Lead(IV) acetate oxidative ring-opening of 2,3-epoxy primary alcohols: A new entry to optically active α-hydroxy carbonyl compounds

Article abstract of DOI:10.1016/j.tetlet.2011.05.116

The treatment of 2,3-epoxy primary alcohols with lead(IV) acetate (LTA) leads to α-acetoxy aldehydes or α-acetoxy ketones, through the nucleophilic ring-opening of an intermediate oxonium and the subsequent carbon-carbon bond cleavage. This reaction repre

Full text of DOI:10.1016/j.tetlet.2011.05.116

Tetrahedron Letters 52 (2011) 4017–4020
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Lead(IV) acetate oxidative ring-opening of 2,3-epoxy primary alcohols: a
new entry to optically active a-hydroxy carbonyl compounds
Enrique Alvarez-Manzaneda a, , Rachid Chahboun a, Esteban Alvarez a, Ramón Alvarez-Manzaneda b,
⇑
Pedro E. Muñoz a, Fermín Jiménez a, Hanane Bouanou a
a Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Universidad de Granada, 18071 Granada, Spain
b Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Almería, 04120 Almería, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
The treatment of 2,3-epoxy primary alcohols with lead(IV) acetate (LTA) leads to a-acetoxy aldehydes or
Received 30 March 2011
Revised 24 May 2011
Accepted 25 May 2011
Available online 1 June 2011
a-acetoxy ketones, through the nucleophilic ring-opening of an intermediate oxonium and the subse-
quent carbon–carbon bond cleavage. This reaction represents a new route to optically active
a-hydroxy
carbonyl compounds.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Hydroxycarbonyl compounds
Allyl alcohols
Asymmetric synthesis
Lead tetraacetate
1. Introduction
Lead(IV) acetate (LTA, lead tetraacetate) has long been consid-
ered one of the most useful reagents in organic chemistry because
of its ability to bring about various reactions under mild conditions
and its low cost.13 LTA is commonly used for oxidative cleavage
(C–C bond cleavage),14 decarboxylations,15 acetoxylation,16 and
formation of cyclic ethers (C–O bond formation).17 It is less often
used for C–C bond formation,18 and C–N bond formation.19 The
The
a-hydroxy carbonyl group occupies a prominent place in
organic chemistry. It is found in a wide variety of biologically
active natural products,1a–e such as the farnesyl-transferase inhib-
itor kurosain A.1e Chiral
a-hydroxy ketones (acyloins) are also
versatile synthetic intermediates in asymmetric synthesis.2
Numerous methods for introducing a hydroxyl group into the
use of LTA for the oxidation of allylic alcohols and a,b-epoxy alco-
a
-position to a carbonyl moiety have been reported. These include
hols to the corresponding carbonyl compounds has been re-
ported.20 More recently, some new applications have been
reported, such as the preparation of aryl lead triacetate, utilized
in the direct arylation of nucleophiles21 and a very interesting mul-
tistage hetero-domino transformation;22 both examples allow the
construction of unique carbon substitution patterns. Very recently
an interesting LTA mediated oxidative fragmentation of homoal-
lylic alcohols23 and an oxidative cleavage of allyl alcohols induced
by the O3/LTA system24 have been reported.
the direct oxidation of ketone/enol3 or the most widely used pro-
cedure, involving enolates.4 Most of the above cited methods are
restricted to ketones. The corresponding
a-hydroxylation of alde-
hydes is often complicated by undesired self-condensation of the
enolates and the instability of the hydroxylated products.4c Fre-
quently, a-hydroxy carbonyl compounds are made using multistep
transformations.5
Several chemical methods for the preparation of chiral a-hydro-
xy carbonyl compounds have been described in the literature,6
including stereoselective versions of some of the above methods.7,8
More recently, the desymmetrization of meso-diols through acyla-
tion and oxidation,9 the asymmetric reductive coupling of alkynes
and aldehydes,10 or the asymmetric dihydroxylation of substituted
In this Letter, we communicate a lead(IV) acetate (LTA) oxida-
tive ring-opening of 2,3-epoxy alcohols leading to
hydes or -acetoxy ketones with complete regioselectivity. The use
of asymmetric Sharpless epoxidation allows the enantioselective
synthesis of -acetoxy carbonyl compounds from the correspond-
a-acetoxy alde-
a
a
allenes,11 have been utilized for synthesizing chiral
a-hydroxy
ing allyl alcohols.
ketones. An alternative procedure to obtain enantiomerically pure
acyloins involves their chemoenzymatic dynamic kinetic
resolution (DKR).12
2. Results and discussion
During our research on the synthesis of bioactive natural
products we found that 2,3-epoxy alcohols were transformed into
⇑
Corresponding author. Tel./fax: +34 958 24 80 89.
