Asymmetric allylation of aryl aldehydes: Studies on the scope and mechanism of the palladium catalysed diethylzinc mediated umpolung using phosphoramidite ligands

Article abstract of DOI:10.1039/b518165h

Using modular, monodentate phosphoramidite ligands, enantioselective palladium catalysed diethylzinc mediated allylation of aldehydes was achieved. The scope of the asymmetric C-C bond formation was investigated with respect to nucleophilic and electrophi

Full text of DOI:10.1039/b518165h

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Asymmetric allylation of aryl aldehydes: studies on the scope and mechanism
of the palladium catalysed diethylzinc mediated umpolung using
phosphoramidite ligands†
Gareth P. Howell, Adriaan J. Minnaard* and Ben L. Feringa*
Received 21st December 2005, Accepted 1st February 2006
First published as an Advance Article on the web 17th February 2006
DOI: 10.1039/b518165h
Using modular, monodentate phosphoramidite ligands, enantioselective palladium catalysed
diethylzinc mediated allylation of aldehydes was achieved. The scope of the asymmetric C–C bond
formation was investigated with respect to nucleophilic and electrophilic components and an alternative
reaction mechanism is proposed based on our findings.
Introduction
The asymmetric allylic alkylation (AAA, Scheme 1) protocol
pioneered by Trost and Tsuji represents one of the most studied
and highly developed tools in current asymmetric catalysis.1 High
levels of stereocontrol have been demonstrated for an impressive
range of allyl (and analogous) systems in conjunction with C, O, N
and S nucleophiles, resulting in a large number of target molecule
syntheses.2 Since an initial publication concerning umpolung
allylation by H. C. Brown in 1987,3 Tamaru et al. have effectively
demonstrated that the latent reactivity of the palladium allyl
complex 1 can be reversed from electrophilic to nucleophilic in
the presence of dialkylzinc or trialkylboron species.4 The resulting
umpolung reaction represents a complementary reaction to the
existing AAA methodology.
Scheme 2
months, Zhou et al. (Scheme 2) described the first enantioselective
example of the presumably analogous, trialkylboron mediated
version of this umpolung reaction, coupling simple allyl and
cinnamyl alcohols with aldehydes in good yield and with increased
levels of enantioselectivity (58–83% ee); the spiro phospholane
ligand 5 was utilised throughout.6
We believe that this umpolung protocol is of significant interest
as the homoallylic alcohol products, and particularly the func-
tionalised cyclohexyl systems 3 described by Zanoni, represent
valuable building blocks for synthesis.7 Moreover, the opportunity
Scheme 1
to gain further mechanistic insight into the origins of stereocontrol
in this interesting and little-studied reaction would be a worthy
exercise. Accordingly, we report the highest enantioselectivities
for the diethylzinc mediated, umpolung allylation of aldehydes yet
disclosed in the literature, using monodentate phosphoramidite
ligands. The results described are comparable to those of Zhou
et al. concerning the analogous trialkylboron umpolung of allylic
alcohols. We also discuss the mechanistic implications of our
results and propose a simple reaction pathway involving r-
allylpalladium intermediates.
To date, there has been one enantioselective example of this
dialkylzinc mediated umpolung allylation reported in the liter-
ature. Zanoni et al. described the coupling of 2-cyclohexenyl
acetate 2 and benzaldehyde (Scheme 2) to yield the syn-homo-
allylic alcohol 3 in modest yield (60%) and ee (50%).5 The authors
found that monodentate phosphorous ligands were well suited to
this particular procedure and an impressive range of ligands was
screened, with phospholane 4 providing the best results. In recent
Department of Organic and Molecular Inorganic Chemistry, Stratingh
Institute, University of Groningen, Nijenborgh 4, 9747, AG, Groningen, The
Netherlands. E-mail: B.L.Feringa@rug.nl; Fax: +31 50 363 4296; Tel: +31
50 363 4235
Results and discussion
† Electronic supplementary information (ESI) available: HPLC traces, 1H
and 13C-NMR spectra for all products. See DOI: 10.1039/b518165h
Our primary goal was to investigate the use of modular, chiral,
monodentate phosphoramidite ligands 6 (Scheme 3) in this
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procedures.8 The modular properties of the phosphoramidite
skeleton allow for facile synthesis of structural variants and, as
such, we hoped to find a readily attainable and high-performing
ligand structure.
