Exploiting the Anders-Ga?ner variant on the Wittig reaction: new methodology for the synthesis of 3,3-dimethylacroyl enol esters

Article abstract of DOI:10.1016/j.tet.2008.04.068

A one pot synthesis of the 3,3-dimethylacroyl enol ester function found in the vibsane type diterpenes has been developed based on the Anders-Ga?ner variant of the Wittig reaction (AGW reaction). This method uses easily accessible acyloxyalkylidene phosphoranes and a variety of aldehydes.

Full text of DOI:10.1016/j.tet.2008.04.068

Tetrahedron 64 (2008) 6482–6487
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Exploiting the Anders–Gaßner variant on the Wittig reaction: new
methodology for the synthesis of 3,3-dimethylacroyl enol esters
,
b
a
Brett D. Schwartz a, Craig M. Williams a , Ernst Anders , Paul V. Bernhardt
*
a School of Molecular and Microbial Sciences, University of Queensland, Brisbane, 4072 Queensland, Australia
b Institut fuer Organische Chemie und Makromolekulare Chemie der Friedrich-Schiller-Universitaet Jena, Humboldtstrasse 10, D-07743 Jena, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A one pot synthesis of the 3,3-dimethylacroyl enol ester function found in the vibsane type diterpenes
has been developed based on the Anders–Gaßner variant of the Wittig reaction (AGW reaction). This
method uses easily accessible acyloxyalkylidene phosphoranes and a variety of aldehydes.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 14 November 2007
Received in revised form 31 March 2008
Accepted 17 April 2008
Available online 22 April 2008
1. Introduction
acid addition to triple bonds is about the only alternative.10–12
The anhydride method is typified by the elegant work of Davies13
The 3,3-dimethylacroyl enol ester function (as highlighted in 5)
is contained only within the vibsane type diterpene natural product
family of which 61 examples currently exist.1–8 Even though the
vibsanane type diterpenes are made up of a number of different
structure types, for example 1–7, the 3,3-dimethylacroyl enol
ester sidechain is maintained nearly throughout the whole family
(Fig. 1).
Synthetic methods to construct the 3,3-dimethylacroyl enol ester
moiety and vinyl esters in general9 from aldehydes are mostly lim-
ited to variations on anhydride (RCOX)/base (or acid) systems. In
comparison, transition metalmediated anti-Markovnikovcarboxylic
who completed the total synthesis of 5,10-bis-epi-vibsanin E 8
(and corresponding Z isomer 9) by treatment of aldehyde 10
with 3,3-dimethylacrylic anhydride (11) under basic conditions
(Scheme 1).
These methods, however, require a homologated aldehyde [i.e.,
one alpha (acidic) protoned carbon unit] to install the vinyl ester
function, which in many cases, including our own,14–17 demands an
extra synthetic step to accommodate homologation. Taking this
into account and the fact that only a handful of synthetic methods
are currently available for building such functionality it became
apparent that new methodologies are required.
O
OH
O
O
O
OH
X
O
O
O
O
O
O
O
O
O
R
OH
Vibsanin E 2 (X=O, R=Me)
Cyclovibsanin A 3 (X=CH2, R=OH)
Vibsanin C 1
Vibsanin O 4
OCH3
O
O
O
MeO
O
O
CHO
O
O
O
O
O
O
O
OMe
Spirovibsanin A 6
Furanovibsanin D 5
Neovibsanin A 7
Figure 1. Examples of vibsane type diterpenes containing 3,3-dimethylacroyl enol ester sidechain.
* Corresponding author.
E-mail address: c.williams3@uq.edu.au (C.M. Williams).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.068

B.D. Schwartz et al. / Tetrahedron 64 (2008) 6482–6487
6483
O
O
O
O
O
O
O
O
O
O
O
O
O
2
8 (19%)
O
+
H
11
10
O
O
9 (10%)
Scheme 1.
O
O
O
O
R3
H
R1
O
R1
O
R1
O
O
O
18
PPh3Cl
O
19
PPh3Cl
PPh3Cl
O
O
O
R3
NaHMDS
14
H
PPh3
13
X
PPh3
12
R2
R2
R2
H
15
CF3
O
O
PPh3Cl
> –60 °C
R1COX
21
20
R1
HO
H
Figure 2.
O
PPh3
X
R2
O
17
16
R2
Scheme 2.
Although yields are moderate to low they are similar, or even better
(see below) to those observed using the base anhydride protocol
(i.e., Scheme 1). Ylids resulting from 19 or 21 failed or gave only
trace amounts of product, respectively.
