A stereoselective palladium-mediated reductive coupling of electron-deficient terminal iodoalkenes

Article abstract of DOI:10.1002/adsc.200700464

Iodoacrylate esters undergo palladium-catalysed reductive homocoupling to derive dienyl diester derivatives. This reductive coupling can be extended to ester-substituted terminal iododienes to derive tetraene diesters. In all cases, the reactions show relatively high levels of stereocontrol, which shows an inversion of stereochemistry about one iodoalkene unit. This process, and the suggestion that the reaction releases diiodine, is consistent with a syn-1,2-addition of an iodopalladium(II)-alkene species across another iodoalkene unit (carbometallation step), followed by reductive syn-elimination of iodopalladium iodide to derive palladium(II) iodide. It appears that under the reaction conditions employed, palladium(II) iodide may equilibrate to palladium(O) and diiodine, which can be observed or trapped out from the reaction mixture.

Full text of DOI:10.1002/adsc.200700464

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DOI: 10.1002/adsc.200700464
A Stereoselective Palladium-Mediated Reductive Coupling of
Electron-Deficient Terminal Iodoalkenes
Andrei S. Batsanov,a Jonathan P. Knowles,a Benedict Samsam,a
and Andrew Whitinga,*
a
Department of Chemistry, Durham University, South Road, Durham, DH1 3 LE, United Kingdom
Fax : (+44)-191-386-1127; e-mail: andy.whiting@durham.ac.uk
Received: September 21, 2007; Published online: January 4, 2008
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Iodoacrylate esters undergo palladium-
catalysed reductive homocoupling to derive dienyl
diester derivatives. This reductive coupling can be
extended to ester-substituted terminal iododienes to
derive tetraene diesters. In all cases, the reactions
show relatively high levels of stereocontrol, which
shows an inversion of stereochemistry about one io-
doalkene unit. This process, and the suggestion that
the reaction releases diiodine, is consistent with a
syn-1,2-addition of an iodopalladium(II)-alkene
species across another iodoalkene unit (carbometal-
lation step), followed by reductive syn-elimination
of iodopalladium iodide to derive palladium(II)
iodide. It appears that under the reaction conditions
employed, palladium(II) iodide may equilibrate to
palladium(0) and diiodine, which can be observed
or trapped out from the reaction mixture.
is typically poor.[8] As part of our endeavours[9] to
construct viridenomycin,[10] palladium-catalysed cross-
coupling reactions have been examined involving
methyl Z-iodoacrylate 1 and a vinylboronate ester[11]
2 which resulted in complications, rather than Heck–
Mizoroki coupling of the vinylboronate.[12] These che-
moselectivity problems were circumvented by use of
kinetic and optimisation studies[13] such that methyl
Z-iodoacrylate 1 could be selectively coupled to give
solely the Heck–Mizoroki product 3. However, a
product resulting from stereoselective homocoupling
of the acrylate was isolated [Eq. (1)] and a mecha-
À
Keywords: alkenes; C C coupling; electron-defi-
cient compounds; palladium; reduction; stereose-
lectivity
The reductive homocoupling of aryl and alkenyl hal-
ides is a synthetically useful reaction and has received
much attention.[1] Three general methods have been
reported: i) transformation to the corresponding orga- nism proposed involving palladium-enolate species re-
nolithium[2] or Grignard[3] and metal-catalysed homo- sulting in a reductive dimerisation product 4 of the io-
coupling; ii) the copper-promoted Ullmann cou- doacrylate.[13] We now report that this type of reduc-
pling;[4] and iii) the nickel-[5,6] or palladium[7]-promot- tive dimerisation is a general phenomenon for elec-
ed coupling. Each method has significant drawbacks; tron-deficient terminal iodoalkenes and polyenes, and
use of organolithium and Grignard reagents may be that such processes are unlikely to proceed through
precluded by other functionality within the molecule, palladium-enolate species.
