A novel approach to γ-hydroxy-α,β-unsaturated compounds

Article abstract of DOI:10.1055/s-0028-1083162

A simple synthesis of (E)-alk-1-enyl mesylates from (E)-alk-1- enylphosphonates is reported. Construction of γ-hydroxy-α,β- unsaturated compounds was achieved by a two-step process involving dihydroxylation of the enol mesylates followed by HWE reaction of the resulting α-hydroxy aldehydes with activated methylphosphonates. Enantioselective synthesis of the title compounds is also reported.

Full text of DOI:10.1055/s-0028-1083162

PAPER
3299
A Novel Approach to g-Hydroxy-a,b-unsaturated Compounds
Synthesis of
g
-Hyd
e
roxy-
a
,
b
-u
n
nsaturated
C
r
ompoun
y
ds k Krawczyk,* Katarzyna Wąsek, Jacek Kędzia
Institute of Organic Chemistry, Technical University of Łódź, Żeromskiego 116, 90-924 Łódź, Poland
Fax +48(42)6365530; E-mail: henkrawc@p.lodz.pl
Received 17 June 2008; revised 1 July 2008
OH
Abstract: A simple synthesis of (E)-alk-1-enyl mesylates from (E)-
alk-1-enylphosphonates is reported. Construction of g-hydroxy-
R
EWG
a,b-unsaturated compounds was achieved by a two-step process in-
volving dihydroxylation of the enol mesylates followed by HWE re-
action of the resulting a-hydroxy aldehydes with activated
methylphosphonates. Enantioselective synthesis of the title com-
pounds is also reported.
1a–c
EWG = (a) COOR, (b) CN, (c) P(O)(OR)2
Figure 1 g-Hydroxy-a,b-unsaturated esters, nitriles, and phosphon-
ates
Key words: alk-1-enyl mesylates, dihydroxylation, a-hydroxy al-
dehydes, Horner–Wadsworth–Emmons reaction, Conant–Swan
fragmentation
The optically active O-protected esters 1a were prepared
by irradiation of enantioenriched a,b-epoxydiazomethyl
ketones in ethanol as well as by the Wittig olefination of
O-protected enantiomeric a-hydroxy aldehydes with sta-
bilized phosphonium ylides.12
In recent years, g-hydroxy-a,b-unsaturated esters 1a and
nitriles 1b have found wide applicability in organic syn-
thesis. To date numerous examples have been provided,
which demonstrate particular utility of these reagents for
constructing various biologically active compounds and
natural products.1 In contrast, much less attention has
been paid to structurally related g-hydroxy-a,b-unsaturat-
ed phosphonates 1c2 (Figure 1).
It has been recently reported that similar Horner–Wads-
worth–Emmons (HWE) reaction of enantio-enriched and
unprotected a-hydroxy aldehydes with methyl diethyl-
phosphonoacetate affords the esters 1a displaying high
optical purity.13 Satisfactory result of the latter synthesis
was achieved owing to a new and effective approach to
the starting aldehydes as well as unconventional protocol
of their HWE olefination. The new approach relies on the
asymmetric dihydroxylation of a,b-unsaturated sulfones
using Sharpless methodology and subsequent elimination
of sulfonic acids from the resulting a,b-dihydroxysul-
fones. Direct HWE reaction of the crude a-hydroxy alde-
hydes allowed avoiding their easy tautomeric
rearrangement into hydroxyl ketones and racemization.14
All these compounds have been preferentially obtained by
hydroxylative Knoevenagel condensation of aldehydes
with sulfinylacetates, sulfinylacetonitriles and sulfinyl-
methylphosphonates, respectively (SPAC-reaction).2,3
Enantioselective approach to esters 1a and nitriles 1b us-
ing S-chiral sulfinylacetates and sulfinylacetonitriles has
been also reported.1e,4
A number of different synthetic routes leading to racemic
esters 1a and nitriles 1b have been described. They are
readily available by regioselective oxidation-reduction re-
actions of a,b,g,d-unsaturated alkadienoates and structur-
ally related nitriles with molecular oxygen and
triethylsilane in the presence of Co(II) porphyrin.5 Other
equally attractive methods involve oxyselenylation–dese-
lenylation of b,g-unsaturated esters or nitriles6 and conju-
gate addition of Grignard reagents to g-hydroxy-
butynenitriles.7 Optically active nitriles 1b are accessible
by b-elimination of water from nonracemic b,g-dihy-
droxyalkanenitriles,8 cyanation of enantiomerically en-
riched g-iodoallylic alcohols with CuCN,9 and
stereoselective SN2¢ substitution reaction of enantiomeric
O-acylated allylic cyanohydrins.10
With these observations in hand, it became of interest to
develop other methodologically similar synthesis of ste-
reochemically defined g-hydroxy-a,b-unsaturated com-
pounds bearing different electron-withdrawing groups.
We envisaged that alk-1-enyl mesylates (aldehyde enol
mesylates) could serve as convenient precursors of a-hy-
droxy aldehydes.
Reported herein is a stereospecific approach to (E)-alk-1-
enyl mesylates and their utility in the preparation of race-
mic g-hydroxy-a,b-unsaturated esters, nitriles, and phos-
phonates. Preliminary studies on their enantioselective
synthesis are also described. The literature contains only
a few examples of simple alk-1-enyl mesylates and there
is no general method for their effective and stereoselective
preparation.15
A simple alternative source of racemic esters 1a is the ad-
dition of Grignard reagents to g-oxo-a,b-alkanoates.11
Our synthesis of these compounds begins with dihydrox-
ylation of (E)-a,b-unsaturated phosphonates 2 with a
catalytic amount of OsO4 in the presence of N-methylmor-
pholine N-oxide (NMO) as a co-oxidant leading to the
SYNTHESIS 2008, No. 20, pp 3299–3306
x
x.
x
x
.
2
0
0
8
corresponding
(Scheme 1).
syn-1,2-dihydroxyphosphonates
316
Advanced online publication: 25.09.2008
DOI: 10.1055/s-0028-1083162; Art ID: Z14108SS
© Georg Thieme Verlag Stuttgart · New York

3300
H. Krawczyk et al.
PAPER
OH
O
OH
O
OH
a
a or b
P(OEt)2
P(OEt)2
H
R
Bu
EWG
R
Bu
OH
3a–e
O
2a–e
OMs
13 EWG = CN
14 EWG = P(O)(OEt)2
8a
O
OMs
O
Scheme 3 Reagents and conditions: (a) (EtO)2P(O)CH2CN (11), (1
equiv), NaH (1 equiv), THF, 20 h, 25 °C; (b) (EtO)2P(O)CH2-
P(O)(OEt)2 (12, 1 equiv), NaH (1 equiv), THF, 20 h, 25 °C.
b
c
P(OEt)2
P(OH)2
R
R
OMs
4a–e
OMs
5a–e
d
OMs
R = (a) Bu, (b) Pent, (c) i-Pr,
(d) c-C6H11, (e) PhCH2CH2
R
OH
6a–e
a, c
Bu
EWG
Scheme 1 Reagents and conditions: (a) NMO (1.1 equiv), OsO4
(cat.), t-BuOH–acetone (4:1), 25 °C, 3 d; (b) Et3N (2.5 equiv),
MeSO2Cl (2 equiv), CH2Cl2, 25 °C, 20 h; (c) Me3SiBr (4 equiv),
CH2Cl2, 25 °C, 5 d, then EtOH; (d) Et2O, aq sat. NaHCO3, 2 h, 25 °C.
