Stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans using an intramolecular allylation strategy employing allylsilanes

Article abstract of DOI:10.1016/j.tetlet.2008.02.088

A Br?nsted acid-mediated intramolecular allylation involving an allylsilane and an aldehyde has been used as the key step in a stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans.

Full text of DOI:10.1016/j.tetlet.2008.02.088

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2514–2518
Stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and
2,3,4-trisubstituted tetrahydrofurans using an intramolecular
allylation strategy employing allylsilanes
Peter J. Jervis, Benson M. Kariuki, Liam R. Cox *
School of Chemistry, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Received 8 February 2008; accepted 18 February 2008
Available online 21 February 2008
Abstract
A Brønsted acid-mediated intramolecular allylation involving an allylsilane and an aldehyde has been used as the key step in a
stereoselective synthesis of 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubstituted tetrahydrofurans.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Allylsilanes; Tetrahydrofurans; Cyclisation; Intramolecular allylation; Brønsted acids
O
Substituted tetrahydrofurans are attractive synthetic
targets owing to their frequent occurrence in natural prod-
ucts.1 Of the range of substitution patterns that are avail-
able, the 2,3,4-trisubstitution pattern is found in a
number of natural products; some examples are shown in
Figure 1. Pachastrissamine (jaspine B) exhibits anti-cancer
activity,2,3 whilst (+)-gynunone, which contains the core
motif within a tricyclic framework, displays anti platelet
aggregation activity.4 Aureonitol is a fungal metabolite of
unknown biological activity.5 As part of a research
programme investigating the use of silyl nucleophiles in
cyclisation strategies,6 we now wish to describe an intra-
molecular allylation approach to this class of substituted
oxygen heterocycle.7
We recently reported an intramolecular allylation route
to 2,4,5-trisubstituted tetrahydropyrans.6c In this work,
Brønsted acid activation of aldehyde 1 effected cyclisation
to afford the corresponding 2,4,5-trisubstituted tetrahydro-
pyran in excellent yield and diastereoselectivity, with only
two out of the four possible tetrahydropyran products, 2
O
NH2
OH
O
CH3(CH2)12
O
HO
pachastrissamine
(jaspine B)
(+)-gynunone
O
OH
aureonitol
Fig. 1. 2,3,4-Trisubstituted tetrahydrofurans occur in a range of natural
products.
and 3, ever being observed. Assuming cyclisation proceeds
through
a chair-like transition state in which the
substituent at the carbinol stereogenic centre adopts a
pseudoequatorial orientation, the observed complete 1,4-
stereoinduction can be explained by the allylsilane
adopting a pseudoequatorial orientation thereby minimis-
ing steric interactions. Excellent 1,3-stereoinduction (up
to 50:1), favouring the pyran product 2 in which the hydro-
xyl substituent occupies an axial orientation, is also achiev-
able by carrying out the reaction in an apolar solvent. This
stereoselectivity can be explained on electrostatic grounds
using a modified Evans dipole model (Scheme 1).8
*
Corresponding author. Tel.: +44 (0)121 414 3524; fax: +44 (0)121 414
4403.
E-mail address: l.r.cox@bham.ac.uk (L. R. Cox).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.088

P. J. Jervis et al. / Tetrahedron Letters 49 (2008) 2514–2518
2515
over-reduction was obtained.12 Having installed the allyl-
silane nucleophile, DIBALH reduction of the ester group
in 8 proceeded uneventfully to release the aldehyde electro-
phile and our cyclisation precursor 9 (Scheme 2).
SiMe3
MeSO3H
O
O
O
toluene, -78 ºC
R
OH
R
OH
R
O
1
2
3
We commenced our intramolecular allylation study with
substrate 9a, which lacks a stereogenic centre at the 2-posi-
tion. Using this substrate would allow us to examine the
relative stereochemistry of the two new stereogenic centres,
which are generated in the cyclisation product, without the
complicating issue of existing stereochemistry in the start-
ing material. Employing the conditions, which had proven
so successful in our previous work,6c aldehyde 9a was trea-
ted with MeSO3H in CH2Cl2 at ꢀ78 °C. To avoid potential
problems associated with isolating the volatile product, the
resulting tetrahydrofuran 10a was trapped in situ with
4-nitrobenzoyl chloride to generate the corresponding
4-nitrobenzoate ester 11 as a single diastereoisomer. Achiral
aldehyde 9b, containing a quaternary centre at the 2-posi-
tion also cyclised smoothly to provide tetrahydrofuran
10b, once again as a single diastereoisomer (Scheme 3).
