Racemisation of 1-arylethylamines with Shvo-type organoruthenium catalysts

Article abstract of DOI:10.1055/s-0033-1341228

Variation of the electronic nature of the tetraphenylcyclopentadienone ligand in organoruthenium complexes influences their utility for racemisation of model chiral amines. Our study highlights the need to balance reactivity and selectivity in the design of racemisation catalysts. Electron-poor Shvo-type catalysts are, at first sight, more effective for racemisation, but yield more by-product; electron-rich complexes are less proficient at racemisation, but lead to less by-product.

Full text of DOI:10.1055/s-0033-1341228

LETTER
▌1391
lRettaercemisation of 1-Arylethylamines with Shvo-type Organoruthenium
Catalysts
Racemisation of 1-Arylethylamines
James F. S. Apps,a Andrew G. Livingston,b Mark R. Parrett,a Ryan J. Pounder,a Paul C. Taylor,*a Andrew R. Turnera
a
Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK
Fax +44(24)7652 4112; E-mail: p.c.taylor@warwick.ac.uk
b
Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Received: 18.02.2014; Accepted after revision: 24.03.2014
in compounds 1, with the aim of determining what fea-
Abstract: Variation of the electronic nature of the tetraphenyl-
tures of Shvo-type complexes 1 lead to effective racemi-
cyclopentadienone ligand in organoruthenium complexes influenc-
sation catalysts. Herein, we report the synthesis and full
characterisation of complexes 1a–1d and 1f–1j (the pub-
es their utility for racemisation of model chiral amines. Our study
highlights the need to balance reactivity and selectivity in the design
of racemisation catalysts. Electron-poor Shvo-type catalysts are, at lished characterisation data for 1a are in our opinion not
consistent with the proposed structure6) and a compara-
tive study of the racemisation of phenylethylamine 5.
first sight, more effective for racemisation, but yield more by-prod-
uct; electron-rich complexes are less proficient at racemisation, but
lead to less by-product.
Synthesis of the desired tetraarylcyclopentadienones 4
Key words: racemisation, amine, alcohol, organoruthenium, DFT
(Scheme 1) was achieved by adaptation of the literature
procedure.13 The appropriate benzoins 2 and dibenzyl ke-
tones 3 were either purchased or prepared using literature
Racemisation reactions are extremely important in indus-
methods. The methoxy group was an obvious choice of π-
try,1 in particular in combination with resolution process-
electron-donating substituent and we thus selected bromo,
es.2 Dynamic kinetic resolution (DKR)3 has attracted a
rather than chloro, as a sterically equivalent electron-with-
great deal of interest since early demonstrations that or-
drawing analogue.
ganometallic catalysts for racemisation are compatible
with enzymatic resolution processes.4
X
X
O
O
X
While the DKR protocol has found wide application to
chiral alcohols as substrates,3 there are fewer accounts of
the DKR of amines,5,6 which generally require more forc-
ing conditions that are less compatible with enzymatic
resolution catalysts.7 Racemisation catalysts for DKR of
amines have exploited four different transition metals,
palladium, ruthenium, nickel and iridium.8 Catalysts
based on the first three metals have generally been used in
conjunction with Candida antarctica lipase B, which can
withstand the elevated temperatures needed for the race-
misation.8 On the other hand, in a major breakthrough,
Blacker et al. reported that an organoiridium complex
could be used at just 40 ºC and so with a less exotic lipase
from Candida rugosa.9 More recently, the use of radicals
to promote low temperature racemisation was reported.10
An alternative approach, from our own laboratories, is to
engineer the separation of the racemisation and resolution
processes.11
X
KOH
2
EtOH
+
O
O
80 ºC
15 min
Y
Y
4
Y
Y
3
Scheme 1
Adaptation of the literature method for preparation of the
Shvo catalyst 1e gave access to the target catalysts 1
(Scheme 2).14 The yields ranged from 42% to 76%; all of
the complexes shown were prepared in two or three steps
from simple, commercially available starting materials,
with little or no purification necessary.