E-mail address: eamr@ugr.es (E. Alvarez-Manzaneda).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.116

4018
E. Alvarez-Manzaneda et al. / Tetrahedron Letters 52 (2011) 4017–4020
Table 1
Reaction of 2,3-epoxy alcohols with LTA
O
R1
R2
O
R1
R2
OH
LTA
R3
R3
Benzene, Δ
OAc
1
2
Entry
1
Epoxy alcohol26
Time
Product26
%
O
AcO
1a 27
2a
20 min
73
OH
O
CHO
OAc
1b 28
2b
OH
2
3
1 h
96
94
OAc
OAc
O
HO
O
O
OAc
1c a, 29
1.5 h
2c a
COOMe
COOMe
2d
H
H
4
5
2 h
2 h
97
1d
AcO
O
OH
O
O
1e 30
Complex mixture
OH
OH
O
O
OAc
2f 32
1f 31
6
2 h
26
H
+
H
Complex mixture
Synthesis of a-acetoxy aldehydes and a-acetoxy ketones.
a Diastereomeric ratio: 6:1.
a
-acetoxy aldehydes or a-acetoxy ketones with complete regiose-
OAc
O
R1
R2
R1
R2
R3
O
R3
lectivity, after treating with one equivalent of LTA in benzene with
heating. The oxidation leading to aldehydes was performed at
50 °C and the reaction leading to ketones was carried out at reflux.
When 2,3-epoxyhexanol (1a) was treated with Pb(OAc)4 in ben-
zene at 50 °C for 20 min 2-acetoxypentanal (2a) was obtained in
73% yield.25 In order to establish the scope and limitations of this
reaction a series of 2,3-epoxy alcohols was studied; Table 1 shows
some representative examples. 2,3-Epoxyalcohols bearing an alkyl
- AcO
O
O
AcO
Pb
Pb
AcO
OAc
OAc
AcO
I
group on the C-2 (compounds 1b–d) led to the corresponding
a-
R3
R3
acetoxy ketones 2b–d; cyclic epoxides of this type (compounds
AcO
R1
AcO
R1
- HCHO
1c–d) gave cyclohexanone derivatives (ketones 2c–d). 3,3-Dial-
kyl-2,3-epoxyalcohols (1e–f) showed a different behaviour to that
of the above mentioned epoxy alcohols, affording a mixture of
products. Acyclic compounds, such as alcohol 1e, always produced
a complex mixture, whereas the more rigid cyclic epoxy alcohols,
such as the bicyclic alcohol 1f, led to a mixture of compounds
O
- Pb(OAc)2
OAc
R2
O
R2
O
Pb
OAc
R1 or R2: H; R3: Alkyl or H
Scheme 1. Mechanism of the reaction of 2,3-epoxy alcohols with LTA.
including the a-acetoxy ketone 2f as a minor constituent.
The results obtained when chiral non-racemic epoxy alcohols
(entries 3 and 4) were utilized as the substrate reaction deserve
special mention. The enantiopure compound 1d was transformed
unsatisfactory results provided by the 3,3-dialkyl-2,3-epoxyalco-
hols, such as compounds 1e–f, can be attributed to the formation
of a tertiary carbenium ion resulting from the oxonium ring open-
ing, which undergoes different side reactions. The retention of con-
figuration observed in the formation of compound 2f is
presumably the result of nucleophilic attack at the less hindered
face of the carbenium ion (entry 6).
into the
a-acetoxy ketone 2d as the only isomer. Epoxy alcohol
1c, a 6:1 mixture of diasteroisomers, gave a mixture of diastereo-
meric acetoxy ketones 2c in identical proportion. In both cases
an inversion of configuration on
the 3,3-dialkyl-2,3-epoxyalcohol 1f afforded the minor
ketone 2f with retention of the configuration on the -carbon.
