1868.
General ruthenium-hydride synthesis prior to use in reductions12
To Ru(TMS-TMS) (22.6 mg, 0.05 mmol) in THF (1 cm3) was
added aqueous sodium hydroxide (0.5 cm3, 1 M, 0.50 mmol) and
stirred for 2.5 h. An excess of H3PO4 (0.3 cm3) was then added and
the reaction extracted using Et2O (3 ¥ 10 cm3), dried over MgSO4
and the solvent removed all under a nitrogen atmosphere to afford
the hydride species as a yellow oil which was used immediately
without further purification. Selected data for each hydride this
formed is given below.
11 (a) A. J. Pearson and R. J. Shively Jr, Organometallics, 1992, 11, 4096–
4104; (b) A. J. Pearson and R. J. Shively Jr, Organometallics, 1994, 13,
578–584.
Reduction of acetophenone using ruthenium hydride complexes
12 (a) Y. Yamamoto, K. Yamashita and M. Nakamura, Organometallics,
2010, 29, 1472–1478; (b) A. Berkessel, S. Reichau, A. van der Ho¨h, N.
Leconte and J.-M. Neudo¨rfl, Organometallics, 2011, 30, 3880–3887.
13 (a) N. A. Bailey, V. S. Jassal, R. Vefghi and C. White, J. Chem. Soc.,
Dalton Trans., 1987, 2815–2822; (b) J. H. Eekhof, H. Hogeveen and R.
M. Kellogg, Chem. Commun., 1977, 705; (c) H.-J. Kno¨lker, E. Baum
and J. Heber, Tetrahedron Lett., 1992, 36, 7647–7650.
Method A: iPrOH. The ruthenium hydride (0.01 mmol,
0.5 mol%) w◦as dissolved in anhydrous iPrOH (10 cm3) and
heated at 60 C over 30 min. Acetophenone (0.22 cm3, 0.2266
g, 1.89 mmol) was then added and the reaction stirred at 60 C
over 7 days and the reaction was monitored by GC.
◦
14 (a) K. Matsumura, S. Hashiguchi, T. Ikariya and R. Noyori, J. Am.
Chem. Soc., 1997, 119, 8738–8739; (b) D. J. Morris, A. M. Hayes and
M. Wills, J. Org. Chem., 2006, 71, 7035–7044; (c) J. A. Marshall, P
Eidam and H. S. Eidam, J. Org. Chem., 2006, 71, 4840–4844.
15 Y. Yamamoto, Y. Miyabe and K. Itoh, Eur. J. Inorg. Chem., 2004,
3651–3661.
Method B: HCOOH/Et3N. The ruthenium hydride
(0.02 mmol, 0.25 mol%) was dissolved in formic acid triethylamine
complex (5 : 2, 4 cm3) and heated at 60 ◦C over 30 min.
Acetophenone (0.92 cm3, 0.9476 g, 7.90 mmol) was then added
and the reaction stirred at 60 ◦C over 7 days and the reaction was
monitored by GC.
16 O. Hamed, P. M. Henry and D. P. Becker, Tetrahedron Lett., 2010, 51,
3514–3517.
17 M. M. Midland, A. Tramontano, A. Kazubski, R. S. Graham, D.
J. S. Tsai and D. B. Cardin, Tetrahedron, 1984, 40, 1371–1380. (R)-
Alpine borane is derived from (+)-a-pinene and gives the (R)-reduction
product illustrated.
18 (a) G. Bauer and K. A. Kirchner, Angew. Chem., Int. Ed., 2011, 50,
5798–5800; (b) A. Naik, T. Maji and O. Reiser, Chem. Commun., 2010,
46, 4475–4477; (c) R. H. Morris, Chem. Soc. Rev., 2009, 38, 2282–2291;
(d) S. Enthaler, K. Junge and M. Beller, Angew. Chem., Int. Ed., 2008,
47, 3317–3321; (e) C. Sui-Seng, F. Freutel, A. J. Lough and R. H.
Morris, Angew. Chem., Int. Ed., 2008, 47, 940–943; (f) A. Mikhailine,
Acknowledgements
We thank EPSRC for financial support of JEDM and
JPH (EP/F019424) and TCJ (Supergen XIV H-delivery
EP/G01244X/1). JG was an MChem project student supported
by Warwick University.
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A. J. Lough and R. H. Morris, J. Am. Chem. Soc., 2009, 131, 1394–
1395; (g) N. Meyer, A. J. Lough and R. H. Morris, Chem.–Eur. J.,
2009, 15, 5605–5610; (h) J.-S. Chen, L.-L. Chen, Y. Xing, G. Chen,
W.-Y. Shen, Z.-R. Dong, Y.-Y. Li and J.-X. Gao, Acta. Chim. Sin.
(Huaxue Xuebao), 2004, 62, 1745–1750; (i) S. Zhou, S. Fleischer, K.
Junge, S. Das, D. Addis and M. Beller, Angew. Chem., Int. Ed., 2010, 49,
8121–8125; (j) A. A. Mikhailine and R. H. Morris, Inorg. Chem., 2010,
49, 11039–11044; (k) P. O. Lagaditis, A. J. Lough and R. H. Morris,
Inorg. Chem., 2010, 49, 10057–10066; (l) K. Junge, K. Schroder and M.
Beller, Chem. Commun., 2011, 47, 4849–4859; (m) S. Zhou, S. Fleischer,
K. Junge and M. Beller, Angew. Chem., Int. Ed., 2011, 50, 5120–
5124.
19 C. J. Taylor, M. Motevalli and C. J. Richards, Organometallics, 2006,
25, 2899–2902.
20 T. Schubert, W. Hummel, M.-R. Kula and M. Mu¨ller, Eur. J. Org.
Chem., 2001, 4181–4187.
21 L. Xu, M. R. Muller, X. Yu and B.-Q. Zhu, Synth. Commun., 2009, 39,
1611–1625.
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The Royal Society of Chemistry 2012
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