Ligand screening
As a test reaction, we studied the combination of cyclohexenyl
3
acetate 2 with benzaldehyde (Scheme 3) using Et2Zn and [(g -
C3H5PdCl)2] as catalyst. A wide range of phosphoramidite
ligands was screened (Fig. 1), and the crude reaction mixtures
were analysed by chiral HPLC to allow determination of the
enantioselectivity of reaction. The results of the stereoselectivity
obtained via this initial screen can be seen in Fig. 2.
Scheme 3
umpolung protocol. We have previously found this ligand family
to be effective in a range of copper and rhodium catalysed
To summarise our findings, simple N,N-dialkyl substi-
tuted phosphoramidites (A1–A10, B5–B8) gave low levels of
Fig. 1
Fig. 2
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Table 1 Variation of reaction parameters
Entry
Solvent
Pd Sourcea
Zn Sourceb
Conversion (%)c
Ee (%)d
3
1
2
3
4
5
6
7
8
9
10
11
12
13
THF
THF
THF
THF
THF
THF
DCM
Toluene
Et2O
TBME
THF
THF
THF
[(g -C3H5PdCl)2]
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
Et2Zn
n-Bu2Zn
i-Pr2Zn
Me2Zn
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
>95
60
70
75
72
60
81
Pd(OAc)2
Pd(CF3CO2)2
Pd(MeCN)2Cl2
Pd(PhCN)2Cl2
Pd(acac)2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
66
(−)15
42
35
28
30
69
>95
(−)25
a 5.0 mol% Pd used throughout with 10.0 mol% ligand A11. b 3.5 eq. used throughout. c Determined by 1H-NMR. d Determined by HPLC.
enantiocontrol, although the sense of induction was the same
in all cases. The introduction of a-branched N-substituents to
the phosphoramidite structure resulted in a marked increase
in the magnitude of enantioselectivity. As in previous studies
by this group8 and others9 concerning phosphoramidite based
asymmetric transformations, N,N-bis-a-methylaryl ligands of the
type A11–A14 and C/D/E11 were found to be particularly
effective, with 70% ee being obtained for the product 3 when using
ligand A11 (S,R,R, as shown in Fig. 1, indicating S configuration
for A and R,R configuration for 11). Interestingly, the R,R,R-
diastereomer of A11 gave the same sense of induction with reduced
(21%) ee.
Scheme 4
Using ligand A11, we investigated the effects of varying the
Pd and Zn source on the reaction (Table 1). Of the Pd(II)
complexes tested, bis-benzonitrile palladium dichloride (entry 5)
gave the highest degree of enantiocontrol (81% ee). Exchange of
the reaction solvent from THF to toluene, DCM, Et2O or TBME
resulted in attenuation of enantioselectivity. The identity of the Zn
source used was found to have a pronounced effect on the reactivity
and enantioselectivity of the reaction, with Et2Zn proving optimal.
The use of Et3B as an umpolung reagent was ineffective in this
reaction with little or no conversion to product 3 being observed.
In conjunction with the observations made by Zhou et al.,6 this
may suggest that Et2Zn is a superior umpolung reagent to Et3B
when applied to allylic acetates, whilst Et3B is better suited to
allylic alcohols. Attempts to vary the stoichiometries of the various
reagents had no beneficial effect, and lowering of the reaction
temperature below 0 ◦C resulted in a severely retarded reaction
requiring excessive reaction times.
ence of electron withdrawing groups in the aldehyde appeared
beneficial (entry 3) compared to electron releasing groups. The
heteroaromatic aldehyde (entry 6) did not perform as well with
lower enantioselectivity being recorded. As suggested by Tamaru
et al.,4 this Et2Zn mediated protocol is not applicable to aliphatic
aldehydes (entries 7 & 8). We found that the allyl-moiety was
consumed with no observed homoallylic alcohol formation and we
were unable to isolate or identify the products of reaction. Ketones
(entries 9 & 10) proved unreactive in this system with the allylic
acetate 2 being recovered, even after prolonged reaction times
(60 h). We also conclude that this catalyst system is sensitive to the
identity of the allyl-fragment, with cyclopentyl and allyl acetate
giving lower enantioselectivities (entries 11 & 12).