a-carbon was observed. However,
a-acetoxy
a
A possible mechanism for this new reaction, which is in agree-
ment with the observed regio- and stereoselectivities, is depicted
in Scheme 1. The complete stereoselectivity exhibited by chiral
epoxydes, such as compounds 1c–d, can be explained by the nucle-
ophilic attack of acetate anion in the intermediate oxonium I. The
In view of the complete stereoselectivity observed for chiral
compounds 1c–d, the enantioselective synthesis of a-acetoxy car-
bonyl compounds from allylic alcohols, via epoxides obtained
through Sharpless reaction,30 was investigated. Epoxy alcohols
3a–d were prepared, with >95% enantiomer excess,37 with the

E. Alvarez-Manzaneda et al. / Tetrahedron Letters 52 (2011) 4017–4020
4019
Table 2
Enantioselective synthesis of
a
-acetoxy aldehydes and
a
-acetoxy ketones
Ti(OPri)4, t-BuOOH
O
O
R1
R2
R1
R2
R3
LTA
R3
OH
R1
R2
R3
Di Et (+)-L-Tartrate
CH2Cl2
Benzene, Δ
OH
AcO
4
3
Entry
1
Epoxy alcohol26
Time
Product26
OAc
%
O
3a 33
n-C7H15
OH
4a
20 min
1 h
93
n-C7H15
CHO
OAc
O
3b34
OH
AcO
AcO
HO
2
3
4
95
59
81
4b
O
O
O
OAc
4c 36
1 h
4 h
3c 30
OAc
3d 35
a
O
4d
OH
O
O
OAc
OH
3e b
O
5
45 min
92
4e b
H
H
COOMe
COOMe
a 70% ee.
b Diastereomeric ratio: 6:1.
Sharpless
pounds with Pb(OAc)4 in benzene under heating afforded in high
yield the corresponding -acetoxy carbonyl derivatives 4a–d.
L
-(+)DET reagent (Table 2). Treatment of these com-
for the International Cooperation and Development (AECID) for
the predoctoral grant provided.
a
Compounds 4a–c were obtained with >95% enantiomer excess, as
it could be expected. The acetoxy cyclohexanone derivative 4d re-
sulted in only 70% enantiomer excess; the lower enantioselectivity
observed in this case can be attributed to the 3,3-dialkyl substitu-
tion pattern of epoxy alcohol 3d, which can react via carbocationic
intermediate. Epoxy alcohol 3e, a 6:1 mixture of diastereomers ob-
tained after the Sharpless epoxidation of the corresponding enan-
References and notes
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D
those reported in the literature.32,36
3. Conclusions
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In summary, the treatment of 2,3-epoxy alcohols with Pb(OAc)4
causes a carbon–carbon cleavage which proves to be a useful syn-
thetic tool. a-Acetoxy aldehydes or a-acetoxy ketones can be effi-
ciently synthesized by treating 2,3-epoxy alcohols with lead
tetraacetate in benzene under heating. The reaction, which pro-
ceeds with complete regio- and high stereoselectivities facilitates
the enantioselective synthesis of
a-acetoxy carbonyl compounds
from allyl alcohols, via Sharpless epoxidation. In order to explore
the scope of this reaction, the behaviour of larger cyclic ethers is
being studied.
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Acknowledgements
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The authors thank the Spanish Ministry of Science and Innova-
tion (Project CTQ2009-09932) and the Regional Government of
Andalucia (Project P07-FQM-03101 and assistance to the FQM-
348 group) for financial support. H.B. thanks the Spanish Agency

4020
E. Alvarez-Manzaneda et al. / Tetrahedron Letters 52 (2011) 4017–4020
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(C), 34.2 (CH2), 37.2 (CH2), 41.1 (CH2), 49.5 (CH), 81.6 (C), 170.0 (C), 214.3 (C).
HRMS (EI) M+ m/z: calcd for C16H26O3 266.1882, found: 266.1894.
Compound 3e: Colourless oil. 1H NMR (CDCl3, 500 MHz) d: 0.54 (s, 3H), 0.93–
1.04 (m, 2H), 1.11 (s, 3H), 1.22 (s, 3H), 1.44 (m, 1H), 1.55–1.96 (m, 9H), 2.10 (br
d, J = 13.5 Hz, 1H), 2.35 (m, 1H), 2.94 (dd, J = 6.8, 4.1 Hz, 1H), 3.44 (d,
J = 12.1 Hz, 1H), 3.54 (s, 3H), 3.60 (d, J = 12.1 Hz, 1H), 4.67 (s, 1H), 4.86 (s,
1H); signals assignable to minor isomer: 3.53 (s, 3H, OCH3), 4.40 (s, 1H,
C@CH2), 4.80 (s, 1H, C@CH2); 13C NMR (CDCl3, 125 MHz) d: 12.4 (CH3), 14.4
(CH3), 20.0 (CH2), 23.3 (CH2), 26.1 (CH2), 28.8 (CH3), 38.2 (CH3), 38.6 (CH2), 39.4
(CH2), 40.2 (C), 44.3 (C), 51.2 (CH3), 54.3 (CH), 56.2 (CH), 62.2 (CH), 59.9 (C),
60.1 (CH), 65.6 (CH2), 107.5 (CH2), 180.9 (C); IR (film): 3446, 1724, 1645, 1449,
1384, 1154, 1033, 891 cmꢁ1. HRMS (EI) M+ m/z: calcd for C20H32O4 336.2301,
found: 336.2308.
