β-Ferrocenyl-β-amino alcohols: a new class of central chiral ferrocene derivatives

Article abstract of DOI:10.1016/S0022-328X(01)01255-4

An efficient procedure for the enantioselective synthesis of β-ferrocenyl-β-amino alcohols, a new class of central chiral ferrocene derivatives suitable for the elaboration of auxiliaries and ligands for asymmetric synthesis, is described. Key steps of the method are the catalytic asymmetric dihydroxylation of 1-ferrocenyl alkenes and the regio- and stereoselective azide substitution of the hydroxyl group adjacent to the ferrocene moiety. The stereochemistry of the substitution step has been established by X-ray diffraction analysis of a cyclic derivative. The first catalytic enantioselective synthesis of a β-ferrocenyl-β-amino acid derivative is also disclosed.

Full text of DOI:10.1016/S0022-328X(01)01255-4

Journal of Organometallic Chemistry 642 (2002) 212–226
www.elsevier.com/locate/jorganchem
b-Ferrocenyl-b-amino alcohols: a new class of central chiral
ferrocene derivatives
Mo`nica Catasu´s a, Agust´ı Bueno a, Albert Moyano a,*, Miguel A. Maestro b,1,
Jose´ Mah´ıa b,1
a Facultat de Qu´ımica, Departament de Qu´ımica Orga`nica, Unitat de Recerca en S´ıntesi Asime`trica (URSA), Uni6ersitat de Barcelona,
Mart´ı i Franque`s 1-11, 08028 Barcelona, Spain
b Ser6icios Xerais de Apoio a´ In6estigacio´n, Campus da Zapateira, s/n, Uni6ersidade da Corun˜a, 15071 A Corun˜a, Spain
Received 31 July 2001; accepted 3 September 2001
Abstract
An efficient procedure for the enantioselective synthesis of b-ferrocenyl-b-amino alcohols, a new class of central chiral ferrocene
derivatives suitable for the elaboration of auxiliaries and ligands for asymmetric synthesis, is described. Key steps of the method
are the catalytic asymmetric dihydroxylation of 1-ferrocenyl alkenes and the regio- and stereoselective azide substitution of the
hydroxyl group adjacent to the ferrocene moiety. The stereochemistry of the substitution step has been established by X-ray
diffraction analysis of a cyclic derivative. The first catalytic enantioselective synthesis of a b-ferrocenyl-b-amino acid derivative is
also disclosed. © 2002 Elsevier Science B.V. All rights reserved.
Keywords: b-Amino acids; b-Amino alcohols; Asymmetric synthesis; Ferrocenes
b substituent by a ferrocenyl group. A number of
advantages could be expected from this transformation:
(i) increasing the steric hindrance at the nitrogenated
stereogenic center, due to the three-dimensional nature
of the ferrocene nucleus, that might result in improved
stereoselectivities [6]; (ii) nucleophilic substitution reac-
tions at positions vicinal to the ferrocene moiety are
highly favoured, and they take place with retention of
configuration [7]; (iii) the ferrocene nucleus is chemi-
cally stable, and its derivatives are in many instances
crystalline. In fact, several very useful chiral ligands
incorporating a ferrocene moiety have been developed
in the last decade [8]. An exhaustive bibliographical
search showed however that while some structural types
of ferrocene-containing amino alcohols have been de-
scribed in the literature [9–14], 3-amino-3-ferrocenyl-
1,2-propanediol (I) and 2-amino-2-ferrocenylethanol
(II) derivatives were still unknown. We report in this
paper the first, highly stereoselective, approach to both
types of compounds.
1. Introduction
The chiral b-amino alcohol moiety is an important
structural motif in several bioactive compounds [1], as
well as in a great number of useful auxiliaries or ligands
used in asymmetric synthesis [2]. Although the most
common sources of chiral b-amino alcohols involve the
reduction or derivatisation of a-amino acids [3] or of
other natural products [4], the search for novel, purely
synthetic chiral b-amino alcohols is a subject of un-
abated interest [5].
With the aim of extending the structural diversity of
b-amino alcohols, we envisaged the replacement of the
* Corresponding author.
E-mail address: amoyano@qo.ub.es (A. Moyano).
1 To whom enquiries about the crystal structure determination
should be addressed.
0022-328X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01255-4

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
213
were able to find suitable conditions for the preparation
of the desired diols in high enantiomeric purity (Table
1).
As previously observed by Baumgartner in the dihy-
droxylation of 1-ferrocenylalkenes [20], ligands based
on the pyrimidine nucleus gave better results than those
derived from phthalazide (compare entries 1 and 2 in
Table 1). Further improvement was attained by chang-
ing the non-aqueous solvent from acetonitrile to tert-
butyl alcohol (entry 3). In these first experiments, we
observed that ferrocenecarbaldehyde (1) was a minor
product of the reaction, and that conversions were
never greater than 62%. We discovered that this was
due to a concurrent Michael addition-retroaldol se-
quence on acrylate 3 arising from the basic aqueous
reaction medium. We performed some further experi-
ments in order to minimise this unwelcome process.
The addition of methanesulfonamide [19] did not im-
prove either the yield or the enantioselectivity of the
reaction (entries 4 and 5). Best results were obtained by
using the conditions of entry 6, which reproducibly led
to highly enantiopure (+)-4 with satisfactory conver-
sions (73%). Further increasing the amount of the
stoichiometric oxidant (entry 7) significantly eroded the
yield of the reaction. We were pleased to find that the
levorotatory enantiomer of 4 could also be obtained in
good enantiomeric excess (94% ee) under the same
optimised conditions, but using the pseudoenantiomeric
(DHQ)2PYR ligand (entry 10 of Table 1). Taking into
account the generally observed sense of asymmetric
induction of Sharpless’ dihydroxylation [19], we as-
signed (2S,3S) and (2R,3R) absolute configurations to
(+)-4 and to (−)-4, respectively. With both enan-
tiomers of the diol 4 in our hands, we proceeded to
their conversion into the target amino alcohols 7
(Scheme 2).
(Structures I and II)
2. Results and discussion
2.1. Synthesis of (2S,3S)- and of
(2R,3R)-3-amino-3-ferrocenyl-1,2-propanediol
We devoted our first efforts to the preparation of the
ferrocenyl-substituted amino alcohols of type I, by an
extension of the methodology developed in our labora-
tory [15] for the enantioselective synthesis of anti-3-
amino-1,2-alkanediols, that implies the asymmetric
Sharpless epoxidation [16] of an (E)-allyl alcohol fol-
lowed by the regio- and stereoselective oxirane ring
opening by a nitrogen nucleophile. To that end, we
obtained the known [17] (E)-3-ferrocenyl-2-propanol
(3) by the improved procedure shown in Scheme 1, that
involves two steps from commercially available fer-
rocenecarbaldehyde (1) and takes place in 84% overall
yield.
However, all our efforts to isolate or trap the
epoxyalcohol derived from 3, either in racemic (by
reaction with m-chloroperbenzoic acid) or in optically
active form (by Sharpless epoxidation), were totally
unsuccessful, probably due to the highly reactive nature
of ferrocenyl-substituted oxiranes [18]. At the light of
these results, we decided to explore an alternative route
based on the asymmetric dihydroxylation of ferrocenyl
acrylate (2) [19,20]. After some experimentation, we
Scheme 1. Reagents and conditions: (i) three equivalents (EtO)2POꢀCH2ꢀCO2Et, two equivalents NaH, benzene, 60 °C, reflux, 20 h, 97%; (ii) 2.4
equivalents DIBAL-H, diethyl ether, −75 °C, 2 h, −20 °C, 1 h, 87%.
Scheme 2. Reagents and conditions: (i) 11 equivalents Ac2O, pyridine, r.t., 17 h, 98%; (ii) six equivalents NaN3, MeOH–water (1:3), r.t., 66 h, 77%;
(iii) seven equivalents LAH, THF, reflux, 3.5 h, 83%.

Table 1
Asymmetric dihydroxylation of ferrocenylacrylate (2)
Entry
Solvent
Ligand (mol.
equiv.)
Fe(III) mol.
equiv.
Os(VI) mol.
equiv.
MeSO2NH2 mol. Reaction time
Conversion (%)
Yield of 1 (%) a
Yield of 4 (%) a
% ee of 4
/
equiv.
(h)
(configuration) b
1
2
CH3CN
CH3CN
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
CH3CN
tBuOH
tBuOH
(DHQD)2PHAL
(0.10)
(DHQD)2PYR
(0.10)
(DHQD)2PYR
(0.10)
(DHQD)2PYR
(0.10)
(DHQD)2PYR
(0.10)
(DHQD)2PYR
(0.20)
(DHQD)2PYR
(0.20)
(DHQ)2PHAL
(0.10)
3
3
0.10
0.10
0.10
0.10
0.10
0.20
0.20
0.10
0.10
0.20
0.12
0
22
37
68
61
61
54
73
87
35
61
84
8
19
30
36
41
38
51
9
57 (2S,3S)
93 (2S,3S)
98 (2S,3S)
98 (2S,3S)
99 (2S,3S)
98 (2S,3S)
95 (2S,3S)
62 (2R,3R)
97 (2R,3R)
94 (2R,3R)
110
62
4
3
3
0
9
4
3
0.40
1.0
0
65
10
8
5
3
138
66
6
6
20
18
n.d. c
6
642
7
12
3
0
70
2
8
0.12
0
44
10
32
47
2
9
(DHQ)2PYR
(0.10)
(DHQ)2PYR
(0.20)
3
66
2
10
6
0
47
26
a Yield of isolated product after chromatographic purification.
b By HPLC (Chiralcel-ODR column).
c Not determined.