Mechanistic discussion
Based on a series of experimental observations concerning the
racemic version of this umpolung reaction, Tamaru et al. proposed
a mechanism involving the generation of a stereochemically
defined allylzinc intermediate (20, Scheme 5),4 and subsequent
combination with the aldehyde electrophile through a closed,
chair transition state (21a/b). Whilst the proposed mechanism
gives a satisfactory explanation for the racemic reaction, it is
more difficult to reconcile with the results gained from the recent,
enantioselective versions of this reaction.
If we consider the proposed mechanism as applied to the
umpolung of cyclohexenyl acetate 2 with benzaldehyde, two di-
astereomeric chair-structures are possible (21a/b), each satisfying
the observed syn-selectivity. As the phosphoramidite ligands are
the only source of chirality in this catalytic umpolung reaction,
Substrate screening
Using the conditions outlined in entry 5 (Table 1), we tested the
scope of this procedure with a range of aromatic and aliphatic
aldehydes and ketones in conjunction with three allylic-substrates
(Scheme 4, Table 2). The absolute stereochemistry of products 3, 16
and 18 was assigned using comparison of [a]D measurements with
literature values. The absolute configuration 1S, 1ꢀR of compounds
3b–f was assigned by analogy with compounds 3 and 16.
This protocol worked efficiently for a range of aromatic
aldehydes (entries 1–5), with good yields and enantioselectivities
being obtained along with very high syn-selectivity. The pres-
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Table 2 Examining the scope of the reaction
Entry
Acetate
Carbonyl
Product
Yield (%)a
syn : antib
Ee (%)c
ꢀ
ꢀ
=
=
=
=
=
=
=
=
=
=
=
=
=
1
2
3
4
5
6
7
8
9
2
R
R
R
R
R
R
R
R
R
R
R
R
H, R C6H5
3
77
73
73
82
79
>20 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
>20 : 1
—
—
—
—
>20 : 1
—
81
71
80
72
68
60
—
—
—
—
45
37
=
2
H, R MeO-4-C6H4
3b
3c
3d
3e
3f
ꢀ
ꢀ
ꢀ
ꢀ
=
2
H, R MeO2C-4-C6H4
=
2
H, R Me-4-C6H4
=
2
H, R Me-2-C6H4
=
2
H, R 2-furyl
80
ꢀ
ꢀ
=
2
H, R Et
—
—
—
—
16
18
<5
<5
<5
<5
66
2
H, R = i-Pr
ꢀ
=
2
R
Me
ꢀ
=
10
11
12
2
Ph, R Me
ꢀ
ꢀ
=
15
17
H, R Ph
=
H, R Ph
73
a Isolated yield after column chromatography. b Determined by 1H-NMR. c Determined by HPLC.
Scheme 6
chiral information and would be incapable of generating product
18 with any enantioselectivity. This is in direct conflict with the
observed experimental data in this study.
Based on experimental observations and computational
1
calculations,11 Szabo´ et al. have shown that g -allylpalladium
species can undergo electrophilic allylation with aldehydes; this re-
quires the presence of electron-releasing substituents on palladium
1
3
to promote the change from g to g . By analogy, we propose that
the role of Et2Zn in this umpolung reaction is to alkylate the g -
3
Scheme 5
allylpalladium species 19 (Scheme 7) and promote the formation of
1
the corresponding g -allylpalladium species 25. This could proceed
we must assume that they are involved in the enantio-determining
step (20 → 21). Thus, the chiral ligands (L*) are required to be
bound to the zinc centre in 20 and will ultimately reside on the
zinc centre in the alcoholate product 22a/b. Since zinc is not
catalytic (3.5 eq.), the source of chirality (L*) would be removed
from any catalytic cycle after a single turnover, unless the ligands
(L*) were capable of continually switching between allyl-Pd, allyl-
Zn (20) and alkoxide-Zn (22) centres. We have studied reaction
systems utilising phosphoramidite ligands in the presence of
dialkylzinc species and have never observed zinc–phosphoramidite
interactions, moreover, we were unable to find any examples of
zinc–phosphoramidite complexes in the literature. Based on this,
and the known stability of palladium/phosphoramidite systems,10
we believe that continual migration of the chiral ligands (L*)
between various zinc and palladium centres is, at best, unlikely.
