Synthesis of a new class of chiral aminoalcohols and their application in the enantioselective addition of diethylzinc to aldehydes

Article abstract of DOI:10.1016/S0957-4166(00)00381-5

Five new aminoalcohols containing a 2,2'-bridged binaphthyl entity were synthesised and applied as auxiliaries in the enantioselective addition of Et₂Zn to ten aldehydes. While reactivities were generally high and low concentrations of aminoalc

Full text of DOI:10.1016/S0957-4166(00)00381-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4207–4219
Synthesis of a new class of chiral aminoalcohols and their
application in the enantioselective addition of diethylzinc to
aldehydes
Nieves Arroyo,a,† Ulrike Haslinger,a Kurt Mereiterb and Michael Widhalma,*
aInstitut fu¨r Organische Chemie, Universita¨t Wien, Wa¨hringerstaße 38, A-1090 Vienna, Austria
bInstitute of Mineralogy, Crystallography and Structural Chemistry, Technical University of Vienna,
Getreidemarkt 9, A-1040 Vienna, Austria
Received 9 September 2000; accepted 19 September 2000
Abstract
Five new aminoalcohols containing a 2,2%-bridged binaphthyl entity were synthesised and applied as
auxiliaries in the enantioselective addition of Et2Zn to ten aldehydes. While reactivities were generally
high and low concentrations of aminoalcohols were found sufficient to achieve complete conversions (<1
mol%), the observed enantioselectivities were highly dependent upon auxiliary and substrate structure. Up
to 97% e.e.s have been observed in the case of aromatic substrates but significantly lower degrees of
asymmetric induction were found for aliphatic substrates (up to ca. 60% e.e.). Suggestions concerning the
structure of the transition states based on molecular mechanics calculations are presented to rationalise
different enantiocontrol. © 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
Carbonꢀcarbon bond-forming reactions conducted under ‘asymmetric’ conditions result in the
formation of new stereogenic centres with defined configuration, and constitute a group of either
stoichiometric or substoichiometric synthetic methods for the construction of a chiral carbon
framework in an enantioselective and subsequently diastereoselective fashion. The stereoselective
generation of the first asymmetric centre in a target molecule is most difficult to achieve and
research in the wide and steadily growing field of catalytic asymmetric synthesis is devoted to
this challenge.1 This represents, in principle, some type of enantioface discrimination of
* Corresponding author. E-mail: m.widhalm@univie.ac.at
† Present address: Instituto Lora-Tamayo, CSIC, Juan de la Cierva, 3, 28002 Madrid, Spain.
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00381-5

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prochiral entities, present either in the substrate or generated during the course of the reaction
and preceding the configuration determining step. The desired enantioselectivity is brought
about by interaction with a chiral auxiliary, usually an enantiopure additive which acts either as
a ligand in (transition) metal catalysed reactions, or as a modifier of a reagent. With few
exceptions the latter type requires at least stoichiometric amounts of auxiliary to ensure
complete formation of the chiral reagent.2 Only in cases when the unmodified reagent is
significantly less reactive do auxiliaries present in substoichiometric amounts give satisfying
levels of asymmetric induction. To the latter group belong organozincs,3 which add to
aldehydes4 or in 1,4-fashion to enones5 if various chiral auxiliaries such as diols,6 amino-
alcohols,7 diamides and diamines,8 oxazoline derivatives,9 diphosphines,10 amidophosphines,11
phosphorus amidites,12 or aminophosphines13 are added. In the case of conjugate addition Ni or
Cu salts are necessary to promote the conversion. Except for some diol and diamide auxiliaries,
which have been applied as orthotitanate complexes, typically no further additives are required
in the alkylation of aldehydes. Mechanistic investigations point to dinuclear zinc intermediates
and equilibria of diastereomeric dimers.14 As a consequence dramatic ‘chiral amplification’
effects have been reported in several cases.15
However, in the overwhelming majority of applications at least 2 mol%, typically 5 mol%, of
auxiliary has to be added for optimum stereocontrol. Since numerous auxiliaries, most of them
with amino and hydroxy groups, have been developed which show excellent enantioselection for
both aromatic and aliphatic substrates, further investigations in this field focus on varying the
structure of the zinc reagents16 and also on economic aspects such as lowering the concentration
and/or recovery of ligands and facilitating work-up procedures by using polymeric or supported
auxiliaries.17 Moreover, a clearer relationship between ligand geometry and asymmetric induc-
tion is desired to enable a rational choice of properly designed ligands for specific applications.
2. Results and discussion
Chiral diols or aminoalcohols have often been derived either from natural sources, such as
amino acids or carbohydrates,18 or make use of structural motifs which have proven their high
efficiency in other asymmetric transformations. 1,1%-Binaphthyl derivatives19 and 1,2-disubsti-
tuted ferrocenes20 belong to the latter group. In view of high enantioselectivities observed with
ligands bearing the 2,2%-bridged binaphthyl fragment 1, which represents a tert amino group
with a C2-symmetrical environment,21 this chiral entity was chosen to prepare new amino-
alcohols 2 and 3 with a rather rigid backbone. Since we were also interested in a combination
of axial and planar chiral elements22 the diastereomeric aminoalcohols 4 and 5 were also
investigated to test for possible synergistic effects. While in 2 and 3 exclusively binaphthyl-orig-
inated effects will operate, the influence of the ferrocene unit in 4 and 5 might become evident
with matched and mismatched pairs of stereogenic centres. For comparative studies compound
6 with primary alcohol functionality was also prepared (Fig. 1). All aminoalcohols were
prepared by lithium/halogen exchange of the corresponding bromides at low temperature (2–5)
or more conveniently via diastereoselective ortho-metallation (4 and 6) and subsequent treat-
ment with benzophenone or paraformaldehyde, respectively.22b Isolated yields of enantiopure
aminoalcohols range from 70 to 90% (Scheme 1).