One of the most widely used catalysts for racemisation of
alcohols and of amines is the Shvo catalyst 1e, which was
adopted and subsequently developed by the Bäckvall
group12 who also showed that the tetramethoxy analogue
1a can be used advantageously for DKR of 1-phenylethyl-
amine.6 Our study aimed to systematically vary the elec-
tronic nature of the tetraphenylcyclopentadienone ligand
Ar1
Ar1
O
O
O
H
Ar1
Ar1
Ar2
Ar2
Ru3(CO)12
Ar2
Ar2
Ar1
Ar1
H
MeOH, 90 °C
72 h
Ru Ru
Ar2
Ar2
OC
CO
OC CO
4
1
Ar1 = 4-C6H4X; Ar2 = 4-C6H4Y
a X = Y = OMe
e X = Y = H
f X = Br, Y = OMe
g X = Br, Y = H
h X = H, Y = Br
j X = Y = Br
b X = OMe, Y = H
c X = H, Y = OMe
b X = OMe, Y = Br
SYNLETT 2014, 25, 1391–1394
Advanced online publication: 08.05.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1341228; Art ID: ST-2014-D0137-L
© Georg Thieme Verlag Stuttgart · New York
Scheme 2

1392
J. F. S. Apps et al.
LETTER
The aim of our study was correlation of the effect of sub-
stitution of 1 with the outcome of racemisation of the
model amine substrate (S)-1-phenylethylamine [(S)-5].
The Bäckvall group has shown that by-products can be
formed during the racemisation process, by reaction of the
starting amine 5 with the intermediate imine 6 (Scheme
3). Thus, we used GC (Varian CP-Chirasil-DEX CB 25 m
× 0.32 mm × 0.25 μm) to assay the proportions of each en-
antiomer of 5 and of by-products 7 and 8 by comparison
with authentic samples.
Table 1 Racemisation of Amine 5b: Enantiomeric Excess Values
and Yields of By-products
Entry
Complex 5 (%)
6 (%)
7 (%)
ee (%) of 5
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
97
90
95
89
80
82
85
77
72
2
8
1
2
2
3
4
4
4
5
6
28
25
26
23
22
19
23
20
19
3
8
16
14
11
18
22
NH2
NH
NH2
Ph
Ph
Ph
1g
1h
1j
(S)-5b
6
(R)-5b
+ 5
– NH3
N
Ph
HN
Ph
Ph
Ph
7
8
performed comparably with the all-methoxy complex 1a.
This suggests that substitution at the 3-position influences
the reactivity of the overall catalyst more strongly than
functionality located at the 2-position.
Scheme 3
The key results are that: all of catalysts 1 are effective for
racemisation of 5; as judged by disappearance of (S)-5, the Density functional theory (DFT) calculations were carried
tetrabromo analogue 1j is at first sight the most effective out to study the effect of substituents on the cyclopentadi-
of the analogues; unfortunately, catalyst 1j leads to low enone ring. The structures were optimised with con-
yields of racemised product 5, due to the leakage of the strained planar geometry in order to simulate the
amine to by-products 7 and 8; therefore, the tetramethoxy conformation of the ligand in the catalyst. The key cyclo-
analogue 1a could be considered to be the most useful cat- pentadienone bond lengths are summarised in Table 2. It
alyst. Indeed, this was the conclusion of the Bäckvall was found that 4-methoxyphenyl substitution at C3 and
group.6 Since, complex 1c can be synthesised in higher C4 had the greatest effect on the structure, clearly elongat-
yield in one less step than 1a and with no purification, for ing bonds C2–C3 and C4–C5 and shortening bonds C1–
practical applications use of 1c should certainly be consid- C2 and C1–C5 in complexes 4a and 4c more than 4b. A
ered.
less marked effect resulted from substitutions at C2 and
C5 and also from bromo substitution at C3 and C4.
We hypothesise that the electron-rich catalyst 1a slows
the racemisation but decreases the quantity of by-product
formed, because the ruthenium centre of the oxidative
species is less electrophilic, decreasing its aptitude for ox-
idising amine 5 to imine 6. The ruthenium hydride of the
reductive species is more nucleophilic, implying that the
reduction of 6 to 5 is more favourable. The electron-poor
catalyst 1j is expected to exhibit the opposite capabilities.
A more fine-grained analysis arises from comparison of
complexes 1d and 1f which possess both electron-donat-
ing and -withdrawing groups and of complexes 1b, 1c, 1g
and 1h that were useful in ascertaining whether substitu-
tion at the 2- or the 3-position has the greater influence on
the reactivity (Table 1).