Ullmann couplings typically require high tempera-
The discovery of homocoupled product 4 (as a
tures as well as stoichiometric copper and although 25:5:1 mixture of E,Z:E,E,Z,E-stereoisomers) from
the nickel- and palladium-promoted process can be Eq. (1)[12] prompted a closer examination of palladi-
made catalytic through the use of a stoichiometric re- um-mediated cross-coupling reactions involving termi-
ductant, the stereoselectivity seen for alkenyl halides nal iodoalkenes under a variety of reaction conditions.
Adv. Synth. Catal. 2008, 350, 227 – 233
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227

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After considerable experimentation, it was found that
Changing the carboxylate iodoalkene substitution
the formation of the reductive dimer 4 is palladium- has interesting effects. Simple ester derivatisation of
mediated, does not require either a phosphine ligand methyl (entry 1, Table 1) to ethyl ester (entry 6) has
or vinylboronate to be present, and seems to be most an small effect in terms of yield (44 to 53%) and ste-
efficient when using Proton Spongeꢁ and silver(I) reocontrol (24:1 to 33:1). Changing the iodoalkene
salts, though it occurs more or less efficiently under a geometry from cis to trans (entry 7, Table 1) has quite
variety of conditions, as outlined in Eq. (2) with the a dramatic effect compared with entry 2; yield drops
from 57 to 22%, and the stereocontrol drops from
17:1 to only 4:1 (E,Z:E,E). In addition, increasing
substitution on the iodoalkene (entry 8), replacing the
acrylate ester with an amide function (entry 9) and
using an ortho-iodobenzoate ester (entry 10) all result
in no observable reaction. In contrast, increasing the
length of the iodoalkene to a dienyl iodide, whether
Z,Z-iodopentadienoate 12 (entry 11, Table 1), or the
corresponding E,E-isomer 14 (entry 12) has a benefi-
cial effect resulting in a 90 and 64% yield of the cor-
responding homocoupled dimer 13. However, the ste-
reochemical outcomes are very different; the all-cis-
iododiene 12 results in a mixture of three of the possi-
ble stereoisomers, with the Z,E,E,E- and E,Z,E,E-iso-
mers being the major products, whereas the all-trans-
iododiene 14 provides essentially a single stereoiso-
corresponding results in Table 1, and appears to be a mer (E,Z,E,E) with only a trace of the Z,E,E,E-
process which is characteristic of terminal, unsubsti- isomer detectable by high-field NMR.
tuted, ester-conjugated iodoalkenes.
Most odd of all the reactions carried out to date,
cis-Iodoacrylate 1 was examined under a range of was the reaction outlined by entry 13 (Table 1), in
reaction conditions (entries 1–5, Table 1), which dem- which the reaction conditions from entry 4 were re-
onstrated that running the reaction with a 5 mol% produced, with the addition of starch to the reaction
palladium loading, a small excess of both Proton mixture to assist with the removal of diiodine which is
Spongeꢁ and silver(I) acetate, in acetonitrile at 508C produced in this reaction (vide supra). The addition
results in a 44% yield of dimer 4 after silica gel chro- of starch does indeed improve the conversion of cis-
matography (entry 1). Increasing the catalyst, Proton iodoalkene 1 to dimer 4 (30 to 50%), however, there
Spongeꢁ and silver(I) loading improves the isolated are major changes in the stereochemical outcome,
yield, however, at the expense of a minor loss of ste- from a 12:1 mixture of E,Z and E,E isomers, respec-
reocontrol (entry 2) from a 24:1 to a 17:1 mixture of tively, to a surprising 1:2:3.7 mixture of E,Z:E,E:Z,Z,
the E,Z- and E,E-diastereoisomers respectively. Using i.e., with the all-cis-diene being the major isomer and
a more polar solvent than in entry 1 (DMF, entry 3) the only conditions under which this isomer has been
at the same temperature (508C) results in considera- observed. Little is known about the affinity and load-
bly reduced dimer 4 yield, however, with an almost ing capability of starch for diiodine, especially in an
doubling in the stereocontrol in favour of the E,Z- aqueous phase, although gas phase measurements
isomer (55:1, E,Z:E,E). Entry 4 (Table 1) demon- have been carried out to give predictions of 10–30%
strates that Proton Spongeꢁ and a silver(I) salt are being possible.[15] For this application, a loading of ap-
not absolutely necessary, since dimer 4 is produced, proximately 18% would in theory be required, how-
albeit in only 30% yield and relatively poor stereo- ever, we cannot be certain at this stage about the
control (12:1, E,Z:E,E), together diiodine (as indicat- mechanism of the diiodine absorption, nor whether
ed by a purple colouration of the reaction mixture).