This problem of ligand migration might be avoided by proposing
that treatment of the p-allylpalladium species 19 with diethylzinc
proceeds directly, and in enantioselective fashion to a configura-
tionally stable, r-allylzinc species 23 (Scheme 6). However, the
analogous reaction with allyl acetate (17, Table 2, entry 12, and
reference 6) would generate a r-allylzinc species 24 that contains no
in enantioselective fashion and allow formation of the observed
product 3 via a transition state such as 26. Although suggested
to be of low nucleophilicity, allyl-alkyl-palladium species have
Scheme 7
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previously been shown to allylate electrophiles12 and have also
been considered as possible intermediates in this reaction pathway
by Tamaru et al.4 We would suggest that a pathway such as
that shown in Scheme 7 provides a more satisfactory explanation
of our results, and the recently reported results of Zanoni5 and
Zhou.6 The possibility that this umpolung reaction proceeds via a
more complex, zinc-palladium aggregated species should also be
considered; detailed studies are required to investigate this further.
The excess PCl3 was removed in vacuo and 3 cycles of toluene
addition/evaporation were completed to give the crude BINOL-
PCl product as a white semi-solid which was dissolved in toluene
(20.0 mL). To a separate flame-dried flask was added (R)-(2-
methoxy-benzyl)-(1-phenylethyl)-amine (1.95 mmol 471 mg). The
flask was placed under nitrogen and dry THF (15.0 mL) was
added. The mixture was cooled to 0 ◦C with stirring and n-BuLi
(2.10 mmol) was added to give a bright red solution. T◦his mixture
was added to the BINOL-PCl–toluene solution at 0 C and the
resulting mixture was stirred for 3 h. The mixture was warmed to
room temperature and Et2O (25.0 mL) was added. The mixture
was filtered (celite) and the solvent was removed in vacuo to give
a pale yellow oil. Flash column chromatography (20 : 1 hexane–
EtOAc) gave phosphoramidite A14 as an off-white solid (340 mg,
35%); [a]2D2 +216.4 (c 1.0 in CHCl3); mmax/cm−1 (solid) 3061, 1589,
1462, 1230, 949, 821 and 750; dH (400 MHz; CDCl3) 1.51 (3H,
d, J 6.8, CHMe), 3.65 (3H, s, OMe), 3.84, (1H, dd, J 16.6,
6.4, NCHHꢀ), 3.94 (1H, dd, J 16.6, 8.4, NCHHꢀ), 4.62, (1H, m,
CHMe), 6.76 (1H, d, J 8.3, Ar–H), 7.00 (1H, t, J 7.3, Ar–H), 7.10
(1H, d, J 8.8, Ar–H), 7.20–7.50 (12H, m, Ar–H), 7.60 (2H, m, Ar–
H), 7.71 (1H, d, J 8.8, Ar–H), 7.84 (1H, d, J 8.3, Ar–H), 7.94 (1H,
d, J 7.8, Ar–H), 8.00 (1H, d, J 8.8, Ar–H); dC (400 MHz; CDCl3)
18.2, 38.7, 52.5, 53.2, 107.6, 116.8, 117.8, 119.4, 119.6, 119.9, 121.9,
122.3, 123.4, 123.5, 124.6, 125.3, 125.4, 125.6, 125.8, 126.1, 126.9,
127.1, 127.7, 128.0, 128.9, 130.1, 130.3, 140.0, 147.0, 147.4, 147.5;
dP (400 MHz; CDCl3) 146.1; m/z (EI+) 555 (7%, M+), 524 (50%),
450 (15%), 434 (100%), 433 (59%), 268 (20%), 121 (17%), 91 (20%),
HRMS C36H30NO3P 555.1946 (requires 555.1963).
Conclusions
In summary, we have shown that phosphoramidites are versatile
ligands in the palladium catalysed diethylzinc mediated umpol-
ung allylation of aldehydes, and provide the highest levels of
enantioselectivity yet reported. We have investigated the scope
of this methodology with regards to both the nucleophilic and
electrophilic reagents and proposed an alternative mechanism that
accounts for the formation of enantio-enriched products.
Experimental
General
1H-NMR spectra were recorded at 200, 300 or 400 MHz with
CDCl3 (referenced to 7.27 ppm) as solvent. 13C-NMR spectra
were recorded at 200 or 300 MHz with CDCl3 (referenced to
77.1 ppm) as solvent. Coupling constants (J) are given in Hz.