N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
4209
Figure 1. Chiral aminoalcohols
Scheme 1.
2.1. X-ray structures
To obtain reasonable starting geometries for molecular mechanics calculations (see below),
crystal structure analyses of two aminoalcohols, (S)-2 (orthorhombic space group P212121,
Z=4) and rac-4 (monoclinic space group P21/n, Z=4) were performed (Figs. 2 and 3).
Expectedly the structures show similar geometric features. In both structures the presence of a
,
distinct hydrogen bond determines the overall geometry (OꢀN=2.60 and 2.70 A, respectively).
Ph rings of the carbinol substituents adopt propeller arrangements. In rac-4 one HOC(29)ꢀC(36)
lies in the Cp plane, while the second Ph ring points away from iron. Also the relative twist of
Ph rings is nearly identical (75.5° in (S)-2 and 77.4° in rac-4). A smaller biaryl angle of 55.5° was
found in the ferrocene compound than for the o-phenylene-bridged analogue with 61.6°.

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Figure 2. Crystal structure of (S)-2
Figure 3. Crystal structure of rac-2; (Sa)(Sm) configuration depicted
Asymmetric ethylations were routinely carried out on a 2 mmol scale in 5 mL of solvent at
room temperature at reaction times of 24 h if not otherwise stated. After extractive work-up, the
crude products were purified by Kugelrohr distillation and e.e. was determined on the basis of
specific rotation and by chiral HPLC (see Section 4). To get a general view of ligand
performance benzaldehyde was investigated first (Table 1). Ligands 2 and 3 showed moderate
and low asymmetric induction reflecting the more efficient steric interaction in a five-membered
than in a six-membered chelate ring. A significant improvement was achieved with the
introduction of the ferrocene unit. Only with ligand 4 with an (Sa)(Sm) configuration did the e.e.
exceed 90%. In the second stereoisomer 5 the ‘wrong’ metallocene configuration had a
deleterious effect with low e.e. Compound 5 obviously represents the stereoisomer with
mismatched stereogenic centres. Also in terms of reactivity and stability 4 was outstanding; only