palladium is also absorbed onto the starch to account
Changing the palladium source from palladium(II) for the different stereochemical outcome to the non-
acetate (entry 1, Table 1) to the iodide (entry 5) starch-based reactions.
shows that palladium(II) iodide is an active catalyst,
The final entry in Table 1, e.g., 14, is a reaction
though it appears to be less efficient than the catalytic which involves the electron-deficient cis-iodoacrylate
species generated from palladium(II) acetate in terms 1 and the relatively electron-rich trans-iodoalkene 15.
of yield. However, the stereocontrol is improved from To our surprise, the dienyl diester 4 was not the sole
24:1, E,Z:E,E to 50:1. In addition, a small amount of product, though it was the major product (77%) and
the Sonogashira product 5[13] is also formed, presuma- showed the expected high level of stereocontrol for
bly by coupling of methyl propiolate, generated in inversion of stereochemistry at one iodoalkene unit.
situ from elimination of HI from acrylate 1.
A more minor product, 18% with respect to 1, was
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Palladium-Mediated Reductive Coupling of Electron-Deficient Terminal Iodoalkenes
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Table 1. Reductive coupling reactions involving different alkenyl iodides.
Entry Substrate/ Product/s
Stereoselectivity
Conditions (equivalents)
s
ACHTREUNG
(Yield [%])[a]
1
1
4 (44)
E,Z:E,E:Z,Z=24:1:0
E,Z:E,E:Z,Z=17:1:0
E,Z:E,E:Z,E=55:1:0
E,Z:E,E:Z,Z=12:1:0
E,Z:E,E:Z,Z=50:1:0
E,Z:E,E:Z,Z=33:1:0
E,Z:E,E:Z,Z=4:1:0
n/a
Pd
AgOAc (1.05), MeCN, 508C
Pd
(OAc)2, (0.10), Proton Spongeꢁ (2.4),
AgOAc (2.4), MeCN, 508C
Pd
(OAc)2, (0.05), Proton Spongeꢁ (1.6),
AgOAc (1.5), DMF, 508C
Pd(OAc)2, (0.05), PPh3 (1.5), Na2CO3
(OAc)2, (0.05), Proton Spongeꢁ (1.2),
ACHTREUNG
2
1
4 (57)
ACHTREUNG
3
1
4 (23)
ACHTREUNG
4
1
4 (30)
ACHTREUNG
(3.5), THF:H2O (9:1), 708C
PdI2, (0.05), Proton Spongeꢁ (1.5), AgOAc
(1.4), MeCN, 508C
5
1
4 (21) + 5 (4)
7 (53)
6
6
Pd
AgOAc (1.3), MeCN, 508C
Pd
(OAc)2, (0.10), Proton Spongeꢁ (2.4),
AgOAc (2.4), MeCN, 508C
Pd
(OAc)2, (0.07), Proton Spongeꢁ (1.6),
AgOAc (1.5), MeCN, 508C
Pd
(OAc)2, (0.07), Proton Spongeꢁ (1.6),
AgOAc (1.5), MeCN, 508C
Pd
(OAc)2, (0.05), Proton Spongeꢁ (1.6),
AgOAc (1.5), MeCN, 508C
Z,E,E,Z:Z,E,E,E:E,Z,E,E=1:4.3:4.6 Pd
(OAc)2, (0.05), Proton Spongeꢁ (1.6),
AgOAc (1.5), MeCN, 508C
Pd
(OAc)2, (0.05), Proton Spongeꢁ (1.6),
AgOAc (1.5), MeCN, 508C
(OAc)2, (0.07), Proton Spongeꢁ (1.5),
ACHTREUNG
7
8
4 (22)
ACHTREUNG
8
9
No reaction
No reaction
No reaction
13 (90)
ACHTREUNG
9
10
11
12
14
1
n/a
ACHTREUNG
10
11
12
13
n/a
ACHTREUNG
AHCTREUNG
13 (64)
E,Z,E,E:Z,E,E,E=>20:1
E,Z:E,E:Z,Z=1:2:3.7
ACHTREUNG
4 (50)
PdAHCTRENU(G OAc)2, (0.05), PPh3 (0.11), Na2CO3
(3.4), Starch (700 gmolÀ1), THF:H2O
(9:1), 708C
Pd
AgOAc (1.5), MeCN, 508C
14
1 + 15
4 (77b) + 16 (18[b])
4: E,Z:E,E:Z,Z=20:1:1; 16:
(OAc)2, (0.05), Proton Spongeꢁ (1.6),
ACHTREUNG
(25[c]) + recovered 15 E,Z:E,E=>20:1
(61)
[a]
[b]
[c]
All reactions conducted over 20 h.