In an attempt to increase yields Horner–Wadsworth–Emmons
type reagents (i.e., 31 and 32) were synthesised, however, on
treatment with base [NaN(SiMe3)2] and subsequent reaction with
4-nitrobenzaldehyde only lactone 33 was obtained (Fig. 4). Lactone
33 arises from selective 1,4-deprotonation of the 3,3-dimethyl-
acroyl function followed by an aldol reaction and subsequent
lactonisation.
It should be noted for comparative purposes that product 30
(entry 9, Table 1) was synthesised using the traditional method [i.e.,
3,3-dimethylacroyl anhydride (11), base and the one carbon ho-
mologue (34)] in 8% yield [E/Z (1.2:1)], which is a much lower yield
to that obtained with the one-step protocol reported herein
(Scheme 3).
Considering that the Wittig reaction18,19 is synonymous
throughout organic chemistry as a means of rapidly and mildly
constructing carbon–carbon double bonds, including vinyl ethers,20
we contemplated applying this methodology to create a 3,3-
dimethylacroyl enol ester function in a single step. A literature
survey, however, revealed the interesting but relatively unknown21
Anders–Gaßner variant of the Wittig reaction (Scheme 2).22–28 This
reaction is exemplified by the process of an acyloxy-
alkylidenephosphorane 12 (obtained via the deprotonation of the
corresponding phosphonium salt 13, synthesised from 16), reacting
with an aldehyde (14) to afford the vinyl ester 15 (Scheme 2).
Two possible explanations can be provided which might be
responsible for the lack of interest in the AGW reaction by the
synthetic community to-date. Firstly, the intermediate acyloxy-
alkylidene phosphoranes 12 exhibit remarkable instability: above
ꢀ60 ꢁC an interesting intramolecular rearrangement occurs (ac-
companied by the elimination of PPh3) which finally results in
the formation of 1,2-diketones 17.22–27 Secondly, hitherto the
AGW reaction offered limited functional group application, for
example, only aryl and heteroaryl groups were demonstrated at
R1 and R2 (Scheme 2). Irrespective of these two issues, this re-
action potentially offers a powerful one-step option to access
certain vinyl ester functionalities and as such we embarked on an
exploration of a wider range of acceptable functional groups at
both R1 and R2 with direct application to the vibsane type
diterpenes.
3. Conclusion
In conclusion, the AGW reaction has been exploited in terms of
being extended in scope to adopt 3,3-dimethylacroyl ester func-
tionality. Although yields are moderate to low it should be noted
that a unique feature of the current methodology is that con-
struction of an acetylenic or homologated aldehyde moiety is not
required, which are the crucial intermediate steps for the other
vinyl ester building methodologies and yields of the one-step
protocol are higher.
2. Results and discussion
4. Experimental
4.1. General
The 3,3-dimethylacroyl phosphonium salt 18 was prepared as
outlined in Scheme 2 (i.e., 16 to 13). Unfortunately, attempts to
prepare the trifluoroacetyl (i.e., 20) failed, however, acetyl (i.e., 19)
and pivaloyl (i.e., 21) were synthesised in acceptable yields (Fig. 2).
A range of both aromatic and aliphatic aldehydes were then sub-
jected to 18 in the deprotonated form [(i.e., 12) Scheme 2], which
gratifyingly afforded the desired products (Table 1 and Fig. 3).
1H and 13C NMR spectra were recorded on Bruker AV400
(400.13 MHz; 100.62 MHz), AV300 (300.13 MHz; 75.47 MHz) and
DRX500 (500.13 MHz; 125.76 MHz) instruments in deuterio-
chloroform (CDCl3). Coupling constants are given in hertz and
chemical shifts are expressed as d values in parts per million. GC/MS

6484
B.D. Schwartz et al. / Tetrahedron 64 (2008) 6482–6487
Table 1
Products 22–30 arising from reaction of selected aldehydes 14 with the ylid 12 (R1¼(CH3)2C]CH, R2¼H; derived from deprotonation of the phosphonium salt 18)
Entry
Aldehyde
Product
Yield (%)
E/Z Ratio
OTBS
OTBS
O
O
O
O
1
32
2.4:1
O
O
OHC
22
O
O
O
O
2
3
4
5
6
21
26
20
41
30
3.4:1
1.5:1
1.5:1
1.5:1
10:1
OHC
O
23
NMe2
O
NMe2
O
24
O
O
O
25
NO2
O
NO2
O
O
O
26
Cl
Cl
O
O
O
27
O
O
7
8
9
29
25
30
3.5:1
1.7:1
1.3:1
O
O
O
O
H
28
S
O
29
S
O
O
6
O
6
30
data were recorded on a Shimadzu GC-17A Ver.3, mass-spectrome-
ter: MS QP5050A, ionisation at 70 eV, column: DB-5ms
2 min at 100 ꢁC, followed by a temperature increase of 16 ꢁC/min
and held at 250 ꢁC for 10 min. High resolution electrospray ion-
isation (HRESIMS) accurate mass measurements were recorded in
positive mode on a Bruker MicrOTOF-Q (quadrupole-Time of Flight)
30 mꢂ0.25
mm, carrier-gas: He, total flow 32.2 mL/min, column
flow 1.3 mL/min, injector temperature: 250 ꢁC, standard program:
Figure 3. ORTEP diagrams of the molecular structures of 26 and 33. Displacement ellipsoids are drawn at the 30% probability level.