9. Mueller, C. E.; Zell, D.; Shreiner, P. R. Chem. Eur. J. 2009, 15, 9647–9650.
10. Miller, K. M.; Huang, W.-H.; Jamison, T. F. J. Am. Chem. Soc. 2003, 125, 3442–
3443.
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14. Criegee, R. Chem. Ber. 1931, 64B, 260–266.
Compound 4a: Colourless oil. ½a D25
ꢀ
= +15.2 (c 1.2, CHCl3). 1H NMR (CDCl3,
500 MHz) d: 0.87 (t, J = 7.2 Hz, 3H), 1.22–1.35 (m, 8H), 1.36–1.45 (m, 2H), 1.67–
1.76 (m, 1H), 1.77–1.86 (m, 1H), 2.17 (s, 3H), 4.98 (dd, J = 8.4, 4.8 Hz, 1H), 9.51
(s, 1H); 13C NMR (CDCl3, 125 MHz) d: 14.1 (CH3), 20.6 (CH2), 22.6 (CH2), 25.0
(CH2), 28.7 (CH2), 29.0 (CH2), 29.2 (CH2), 31.7 (CH2), 78.4 (CH), 170.3 (C), 198.4
(C); IR (film): 1742, 1371, 1233, 1045 cmꢁ1. HRMS (EI) M+ m/z: calcd for
15. (a) Starnes, W. H., Jr. J. Am. Chem. Soc. 1964, 86, 5603–5611; (b) Sheldon, R. A.;
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and references cited therein.
C11H20O3 200.1412, found: 200.1406.
Compound 4c: Colourless oil, ½a D25
ꢀ
= +76.0 (c 1.2, MeOH). 1H NMR (CDCl3,
500 MHz) d: 1.57 (ddd, 13.3, 13.3, 4.1 Hz, 1H), 1.64–1.76 (m, 2H), 1.91 (m, 1H),
2.02 (m, 1H), 2.09 (s, 3H), 2.23 (m, 1H), 2.39 (ddt, J = 13.7, 6.1, 1.0 Hz, 1H), 2.51
(m, 1H), 5.10 (m, 1H); 13C NMR (CDCl3, 125 MHz) d: 20.7 (CH3), 23.8 (CH2), 27.1
(CH2), 33.1 (CH2), 40.7 (CH2), 76.5 (CH), 170.0 (C), 204.5 (C). HRMS (EI) M+ m/z:
calcd for C8H12O3 156.0786, found: 156.0795.
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25. Typical procedure for the reaction of 2,3-epoxy alcohols with lead (IV) acetate:
To a solution of epoxy alcohols (1 mmol) in dry benzene (10 mL) was added
lead (IV) acetate (1.3 mmol) and the reaction mixture was heated at 50 °C or at
reflux for the specified time (monitorized by TLC). Then, the reaction was
quenched with 5% Na2SO3, extracted with Et2O, washed with water, brine,
dried (Na2SO4) and concentrated. The residue was chromatographed on silica
gel (hexanes/ether) to give acetoxy carbonyl compounds.