N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
4211
Table 1
Addition of diethylzinc to benzaldehyde in the presence of aminoalcohols 2–6a
Entry
Solvent
Ligand
Temp.
Reaction time (h)
Ligand (mol%)
Isolated yieldb
e.e.c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
THF
2
3
4
4
4
4
4
4
4
4
4
4
5
6
rt
rt
rt
rt
rt
rt
rt
rt
24
24
72
48
24
24
24
24
48
48
24
24
24
24
1
1
0.1
0.3
1
3
5
10
5
5
89
69
78d
77
84
81
84
75
77
79
76
79
79
79
51 S
19 R
72 S
95 S
96 S
96 S
95 S
96 S
94 S
94 S
95 S
97 S
2 S
0°C
−10°C
rt
rt
rt
5
5
1
5
Hexane
Toluene
Toluene
rt
78 S
a 2 mmol scale; for details see Section 4.
b After Kugelrohr distillation.
c By HPLC: Daicel® OD-H.
d Conversion (NMR).
0.3 mol% were required to effect complete conversion after 48 h at room temperature. At this
concentration the enantioselectivity was nearly unchanged. Neither temperature nor the nature
of solvent had a significant effect on the stereoselectivity of the reaction. The primary
aminoalcohol 6 proved to be less selective with 78% e.e., which may be attributed to the absence
of a screw-shaped arrangement of phenyl groups, a structural feature often considered
favourable for efficient chirality transfer.
Table 2
Asymmetric induction in the addition of diethylzinc to aldehydesa
R=
Auxiliary (e.e. product configuration (isolated yield))
(Sa)-2
(Sa)-3
(Sa)(Sm)-4
(Sa)(Rm)-5
C6H5
51 S (86)
n.d.
n.d.
19 R (69)
22 R (85)
12 R (52)
24 R (71)
40 R (82)
9 R (74)
7 Rb (53)
6 R (73)
7 R (46)
11 S (74)
96 S (84)
92 S (91)
93 S (80)
92 S (90)
94 S (82)
59 S (86)
63 Sb (77)
47 S (72)
92 S (87)
56 S (76)
2 S (79)
6 S (90)
1 R (97)
9 S (79)
62 R (83)
7 R (90)
1 Sb (62)
17 R (73)
22 S (80)
2 R (74)
p-CH3OꢀC6H4
p-ClꢀC6H4
2-Naphthyl
C5H5FeC5H4
C6H5ꢀCHꢁCH
CH3ꢀCHꢁCH
(CH3)2CH
c-C6H11
n.d.
74 S (87)
18 S (82)
n.d.
n.d.
58 S (73)
55 S (80)
n-C5H11
a 2 mmol scale in toluene for aromatic substrates; in n-hexane for aliphatic substrates, with 1 mol% of
aminoalcohol; reaction time: 24 h at room temperature; for details see Section 4.
b Tentative assignment.

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Further application to other aromatic and aliphatic aldehydes showed similar trends (Table
2). Enantioselectivities with 4 ranging between 92 and 96% e.e. and for aromatic substrates were
found to be close to the results obtained with solely planar chiral ferrocenyl aminoalcohols such
as 7.23 In contrast aliphatic substrates showed generally moderate asymmetric induction (47–
63% e.e.) with the exception of c-hexylcarbaldehyde (92% e.e.). With ligands 3 and 5 the degree
of asymmetric induction is low with prevailing R-configuration of products in the case of 3.
Application of aminoalcohol 2 afforded exclusively products with opposite configuration and
improved enantioselectivity, which can be attributed to increased conformational stability.
A rationalisation of our findings was attempted on the basis of reported mechanisms and
suggested structures for transition states.14,21c Depending on the backbone of the auxiliary the
ethylzinc alcoholate forms five- to seven-membered chelates and coordinates a second molecule
of diethylzinc at the oxygen atom of the chelate. This arrangement might be well suited to form
a chair-like transition state with the aldehyde substrate in which the substituent R adopts either
a pseudo-equatorial or axial position (Fig. 4). To get some insight into relative stabilities of
transition states molecular mechanics calculations were performed for 2–5 and the ferrocene
ligand 7 with benzaldehyde as the substrate. We used the commercial program SYBYL with the
Tripos force field24 and introduced reasonable constraints for distances (ZnꢀO, ZnꢀN,
ZnꢀCH2ꢀ) and the bite angle (OꢀZnꢀN) from X-ray structures.14b,25 The distance constraints
within the proposed six-membered transition state were set to reasonable values, while angles
were fixed to 109° except for ZnꢀOꢀC, where 120° seemed a better approximation. This simple
model for a more product-like transition state should be useful to give minimum geometries
based solely on steric interactions and at least identify the more stable transition states. In the
case of a seven-membered chelate ring (I) a chair-like conformation is found (3–5 and 7), while
for 2, with a six-membered chelate, an envelope geometry was found. For the six-membered
transition state (II) a chair or half-chair geometry resulted, independent of the substrate (R=Ph)
being in an axial or equatorial position. Expectedly, in all cases the equatorial Ph gives rise to
the more stable species. Their configurations agree with the predominantly formed enantiomer
(Fig. 5). Despite the simplicity of the model applied, the different degrees of asymmetric
induction are well reflected by relative energy differences between axial and equatorial Ph in the
Figure 4. Proposed transition state