B.D. Schwartz et al. / Tetrahedron 64 (2008) 6482–6487
6485
O
O
4.4. General procedure for preparation of 3,3-dimethylacroyl
esters (Table 1)
O
O
31
PPh2
O
O
2-Chlorostyryl 3-methylbut-2-enoate (27). A suspension of 18
(700 mg, 1.70 mmol) in anhydrous tetrahydrofuran (25 mL) under
argon was sonicated for 10 min until a uniform milky dispersion
had formed. The mixture was then cooled to ꢀ78 ꢁC and a solution
of sodium hexamethyldisilazide (1.70 mL, 1.70 mmol, 1 M solution
in THF) was added strictly dropwise. The reaction was stirred for
33
O
32
O2N
P(OEt)2
O
Figure 4.
30 min, then
a solution of 2-chlorobenzaldehyde (160 mg,
1.13 mmol) in anhydrous tetrahydrofuran (5 mL) was added drop-
wise and stirred for a further 30 min. The mixture was then poured
into saturated ice-cold sodium bicarbonate (10 mL) and extracted
with diethyl ether (3ꢂ15 mL). The combined organic layer was
washed with brine, dried over sodium sulfate and concentrated in
vacuo. The residue was purified by flash chromatography (diethyl
ether/pet. spirit, 1:25) to give the title compound (27) as a colour-
less oil (80 mg, 30%) [E/Z (10:1)]. Rf (diethyl ether/pet. spirit, 1:20)
0.73; nmax (neat) 1728 (s), 1636 (s), 1438 (m),1350 (m),1210 (s), 1122
O
O
O
2
O
O
30
7
6
11
34
Scheme 3.
(vs), 1050 (s), 958 (s), 844 (s), 750 (s) cmꢀ1
; dH (300 MHz, CDCl3, E
instrument with a Bruker ESI source. Accurate mass measurements
were carried out with external calibration using sodium formate as
a reference calibrant. Microanalyses were performed by the Uni-
versity of Queensland Microanalytical Service. Column chroma-
tography was undertaken on silica gel (Flash Silica gel 230–400
mesh), with distilled solvents. Anhydrous solvents were prepared
according to Perin and Armarego, ‘Purification of laboratory sol-
vents’, 3rd ed. Tetrahydrofuran was freshly distilled from a sodium/
benzophenone still. Melting points were determined on a Fischer
Johns melting point apparatus and are uncorrected. Fine chemicals
were purchased from the Aldrich Chem. Co.
isomer only) 7.89 (1H, d, J¼12.7 Hz), 7.43–7.49 (1H, m), 7.30–7.37
(1H, m), 7.10–7.23 (2H, m), 6.73 (1H, d, J¼12.7 Hz), 5.77 (1H, sept,
J¼1.2 Hz), 2.22 (3H, d, J¼1.2 Hz), 1.96 (3H, d, J¼1.2 Hz); dC (75 MHz,
CDCl3, E isomer only) 163.1, 160.8, 137.8, 132.9, 132.9, 129.7, 128.2,
ꢃ
126.9, 126.5,114.6, 111.3, 27.7, 20.7; GC/MS (EI): m/z (%) 236 (Mþ , 2),
190 (0.04), 176 (0.02), 154 (1), 125 (6), 83 (100), 63 (8), 55 (38);
HRMS (ESI): MNaþ, found 259.0496. C13H13ClO2Naþ requires
259.0502.
