A regioselective tsuji-trost pentadienylation of 3-allyltetronic acid

Article abstract of DOI:10.1055/s-0029-1216898

A regioselective Tsuji-Trost reaction of sodium 3-allyltetronate with methyl 5-trimethylsilylpenta-2,4-dienyl carbonate was developed. Carbon-carbon bond formation at the more highly substituted terminus of the pentadienyl residue was possible by introduc

Full text of DOI:10.1055/s-0029-1216898

2
778
PAPER
A Regioselective Tsuji–Trost Pentadienylation of 3-Allyltetronic Acid
T
R
suji–Trost
P
enta
a
dienylatio ni ner Schobert,* Bertram Barnickel
Organisch-chemisches Laboratorium der Universität Bayreuth, Gebäude NW I, 95440 Bayreuth, Germany
Fax +49(921)552671; E-mail: Rainer.Schobert@uni-bayreuth.de
Received 16 March 2009; revised 29 April 2009
fording up to three regioisomeric product dienes upon re-
action with nucleophiles. The factors influencing this
equilibrium and the site of nucleophilic attack have been
intensively studied, including the substituents on the di-
Abstract: A regioselective Tsuji–Trost reaction of sodium 3-allyl-
tetronate with methyl 5-trimethylsilylpenta-2,4-dienyl carbonate
was developed. Carbon–carbon bond formation at the more highly
substituted terminus of the pentadienyl residue was possible by in-
13b,21–24
25
troduction of an easy to remove SiMe shielding group at the remote ene,
the nature of the nucleophile, and the ligands
3
end of the p-system. This carbonate reacted fast enough to avoid on palladium.26
scrambling and formation of symmetric bisallyl tetronic acids. The
For the Tsuji–Trost synthesis of bakkenolide A precursor
3-allyl-3-penta-2,4-dienyltetronic acid thus obtained is a key inter-
mediate en route to the natural spirolactone bakkenolide A.
4
2
2
from tetronate 2 we prepared methyl 2,3-dimethylpenta-
,4-dienyl methyl carbonate (3a) and 2,3-dimethylpenta-
,4-dienyl acetate (3b) (Scheme 2). Maleic anhydride (5)
Key words: allylation, regioselectivity, palladium, tetronic acid,
Schlosser–Wittig reaction
2
7
was dimethylated in the presence of 2-aminopyridine.
Deviating from the literature procedure, the crude product
was purified by sublimation to leave anhydride 6 in 55%
yield.
We had previously reported that sodium 3-allyltetronates
1
are amenable to a Tsuji–Trost reaction with allyl acetates
to yield 3,3-bisallyltetronic acids without scrambling of
2
residues. For a synthesis of the natural spirolactone
3–6
LiAlH(Ot-Bu)3
Et2O–THF (2:1)
–17 °C (1 h), r.t. (16 h)
O
O
O
2-aminopyridine
AcOH, Δ, 90 min
7–11
bakkenolide A (1)
we now wanted to introduce penta-
O
O
O
dienyl rather than allyl residues under similar conditions.
This would enable us to eventually generate the carbocy-
cle 1 by a Diels–Alder reaction. Hence, we considered a
Tsuji–Trost pentadienylation of the sodium salt 2 of 3-al-
lyltetronic acid, which is readily accessible by Claisen re-
(55%)
(82%)
O
O
OH
5
6
7
Ph3P=CH2
THF, r.t.,17 h
CO2H (Cl3C)2CO, Ph3P
CH2Cl2, 0 °C, 1.5 h
COCl
LiAlH4
Et2O, r.t.,1.5 h
1
2
arrangement of 4-O-allyl tetronate (Scheme 1).
(89%)
(quant.)
(66%)
OR
8
9
O
O
O
Diels–
Alder
Tsuji–
Trost
O
O
O
+
a: ClCO2Me, DMAP
py, CH2Cl2, r.t., 1.5 h
OH
OCOR
3
a: R = OMe (80%)
b: R = Me (84%)
O
O
Na
b: Ac2O, py, r.t., 1 h
3
1
4
2
3
1
0
Scheme 1 Retrosynthesis of bakkenolide A (1)
Scheme 2 Synthesis of 1-acyloxy-2,3-dimethylpenta-2,4-dienes 3
Tsuji–Trost allylations are mechanistically well under-
1
stood. They have been widely used in natural product The anhydride 6 was reduced to the lactol 7 with Li-
3
1
synthesis due to their regio- and stereoselectivity. The AlH(Ot-Bu) in diethyl ether–tetrahydrofuran at –17 °C.
4
28
3
3
intermediate (h -allyl)palladium complexes can react Wittig methylenation of 7 afforded (2Z)-2,3-dimethyl-
2
9
with nucleophiles at either end, but directing methods penta-2,4-dienoic acid (8) in ca. 90% yield. Not many
were developed. For instance, the so-called memory ef- alkenations of 5-hydroxybutenolides by an unstabilized
1
5–18
29–31
fect,
that is, the nucleophilic attack at the C-atom that phosphorus ylide have been reported, so far.
originally bore the leaving group, is observed with bulky chloride 9 was obtained almost quantitatively according
Acid
1
chiral ligands on palladium such as MeOMOP, PHOX,
9
20
32
to the general protocol by Villeneuve et al. while proce-
1
and PCy . With penta-2,4-dienyl acetates or carbonates dures using thionyl chloride or oxalyl chloride led to an
6
3
3
in Tsuji–Trost reactions there are two inter-mediate (h - isomerization of the 2Z-double bond. Reduction of crude
pentadienyl)-palladium complexes in equili-brium, af- chloride 9 with LiAlH furnished alcohol 10 in 66% over
4
two steps. Its acylation gave the carbonate 3a and the ace-
tate 3b, respectively, which were submitted as the allylic
component to the Tsuji–Trost reaction with sodium
SYNTHESIS 2009, No. 16, pp 2778–2784
x
x.
x
x
.
2
0
0
9
Advanced online publication: 14.07.2009
DOI: 10.1055/s-0029-1216898; Art ID: T06009SS
Georg Thieme Verlag Stuttgart · New York
2
tetronate (2) (Scheme 3). In either case we obtained a
©

PAPER
Tsuji–Trost Pentadienylation
2779
1
0:70 mixture (determined by H NMR spectra) of the re- 5-bromopenta-2,4-dienoic acid (20). It is worthy of note
3
gioisomers 4 and 11, the former originating from an attack that olefination of 7 by the same ylide prepared with NaH-
of the 3-allyltetronate at the vinyl(p-allyl) complex 12, the MDS as the base proceeded with only moderate 4E-selec-
latter from the preferred reaction of complex 13. 3,3-Dial- tivity (E/Z = 75:25). The high selectivity in the case of
lylfuran-(2H)-2,4-dione was also formed as a byproduct LiHMDS is untypical of semi-stabilized ylides. It can be
via self reaction of tetronate 2, especially when 3b with rationalized by assuming an intramolecular Schlosser-
3
9,40
the poor leaving group acetate was used.
type mechanism.
O
R2
R4
Ph3PCH2Br Br
LiHMDS, THF
–47 °C (3 h); r.t.
O
PPh3
Br•LiX
O
PPh3
Li
(
(
Ph3P)4Pd
5 mol%)
PdLn
+ 2 O
3a,b
7
H
H
H
Br
THF–MeOH
r.t.