Table 2 Bond Lengths (Å) of Cyclopentadienone Bonds in 4
Ligand C1–C2
C1–C5
C2–C3
C4–C5
4a
4b
4c
4d
4e
4f
1.52116
1.52486
1.52144
1.52513
1.52520
1.51958
1.52359
1.52559
1.52393
1.52125
1.52513
1.52142
1.52523
1.52514
1.51957
1.52347
1.52552
1.52380
1.38525
1.38090
1.38196
1.38146
1.37994
1.38298
1.38073
1.38018
1.38103
1.38247
1.38099
1.38188
1.38136
1.37983
1.38288
1.38063
1.38008
1.38094
4g
Overall, the data show that there is not a large variation in
ee, with a range of 19% to 28% across the nine complexes 4h
tested. A greater difference is seen in the by-product for-
mation, with a range of 3% to 28% total yield of 7 and 8
4j
observed. Complex 1d (entry 4), with methoxy function-
ality in the 2-positions and the bromo groups in the 3-po-
sitions, gave results similar to the all-bromo complex 1j.
Catalyst 1f (entry 6), which is bromo functionalised in the
2-positions and has methoxy groups in the 3-positions,
This observation is confirmed by comparison of catalysts
1b, 1c, 1g and 1h (entries 2, 3, 7, and 8). The 3-substituted
complexes 1c and 1h do give similar results to their re-
spective tetrasubstituted catalysts 1a and 1j, whereas cat-
alysts 1b and 1g, functionalised in the 2-positions, exhibit
Synlett 2014, 25, 1391–1394
© Georg Thieme Verlag Stuttgart · New York

LETTER
Racemisation of 1-Arylethylamines
1393
behaviour similar to that of parent complex 1e. While not Studies on the importance of the position of the functional
completely conclusive, this data indicates that substitution groups on the ligand have highlighted that the 3-position
at the 3- and 4-positions has the greater impact on the re- on the tetraphenylcyclopentadienone has a significantly
activity of the catalyst.
greater influence on the catalyst’s reactive behaviour than
the 2-position.
Our results indicate that complexes 1a (entry 1) and 1c
(entry 3) are potentially interesting for combination in a
DKR process. The low by-product formation exhibited by
these catalysts make them very attractive.
Acknowledgment
We thank the EPSRC for funding and Peter R. Taylor for advice.
Returning to the racemisation of alcohols, we explored
whether complex 13 exhibits similar substituent effects.
Complex 13 was, at the time, the most effective racemisa-
tion catalyst for alcohol 14,15 however it was supersed-
ed.16
References and Notes
(1) Ebbers, E. J.; Ariaans, G. J. A.; Houbiers, J. P. M.; Bruggink,
A.; Zwanenberg, B. Tetrahedron 1997, 28, 9417.
(2) Stecher, H.; Faber, K. Synthesis 1997, 1.
The key ligand of complex 13, iminocyclopentadienyl 15,
was synthesised in one step from methoxy-substituted cy-
clopentadienone 4 and isopropylamine (Scheme 4).13,17
An efficient synthesis of complex 17 was reported by Gib-
bins et al.18
(3) (a) Hoyos, P.; Pace, V.; Alcantara, A. R. Adv. Synth. Catal.
2012, 354, 2585. (b) Ahmed, M.; Kelly, T.; Ghanem, A.
Tetrahedron 2012, 68, 6781. (c) Cohen, D. T.; Eichman, C.
C.; Phillips, E. M.; Zarefsky, E. R.; Scheidt, K. A. Angew.
Chem. Int. Ed. 2012, 16, 7309. (d) Pellissier, H. Adv. Synth.
Catal. 2011, 353, 659. (e) Lee, J. H.; Han, K.; Kim, M.-J.;
Park, J. Eur. J. Org. Chem. 2010, 999. (f) Parvulescu, A.;
Janssens, J.; Vanderleyden, J.; de Vos, D. Top. Catal. 2010,
53, 931. (g) Kamaruddin, A. H.; Uzir, M. H.; Aboul-Enein,
H. Y.; Halim, H. N. Chirality 2009, 21, 449. (h) Kamal, A.;
Azhar, M. A.; Krishnaji, T.; Malik, M. S.; Azeeza, S. Coord.