4.4.1. Compound 22
Colourless oil. Yield 32% [E/Z (2.4:1)]. Rf (EtOAc/pet. spirit, 1:20)
0.41; dH (400 MHz, C6D6, mixture of cis and trans isomers) 7.56 (1H,
d, J¼12 Hz), 7.40 (1H, dd, J¼6.4, 0.8 Hz), 6.20 (1H, dd, J¼12, 11 Hz),
5.70 (1H, sept, J¼1.2 Hz), 5.62 (1H, sept, J¼1.2 Hz), 5.43 (1H, dd,
J¼10, 6.4 Hz), 4.87 (1H, br d, J¼12 Hz), 4.86 (1H, br d, J¼12 Hz), 3.85
(1H, br d, J¼12 Hz), 3.82 (1H, br d, J¼11.6 Hz), 3.13–3.19 (1H, m),
3.01–3.08 (1H, m), 2.74 (1H, br s), 2.71 (1H, br s), 2.39 (1H, dt, J¼14,
3.2 Hz), 2.30 (1H, dt, J¼14, 3.2 Hz), 2.23 (1H, dt, J¼10.8, 4.0 Hz), 2.04
(3H, d, J¼1.2 Hz), 2.03 (3H, d, J¼1.2 Hz), 1.86–1.94 (1H, m), 1.69–1.81
(2H, m),1.37 (3H, d, J¼1.6 Hz),1.36 (3H, d, J¼1.6 Hz),1.25 (3H, s),1.13
(3H, s), 1.15 (3H, d, J¼3.2 Hz), 1.10 (3H, s), 0.93 (18H, s), 0.83 (3H, s),
0.72–1.03 (15H, m), 0.12 (3H, s), 0.06 (3H, s), 0.05 (3H, s), 0.02 (3H,
s); dC (100 MHz, C6D6, mixture of cis and trans isomers) 163.4,162.9,
159.3, 158.7, 144.3, 144.1, 136.2, 134.3, 116.0, 115.6, 115.5, 115.3, 115.2,
73.6, 73.5, 61.0, 48.6, 47.4, 47.3, 44.9, 41.3, 40.9, 38.0, 37.6, 37.2, 36.9,
36.4, 36.1, 35.0, 34.1, 34.0, 27.8, 27.7, 27.0, 25.9, 23.6, 22.2, 21.7, 20.3,
4.2. X-ray crystallography
Crystallographic data for structures 26 and 33 have been de-
posited with the Cambridge Crystallographic Data Centre as sup-
plementary publication nos. CCDC-665996 and CCDC-665997 and
can be obtained free of charge via http://www.ccdc.cam.ac.uk/
conts/retrieving.html, or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: þ44 1223 336
033, or e-mail: deposit@ccdc.cam.ac.uk.
4.3. [(3-Methylbut-2-enoyloxy)methyl]triphenylphos-
phonium chloride 18
ꢃ
To a solution of (hydroxymethyl)triphenylphosphonium chlo-
ride29 (13.8 g, 42 mmol) in anhydrous dichloromethane (10 mL)
under an argon atmosphere was added 3,3-dimethylacroyl chloride
(10 g, 85 mmol) dropwise. The mixture was refluxed for 16 h,
cooled to room temperature and transferred by pipette to vigor-
ously stirred diethyl ether (50 mL). A white gum formed which was
isolated by decanting off the mother liquor and then re-dissolved in
dichloromethane (25 mL). The trituration process was repeated
with diethylether/dichloromethane until pure by 1H NMR and then
the product was placed under high vacuum (0.05 mmHg) for 48 h
20.2, 18.3, 18.2, ꢀ3.6, ꢀ3.9, ꢀ4.1; GC/MS (EI): m/z (%) 474 (Mþ , 3)
459 (0.2), 417 (1), 391 (10), 363 (3), 317 (3), 238 (4), 181 (4), 157 (11),
83 (100), 73 (37), 55 (17).
4.4.2. Compound 23
Colourless oil. Yield 21% [E/Z (3.4:1)]. Rf (EtOAc/pet. spirit, 1:10)
0.33; dH (400 MHz, C6D6, mixture of cis and trans isomers) 7.49 (1H,
d, J¼12 Hz), 7.38 (1H, dd, J¼6.4, 0.8 Hz), 5.76 (1H, dd, J¼12, 11 Hz),
5.67 (1H, sept, J¼1.2 Hz), 5.66 (1H, sept, J¼1.2 Hz), 4.96 (1H, dd,
J¼11, 6.4 Hz), 4.35 (1H, d, J¼12 Hz), 3.32 (1H, dd, J¼12, 4 Hz), 3.27
(1H, dd, J¼12, 3.6 Hz), 2.98–3.05 (1H, m), 2.56 (1H, dd, J¼12, 6 Hz),
2.48 (1H, dd, J¼12, 6.8 Hz), 2.32 (1H, dd, J¼13, 6 Hz), 2.21 (1H, dd,
J¼12, 4.8 Hz), 2.06 (3H, d, J¼1.6 Hz), 2.04 (3H, d, J¼1.6 Hz), 2.01–
2.10 (3H, m), 1.93–2.00 (2H, m), 1.62–1.80 (6H, m), 1.55–1.59 (1H,
m), 1.381 (3H, s), 1.378 (3H, s), 1.14–1.29 (4H, m), 1.10 (3H, s), 1.06