(72%)
LnPd
13
O
O
O
OH
O
12
4 (30%) + 11 (70%)
2
19a
19b
2
R = Me
4
R = H
4
R = H
R = Me
CO2H
O
PPh3
H
1. (COCl)2
CH2Cl2, r.t.
OH
Br
Scheme 3 Unselective Tsuji–Trost pentadienylation of sodium 3-
allyltetronate (2) with either compound 3a or 3b
H
Br
2. LiAlH4
Et2O, r.t. 1 h
O
OLi
Br
(88%)
In line with the mechanistic rationale of an equilibrium of
3
two isomeric (h -pentadienyl)palladium complexes 12
19c
20
21
and 13, the pentadienyl carbonate 14 gave virtually the
same product mixture of 4 (32%) and 11 (68%) upon re-
TsOH
OEE THF–H O (10:1)
r.t., 36 h
EtOCH=CH2
PPTS, r.t.
OEE 1. tBuLi
2
1
action with tetronate 2 as evidenced by H NMR spec-
–78 °C, 0.5 h
3
3
trum. Compound 14 was prepared from g-keto ester 15
in three steps, a Wittig reaction leading to pentadienoate
6, followed by a reduction to alcohol 17, which was fi-
(82%)
2. TMSCl
78 °C, 1 h
88%)
(95%)
SiMe3
–
Br
(
2
2
23
1
nally converted into carbonate 14 with methyl chlorofor-
mate (Scheme 4).
ClCO Me
2
CH2Cl2, py
OH
OCO2Me
0
°C, 2h
HO
MeO2CO
ClCO2Me
py, DMAP
MeO2C
MeO2C
(84%)
LiAlH4
r.t., 28 h
Ph3P=CH2
THF, r.t.
SiMe3
SiMe3
2
4
18
(
54%)
(89%)
(54%)
O
Scheme
lyl)penta-2,4-dienyl methyl carbonate (18)
5
Synthesis of (2Z,4E)-2,3-dimethyl-5-(trimethylsi-
15
16
17
14
Scheme 4 Synthesis of 3,4-dimethylpenta-2,4-dienyl methyl carbo-
nate (14)
In the presence of Li salts the initial mixture of erythro-
1
9a and threo-oxaphosphetanes is deprotonated/lithiated
1
Replacement of Ph P by the MeOMOP ligand in Tsuji–
Trost reactions of 3a and 2 in order to exploit the above
mentioned memory effect merely led to mixtures of 4 and
9
to give predominantly the lithiated threo-oxaphos-phet-
ane 19b. This gets reprotonated with retention by the ad-
jacent carboxylic acid thus leaving the threo-oxaphos-
phetane 19c that collapses to the corresponding (2Z,4E)-
5-bromo-2,3-dimethylpenta-2,4-dienoic acid (20). It was
converted to the acid chloride and immediately reduced
3
1
5
1 with ratios no better than 28:72. In addition, heating to
0 °C was necessary for the reaction to take place. Appar-
ently, regioselectivity in Tsuji–Trost pentadienylations of
tetronates mainly arises from differences in the sterical ac-
cessibility of the two possible allyl ligands, for example,
with LiAlH to the alcohol 21, which was protected with
4
4
1
a 1-ethoxyethyl (EE) group to give 22. Other protective
groups such as THP and MOM were unsuitable. With
1
a bulky electron-releasing group such as SiMe is attached
2 and 13. Reaction of the former will predominate when
4
THP the Li–Br exchange failed, while MOM could not
2
3
be cleaved without removal of the SiMe group. Vinyl
3
at the methylene terminus C-5 of 3a or 3b. The finding
that vinylic SiMe groups facilitate nucleophilic attack on
bromide 22 was converted with retention to the vinyl si-
lane 23 under carefully optimized conditions. Treatment
first with t-BuLi at –78 °C for 30 minutes and then with
3
the remote end of p-allyl palladium complexes even if
other sterically demanding residues are present came to be
3
4–36
Me SiCl at this temperature furnished the product diene
3
known as the silicon effect.
2,3-Dimethyl-5-(trimeth-
2
3 in 88% yield. High-yielding acid-catalyzed deprotec-
ylsilyl)penta-2,4-dienyl methyl carbonate (18) was thus
prepared as depicted in Scheme 5. Lactol 7 was alkenated
tion of acetal 23 afforded the alcohol 24, which was con-
verted to the target carbonate 18 using methyl chloro-
formate.
3
7,38
by Ph P=CHBr, generated from [Ph PCH Br]Br
and
LiHMDS as the base, to give pure (2Z,4E)-2,3-dimethyl-
3
3
2
Synthesis 2009, No. 16, 2778–2784 © Thieme Stuttgart · New York

2
780
R. Schobert, B. Barnickel
PAPER
Gratifyingly, the Tsuji–Trost reaction of carbonate 18 Melting points were recorded on an Electrothermal 9100 apparatus
and are uncorrected. IR spectra were recorded on a Perkin-Elmer
Spectrum One FT-IR spectrophotometer equipped with an ATR
sampling unit. NMR spectra were recorded under conditions as in-
dicated on a Bruker Avance 300 spectrometer. Chemical shifts are
given in parts per million (d) downfield from TMS as internal stan-
dard. Analytical gas chromatography was conducted on a DB-5 sil-
with sodium 3-allyltetronate (2) under standard condi-
tions afforded the 3-allyl-3-(penta-2,4-dienyl)furan-(2H)-
2
,4-dione (25) in over 50% yield as the sole product. Nei-
ther symmetric bisallyl derivatives from self reaction of 2
nor regioisomers stemming from attack at C-5 of 18 were
found (Scheme 6). It should be noted that acetates and ica column (l = 30 m; ∅ = 0.32 mm; J & W Scientific). Mass
carbonates derived from vinyl bromide 21 did not react spectra were recorded using a Varian MAT 311A spectrometer (EI,
7
0 eV). Microanalyses were carried out with a Perkin-Elmer 2400
CHN elemental analyzer. For chromatography Merck silica gel 60
230–400 mesh) was used.
with 2. The silyl group of 25 was removed almost quanti-
tatively with TFA to give compound 4.
(
OCO2Me
27
3
,4-Dimethylmaleic Anhydride (6)
O
O
(
(
Ph3P)4Pd
5 mol%)
A solution of maleic anhydride (5; 196.2 g, 2.0 mol) in AcOH (300
mL) was added within 1 h to a refluxing solution of 2-aminopyri-
dine (94.1 g, 1.0 mol) in AcOH (200 mL). After refluxing for 2.5 h,
the solvent was removed, aq 2 M H SO (600 mL) was added, and
O
+
O
THF–MeOH
r.t., 48 h
R
2
4
O
Na
SiMe3
(54%)
O
the mixture was refluxed for another 2 h. Cooling to r.t. resulted in
the formation of a brown precipitate, which was collected by filtra-
tion, washed with aq 2 M H SO (50 mL) and H O (2 × 50 mL), and
18
2
TFA
CH2Cl2, r.t.
91%)
25: R = SiMe3
4
: R = H
2
4
2
(
finally dried over P O . Sublimation at 60 °C/0.02 mbar yielded 6
2
as colorless crystals (68.0 g, 54%); mp 92 °C (Lit. mp 95 °C);
= 0.46 (cyclohexane–EtOAc, 1:1).