Yield based on 1 consumed.
Yield based on 15 consumed.
the heterodimer product 16, notably showing the iodoalkene complex with an electron-withdrawing
same major inversion across the acrylate iodoalkene group. The fact that the major product derives from
bond. This suggests that the dimerisation process may acrylate 1 dimerisation is likely to be a reflection of
be more dependent upon having an electron-deficient the relative rates of the formation of the iodopalladi-
iodoalkene as an electrophilic acceptor, rather than
ACHTREuUNG m(II)-alkene complex from an electron-deficient io-
necessarily requiring an intermediate palladium(II)- doalkene versus and electron-rich iodoalkene. It is
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229

Andrei S. Batsanov et al.
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also noteworthy that this reaction (entry 14) produces
the highest yield of reductive dimerisation, however,
unreacted iodoalkene is recovered in high yield ac-
counting for 86% of the starting iodoalkene 15, hence
15 is not responsible for reacting with the diiodine by-
product although its facilitation of the overall dimeri-
sation process is clearly inferred.
The results (Table 1) necessarily require a revision
of our previously proposed mechanism.[13] The finding
of the formation of reductive dimer 4 from the reac-
tion described in Eq. (1) led us propose a palladi-
ACHTREUNGum(II) acrylate-iodide complex undergoing Michael-
type addition to provide and palladium(II)-enolate
species. However, there is a clear indication of pre-
dominant inversion of iodoalkene stereochemistry
upon reductive dimerisation even with iododiene sys-
tems. This is exemplified by entries 1–7 which all
demonstrate that the major isomer results from geom-
etry inversion across one coupling partner, and dienyl
iodide 14 results in highly selective formation of the
E,E,Z,E-isomer (entry 12) which requires selective
olefin inversion across one terminal alkene. With the
Z,Z-dienyl iodide 12, the expected major product ste-
reoisomer would have the Z,Z,E,Z-tetraene geome-
try, however, this is not observed, even in the crude
reaction mixture. However, in this case of tetraenes
Scheme 1. Proposed mechanistic scheme for the reductive
dimerisation of terminal, electron-deficient iodoalkenes ex-
emplified by Z-iodoacrylate 1.
13, there are clear indications of thermodynamic in- the more efficient reactions involving silver(I) and
stability and the isolated ratio of stereoisomers is un- Proton Spongeꢁ, it is also possible that silver(I) acts
likely to reflect the kinetic product ratio directly as a as a reducing agent for diiodine, however, we believe
result of the reductive coupling. For example, CDCl3 that Proton Spongeꢁ is more important for removing
solutions of either Z,E,E,Z- or Z,E,E,E-tetraene 13 diiodine from the reaction. Evidence of this is pre-
undergo slow isomerisation in ambient light over a liminary, however, heating a 1:1 mixture of palladi-
few months, eventually providing the all-trans-
ACHTREuUNG m(II) iodide and Proton Spongeꢁ dissolved in
(E,E,E,E)-isomer. Similar effects result from heating MeCN-d3 at 508C slowly produces an unsymmetric
toluene solutions at 1108C over a matter of hours, Proton Spongeꢁ adduct in which the aromatic system
with the Z,E,E,E-isomer being slowest to isomerise. is intact. This process is considerably faster in the
Taken together, we propose the broad overall mecha- presence of silver(I) acetate, and if the reaction is car-
nistic process outlined in Scheme 1 to explain the gen- ried out at 708C for 24 h eventually results in reaction
erally major product formation, i.e., involving a palla- on the aromatic ring, presumably resulting in ring io-
dium(II) complex 17 from addition of a palladium(0) dination, though the products are unstable and to
complex to iodoalkene 1, syn-addition another iodoal- date have not been isolated or characterised. Consid-
kene 1 to provide C-attached[14] intermediate 18a. erable further work is required to obtain a detailed
Bond rotation to allow syn-elimination can occur understanding of the unusual processes operating in
from conformation 18b, resulting in reductive dimer 4 these types of reductive dimerisation reactions, how-
and the palladium(II) iodide complex 19, from which ever, even at this stage, the dimerisation of terminal
diiodine is lost to return palladium(0) complex 20.