(S)-10a, (S)-13, (S)-14
OMs
Bu
6a
OH
b, c
Bu
EWG
OH
(R)-10a, (R)-13, (R)-14
a
OMs
OMs
R
R
Scheme 4 Reagents and conditions: (a) AD-mix-a, K2SO4·H2O (0.8
mol%), t-BuOK/H2O (1:1), MeSO2NH2 (2 equiv), 72 h, 25 °C; (b)
AD-mix-b, K2SO4·H2O (0.8 mol%), t-BuOK/H2O (1:1), MeSO2NH2
(2 equiv), 72 h, 25 °C; (c) (EtO)2P(O)CH2CO2Et (9, 1 equiv) or
(EtO)2P(O)CH2CN (11, 1 equiv) or (EtO)2P(O)CH2P(O)(OEt)2 (12, 1
equiv), NaH (1 equiv), THF, 20 h, 25 °C.
6a–e
OH
7a–e
OH
OH
b
H
R
R
COOEt
O
8a–e
10a–e
R = (a) Bu, (b) Pent, (c) i-Pr, (d) c-C6H11, (e) PhCH2CH2
(E)-3-hydroxyhept-1-enylphosphonate (14), respectively
(Scheme 3).
Scheme 2 Reagents and conditions: (a) NMO (1.1 equiv), OsO4
(cat.), t-BuOH–acetone (4:1), 25 °C, 3 days; (b) (EtO)2P(O)CH2-
CO2Et (9, 1 equiv), NaH (1 equiv), THF, 20 h, 25 °C.
We anticipated that asymmetric Sharpless dihydroxyla-
tion of the enol mesylates would allow enantioselective
synthesis of a-hydroxy aldehydes with predicable abso-
lute configuration. Thus, the reactions of enol mesylate 6a
with AD-mix-a and AD-mix-b in the presence of addi-
tional K2OsO4·H2O in t-BuOH–H2O solvent system (1:1)
were carried out for 72 hours at room temperature and
provided (S)-8a and (R)-8a a-hydroxyhexanals, respec-
tively. The crude aldehydes were subjected to HWE olefi-
nation with the previously used activated methyl-
phosphonates to give the corresponding g-hydroxy-a,b-
unsaturated octenoates (S)-10a, (R)-10a, octenenitriles
(S)-13, (R)-13, and heptenylphosphonates (S)-14, (R)-14
(Scheme 4).
Subsequent mesylation of both hydroxyl groups in 3 af-
forded syn-1,2-dimesyloxyphosphonates 4.17 Routine
deesterification of phosphonates 4 by sequential treatment
with bromotrimethylsilane and ethanol gave the syn-1,2-
dimesyloxyphosphonic acids 5.18 Finally, treatment of the
crude acids 5 with aqueous saturated sodium hydrogen
carbonate resulted in the Conant–Swan fragmentation19 to
afford (E)-alk-1-enyl mesylates 6, which were purified by
column chromatography.
Our attempts to use the enol mesylates 6 as substrates for
the preparation of g-hydroxy-a,b-unsaturated esters 10
met with full success (Scheme 2). Dihydroxylation of the
enol mesylates 6 by the standard procedure with a catalyt-
ic amount of OsO4 in the presence of NMO was complet-
ed within 3 days at 25 °C.
The enantiomeric purities of the products 10a, 13, and 14
were established unambiguously by chiral GC analysis
1
and compared with those obtained by H NMR experi-
ments using Eu(hfc)3 as the chiral shift reagent (Table 1).
A slight divergence of the found ee values is in line with
the accuracy of the latter measurements. Enantiomeric pu-
rities of g-hydroxyphosphonates (S)-14 and (R)-14 could
not be determined by GC using available chiral columns.
In all cases, the obtained dihydroxyalkyl mesylates 7
spontaneously eliminated methanesulfonic acid frag-
ments to produce a-hydroxy aldehydes 8. Subsequent
HWE olefination of the crude aldehydes 8 with sodium
triethylphosphonoacetate, generated from the phospho-
nate 9 and NaH, resulted in a rapid and effective conver-
sion into the corresponding g-hydroxy-a,b-unsaturated
esters 10 with complete E-stereoselectivity. Similarly, the
HWE reaction of a-hydroxyhexanal 8a with activated
methylphosphonates, such as diethyl cyanomethylphos-
phonate (11) and tetraethyl methylenediphosphonate (12)
provided (E)-4-hydroxyoct-2-enenitrile (13) and diethyl
As illustrated in Table 1, the target products were pre-
pared with high enentioselectivities. It is reasonable to as-
sume that asymmetric dihydroxylation afforded (R)- and
(S)-a-hydroxyhexanals (R)- and (S)-8a with at least the
same level of enantiomeric excess. Notably, asymmetric
dihydroxylations using AD-mix-a led to the a-hydroxy-
hexanal (S)-8a with somewhat lower enantiomeric excess.
Synthesis 2008, No. 20, 3299–3306 © Thieme Stuttgart · New York

PAPER
Synthesis of g-Hydroxy-a,b-unsaturated Compounds
3301
Diethyl 1,2-Dihydroxyalkylphosphonate 3a–e; General Proce-
dure
Table 1 g-Hydroxy-a,b-unsaturated Compounds Prepared
Entry
1
Product
eea
eeb
78
To a solution of phosphonate 2 (0.03 mol) in acetone (10 mL) and
t-BuOH (40 mL) was added NMO (4.5 g, 0.033 mol) and OsO4
(0.25 mg, 0.1 mmol). The resulting mixture was stirred at 25 °C for
3 d. The mixture was then quenched with aq Na2S2O3 (15 mL) and
extracted with CHCl3 (3 × 50 mL). The combined organic layers
were dried (MgSO4), filtered, and concentrated under reduced pres-
sure. The crude product was purified by column chromatography
(CHCl3–acetone, 4:1) affording pure 3.
OH
(S)-10a
(R)-10a
82
Bu
COOEt
COOEt
CN
OH
2
3
4
5
6
91
82
91
–
89
78
88
76
86
Bu
OH
(S)-13
(R)-13
(S)-14
(R)-14
Diethyl 1,2-Dihydroxyhexylphosphonate (3a)
Yield: 85%, yellow oil; Rf = 0.20.
IR (film): 3360, 1216, 1048 cm–1.
Bu
OH
Bu
CN
1H NMR (CDCl3): d = 0.91 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2), 1.35
3
3
OH
(t, JH,H = 7.0 Hz, 3 H, CH3CH2O, 1.36 (t, JH,H = 7.2 Hz, 3 H,
CH3CH2O, 1.54–1.80 (m, 6 H, 3 × CH2), 3.40 (br s, 1 H, OH), 3.71
(br s, 1 H, OH), 3.76–3.79 (m, 1 H, PCHCH), 3.96–4.07 (m, 1 H,
Bu
P(O)(OEt)2
PCH), 4.19 (dq, JP,H = 3JH,H = 7.0 Hz, 2 H, CH3CH2O), 4.15 (dq,
3
OH
–
3JP,H = 3JH,H = 7.2 Hz, 2 H, CH3CH2O).
Bu
P(O)(OEt)2
3
13C NMR (CDCl3): d = 13.81 (s, CH3CH2), 16.23 (d, JP,C = 5.60
a Enantiomeric excess was determined by GC.
Hz, CH3CH2O), 22.40 (s, CH2), 27.70 (s, CH2), 32.62 (d,
3JP,C = 10.5 Hz, CH2), 62.52 (d, 2JP,C = 7.3 Hz, CH3CH2), 62.92 (d,
2JP,C = 7.0 Hz, CH3CH2O), 70.34 (d, 2JP,C = 2.1 Hz, PCHCH), 70.63
(d, 1JP,C = 159.4 Hz, PCH).
b Enantiomeric excess was determined by 1H NMR spectroscopy.
The absolute configurations of the nitriles (S)-(+)-13 and
(R)-(–)-13 obtained were established by comparison of 31P NMR (CDCl3): d = 24.41.
their sign of optical rotation with the literature data.4d
Anal. Calcd for C10H23O5P: C, 47.24; H, 9.12. Found: C, 47.05; H,
Therefore, dihydroxylation of the mesylate 6a with AD-
mix-a leads to the (S)-a-hydroxyhexanal, while that with
AD-mix-b gives the R-enantiomer. As a consequence, the
absolute configuration of the g-hydroxy-a,b-unsaturated
HWE reaction products 10a, 13, and 14 could be assigned
as S and R, respectively. This result is in agreement with
the Sharpless model for asymmetric dihydroxylation.20
According to this model AD-mix-a should favor the for-
mation of (S)-a-hydroxy aldehydes from the correspond-
ing (E)-alk-1-enyl mesylates.