Compound 4e: Colourless oil. ½a D25
ꢀ
= +14.1 (c 1.6, CHCl3). 1H NMR (CDCl3,
500 MHz) d: 0.50 (s, 3H), 1.06 (ddd, J = 13.3, 13.3, 4.0 Hz, 1H), 1.07 (ddd,
J = 13.8, 13.8, 3.0 Hz, 1H), 1.18 (s, 3H), 1.33 (dd, J = 12.5, 3.1 Hz, 1H), 1.53 (m,
1H), 1.70–1.94 (m, 8H), 2.00 (m, 1H), 2.13 (s, 3H), 2.17 (s, 3H), 2.42 (dt, J = 11.7,
3.1 Hz, 1H), 3.61 (s, 3H), 4.59 (s, 1H), 4.94 (s, 1H), 4.97 (d, 10.0 Hz, 1H); signals
assignable to minor isomer: 3.60 (s, 3H, OCH3), 4.62 (s, 1H, C@CH2), 4.90 (s, 1H,
C@CH2); 13C NMR (CDCl3, 125 MHz) d: 12.7 (CH3), 19.9 (CH2), 20.8 (CH3), 25.2
(CH3), 26.17 (CH3), 26.20 (CH2), 28.8 (CH3), 38.2 (CH2), 38.6 (CH2), 39.1 (CH2),
40.1 (C), 44.4 (C), 51.3 (CH3), 51.6 (CH), 56.3 (CH), 77.8 (CH), 107.0 (CH2), 147.3
(C), 170.8(C), 177.6 (C), 205.9 (C); IR (film): 1750, 1725, 1644, 1445, 1374,
1248, 1227, 1155, 1046, 983, 893, 756 cmꢁ1. HRMS (EI) M+ m/z: calcd for
C21H32O5 364.2250, found: 364.2242.
27. Malkov, A. V.; Czemerys, L.; Malyshev, D. A. J. Org. Chem. 2009, 74, 3350–3355.
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29. Mori, K. Tetrahedron: Asymmetry 2006, 17, 2133–2142.
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Am. Chem. Soc. 1987, 109, 5765–5780.
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26. All new compounds were fully characterized spectroscopically and had
satisfactory high resolution mass spectroscopy data. Selected data:
Compound 1d: Colourless oil.
½
a 2D5
ꢀ
= +4.8 (c 0.5, CHCl3). 1H NMR (CDCl3,
500 MHz) d: 0.76 (d, J = 6.6 Hz, 3H), 0.79 (s, 3H), 0.92 (d, J = 6.6 Hz, 3H), 1.24
(dd, J = 3.9, 3.9 Hz, 1H), 1.08 (s, 3H), 1.12 (m, 1H), 1.17 (s, 3H), 1.13 (m, 1H),
1.22–1.34 (m, 3H), 1.34–1.42 (m, 2H), 1.46–1.60 (m, 2H), 1.80–1.89 (m, 3H),
1.97 (m, 1H), 2.04 (m, 1H), 2.13 (dd, J = 14.8, 8.1 Hz, 1H), 2.31 (dd, J = 14.8,
6.0 Hz, 1H), 3.29 (d, J = 3.2 Hz, 1H), 3.63. (dd, J = 12.3, 8.7 Hz, 1H), 3.64 (s, 3H),
3.99 (dd, J = 12.3, 2.2 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d: 15.7 (CH3), 16.7
(CH2), 19.6 (CH3), 19.9 (CH3), 22.7 (CH3), 29.08 (CH2), 29.14 (CH2), 29.26 (CH3),
31.1 (CH), 34.5 (CH2), 34.6 (C), 35.6 (CH2), 37.5 (CH), 39.0 (C), 41.6 (CH2), 44.3
(CH), 51.4 (CH3), 57.5 (CH), 61.2 (CH2), 63.9 (C), 173.6 (C); IR (film): 3450, 1739,
34. Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980, 102, 5974–5976.
35. Abad, A.; Agulló, C.; Arnó, M.; Cuñat, A. C.; Zaragozá, R. J. Synlett 1993, 895–896.
36. Sugimura, T.; Iguchi, H.; Tsuchida, R.; Tai, A.; Nishiyama, N.; Hakushi, T.
Tetrahedron: Asymmetry 1998, 9, 1007–1013.
1716, 1699, 1684, 1558, 1507, 1457, 1306, 1233, 1038, 897, 788, 747 cmꢁ1
.
HRMS (EI) M+ m/z: calcd for C21H36O4 352.2614, found: 352.2608.
37. The enantiomeric excesses were determined by 1H NMR, utilizing europium
(III) tris [3-(heptafluoropropylhydroxymethylene)-d-camphorate] [Eu(hfc)3] as
chiral shift reagent.
Compound 2a: Colourless oil.