iodoalkenes can be useful for the highly stereoselec-
The fate of the resulting diiodine is still in question, tive synthesis of polyenes, particularly substituted by
however, as previously noted, certain reactions (such electron-withdrawing groups. This area of polyene
as entry 4, Table 1) appear to have free diiodine pres- synthesis is still rather underdeveloped and invariably
ent, suggesting that the palladium(II) iodide complex produces the all-trans-isomers, which does not occur
19 undergoes facile reductive elimination of diiodine. with reductive dimerisation except by thermodynamic
In addition, none of the reactions examined to date equilibration (vide supra). For example, E,E,E-1,8-
provide quantitative reductive dimerisation product hexatrienoate derivatives have been prepared by pho-
formation, hence, it is very likely that diiodine can tochemical,[16] E,E,E,E-1,10-hexatetraenoic acid has
react with both the starting materials, such as 1 been prepared by alkyne or tetraene isomerisation, as
(known reaction for iodoacrylate isomerisation[13]), or have the corresponding penta- and hexa-ene ana-
the products, resulting in non-isolable products. For logues,[17] and by using Wittig-related methods.[18] In
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(35 mL). Drying (MgSO4) and evaporation gave crude prod-
uct as a brown oil. Purification by silica gel chromatography
(EtOAc: petroleum ether, 1:9) gave 7 as a pale yellow oil,
yield: 92 mg (53%).
contrast, the reductive coupling approach allows the
rapid construction of other isomers of such electron-
deficient polyene systems, which may have benefit
not only for polyene-containing natural product syn-
thesis[19] but also for application as molecular wires.[20]
In addition, the continued study of this type of pro-
cess is likely to result in potentially efficient ap-
proaches to otherwise unaccessible polyene geome-
tries. Entry 13 in Table 1 clearly shows the potential
for future developments, in this case not only produc-
ing some of the all-cis-diene 4, but these reaction con-
ditions also avoid the use of expensive silver(I) salts
and Proton Sponge.ꢁ
Although these results are clearly preliminary, they
do show that there is still much to be learnt about
palladium coupling reactions. In addition, this type of
reductive homocoupling has the potential to be an-
other useful tool for the rapid assembly of polyenyl
systems, with moderate to high stereocontrol. The ini-
tial signs of heterodimerisation of different iodoal-
kenes have also been demonstrated, which potentially
widens the scope of such reactions enormously, and
clearly has mechanistic repercussions. Further investi-
gations into these highly stereocontrolled, efficient re-
ductive dimerisation reactions of terminal haloalkenes
is underway, particularly with respect to the mecha-
nism and fate of the diiodine by product.