The relative stereochemistry in these two products was
readily determined by NOE experiments (figure inset,
Scheme 3).
We next switched our attention to aldehyde 9c, which
contains a stereogenic centre a to the carbonyl group. Cycli-
sation of this class of substrate could generate up to four
diastereoisomeric products. In the event however, aldehyde
9c reacted under our favoured conditions (MeSO3H,
CH2Cl2, ꢀ78 °C) with complete 1,2-stereoinduction (vide
infra), to afford two out of the possible four diastereoiso-
mers 10c and 12c (Table 1, entry 1). In a bid to improve
the more modest 1,3-stereoinduction (5.5:1), a variety of
different solvents were screened over a range of tempera-
tures (Table 1, entries 1–7). In all cases, the same two allyl-
ation products were observed on analysis of the crude
reaction mixture by 1H NMR spectroscopy; however
major
minor
O
SiMe3
R
OH
Scheme 1. Stereoselective synthesis of 2,4,5-trisubstituted tetrahydro-
pyrans.
Removing the methylene unit between the aldehyde and
carbinol stereogenic centre in 1 would provide a system 9
that is set up to afford the corresponding 2,3,4-trisubsti-
tuted tetrahydrofuran on activation. Synthesis of this cycli-
sation precursor began with etherification of a-hydroxy
ester 6 (Scheme 2). In order to avoid epimerisation of the
stereogenic centre (vide infra) in this alcohol starting mate-
rial, we elected to introduce the propargylsilane using a
non-basic etherification procedure.9 To this end, trichloro-
acetimidate 5 was synthesised as described previously from
propargyl alcohol 4.6c Acetimidate 5 was then used
directly, without purification, in a TMSOTf-mediated
etherification with a-hydroxy ester 6,10 to afford ether 7
in good yield. The next step required the partial hydrogena-
tion of the triple bond in 7. This was best achieved using
Raney-nickel under a hydrogen atmosphere,11 which gen-
erated the desired (Z)-allylsilane 8 with excellent selectivity.
Even under these optimised conditions, however, trace
amounts of the over-reduction product were still observed
for all substrates except for 8b, where approximately 10%
NH
Cl3CCN, Na
HO
Cl3C
OH
O
SiMe3
quant.
SiMe3
4
5
SiMe3
OEt
R1
cat. TMSOTf,
MeSO3H,
R2
O
cyclohexane
52-65%
CH2Cl2
O
O
H
R
6a-g
-78 ºC
SiMe3
R
R
OH
R
O
9a, R = H; 9b, R = Me
10a, R = H (not isolated);
10b, R = Me, 88%
O
O
Raney-Nickel
H2, EtOH
86-96%
SiMe3
OEt
OEt
R1
R1
R2
R2
>99 : <1 anti : syn
O
O
4-NO2C6H4COCl
pyridine, DMAP
(for 10a)
8a-g
7a-g
DIBALH, CH2Cl2, -78 ºC
86-93%
H
HO
H
Me
Me
H
O
a: R1 = R2 = H
O
SiMe3
H
b: R1 = R2 = Me
O
O
c: R1 = Ph, R2 = H
H
O
d: R1 = Me, R2 = H
e: R1 = TBDPSOCH2, R2 = H
f: R1 = PhCH2CH2, R2 = H
11
82% (from 9a)
H
R1
selected nOes
R2
for 10b
O
g: R1
=
nBu, R2 = H
NO2
9a-g
Scheme 3. Intramolecular allylation was completely stereoselective in the
absence of existing stereochemical information.
Scheme 2. Synthesis of cyclisation precursors.

2516
P. J. Jervis et al. / Tetrahedron Letters 49 (2008) 2514–2518
Table 1
Optimisation of the intramolecular allylation and investigation of reaction
scope
H
H
HO
H
H
O
H
Ph
SiMe3
H
O
MeSO3H
O
O
10f
H
10c
solvent, temp.