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
215
Scheme 3. Reagents and conditions: (i) 1.2 equivalents Boc2O, three equivalents NaHCO3, MeOH, ultrasound, r.t., 2 h, 78%; (ii) 2.2 equivalents
t
imidazole, 1.1 equivalents BuPh2SiCl, DMF, r.t., 24 h, 89%; (iii) 10 equivalents (MeO)2CMe2, cat. pTsOH, benzene, reflux, 5.5 h, 69%; (iv) 2.5
equivalents NaH, DMF, r.t., 1.5 h; 1 M aq. HCl, r.t., 83%.
Reaction of (+)-4 with acetic anhydride in pyridine
led in essentially quantitative yield to the diacetate
(+)-5, that was treated with a solution of sodium azide
in methanol–water to afford the azido acetate (+)-6 in
77% yield after chromatographic purification. Spectral
analysis of this compound clearly showed that, as antic-
ipated, the substitution had taken place with complete
regio- and stereoselectivity (only one diastereomer was
detected). Moreover, the enantiomeric purity of (+)-6
(98% ee) was totally coincident with that of the starting
diol. When a tetrahydrofuran solution of (+)-6 was
heated in the presence of lithium aluminum hydride, the
reduction of the azido, acetate and ethoxycarbonyl
groups took concomitantly place, giving rise to 3-
amino-3-ferrocenyl-1,2-propanediol (+)-7—to which
we assign a (2S,3S) configuration—in 83% yield. In a
totally similar way, (−)-4 was transformed into (−)-7.
In order to establish without doubt that the azide
substitution step had taken place with retention of
configuration, we synthesised some cyclic derivatives of
7 (Scheme 3).
tion analysis. The resolved structure (Fig. 1 and Table
2) fully confirmed our assumptions on the regio- and
stereochemical course of azide substitution in 5.
No significant deviations were found in the structure
of the ferrocene nucleus in 11 relative to those of other
monosubstituted ferrocene derivatives [23]. Thus, the
ironꢀcyclopentadienyl carbon bond lengths fall in the
,
2.03–2.05 A range. The two cyclopentadienyl rings are
oriented in an eclipsed fashion. On the other hand, the
oxazolidinone ring is essentially planar, with a small
torsion of ca. 8° around the two sp3 carbons. Interest-
ingly enough, the ferrocenyl moiety adopts a conforma-
tion such that the interactions with the hydroxymethyl
substituent are minimised, and is disposed away from
the heterocycle. This fact results in a substantial steric
hindrance on one of the two diastereotopic faces of the
planar C(1)ꢀNHꢀC(2) moiety (the Si-face for the
(4S,5S) enantiomer of 11), a phenomenon that could be
very important for the application of auxiliaries or
ligands derived from 7 in asymmetric synthesis.
Following protection of the amino and of the pri-
mary hydroxyl groups of (+)-7 as tert-butyl carbamate
and tert-butyldiphenylsilyl ether, respectively, (+)-9
was converted into the 2,2-dimethyl-1,3-oxazolidine
(10). In this compound, the coupling constant between
the two vicinal protons of the heterocycle was of 6.3
Hz, a value that is compatible with that of a trans-4,5-
disubstituted-1,3-oxazolidine [21]. On the other hand,
when (+)-9 was treated with sodium hydride in N,N-
dimethylformamide, highly crystalline oxazolidinone
(+)-11 was isolated in 83% yield after acidic hydrolysis
of the silyl ether. Again, the 6.4 Hz value of the
coupling constant between the two vicinal ring protons
was compatible with a trans stereochemistry for this
compound [22]. Recrystallisation of (+)-11 from
methanol afforded crystals suitable for X-ray diffrac-
Fig. 1. ORTEP representation of the crystal structure of (+)-11.
Hydrogen atoms have been omitted for clarity.

216
M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
Table 2
2.2. Synthesis of (2S)- and of (2R)-2-amino-2-
,
Selected bond lengths (A) and angles (°) for 4-(ferro-
cenyl)oxazolidinone ((+)-11)
ferrocenylethanol
Having established the feasibility of effecting a highly
regio- and stereoselective azide substitution of the hy-
droxyl group adjacent to the ferrocene moiety in 1-fer-
rocenyl-1,2-alkanediol derivatives, we applied this
strategy to the synthesis of 2-amino-2-ferrocenylethanol
(Scheme 4).
Bond lengths
N(1)ꢀC(1)
N(1)ꢀC(2)
C(1)ꢀC(3)
C(1)ꢀC(5)
O(1)ꢀC(2)
O(2)ꢀC(2)
Fe(1)ꢀC(10)
Fe(1)ꢀC(12)
Fe(1)ꢀC(14)
Fe(1)ꢀC(5)
Fe(1)ꢀC(6)
Fe(1)ꢀC(8)
1.456(2)
1.330(2)
1.555(2)
1.496(2)
1.361(2)
1.215(2)
2.037(2)
2.0273(19)
2.0391(18)
2.0330(15)
2.0468(14)
2.0329(17)
Asymmetric dihydroxylation of vinylferrocene (12)
using (DHQD)2PYR as the chiral ligand [20] afforded
(+)-13—for which a (1S) configuration was as-
sumed—in good yield and with excellent optical purity
(98% ee). When the corresponding diacetate (+)-14
was reacted with sodium azide in aqueous methanol,
monosubstitution cleanly took place to afford (+)-15.
The enantiomeric purity, checked by HPLC, of this
compound was identical to that of (+)-13, establishing
that this process is racemisation-free. Although (+)-15
could be converted into the target 2-amino-2-ferro-
cenylethanol (17) by reaction with lithium aluminum
hydride, better results were obtained by means of a two
step sequence involving diisobutylaluminum hydride-
mediated reduction of the acetate and catalytic hydro-
genation, that afforded (+)-17 in 97% yield. The
reactions summarised in Scheme 4 also allowed the
transformation of diol (−)-13 (obtained in 86% yield
by asymmetric dihydroxylation of 12 using
(DHQ)2PYR as a ligand) [20] into the amino alcohol
(−)-17, whose enantiomeric excess (measured by
HPLC at the level of azido acetate (−)-15) was 87%.
In order to illustrate the applicability of these new
b-amino alcohols in the preparation of chiral auxiliaries
Bond angles
C(12)ꢀFe(1)ꢀC(7)
C(5)ꢀFe(1)ꢀC(10)
Fe(1)ꢀC(5)ꢀC(1)
C(5)ꢀC(1)ꢀC(3)
C(1)ꢀC(3)ꢀC(4)
O(3)ꢀC(4)ꢀC(3)
O(2)ꢀC(2)ꢀO(1)
N(1)ꢀC(2)ꢀC(1)
106.86(9)
109.07(8)
132.57(11)
110.06(12)
115.49(14)
110.15(14)
121.58(6)
109.84(14)
Torsional angles
C(5)ꢀC(51)ꢀC(3)ꢀC(4)
N(1)ꢀC(1)ꢀC(5)ꢀC(9)
C(2)ꢀN(1)ꢀC(1)ꢀC(3)
C(1)ꢀN(1)ꢀC(2)ꢀO(1)
C(10)ꢀFe(1)ꢀC(5)ꢀC(1)
109.92(15)
155.36(15)
7.44(17)
176.73(17)
0.82(17)
and ligands, we synthesised the oxazolidinone (−)-18,
the bis(oxazoline) (−)-19 and the phosphinooxazoline
(−)-22 from (−)-17 in the way shown in Scheme 5.
Scheme 4. Reagents and conditions: (i) three equivalents K3[Fe(CN)6], three equivalents K2CO3, 0.1 equivalents (DHQD)2PYR, 0.1 equivalents
K2OsO2(OH)4, CH3CN–water (1:1), r.t., 12 h, 79% (98% ee); (ii) nine equivalents Ac2O, pyridine, r.t., 12 h, 97%; (iii) 5.5 equivalents NaN3,
MeOH–water (1:3), r.t., 12 h, 72%; (iv) 2.5 equivalents DIBAL-H, diethyl ether, −78 °C, 1 h, 97%; (v) H2 (1 atm), cat. 10% Pd/C, ethyl acetate,
r.t., 12 h, 100%.

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
217
Scheme 5. Reagents and conditions: (i) 1.5 equivalents triphosgene, 4.4 equivalents aq. NaOH, DCM, r.t., 1 h, 74%; (ii) one equivalent
Me2C(CO2H)2, 2.4 equivalents N-hydroxysuccinimide, 2.4 equivalents DCCI, THF, r.t., 2.5+15 h, 77%; five equivalents NEt3, 0.1 equivalents
DMAP, 1.4 equivalents pTsCl, 1,2-dichloroethane, reflux, 2 h, 29%; (iii) 1.9 equivalents NEt3, one equivalents 2-fluorobenzoyl chloride, THF,
0 °C to r.t., 2 h, 89%; (iv) 4.9 equivalents NEt3, 0.5 equivalents DMAP, 1.4 equivalents pTsCl, DCM, reflux, 1 h, 78%; (v) three equivalents
LiPPh2, THF, −20 °C, 2 h, r.t., 12 h, 76%.
Scheme 6. Reagents and conditions: (i) one equivalent NaEtO, EtOH, 0 °C, 1.5 h, 85%; (ii) H2 (1 atm), cat. 10% Pd/C, ethyl acetate, r.t., 18 h,
82%.
2.3. Synthesis of (2S,3S)-3-amino-3-ferrocenyl-2-
hydroxypropanoate
represents the first catalytic asymmetric synthesis of a
b-ferrocenyl-b-amino acid derivative. Given the easy
availability of (−)-6, the levorotatory enantiomer of 24
should be equally accessible by this route.
The introduction of ferrocene derivatives into bioac-
tive molecules has received much attention in the last
years, due to the unique redox and geometrical proper-
ties of the ferrocene nucleus [24]. Up to now, however,
the incorporation of ferrocenes into peptide or bis(pep-
tide) chains has been effected exclusively in the form of
N-ferrocenoyl derivatives, since ferrocenyl-a- or b-
amino acids are virtually unknown compounds [25]. We
envisioned that the strategy that we had developed for
the synthesis of 7 could also provide an excellent entry
to highly enantiopure b-ferrocenyl-b-amino acid deriva-
tives. This possibility was exemplified by the prepara-
tion of the ethyl ester of syn-3-amino-3-ferrocenyl-
2-hydroxypropanoic acid from the azido acetate inter-
mediate 6 (Scheme 6). Base-catalysed transesterification
with ethanol followed by catalytic hydrogenation gave
access to (+)-24 in 70% overall yield from (+)-6. This
In summary, we have developed an efficient proce-
dure for the enantioselective synthesis of b-ferrocenyl-b-
amino alcohols, a new class of ferrocene-derived chiral
scaffolds for the construction of auxiliaries or ligands
for asymmetric synthesis. This method, whose key steps
are the catalytic asymmetric dihydroxylation of ferro-
cenyl alkenes and the totally regio- and stereoselective
azide substitution of the hydroxyl group adjacent to the
ferrocene nucleus, not only allows the preparation of
both enantiomeric series of these previously unknown
b-amino alcohols, but also constitutes a convenient
entry to b-ferrocenyl-b-amino acids. Both the extension
of this strategy to the preparation of other b-ferrocenyl-
b-amino alcohols and the application of the derived
auxiliaries and ligands to asymmetric synthesis are be-
ing actively pursued in our laboratories.