Varian Gemini 200, VXR300 and AMX400 spectrometers were
used throughout. HRMS data was obtained using a Jeol JMS-
600H spectrometer. Infra-red spectra were recorded using an
Avatar-series spectrometer. A Shimadzu 10A system was used
for HPLC and Hewlett-Packard HP6890 for GC analysis. Optical
rotations were measured using a Schmidt & Haendsch polarimeter
(Polartronic MH8) with a 10 cm cell (c given in g per 100 mL
and measurements are given in 10−1 deg cm2 g−1). Thin layer
chromatography was performed on commercial Kieselgel 60F254
silica gel plates; KMnO4 and H3[P(Mo3O10)4].H2O were used for
visualisation. Flash chromatography was performed using silica
gel.
General procedure for the palladium catalysed,
diethylzinc-mediated umpolung allylation of aldehydes
To a flame-dried, round-bottom flask was added Pd(PhCN)2Cl2
(0.05 eq., 10 lmol, 3.80 mg) and ligand A11 (0.10 eq., 20 lmol,
10.80 mg). The flask was placed under nitrogen, THF (1.50 mL)
was added and the mixture was stirred at 0 ◦C for 15 min.
The allyl acetate (1.20 eq., 0.24 mmol) and aldehyde (1.00 eq.,
0.20 mmol) were added, followed by Et2Zn (1.0 M in hexanes,
3.50 eq., 0.70 mmol, 0.70 mL). The mixture was allowed to warm
to room temperature over 16 h before quenching with saturated
NH4Cl (aq.). After stirring for 30 min, Et2O (5 mL) was added
and the organic phase was separated, washed with brine (2 ×
10 mL), dried (MgSO4) and evaporated to give the crude homo-
allylic alcohol product. Purification was achieved via flash column
chromatography (hexane–EtOAc).
Synthesis of allylic acetates
Allylic acetate 17 was purchased from Aldrich and used without
further purification. Racemic 2-cyclohexenyl acetate 213 and 2-
cyclopentenyl acetate 1514 are known compounds and were
synthesised via a 2-step procedure comprising ‘Luche’ reduction15
of the corresponding cyclic enone and acylation of the resulting
allylic alcohol.13
(1S, 1ꢀR)(Cyclohex-2-enyl)(phenyl)methanol (3). Obtained as
a clear oil (29 mg, 77%); absolute stereochemistry assigned
by optical rotation [a]D22 +14.8 (c 0.85 in C6H6) (lit.,22 +11.1);
HPLC (Chiralcel OD-H [300 mm], heptane–propan-2-ol 99 : 1,
0.50 mL min−1, 30.3 min [major], 35.6 min [minor]) shows 81% ee;
1H and 13C-NMR in full agreement with literature.23
Synthesis of phosphoramidite ligands
Ligand A1 was kindly donated by DSM. Ligands A2, A4, A8, A6,
A11;16 A3, A5, A7, A9, A10, B8, B7, B5;17 A13;18 C11;19 D1120 and
E1121 have been reported previously in the literature.
O,Oꢀ -(S)-(1,1ꢀ -Dinaphthyl-2,2ꢀ -diyl)-N-2-methoxy-benzyl-Nꢀ -
(1S, 1ꢀR)(Cyclohex-2-enyl)(4-methoxy-phenyl)methanol (3b).
Obtained as a clear oil (32 mg, 73%); absolute stereochemistry
assigned by analogy to compounds 3 and 16; HPLC (Chiralcel
OD–H [300 mm], heptane–propan-2-ol 99 : 1, 0.50 mL min−1,
(R)-1-phenylethylphosphoramidite (A14). To
a
flame-dried,
round-bottomed flask fitted with a reflux condenser was added
(S)–BINOL (1.76 mmol, 490 mg). The system was placed under
nitrogen and PCl3 (2.50 mL) was added. The mixture was heated
to reflux for 16 h, then allowed to cool to room temperature.