R
R
OH
10c-g
R
OH
12c-g
O
9c-g
H
H
HO
H
H
O
Entry
R
Solvent Temp (°C) Ratio 10:12 Yielda (%)
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CH2Cl2 ꢀ78
5.5:1.0
4.0:1.0
3.5:1.0
4.0:1.0
3.5:1.0
4.0:1.0
7.0:1.0
5.0:1.0
8.0:1.0
10.0:1.0
7.0:1.0
90
81
62
68
78
81
88
91
86
85
89
H
Ph
H
PhMe
THF
Et2O
ꢀ78
ꢀ78
ꢀ78
12c
12c
MeCN ꢀ40
acetone ꢀ78
CHCl3
CHCl3
ꢀ50
ꢀ50
ꢀ50
ꢀ50
ꢀ50
H
H
H
H
Me
O
TBDPSOCH2 CHCl3
PhCH2CH2
nBu
H
Ph
10
11
a
CHCl3
CHCl3
HO
Isolated yield of 10 and 12 combined.
14
Fig. 2. Selected NOE data for 10c (top), 12c (middle) and 14 (bottom) and
ORTEP plots for 10f (top), 12c (middle) and 14 (bottom). Atomic
displacement parameters at 293 K are drawn at the 30% probability level.
disappointingly, significant improvements in 1,3-stereo-
induction were not observed, with the use of chloroform
as the solvent at ꢀ50 °C providing the best result (7:1)
(Table 1, entry 7).13 These optimised conditions were then
extended to a range of aldehydes 9d–g (Table 1, entries
8–11). In all cases, reaction was rapid (<10 min) and the
tetrahydrofuran products were isolated in excellent yield.
Moreover, the cyclisation again proceeded with complete
1,2-stereoinduction for all substrates, with the levels of
1,3-stereoinduction being more modest, ranging from 5:1
in the worst case (Table 1, entry 8) up to 10:1 for the best
(Table 1, entry 10). The two diastereoisomeric tetrahydro-
furan products 10 and 12 were generally isolated and char-
acterised as a mixture apart from the phenyl and phenethyl
derivatives, which were readily separable by flash column
chromatography.
O
O
O
L-Selectride
Dess-Martin
Ph
OH
10c
Ph
O
Ph
OH
13
14
84% over 2 steps
95% d.e.
Scheme 4. An oxidation–reduction sequence on the major diastereoisomer
10c provided epimeric tetrahydrofuran 14.
diastereoface.16 This set of experiments provided an indi-
rect elucidation of the major diastereoisomer; however final
proof was obtained by X-ray analysis of the phenethyl
derivative 10f (Fig. 2).15 Having identified the two dia-
1
The H NMR spectra for the major diastereoisomers
10c–g displayed similar patterns (appearance of the
resonances for the protons around the common tetra-
hydrofuran unit), which suggested the same relative stereo-
chemistry was present in all cases. Assignment of the
relative stereochemistry in this diastereoisomer was provi-
sionally made on the basis of NOE experiments (Fig. 2).
Further proof was obtained by oxidising phenyl derivative
10c to the corresponding ketone 13 with Dess Martin peri-
odinane (Scheme 4). Subsequent reduction of 13 with the
bulky reducing agent, L-Selectride, afforded the epimeric
tetrahydrofuran 14 with high stereoselectivity.14 Such high
stereoselectivity in this reduction is consistent with a 1,3-
syn relationship in the starting ketone, which ensures the
diastereotopic faces of the carbonyl group are strongly dif-
ferentiated on steric grounds by the two a-substituents. The
structure of 14 was elucidated by X-ray crystallography
(Fig. 2),15 which confirmed that reduction of ketone 13
had indeed occurred by hydride attack on the less hindered
stereoisomeric tetrahydrofurans possessing
a 1,3-syn
relationship, the minor diastereoisomer 12 had to contain
a 1,3-anti relationship by default. This was confirmed by
NOE experiments which also identified a 1,2-anti-2,3-syn
stereochemical relationship in this product. Final proof
of structure was again obtained by X-ray analysis of the
phenyl derivative 12c (Fig. 2).15
Although we had been careful to employ a non-basic
etherification procedure to form our ether linkage in alde-
hyde 9c, we were still keen to check that possible erosion of
stereochemical information in our starting material had not
occurred at any point along our synthetic route. To this
end, tetrahydrofuran 10c, which was accessed from racemic
ethyl mandelate, was analysed by chiral HPLC and base-
line separation of the two enantiomers was readily achieved
(Fig. 3a). Repeating the synthesis, but this time starting
from (S)-ethyl mandelate, we were pleased to observe that

P. J. Jervis et al. / Tetrahedron Letters 49 (2008) 2514–2518
2517
Fig. 3. HPLC data showing erosion of stereochemical information is not observed in the synthetic sequence.