(6H, s), 1.05 (3H, s), 1.00 (3H, s), 0.77 (3H, s), 0.56–0.76 (4H, m); dC
(100 MHz, C6D6, mixture of cis and trans isomers) 209.8, 209.6,
163.4, 162.9, 159.6, 159.2, 135.9, 134.2, 115.4, 115.2, 115.0, 114.0, 72.8,
72.7, 60.1, 59.7, 50.9, 50.7, 48.0, 47.4, 43.7, 43.5, 43.4, 43.3, 42.4, 39.9,
35.8, 35.1, 34.9, 34.8, 30.4, 30.3, 28.1, 27.0, 23.5, 23.3, 21.5, 21.0, 20.3;
which
afforded
((3-methylbut-2-enoyloxy)methyl)triphenyl-
phosphonium chloride as white powder (15.8 g, 92%). [Note: highly
hygroscopic.] nmax (neat) 2913 (br), 1732 (m), 1642 (m), 1437 (s),
1114 (vs), 1073 (vs), 996 (m), 749 (vs), 724 (vs) cmꢀ1
; dH (400 MHz,
CDCl3) 7.77–7.86 (9H, m), 7.64–7.72 (6H, m), 6.53 (d, 2H, J¼2.8 Hz),
5.53 (1H, sept, J¼1.2 Hz), 1.94 (3H, d, J¼1.2 Hz), 1.82 (3H, d, J¼1.2
Hz); dC (100 MHz, CDCl3) 163.6 (d, J¼4.6 Hz), 162.0, 135.6 (d, J¼3
Hz), 134.2 (d, J¼10 Hz), 130.5 (d, J¼13 Hz), 115.9 (d, J¼86 Hz), 113.2,
55.7 (d, J¼65 Hz), 27.5, 20.6. HRMS (ESI): MꢀClþ, found 375.1498.
C
24H24O2P requires 375.1508.

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B.D. Schwartz et al. / Tetrahedron 64 (2008) 6482–6487
ꢃ
GC/MS (EI): m/z (%) 360 (Mþ ,0.1), 345 (0.1), 277 (1), 260 (1), 135 (1),
83 (100), 55 (19); HRMS (ESI): MNaþ, found 383.2203. C22H32NaO4
requires 383.2198.
4.4.7. 2-(Thiophen-3-yl)vinyl 3-methylbut-2-enoate 29
Colourless oil. Yield 25% [E/Z (1.7:1)]. Rf (diethyl ether/pet. spirit,
1:20) 0.39; nmax (neat) 1721 (s),1691 (m),1642 (s),1350 (m),1219 (s),
1127 (vs), 1074 (s), 844 (s), 640 (m) cmꢀ1
; dH (400 MHz, CDCl3, trans
4.4.3. 4-(Dimethylamino)styryl 3-methylbut-2-enoate 24
isomer) 7.83 (1H, dd, J¼12.8, 0.3 Hz), 7.27 (1H, ddd, J¼5.1, 2.9, 0.6 Hz),
7.14 (1H, ddd, J¼5.1, 1.3, 0.4 Hz), 7.08–7.09 (1H, m), 6.39 (1H, ddd,
J¼12.7,1.1, 0.6 Hz), 5.73–5.75 (1H, m), 2.21 (3H, d, J¼1.3 Hz),1.94 (3H,
d, J¼1.3 Hz); dC (100 MHz, CDCl3, trans isomer) 163.2, 160.2, 136.3,
135.9,126.2,124.7,121.3,114.7,109.4, 27.6, 20.6; dH (400 MHz, CDCl3,
cis isomer) 7.46–7.47 (1H, m), 7.37 (1H, dd, J¼5.0, 1.2 Hz), 7.33 (1H,
dd, J¼7.0, 0.3 Hz), 7.27 (1H, ddd, J¼5.1, 3.0, 0.5 Hz), 5.87–5.89 (1H, m),
5.81 (1H, ddd, J¼7.0, 0.9, 0.5 Hz), 2.27 (3H, d, J¼1.3 Hz), 2.01 (3H, d,
J¼1.3 Hz); dC (100 MHz, CDCl3, cis isomer) 162.62,160.9,135.2,133.0,
128.5, 125.0, 123.8, 114.6, 106.0, 27.6, 0.6; GC/MS (EI): m/z (%) 208
Grey powder, mp 55–60 ꢁC. Yield 26% [E/Z (1.5:1)]. Rf (diethyl
ether/pet. spirit, 1:20) 0.28; dH (400 MHz, C6D6, cis isomer) 7.65–
7.72 (2H, m), 7.59 (1H, d, J¼6.6 Hz), 6.58–6.63 (2H, m), 5.76 (1H,
sept, J¼1.2 Hz), 5.59 (1H, d, J¼6.6 Hz), 2.5 (6H, s), 2.06 (3H, d,
J¼1.2 Hz), 1.39 (3H, d, J¼1.2 Hz); dH (400 MHz, C6D6, trans isomer)
8.27 (1H, d, J¼12.8 Hz), 7.15–7.20 (2H, m), 6.56 (1H, d, J¼12.8 Hz),
6.43–6.48 (2H, m), 5.70 (1H, sept, J¼1.2 Hz), 2.47 (6H, s), 2.08 (3H, d,
J¼1.2 Hz), 1.4 (3H, d, J¼1.2 Hz); dC (100 MHz, C6D6, mixture of cis
and trans isomers) 163.4, 162.8, 159.4, 158.9, 150.1, 149.8, 134.1,
131.7, 130.7, 127.5, 123.8, 123.1, 115.5, 115.5, 115.4, 113.0, 112.5, 112.2,
ꢃ
(Mþ , 4), 177 (0.03), 147 (0.1), 125 (0.3), 97 (11), 83 (100), 55 (40);
ꢃ
40.1, 40.0, 27.1, 27.0, 20.3, 20.3; GC/MS (EI): m/z (%) 245 (Mþ , 6), 187
HRMS (ESI): MNaþ, found 231.0450. C11H12NaO2S requires 231.0456.