9.18.
Diethyl 1,2-Dihydroxyheptylphosphonate (3b)16
Yield: 83%; yellow oil; Rf = 0.12.
1H NMR (CDCl3): d = 0.95 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2), 1.35
3
3
(t, JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.37 (t, JH,H = 7.0 Hz, 3 H,
CH3CH2O), 1.54–1.80 (m, 8 H, 4 × CH2), 3.73 (br s, 1 H, OH), 3.96
(br s, 1 H, OH), 4.00–4.11 (m, 1 H, PCHCH), 4.14–4.29 (m, 5 H,
2 × CH3CH2O, PCH).
31P NMR (CDCl3): d = 24.24.
Diethyl 1,2-Dihydroxy-3-methylbutylphosphonate (3c)16
Yield: 92%; colorless crystals; mp 82–84 °C.
In summary, the ready access to methanesulfonates of E-
aldehyde enols coupled with their easy conversion to a-
hydroxy aldehydes is described as a profitable method for
the preparation of g-hydroxy-a,b-unsaturated com- (d, JH,H = 6.5 Hz, 3 H, CH3CH), 1.35 (t, JH,H = 7.0 Hz, 3 H,
pounds. In addition, asymmetric Sharpless dihydroxyla-
tion of the enol mesylates provided a-hydroxy aldehydes
with high enantiomeric excess, which opens a new gener-
al route to the highly enantioselective synthesis of g-hy-
droxy alkanoates and related compounds.
1H NMR (CDCl3): d = 0.93 (d, 3JH,H = 6.5 Hz, 3 H, CH3CH), 1.04
3
3
CH3CH2O), 1.36 (t, 3JH,H = 7.2 Hz, 3 H, CH3CH2O), 1.89–2.01 [m,
3
2
1 H, (CH3)3CH], 3.50 (ddd, JH,H = 8.0 Hz, JP,H = 6.0 Hz,
3JH,H = 3.5 Hz, 1 H, PCH), 3.72 (br s, 1 H, OH), 4.00–4.10 (m, 2 H,
PCHCH, OH), 4.15 (dq, JP,H = 3JH,H = 7.0 Hz, 2 H, CH3CH2O),
3
4.19 (dq, 3JP,H = 3JH,H = 7.2 Hz, 2 H, CH3CH2O).
31P NMR (CDCl3): d = 25.24.
Diethyl 2-Cyclohexyl-1,2-dihydroxyethylphosphonate (3d)
Yield: 70%; colorless oil; Rf = 0.19.
NMR spectra were recorded on a Bruker DPX 250 instrument at
250.13 MHz for 1H, and 62.9 MHz for 13C, and 101.3 MHz for 31
P
NMR using tetramethylsilane as internal and 85% H3PO4 as exter-
nal standard, respectively. The multiplicities of carbons were deter-
mined by DEPT experiments. IR spectra were measured on Specord
M80 (Zeiss) instrument. The ee values were determined by GC
analysis on Hewlett-Packard 5900 II instrument equipped with g-
Dex-225 column by comparison with the racemates. Elemental
analyses were performed on PerkinElmer PE 2400 analyzer. Melt-
ing points were determined in open capillaries and were uncorrect-
ed. Diethyl alk-1-enylphosphonates 2 were prepared according to
the literature procedure.16
IR (film): 3352, 1228, 1044 cm–1.
1H NMR (CDCl3): d = 1.00–1.15 (m, 4 H, 2 × CH2), 1.34 (t,
3JH,H = 7.2 Hz, 3 H, CH3CH2O), 1.35 (t, JH,H = 7.2 Hz, 3 H,
3
CH3CH2O), 1.60–1.94 [m, 7 H, 3 × CH2, CH(CH2)5], 3.25 (ddd,
3JH,H = 7.5 Hz, 3JH,H = 6.25 Hz, 3JP,H = 6.0 Hz, 1 H, PCHCH), 3.64
(br s, 1 H, OH), 3.92–4.04 (m, 2 H, PCH, OH), 4.18 (dq,
3JP,H = 3JH,H = 7.2 Hz, 2 H, CH3CH2O), 4.20 (dq, 3JP,H = 3JH,H = 7.2
Hz, 2 H, CH3CH2O).
13C NMR (CDCl3): d = 16.24 (d, 3JP,C = 5.6 Hz, CH3CH2O), 16.27
3
(d, JP,C = 5.5 Hz, CH3CH2OP), 25.60 (s, CH2), 26.11 [d,
3JP,C = 15.5 Hz, CH(CH2)5], 30.0 (s, 2 × CH2), 31.14 (s, 2 × CH2),
2
2
62.46 (d, JP,C = 6.5 Hz, CH3CH2O), 62.49 (d, JP,C = 7.1 Hz,
Synthesis 2008, No. 20, 3299–3306 © Thieme Stuttgart · New York

3302
H. Krawczyk et al.
PAPER
CH3CH2O), 70.42 (d, 1JP,C = 160.2 Hz, PCH), 75.14 (d, 2JP,C = 10.2
Hz, PCHCH).
31P NMR (CDCl3): d = 23.14.
13C NMR (CDCl3): d = 12.92 (s, CH3), 15.38 (d, 3JP,C = 5.6 Hz, 2 ×
CH3CH2O), 20.87 (s, CH2), 22.00 (s, CH2), 25.91 (s, CH2), 31.11 (d,
3JP,C = 3.5 Hz, CH2), 38.75 (s, CH3S), 39.21 (s, CH3S), 63.03 (d,
1
2JP,C = 6.5 Hz, 2 × CH3CH2O), 74.19 (d, JP,C = 167.5 Hz, PCH),
78.12 (d, 2JP,C = 7.2 Hz, PCHCH).
31P NMR (CDCl3): d = 14.86.
Anal. Calcd for C12H25O5P: C, 51.42; H, 8.99. Found: C, 51.31; H,
9.05.
Diethyl 1,2-Dihydroxy-4-phenylbutylphosphonate (3e)
Yield: 82%; light yellow oil.
Anal. Calcd for C13H29O9PS2: C, 36.78; H, 6.89. Found: C, 36.89;
H, 6.84.
IR (film): 3352, 1264, 1024 cm–1.
Diethyl 1,2-Di(methylsulfonyloxy)-3-methylbutylphosphonate
(4c)
Yield: 78%; light yellow crystals; Rf = 0.41; mp 112–114 °C.
IR (film): 1216, 1016 cm–1.
1H NMR (CDCl3): d = 1.30 (t, 3JH,H = 7.0 Hz, 6 H, 2 × CH3CH2O),
1.74 (br s, 1 H, OH), 1.84–2.09 (m, 2 H, CH2), 2.63–2.78 (m, 2 H,
PhCH2), 3.46 (br s, 1 H, OH), 3.72–3.79 (m, 1 H, PCHCH), 3.92–
4.06 (m, 1 H, PCH), 4.14 (dq, JP,H = 3JH,H = 7.0 Hz, 2 H,
3
CH3CH2O), 4.22 (dq, 3JP,H = 3JH,H = 7.0 Hz, 2 H, CH3CH2O), 7.15–
1H NMR (CDCl3): d = 1.03 (d, 3JH,H = 6.7 Hz, 3 H, CH3CH), 1.14
7.31 (m, 5 H, CHAr).