5
2
7
Scheme 6 Regioselective Tsuji–Trost pentadienylation of tetronate
with 5-silylated pentadienyl carbonate 18
2
R
f
–
IR (ATR): 1815, 1791, 1734, 1687, 1278, 1123 cm .
1
1
In summary, we have developed a regioselective Pd-cata-
lyzed 3-pentadienylation of sodium 3-allyltetronate 2,
which should be also applicable to tetronic acids with oth-
er patterns of substitution and to tetramic acids as well.
The nucleophilic attack by the tetronate was directed ex-
clusively to the more hindered terminus of the pentadienyl
H NMR (CDCl ): d = 2.02 (s, 6 H, CH ).
3
3
13
C NMR (75 MHz, CDCl ): d = 9.2, 140.7, 166.0.
3
+
MS: m/z (%) = 126 (15, [M ]), 82 (38), 54 (91), 50 (30), 39 (100).
HRMS (EI): m/z calcd for C H O : 126.0317; found: 126.0317.
6
6
3
2
8
5
A solution of LiAlH(Ot-Bu) (22.38 g, 88 mmol) in THF–Et O (2:1,
-Hydroxy-3,4-dimethylfuran-(5H)-2-one (7)
electrophile by attaching a SiMe group to the methylene
3
3
2
terminus of the starting pentadienyl carbonate 3a. This
SiMe group tolerates the conditions of the Tsuji–Trost re- BuOH (25.1 mL, 264 mmol), was added within 20 min to a solution
2
40 mL), freshly prepared from LiAlH (3.34 g, 88 mmol) and t-
4
3
action, but can be easily removed afterwards with TFA.
of 6 (10.09 g, 80 mmol) in Et O (300 mL) at –17 °C. After stirring
2
at –17 °C for another hour, the reaction was allowed to warm to r.t.
and stirred for a further 16 h. Aq 2 M H SO (300 mL) was added
and the aqueous layer was extracted with Et O (2 × 80 mL). The
2
,14
We are currently investigating asymmetric variants of
this Tsuji–Trost reaction. First experiments with chiral
2
4
2
ligands such as BINAP, phenyl Trost ligand, MeOMOP, combined organic phases were dried (Na SO ), filtered, and evapo-
and PhBOX were unsuccessful. No reaction took place, rated to dryness. The crude product was dissolved in a minimum
2
4
amount of CHCl , precipitated by the addition of pentane, filtered
3
except with BINAP, which led to tetronate 2 being con-
sumed by self reaction to yield 3,3-diallyltetronate. We
have also begun to explore the planned Diels–Alder step.
While 3-allyl-3-penta-2,4-dienyl derivatives with R = H
6
such as 11 reacted readily under Back’s conditions to af-
ford the corresponding tricyclic products such as 26 (in-
separable unassigned 6:6:1:1 mixture of stereoisomers
according to GC) no conversion was yet obtained under
these conditions with the analogues 4 or 25 (Scheme 7).
off after 18 h at –20 °C and washed with pentane (2 × 10 mL) to
2
8
yield 7 as colorless crystals (8.29 g, 81%); mp 80 °C (Lit. mp 81–
2 °C); R = 0.41 (Et O).
8
2
f
2
–
1
IR (ATR): 3350, 1729, 1694, 1439, 1338, 1079 cm .
1
H NMR (CDCl ): d = 1.75 (s, 3 H, CH ), 1.95 (s, 3 H, CH ), 5.80
3
3
3
(
s, 1 H, OH), 5.86 (s, 1 H, H-5).
1
3
C NMR (75 MHz, CDCl
73.6.
): d = 8.1, 11.3, 98.7, 125.5, 156.6,
3
1
+
MS: m/z (%) = 128 (1, [M ]), 100 (100), 83 (41), 55 (67).
BHT
(5 mol%)
HRMS (EI): m/z calcd for C H O : 128.0473; found: 128.0473.
3
6
8
O
O
toluene, 190 °C, 24 h
bomb tube
2
9
O
O
(Z)-2,3-Dimethylpenta-2,4-dienoic Acid (8)
A solution of methylidenetriphenylphosphorane (16.71 g, 60.5
mmol) in THF (300 mL) was treated with 7 (3.68 g, 28.7 mmol) and
stirred at r.t. for 17 h. The solvent was removed and the residue was
(
97%)
O
O
11
26
taken up with aq NaHCO (200 mL, 10% w/w) and washed with
3
Scheme 7 Preliminary test reaction towards the intramolecular
Diels–Alder reaction of 3-allyl-3-penta-2,4-dienylfuran(2H)-2,4-di-
ones
EtOAc (3 × 50 mL). The aqueous layer was acidified with concd
HCl and then extracted with Et O (3 × 50 mL). The combined Et O
extracts were dried (Na SO ) and concentrated to leave 8 as color-
2
2
2
4
less crystals (3.21 g, 89%); mp 47 °C; R = 0.58 (Et O).
f
2
–
IR (ATR): 2927, 2612, 1673, 1578, 1404, 1292 cm .
1
Synthesis 2009, No. 16, 2778–2784 © Thieme Stuttgart · New York

PAPER
Tsuji–Trost Pentadienylation
2781
1
H NMR (CDCl ): d = 1.96 (s, 3 H, CH ), 2.02 (s, 3 H, CH ), 5.27
3
(Z)-2,3-Dimethylpenta-2,4-dienyl Acetate (3b)
A solution of 10 (1.92 g, 17.1 mmol) in pyridine (40 mL) was treat-
ed with Ac O (6.80 mL, 68.4 mmol) and the mixture was stirred at
2
3
3
(d, J = 11.1 Hz, 1 H, H-5), 5.46 (d, J = 17.4 Hz, 1 H, H-5), 7.37 (dd,
J = 17.4, 11.1 Hz, 1 H, H-4), 11.29 (s, 1 H, CO H).
2
1
3
r.t. for 30 min. MeOH (20 mL) was added and stirring was contin-
ued for 30 min. The volatiles were removed under reduced pressure
and H O (40 mL) was added. The aqueous layer was extracted with
C NMR (75 MHz, CDCl ): d = 15.4, 16.6, 117.3, 125.2, 136.0,
3
1
43.3, 174.0.
2
+
MS: m/z (%) = 126 (100, [M ]), 125 (62), 111 (75), 96 (33), 83 (43),
CH Cl (3 × 30 mL), the combined organic phases were washed
2
2
8
1 (38), 79 (64).
with aq 2 M HCl (5 × 50 mL), dried (Na SO ), and evaporated to
2
4
dryness. The crude product was purified by column chromatogra-
phy on silica gel to leave 3b as a colorless liquid (2.22 g, 84%);
HRMS (EI): m/z calcd for C H O : 126.0681; found: 126.0681.
7
10
2
3
2
Rf = 0.40 (cyclohexane–EtOAc, 9:1).
(
Z)-2,3-Dimethylpenta-2,4-dienoyl Chloride (9)
A mixture of 8 (2.92 g, 23.1 mmol), hexachloroacetone (1.75 mL,
1.6 mmol), and CH Cl (120 mL) was cooled to 0 °C, treated with
–1
IR (ATR): 2926, 1736, 1375, 1224, 1021, 986 cm .