218
M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
3. Experimental
1H). 13C-NMR (50 MHz, CDCl3): l (ppm) 14.4 (CH3),
60.2 (CH2), 68.5 (CH), 69.6 (CH), 70.8 (CH), 78.7 (Cq,
Cp), 114.8 (CH), 145.5 (CH), 167.1 (Cq, CO).
3.1. General and analytical methods
3.1.2. (E)-3-Ferrocenyl-2-propen-1-ol (3)
Melting points were determined in an open capillary
tube and are uncorrected. Optical rotations were mea-
sured at room temperature (r.t.) (23 °C) on a Perkin–
Elmer 241 MC polarimeter. Concentrations are given in
g 100 ml−1. Infrared spectra were recorded in a Fourier
transform mode, using NaCl film or KBr pellet tech-
To a cold (−75 °C), stirred solution of ferroceny-
lacrylate (2) (0.130 g, 0.46 mmol) in anhydrous Et2O (2
ml), 1.1 ml (1.1 mmol) of a 1 M solution of diisobutyla-
luminum hydride in hexanes were added with a cali-
brated syringe, and stirring was maintained for 2 h at
the same temperature and for 1 h at −20 °C. At this
point, TLC analysis showed that only a trace of start-
ing material remained; MeOH (1 ml) was added drop-
wise, the reaction mixture was warmed up to r.t. and
stirred until a white precipitate was formed. The solids
were filtered off, washed with Et2O and the filtrates
were washed with brine, dried over Na2SO4 and evapo-
rated at reduced pressure to afford a crude product that
upon chromatographic purification (silica gel, C6H14–
EtOAc mixtures of increasing polarity) yielded 0.097 g
(87%) of pure (E)-3-ferrocenyl-2-propen-1-ol (3) as a
yellow solid.
1
niques. The H-NMR spectra were recorded at 200 or
at 300 MHz (s=singlet, d=doublet, t=triplet, m=
multiplet, br=broad), and the 13C-NMR spectra were
recorded at 50.3 or at 75.4 MHz. Chemical shifts are
given in ppm and referenced to Me4Si or CHCl3. J
values are given in Hz. Carbon multiplicities were
established by DEPT experiments. Elemental analyses
were performed by the ‘Servei de Microana`lisi del CSIC
de Barcelona’ and by the ‘Servicios Xerais de Apoio a´
Investigacion, Universidade da Corun˜a’. Exact mass
measurements (HRMS) were performed by the ‘Servi-
cio de Espectroscop´ıa de Masas de la Universidad de
Co´rdoba’ or by the ‘Unidad de Espectrometr´ıa de
Masas de la Universidad de Santiago de Compostela’.
All reactions were run in flame or oven-dried glassware
under a N2 atmosphere. Reaction progress was fol-
lowed by TLC (Merck DC-Alufolien KIESELGEL 60
F254). Silica gel (70–230 mesh) was used for column
chromatography. Vinylferrocene (12) was prepared by a
literature procedure [26].
M.p. 68.5–70 °C (lit: 69–70 °C) [17a]. IR (KBr):
w=3240, 1656, 1370, 1208, 1106, 1001, 961, 816 cm−1
.
1H-NMR (200 MHz, CDCl3): l (ppm) 1.34 (t, J=6
Hz, 1H, OH), 4.20 (m, 11H), 5.97 (dt, J=15.6 Hz,
J%=6 Hz, 1H), 6.36 (d, J=15.8 Hz, 1H). 13C-NMR
(50 MHz, CDCl3): l (ppm) 64.0 (CH), 66.9 (CH), 68.7
(CH2), 69.2 (CH), 82.4 (Cq), 125.7 (CH), 129.4 (CH).
MS (CI, NH3) m/e=225 [M−OH+, 100%], 243 [M+
1+, 4%], 260 [M+18+, 1%]. Anal. Calc. for
C13H14FeO: C, 64.50; H, 5.83; O, 6.61. Found: C,
64.65; H, 5.87; O, 6.65%.
3.1.1. (E)-3-Ferrocenyl-2-propenoic acid ethyl ester (2)
To a cold (0 °C), stirred suspension of NaH (2.45 g,
55% in paraffine oil, 56 mmol) in anhydrous C6H6 (50
ml), triethyl phosphonoacetate (14 ml, 70 mmol) was
added dropwise. When the addition was finished and
H2 evolution subsided, the mixture was stirred 1 h at
r.t. A solution of ferrocenecarbaldehyde (1) (5.00 g,
23.4 mmol) in dry C6H6 (20 ml) was added via cannula
and the resulting mixture was heated to reflux for 20 h,
after which time TLC analysis showed the complete
disappearance of starting product 1. After cooling to
r.t., the reaction mixture was treated with water (70
ml), transferred to a separation funnel and extracted
with Et2O (2×100 ml). The organic extracts were
washed with brine and dried over Na2SO4. Evaporation
of the solvent afforded a crude product that was
purified by column chromatography on silica gel, elut-
ing with C6H14–EtOAc mixtures of increasing polarity,
to give 6.40 g (97%) of pure ester 2 as an orange-
coloured solid.
3.1.3. (2S,3S)-2,3-Dihydroxy-3-ferrocenylpropionic acid
ethyl ester ((+)-4) and (2R,3R)-2,3-dihydroxy-3-
ferrocenylpropionic acid ethyl ester ((−)-4)
To a solution of K3Fe(CN)6 (3.49 g, 10.6 mmol),
K2CO3 (1.47 g, 10.6 mmol) and (DHQD)2PYR (0.313
g, 0.35 mmol) in tert-butyl alcohol (300 ml) and water
(300 ml), solid K2OsO2(OH)4 (0.129 g, 0.35 mmol) was
added in one portion, and the resulting mixture was
vigorously stirred until complete solution of the osmate
(2 h). Ethyl (E)-3-ferrocenylpropionate (2) (0.50 g, 1.8
mmol) was added in 0.10 g portions over 1.5 h, and
stirring was maintained for 66 h at r.t. After addition of
Na2SO3 (2.7 g), the reaction mixture was extracted with
EtOAc (3×300 ml). The organic extracts were washed
with brine and dried over Na2SO4. Following evapora-
tion of the solvents at reduced pressure, column chro-
matography of the crude product (silica gel,
C6H14–EtOAc mixtures as eluent) gave 0.136 g (27%
recovery) of 2, 74 mg (20%) of 1 and 0.287 g (51%) of
M.p. 69–70 °C (lit: 69.5–70 °C) [27]. IR (KBr):
w=2975, 1704, 1636, 1316, 1208, 1175, 1044, 980
ethyl
(2S,3S)-2,3-dihydroxy-3-ferrocenylpropanoate
1
cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 1.33 (t,
((+)-4) (98% ee) as a yellow solid.
J=7 Hz, 3H), 4.16 (s, 5H), 4.22 (q, J=7 Hz, 2H), 4.44
(m, 4H), 6.03 (d, J=15.6 Hz, 1H), 7.57 (d, J=15.8 Hz,
M.p. 54–55.5 °C. [h]D= +35.4° (c=1.28, CHCl3).
IR (KBr): w=3448, 2983, 1735, 1412, 1270, 1106, 1025