(0.6), 163 (33), 134 (47), 118 (21), 83 (91), 55 (100), 51 (26); HRMS
(ESI): MNaþ, found 246.1475. C15H20NO2 requires 246.1494.
4.4.8. Undeca-1,10-dienyl 3-methylbut-2-enoate 30
Colourless oil. Yield 30% [E/Z (1.3:1)]. Rf (diethyl ether/pet. spirit,
1:20) 0.31; nmax (neat) 1776 (m), 1717 (m), 1635 (m), 1443 (m), 1379
4.4.4. Styryl 3-methylbut-2-enoate 25
Colourless oil. Yield 20% [E/Z (1.5:1)]. Rf (diethyl ether/pet. spirit,
1:20) 0.44; nmax (neat) 1730 (s), 1642 (s), 1440 (m), 1217 (s), 1122
(m),1205 (m),1092 (m),1022 (vs), 940 (s), 896 (m), 841 (m) cmꢀ1
; dH
(400 MHz, CDCl3, trans isomer) 7.10 (1H, dt, J¼12.4,1.5 Hz), 5.79 (1H,
ddt, J¼16.9, 10.2, 6.7 Hz), 5.66–5.68 (1H, m), 5.38 (1H, dt, J¼12.3,
7.6 Hz), 4.94–5.00 (2H, m), 4.89–4.92 (1H, m), 2.17 (3H, d, J¼1.3 Hz),
1.95–2.05 (4H, m), 1.90 (3H, d, J¼1.3 Hz), 1.23–1.39 (10H, m); dH
(400 MHz, CDCl3, cis isomer) 7.05 (1H, dt, J¼6.4, 1.5 Hz), 5.79 (1H,
ddt, J¼16.9, 10.2, 6.7 Hz), 5.71–5.73 (1H, m), 4.83 (1H, td, J¼7.5,
6.5 Hz), 2.18 (3H, m), 2.09–2.15 (2H, m), 1.95–2.05 (2H, m), 1.92 (3H,
m), 1.23–1.39 (10H, m); dC (100 MHz, CDCl3, mixture of cis and trans
isomers) 163.6, 163.5, 159.0, 159.0, 139.2, 135.2, 133.8, 115.2, 115.1,
114.5, 114.1, 114.1, 113.8, 33.8, 29.6, 29.3, 29.2, 29.2, 29.1, 29.1, 29.0,
29.0, 28.9, 28.9, 27.5, 27.4, 24.5, 20.5, 20.4; GC/MS (EI): m/z (%) 250
(vs), 1073 (s), 932 (m), 844 (m), 692 (m) cmꢀ1
; dH (400 MHz, C6D6,
mixture of cis and trans isomers) 8.40 (1H, d, J¼12.9 Hz), 7.57 (1H,
d, J¼7.3 Hz), 7.16–7.23 (2H, m), 6.95–7.10 (6H, m), 6.41 (1H, d,
J¼12.9 Hz), 5.65 (1H, sept, J¼1.3 Hz), 5.63 (1H, sept, J¼1.2 Hz), 5.47
(1H, d, J¼7.3 Hz), 2.05 (3H, d, J¼1.2 Hz), 2.02 (3H, d, J¼1.3 Hz), 1.38
(3H, d, J¼1.2 Hz), 1.33 (3H, d, J¼1.3 Hz); dC (100 MHz, C6D6, mixture
of cis and trans isomers) 163.0, 162.5, 160.4, 159.9, 136.8, 135.2,
135.0, 134.4, 129.6, 128.9, 128.6, 128.1, 127.9, 127.2, 126.5, 115.0,
ꢃ
111.6, 27.0, 26.9, 20.3, 20.3; GC/MS (EI): m/z (%) 202 (Mþ , 0.1), 187
(0.03), 177 (0.03), 156 (0.1), 120 (1), 102 (0.5), 91 (7), 83 (100), 55
(33); HRMS (ESI): MNaþ, found 225.0886. C13H14NaO2 requires
225.0891.