(d, 3JH,H = 6.7 Hz, 3 H, CH3CH), 1.39 (td, 3JH,H = 7.0 Hz, 4JP,H = 0.5
3
4
Hz, 3 H, CH3CH2O), 1.40 (td, JH,H = 7.0 Hz, JP,H = 0.5 Hz, 3 H,
13C NMR (CDCl3): d = 16.28 (d, 3JP,C = 5.5 Hz, CH3CH2O), 16.32
3
3
CH3CH2O), 2.29 [sept d, JH,H = 6.7 Hz, JH,H = 3.0 Hz, 1 H,
(CH3)2CH], 3.20 (s, 3 H, CH3S), 3.27 (s, 3 H, CH3S), 4.25 (dq,
3JP,H = 8.2 Hz, 3JH,H = 7.0 Hz, 2 H, CH3CH2O), 4.27 (dq, 3JP,H = 8.2
3
(d, JP,C = 5.8 Hz, CH3CH2O), 30.11 (s, PhCH2), 36.11 (d,
3JP,C = 10.5 Hz, CH2), 62.24 (d, 2JP,C = 6.5 Hz, CH3CH2O), 62.27 (d,
2JP,C = 7.0 Hz, CH3CH2O), 70.23 (d, 1JP,C = 160.0 Hz, PCH), 75.78
3
3
Hz, JH,H = 7.0 Hz, 2 H, CH3CH2O), 4.86 (ddd, JH,H = 8.2 Hz,
2
(d, JP,C = 10.1 Hz, PCHCH), 126.11 (s, 2 × CHAr), 128.27 (s,
3JP,H = 5.0 Hz, JH,H = 3.0 Hz, 1 H, PCHCH), 5.00 (dd, JP,H = 9.5
3
2
CHAr), 128.40 (s, 2 × CHAr), 139.86 (s, CAr).
31P NMR (CDCl3): d = 19.84.
Hz, 3JH,H = 8.2 Hz, 1 H, PCH).
13C NMR (CDCl3): d = 15.84 (s, CH3CH), 16.31 (d, 3JP,C = 5.6 Hz,
CH3CH2O), 20.18 (s, CH3CH), 29.07 [s, (CH3)2CH], 39.24 (s,
Anal. Calcd for C14H23O5P: C, 55.64; H, 7.67. Found: C, 55.75; H,
7.71.
2
CH3S), 39.63 (s, CH3S), 63.89 (d, JP,C = 7.2 Hz, CH3CH2OP),
2
1
64.00 (d, JP,C = 7.0 Hz, CH3CH2O), 74.78 (d, JP,C = 164.0 Hz,
PCH), 82.82 (d, 2JP,C = 10.7 Hz, PCHCH).
Diethyl 1,2-Di(methylsulfonyloxy)alkylphosphonates 4a–e;
General Procedure
31P NMR (CDCl3): d = 15.40.
To a solution of phosphonate 3 in CH2Cl2 (30 mL) were added Et3N
(3.45 mL, 0.025 mol) and MeSO2Cl (1.55 mL, 0.02 mol) at 0 °C and
the resulting mixture was stirred for 20 h at 25 °C. The mixture was
washed with aq NH4Cl (20 mL) and dried. Evaporation of the sol-
vent under reduced pressure afforded the crude product, which was
purified by column chromatography (CHCl3–acetone, 9:1) to give
pure 4.
Anal. Calcd for C11H25O9PS2: C, 33.33; H, 6.36. Found: C, 33.21;
H, 6.34.
Diethyl 2-Cyclohexyl-1,2-di(methylsulfonyloxy)ethylphospho-
nate (4d)
Yield: 75%; light yellow oil; Rf = 0.49.
IR (film): 1224, 1020 cm–1.
Diethyl 1,2-Di(methylsulfonyloxy)hexylphosphonate (4a)
Yield: 94%; yellow oil; Rf = 0.50.
IR (film): 1216, 1024 cm–1.
1H NMR (CDCl3): d = 1.22–1.31 (m, 4 H, 2 × CH2), 1.39 (t,
3JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.40 (t, JH,H = 7.0 Hz, 3 H,
3
CH3CH2O), 1.65–1.92 [m, 7 H, 3 × CH2, CH(CH2)5], 3.19 (s, 3 H,
1H NMR (CDCl3): d = 0.93 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2), 1.39
CH3S), 3.27 (s, 3 H, CH3S), 4.25 (dq, 3JP,H = 8.0 Hz, 3JH,H = 7.0 Hz,
3
3
3
3
(t, JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.40 (t, JH,H = 7.0 Hz, 3 H,
CH3CH2O), 1.41–1.48 (m, 4 H, 2 × CH2), 1.86–2.00 (m, 2 H, CH2),
3.14 (s, 3 H, CH3S), 3.25 (s, 3 H, CH3S), 4.26 (dq, 3JP,H = 3JH,H = 7.0
2 H, CH3CH2O), 4.26 (dq, JP,H = 8.2 Hz, JH,H = 7.0 Hz, 2 H,
CH3CH2O), 4.82 (ddd, 3JH,H = 8.0 Hz, 3JP,H = 5.5 Hz, 3JH,H = 3.2 Hz,
1 H, PCHCH), 5.06 (dd, 2JP,H = 9.7 Hz, 3JH,H = 8.0 Hz, 1 H, PCH).
Hz, 2 H, CH3CH2O), 4.27 (dq, JP,H = 3JH,H = 7.0 Hz, 2 H,
3
13C NMR (CDCl3): d = 16.30 (d, 3JP,C = 5.1 Hz, CH3CH2O), 16.34
(d, 3JP,C = 5.0 Hz, CH3CH2O), 25.75 (s, CH2), 26.28 [d, 3JP,C = 18.6
Hz, CH(CH2)5], 30.36 (s, 2 × CH2), 31.49 (s, 2 × CH2), 39.26 (s,
CH3S), 39.60 (s, CH3S), 63.89 (d, 2JP,C = 6.9 Hz, CH3CH2O), 63.99
CH3CH2O), 4.92–5.00 (m, 2 H,, PCH, PCHCH).
13C NMR (CDCl3): d = 13.51 (s, CH3 at C-6), 16.14 (d, 3JP,C = 5.6
Hz, CH3CH2OP), 22.04 (s, CH2), 25.98 (s, CH2), 31.01 (d,
3JP,C = 3.4 Hz, CH2), 38.78 (s, CH3S), 39.25 (s, CH3S), 63.76 (d,
2
1
(d, JP,C = 6.4 Hz, CH3CH2O), 74.33 (d, JP,C = 164.5 Hz, PCH),
2JP,C = 6.8 Hz, 2 × CH3CH2O), 74.92 (d, JP,C = 165.9 Hz, PCH),
82.52 (d, 2JP,C = 10.1 Hz, PCHCH).
1
78.90 (d, 2JP,C = 7.1 Hz, PCHCH).
31P NMR (CDCl3): d = 14.87.
31P NMR (CDCl3): d = 15.55.
Anal. Calcd for C14H29O9PS2: C 38.53, H 6.70. Found: C 38.68, H
6.67.
Anal. Calcd for C12H27O9PS2: C, 35.12; H, 6.63. Found: C, 35.38;
H, 6.61.
Diethyl 1,2-Di(methylsulfonyloxy)-4-phenylbutylphosphonate
(4e)
Diethyl 1,2-Di(methylsulfonyloxy)heptylphosphonate (4b)
Yield: 84%; yellow oil; Rf = 0.50.
Yield: 79%; yellow oil; Rf = 0.30.
IR (film): 1226, 1044 cm–1.
IR (film): 1264, 1024 cm–1.
1H NMR (CDCl3): d = 0.90 (t, 3JH,H = 6.7 Hz, 3 H, CH3CH2), 1.24–
1.35 (m, 2 H, CH2),1.39 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.40 (t,
3JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.40–1.49 (m, 4 H, 2 × CH2), 1.90–
2.00 (m, 2 H, CH2), 3.14 (s, 3 H, CH3S), 3.24 (s, 3 H, CH3S), 4.15–
4.28 (m, 4 H, 2 × CH3CH2O), 4.92–5.00 (m, 2 H, PCH, PCHCH).