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
219
1
cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 1.35 (t,
pressure and addition of brine (5.2 ml), the mixture was
extracted with methylene chloride (3×25 ml). The
organic extracts were dried over Na2SO4. Elimination
of the solvents followed by chromatographic purifica-
tion (silica gel, C6H14–EtOAc mixtures as eluents) gave
0.225 g (77% yield, 98% ee) of ethyl (2S,3S)-2-acety-
loxy-3-azido-3-ferrocenylpropanoate ((+)-6) as a yel-
low–orange oil.
J=7 Hz, 3H), 2.33 (br d, J=7 Hz, 1H, OH), 3.11 (br
d, J=6.2 Hz, 1H, OH), 4.28 (m, 12H), 4.75 (br d,
J=5.2 Hz, 1H). 13C-NMR (50 MHz, CDCl3): l (ppm)
14.2 (CH3), 62.1 (CH2), 67.0 (CH), 67.5 (CH), 68.3
(CH), 68.4 (CH), 68.6 (CH), 70.9 (CH), 73.8 (CH), 88.5
(Cq, Cp), 172.8 (Cq, CO). MS (CI, NH3) m/e=301
[M−OH+, 100%], 319 [M+1+, 1%], 336 [M+18+,
60%]. Anal. Calc. for C15H18FeO4: C, 56.63; H, 5.70.
Found: C, 56.64; H, 5.82%.
[h]D= +15.6° (c=0.77, CHCl3). IR (NaCl film):
w=2927, 2109, 1752, 1374, 1221, 1108, 1028 cm−1
.
1H-NMR (200 MHz, CDCl3): l (ppm) 1.30 (t, J=7.4
Hz, 3H), 2.21 (s, 3H), 4.23 (m, 11H), 4.74 (d, J=3 Hz,
1H), 5.43 (d, J=3 Hz, 1H). 13C-NMR (50 MHz,
CDCl3): l (ppm) 14.1 (CH3), 20.7 (CH3), 61.5 (CH2),
62.1 (CH), 67.2 (CH), 68.1 (CH), 68.59 (CH), 68.63
(CH), 69.1 (CH), 75.4 (CH), 82.8 (Cq, Cp), 167.3 (Cq,
CO), 169.8 (Cq, CO). MS (CI, NH3) m/e=343 (M−
N+3 , 69%), 386 [M+1+, 1%], 403 [M+18+, 25%].
HRMS (EI) Calc. for C17H19FeN3O4: 385.0725. Found:
385.0726.
In a similar way, but using (DHQ)2PYR as a ligand,
ferrocenylacrylate (2) (0.51 g, 1.8 mmol) gave 82 mg
(16% recovery) of 2, 97 mg (26%) of 1 and 0.261 g
(47%) of ethyl (2R,3R)-2,3-dihydroxy-3-ferrocenyl-
propanoate ((−)-4) (94% ee). Conditions for the
HPLC determination of the enantiomeric purity of 4:
Chiralcel-ODR column, 85% 0.5 M aq. NaClO4–15%
MeOH, b=0.5 ml min−1, T=25 °C, u=220 nm,
tR(2S,3S)=11.5 min, tR(2R,3R)=10.7 min.
In a similar way, 0.300 g of the (2R,3R)-diacetate
((−)-5) and 0.289 g (4.55 mmol) of NaN3 afforded
0.186 g (65%) of ethyl (2S,3S)-2-acetyloxy-3-azido-3-
ferrocenylpropanoate ((−)-6). Conditions for the
HPLC determination of the enantiomeric purity of 6:
Chiralcel-OD column, 99% C6H14–1% isopropyl alco-
3.1.4. Ethyl (2S,3S)-2,3-diacetyloxy-3-
ferrocenylpropanoate ((+)-5) and ethyl (2R,3R)-
2,3-diacetyloxy-3-ferrocenylpropanoate ((−)-5)
To a solution of diol (+)-4 (0.242 g, 0.76 mmol) in
Py (1.5 ml), Ac2O (0.76 ml, 8.1 mmol) was added in one
portion. The mixture was stirred at r.t. for 17 h, and
both Py and excess Ac2O were removed at reduced
pressure to afford 0.300 g (98%) of ethyl (2S,3S)-2,3-di-
acetyloxy-3-ferrocenylpropanoate ((+)-5) as an or-
ange-coloured oil, that was not further purified.
[h]D= +33° (c=1.22, CHCl3). IR (NaCl film): w=
hol, b=0.3 ml min−1
R(2S,3S)=39.6 min, tR(2R,3R)=36.7 min.
, T=25 °C, u=254 nm,
t
3.1.6. (2S,3S)-3-Amino-3-ferrocenylpropane-1,2-diol
((+)-7) and (2R,3R)-3-amino-3-ferrocenyl-
propane-1,2-diol ((−)-7)
2985, 1750, 1374, 1219, 1106, 1046 cm−1 1H-NMR
.
To a stirred solution of azido acetate (+)-6 (0.237 g,
0.62 mmol) in anhydrous THF (6 ml) LiAlH4 (0.164 g,
4.31 mmol) was added in one portion, and the resulting
mixture was heated to reflux for 2 h. After cooling to
r.t., water (0.1 ml), 15% aq. NaOH (0.1 ml) and water
(3×0.1 ml) were added sequentially. Stirring was con-
tinued for 30 min, until a crystalline white precipitate
settled out. Ethyl acetate (10 ml) was added and stirring
was maintained for 30 min, after which time the solids
were filtered out, the filtrates were dried over Na2SO4
and the solvents were eliminated at reduced pressure, to
afford 0.141 g (83%) of (2S,3S)-3-amino-3-ferrocenyl-
propane-1,2-diol ((+)-7) as a yellow solid, that can be
further purified by recrystallisation from CH2Cl2–
C6H14.
(200 MHz, CDCl3): l (ppm) 1.28 (t, J=7.2 Hz, 3H),
2.12 (s, 3H), 2.19 (s, 3H), 4.19 (m, 11H), 5.40 (d, J=2.6
Hz, 1H), 6.29 (d, J=2.6 Hz, 1H). 13C-NMR (50 MHz,
CDCl3): l (ppm) 14.0 (CH3), 20.6 (CH3), 20.8 (CH3),
61.9 (CH2), 67.3 (CH), 68.2 (CH), 68.3 (CH), 68.4
(CH), 68.9 (CH), 70.3 (CHꢀO), 74.4 (CH), 83.3 (Cq,
Cp), 167.1 (Cq, CO), 169.6 (Cq, CO), 170.1 (Cq, CO).
MS (CI, NH3) m/e=343 [M−OAc+, 100%], 420
[M+18+, 5%]. HRMS (EI) Calc. for C19H22FeO6:
402.0766. Found: 402.0768.
In an analogous way, 0.254 g (0.80 mmol) of diol
(2R,3R)-4, treated with 1.5 ml Py and 0.80 ml (8.47
mmol) of Ac2O gave 0.311 g (97%) of ethyl (2R,3R)-
2,3-diacetyloxy-3-ferrocenylpropanoate ((−)-5) as an
orange oil.
M.p. 91.5–93.0 °C. [h]D= +42.5° (c=1.46,
CHCl3). IR (KBr): w=3354, 2923, 1571, 1104, 1040,
1
812 cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 2.85
3.1.5. Ethyl (2S,3S)-2-acetyloxy-3-azido-3-
ferrocenylpropanoate ((+)-6) and ethyl (2R,3R)-
2-acetyloxy-3-azido-3-ferrocenylpropanoate ((−)-6)
To a stirred suspension of diacetate (+)-5 (0.300 g,
0.75 mmol) in 3:1 MeOH–water (21 ml), sodium azide
(0.296 g, 4.55 mmol) was added in one portion, and the
resulting mixture was stirred for 66 h at r.t. After
elimination of MeOH by rotary evaporation at reduced
(br s, 4H, NH2, 2OH), 3.63 (m, 4H), 4.17 (m, 9H).
13C-NMR (50 MHz, CDCl3): l (ppm) 52.9 (CH), 64.7
(CH2), 65.2 (CH), 67.8 (CH), 67.9 (CH), 68.4 (CH),
68.8 (CH), 74.8 (CH), 91.5 (Cq, Cp). MS (CI, NH3)
m/e=199 [M−76+, 16%], 214 [M−61+, 4%], 259
[M−NH+2 , 78%], 276 [M+1+, 100%]. HRMS (EI)
Calc. for C13H17FeNO2: 275.0609. Found: 275.0605.