Reductive Dimerisation of Iodide 12
To a dried Schlenk tube under a positive pressure of argon
was added palladium(II) acetate (7.5 mg, 0.033 mmol), sil-
ver(I) acetate (168 mg, 1.0 mmol), Proton Sponge (229 mg,
1.1 mmol) and a solution of iodide 12 (160 mg, 0.67 mmol)
in dry MeCN (6 mL), the mixture was degassed using the
freeze-pump-thaw method (3”) and heated to 508C with
vigorous stirring. After 19.5 h the mixture was cooled, dilut-
ed with Et2O (60 mL), passed through Celite and washed
with 5% HCl (20 mL) and brine (20 mL). Drying (MgSO4)
and evaporation gave crude product as a brown solid. Purifi-
cation by silica gel chromatography (EtOAc: pet. ether, 1:19
then 1:9) gave Z,E,E,Z-13 (mp 110–1128C, yield: 7 mg,
9%), Z,E,E,E-13 (mp 98–1008C, yield: 29 mg, 39%) and
E,Z,E,E-13 (yield: 31 mg, 42%), all pale yellow solids.
Synthesis of Iodide 14
To a dried Schlenk tube under a positive pressure of argon
was added a solution of the corresponding diene boronate
methyl ester,[1] (230 mg, 0.965 mmol) in dry THF (5.5 mL),
and the tube cooled to À788C in the absence of light.
NaOMe (2.4 mL of a 0.5M solution in MeOH, 1.2 mmol)
was added dropwise, the mixture stirred for 30 min and ICl
(1.5 mL of a 1M solution in DCM, 1.50 mmol) added drop-
wise. The mixture was stirred for 1 hour, warmed to room
temperature, diluted with diethyl ether (65 mL) and washed
with 5% aqueous sodium metabisulfite (35 mL), water
(35 mL), and brine (35 mL). Drying (MgSO4) and evapora-
tion gave the crude product as a yellow solid which was pu-
rified by silica gel chromatography (EtOAc:petroleum
ether, 5:95) to give 14 as a white powder; yield: 206 mg
(90%), mp 56–618C (decomposition). Recrystalisation by
cooling a hexane solution gave crystals suitable for X-ray
diffraction.
Experimental Section
Synthesis Dienyl Diester 4 (Table 1, entry 2)
To a dried Schlenk tube under a positive pressure of argon
was added 1 (267 mg, 1.25 mmol) and dry MeCN (7 mL),
the mixture was degassed using the freeze-pump-thaw
method (1”), palladium(II) acetate (27.5 mg, 0.12 mmol),
Proton Sponge (650 mg, 3 mmol) and silver(I) acetate
(500 mg, 3 mmol) were added, then the mixture was further
degassed using the freeze-pump-thaw method (2”) and
heated to 508C under argon. After 20 h the reaction mixture
was cooled, diluted with Et2O (70 mL), passed through
Celite and washed with 5% HCl (30 mL) and brine
(30 mL). Drying (MgSO4) gave crude product as a brown
solid. Purification by silica gel chromatography (EtOAc:pe-
troleum ether, 1:4) gave 4; yield: 61 mg (57%). All spectro-
scopic and analytical properties for E,E-,[5] Z,-,Z-[5] and E,Z-
isomers[1] were identical to those reported.
Reductive Dimerisation of Iodide 14
To a dried Schlenk tube under a positive pressure of argon
was added iodide 14 (100 mg, 0.42 mmol), palladium(II) ace-
tate (5 mg, 0.02 mmol), silver(I) acetate (105 mg,
0.63 mmol), Proton Sponge (143 mg, 0.67 mmol) and dry
MeCN (4 mL), then the mixture was degassed using the
freeze-pump-thaw method (3”) and heated to 508C with
vigorous stirring. After 20 h the mixture was cooled, diluted
with Et2O (30 mL), passed through Celite and washed with
5% HCl (10 mL), water (10 mL) and brine (10 mL). Drying
(MgSO4) and evaporation gave the crude product as a
yellow solid. Purification by silica gel chromatography
(EtOAc:petroleum ether, 5:95 then 1:9) gave E,Z,E,E-13 as
a white solid; yield: 30 mg (64%).