/
(
9
Figure 5. Proposed transition states for enantioselective addition of Et2Zn to benzaldehyde (only the more stable arrangement with equatorial Ph-CHO
depicted)

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N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
transition states. We therefore speculate that steric effects of this type will have the most
dominating effect on the enantioselectivity. Nevertheless, in addition the conformational stabil-
ity of the chelate may play an important role: tentatively we assume that particularly in the case
of aminoalcohol 3 in addition to a ‘most stable’ chelate also one or more other conformers may
be populated which eventually favour opposite product configurations (Fig. 6). It seems that
conformationally more stable chelates generally afford higher degrees of enantioselectivity. This
might be better met with five- or six-membered chelates but also through the incorporation of
bulky substituents or condensed systems like ferrocene, which might slow down the interconver-
sion of conformers, at least on the time-scale of the catalytic reaction.
Figure 6.
3. Conclusions
These results show once more that a combination of highly enantioselective entities with
efficient chiral bias is not always sufficient to amplify asymmetric induction. It seems indeed just
as important to arrange stereogenic centres relative to each other in a proper way to improve the
enantioselectivity, a requirement not sufficiently fulfilled in the present case.
4. Experimental
4.1. General
Melting points: Kofler melting point apparatus, uncorrected. NMR: Bruker AM 400 spec-
trometer at 400.13 (1H) and 100.61 MHz (13C), respectively, in CDCl3; chemical shifts l are
reported in ppm relative to CHCl3 (7.24 or 77.00 ppm, respectively). Coupling patterns are
designated as s (singlet), d (doublet), t (triplet), p (pseudo), and b (broad). 13C{1H} NMR
spectra were recorded in a J-modulated mode; undesignated signals refer to CH-resonances.
MS: MAT 900 EI (70 eV). Optical rotations were measured on a Perkin–Elmer polarimeter 241
in a 1 dm cell, thermostated. HPLC analyses were performed on an HP 1090 equipped with a
diode array detector.
Petroleum ether (PE) and CH2Cl2 and ethyl acetate (EE) were distilled, absolute CH2Cl2 and
toluene were distilled from CaH2, THF from potassium benzophenone ketyl, Et2O and n-hexane