1H NMR (CDCl3): d = 1.34 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.35
(t, 3JH,H = 7.0 Hz, 3 H, CH3CH2O), 2.24–2.32 (m, 2 H, CH2), 2.79–
2.85 (m, 2 H, PhCH2), 3.14 (s, 3 H, CH3S), 3.23 (s, 3 H, CH3S),
3.99–4.05 (m, 1 H, PCHCH), 4.21 (dq, 3JP,H = 3JH,H = 7.0 Hz, 2 H,
CH3CH2O), 4.22 (dq, 3JP,H = 3JH,H = 7.0 Hz, 2 H, CH3CH2O), 4.96–
5.06 (m, 1 H, PCH), 7.18–7.30 (m, 5 H, CHAr).
Synthesis 2008, No. 20, 3299–3306 © Thieme Stuttgart · New York

PAPER
Synthesis of g-Hydroxy-a,b-unsaturated Compounds
3303
13C NMR (CDCl3): d = 16.20 (s, CH3CH2O), 16.27 (s, CH3CH2O),
1H NMR (acetone-d6): d = 1.18–1.32 (m, 6 H, 3 × CH2), 1.43–1.84
[m, 5 H, CH(CH2)5, 2 × CH2], 3.18 (s, 3 H, CH3S), 3.22 (s, 3 H,
3
30.24 (s, CH2), 33.14 (d, JC,P = 3.5 Hz, CH2), 38.91 (s, CH3S),
2
2
39.36 (s, CH3S), 63.93 (d, JC,P = 6.2 Hz, CH3CH2O), 64.02 (d,
CH3S), 4.84–4.88 (m, 1 H, PCHCH), 5.05 (dd, JP,H = 12.5 Hz,
2JC,P = 5.0 Hz, CH3CH2O), 74.84 (d, 1JC,P = 166.3 Hz, PCH), 78.08
(d, 2JC,P = 7.1 Hz, PCHCH), 126.17 (s, 2 × CHAr), 128.35 (s, CHAr),
128.42 (s, 2 × CHAr), 139.98 (s, CAr).
3JH,H = 7.5 Hz, 1 H, PCH).
13C NMR (acetone-d6): d = 25.01 (s, CH2), 26.02 [s, CH(CH2)5],
30.36 (s, 2 × CH2), 31.49 (s, 2 × CH2), 39.11 (s, CH3S), 39.49 (s,
31P NMR (CDCl3): d = 14.69.
CH3S), 74.47 (d, JP,C = 164.9 Hz, PCH), 82.32 (d, JP,C = 5.1 Hz,
PCHCH).
1
2
Anal. Calcd for C16H27O9PS2: C, 41.91; H, 5.94. Found: C, 41.79;
H, 5.97.
31P NMR (acetone-d6): d = 14.22.
1,2-Di(methylsulfonyloxy)alkylphosphonicAcids 5a–e; General
Procedure
1,2-Di(methylsulfonyloxy)-4-phenylbutylphosphonic Acid (5e)
Yield; 92%; light yellow oil.
A mixture of phosphonate 4 (0.01 mol) and bromotrimethylsilane
(4.30 mL, 0.04 mol) in CH2Cl2 (50 mL) was left for 5 d at 25 °C.
The solvent was evaporated under reduced pressure and the residue
was dissolved in EtOH (10 mL) and stirred for 15 min. Evaporation
of the solvent afforded crude 6, which was used in the next step.
IR (film): 1244, 1048 cm–1.
1H NMR (acetone-d6): d = 2.21–2.35 (m, 2 H, CH2), 2.76–2.91 (m,
2 H, PhCH2), 3.22 (s, 3 H, CH3S), 3.31 (s, 3 H, CH3S), 5.11–5.14
(m, 1 H, PCHCH), 5.15 (dd, JP,H = 12.5 Hz, JH,H = 5.7 Hz, 1 H,
PCH), 7.20–7.35 (m, 5H, CHAr).
2
3
13C NMR (acetone-d6): d = 30.04 (s, CH2), 32.97 (s, CH2), 38.90 (s,
CH3S), 39.34 (s, CH3S), 74.25 (d, 1JC,P = 164.8 Hz, PCH), 78.18 (d,
2JC,P = 7.1 Hz, PCHCH), 126.19 (s, 2 × CHAr), 128.15 (s, CHAr),
128.33 (s, 2 × CHAr), 139.74 (s, CAr).
1,2-Di(methylsulfonyloxy)hexylphosphonic Acid (5a)
Yield: 95%; light yellow oil.
IR (film): 1216, 1024 cm–1.
3
1H NMR (acetone-d6): d = 0.92 (t, JH,H = 7.0 Hz, 3 H, CH3CH2),
31P NMR (acetone-d6): d = 13.02.
1.29–1.41 (m, 2 H, CH2), 1.44–1.55 (m, 2 H, CH2), 1.92–2.04 (m, 2
H, CH2), 3.19 (s, 3 H, CH3S), 3.29 (s, 3 H, CH3S), 4.94–5.08 (m, 2
H,, PCH, PCHCH).
(E)-Alk-1-enylmethanesulfonates 6a–e; General Procedure
To a solution of a corresponding phosphonic acid 5 (0.01 mol) in
Et2O (10 mL) was added aq sat. NaHCO3 (5 mL). The mixture was
stirred for 2 h at 25 °C. The organic layer was separated and the
aqueous layer was extracted with Et2O (3 × 10 mL). The combined
organic layers were dried (MgSO4), filtered, and concentrated under
reduced pressure. The crude product was purified by column chro-
matography (CHCl3–acetone, 7:3) affording pure 6.
13C NMR (acetone-d6): d = 13.15 (s, CH3), 17.26 (s, CH2), 21.95 (s,
CH2), 25.94 (s, CH2), 38.18 (s, CH3S), 38.78 (s, CH3S), 75.94 (d,
1JP,C = 164.7 Hz, PCH), 79.38 (d, 2JP,C = 5.5 Hz, PCHCH).
31P NMR (acetone-d6): d = 13.65.
1,2-Di(methylsulfonyloxy)heptylphosphonic Acid (5b)
Yield: 95%; yellow oil.
(E)-Hex-1-enyl Methanesulfonate (6a)
Yield: 80%; light yellow oil; Rf = 0.44.
IR (film): 1648 cm–1.
IR (film): 1232, 1024 cm–1.
1H NMR (acetone-d6): d = 0.90 (t, 3JH,H = 7.0 Hz, 3 H, CH3), 1.16–
1.36 (m, 4 H, 2 × CH2), 1.43–1.54 (m, 2 H, CH2), 1.92–2.05 (m, 2
H, CH2), 3.19 (s, 3 H, CH3S), 3.29 (s, 3 H, CH3S), 4.96–5.10 (m, 2
H, PCH, PCHCH).
1H NMR (CDCl3): d = 0.91 (t, 3JH,H = 6.7 Hz, 3 H, CH3), 1.25–1.42
3
3
(m, 4 H, 2 × CH2), 2.03 (tdd, JH,H = 7.5 Hz, JH,H = 7.2 Hz,
4JH,H = 1.2 Hz, 2 H, CH2CH=), 3.04 (s, 3 H, CH3S), 5.63 (dt,
13C NMR (acetone-d6): d = 13.21 (s, CH3), 18.77 (s, CH2), 21.11 (s,
3
3JH,H = 12.0 Hz, JH,H = 7.5 Hz, 1 H, CH=CHO), 6.47 (dt,
CH2), 25.46 (s, CH2), 30.94 (s, CH2), 38.76 (s, CH3S), 39.32 (s,
3JH,H = 12.0 Hz, 4JH,H = 1.2 Hz, 1 H, OCH=CH).
1
2
CH3S), 74.79 (d, JP,C = 164.5 Hz, PCH), 78.86 (d, JP,C = 5.8 Hz,
PCHCH).