ꢃ
(Mþ , 0.1), 235 (0.01), 222 (0.2), 207 (0.02), 83 (100), 67 (6), 55 (54),
41 (33); HRMS (EI): Mþ, found 250.1931. C16H26O2 requires 250.1933.
4.4.5. 4-Nitrostyryl 3-methylbut-2-enoate 26
4.5. (Diphenylphosphoryl)methyl 3-methylbut-2-enoate 31
Pale yellow solid, mp 79–82 ꢁC. Yield 41% [E/Z (1.5:1)]. [Found: C,
63.33; H, 5.36; N, 5.63. C13H13NO4 requires C, 63.15; H, 5.30; N
5.67%.] Rf (diethyl ether/pet. spirit, 1:20) 0.35; nmax (neat) 1735 (s),
1633 (s), 1597 (s), 1517 (s), 1342 (vs), 1214 (s), 1121 (vs), 1050 (m),
To a solution of dicyclohexylcarbodiimide (1.7 g, 8.14 mmol),
3,3-dimethylacrylic acid (814 mg, 8.14 mmol) and (diphenylphos-
phoryl)methanol30 (1.73 g, 7.40 mmol), in dichloromethane
(20 mL) at 0 ꢁC was added 4-dimethylaminopyridine (100 mg,
0.81 mmol) and the reaction mixture was stirred for 2 h. The re-
action was warmed to room temperature overnight, filtered
through a plug of Celite, concentrated in vacuo and purified by flash
chromatography (EtOAc/DCM, 1:1) affording (diphenylphosphor-
yl)methyl 3-methylbut-2-enoate (31) (606 mg, 26%) as colourless
needles, mp 85–88 ꢁC. Rf (EtOAc/dichloromethane, 1:1) 0.71; nmax
(neat) 2970 (br), 1747 (m), 1725 (s), 1650 (m), 1438 (s), 1186 (vs),
952 (s), 925 (vs), 861 (vs), 747 (s), 688 (s) cmꢀ1
; dH (300 MHz, C6D6,
trans isomer) 8.13–8.19 (2H, m), 8.08 (1H, d, J¼12.9 Hz), 7.42–7.47
(2H, m), 6.40 (1H, d, J¼12.9 Hz), 5.75–5.78 (1H, m), 2.24 (3H, d,
J¼1.3 Hz), 1.98 (3H, d, J¼1.3 Hz,); dH (300 MHz, CDCl3, cis isomer)
8.16–8.21 (2H, m), 7.70–7.75 (2H, m), 7.3 (1H, d, J¼7.3 Hz), 5.85–5.87
(1H, m), 5.74 (1H, d, J¼7.3 Hz), 2.26 (3H, d, J¼1.3 Hz), 2.02 (3H, d,
J¼1.3 Hz); dC (125 MHz, C6D6, mixture of cis and trans isomers)
162.6,162.2,161.8,161.7,146.9,146.6,141.2,140.9,139.6,137.0,129.5,
126.3, 124.0,123.7, 114.5,114.3, 112.9, 109.3, 27.1, 27.1, 20.5, 20.5; GC/
1132 (vs), 1077 (vs), 848 (s), 718 (vs), 693 (vs) cmꢀ1
; dH (300 MHz,
ꢃ
MS (EI): m/z (%) 247 (Mþ ,1), 217 (0.2), 204 (0.03),171 (0.03),118 (4),
CDCl3) 7.72–7.82 (4H, m), 7.40–7.60 (6H, m), 5.61 (1H, sept,
J¼1.3 Hz), 4.85 (2H, d, J¼5.3 Hz), 2.05 (3H, d, J¼1.3 Hz), 1.84 (3H, d,
J¼1.3 Hz); dC (125 MHz, CDCl3) 165.2 (d, J¼7.8 Hz), 159.3, 132.3–
132.4 (m), 131.2–131.5 (m), 130.3 (d, J¼101.8 Hz), 128.5–128.9 (m),
114.6, 59.9 (d, J¼86.8 Hz), 27.4, 20.3; HRMS (ESI): MNaþ, found
337.0964. C18H19NaO3P requires 337.0970.
89 (20), 83 (100), 55 (65); HRMS (ESI): MNaþ, found 270.0737.