the major diastereoisomer 10c was of a single configuration
when analysed by chiral HPLC (Fig. 3b). This result con-
clusively demonstrates that no erosion of stereochemistry
had occurred at any point along the synthetic route.
Attaching the allylsilane to the aldehyde through a rela-
tively short tether of just three atoms limits the number of
possible approach trajectories for the nucleophile on the
electrophile. To rationalise the stereochemical outcome of
the cyclisation reaction involving aldehydes 9, we propose
the two transition states shown in Figure 4. In both cases,
the R substituent occupies a pseudoequatorial orientation
on steric grounds. The complete 1,2-stereoinduction can
then be understood by the aldehyde adopting a pseudoequa-
torial position, which orients the dipole moments across
the polar C–O and C@O bonds in opposite directions.17
Rationalising the observed 1,3-stereoinduction is more
difficult although we tentatively propose that the transition
state (T.S.1) in which the allylsilane adopts a pseudoaxial
orientation is favoured by minimising eclipsing steric inter-
actions between the carbonyl electrophile and approaching
nucleophile.
complex when a stereogenic centre is introduced into the
substrate. In these cases, cyclisation provides two of the
four possible tetrahydrofurans. Transition states have been
proposed to rationalise the stereoselectivity of these reac-
tions. Future work will now focus on the application of this
methodology to the synthesis of biologically important
natural products.
Acknowledgements
We thank the Engineering and Physical Sciences
Research Council and The University of Birmingham for
a studentship (to P.J.J.).
References and notes
1. (a) Sefkow, M. Top. Curr. Chem. 2005, 243, 185–224; (b) Hoppe, R.;
Scharf, H.-D. Synthesis 1995, 1447–1464.
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Gravalos, D. G.; Higa, T. J. Nat. Prod. 2002, 65, 1505–1506; (b)
Ledroit, V.; Debitus, C.; Lavaud, C.; Massiot, G. Tetrahedron Lett.
2003, 44, 225–228.
3. For a recent synthesis see: Passiniemi, M.; Koskinen, A. M. P.
Tetrahedron Lett. 2008, 49, 980–983.
4. Lin, W.-Y.; Teng, C.-M.; Tsai, I.-L.; Chen, I.-S. Phytochemistry 2000,
53, 833–836.
5. (a) Bohlmann, F.; Ziesche, J. Phytochemistry 1979, 18, 664–665; (b)
Abraham, W. R.; Arfmann, H. A. Phytochemistry 1992, 18, 2405–
2408; see also: (c) Marwah, R. G.; Fatope, M. O.; Deadman, M. L.;
Al-Maqbali, Y. M.; Husband, J. Tetrahedron 2007, 63, 8174–8180.
6. (a) Ramalho, R.; Jervis, P. J.; Kariuki, B. M.; Humphries, A. C.; Cox,
L. R. J. Org. Chem. 2008, 73, 1631–1634; (b) Jervis, P. J.; Cox, L. R.
Beilstein J. Org. Chem. 2007, 3, 6; (c) Jervis, P. J.; Kariuki, B. M.;
Cox, L. R. Org. Lett. 2006, 8, 4649–4652; (d) Ramalho, R.; Beignet,
J.; Humphries, A. C.; Cox, L. R. Synthesis 2005, 3389–3397; (e)
Beignet, J.; Tiernan, J.; Woo, C. H.; Kariuki, B. M.; Cox, L. R. J.
Org. Chem. 2004, 69, 6341–6356; (f) Beignet, J.; Cox, L. R. Org. Lett.
2003, 5, 4231–4234.