13C NMR (CDCl3): d = 13.51 (s, CH3), 21.79 (s, CH2), 26.37 (s,
CH2), 30.91 (s, CH2CH=CH), 36.60 (s, CH3S), 121.13 (s,
CH=CHO), 135.01 (s, OCH=CH).
31P NMR (acetone-d6): d = 13.51.
1,2-Di(methylsulfonyloxy)-3-methylbutylphosphonic Acid (5c)
Yield: 94%; light yellow oil.
Anal. Calcd for C7H14O3S: C, 47.17; H, 7.92. Found: C, 47.26; H,
7.89.
IR (film): 1216, 1016 cm–1.
(E)-Hept-1-enyl Methanesulfonate (6b)
Yield: 75%; light yellow oil; Rf = 0.44.
IR (film): 1648 cm–1.
1H NMR (acetone-d6): d = 1.03 (d, 3JH,H = 6.2 Hz, 3 H, CH3), 1.09
(d, 3JH,H = 6.2 Hz, 3 H, CH3), 2.30–2.42 (m, 1 H, CH), 3.21 (s, 3 H,
3
3
CH3S), 3.26 (s, 3 H, CH3S), 4.85 (ddd, JP,H = 9.7 Hz, JH,H = 7.7
3
2
Hz, JH,H = 3.0 Hz, 1 H, PCHCH), 5.00 (dd, JP,H = 10.7 Hz,
1H NMR (CDCl3): d = 0.92 (t, 3JH,H = 6.7 Hz, 3 H, CH3CH2), 1.20–
1.43 (m, 4 H, 2 × CH2), 1.78–1.85 (m, 2 H, CH2), 2.00 (tdd,
3JH,H = 7.7 Hz, 1 H, PCH).
3
4
3JH,H = 7.5 Hz, JH,H = 7.2 Hz, JH,H = 1.2 Hz, 2 H, CH2CH=CH),
13C NMR (acetone-d6): d = 15.89 (s, CH3), 20.06 (s, CH3), 28.79 [s,
(CH3)2CH], 39.25 (s, CH3S), 39.62 (s, CH3S), 74.23 (d,
1JP,C = 164.8 Hz, PCH), 82.13 (d, 2JP,C = 5.7 Hz, PCHCH).
31P NMR (acetone-d6): d = 13.93.
3.06 (s, 3 H, CH3S), 5.75 (dt, JH,H = 12.0 Hz, 3JH,H = 7.2 Hz, 1 H,
CH=CHO), 6.42 (dt, JH,H = 12.0 Hz, JH,H = 1.2 Hz, 1 H,
OCH=CH).
3
3
4
13C NMR (CDCl3): d = 13.50 (s, CH3CH2), 21.74 (s, CH2), 22.81 (s,
CH2), 26.33 (s, CH2), 30.65 (s, CH2CH=CH), 36.54 (s, CH3S),
121.14 (s, CH=CHO), 135.11 (s, CH=CHO).
2-Cyclohexyl-1,2-di(methylsulfonyloxy)ethylphosphonic Acid
(5d)
Yield: 96%; light yellow oil.
IR (film): 1264, 1024 cm–1.
Anal. Calcd for C8H16O3S: C, 49.97; H, 8.39. Found: C, 49.81; H,
8.43.
Synthesis 2008, No. 20, 3299–3306 © Thieme Stuttgart · New York

3304
H. Krawczyk et al.
PAPER
(E)-3-Methylbut-1-enyl Methanesulfonate (6c)
Yield: 70%; light yellow oil; Rf = 0.46.
IR (film): 1668 cm–1.
Ethyl (E)-4-Hydroxyalk-2-enoates 10a–e; (E)-4-Hydroxyoct-2-
enenitrile (13); Diethyl (E)-3-Hydroxyhept-1-enylphosphonate
(14); General Procedure
To a solution of NaH (0.12 g, 0.5 mmol) in THF (10 mL) were add-
ed 9, 11, or 12 (0.5 mmol) and the a-hydroxy aldehyde 8 and the re-
sulting mixture was stirred at 25 °C for 20 h. H2O (20 mL) was
added and the solvent was evaporated under reduced pressure. The
residue was extracted with Et2O (3 × 10 mL). The combined organ-
ic layers were dried (MgSO4), filtered, and evaporated under
reduced pressure. The crude product was purified by column chro-
matography to give pure 10a–e, 13, and 14, respectively.
1H NMR (CDCl3): d = 1.05 [d, 3JH,H = 6.7 Hz, 6 H, (CH3)2CH], 2.37
3
3
4
[dseptd, JH,H = 7.7 Hz, JH,H = 6.7 Hz, JH,H = 1.3 Hz, 1 H,
3
(CH3)2CH], 3.04 (s, 3 H, CH3S), 5.61 (dd, JH,H = 12.0 Hz,
3
3JH,H = 7.6 Hz, 1 H, CH=CHO), 6.47 (dd, JH,H = 12.0 Hz,
4JH,H = 1.3 Hz, 1 H, OCH=CH).
13C NMR (CDCl3): d = 21.87 (s, CH3CH), 22.11 (s, CH3CH), 26.66
[s, (CH3)2CH], 36.35 (s, CH3S), 127.58 (s, CH=CHO), 133.88 (s,
OCH=CH).
Ethyl (E)-4-Hydroxyoct-2-enoate (10a)11
Yield: 66%; light yellow oil; Rf = 0.29 (hexane–EtOAc, 4:1).
IR (film): 1648 cm–1.
Anal. Calcd for C6H12O3S: C, 43.88; H, 7.37. Found: C, 43.59; H,
7.33.
1H NMR (CDCl3): d = 0.91 (t, 3JH,H = 6.7 Hz, 3 H, CH3CH2), 1.30
(E)-2-Cyclohexylvinyl Methanesulfonate (6d)
Yield: 63%; light yellow oil; Rf = 0.54.
IR (film): 1664 cm–1.
1H NMR (CDCl3): d = 1.04–1.26 (m, 6 H, 3 × CH2), 1.65–1.76 (m,
4 H, 2 × CH2), 1.97–2.09 [m, 1 H, CH(CH2)5], 3.03 (s, 3 H, CH3S),
5.58 (dd, 3JH,H = 12.0 Hz, 3JH,H = 7.5 Hz, 1 H, CH=CHO), 6.46 (dd,
3JH,H = 12.0 Hz, 4JH,H = 1.2 Hz, 1 H, OCH=CH).
3
(t, JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.26–1.39 (m, 4 H, 2 × CH2),
1.52–1.61 (m, 2 H, CH2), 4.21 (q, 3JH,H = 7.0 Hz, 2 H, CH3CH2O),
3
3
4
4.31 (tdd, JH,H = 6.7 Hz, JH,H = 5.0 Hz, JH,H = 1.5 Hz, 1 H,
3
4
CHOH), 6.03 (dd, JH,H = 15.7 Hz, JH,H = 1.5 Hz,
O=CCH=CH), 6.95 (dd, JH,H = 15.7 Hz, JH,H = 5.0 Hz, 1 H,
CH=CHC=O).
1 H,
3
3
13C NMR (CDCl3): d = 25.47 (s, CH2), 25.56 (s, 2 × CH2), 32.50 (s,
2 × CH2), 36.10 [s, CH(CH2)5], 36.50 (s, CH3S), 126.55 (s,
CH=CHO), 134.21 (s, OCH=CH).
(R)-10a
[a]D20 –21.59 (c = 1.00, CHCl3).
(S)-10a
Anal. Calcd for C6H12O3S: C, 52.92; H, 7.89. Found: C, 53.00; H,
7.93.
[a]D20 +18.19 (c = 1.00, CHCl3).
Ethyl (E)-4-Hydroxynon-2-enoate (10b)
Yield: 64%: light yellow oil; Rf = 0.29 (hexane–EtOAc, 4:1).
IR (film): 1660 cm–1.
(E)-4-Phenylbut-1-enyl Methanesulfonate (6e)
Yield: 74%; light yellow oil; Rf = 0.40.