Chem. Rev. 2008, 252, 569. (i) Pellissier, H. Tetrahedron
2008, 64, 1563. (j) Martin-Matute, B.; Bäckvall, J.-E. Curr.
Opin. Chem. Biol. 2007, 11, 226. (k) Turner, N. J. Curr.
Opin. Chem. Biol. 2004, 8, 114.
Ni-Pr
Ar
Ar
NHi-Pr
Ru3(CO)12
Ar
Ar
Ar
Ar
Ru
CHCl3
65 °C, 120 h
OC
Cl
OC
Ar
Ar
13 Ar = 4-MeOC6H4
17 Ar = Ph
15
Scheme 4
(4) Allen, J. V.; Williams, J. M. J. Tetrahedron Lett. 1996, 37,
1859.
(5) Reetz, M. T.; Schimossek, K. Chimia 1996, 50, 668.
(6) Paetzold, J.; Bäckvall, J.-E. J. Am. Chem. Soc. 2005, 127,
17620.
(7) Caddick, S.; Jenkins, K. Chem. Soc. Rev. 1996, 25, 447.
(8) Kim, Y.; Park, J.; Kim, M.-J. ChemCatChem 2011, 3, 271.
(9) (a) Stirling, M.; Blacker, J.; Page, M. I. Tetrahedron Lett.
2007, 48, 1247. (b) Blacker, A. J.; Stirling, M. J.; Page, M.
I. Org. Process Rev. Dev. 2007, 11, 642.
The effectiveness of complex 13, in terms of rate of race-
misation and formation of by-product, was compared with
that of the nonsubstituted parent complex 17. After 24
hours, both complexes had completely racemised alcohol
14 (i.e., 0% ee); the all-methoxy complex 13 gave 4% of
by-product 16 after 24 hours, the parent complex yielded
6% of 16 (Scheme 5). Whilst this result mirrors the trend
seen with the Shvo complex series, the improvement is
not great enough to offset the time required to synthesise
13 against the commercially available 17.
(10) Poulhès, F.; Vanthuyne, N.; Bertrand, M. P.; Gastaldi, S.;
Gil, G. J. Org. Chem. 2011, 76, 7281.
(11) Roengpithya, C.; Patterson, D.; Livingston, A. G.; Taylor, P.
C.; Irwin, J. L.; Parrett, M. R. Chem. Commun. 2007, 3462.
(12) Pàmies, O.; Ell, A. H.; Samec, J. S. M.; Hermanns, N.;
Bäckvall, J.-E. Tetrahedron Lett. 2002, 43, 4699.
(13) Johnson, J. R.; Grummitt, O. Organic Synth., Coll. Vol. 3
1955, 806.
13 or 17 (4 mol%)
KOt-Bu (6 mol%)
OH
OH
OH
O
+
+
Ph
(S)-14
Ph
(S)-14
Ph
(R)-14
Ph
toluene
25 °C, 24 h
16
(14) Casey, C. P.; Singer, S. W.; Powell, D. R.; Hayashi, R. K.;
Kavana, M. J. Am. Chem. Soc. 2001, 123, 1090.
(15) Choi, J. H.; Choi, Y. K.; Kim, Y. H.; Park, E. S.; Kim, E. J.;
Kim, M.-J.; Park, J. J. Org. Chem. 2004, 69, 1972.
(16) Martín-Matute, B.; Edin, M.; Bogár, K.; Bäckvall, J.-E.
Angew. Chem. Int. Ed. 2004, 43, 6535.
(17) Dai, W.; Srinivasan, R.; Katzenellenbogen, J. A. J. Org.
Chem. 1989, 54, 2204.
(18) Gibbins, E. J.; Irwin, J. L.; Livingston, A. G.; Muir, J. C.;
Patterson, D. A.; Roengpithya, C.; Taylor, P. C. Synlett
2005, 2993.
(19) General Procedure for the Racemisation of Amine 5b:
Shvo-type complex 1a–j (13 μmol) was placed in a flame-
dried Schlenk tube under dry N2 gas. Anhydrous toluene (2
mL) and (S)-(–)-1-phenylethylamine (S)-5b (16.8 μL, 130
μmol) were added via syringe. The reaction was heated to
100 °C and stirred for 24 h. Samples were taken after 1, 2, 4
Scheme 5
In conclusion, several new Shvo-type complexes were
synthesised and shown to be efficient for the racemisation
of amines.19 A literature method for the synthesis of Shvo-
type catalysts has been extended and shown to be robust
and scalable.