1
2
2
1
H NMR (CDCl ): d = 1.77 (s, 3 H, CH ), 1.79 (s, 3 H, CH ), 2.00
3
3
3
PPh (6.06 g, 23.1 mmol) and stirred for 1.5 h. The solvent was re-
3
moved under reduced pressure to yield 9 as a colorless liquid (3.34
g, 100%), which was used in the next step; bp 94 °C/11 mbar.
(
s, 3 H, CH ), 4.68 (s, 2 H, H-1), 5.04 (d, J = 11.0 Hz, 1 H, H-5),
3
5
4
.19 (d, J = 17.0 Hz, 1 H, H-5), 6.79 (dd, J = 17.0, 11.0 Hz, 1 H, H-
).
–
IR (ATR): 2926, 1764, 1569, 1171, 984, 907 cm .
1
1
3
C NMR (75 MHz, CDCl ): d = 14.5, 18.3, 21.2, 64.6, 114.3,
3
1
H NMR (CDCl ): d = 1.95 (s, 3 H, CH ), 2.10 (s, 3 H, CH ), 5.35
3
3
3
128.7, 133.4, 134.6, 171.4.
(d, J = 11.0 Hz, 1 H, H-5), 5.54 (d, J = 17.1 Hz, 1 H, H-5), 6.92 (dd,
J = 17.1, 11.0 Hz, 1 H, H-4).
+
MS: m/z (%) = 154 (7, [M ]), 112 (15), 97 (8), 94 (31), 79 (100).
1
3
HRMS (EI): m/z calcd for 154.0993: C
H O ; found: 154.0988.
9 14 2
C NMR (75 MHz, CDCl ): d = 15.1, 17.0, 119.5, 130.2, 134.7,
3
1
42.3, 168.5.
(E)-Methyl 3,4-Dimethylpenta-2,4-dienoate (16)
A solution of 15 (3.30 g, 23.2 mmol, E/Z = 69:31) in THF (30 mL)
(Z)-2,3-Dimethylpenta-2,4-dien-1-ol (10)
A solution of crude 9 (640 mg, 4.75 mmol) in Et O (80 mL) was
was added to a solution of Ph P=CH (7.04 g, 25.5 mmol) in THF
3
2
2
(100 mL) at r.t. The mixture was stirred for 28 h, the solvent evap-
orated, and the crude product purified by column chromatography
on silica gel to yield 16 as a yellowish liquid (1.67 g, 51%); R = 0.57
f
treated with LiAlH (210 mg, 5.54 mmol) and the resulting mixture
4
was stirred at r.t. for 1.5 h. After cooling to 0 °C, it was treated with
aq 2 M H SO (50 mL). The aqueous phase was extracted with Et O
2
4
2
(
cyclohexane–Et O, 2:1).
2
(3 × 20 mL). The combined organic layers were washed with brine
(20 mL), dried (Na SO ) and concentrated. The crude product was
–
IR (ATR): 2950, 1717, 1625, 1606, 1294, 1177 cm .
1
2
4
purified by column chromatography on silica gel to give 10 as a col-
orless oil (350 mg, 66%); R = 0.23 (cyclohexane–Et O, 2:1); bp
1
H NMR (CDCl ): d = 1.93 (s, 3 H, CH ), 2.32 (d, J = 1.1 Hz, 3 H,
3
3
f
2
CH ), 3.71 (s, 3 H, OCH ), 5.23 (s, 1 H, H-5), 5.42 (s, 1 H, H-5),
3
3
1
10 °C/19 mbar.
5
.90 (q, J = 1.1 Hz, 1 H, H-2).
–
IR (ATR): 3348, 2925, 1380, 1000, 897 cm .
1
13
C NMR (75 MHz, CDCl ): d = 15.0, 20.6, 51.0, 115.7, 118.1,
3
1
H NMR (CDCl ): d = 1.81 (s, 3 H, CH ), 1.90 (s, 3 H, CH ), 2.89
3
144.1, 154.2, 167.7.
MS: m/z (%) = 140 (94, [M ]), 139 (90), 125 (100), 109 (77), 81
92), 79 (67).
Anal. Calcd for C H O : C, 68.55; H, 8.63. Found: C, 68.74; H,
3
3
(
(
1
s, 1 H, OH), 4.28 (s, 2 H, H-1), 5.07 (d, J = 10.9 Hz, 1 H, H-5), 5.23
d, J = 17.1 Hz, 1 H, H-5), 6.88 (dd, J = 17.1, 10.9 Hz, 1 H, H-4).
+
(
3
C NMR (75 MHz, CDCl ): d = 14.1, 17.9, 62.9, 113.4, 131.0,
3
8
12
2
1
33.5, 134.3.
MS: m/z (%) = 112 (39, [M ]), 97 (71), 94 (42), 83 (56), 79 (60), 77
40), 69 (28), 67 (27), 55 (74), 53 (36), 43 (90), 41 (100).
HRMS (EI): m/z calcd for C H O: 112.0888; found: 112.0888.
8
.56.
+
(
(E)-3,4-Dimethylpenta-2,4-dien-1-ol (17)
A mixture of 16 (701 mg, 5.0 mmol), Et O (30 mL), and LiAlH
(216 mg, 5.70 mmol) was stirred at r.t. for 1 h, then cooled to 0 °C,
and treated with aq 2 M H SO (50 mL). The aqueous phase was ex-
2
4
7
12
2
4
(Z)-2,3-Dimethylpenta-2,4-dienyl Methyl Carbonate (3a)
A mixture of 10 (561 mg, 5.0 mmol), CH Cl (5 mL), and pyridine
tracted with Et O (3 × 30 mL), the combined organic layers were
2
2
2
washed with brine (20 mL), dried (Na SO ), and concentrated. The
2
4
(
2.0 mL, 25.0 mmol) was cooled to 0 °C, treated with methyl chlo-
crude product was filtered over a column of silica gel to leave 17 as
a colorless liquid (315 mg, 56%), which was used without further
purification; R = 0.32 (cyclohexane–Et O, 1:1).
roformate (0.96 mL, 12.5 mmol), and stirred at for 2 h. MeOH (2
mL) and then aq 1 M HCl (30 mL) were added and the aqueous lay-
er was extracted with CH Cl (2 × 30 mL). The combined organic
f
2
2
2
–
IR (ATR): 3326, 2949, 1609, 1441, 1375, 1089 cm .
1
phases were washed with aq 1 M HCl (30 mL), brine (30 mL), and
dried (Na SO ). After evaporation of the solvent, the crude product
2
4
1
H NMR (CDCl ): d = 1.79 (s, 3 H, CH ), 1.89 (s, 3 H, CH ), 2.52
3
3
3
was purified by column chromatography on silica gel to yield 3a as
a colorless liquid (682 mg, 80%); R = 0.30 (cyclohexane–Et O,
(
(
1
s, 1 H, OH), 4.26 (d, J = 6.5 Hz, 2 H, H-1), 4.94 (s, 1 H, H-5), 5.05
s, 1 H, H-5), 5.72 (t, J = 6.5 Hz, 1 H, H-2).
f
2
9
:1).
3
C NMR (75 MHz, CDCl ): d = 13.7, 20.6, 59.7, 112.6, 126.2,
3
–
1
IR (ATR): 2960, 1746, 1442, 1253, 983 cm .
1
36.8, 143.9.