C
13H13NNaO4 requires 270.0742.
4.4.6. 2-(Furan-2-yl)vinyl 3-methylbut-2-enoate 28
Colourless oil. Yield 29% [E/Z (3.5:1)]. dH (400 MHz, C6D6, trans
isomer) 8.36 (1H, d, J¼12.7 Hz), 6.92–6.93 (1H, m), 6.22 (1H, d,
J¼12.6 Hz), 6.01 (1H, dd, J¼3.3, 1.9 Hz), 5.87–5.88 (1H, m), 5.58 (1H,
sept, J¼1.3 Hz), 1.99 (3H, d, J¼1.3 Hz), 1.35 (3H, d, J¼1.3 Hz); dH
(400 MHz, C6D6, cis isomer) 7.40–7.42 (1H, d, J¼7.1 Hz), 7.07–7.08
(1H, m), 6.70–6.71 (1H, m), 6.20 (1H, ddd, J¼3.4, 1.8, 0.6 Hz), 5.64
(1H, sept, J¼1.3 Hz), 5.62–5.64 (1H, m), 2.01 (3H, d, J¼1.3 Hz), 1.36
(3H, d, J¼1.3 Hz); dC (100 MHz, C6D6, mixture of cis and trans iso-
mers) 162.7, 162.2, 160.6, 160.0, 150.3, 141.8, 141.4, 136.4, 132.9,
114.9, 114.8, 111.8, 111.3, 110.4, 107.8, 104.4, 101.7, 27.3, 27.0, 20.3,
4.6. (Diethoxyphosphoryl)methyl 3-methylbut-2-enoate 32
(Diethoxyphosphoryl)methyl 3-methylbut-2-enoate (32) (58%,
colourless oil) was synthesised from diethyl hydroxymethylphos-
phonate31 following the analogous procedure for that of 31. Rf
(dichloromethane) 0.43; nmax (neat) 2984 (br), 1724 (m), 1650 (m),
1221 (m), 1140 (s), 1019 (vs), 962 (s), 845 (m) cmꢀ1
; dH (300 MHz,
CDCl3) 5.72 (1H, sept, J¼1.3 Hz), 4.36 (2H, d, J¼8.6 Hz), 4.15 (4H, dq,
J¼8.0, 7.1 Hz), 2.15 (3H, d, J¼1.3 Hz), 1.89 (3H, d, J¼1.3 Hz), 1.31 (6H,
dt, J¼7.0, 0.4 Hz); dC (75 MHz, CDCl3) 164.9 (d, J¼8.6 Hz); 158.6,114.4,
ꢃ
20.3; GC/MS (EI): m/z (%) 208 (Mþ , 2), 180 (0.04), 166 (0.1), 149
(0.02), 108 (1), 83 (100), 55 (30).

B.D. Schwartz et al. / Tetrahedron 64 (2008) 6482–6487
6487
62.4 (d, J¼6.2 Hz), 55.5 (d, J¼169 Hz), 27.2, 20.1, 16.1 (d, J¼5.8 Hz);
References and notes
HRMS (ESI): MHþ, found 251.1043. C10H20O5P requires 251.1048.
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enoate (31) (880 mg, 2.82 mmol) in anhydrous tetrahydrofuran
(25 mL) at ꢀ78 ꢁC was added a solution of sodium hexamethyldisi-
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benzaldehyde (430 mg, 2.82 mmol) in anhydrous tetrahydrofuran
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C
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(vs), 1083 (s), 1048 (s), 851 (s), 748 (s), 694 (s) cmꢀ1
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;
CDCl3) 8.17–8.22 (2H, m), 7.54–7.59 (2H, m), 5.87–5.90 (1H, m), 5.50
(1H, dd. J¼11.1, 5.0 Hz), 2.46–2.65 (2H, m), 2.01–2.02 (3H, m); dC
(75 MHz, CDCl3) 163.8, 156.8, 147.7, 145.6, 126.7, 123.8, 116.6, 77.1,
ꢃ
36.5, 22.8; GC/MS (EI): m/z (%) 233 (Mþ , 0.1), 217 (0.1), 208 (0.02),
203 (0.1), 150 (2), 115 (3), 82 (100), 77 (11), 54 (25); HRMS (ESI):
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Acknowledgements
The authors thank The University of Queensland and the Aus-
tralian Research Council (DP0666855) for financial support.
Supplementary data
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Copies of 1H and 13C NMR spectra. Supplementary data associ-
ated with this article can be found in the online version, at
doi:10.1016/j.tet.2008.04.068.