½
a 2D5
ꢀ
= ꢁ7.2 (c 1.2, CHCl3). 1H NMR (CDCl3,
500 MHz) d: 0.93 (t, J = 7.3 Hz, 3H), 1.34–1.52 (m, 2H), 1.61–1.86 (m, 2H), 2.15
(s, 3H), 4.98 (dd, J = 8.4, 4.6 Hz, 1H), 9.50 (s, 1H); 13C NMR (CDCl3, 125 MHz) d:
13.8 (CH3), 18.3 (CH2), 20.6 (CH3), 30.7 (CH2), 78.2 (CH), 170.7 (C), 198.3 (C); IR
Typical experimental procedure: 10 mg of Europium(III) tris[3-
(heptafluoropropylhydroxymethelene)-d-camphorate] (Eu(hfc)3) was added
to a solution of benzoates obtained from alcohols 3a–d (15 mg) in CDCl3
(0.5 mL) containing 1% of TMS, and the resulting yellow solution was stand for
15 min. Then, the solution was added to an NMR tube and the 1H NMR
spectrum recorded. The relative intensities (peak heights or peak areas) of the
resonance signal of oxygenated methylene protons were measured and the
percentage of each enantiomer in the sample calculated.
(film): 1737, 1729, 1468, 1372, 1247, 1105, 1017, 799, 750 cmꢁ1
.
Compound 2d: Colourless oil. ½a D25
ꢀ
= +16.4 (c 0.5, CHCl3). 1H NMR (CDCl3,
500 MHz) d: 0.66 (s, 3H), 0.73 (d, J = 6.7 Hz, 3H), 0.97 (d, J = 6.7 Hz, 3H), 1.33 (s,
3H), 1.42 (ddd, J = 13.3, 13.3, 3.5 Hz, 1H), 1.45 (ddd, J = 13.2, 13.3, 3.6 Hz, 1H),
1.80 (m, 1H), 1.85 (m, 1H), 1.95 (m, 1H), 2.13 (s, 3H), 2.29 (dt, J = 13.4, 3.5 Hz,
1H), 2.31 (dd, J = 14.9, 6.1 Hz, 1H), 3.66 (s, 3H), 5.65 (dd, J = 11.3, 8.6 Hz, 1H);
13C NMR (CDCl3, 125 MHz) d: 15.6 (CH3), 18.9 (CH2), 19.1 (CH3), 19.8 (CH3),
20.7 (CH3), 27.3 (CH2), 28.9 (CH2), 30.1 (CH3), 30.9 (CH), 30.95 (CH2), 35.05
(CH2), 35.12 (CH2), 37.2 (CH), 40.1 (C), 41.4 (CH2), 48.2 (C), 49.8 (CH), 51.4
(CH3), 72.4 (CH), 170.2 (C), 173.5 (C), 209.6 (C); IR (film): 1746, 1722, 1462,
1437, 1373, 1238, 1173, 1089, 1013, 984, 789, 753 cmꢁ1. HRMS (EI) M+ m/z:
calcd for C22H36O5 380.2563, found: 380.2572.
Chemical shifts of signals for the oxygenated methylene groups on benzoate
derivatives of 3a–d (d, ppm):
3a benzoate: Racemic mixture: 6.61 (br s, 1H), 6.67 (br s, 1H) and 6.74 (br s,
1H), 6.92 (br s, 1H); chiral compound (>95%): 6.71 (br s, 1H) and 6.87 (br s, 1H).
3b benzoate: Racemic mixture: 6.87 (br s, 1H), 6.97 (br s, 1H) and 7.04 (br s,
1H), 7.11 (br s, 1H); chiral compound (>95%): 6.98 (br s, 1H) and 7.06 (br s, 1H).
3c benzoate: Racemic mixture: 6.52 (br s, 1H), 6.57 (br s, 1H) and 6.64 (br s,
1H), 6.69 (br s, 1H); chiral compound (>95%): 6.62 (br s, 1H) and 6.66 (br s, 1H).
3d benzoate: Racemic mixture: 6.77 (br s, 1H), 6.80 (br s, 1H) and 6.85 (br s,
1H), 6.91 (br s, 1H); chiral compound (>95%): 6.93 (br s, 1H) and 7.01 (br s, 1H).
Compound 2f: Colourless oil. ½a D25
ꢀ
= +72.0 (c 1.0, CHCl3). 1H NMR (CDCl3,
500 MHz) d: 0.87 (s, 3H), 0.93 (s, 3H), 1.12 (s, 3H), 1.44 (s, 3H), 1.14–1.67 (m,
7H), 3.49 (br d, J = 12.3 Hz, 1H), 1.84 (m, 1H), 1.96 (dt, J = 12.8, 3.2 Hz, 1H), 2.02
(s, 3H), 2.31 (ddd, J = 13.2, 13.2, 5.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d: 18.2
(CH2), 19.3 (CH2), 19.7 (CH3), 21.5 (CH3), 22.1 (CH3), 26.7 (CH2), 33.0 (CH3), 33.9