220
M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
In a similar way, 0.273 g (0.71 mmol) of (2R,3R)-
133.0 (CH), 134.7*, 135.5 (CH), 155.8 (Cq, CO) (*
signal corresponding to a rotamer of the N-Boc group).
MS (CI, NH3) m/e=497 [M−NHBoc+, 32%], 556
[M−tBu+, 100%], 613 [M+, 55%], 614 [M+1+, 47%],
393 [M+18+, 6%]. HRMS (EI) Calc. for
C34H43FeNO4Si: 613.2311. Found: 613.2299.
azido acetate ((−)-6), treated with 0.188 g (4.96 mmol)
of LiAlH4 in 7 ml THF, gave 0.124 g (64%) of
(2R,3R)-3-amino-3-ferrocenylpropane-1,2-diol ((−)-7).
3.1.7. (2S,3S)-3-(tert-Butoxycarbonylamino)-3-
ferrocenylpropane-1,2-diol ((+)-8)
A mixture of 3-amino-3-ferrocenyilpropane-1,2-diol
((+)-7) (69 mg, 0.25 mmol), di-tert-butyl dicarbonate
(66 mg, 0.30 mmol) and NaHCO3 (63 mg, 0.75 mmol)
in MeOH (1.3 ml) was sonicated in a cleaning bath at
r.t. for 2 h. The solids were filtered off and washed with
MeOH. Concentration of the filtrate and column chro-
matography on Et3N-pretreated silica gel (2.5% v/v),
eluting with C6H14–EtOAc mixtures of increasing po-
larity, gave 73 mg (78%) of the N-Boc amino alcohol
(+)-8 as an orange-coloured semi-solid.
3.1.9. (4S,5S)-N-(tert-Butoxycarbonyl)-2,2-
dimethyl-4-ferrocenyl-5-[(tert-butyldiphenylsilyloxy)-
methyl]-1,3-oxazolidine (10)
A solution of (+)-9 (30 mg, 0.05 mmol) and 2,2-
dimethoxypropane (65 ml, 0.50 mmol) in C6H6 (0.2 ml)
was heated to reflux for 5.5 h in the presence of a trace
of p-toluenesulfonic acid, diluted with EtOAc (10 ml)
and washed with aq. sat. NaHCO3 and with brine.
After drying over Na2SO4, elimination of the solvents
followed by chromatographic purification on Et3N-pre-
treated silica gel using C6H14–EtOAc mixtures of in-
creasing polarity as eluents afforded 22 mg (69%) of the
oxazolidine 10 as an orange–yellow oil.
[h]D= +17.9° (c=1.75, CHCl3). IR (NaCl film):
w=3406, 3097, 2979, 1686, 1507, 1368, 1250, 1169,
1
1050 cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 1.26
(t, J=4 Hz, 1H, OH), 1.50 (s, 9H), 2.85 (br, 1H, OH),
3.52 (m, 2H), 3.79 (m, 1H), 4.20 (m, 9H), 4.61 (dd,
J=8.8 Hz, J%=2.6 Hz, 1H), 5.19 (br d, J=8.8 Hz,
1H, NH). 13C-NMR (50 MHz, CDCl3): l (ppm) 28.4
(CH3), 51.0 (CH), 63.3 (CH2), 65.8 (CH), 67.8 (CH),
68.0 (CH), 68.8 (CH), 74.9 (CH), 80.3 (Cq), 87.8 (Cq,
Cp), 157.1 (Cq, CO). MS (CI, NH3) m/e=259 [M−
NHBoc+, 16%], 375 [M+, 51%], 376 [M+1+, 11%],
393 [M+18+, 2%]. HRMS (EI) Calc. for
C18H25FeNO4: 375.1133. Found: 375.1132.
IR (NaCl film): w=3074, 2933, 2860, 1700, 1378,
1108 cm−1 1H-NMR (300 MHz, 55 °C, CDCl3): l
.
(ppm)=1.10 (m, 12H), 1.46 (m, 9H), 3.77 (d, J=6.3
Hz, 2H), 4.13 (m, 9H), 4.69 (m, 1H, CH), 4.93 (m, 1H,
CH), 7.41 (m, 6H), 7.72 (m, 4H). 13C-NMR (75 MHz,
55 °C, CDCl3): l (ppm) 19.3 (Cq), 26.7 (CH3), 27.0
(CH3), 28.6 (CH3), 58.1 (CH), 65.8 (CH2), 66.7 (CH),
67.6 (CH), 68.6 (CH), 79.8 (Cq, Cp), 127.7 (CH), 129.6
(CH), 129.8 (CH), 133.3 (CH), 133.4 (CH), 133.4 (CH),
134.9 (CH), 135.7 (CH), 151.8 (Cq, CO). MS (CI, NH3)
m/e=654 [M+1+, 57%], 671 [M+18+, 4%]. HRMS
(EI) Calc. for C37H47FeNO4Si: 653.2624. Found:
653.2638.
3.1.8. (2S,3S)-1-(tert-Butyldiphenylsilyloxy)-3-
(tert-butoxycarbonylamino)-3-ferrocenyl-2-propanol
((+)-9)
A mixture of the N-Boc amino alcohol (+)-8 (0.100
g, 0.27 mmol), DMF (1.3 ml), imidazole (41 mg, 0.59
mmol) and tert-butyldiphenilsilylchloride (0.78 ml, 0.30
mmol) was stirred at r.t. for 24 h, diluted with Et2O (5
ml) and washed with aq. sat. NH4Cl solution (3×5
ml). The aq. phase was washed with Et2O (3×5 ml),
and the combined organic phase was dried over
Na2SO4. Elimination of the solvents, followed by chro-
matographic purification on Et3N-pretreated silica gel
using C6H14–EtOAc mixtures of increasing polarity as
eluents afforded 0.145 g (89%) of the title compound as
an orange–yellow semi-solid.
3.1.10. (4S,5S)-4-Ferrocenyl-5-(hidroxymethyl)-1,3-
oxazolidin-2-one ((+)-11)
To an stirred suspension of NaH (60% in paraffine
oil, 12 mg, 0.30 mmol) in DMF (1 ml), a solution of
(+)-9 (73 mg, 0.12 mmol) in DMF (0.76 ml) was
added via cannula. The resulting mixture was stirred at
r.t. for 1.5 h, treated with aq. 1 M HCl (1.5 ml) and
extracted with CH2Cl2 (3×5 ml). The organic extracts
were washed with brine, dried over Na2SO4 and submit-
ted to rotative evaporation to give a crude product that
after chromatographic purification (Et3N-pretreated sil-
ica gel, C6H14–EtOAc mixtures) afforded 30 mg (83%)
of the oxazolidinone (+)-11 as a yellow solid.
M.p. 178 °C (dec.). [h]D= +41.8° (c=0.45,
C2H4O). IR (KBr): w=3365, 2925, 1729, 1414, 1364,
1106, 1052, 1027 cm−1. 1H-NMR (200 MHz, CDCl3): l
(ppm) 3.68 (br s, 1H, OH), 3.75 (m, 1H), 3.90 (m, 1H),
4.20 (m, 9H), 4.38 (m, 1H), 4.60 (d, J=6.4 Hz, 1H),
5.26 (br s, 1H, NH). 13C-NMR (75 MHz, Me2SO-d6): l
(ppm) 52.5 (CH), 62.1 (CH2), 65.9 (CH), 66.3 (CH),
68.1 (CH), 68.4 (CH), 68.8 (CH), 82.9 (CH), 90.0 (Cq,
Cp), 158.5 (Cq, CO). MS (CI, NH3) m/e=302 [M+1+,
[h]D= +8.3° (c=1.10, CHCl3). IR (NaCl film): w=
3438, 3074, 2933, 1694, 1505, 1428, 1169, 1113 cm−1
.
1H-NMR (200 MHz, CDCl3): l (ppm) 1.08 (s, 9H),
1.43 (s, 9H), 2.66 (br s, 1H, OH), 3.61 (m, 2H), 3.93 (m,
1H), 4.11 (m, 9H), 4.55 (br d, J=7.8 Hz, 1H), 5.21 (br
d, J=8.0 Hz, 1H, NH), 7.41 (m, 6H), 7.64 (m, 4H).
13C-NMR (50 MHz, CDCl3): l (ppm) 19.3 (Cq), 26.6
(CH3), 26.9 (CH3), 28.4 (CH3), 50.5 (CH), 65.3 (CH2),
66.6 (CH), 67.3 (CH), 67.7 (CH), 68.7 (CH), 74.5 (CH),
89.1 (Cq, Cp), 127.6*, 127.7 (CH), 129.6*, 129.8 (CH),

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
221
6%], 319 [M+18+, 100%]. HRMS (EI) Calc. for
C14H15FeNO3: 301.0401. Found: 301.0402.
wR2=0.0590 [for all data], 275 parameters, with al-
lowance for the thermal anisotropy for all non-hydro-
gen atoms. The weighting scheme employed was
2
3.1.11. X-ray structure determination and refinement of
compound (+)-11
A suitable crystal grown from a MeOH solution
(block, brown, dimensions 0.35×0.20×0.15 mm) was
used for the structure determination. X-ray data were
collected using a Bruker SMART CCD area detector
single-crystal diffractometer with graphite monochro-
w=[|2(Fo2 +(0.0373P)2+0.0590P] and P=(ꢁFoꢁ +
2
2ꢁFcꢁ )/3 and the goodness-of-fit on F2 was 1.044 for all
observed reflections. Residual electron densities ex-
−3
,
tremes were 0.21 and −0.32 e A
(Table 3).
3.1.12. (S)-1-Ferrocenylethane-1,2-diol ((+)-13) and
(R)-1-ferrocenylethane-1,2-diol ((−)-13)
,
matised Mo–Ka radiation (u=0.71073 A) by the ƒ–ꢀ
To a stirred solution of K3[Fe(CN)6] (0.986 g, 3.0
mmol) and K2CO3 (0.415 g, 3.0 mmol) in 1:1 MeCN–
water (100 ml), were added (DHQD)2PYR (88 mg, 0.10
mmol) and K2OsO2(OH)4 (37 mg, 0.10 mmol), and
stirring was maintained at r.t. until complete dissolu-
tion of the osmate. At this point, vinylferrocene (12)
(0.212 g, 1.0 mmol) was added in one portion. The
reaction was monitored by TLC. When no starting
vinylferrocene remained (12 h stirring at r.t.), Na2SO3
(1.7 g, 13 mmol) was added and stirring maintained for
30 min. The reaction mixture was extracted with EtOAc
(3×15 ml); the organic extracts were dried over
Na2SO4 and the solvents were removed at reduced
pressure. Column chromatography of the crude
product (silica gel, C6H14–EtOAC mixtures as eluent)
afforded 0.196 g (79%) of (S)-1-ferrocenyl-1,2-ethane-
diol ((+)-13) (98% ee) as a yellow solid.
scan method at r.t. Crystal data: C14H15FeNO3, M=
301.12; Orthorhombic; space group P212121 (No. 19);
,
,
,
a=7.2281(16) A, b=10.6983(17) A, c=16.010(5) A;
3
V=1238.0(5) A ; Z=4; Dcalc=1.616 g cm−3; air-sta-
,
ble crystals, v(Mo–Ka)=1.220 mm−1. A total of 1271
frames of intensity data were collected. The first 50
frames were recollected at the end of data collection to
monitor for decay. The integration process yielded a
total of 8568 reflections in the range 2.3BqB28.3, of
which 3065 [Rint=0.0178] were independent. Absorp-
tion corrections were applied using the SADABS [28]
program (maximum and minimum transmission coeffi-
cients 0.838 and 0.675). The structure was solved using
the Bruker SHELXTLC-PC [29] software by direct meth-
ods and refined by full-matrix least-squares procedures
on F2. Hydrogen atoms were included in calculated
positions and refined in the riding mode. Convergence
was reached at a final R1=0.0225 [R1=ꢀ ꢁꢁFoꢁ−ꢁFcꢁꢁ/
ꢀ ꢁFoꢁ] and wR2=0.0581 [wR2={ꢀ [w(F2o−Fc2)2]/
ꢀ [w[(F2o)2]}1/2], for I\2|(I); and R1=0.0244 and
M.p. 98.2–100.2 °C. (lit: 98–100 °C) [20]. [h]D=
1
+32.3° (c=0.38, CH2Cl2). (lit: +23.8) [20]. H-NMR
(200 MHz, CDCl3): l (ppm) 2.08 (m, 1H, OH), 2.15 (m,
1H, OH), 3.66 (m, 1H), 3.76 (m, 1H), 4.23 (m, 9H),
4.47 (m, 1H).
Table 3
In a similar way, but using (DHQ)2PYR as the chiral
ligand, vinylferrocene (12) (1.0 mmol) afforded 0.211 g
(86%) of (R)-1-ferrocenyl-1,2-ethanediol ((−)-13) (ee
\80%) as a yellow solid. M.p. 95.5–96.7 °C. (lit:
101–103 °C) [20]. [h]D= −23.1° (c=0.38, CH2Cl2).
(lit: −23.3) [20]. Conditions for the HPLC determina-
tion of the enantiomeric purity of 13: Chiralcel-OD
column, 95% C6H14–5% isopropyl alcohol, b=0.8 ml
Atomic coordinates (×104) and equivalent isotropic displacement
2
3
,
parameters (A ×10 ) for (+)-11
a
Atom
x
y
z
Ueq
Fe(1)
O(1)
O(2)
O(3)
N(1)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
8305(1)
10080(1)
6760(1)
6368(1)
8877(1)
8089(1)
8689(1)
7034(2)
7667(1)
8115(2)
8965(1)
8244(1)
8763(2)
9793(2)
9921(2)
10953(2)
10200(2)
10635(2)
11653(2)
11839(2)
4945(1)
7388(1)
7615(1)
7023(1)
6883(1)
6651(1)
7313(1)
6930(1)
7485(1)
5739(1)
5056(1)
4308(1)
4524(1)
5410(1)
5591(2)
4960(2)
4183(2)
4355(1)
5223(1)
23(1)
39(1)
41(1)
43(1)
32(1)
25(1)
30(1)
28(1)
38(1)
24(1)
27(1)
33(1)
35(1)
30(1)
51(1)
61(1)
60(1)
51(1)
45(1)
9861(2)
6844(2)
13750(2)
7820(2)
9554(2)
8030(2)
10955(2)
12508(2)
9752(2)
9060(2)
9783(2)
10924(2)
10915(2)
6249(3)
5504(2)
6221(3)
7404(3)
7408(3)
min−1
R(R)=38.5 min.
, T=25 °C, u=220 nm, tR(S)=36.4 min,
t
3.1.13. (S)-2-Acetyloxy-1-ferrocenylethyl acetate
((+)-14) and (R)-2-acetyloxy-1-ferrocenylethyl acetate
((−)-14)
A solution of (S)-ferrocenylethanediol ((+)-13) (1.50
g, 6.1 mmol) in anhydrous Py (12 ml) was treated with
Ac2O (6 ml, 54 mmol) and the resulting mixture was
stirred at r.t. for 12 h (when TLC monitoring showed
that the reaction was complete). Evaporation of the
solvents at reduced pressure afforded the diacetate (+)-
14 (1.942 g, 97%) as a brown–orange dense oil that was
used without further purification, since extensive de-
composition took place during column chromatogra-
a Ueq is defined as one-third of the trace of the orthogonalised Uij
tensor.