N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
4215
from LiAlH4. n-BuLi and s-BuLi were used as 1.6 and 1.3 M solutions, respectively, in hexane
(Aldrich); the actual content of Li-organyl was determined prior to use by difference titration
according to the method of Gilman et al.26 Column chromatography was performed on silica gel
Si 60, 25–40 mm (Merck). All the other chemicals were analytical grade and used without further
purification.
(S)-N-(2-Bromobenzyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine, (S)-N-(2-bromophenyl)-
3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine, (Sa)(Rm)-N-(1-bromo-2-ferrocenyl-methyl)-3,5-
dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine, (Sa)(Sm)-N-(1-hydroxymethyl-2-ferro-cenylmethyl)-
3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine 6, and (Sa)(Sm)-N-(1-diphenylhydroxymethyl-2-
ferrocenylmethyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine 4 were prepared according to
reported procedures.21h,22b
4.2. (S)-N-(2-Diphenylhydroxymethylphenyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine 2
(S)-N-(2-Bromophenyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine (450 mg, 1 mmol) was
dissolved in 20 mL of dry ether, cooled to −40°C and n-BuLi solution (1.5 mmol) was added.
After stirring for 3 h the temperature was lowered to −78°C and solid benzophenone (364 mg,
2 mmol) was introduced in one portion. Stirring was continued overnight, while the mixture
reached room temperature. The reaction was quenched with water; extractive work-up with
EtOAc and evaporation of solvent left the crude aminoalcohol which was purified by column
chromatography (70×2 cm, EtOAc/PE, 5:95) to give (S)-2 (498 mg, 90%) as a white solid.
Crystallisation from Et2O/n-hexane gave a crystalline sample which softened above 200°C.
During melting between 250 and 300°C reformation of crystals took place which decomposed at
1
ca. 311°C. H NMR l: 3.37 (1H, d, J=14.3 Hz), 3.68 (1H, d, J=10.9 Hz), 3.69 (1H, d, J=14.3
Hz), 3.76 (1H, d, J=10.9 Hz), 6.82 (1H, dd, J=7.8, 1.7 Hz), 7.00 (1H, dd, J=7.8, 1.3 Hz), 7.13
(1H, ptd, J=7.3, 1.3 Hz), 7.21 (1H, ptd, J=7.6, 1.5 Hz), 7.24–7.57 (18H, m), 7.99–8.05 (4H, m),
9.55 (1H, s). 13C NMR l: 55.64 (CH2), 56.06 (CH2), 82.98 (C), 125.59, 125.66, 125.79, 125.83,
125.99, 126.83, 127.08, 127.30, 127.36, 127.49, 127.53, 127.74‡, 127.76‡, 127.99, 128.05‡, 128.23,
128.36‡, 128.56‡, 128.63, 129.24, 130.53, 131.26 (C), 131.38 (C), 132.36 (C), 133.24 (C), 133.25
(C), 133.35 (C), 135.05 (C), 135.12 (C), 143.82 (C), 147.54 (C), 147.57 (C), 150.80 (C). MS
(150°C) m/z: 535 (8%, M+). HRMS: calcd for C41H31NO: 553.2406; found: 553.2411. [h]D22
+135.0 (c 0.739, CH2Cl2).
4.3. (S)-N-(2-Diphenylhydroxymethylbenzyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine 3
The preparation was conducted essentially the same way as described for (S)-2 but with
(S)-N-(2-bromobenzyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine as the educt to give (S)-3
1
as white foam (89%). H NMR l: 3.08 (1H, d, J=12.9 Hz), ꢀ3.15 (2H, bs), 3.22 (1H, d,
J=12.9 Hz), 3.41 (2H, d, J=12.5 Hz), 6.74 (1H, d, J=8.0 Hz), 7.16 (1H, m), 7.22–7.56 (20H,
m), 7.93 (2H, d, J=8.0 Hz), 7.95 (2H, d, J=8.0 Hz), 10.02 (1H, s). 13C NMR l: 58.70 (CH2),
81.93 (C), 125.64, 125.89, 126.72, 126.85, 127.26, 126.40, 127.62, 127.76 (2×CH), 127.80, 127.86,
128.09, 128.31, 128.64 (b), 130.64, 131.38 (C), 133.23, 133.28 (C), 135.14 (C), 136.16 (C), 147.48
(C), 147.89 (C), 149.32 (C) (signals due to one C and one CH2 were missing). MS (220°C) m/z:
‡ One of these five signals corresponds accidentally to two chemically different CHar, the remaining four resonances
arise from ortho and meta CH of phenyl groups.