1
H NMR (CDCl ): d = 1.81 (s, 3 H, CH ), 1.85 (s, 3 H, CH ), 3.76
3
+
MS: m/z (%) = 112 (18, [M ]), 97 (43), 94 (56), 91 (25), 83 (76), 79
(
3
3
(s, 3 H, OCH ), 4.79 (s, 2 H, H-1), 5.11 (d, J = 10.9 Hz, 1 H, H-5),
3
100).
5
4
.24 (d, J = 17.1 Hz, 1 H, H-5), 6.86 (dd, J = 17.1, 10.9 Hz, 1 H, H-
).
(
E)-3,4-Dimethylpenta-2,4-dienyl Methyl Carbonate (14)
1
3
C NMR (75 MHz, CDCl ): d = 14.2, 17.8, 54.7, 67.8, 114.4,
3
A mixture of 17 (112 mg, 1.0 mmol), CH Cl (10 mL), pyridine
2 2
1
27.8, 133.7, 134.2, 155.9.
(0.32 mL, 4.0 mmol), and DMAP (25 mg, 0.2 mmol) was cooled to
0 °C and treated with methyl chloroformate (1.24 mL, 16.0 mmol).
The mixture was stirred at r.t. for 2 h, quenched with MeOH (2 mL),
+
MS: m/z (%) = 170 (20, [M ]), 111 (15), 95 (42), 94 (53), 79 (100).
Synthesis 2009, No. 16, 2778–2784 © Thieme Stuttgart · New York

2
782
R. Schobert, B. Barnickel
PAPER
+
MS: m/z (%) = 192 (3, [M ]), 190 (3, [M ]), 174 (5), 172 (5), 111
(27), 93 (33), 91 (48), 77 (25), 36 (100).
+
and treated with aq 1 M HCl (30 mL). The aqueous layer was ex-
tracted with CH Cl (2 × 30 mL), the combined organic phases were
2
2
washed with aq 1 M HCl (30 mL) and brine (30 mL), dried
Na SO ), and concentrated. Column chromatography (silica gel,
cyclohexane–Et O, 9:1) gave 14 as a colorless liquid (92 mg, 54%);
Anal. Calcd for C H BrO: C, 44.00; H, 5.80. Found: C, 43.76; H,
11
7
(
2
4
5
.55.
2
R = 0.40 (cyclohexane–Et O, 2:1).
f
2
(1E,3Z)-1-Bromo-5-(1¢-ethoxyethoxy)-3,4-dimethylpenta-1,3-
41
diene (22)
–
IR (ATR): 2956, 1744, 1611, 1442, 1373, 1248 cm .
1
1
A mixture of 21 (1.60 g, 8.35 mmol), ethyl vinyl ether (16 mL) and
PPTS (50 mg, 0.20 mmol) was stirred at r.t. for 2 h, then filtered
over a short plug of silica gel, which was washed with CH Cl (180
mL). Concentration of the combined filtrates and Kugelrohr distil-
lation of the residue (160 °C/0.13 mbar) yielded 22 as a yellow liq-
H NMR (CDCl ): d = 1.87 (s, 3 H, CH ), 1.90 (s, 3 H, CH ), 3.78
3
3
3
(
5
s, 3 H, OCH ), 4.80 (d, J = 6.8 Hz, 2 H, H-1), 5.00 (s, 1 H, H-5),
3
.12 (s, 1 H, H-5), 5.70 (t, J = 6.8 Hz, 1 H, H-2).
2
2
1
3
C NMR (75 MHz, CDCl ): d = 14.0, 20.6, 54.7, 65.2, 113.7,
3
1
20.2, 140.1, 143.7, 155.8.
uid (1.80 g, 82%); R = 0.63 (cyclohexane–EtOAc, 1:1).
f
+
MS: m/z (%) = 170 (21, [M ]), 111 (33), 95 (53), 94 (63), 91 (23),
IR (ATR): 2979, 2924, 1583, 1448, 1383, 1337, 1212, 1128, 1094,
1
7
9 (100), 77 (47).
–1
084 cm .
1
H NMR (CDCl ): d = 1.21 (dd, J = 7.1, 7.1 Hz, 3 H, H-4¢), 1.30 (d,
3
(
2Z,4E)-5-Bromo-2,3-dimethylpenta-2,4-dienoic Acid (20)
J = 5.4 Hz, 3 H, H-2¢), 1.76 (s, 3 H, CH ), 1.80 (s, 3 H, CH ), 3.48
3
3
BuLi (2.4 M in hexane, 11.77 mL, 28.0 mmol) was added at 0 °C to
a solution of hexamethyldisilazane (6.50 mL, 29.4 mmol) in THF
(
(
dq, J = 9.3, 7.1 Hz, 1 H, H-3¢a), 3.62 (dq, J = 9.3, 7.1 Hz, 1 H, H-
¢b), 4.09 (s, 2 H, H-1), 4.67 (q, J = 5.4 Hz, 1 H, H-1¢), 6.26 (d,
J = 13.5 Hz, 1 H, H-5), 7.19 (d, J = 13.5 Hz, 1 H, H-4).
3
120 mL). After stirring at r.t. for 1 h, the mixture was cooled to
47 °C and [Ph PCH Br]Br (6.72 g, 15.4 mmol) was added. The re-
–
3
2
1
3
sulting bright yellow suspension was stirred at –47 °C for 1 h, 7
1.78 g, 13.89 mmol) was added, and stirring was continued at
47 °C for 4 h and finally at r.t. for 16 h. Aq KHCO (100 mL, 10%
C NMR (75 MHz, CDCl ): d = 14.6, 15.3, 18.2, 19.7, 60.5, 64.8,
3
(
–
98.9, 106.2, 129.9, 132.3, 135.8.
3
MS: m/z (%) = 191 (3), 189 (3), 175 (16), 173 (16), 149 (8), 111
(22), 110 (19), 109 (23), 94 (42), 73 (100).
w/w) was added, the volatiles were removed under reduced pres-
sure, and the aqueous layer was washed with EtOAc (3 × 100 mL).
Anal. Calcd for C H BrO : C, 50.20; H, 7.28. Found: C, 50.36; H,
11 19
The combined organic layers were extracted with aq KHCO (2 ×
3
2
7
.18.
5
concd HCl. The product was extracted with Et O (3 × 100 mL), the
0 mL, 10%) and the combined aqueous layers were acidified with
2
(
lyl)penta-1,3-diene (23)
A solution of vinyl bromide 22 (1.74 g, 6.61 mmol) in THF (50 mL)
was cooled to –78 °C and slowly treated with t-BuLi (7.0 mL, 1.9
M, 13.3 mmol) via syringe/septa technique. The pink solution was
1E,3Z)-5-(1¢-Ethoxyethoxy)-3,4-dimethyl-1-(trimethylsi-
4
combined Et O layers were dried (Na SO ), and evaporated to dry-
2
2
4
2
ness. The crude product was dissolved in a minimum amount of
EtOAc, precipitated by the addition of pentane, filtered off after 3 d
at –20 °C, and washed with pentane (2 × 10 mL) to leave 20 as col-
orless crystals (2.05 g, 72%); mp 82 °C; R = 0.49 [cyclohexane–
f
stirred at this temperature for 30 min and then treated with Me SiCl
3
Et O (1:1) + 0.5% AcOH].
2
(
immediately turned colorless and was stirred for another hour be-
fore it was quenched with aq KHCO (30 mL, 10% w/w) and al-
3
2.10 mL, 16.53 mmol), freshly distilled from CaH . The solution
2
–
IR (ATR): 2870, 1676, 1627, 1576, 1410, 1292 cm .