ACHTREUNG(2Z,4E)-Diethyl Hexa-2,4-dienedioate 7
To a dried Schlenk tube under a positive pressure of argon
was added 6 (400 mg, 1.77 mmol) and dry MeCN (15 mL),
the mixture was degassed using the freeze-pump-thaw
method (1”), palladium(II) acetate (27 mg, 0.12 mmol), sil-
ver(I) acetate (387 mg, 2.3 mmol) and Proton Sponge
(585 mg, 2.7 mmol) were added, then the mixtue was further
degassed (2”) and heated to 508C. After 20 h the mixture
was cooled, diluted with Et2O (100 mL), passed through
Celite and washed with 5% HCl (35 mL) and brine
2-[(E)-2-Cyclohexylvinyl]-4,4,6-trimethyl-1,3,2-
dioxaborinane
Stirred cyclohexylacetylene (3 mL, 23 mmol) was cooled to
08C under argon, catecholborane (2.55 mL, 26 mmol) added
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Andrei S. Batsanov et al.
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dropwise and the mixture heated to 708C. After 2 h the mix-
ture was cooled to room temperature, diluted with water
(5 mL) and stirred for 30 min before the addition of saturat-
ed aqueous NaHCO3 (20 mL) and a solution of 2-methyl-
pentane-2,4-diol (3.3 mL, 26 mmol) in Et2O (10 mL). The
solution was stirred vigorously for 100 min, diluted with
Et2O (50 mL) and water (25 mL), separated, washed with
saturated aqueous NaHCO3 (40 mL), water (40 mL) and
brine (20 mL), dried (MgSO4) and evaporated to give the
crude product as a pale brown oil. Cooling to À158C caused
precipitation and the mixture was extracted with Et2O/pe-
troleum ether (5:95, 3”5 mL) and the solution purified by
silica gel chromatography (Et2O:peroleum ether, 5:95) to
give 2-[(E)-2-cyclohexylvinyl]-4,4,6-trimethyl-1,3,2-dioxabor-
inane as a pale yellow oil; yield: 4.33 g (89%).
[2] I. M. Pastor, M. Yus, Tetrahedron Lett. 2000, 41, 1589–
1592.
[3] a) M. S. Kharasch, O. Reinmuth, Grignard Reactions of
Non-metallic Substances, Constable and Co. Ltd.,
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[(E)-2-Iodovinyl]cyclohexane 15
To a solution of 2-[(E)-2-cyclohexylvinyl]-4,4,6-trimethyl-
1,3,2-dioxaborinane (274 mg, 1.30 mmol) in THF (7 mL)
was added NaOMe (3.0 mL of a 0.5M solution in MeOH,
1.5 mmol) dropwise, the mixture stirred for 15 min prior to
the addition of ICl (1.5 mL of a 1.0M solution in DCM,
1.5 mmol) and the mixture stirred at room temperature in
the absence of light. After 1 h the mixture was diluted with
Et2O (60 mL), washed with 5% aqueous sodium metabisul-
phite (20 mL), water (40 mL) and brine (20 mL), dried
(MgSO4) and evaporated to give the crude product as a
yellow oil. Purification by silica gel chromatography (petro-
leum ether) gave 15 as a clear oil; yield: 174 mg (62%).
ACHTREUNG(2E,4E)-Methyl 5-Cyclohexylpenta-2,4-dienoate 16
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To a dried Schlenk tube under a positive pressure of argon
was added palladium(II) acetate (18 mg, 0.08 mmol), sil-
ver(I) acetate (280 mg, 1.6 mmol), Proton Sponge (390 mg,
1.8 mmol), dry MeCN (10 mL), 15 (184 mg, 0.78 mmol) and
1 (236 mg, 1.1 mmol), then the mixture was degassed using
the freeze-pump-thaw method (3”) and heated to 508C
under argon. After 20 h the reaction mixture was cooled, di-
luted with Et2O (80 mL), passed through Celite and washed
with 5% HCl (30 mL) and brine (30 mL). Drying (MgSO4)
gave crude product as a brown oil. Purification by silica gel
chromatography (gradient elution, EtOAc:petroleum ether,
0:1 to 15:85) gave 15 (yield: 113 mg, 61%), 16 (yield: 38 mg,
18% based on 1, 25% based on 15) and 4 (yield: 72 mg,
77%).
Hasegawa, T. Kamiya, T. Henmi, H.
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Acknowledgements
We thank the EPSRC for a research grant and DTA student-
ship (JPK) and the National Mass Spectrometry Service at
Swansea.
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