222
M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
phy (silica gel, C6H14–EtOAc mixtures of increasing
polarity).
dropwise, the reaction mixture was warmed up to r.t.
and stirred until a white precipitate was formed. The
solids were filtered out, washed with EtOAc and the
filtrates were evaporated at reduced pressure to afford
0.395 g (97%) of pure azido alcohol (+)-16 as a yellow
solid.
M.p. 64.8–69.8 °C. [h]D= +9.5° (c=1.03, CHCl3).
IR (NaCl film): w=1740, 1371, 1240, 1107, 1045, 820
1
cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 2.09 (s,
3H), 2.10 (s, 3H), 4.19 (m, 9H), 4.26 (m, 1H), 4.62 (m,
1H), 5.90 (m, 1H). 13C-NMR (50 MHz, CDCl3): l
(ppm) 20.8 (CH3), 21.1 (CH3), 65.7 (CH2), 66.4 (CH),
68.1 (CH), 68.3 (CH), 68.4 (CH), 68.9 (CH), 69.9 (CH),
83.1 (Cq, Cp), 170.4 (Cq, CO), 170.8 (Cq, CO). MS
(CI, NH3) m/e=330 [M+, 1%], 331 [M+1+, 1%], 271
[M−59+, 100%].
M.p. 41–43 °C. [h]D= +50.5° (c=0.49, CHCl3).
IR (KBr): w=3386, 2929, 2105,1258, 1107, 1044, 821
1
cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 1.99 (br,
1H), 3.72 (m, 1H), 3.91 (m, 1H), 4.19 (m, 9H), 4.44 (dd,
J1=8 Hz, J2=4 Hz, 1H). 13C-NMR (50 MHz,
CDCl3): l (ppm) 63.9 (CH), 65.8 (CH2), 66.3 (CH),
67.2 (CH), 68.3 (CH), 68.5 (CH), 68.9 (CH), 84.0 (Cq).
MS (CI, NH3) m/e=271 [M+, 2%], 289 [M+18+,
20%], 229 [M−42+, 100%]. HRMS (EI) Calc. for
C12H13FeN3O: 271.0408. Found: 271.0420.
In a similar way, azido acetate (−)-15 afforded
azido alcohol (−)-16, [h]D= −42.1° (c=1.05,
CHCl3).
In a similar way, diol (−)-13 afforded diacetate
(−)-14, [h]D= −9.2° (c=1.05, CHCl3).
3.1.14. (S)-2-Azido-2-ferrocenylethyl acetate ((+)-15)
and (R)-2-azido-2-ferrocenylethyl acetate ((−)-15)
To a solution of diacetate (+)-14 (1.20 g, 3.64
mmol) in a 1:3 MeOH–water mixture (100 ml) sodium
azide (1.31 g, 20.1 mmol) was added in one portion.
The mixture was stirred at r.t. until TLC analysis
showed no presence of the starting product (12 h).
After eliminating most of the MeOH at reduced pres-
sure, saturated brine solution (25 ml) was added and
the mixture was extracted with CH2Cl2 (3×20 ml). The
organic phases were dried over MgSO4, stripped of
solvents at reduced pressure and purified by column
chromatography (silica gel, C6H14–EtOAc mixtures of
increasing polarity) to afford 0.82 g (72%) of the azido
acetate (+)-15 (98% ee) as a yellow solid.
3.1.16. (S)-2-Amino-2-ferrocenylethanol ((+)-17) and
(R)-2-amino-2-ferrocenylethanol ((−)-17)
To a stirred suspension of 10% Pd/C (0.100 g) in
EtOAc (15 ml) under a H2 atmosphere, a solution of
(S)-2-azido-2-ferrocenylethanol ((+)-16) (1.07 g, 3.95
mmol) in EtOAc (15 ml) was added via cannula. The
mixture was stirred at r.t. for 12 h under H2; the
mixture was filtered through a Celite® pad and the
solvent was removed under vacuum, to afford 0.967 g
(100%) of the desired amino alcohol (+)-17 as a yellow
solid.
M.p. 48.5–50.5 °C. [h]D= +21.4° (c=0.99,
CHCl3). IR (KBr): w=3096, 2957, 2105, 1746, 1383,
M.p. 97.8–101.5 °C. [h]D= +11.1° (c=1.03,
MeOH). IR (KBr): w=3095, 2925, 1653, 1559, 1458,
1225, 1108, 1043, 1003, 822 cm−1 1H-NMR (200
.
MHz, CDCl3): l (ppm) 2.25 (s, 3H), 4.53 (m, 2H), 4.18
(m, 10H). 13C-NMR (50 MHz, CDCl3): l (ppm) 20.9
(CH3), 60.4 (CH2), 66.3 (CH), 66.7 (CH), 67.3 (CH),
68.4 (CH), 68.5 (CH), 69.0 (CH), 84.0 (Cq, Cp), 170.4
(Cq, CO). MS (CI, NH3) m/e=13 [M+, 2%], 271
[M−42+, 90%]. HRMS (EI) Calc. for C14H15FeN3O2:
313.0514. Found: 313.0514.
In a similar way, diacetate (−)-14 afforded azido
acetate (−)-15 (87% ee), [h]D= −20.7° (c=1.00,
CHCl3). Conditions for the HPLC determination of the
enantiomeric purity of 15: Chiralcel-OD column, 90%
C6H14–10% isopropyl alcohol, b=0.5 ml min−1, T=
25 °C, u=220 nm, tR(S)=17.9 min, tR(R)=16.6 min.
1
1412, 1258, 1105, 1040, 1001, 818, 733 cm−1. H-NMR
(200 MHz, CDCl3): l (ppm) 2.10 (br s, 3H), 3.46 (m,
1H), 3.75 (m, 2H), 4.18 (m, 9H). 13C-NMR (50 MHz,
CDCl3): l (ppm) 51.9 (CH), 65.7 (CH), 66.4 (CH), 67.2
(CH2), 67.7 (CH), 67.8 (CH), 68.4 (CH), 90.8 (Cq). MS
(CI, NH3) m/e=245 [M+, 2%], 246 [M+1+, 7%], 229
[M−16+, 100%]. HRMS (EI) Calc. for C12H15FeNO:
245.0503. Found: 245.0492.
In a similar way, azido alcohol (−)-16 afforded
amino alcohol (−)-17, [h]D= −9.7° (c=1.18,
MeOH).
3.1.17. (S)-4-Ferrocenyl-1,3-oxazolidin-2-one ((+)-18)
and (R)-4-ferrocenyl-1,3-oxazolidin-2-one ((−)-18)
To a solution of (S)-2-amino-2-ferrocenylethanol
((+)-17) (0.100 g, 0.41 mmol) in CH2Cl2 (2 ml) was
added a 6 M NaOH aq. solution (0.3 ml, 1.8 mmol).
The resulting mixture was cooled to 0 °C and triphos-
gene (60 mg, 0.2 mmol) was added in one portion;
stirring was maintained for 1 h at the same temperature
and at this point TLC analysis showed that the reaction
was complete. The dark-brown mixture was diluted
3.1.15. (S)-2-Azido-2-ferrocenylethanol ((+)-16) and
(R)-2-azido-2-ferrocenylethanol ((−)-16)
To a cold (−78 °C), stirred solution of the azido
acetate (+)-15 (0.470 g, 1.5 mmol) in anhydrous Et2O
(4 ml), 3.8 ml (3.8 mmol) of a 1 M solution of di-
isobutylaluminum hydride in hexanes were added via
syringe, and stirring was maintained for 1 h at the same
temperature. At this point, TLC analysis showed that
no starting material remained; MeOH (5 ml) was added