1
1
H NMR (CDCl ): d = 1.94 (s, 3 H, CH ), 1.98 (s, 3 H, CH ), 6.63
3
3
3
(
d, J = 13.8 Hz, 1 H, H-5), 7.89 (d, J = 13.8 Hz, 1 H, H-4).
lowed to reach r.t. The aqueous layer was extracted with Et O (3 ×
2
1
3
30 mL), the combined organic phases were washed with brine (30
mL), dried (Na SO ), and concentrated to yield 23 (1.49 g, 88%) as
C NMR (75 MHz, CDCl ): d = 15.8, 16.3, 111.4, 125.7, 136.6,
3
2
4
1
41.0, 173.0.
a yellow liquid, which was used in the next step without purifica-
tion; R = 0.61 (cyclohexane–EtOAc, 4:1).
+
MS: m/z (%) = 205 (6, [M ]), 189 (9), 125 (100), 80 (17), 79 (16),
f
7
7 (19), 53 (13), 43 (34), 41(42).
IR (ATR): 2955, 2896, 1570, 1443, 1379, 1247, 1127, 1083, 1057,
–1
1029, 979, 865, 835, 731 cm .
HRMS (EI): m/z calcd for C H BrO : 205.9765; found: 205.9776.
2
7
9
1
H NMR (CDCl ): d = 0.08 [s, 9 H, Si(CH ) ], 1.21 (dd, J = 7.1, 7.1
3
3 3
(2Z,4E)-5-Bromo-2,3-dimethylpenta-2,4-dien-1-ol (21)
A solution of 20 (1.95 g, 9.50 mmol) in CH Cl (50 mL) was treated
Hz, 3 H, H-4¢), 1.32 (d, J = 5.3 Hz, 3 H, H-2¢), 1.80 (s, 3 H, CH3),
.86 (s, 3 H, CH ), 3.50 (dq, J = 9.4, 7.1 Hz, 1 H, H-3¢a), 3.65 (dq,
2
2
1
3
with oxalyl chloride (2.01 mL, 23.75 mmol) and the mixture was
stirred at r.t. for 1 h. All volatiles were removed under reduced pres-
sure and the oily residue was redissolved in Et O (75 mL). After ad-
J = 9.4, 7.1 Hz, 1 H, H-3¢b), 4.20 (s, 2 H, H-1), 4.70 (q, J = 5.3 Hz,
H, H-1¢), 5.85 (d, J = 18.9 Hz, 1 H, H-5), 7.06 (d, J = 18.9 Hz, 1
H, H-4).
1
2
dition of LiAlH (378 mg, 9.98 mmol), the mixture was stirred at r.t.
4
1
3
for another hour and finally quenched by the addition of aq 1 M
H SO (40 mL). The aqueous layer was extracted with Et O (3 × 30
C NMR (75 MHz, CDCl ): d = –1.2, 14.3, 15.3, 18.6, 19.7, 60.3,
3
64.7, 98.7, 128.4, 131.4, 133.0, 141.4.
2
4
2
mL), the combined organic phases were washed with brine (40 mL),
dried (Na SO ), and concentrated under reduced pressure. Column
MS: m/z (%) = 183 (4), 167 (4), 147 (3), 137 (4), 109 (5), 95 (7), 75
(
2
4
6), 73 (100).
chromatography (silica gel, cyclohexane–EtOAc, 3:1) gave alcohol
1 (1.59 g, 88%) as a yellowish liquid; R = 0.24 (cyclohexane–
EtOAc, 3:1).
2
f
(
2Z,4E)-2,3-Dimethyl-5-(trimethylsilyl)penta-2,4-dien-1-ol (24)
A mixture of 23 (1.49 g, 5.83 mmol) and TsOH·H O (100 mg, 0.53
2
–
IR (ATR): 3310, 2921, 1579, 1439, 1382, 1211 cm .
1
mmol) in THF–H O (10:1, 22 mL) was stirred at r.t. for 40 h. Aq
2
1
KHCO
(30 mL, 10% w/w) was added and the aqueous layer was
3
H NMR (CDCl ): d = 1.75 (s, 3 H, CH ), 1.81 (s, 3 H, CH ), 2.54
3
3
3
extracted with CH Cl (3 × 30 mL). The combined organic layers
2
2
(
(
1
s, 1 H, OH), 4.16 (s, 2 H, H-1), 6.26 (d, J = 13.6 Hz, 1 H, H-5), 7.18
d, J = 13.6 Hz, 1 H, H-4).
were dried, concentrated, and the residue purified by column chro-
matography on silica gel to leave 24 (1.02 g, 95%) as a yellow liq-
uid; R = 0.40 (cyclohexane–EtOAc, 4:1).
f
3
C NMR (75 MHz, CDCl ): d = 14.6, 17.7, 62.5, 106.3, 128.8,
3
1
34.7, 135.5.
Synthesis 2009, No. 16, 2778–2784 © Thieme Stuttgart · New York

PAPER
Tsuji–Trost Pentadienylation
2783
IR (ATR): 3364, 2954, 1738, 1365, 1247, 1217, 1162, 1056, 1014,
9
IR (ATR): 2940, 1755, 1435, 1379, 1353, 1262, 1215, 1161, 1088,
–1
1051, 994, 929, 840, 798, 667 cm .
–
79, 864, 834, 743 cm .
1
1
1
H NMR (CDCl ): d = 0.09 [s, 9 H, Si(CH ) ], 1.81 (s, 3 H, CH ),
3
H NMR (CDCl ): d = 1.74 (s, 3 H, CH ), 1.76 (s, 3 H, CH ), 2.55
3
3
3
3
3
3
1
J = 18.8 Hz, 1 H, H-5), 7.06 (d, J = 18.8 Hz, 1 H, H-4).
.90 (s, 3 H, CH ), 2.34 (s, 1 H, OH), 4.32 (s, 2 H, H-1), 5.88 (d,
(d, J = 7.6 Hz, 2 H, H-1¢), 2.67 (d, J = 13.6 Hz, 1 H, H-1¢¢a), 2.94
(d, J = 13.6 Hz, 1 H, H-1¢¢b), 4.32–4.36 (m, 2 H, H-5), 5.09 (d,
J = 10.9 Hz, 1 H, H-5¢¢), 5.13 (d, J = 10.0 Hz, 1 H, H-3¢), 5.15 (d,
J = 17.2 Hz, 1 H, H-3¢), 5.19 (d, J = 17.1 Hz, 1 H, H-5¢¢), 5.59 (ddt,
J = 17.2, 10.0, 7.6 Hz, 1 H, H-2¢), 6.75 (dd, J = 17.1, 10.9 Hz, 1 H,
H-4¢¢).
3
1
3
C NMR (75 MHz, CDCl ): d = –1.1, 14.3, 18.2, 62.7, 128.9,
3
1
32.1, 134.0, 140.9.
+
MS: m/z (%) = 184 (25, [M ]), 169 (33), 111 (11), 94 (8), 75 (90),
7
3 (100).
1
3
C NMR (75 MHz, CDCl ): d = 14.2, 21.0, 39.6, 40.2, 53.8, 73.4,
3
HRMS (EI): m/z calcd for C H OSi: 184.1283; found: 184.1322.
1
0
20
113.8, 121.3, 127.3, 130.2, 132.9, 134.4, 176.2, 210.0.