1
47.8 min [minor], 52.8 min [major]) shows 71% ee; H and 13C-
NMR in full agreement with literature.24
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(1S, 1ꢀR)-4-(Cyclohex-2-enyl-hydroxy-methyl)-benzoic acid
methyl ester (3c). Obtained as a clear oil (36 mg, 73%); absolute
stereochemistry assigned by analogy to compounds 3 and 16;
HPLC (Chiralcel OD-H [300 mm], heptane–propan-2-ol 95 : 5,
0.50 mL min−1, 23.5 min [minor], 27.8 min [major]) shows 80%
ee; mmax/cm−1 (deposited on KBr powder) 3507 (OH), 2928, 1723
(CO), 1436, 1280, 1112; dH (400 MHz; CDCl3) 1.42–1.70 (6H, m),
1.93 (2H, m), 2.46 (1H, br-s, OH), 3.86 (3H, s, COMe), 4.64 (1H,
d, J 5.9, CHOH), 5.35 (1H, d, J 10.2), 5.80 (1H, m), 7.35 (2H, d,
J 8.0, Ar–H), 7.95 (2H, d, J 8.0, Ar–H); dC (200 MHz; CDCl3)
18.5, 20.8, 22.6, 40.5, 49.5, 74.2 (COMe), 123.9, 125.0, 126.5,
127.0, 128.6, 145.5, 164.5; m/z (EI+) 215 (3%, M+), 166 (14%),
165 (100%); HRMS C15H18O3 246.1253 (requires 246.1256).
[a]2D2 +22.8 (c 1.00 in C6H6) (lit.,27 +45.0); HPLC (Chiralcel OD-H
[300 mm], heptane–propan-2-ol 99 : 1, 0.50 mL min−1, 35.2 min
[major], 39.0 min [minor]) shows 37% ee; 1H and 13C-NMR in full
agreement with literature.27
Acknowledgements
We thank The Leverhulme Trust (UK) for a European Fellowship
to G. P. H and general financial support.
References
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Tetrahedron Lett., 2005, 46, 5823; R. Weihofen, A. Dahnz, O. Tverskoy
and G. Helmchen, Chem. Commun., 2005, 28, 3541; R. Sebesta, M. G.
Pizzuti, A. J. Boersma, A. J. Minnaard and B. L. Feringa, Chem.
Commun., 2005, 13, 1711.
10 K. N. Gavrilov, S. E. Lyubimov, S. V. Zheglov, E. B. Benetsky and V. A.
Davankov, J. Mol. Catal. A: Chem., 2005, 231(1–2), 255; R. Imbos,
A. J. Minnaard and B. L. Feringa, Dalton Trans., 2003, 10, 2017.
11 For a recent review, see: K. J. Szabo´, Chem.–Eur. J., 2004, 10, 5268.
12 H. Kurosawa, A. Urabe, K. Miki and N. Kasai, Organometallics, 1986,
5, 2002.
(1S, 1ꢀR)(Cyclohex-2-enyl)(o-tolyl)methanol (3e). Obtained as
a clear oil (32 mg, 82%); absolute stereochemistry assigned
by analogy to compounds 3 and 16; HPLC (Chiralcel OD–H
[300 mm], heptane–propan-2-ol 99 : 1, 0.50 mL min−1, 27.4 min
[major], 32.3 min [minor]) shows 68% ee; mmax/cm−1 (deposited
on KBr powder) 3403 (OH), 2927, 1488, 1448, 1017, 760, 730;
dH (400 MHz; CDCl3) 1.40–1.80 (4H, m), 1.95 (2H, m), 2.27
(3H, ArMe), 2.42 (1H, m, CHCHOH), 4.80 (1H, dd, J 6.6, 2.6,
CHOH), 5.27 (1H, dd, J 10.3, 2.2), 5.77 (1H, m), 7.05–7.22 (3H,
m, Ar–H), 7.44 (1H, d, J 7.7, Ar–H); dC (200 MHz; CDCl3) 17.9,
19.6, 22.6, 23.7, 40.4, 71.8 (CHOH), 124.5, 124.6, 125.6, 126.5,
128.7, 128.9, 133.3, 139.6; m/z (EI+) 202 (1%, M+), 122 (9%), 121
(100%), 93 (25%), 91 (14%), 77 (11%); HRMS C14H18O 202.1361
(requires 202.1357).