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
223
with water (8 ml) and the aq. phase was extracted with
CH2Cl2 (3×10 ml). The combined organic extracts
were dried over Na2SO4 and the solvents were distilled
off under vacuum. Chromatographic purification (silica
gel, C6H14–EtOAc mixtures of increasing polarity) af-
forded 82 mg (74%) of the title compound as an orange
solid.
sequentially. The resulting mixture was heated to reflux
for 2 h. Elimination of the solvent under vacuum
followed by chromatographic purification (silica gel,
C6H14–EtOAc mixtures) afforded 25 mg (29%) of the
title compound as a brown semi-solid.
[h]D= −45.4° (c=0.56, CHCl3). IR (NaCl film):
w=3095, 2910, 1737, 1655, 1498, 1470, 1245, 1110
1
M.p. 154.2–155.0 °C. [h]D= +24.9° (c=1.00,
CHCl3). IR (KBr): w=3250, 3095, 2910, 1790, 1755,
cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 1.60 (s,
6H), 4.14 (m, 18H), 4.40 (t, J=7.7 Hz, 2H), 4.57 (dd,
J1=9.8 Hz, J2=8.0 Hz, 2H), 4.93 (dd, J1=9.8 Hz,
J2=7.7 Hz, 2H). 13C-NMR (50 MHz, CDCl3): l (ppm)
24.5 (CH3), 38.8 (Cq), 64.8 (CH), 66.4 (CH), 66.9 (CH),
67.86 (CH), 67.94 (CH), 68.4 (CH), 74.1 (CH2), 90.4
(Cq, Cp), 168.8 (Cq). MS (CI, NH3) m/e=550 [M+,
100%], 551 [M+1+, 37%], 568 [M+18+, 14%].
HRMS (EI) Calc. for C29H30Fe2N2O2: 550.1006.
Found: 550.1033.
1
1415, 1390, 1245, 1110, 1035, 815 cm−1. H-NMR (300
MHz, CDCl3): l (ppm) 4.21 (m, 10H), 4.66 (m, 2H),
5.30 (br s, 1H). 13C-NMR (75 MHz, CDCl3): l (ppm)
52.1 (CH), 66.0 (CH), 66.4 (CH), 68.6 (CH), 68.6 (CH),
68.9 (CH), 71.5 (CH2), 87.0 (Cq, Cp), 159.2 (Cq, CO).
MS (CI, NH3) m/e=271 [M+, 1%], 289 [M+18+,
74%], 306 [M+35+, 100%]. HRMS (EI) Calc. for
C13H13FeNO2: 271.0296. Found: 271.0298.
In a similar way, amino alcohol (−)-17 furnished
(R)-4-ferrocenyl-1,3-oxazolidin-2-one ((−)-18), [h]D=
−23.7° (c=1.09, CHCl3).
3.1.19. (R)-N-(1-Ferrocenyl-2-hydroxyethyl)-
(2-fluorophenyl)carboxamide ((−)-20)
To
a
stirred solution of (R)-2-amino-2-ferro-
3.1.18. (R,R)-4-Ferrocenyl-2-[1-methyl-1-( ferrocenyl-
(1,3-oxazolin-2-yl))ethyl]-1,3-oxazoline ((−)-19)
cenylethanol ((−)-17) (0.500 g, 2.04 mmol) in anhy-
drous THF (3 ml) freshly distilled Et3N (0.55 ml, 3.95
mmol) was added with a calibrated syringe. The result-
ing mixture was cooled to 0 °C, a solution of 2-
fluorobenzoyl chloride (0.310 g, 1.96 mmol) in
anhydrous THF (2.5 ml) was added dropwise, and the
mixture was stirred at r.t. for 2 h, at which point TLC
analysis showed the complete disappearance of the
starting amino alcohol. The solvents were distilled un-
der vacuum, the residue was taken up in CH2Cl2 (10
ml) and washed with brine (10 ml). The organic phase
was dried over Na2SO4 and stripped of solvents at
reduced pressure. Chromatographic purification (silica
gel, C6H14–EtOAc mixtures) afforded 0.641 g (89%) of
hydroxyamide (−)-20 as a yellow solid.
To a stirred solution of dimethylmalonic acid (27 mg,
0.20 mmol) in anhydrous THF (2 ml) were added a
solution of N-hydroxysuccinimide (57 mg, 0.49 mmol)
in anhydrous THF (1.5 ml) and a solution of N,N%-di-
cyclohexylcarbodiimide (101 mg, 0.49 mmol) in anhy-
drous THF (1.5 ml). The resulting mixture was stirred
at r.t. for 2.5 h, and a solution of (R)-2-amino-2-ferro-
cenylethanol ((−)-17) (100 mg, 0.41 mmol) in anhy-
drous THF (2 ml) was added with a calibrated syringe.
The reaction was monitored by TLC. When no starting
amino alcohol remained (15 h), the solvent was re-
moved at reduced pressure, the residue was taken up in
EtOAc (15 ml) and washed with brine (3×10 ml). The
combined organic extracts were dried over Na2SO4.
Elimination of the solvent afforded a crude product
that was purified by column chromatography on silica
gel, eluting with C6H14–EtOAc mixtures of increasing
polarity, to give 92 mg (77%) of the expected bis(hy-
droxyamide) as a yellow solid.
M.p. 101.5–103.0 °C. [h]D= −3.6° (c=1.00,
CH2Cl2). IR (KBr): w=3037, 2915, 1727, 1640, 1510,
1
1473, 1105, 1035, 815, 757 cm−1. H-NMR (200 MHz,
CDCl3): l (ppm) 3.36 (br s, 1H), 3.86 (dd, J1=10.8 Hz,
J2=3.8 Hz, 1H), 4.00 (dd, J1=10.8 Hz, J2=3.8 Hz,
1H), 4.12 (dd, J1=6.0 Hz, J2=3.8 Hz, 1H), 4.23 (s,
9H), 5.10 (br, 1H), 7.1–7.6 (m, 3H), 8.17 (m, 1H).
13C-NMR (50 MHz, CDCl3): l (ppm) 51.3 (CH), 66.1
(CH), 66.5 (CH), 66.8 (CH2), 66.9 (CH), 68.1 (CH),
68.6 (CH), 86.4 (Cq, Cp), 116.0 (CH), 120.2 (Cq), 124.8
(CH), 132.1 (CH), 133.5 (CH), 158.1 (Cq), 163.2 (Cq).
MS (FAB(+)) m/e=367 [M+], 349 [M−18+], 399
[M+23+]. HRMS (EI) Calc. for C19H18FFeNO2:
367.0671. Found: 367.0679.
M.p. 54.2–57.0 °C. IR (KBr): w=3315, 3090, 2915,
1730, 1655, 1505, 1185, 1125, 1110, 970, 820, 735 cm−1
.
1H-NMR (300 MHz, CDCl3): l (ppm) 1.58 (s, 3H),
1.63 (s, 3H), 3.32 (m, 2H), 3.99 (m, 4H), 4.22 (m, 18H),
4.90 (m, 2H), 6.87 (m, 2H). 13C-NMR (75 MHz,
CDCl3): l (ppm) 23.6 (CH3), 50.8 (CH), 66.2 (CH),
66.4 (CH), 66.5 (CH), 68.2 (CH2), 68.8 (CH), 86.0(CH),
86.0 (Cq, Cp), 173.7 (Cq, CO). MS (posit. electrospray)
m/e=587 [M+1+], 569.
To a stirred solution of the above-obtained com-
pound (90 mg, 0.16 mmol) in 1,2-dichloroethane (3 ml),
Et3N (0.22 ml, 1.57 mmol), 4-(N,N-dimethy-
lamino)pyridine (2 mg, 0.016 mmol) and p-toluene-
sulphonyl chloride (84 mg, 0.44 mmol) were added
3.1.20. (R)-4-Ferrocenyl-2-(2-fluorophenyl)-1,3-
oxazoline ((−)-21)
To a solution of the hydroxyamide (−)-20 (0.560 g,
1.53 mmol) in anhydrous CH2Cl2 (4.5 ml), 4-(N,N-
dimethylamino)pyridine (93 mg, 0.76 mmol), freshly