+
MS: m/z (%) = 234 (17, [M ]), 205 (4), 193 (7), 176 (20), 113 (7),
(2Z,4E)-2,3-Dimethyl-5-(trimethylsilyl)penta-2,4-dienylMethyl
Carbonate (18)
Analogous to the synthesis of carbonate 3a, compound 18 (1.13 g,
9
3 (36), 77 (35), 67 (83), 55 (100).
Anal. Calcd for C H O : C, 71.77; H, 7.74. Found: C, 71.56; H,
1
4
18
3
84%) was obtained from 24 (1.02 g, 5.53 mmol) as a yellow oil;
Rf = 0.51 (cyclohexane–EtOAc, 4:1).
7.52.
–
IR (ATR): 2956, 1748, 1442, 1373, 1247, 977 cm .
1
(Z)-3-Allyl-3-(3,4-dimethylpenta-2,4-dienyl)furan-2,4(5H)-di-
2
one (11)
1
H NMR (CDCl ): d = 0.08 [s, 9 H, Si(CH ) ], 1.80 (s, 3 H, CH ),
3
3
3
3
Analogous to the synthesis of 25, compound 11 (114 mg, 22%) was
obtained from 3a (354 mg, 2.20 mmol) and 2 (360 mg, 2.22 mmol)
as a colorless oil after column chromatography on silica gel; R =
1.84 (s, 3 H, CH ), 3.76 (s, 3 H, OCH ), 4.83 (s, 2 H, H-1), 5.91 (d,
3 3
J = 18.7 Hz, 1 H, H-5), 7.02 (d, J = 18.7 Hz, 1 H, H-4).
f
1
3
0.14 (cyclohexane–Et O, 95:5).
2
C NMR (75 MHz, CDCl ): d = –1.2, 14.5, 18.1, 54.7, 67.7, 128.1,
3
1
30.1, 134.8, 140.8, 155.9.
–1
IR (ATR): 2933, 1804, 1758, 1437, 1344, 1217 cm .
+
MS: m/z (%) = 242 (29, [M ]), 153 (7), 146 (16), 94 (100), 91 (94),
1
H NMR (CDCl ): d = 1.78 (s, 3 H, CH ), 1.82 (s, 3 H, CH ), 2.55
3
3
3
7
7 (38).
(
2
d, J = 7.5 Hz, 2 H, H-1¢), 2.62 (dd, J = 13.8, 7.5 Hz, 1 H, H-1¢¢a),
.71 (dd, J = 13.8, 8.7 Hz, 1 H, H-1¢¢b), 4.30 (d, J = 17.2 Hz, 1 H,
H-5a), 4.37 (d, J = 17.2 Hz, 1 H, H-5b), 4.95 (s, 1 H, H-5¢¢), 5.03 (s,
H, H-5¢¢), 5.15 (d, J = 9.9 Hz, 1 H, H-3¢), 5.16 (d, J = 17.1 Hz, 1
Anal. Calcd for C H O Si: C, 59.46; H, 9.15. Found: C, 59.33; H,
22
8
12
3
.98.
1
H, H-3¢), 5.39 (dd, J = 8.7, 7.5 Hz, 1 H, H-2¢¢), 5.64 (ddt, J = 17.1,
9.9, 7.5 Hz, 1 H, H-2¢).
3-Allyl-3-[(2¢Z,4¢E)-2¢,3¢-dimethyl-5¢-(trimethylsilyl)penta-2¢,4¢-
2
dienyl]furan(5H)-2,4-dione (25)
A suspension of sodium allyltetronate (2; 163 mg, 1.0 mmol) in
THF (10 mL) was treated with MeOH until a clear solution was ob-
tained (ca. 3 mL). Carbonate 18 (271 mg, 1.06 mmol) dissolved in
THF (4 mL) and Pd(Ph ) (58 mg, 5 mol%) were added and the mix-
ture was stirred at r.t. until complete consumption of 18 (GC con-
trol). Filtration over a plug of silica gel, washing of the latter with
13
C NMR (75 MHz, CDCl ): d = 13.8, 20.8, 34.5, 38.9, 54.2, 73.3,
3
1
13.4, 118.0, 121.2, 130.1, 140.4, 143.7, 176.0, 210.3.
+
MS: m/z (%) = 234 (5, [M ]), 219 (11), 201 (6), 193 (10), 175 (10),
3
4
1
9
47 (8), 139 (10), 133 (13), 122 (20), 121 (89), 114 (74), 107 (57),
6 (28), 95 (100).
Et O (60 mL), concentration of the combined filtrates, and column
2
HRMS (EI): m/z calcd for C H O : 234.1256; found: 234.1251.
14 18 3
chromatography of the residue on silica gel yielded 25 as a colorless
oil (175 mg, 54%); R = 0.09 (cyclohexane–Et O, 95:5).
3-Spiro[2¢-(1¢,3¢,3a¢,4¢,5¢,7a¢-hexahydro-6¢,7¢-dimethyl)inde-
nyl]furan-(5H)-2,4-dione (26)
f
2
–
IR (ATR): 2924, 2853, 1760, 1465, 1260, 1092 cm .
1
A mixture of 11 (71 mg, 0.30 mmol), toluene (15 mL), and BHT (10
mg, 0.05 mmol) was sealed in a 20 mL bomb tube and heated at
190 °C for 25 h. The solvent was removed and the crude product
was purified by column chromatography (silica gel, cyclohexane–
1
H NMR (CDCl ): d = 0.12 [s, 9 H, Si(CH ) ], 1.72 (s, 3 H, CH ),
3
3
3
3
1
.77 (s, 3 H, CH ), 2.54 (d, J = 7.4 Hz, 2 H, H-1¢), 2.65 (d, J = 13.7
3
Hz, 1 H, H-1¢¢a), 3.00 (d, J = 13.7 Hz, 1 H, H-1¢¢b), 4.25 (d, J = 17.1
Hz, 1 H, H-5a), 4.32 (d, J = 17.1 Hz, 1 H, H-5b), 5.11 (d, J = 10.1
Hz, 1 H, H-3¢), 5.14 (d, J = 17.0 Hz, 1 H, H-3¢), 5.60 (ddt, J = 17.0,
Et O, 2:1) to yield an inseparable crystalline 6:6:1:1 mixture (GC)
2
of unassigned stereoisomers of 26 (69 mg, 97%); R = 0.26 (cyclo-
f
10.1, 7.4 Hz, 1 H, H-2¢), 5.83 (d, J = 18.7 Hz, 1 H, H-5¢¢), 6.89 (d,
J = 18.7 Hz, 1 H, H-4¢¢).
hexane–Et O, 2:1).
2
IR (ATR): 2924, 1799, 1753, 1437, 1338, 1260, 1091, 1048, 798,
–1
747 cm .
1
3
C NMR (75 MHz, CDCl ): d = –1.3, 14.3, 21.6, 39.4, 40.1, 53.7,
3
7
3.4, 121.1, 127.7, 129.2, 130.2, 133.9, 141.1, 176.1, 209.6.
1
H NMR (CDCl ): d = 1.56–1.62 (m, 6 H), 1.64–2.40 (m, 10 H),
3
+
MS: m/z (%) = 306 (5, [M ]), 265 (13), 213 (5), 197 (12), 181 (11),
4
.60 (d, J = 16.9 Hz, 1 H, H-5a), 4.68 (d, J = 16.9 Hz, 1 H, H-5b).