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N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
567 (60%, M+), 549 (7%), 490 (19%), 465 (5%), 385 (5%), 294 (100%). HRMS: calcd for
C42H33NO: 567.2562; found: 567.2573. [h]2D0 +76.7 (c 0.788, CH2Cl2).
4.4. (Sa)(Rm)-N-(1-Diphenylhydroxymethyl-2-ferrocenylmethyl)-3,5-dihydro-4H-dinaphth-
[2,1-c:1%,2%-e]azepine 5
A similar procedure was applied as given for the preparation of (S)-2, except that (Sa)(Rm)-N-
(1-bromo-2-ferrocenylmethyl)-3,5-dihydro-4H-dinaphth[2,1-c:1%,2%-e]azepine was used as start-
ing material and the lithiation was performed at room temperature with s-BuLi; yield: 66%,
1
yellow foam. H NMR l: 2.82 (1H, d, J=13.4 Hz), 3.00 (2H, bd, J=11.0 Hz), 3.52 (2H, bd,
J=11.0 Hz), 3.87 (1H, m), 3.91 (1H, d, J=13.4 Hz), 4.00 (1H, m), 4.05 (5H, s), 4.07 (1H, pt,
J=2.5 Hz), 7.01 (2H, bd, J=7.5 Hz), 7.19–7.45 (14H, m), 7.55 (2H, bd, J=7.5 Hz), 7.83 (2H,
d, J=8.5 Hz), 7.90 (2H, d, J=8.0 Hz), 8.48 (1H, s). 13C NMR l: 54.22 (CH2), 54.43 (CH2),
65.42, 69.85 (Cp), 70.57, 71.20, 77.59 (C), 81.91 (C), 96.09 (C), 125.52, 125.77, 126.23, 126.70,
127.08, 127.22, 127.36, 127.66, 127.80, 127.82, 128.23, 128.34, 131.30 (C), 132.87 (C), 133.19 (C),
135.05 (C), 147.44 (C), 150.26 (C). MS (230°C) m/z: 675 (100%, M+), 610 (25%), 537 (5%), 493
(6%), 366 (42%). HRMS: calcd for C46H37FeNO: 675.2225; found: 675.2227. [h]2D0 +38.6 (c 1.04,
CH2Cl2).
4.5. Enantioselective addition of Et2Zn to aldehydes (general procedure)
A degassed solution of aminoalcohol in 2 mL of the specified solvent was prepared in a 10 mL
Schlenk tube. The substrate (2 mmol) was added at room temperature, followed by addition of
Et2Zn (3.2 mmol) via syringe at the intended reaction temperature. The reaction was kept under
Ar with stirring routinely for 24–72 h. Et2O (20 mL) and saturated NH4Cl solution (10 mL)
were added carefully and the organic layer was separated. The aqueous layer was extracted twice
with Et2O (5 mL). The combined extracts were again washed with NH4Cl and dried with
MgSO4. After careful evaporation of solvent under vacuum without heating to avoid loss of low
boiling products, the carbinols were purified by bulb-to-bulb distillation or chromatography
1
(1-ferrocenylpropan-1-ol). Chemical integrity was checked by H NMR, the enantiomeric excess
was determined directly by enantioselective HPLC and specific rotation, or of the corresponding
benzoate in the case of aliphatic products (see below).
4.6. Derivatisation of carbinols with benzoyl chloride (gereral procedure)
To 20–25 mL of carbinol in a vial was added subsequently 0.2 mL of CCl4 p.a., 25 mL of
freshly distilled benzoyl chloride and three drops of pyridine. The vial was stoppered and kept
overnight at room temperature. Water (1 mL) and Et2O (2 mL) were added. After shaking the
aqueous layer was removed and the organic phase was dried with a small amount of MgSO4.
The solvent was evaporated and the sample was evacuated at an oil pump to remove traces of
pyridine (10–20 min). If side products are present (DC) the benzoate may be filtered over a short
column of SiO2 (Pasteur pipette) in Et2O.
4.7. Enantioselective HPLC of products
HPLC: Chiralcel OD-H (Daicel) 250×4.6 mm, room temperature, flow rate: 0.5 mL min−1,