In summary, we have developed a stereoselective route
to 3,4-disubstituted tetrahydrofurans and 2,3,4-trisubsti-
tuted tetrahydrofurans. Ring formation is achieved
through Brønsted acid-mediated allylation of an allylsilane
and an aldehyde. When stereochemical information is
absent from the cyclisation precursor, the reaction is highly
diastereoselective for a single product. The problem is more
H
R
OH
H
R
O
OH
O
H
10
7. For other recent approaches see: (a) Wolfe, J. P.; Hay, M. B.
Tetrahedron 2007, 63, 261–290; (b) Reddy, L. V. R.; Roy, A. D.; Roy,
R.; Shaw, A. K. Chem. Commun. 2006, 3444–3446; (c) Nasveschuk, C.
G.; Jui, N. T.; Rovis, T. Chem. Commun. 2006, 3119–3121; (d) Yoda,
H.; Kimura, K.; Takabe, K. Synlett 2001, 400–402; (e) Angle, S. R.;
Bernier, D. S.; Chann, K.; Jones, D. E.; Kim, M.; Neitzel, M. L.;
White, S. L. Tetrahedron Lett. 1998, 39, 8195–8198.
8. (a) Bonini, C.; Esposito, V.; D’Auria, M.; Righi, G. Tetrahedron 1997,
53, 13419–13426; (b) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M.
G. J. Am. Chem. Soc. 1996, 118, 4322–4343; (c) Evans, D. A.; Duffy,
major
SiMe3
T.S.1
H
R
OH
H
R
O
OH
SiMe3
T.S.2
O
H
12
minor
Fig. 4. Transition states leading to the two allylation products.

2518
P. J. Jervis et al. / Tetrahedron Letters 49 (2008) 2514–2518
J. L.; Dart, M. J. Tetrahedron Lett. 1994, 35, 8537–8540; (d) Evans, D.
A.; Dart, M. J.; Duffy, J. L. Tetrahedron Lett. 1994, 35, 8541–
8544.
119 (6), 107 (100), 91 (13), 79 (15), 55 (8); and then alcohol 12c as a
white solid (12 mg, 11%); mp 64–65 °C; Rf = 0.22 (6% EtOAc in
23
CH2Cl2); ½aꢂD +3.2 (c 1.00, CHCl3); mmax(film)/cmꢀ1 3416 br s (OH),
9. (a) Iversen, T.; Bundle, D. R. J. Chem. Soc., Chem. Commun. 1981,
1240–1241; (b) Clark, J. S.; Fessard, T. C.; Wilson, C. Org. Lett. 2004,
6, 1773–1776.
10. We have found the use of 0.1 equiv of TMSOTf to be more effective
than our previously described approach (see Ref. 6c) using stoichi-
ometric TMSOTf in the presence of a Brønsted acid scavenger.
11. Use of Lindlar catalyst led to appreciable amounts of over-reduction.
12. The over-reduction product was not separated from the desired
allylsilane but was readily separable from the tetrahydrofuran
cyclisation products.
1643 m (C@C); dH (300 MHz) 2.12 (1H, br s, OH), 2.87–3.12 (1H, m,
4-H), 4.00 (1H, app. t, J 9.0, 5-Ha), 4.15 (1H, dd, J 5.1, 2.6, 3-H), 4.27
(1H, app. t, J 8.1, 5-Hb), 4.96 (1H, d, J 2.6, 2-H), 5.20 (1H, d with
unresolved fine coupling, J 17.3, CH@CHcisHtrans), 5.28 (1H, d with
unresolved fine coupling, J 10.3, CH@CHcisHtrans), 5.83–5.98 (1H, m,
CH@CH2), 7.21–7.32 (5H, m, PhH); dC (125 MHz) 47.0 (CH, C-4),
70.8 (CH2, C-5), 80.4 (CH, C-2), 87.6 (CH, C-3), 119.4 (CH2, CH@
CH2), 125.3 (CH, Ph), 127.4 (CH, Ph), 128.4 (CH, Ph), 132.7 (CH,
CH@CH2), 140.9 (quat. C, ipsoPh); m/z (EI) 191 ([M+H]+, 0.5%), 173
(83, [MꢀOH]+), 151 (100), 121 (25), 106 (89), 92 (14), 84 (45), 77 (15),
56 (24), 44 (5).