224
M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
distilled Et3N (1.05 ml, 7.53 mmol) and p-toluene-
sulphonyl chloride (0.407 g, 2.13 mmol) were added
sequentially. The resulting mixture was heated to reflux
for 1 h, when TLC analysis showed that the reaction
was complete, and cooled to r.t. After the addition of
water (0.1 ml), stirring was maintained for 30 min and
the reaction mixture was washed with water (3×5 ml).
The organic phase was extracted with CH2Cl2 (5 ml).
The combined organic phases were dried over Na2SO4
and the solvent was distilled off at reduced pressure.
Chromatographic purification (silica gel, C6H14–EtOAc
mixtures) gave 0.415 g (78%) of the desired oxazoline
(−)-21 as an orange solid.
129.2, 129.9, 130.0, 130.4 (CHꢀAr), 131.8 (CqꢀAr,
CꢀP=20 Hz), 133.5, 133.8, 133.9, 134.2 (CHꢀAr),
138.0 (CqꢀAr, JCꢀP=10.4 Hz), 138.1 (CqꢀAr, JCꢀP
11.8 Hz), 138.7 (CqꢀAr, JCꢀP=25.5 Hz), 163.2 (Cq).
MS (FAB(+)) m/e=516 [M+], 331 [M−185+].
HRMS (EI) Calc. for C31H27FeNOP 516.1180. Found:
516.1190.
J
=
3.1.22. Ethyl (2S,3S)-3-azido-3-ferrocenyl-2-
hydroxypropanoate ((−)-23)
A cold (0 °C) solution of sodium ethoxide, prepared
from 12 mg (0.52 mmol) of Na and anhydrous EtOH
(12 ml), was added via cannula to azido acetate (+)-6
(0.197 g, 0.51 mmol), and the resulting mixture was
stirred at 0 °C until TLC showed that no starting
product remained (1.5 h). A 10% aq. solution of citric
acid (12 ml) was added and the mixture was extracted
with CH2Cl2 (3×20 ml). The organic extracts were
dried over Na2SO4 and the solvents were eliminated at
reduced pressure. Column chromatography on silica
gel, eluting with C6H14–EtOAc mixtures of increasing
polarity, afforded 0.150 g (85%) of the desired 2-hy-
droxypropanoate (−)-23 as a yellow–orange solid.
M.p. 85.5–87.0 °C. [h]D= −61.7° (c=0.9, CHCl3).
IR (KBr): w=3496, 3097, 2929, 2109, 1735, 1266, 1108
M.p. 175.0–177.4 °C. [h]D= −118° (c=1.02,
CH2Cl2). IR (KBr): w=2362, 1636, 1560, 1497, 1457,
1
780 cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 4.17
(m, 9H), 4.54 (t, J=8 Hz, 1H), 4.71 (dd, J1=9.8 Hz,
J2=8 Hz, 1H), 5.15 (dd, J1=10 Hz, J2=7.8 Hz, 1H),
7.20 (m, 2H), 7.46 (m, 1H), 7.93 (m, 1H). 13C-NMR (50
MHz, CDCl3): l (ppm) 65.5 (CH), 66.3 (CH), 67.3
(CH), 68.0 (CH), 68.2 (CH), 68.5 (CH), 73.3 (CH2),
89.9 (Cq, Cp), 116.2 (Cq), 116.6 (CH), 123.9 (CH),
131.3 (CH), 132.9 (CH), 160.4 (Cq), 162.9 (Cq). MS
(CI, NH3) m/e=349 [M+, 100%], 350 [M+1+, 25%].
HRMS (EI) Calc. for C19H16FFeNO: 349.0565. Found:
349.0565.
1
cm−1. H-NMR (200 MHz, CDCl3): l (ppm) 1.37 (t,
J=7.4 Hz, 3H), 3.15 (d, J=6 Hz, 1H, OH), 4.25 (m,
11H), 4.55 (d, J=2 Hz, 1H), 4.61 (dd, J=6 Hz, J=2
Hz, 1H). 13C-NMR (50 MHz, CDCl3): l (ppm) 14.3
(CH3), 62.5 (CH2), 63.2 (CH), 68.1 (CH), 68.5 (CH),
68.6 (CH), 68.8 (CH), 68.9 (CH), 74.1 (CH), 84.0 (Cq,
Cp), 172.1 (Cq, CO). MS (CI, NH3) m/e=301 [M−
N+3 , 100%], 344 [M+1+, 6%], 361 [M+18+, 71%].
HRMS (EI) Calc. for C15H17FeN3O3: 343.0619. Found:
343.0629.
3.1.21. (R)-Diphenyl[2-(4-ferrocenyl(1,3-oxazolin-
2-yl))phenil]phosphine ((−)-22)
To a cold (−78 °C), stirred suspension of (R)-4-fer-
rocenyl-2-(2-fluorophenyl)-1,3-oxazoline
((−)-21)
(0.100 g, 0.29 mmol) in anhydrous THF (2 ml), under
Ar atmosphere, a filtered THF solution of lithium
diphenylphosphide (prepared from 13 mg (1.9 mmol) of
Li, 0.262 g (1.0 mmol) of triphenylphosphine and 0.110
g (1.12 mmol) of NH4Br in 4 ml of anhydrous THF)
was added via cannula. The resulting mixture was
stirred at −20 °C for 2 h and at r.t. for 12 h, and
treated with a solution of Na2SO4 (0.425 g) in water
(0.55 ml). The organic layer was filtered through a short
pad of silica gel, that was subsequently washed with
EtOAc. Elimination of the solvents under vacuum af-
forded a crude product that was purified by column
chromatography on silica gel, eluting with C6H14–
EtOAc mixtures of increasing polarity, to give 0.112 g
(76%) of the title compound as an orange solid.
3.1.23. Ethyl (2S,3S)-3-amino-3-ferrocenyl-2-
hydroxypropanoate ((+)-24)
A solution of the azido ester (−)-23 (0.100 g, 0.29
mmol) in EtOAc (1 ml) was stirred under an atmo-
sphere of H2 at r.t. for 18 h, in the presence of 10%
Pd/C (10 mg). The reaction mixture was filtered
through a Celite® pad, that was thoroughly washed
with EtOAc. Elimination of the solvent at reduced
pressure followed by chromatographic purification on
Et3N-pretreated silica gel (2.5% v/v) using C6H14–
EtOAc mixtures of increasing polarity as eluents af-
forded 75 mg (82%) of ethyl (2S,3S)-3-amino-3-
ferrocenyl-2-hydroxypropanoate ((+)-24) as an or-
ange-coloured dense oil.
M.p. 54.5–56.3 °C. [h]D= −72.4° (c=0.76,
CH2Cl2). IR (KBr): w=3069, 1653, 1476, 1434, 1355,
1
1090, 1032, 959, 909, 743, 697 cm−1. H-NMR (200
MHz, CDCl3): l (ppm) 4.05 (m, 9H), 4.22 (t, J=7.9
Hz, 1H), 4.38 (dd, J1=9.8 Hz, J2=8.1 Hz, 1H), 4.92
(dd, J1=9.8 Hz, J2=8.1 Hz, 1H), 6.93 (m, 2H), 7.2–
7.5 (m, 10H), 7.95 (m, 2H). 13C-NMR (50 MHz,
CDCl3): l (ppm) 65.4 (CH), 66.5 (CH), 66.9 (CH), 67.6
(CH), 67.9 (CH), 68.4 (CH), 73.1 (CH2), 90.1 (Cq, Cp),
128.0, 128.2, 128.26, 128.32, 128.37, 128.41, 128.46,
[h]D= +49.5° (c=0.85, CHCl3). IR (NaCl film):
w=IR (KBr): 3380, 2990, 2910, 1715, 1550, 1395, 1248,
1090, 1010 cm−1 1H-NMR (200 MHz, CDCl3): l
.
(ppm) 1.31 (t, J=7.4 Hz, 3H), 2.35 (br s, 3H, NH2+
OH), 4.32 (m, 13H). 13C-NMR (50 MHz, CDCl3): l
(ppm) 14.2 (CH3), 53.4 (CH), 61.7 (CH2), 66.2 (CH),

M. Catasu´s et al. / Journal of Organometallic Chemistry 642 (2002) 212–226
225
(c) A. Abiko, S. Masamune, Tetrahedron Lett. 33 (1992) 5517;
(d) A.I. Meyers, M.J. McKennon, J. Org. Chem. 58 (1993) 3568;
(e) H.M. Moody, B. Kaptein, Q.B. Broxterman, W.H.J. Boesten,
J. Kamphuis, Tetrahedron Lett. 35 (1994) 1777;
(f) S. Narasimhan, S. Madhavan, K.G. Prasad, Synth. Commun.
26 (1996) 703;
67.2 (CH), 67.7 (CH), 67.9 (CH), 68.4 (CH), 74.5 (CH),
91.1 (Cq, Cp), 173.4 (Cq, CO). MS (CI, NH3) m/e=
301 [M−NH+2 , 100%], 318 [M+1+, 36%]. HRMS
(EI) Calc. for C15H19FeNO3: 317.0714. Found:
317.0705.
(g) R.C. Anand, Vimal, Tetrahedron Lett. 39 (1998) 917;
(h) M.T. Reetz, A. Schmitz, Tetrahedron Lett. 40 (1999) 2737.
[4] (a) M. Kitamura, S. Suga, K. Kawai, R. Noyori, J. Am. Chem.
Soc. 108 (1986) 6071;
4. Supplementary material
(b) P.A. Chaloner, S.A.R. Perera, Tetrahedron Lett. 28 (1987)
3013;
Crystallographic data (excluding structure factors)
for the structure reported in this paper have been
deposited with the Cambridge Crystallographic Data
Center as supplementary publication no. CCDC-167245
for compound (+)-11. Copies of this data can be
obtained free of charge on application to The Director,
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: +44-1223-336033; e-mail: deposit@ccdc.cam.
ac.uk or www: http://www.ccdc.cam.ac.uk).
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Acknowledgements
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We gratefully acknowledge financial support from
DGI (grant BQU2000-0648) and from DGES (grant
PB98-1246). M.C. is grateful to the University of
Barcelona for a predoctoral fellowship.
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