N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
4217
detection at 230 and 254 nm, samples: 1 mg mL−1 dissolved in 2-PrOH/n-hexane (5:95), 5 mL
injected. For specific rotations highest reported values are given, if necessary corrected for
enantiomerically pure compounds.
1-Phenyl-1-propanol: MW 136.19, Kp: 103°C (14 mm), [h]2D2 −48.5 (c 4, CHCl3),23 HPLC in
3.8% 2-PrOH, 0.2% HOAc, 96% n-hexane, 16.63 min (+)-(R), 17.86 min (−)-(S).
1-(4-Chlorophenyl)-1-propanol: MW 170.64, Kp: 91°C (1 mm), [h]2D1 −28.6 (c 5.1, benzene),27
HPLC in 3.8% 2-PrOH, 0.2% HOAc, 96% n-hexane, 15.04 min (−)-(S), 16.08 min (+)-(R).
1-(4-Methoxyphenyl)-1-propanol: MW 166.22, Kp: 102°C (0.7 mm), [h]2D1 −36.5 (c 5.1,
benzene),27 HPLC in 3.8% 2-PrOH, 0.2% HOAc, 96% n-hexane, 21.21 min (+)-(R), 24.13 min
(−)-(S).
1-Phenylpent-1-en-3-ol: MW 162.23, Kp: 121–123°C (1.5 mm), [h]2D1 −6.53 (c 3.2, CHCl3),27
HPLC in 10% 2-PrOH, 0.5% HOAc, 89.5% n-hexane, 10.22 min (+)-(R), 13.31 min (−)-(S).
1-(2-Naphthyl)-1-propanol: MW 186.25, [h]D −28.2 (c 3.4, benzene),28 HPLC in 10% 2-PrOH,
90% n-hexane, 18.37 min (−)-(S), 20.61 min (+)-(R).
1-Ferrocenylpropan-1-ol: MW 244.12, [h]2D0 +56 (c 1.40, benzene), HPLC: Daicel OD-H, 2%
2-PrOH, 0.1% HOAc, 97.9% n-hexane, 16.67 min (−)-(R), 17.64 min (+)-(S).
3-Octanol: MW 130.23, Kp: 175–177°C, [h]2D0 +12.5 (c 1.29, CHCl3),29 HPLC (benzoate) in
0.06% 2-PrOH, 99.94% n-hexane, 13.66 min (S), 14.35 min (R).
5-Methyl-3-hexanol: MW 116.20, Kp: 146–148°C, [h]2D2 +20.3 (c 3.7, EtOH),23 HPLC (ben-
zoate) in 0.06% 2-PrOH, 99.94% n-hexane, 11.81 min (S), 12.51 min (R).
1-Cyclohexyl-1-propanol: MW 142.29, Kp: 85–86°C (9 mm), [h]D −8.1 (c 7, Et2O),23 HPLC
(benzoate) in 0.1% 2-PrOH, 99.9% n-hexane, 12.80 min (R), 13.33 min (S).
Hex-4-en-3-ol: MW 100.16, Kp: 133–135°C, [h]D −2.8 (c 1.3, CHCl3),6d HPLC (benzoate): in
0.07% 2-PrOH, 99.93% n-hexane, 14.40 min (R), 15.14 min (S).
4.8. X-ray structure analyses
4.8.1. Crystal data for (S)-2
C41H31NO, M=553.67, orthorhombic, space group P212121, a=8.987(4), b=14.493(6), c=
3
−3
,
,
23.238(9) A, h=90, i=90, k=90°, U=3027(2) A , Z=4, Dc=1.215 g cm , T=297(2) K,
−1
,
v=0.072 mm , u=0.71073 A, F(000)=1168, colourless block (0.76×0.60×0.42 mm). Data were
collected on a Siemens SMART 3-circle diffractometer with a CCD area detector and graphite
monochromatised Mo Ka radiation by recording 4×606 ꢀ-scan frames (Dꢀ=0.3°, t=15 s)
covering a complete sphere of the reciprocal space, qmax=30°. Corrections for absorption
applied. Structure solution by direct methods, refinement by full-matrix least-squares on F2,
absolute structure known from chemistry, data/restraints/parameters=8722/0/393; final R1=
0.0465, wR2=0.1031 (all data). CCDC 182/151223.
4.8.2. Crystal data for ( )-4
C46H37FeNO, M=675.62, monoclinic, space group P21/n, a=8.750(8), b=25.89(2), c=
3
−3
,
,
15.354(14) A, h=90, i=98.57(2), k=90°, U=3440(5) A , Z=4, Dc=1.304 g cm , T=297(2)
−1
,
K, v=0.476 mm , u=0.71073 A, F(000)=1416, orange block (0.70×0.55×0.35 mm). Data
collected on a Siemens SMART diffractometer (see above), qmax=27.5°. Corrections for

4218
N. Arroyo et al. / Tetrahedron: Asymmetry 11 (2000) 4207–4219
absorption applied. Structure solution by direct methods, refinement by full-matrix least-squares
on F2 (SHELX-97).30 Data/restraints/parameters=7890/0/446; final R1=0.0523, wR2=0.1063
(all data). CCDC 182/151224.
Acknowledgements
This work was generously supported by the Fonds zur Fo¨rderung der Wissenschaftlichen
8
Forschung in Osterreich (P11990-CHE). N.A. thanks the European Union for a grant within the
SOKRATES program.
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