13. Representative experimental procedure: MeSO3H (42 lL, 0.63 mmol)
was added to a solution of aldehyde 9c (150 mg, 0.57 mmol, prepared
from (S)-ethyl mandelate) in CHCl3 (6 mL) at ꢀ50 °C. After 5 min,
satd NaHCO3 solution (6 mL) was added and the reaction mixture
was allowed to warm to rt over 30 min. The two phases were
separated and the aqueous phase was extracted with CH2Cl2
(2 ꢁ 6 mL). The combined organic fractions were washed with H2O
(6 mL), and brine (6 mL) and then dried (MgSO4). Filtration and
evaporation of the solvent under reduced pressure provided a mixture
of tetrahydrofurans (7:1 10c:12c) which were separated by flash
column chromatography (6% EtOAc in CH2Cl2) to provide, in order
of elution, alcohol 10c as a viscous, colourless oil (83 mg, 77%);
14. Data for 14 (prepared from (S)-ethyl mandelate): Rf = 0.28 (6%
23
EtOAc in CH2Cl2); ½aꢂD ꢀ8.7 (c 1.00, CHCl3); mmax(film)/cmꢀ1 3406
br s (OH), 1645 w (C@C); dH (300 MHz) 1.25 (1H, br s, OH), 3.08–
3.21 (1H, m, 4-H), 4.06 (1H, dd, J 10.7, 8.1, 5-Ha), 4.15 (1H, app. t, J
8.1, 5-Hb), 4.23 (1H, app. t, J 3.0, 3-H), 5.10 (1H, d, J 3.0, 2-H), 5.16
(1H, d, J 11.4, CH@CHcisHtrans), 5.21 (1H, d, J 16.9, CH@CHcis
-
Htrans), 5.91–6.06 (1H, m, CH@CH2), 7.25–7.42 (5H, m, PhH); dC
(75 MHz) 49.8 (CH, C-4), 70.9 (CH2, C-5), 75.8 (CH, C-3), 85.6 (CH,
C-2), 118.1 (CH2, CH@CH2), 126.7 (CH, Ph), 127.9 (CH, Ph), 128.5
(CH, Ph), 133.5 (CH, CH@CH2), 137.0 (quat. C, ipsoPh); m/z (EI)
190 (M+, 1%), 161 (4), 136 (7), 119 (12), 115 (5), 107 (100), 91 (42), 91
(44), 79 (53), 55 (47), 51 (14); HRMS m/z (EI) 190.1002. C12H14O2
requires 190.9940.
23
Rf = 0.24 (6% EtOAc in CH2Cl2); ½aꢂD ꢀ29.9 (c 1.00, CHCl3); (found:
C, 75.41; H, 7.12%. C12H14O2 requires C, 75.76; H, 7.42%);
m
max(film)/cmꢀ1 3401 br s (OH), 1643 m (C@C); dH (300 MHz)
15. Crystallographic data (excluding structure factors) for the structures
in this Letter have been deposited with the Cambridge Crystallo-
graphic Data Centre as supplementary publications nos. 10f CCDC
677099; 12c CCDC 677098; 14 CCDC 677100. Copies of the data can
be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: +44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
16. Brinza, I. M.; Fallis, A. G. J. Org. Chem. 1996, 61, 3580–3581.
17. Cornforth, J. W.; Cornforth, R. H.; Mathew, K. K. J. Chem. Soc.
1959, 112–127.
1.87 (1H, br s, OH), 2.97 (1H, app. quintet, J 8.1, 4-H), 3.88 (1H, app.
t, J 5.9, 3-H), 3.93 (1H, app. t, J 8.8, 5-Ha), 4.26 (1H, app. t, J 7.3, 5-
Hb), 4.64 (1H, d, J 7.4, 2-H), 5.13 (1H, d with unresolved fine
coupling, J 10.3, CH@CHcisHtrans), 5.21 (1H, d with unresolved fine
coupling, J 17.3, CH@CHcisHtrans), 5.67–5.82 (1H, m, CH@CH2),
7.21–7.43 (5H, m, PhH); dC (125 MHz) 52.4 (CH, C-4), 71.1 (CH2, C-
5), 83.2 (CH, C-3), 85.6 (CH, C-2), 117.6 (CH2, CH@CH2), 125.8
(CH, Ph), 127.8 (CH, Ph), 128.5 (CH, Ph), 136.2 (CH, CH@CH2),
140.3 (quat. C, ipsoPh); m/z (EI) 190 ([M]+, 0.5%), 161 (4), 136 (5),