IR (film): 1640 cm–1.
1H NMR (CDCl3): d = 0.91 (t, 3JH,H = 6.7 Hz, 3 H, CH3CH2), 1.28
1H NMR (CDCl3): d = 2.31–2.40 (m, 2 H, CH2CH=), 2.73 (t,
3
(t, JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.26–1.39 (m, 4 H, 2 × CH2),
3JH,H = 7.2 Hz, 2 H, PhCH2), 2.92 (s, 3 H, CH3S), 5.62 (dt,
3
1.52–1.61 (m, 5 H, 2 × CH2, OH), 4.20 (q, JH,H = 7.0 Hz, 2 H,
3
3JH,H = 12.0 Hz, JH,H = 7.5 Hz, 1 H, CH=CHO), 6.43 (dt,
CH3CH2O), 4.30 (tdd, 3JH,H = 6.7 Hz, 3JH,H = 5.0 Hz, 4JH,H = 1.5 Hz,
3JH,H = 12.0 Hz, 4JH,H = 1.5 Hz, 1 H, OCH=CH), 7.14–7.29 (m, 5 H,
3
4
1 H, CHOH), 6.05 (dd, JH,H = 15.7 Hz, JH,H = 1.5 Hz, 1 H,
CHAr).
3
3
O=CCH=CH), 6.94 (dd, JH,H = 15.7 Hz, JH,H = 5.0 Hz, 1 H,
CH=CHC=O).
13C NMR (CDCl3): d = 28.57 (s, CH2), 35.24 (s, CH2CH=), 36.65
(s, CH3S), 119.97 (s, CH=CHO), 126.09 (s, 2 × CHAr), 128.37 (s,
3 × CHAr), 135.71 (s, CH=CHO), 140.51 (s, CAr).
13C NMR (CDCl3): d = 13.71 (CH3CH2), 13.96 (CH3CH2O), 17.48
(CH2), 22.21 (CH2), 27.31 (CH2), 36.00 (CH2), 60.20 (CH2O),
70.87 (CHOH), 119.25 (O=CCH=CH), 150.03 (CH=CHC=O),
166.25 (C=O).
Anal. Calcd for C11H14O3S: C, 58.38; H, 6.24. Found: C, 58.46; H,
6.20.
Anal. Calcd for C11H20O3: C, 65.97; H, 10.07. Found: C, 65.73; H,
10.10.
a-Hydroxy Aldehydes 8a–e; General Procedure
To a solution of a corresponding alk-1-enyl mesylate 6 (5.0 mmol)
in acetone (4 mL) and t-BuOH (16 mL) were added NMO (0.64 g,
5.5 mmol) and OsO4 (4 mg, 0.016 mmol) and the resulting mixture
was stirred at 25 °C for 3 d. H2O (10 mL) was added and the mixture
was extracted with CH2Cl2 (3 × 10 mL). The combined organic lay-
ers were dried (MgSO4), filtered, and evaporated under reduced
pressure. The corresponding crude product was used in the next step
(see below).
Ethyl (E)-4-Hydroxy-5-methylhex-2-enoate (10c)11
Yield: 63%; light yellow oil; Rf = 0.25 (hexane–EtOAc, 4:1).
1H NMR (CDCl3): d = 0.95 (d, 3JH,H = 6.7 Hz, 3 H, CH3CH), 0.96
3
3
(d, JH,H = 6.7 Hz, 3 H, CH3CH), 1.30 (t, JH,H = 7.0 Hz, 3 H,
3
3
CH3CH2O), 2.37 [sept d, JH,H = 6.7 Hz, JH,H = 5.2 Hz, 1 H,
(CH3)2CH], 4.10 (ddd, JH,H = 3JH,H = 5.2 Hz, JH,H = 1.7 Hz, 1 H,
3
4
3
CHOH), 4.21 (q, JH,H = 7.0 Hz, 2 H, CH3CH2O), 6.05 (dd,
3JH,H = 15.7 Hz, JH,H = 1.7 Hz, 1 H, O=CCH=CH), 6.96 (dd,
4
(R)- and (S)-a-Hydroxyhexanals 8a
3JH,H = 15.7 Hz, 3JH,H = 5.2 Hz, 1 H, CH=CHC=O).
AD-mix-a or AD-mix-b (2.0 g), K2OsO4·H2O (4.5 mg, 0.8 mol%)
were dissolved in t-BuOH–H2O (1:1, 15 mL) at 25 °C. MeSO2NH2
(0.19 g, 2.0 mmol) was added to the mixture at 0 °C, followed by
hex-1-enyl mesylate (6a; 0.36 g, 2.0 mmol). The mixture was
stirred at 25 °C for 3 d. H2O (10 mL) was added and the resulting
mixture was extracted with CH2Cl2 (3 × 10 mL). The combined or-
ganic layers were dried (MgSO4), filtered, and evaporated under re-
duced pressure. The corresponding crude product was used in the
next step (see below).
Ethyl (E)-4-Cyclohexyl-4-hydroxybut-2-enoate (10d)11
Yield: 62%; light yellow oil; Rf = 0.29 (hexane–EtOAc, 3:1).
IR (film): 1724, 1660 cm–1.
1H NMR (CDCl3): d = 1.00–1.29 (m, 4 H, 2 × CH2), 1.30 (t,
3JH,H = 7.0 Hz, 3 H, CH3CH2O), 1.45–1.51 (m, 6 H, 3 × CH2), 1.63–
1.76 [m, 1 H, CH(CH2)5], 4.00–4.10 (m, 2 H, CHOH, OH), 4.21 (q,
3
3JH,H = 7.0 Hz, 2 H, CH3CH2O), 6.02 (dd, JH,H = 15.7 Hz,
Synthesis 2008, No. 20, 3299–3306 © Thieme Stuttgart · New York

PAPER
Synthesis of g-Hydroxy-a,b-unsaturated Compounds
3305
3
4JH,H = 1.0 Hz, 1 H, O=CCH=CH), 6.96 (dd, JH,H = 15.7 Hz,
(S)-14
3JH,H = 5.2 Hz, 1 H, CH=CHC=O).
[a]D20 +18.25 (c = 1.45, CHCl3).
Ethyl (E)-4-Hydroxy-6-phenylhex-2-enoate (10e)
Yield: 61%; light yellow oil; Rf = 0.42 (hexane–EtOAc, 4:1).
Acknowledgment
IR (film): 1724, 1648 cm–1.
The authors thank Professor Ryszard Bodalski (Technical Universi-
ty of Lodz) for stimulating discussions.
1H NMR (CDCl3): d = 1.22 (t, JH,H = 7.0 Hz, 3 H, CH3CH2O),
3
1.27–1.38 (m, 2 H, CH2), 3.00 (br s, 1 H, OH), 4.10 (q, 3JH,H = 7.0
Hz, 2 H, CH3CH2O), 4.15–4.26 (m, 1 H, CHOH), 6.07 (dd,
References
4
3JH,H = 15.7 Hz, JH,H = 1.0 Hz, 1 H, O=CCH=CH), 6.98 (dd,
3JH,H = 15.7 Hz, 3JH,H = 5.5 Hz, 1 H, CH=CHC=O), 7.18–7.29 (m, 5
(1) (a) Trost, B. M.; Rigby, J. H. J. Org. Chem. 1978, 43, 2938.
(b) Bartlett, P. A.; Green, F. R. I. I. I. J. Am. Chem. Soc.
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Lett. 1990, 31, 7555. (d) Nokami, J.; Ohkura, M.; Dan-oh,
Y.; Sakamoto, Y. Tetrahedron Lett. 1991, 32, 2409.
(e) Burgess, K.; Cassidy, J.; Henderson, I. J. Org. Chem.
1991, 56, 2050. (f) Tian, J.; Yamagiwa, N.; Matsunaga, S.;
Shibasaki, M. Org. Lett. 2003, 3, 3021. (g) Trost, B. M.;
Dong, L.; Schroeder, G. M. J. Am. Chem. Soc. 2005, 127,
10259. (h) Trost, B. M.; Dong, L.; Schroeder, G. M. J. Am.