(1S, 1ꢀR)(Cyclohex-2-enyl)(furan-2-yl)methanol (3f). Obtained
as a clear oil (28 mg, 80%); absolute stereochemistry assigned
by analogy to compounds 3 and 16; HPLC (Chiralcel OD–H
[300 mm], heptane–propan-2-ol 99 : 1, 0.50 mL min−1, 29.6 min
[major], 33.1 min [minor]) shows 60% ee; mmax/cm−1 (deposited
on KBr powder) 3399 (OH), 2927, 2856, 1448, 1148, 1009, 734;
dH (400 MHz; CDCl3) 1.42–1.58 (2H, m), 1.64–1.84 (3H, m),
1.88–2.00 (2H, m), 2.60 (1H, m, CHCHOH), 4.49 (1H, d, J 7.3,
CHOH), 5.33 (1H, dd, J 10.2, 2.2), 5.75 (1H, m), 6.21 (1H, d, J 2.9,
furyl-H), 6.28 (1H, dd, J 2.9, 1.9, furyl-H), 7.38 (1H, d, J 1.9,
furyl-H); dC (200 MHz; CDCl3) 19.4, 22.9, 23.6, 39.2, 69.8, 105.3,
108.6, 125.7, 128.6, 140.3, 157.5; m/z (EI+) 178 (6%, M+), 157
(28%), 149 (13%), 132 (34%), 131 (37%), 116 (19%), 103 (13%), 97
(100%), 91 (30%); HRMS C11H14O2 178.0999 (requires 178.0994).
13 J. Cossy, L. Tresnard and L. Tresnard, Eur. J. Org. Chem., 1999, 8, 1925.
14 M. Fujita, W. H. Kim, K. Fujiwara and T. Okuyama, J. Org. Chem.,
2005, 70, 480.
15 J. M. Luche, J. Am. Chem. Soc., 1978, 100, 2226.
16 L. A. Arnold, R. Imbos, A. Mandoli, A. H. M. de Vries, R. Naasz and
B. L. Feringa, Tetrahedron, 2000, 56, 2865.
17 H. Bernsmann, M. van den Berg, R. Hoen, A. J. Minnaard, G. Mehler,
M. T. Reetz, J. G. de Vries and B. L. Feringa, J. Org. Chem., 2005, 70,
943.
18 D. Pen˜a, A. J. Minnaard, A. H. M. de Vries, J. G. de Vries and B. L.
Feringa, Org. Lett., 2003, 5, 475.
19 A. Rimkus and N. Sewald, Synthesis, 2004, 135.
(1S, 1ꢀR)(Cyclopent-2-enyl)(phenyl)methanol (16). Obtained
as a clear oil (23 mg, 66%); absolute stereochemistry assigned
by optical rotation [a]D22 +13.8 (c 1.00 in CHCl3) (lit.,22 +27.2); GC
(Chiralsil-L-val, [25.0 m × 0.25 mm], 0.50 mL min−1, initial temp.
120 ◦C for 15 min, then 5 ◦C min−1 to final temp. 160 ◦C, 22.7 min
[minor], 22.8 min [major]) shows 45% ee; 1H and 13C-NMR in full
agreement with literature.26
20 R. Hoen, M. van den Berg, H. Bernsmann, A. J. Minnaard, J. G. de
Vries and B. L. Feringa, Org. Lett., 2004, 6, 1433.
21 K. Tissot-Croset, D. Polet and A. Alexakis, Angew. Chem., Int. Ed.,
2004, 43, 2426.
22 T. Hayashi, J. W. Han, A. Takeda, J. Tang, K. Nohmi, K. Mukaide, H.
Tsuji and Y. Uozumi, Adv. Synth. Catal., 2001, 343, 279.
23 S. Kobayashi and K. Nishio, J. Org. Chem., 1994, 59, 6620.
24 F. A. Khan and B. Prabhudas, Tetrahedron, 2000, 56, 7595.
25 P. D. Ren, D. Shao and T. W. Dong, Synth. Commun., 1997, 27, 2569.
26 A. G. Griesbeck and S. Stadtmu¨ller, J. Am. Chem. Soc., 1991, 113,
6923.
(R)-1-Phenyl-but-3-en-1-ol (18). Obtained as a clear oil (22 mg,
73%); absolute stereochemistry assigned by optical rotation
27 E. J. Corey and S. S. Kim, Tetrahedron Lett., 1990, 31, 3715.
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