Electron-poor catalysts are, at first sight, more effective
for racemisation but produce more by-product, electron-
rich complexes are less proficient at racemisation but re-
duce the production of by-products. Overall, complexes
1a and 1c appear to be the most attractive for use in a DKR
reaction.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1391–1394

1394
J. F. S. Apps et al.
LETTER
Ruthenium carbonyl (0.30 g, 0.47 mmol) and 15 (0.38 g,
and 24 h and were analysed by GC in order to ascertain the
ee of amine 5b and the relative quantities of 5b, imine 7 and
amine 8.
General Procedure for the Preparation of Substituted
Shvo-Type Complexes 1:10 Triruthenium dodecacarbonyl
(0.30 g, 0.47 mmol) and para-substituted
0.71 mmol) were dissolved in anhyd CHCl3 (9 mL) under
nitrogen gas. The reaction mixture was heated to reflux and
left for 5 d. The solution was cooled and the solvent removed
via evaporation under vacuum. The product was purified by
flash chromatography (SiO2, 1st pentane, 2nd 10:90 EtOAc–
pentane, 3rd 50:50 EtOAc–pentane) to yield 13 as a dark red
powder (0.27 g, 53%); mp 134 °C (dec.). IR: 3352, 2015,
1957, 1515 cm–1. 1H NMR (300 MHz, CDCl3): δ = 7.47 (AA′
of AA′BB′, J = 7.7 Hz, 4 H, ArH), 6.86 (m, 8 H, ArH), 6.56
(BB′ of AA′BB′, J = 7.7 Hz, 4 H, ArH), 4.12 (d, J = 7.7 Hz,
1 H, NH), 3.83 (s, 6 H, Me), 3.71 (s, 6 H, Me), 3.30 (oct, J =
7.7 Hz, 1 H, CH), 0.87 (d, J = 7.7 Hz, 6 H, Me). 13C NMR
(75 MHz, CDCl3): δ = 198.9, 165.0, 159.9, 159.3, 135.1,
133.4, 123.0, 122.8, 114.5, 113.3, 101.2, 81.1, 55.7, 55.5,
45.5, 25.4. MS (EI): m/z (%) = 743 (2) [M+], 560 (29), 368
(48), 135 (100). Anal. Calcd for C38H36ClNO6Ru: C, 61.74;
H, 4.91; N, 1.89; Cl, 4.79 (Inaccurate). Found: C, 60.91; H,
4.95; N, 1.78; Cl, 4.88.
tetraphenylcyclopentadienone 4 (1.43 mmol) was dissolved
in MeOH (80 mL). The mixture was heated at reflux for 72
h and the precipitate collected by filtration under suction.
The residue was washed with MeOH (3 × 10 mL).
Complex 1a: The compound was prepared by the general
procedure, using 2,3,4,5-tetra(4-methoxyphenyl)cyclo-
pentadienone (0.72 g, 1.43 mmol) and triruthenium
dodecacarbonyl (0.30 g, 0.47 mmol) to yield 1a as a yellow
powder (0.69 g, 74%); mp 218–220 °C. IR: 834, 2029, 2006,
1986, 1962, 1608, 1577, 1516, 1030 cm–1. 1H NMR (300
MHz, CDCl3): δ = 6.95 (AA′ of AA′BB′, J = 7.6 Hz, 8 H,
ArH), 6.85 (AA′ of AA′BB′, J = 7.6 Hz, 8 H, ArH), 6.45 (m,
16 H, ArH), 3.70 (s, 12 H, Me), 3.60 (s, 12 H, Me), –18.60
(s, 1 H, RuHRu). 13C NMR (75 MHz, CDCl3): δ = 201.3,
159.3, 158.5, 154.0, 133.6, 132.7, 123.3, 122.9, 113.4,
113.3, 102.5, 87.9, 55.5, 55.4. MS (EI): m/z (%) = 1326 (15)
[M + H+], 1212 (20), 607 (100), 635 (25). Anal. Calcd for
C70H58O14Ru2: C, 63.44; H, 4.41. Found: C, 63.37; H, 4.37.