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K.; Shimawaki, K.; Murai, A.; Kawai, H.; Suzuki, T.
Tetrahedron 2005, 61, 7392.
H, CHAr).
13C NMR (CDCl3): d = 14.84 (CH3CH2O), 28.57 (PhCH2), 28.97
(CH2), 31.11 (CH2), 32.69 (CH2), 60.22 (CH2O), 69.87 (CHOH),
120.25 (CH=CHC=O), 126.09 (2 × CHAr), 128.98 (3 × CHAr),
135.71 (CH=CHC=O), 140.14 (CAr), 149.01 (O=CCH=CH),
168.98 (C=O).
Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.50; H,
7.69.
(E)-4-Hydroxyoct-2-enenitrile (13)
Yield: 60%; light yellow oil; Rf = 0.25 (hexane–EtOAc, 4:1).
IR (film): 2225, 1664 cm–1.
(2) Nokami, J.; Taniguchi, A.; Honda, M.; Fututake, S. Chem.
Lett. 1995, 1025.
1H NMR (CDCl3): d = 0.92 (t, 3JH,H = 7.2 Hz, 3 H, CH3), 1.22–1.40
(m, 4 H, 2 × CH2), 1.51–1.63 (m, 3 H, CH2, OH), 4.32 (tdd,
(3) (a) Cass, Q. B.; Jaxa-Chamiec, A. A.; Sammes, P. G.
J. Chem. Soc., Chem. Commun. 1981, 1248. (b) Tanikaga,
R.; Nozaki, Y.; Tanaka, K.; Kaji, A. Chem. Lett. 1982,
1703. (c) Tanikaga, R.; Nozaki, Y.; Tamura, T.; Kaji, A.
Synthesis 1983, 134. (d) Nokami, J.; Mandai, T.; Ikamura,
Y.; Nishiuchi, K.; Kawada, M.; Wakabayashi, S.
Tetrahedron Lett. 1981, 22, 4489. (e) Ono, T.; Tamaoka, T.;
Yuasa, Y.; Matsuda, T.; Nokami, J.; Wakabayashi, S. J. Am.
Chem. Soc. 1984, 106, 7890. (f) Trost, B. M.; Tometzki, G.
B. Synthesis 1991, 1235.
3
4
3JH,H = 7.2 Hz, JH,H = 4.0 Hz, JH,H = 2.0 Hz, 1 H, CH), 5.68 (dd,
4
3JH,H = 16.2 Hz, JH,H = 2.0 Hz, 1 H, NCCH=CH), 6.77 (dd,
3JH,H = 16.2 Hz, 3JH,H = 4.0 Hz, 1 H, NCCH=CH).
13C NMR (CDCl3): d = 13.83 (CH3CH2), 22.39 (CH2), 27.14 (CH2),
35.99 (CH2), 70.86 (CH), 98.49 (CN), 117.36 (NCCH=CH), 156.90
(CNCH=CH).
Anal. Calcd for C8H13NO: C, 69.03; H, 9.41; N, 10.15. Found: C,
68.87; H, 9.48; N, 10.10.
(4) (a) Kosugi, H.; Kitaoka, M.; Takayashi, A.; Uda, H.
J. Chem. Soc., Chem. Commun. 1986, 1286. (b) Burgess,
K.; Henderson, I. Tetrahedron: Asymmetry 1990, 1, 57.
(c) Trost, B. M.; Mallart, S. Tetrahedron Lett. 1993, 34,
8025. (d) Nokami, J.; Mandai, T.; Nishimura, A.; Takeda,
T.; Wakabayashi, S. Tetrahedron Lett. 1986, 27, 5109.
(5) Matsushita, Y.; Sugamoto, K.; Nakama, T.; Sakamoto, T.;
Matsui, T. Tetrahedron Lett. 1995, 36, 1879.
(6) (a) Tiecco, M.; Testaferri, L.; Tingoli, M.; Bagnoli, L.; Santi,
C. J. Chem. Soc., Chem. Commun. 1993, 637. (b) Tiecco,
M.; Testaferri, L.; Marini, F.; Santi, C.; Bagnoli, L.;
Temperini, A. Tetrahedron: Asymmetry 1999, 10, 747.
(7) Fleming, F. F.; Gudipati, V.; Steward, O. W. Org. Lett. 2002,
4, 659.
(R)-13
[a]D20 –21.45 (c = 1.30, CHCl3).
(S)-13
[a]D20 +18.11 (c = 1.30, CHCl3).
Diethyl (E)-3-Hydroxyhept-1-enylphosphonate (14)2
Yield: 59%; light yellow oil; Rf = 0.27 (EtOAc).
IR (film): 1662, 1256, 1040 cm–1.
1H NMR (CDCl3): d = 0.91 (t, JH,H = 7.2 Hz, 3 H, CH3), 1.34 (t,
3
3JH,H = 7.0 Hz, 6 H, 2 × CH3CH2O), 1.34–1.43 (m, 4 H, 2 × CH2),
1.54–1.60 (m, 2 H, CH2), 4.07 (dq, 3JP,H = 3JH,H = 7.0 Hz, 4 H, 2 ×
CH3CH2O), 4.24–4.30 (m, 1 H, CHOH), 5.93 (ddd, 2JP,H = 21.0 Hz,
(8) (a) Tanikaga, R.; Hosoya, K.; Kaji, A. Chem. Lett. 1987,
829. (b) Kang, S.-K.; Lee, D.-H.; Kim, Y.-S. C.; Kang, S.-C.
Synth. Commun. 1992, 22, 1109.
3JH,H = 17.0 Hz, JH,H = 1.5 Hz, 1 H, PCH=CH), 6.79 (ddd,
4
3JP,H = 22.5 Hz, 3JH,H = 17.00 Hz, 3JH,H = 4.0 Hz, 1 H, PCH=CH).
(9) (a) Kitano, Y.; Matsumoto, T.; Wakasa, T.; Okamoto, S.;
Shimazaki, T.; Kobayashi, Y.; Sato, F.; Miyaji, K.; Arai, K.
Tetrahedron Lett. 1987, 28, 6351. (b) Yamakawa, I.; Urabe,
H.; Kobayashi, Y.; Sato, F. Tetrahedron Lett. 1991, 32,
2045. (c) Ostwald, R.; Chavant, P.-Y.; Stadtmuller, H.;
Knochel, P. J. Org. Chem. 1994, 59, 4143.
(10) (a) Baeza, A.; Casas, J.; Najera, C.; Sansano, J. M. J. Org.
Chem. 2006, 71, 3837. (b) Perrone, S.; Metzger, A.;
Knochel, P. Synlett 2007, 1047.
3
13C NMR (CDCl3): d = 13.84 (s, CH3), 16.20 (d, JP,C = 6.4 Hz,
CH3CH2O), 22.45 (s, CH2), 27.36 (s, CH2), 36.03 (d, 4JP,C = 1.6 Hz,,
CH2), 61.69 (d, 2JP,C = 5.6 Hz, CH3CH2O), 71.37 (d, 3JP,C = 21.2 Hz,
CHOH), 114.64 (d, JP,C = 188.6 Hz, PCH=CH), 155.62 (d,
1
2JP,C = 4.4 Hz, PCH=CH).
31P NMR (CDCl3): d = 19.33.
Anal. Calcd for C11H23O4P: C, 52.79; H, 9.26. Found: C, 52.94; H,
9.21.
(11) Rodriguez, S.; Kneeteman, M.; Izquierdo, J.; López, I.;
González, F. V.; Peris, G. Tetrahedron 2006, 62, 11112.
(R)-14
[a]D20 –21.89 (c = 1.45, CHCl3).
Synthesis 2008, No. 20, 3299–3306 © Thieme Stuttgart · New York

3306
H. Krawczyk et al.
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