Complex 1c: The compound was prepared by the general
procedure, using 2,5-diphenyl-3,4-di(4-
methoxyphenyl)cyclopentadienone (0.63 g, 1.43 mmol) and
triruthenium dodecacarbonyl (0.30 g, 0.47 mmol) to yield 1c
as a yellow powder (0.64 g, 76%); mp 217–219 °C. IR: 2025,
1995, 1962, 1956, 1608, 1073, 762 cm–1. 1H NMR (300
MHz, CDCl3): δ = 7.10 (AA′ of AA′BB′, J = 6.9 Hz, 8 H,
ArH), 7.01 (m, 12 H, ArH), 6.90 (BB′ of AA′BB′, J = 6.9 Hz,
8 H, ArH), 6.54 (AA′ of AA′BB′, J = 9.2 Hz, 8 H, ArH), 3.69
(s, 12 H, Me), –18.46 (s, 1 H, RuHRu). 13C NMR (75 MHz,
CDCl3): δ = 201.0, 158.9, 133.2, 131.3, 130.5 (2 ×), 127.7,
126.7, 122.6, 112.9, 102.8, 87.9, 55.0. MS (EI): m/z (%) =
1206 (53) [M + H+], 1150 (35), 1092 (45), 546 (100), 154
(29). Anal. Calcd for C66H50O10Ru2: C, 65.77; H, 4.18.
Found: C, 65.82; H, 4.15.
Computational Studies: DFT calculations20 were carried
out using the Gaussian03 suite of programs.21 Geometry
optimisations, vibrational frequencies and single-point
energies were obtained with the B3LYP functional22,23 and
3-21G(d,p) basis set. The structures were optimised with
constrained planar geometry in order to simulate the
conformation of the ligand in the catalyst. Vibrational
frequency calculations resulted in only one imaginary
frequency corresponding to the rotational constraint
imposed along the aryl cyclopentadienone C–C bonds..
(20) (a) Hohenberg, P.; Kohn, W. Phys. Rev. 1964, 136, B864.
(b) Kohn, W.; Sham, L. J. Phys. Rev. 1965, 140, A1133.
(c) Salahub, D. R.; Zerner, M. C. The Challenge of d and f
Electrons; American Chemical Society: Washington DC,
1989. (d) Parr, R. G.; Yang, W. Density-Functional Theory
of Atoms and Molecules; Oxford University Press: Oxford,
1989.
(21) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A. Jr.;
Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.;
Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi,
M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.;
Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.;
Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.;
Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V.
G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.;
Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.;
Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith,
T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.;
Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.;
Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
Revision B.05; Gaussian Inc: Wallingford CT, 2004.
(22) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
General Procedure for the Racemisation of Alcohol 14
(Ref. 11): Ruthenium complex (0.02 mmol) and potassium
tert-butoxide (3.4 mg, 0.03 mmol) were placed in a flame-
dried Schlenk tube under dry nitrogen gas. Anhydrous
toluene (2 mL) and (S)-(–)-1-phenylethanol [(S)-14; 60.4
μL, 0.5 mmol] were added with a syringe. Samples were
taken after 1, 2, 4 and 24 h and were analysed by GC in order
to ascertain the ee of alcohol 14 and the relative quantities of
14 and acetophenone 16. The protocol is shown in the
supporting information.
Synthesis of Complex 13:13,14 A solution of 2,3,4,5-tetra(4-
methoxyphenyl)cyclopentadienone (0.75 g, 1.50 mmol) and
isopropylamine (0.57 mL, 6.70 mmol) in anhyd toluene (10
mL) was stirred well under nitrogen gas at 0 °C. Titanium
tetrachloride (1.0 M solution in toluene; 0.37 mL, 0.36
mmol) was added dropwise and the reaction mixture was
heated to reflux for 2 h. After being cooled to 15 °C the
reaction mixture was diluted with Et2O (15 mL). The
reaction mixture was filtered through celite, and the
collected precipitate washed with Et2O. Concentration of the
combined fractions via evaporation of the solvent under
vacuum yielded 15 as a red powder (0.52 g, 64%); mp 275–
277 °C.
(23) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1998, 37,
785. (b) Miehlich, B.; Savin, A.; Stoll, H.; Preuss, H. Chem.
Phys. Lett. 1989, 157, 200.
Synlett 2014, 25, 1391–1394
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