1
75 (8), 151 (9), 107 (9), 75 (40), 73 (100).
1
3
C NMR (75 MHz CDCl ): d = 15.80, 15.85, 18.5, 27.1, 27.2, 33.6,
3
HRMS (EI): m/z calcd for C H O Si: 306.1651; found: 306.1657.
1
7
26
3
33.7, 38.8, 39.3, 40.8, 41.3, 44.2, 44.4, 48.7, 48.8, 51.6, 71.9, 72.3,
1
26.3, 126.4, 127.4, 127.5, 178.8, 210.6.
(
Z)-3-Allyl-3-(2¢,3¢-dimethylpenta-2¢,4¢-dienyl)furan-(5H)-2,4-
dione (4)
+
MS: m/z (%) = 234 (14, [M ]), 219 (4), 121 (97), 114 (100), 107
(
31), 105 (39), 95 (43), 93 (19), 91 (18), 79 (16), 77 (15).
A solution of 25 (34 mg, 0.11 mmol) in CH Cl (5 mL) was treated
2
2
with TFA (0.02 mL, 0.24 mmol) and the mixture was stirred at r.t.
for 75 min. Aq KHCO (30 mL, 10% w/w) was added, the aqueous
HRMS (EI): m/z calcd for C H O : 234.1256; found: 234.1253.
18
1
4
3
3
layer was extracted with CH Cl (3 × 30 mL), and the combined or-
2
2
Acknowledgment
ganic phases were washed with brine (30 mL), dried (Na SO ) and
2
4
concentrated under reduced pressure to give 4 as a yellow oil (23
mg, 91%); R = 0.40 (cyclohexane–EtOAc, 4:1).
This work was supported by a grant from the Deutsche Forschungs-
gemeinschaft (Scho 402/9-1).
f
Synthesis 2009, No. 16, 2778–2784 © Thieme Stuttgart · New York

2
784
R. Schobert, B. Barnickel
PAPER
References
(16) Faller, J. W.; Sarantopoulos, N. Organometallics 2004, 23,
2179.
(
(
1) (a) Tsuji, J. Palladium Reagents and Catalysis; Wiley: New
York, 1995. (b) Tsuji, J. In Handbook of Organopalladium
Chemistry for Organic Synthesis, Vol. 2; Negishi, E., Ed.;
Wiley: New York, 2002, Chap. V2.1. (c) Lu, Z.; Ma, S. M.
Angew. Chem. Int. Ed. 2008, 47, 258.
(
(
17) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1996, 118, 235.
18) Fristrup, P.; Jensen, T.; Hoppe, J.; Norrby, P. O. Chem. Eur.
J. 2006, 12, 5352.
(19) Hayashi, T.; Kawatsura, M.; Uozumi, Y. J. Am. Chem. Soc.
1998, 120, 1681.
2) (a) Schobert, R.; Urbina-Gonzalez, J. M. Tetrahedron Lett.
(
(
20) Pretot, R.; Pfaltz, A. Angew. Chem. Int. Ed. 1998, 37, 323.
21) Shimizu, I.; Matsumoto, Y.; Nishikawa, M.; Kawahara, T.;
Satake, A.; Yamamoto, A. Chem. Lett. 1998, 983.
2
005, 46, 3657. For a similar reaction, see: (b) Prat, M.;
Moreno-Mañas, M.; Ribas, J. Tetrahedron 1988, 44, 7205.
c) Moreno-Mañas, M.; Prat, M.; Ribas, J.; Virgili, A.
(
(22) Kang, S. K.; Park, D. C.; Jeon, J. H.; Rho, H. S.; Yu, C. M.
Tetrahedron Lett. 1994, 35, 2357.
(23) Trost, B. M.; Urch, C. J.; Hung, M. H. Tetrahedron Lett.
(
Tetrahedron Lett. 1988, 29, 581.
3) Evans, D. A.; Sims, C. L.; Andrews, G. C. J. Am. Chem. Soc.
(
(
(
(
(
(
(
1977, 99, 5453.
1986, 27, 4949.
4) Greene, A. E.; Coelho, F.; Depres, J. P.; Brocksom, T. J.
Tetrahedron Lett. 1988, 29, 5661.
5) Ferraz, H. M. C.; Vieira, T. O.; Silva, L. F. Jr. Synthesis
24) Trost, B. M.; Lautens, M.; Hung, M. H.; Carmichael, C. S.
J. Am. Chem. Soc. 1984, 106, 7641.
25) Trost, B. M.; Bunt, R. C. J. Am. Chem. Soc. 1998, 120, 70.
26) Nilsson, Y. I.; Andersson, P. G.; Bäckvall, J. E. J. Am. Chem.
Soc. 1993, 115, 6609.
27) Baumann, M. E.; Bosshard, H.; Breitenstein, W.; Rihs, G.;
Winkler, T. Helv. Chim. Acta 1984, 67, 1897.
28) Harrison, T.; Myers, P. L.; Pattenden, G. Tetrahedron 1989,
(
(
2
006, 2748.
6) Back, T. G.; Nava-Salgado, V. O.; Payne, J. E. J. Org. Chem.
001, 66, 4361.
2
(
(
(
(
(
(
(
7) Jamieson, G. R.; Reid, E. H.; Turner, B. P.; Jamieson, A. T.
Phytochemistry 1976, 15, 1713.
8) Kano, K.; Hayashi, K.; Mitsuhashi, H. Chem. Pharm. Bull.
4
5, 5247.
29) Inoue, M.; Sato, T.; Hirama, M. Angew. Chem. Int. Ed. 2006,
5, 4843.
1
982, 30, 1198.
9) Nawrot, J.; Harmatha, J.; Novotny, L. Biochem. Syst. Ecol.
984, 12, 99.
4
1
30) Parmee, E. R.; Steel, P. G.; Thomas, E. J. J. Chem. Soc.,
Chem. Commun. 1989, 1250.
31) Alhakim, A. H.; Haines, A. H. Tetrahedron Lett. 1982, 23,
(
(
(
10) Abe, N.; Onoda, R.; Shirahata, K.; Kato, T.; Woods, M. C.;
Kitahara, Y. Tetrahedron Lett. 1968, 9, 369.
11) Naya, K.; Takagi, I.; Hayashi, M.; Nakamura, S.; Kobayashi,
M.; Katsumura, S. Chem. Ind. (London) 1968, 318.
12) (a) Löffler, J.; Schobert, R. J. Chem. Soc., Perkin Trans. 1
5
295.
32) Villeneuve, G. B.; Chan, T. H. Tetrahedron Lett. 1997, 38,
489.
6
1996, 2799. (b) Schobert, R.; Gordon, G. J.; Mullen, G.;
Stehle, R. Tetrahedron Lett. 2004, 45, 1121.
33) Ley, S. V.; Somovilla, A. A.; Broughton, H. B.; Craig, D.;
Slawin, A. M.; Toogood, P. L.; Williams, D. J. Tetrahedron
(
13) (a) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1980,
102, 4730. (b) Trost, B. M.; Hung, M. H. J. Am. Chem. Soc.
1
989, 45, 2143.
(
34) Hirao, T.; Enda, J.; Ohshiro, Y.; Agawa, T. Tetrahedron
Lett. 1981, 22, 3079.
1984, 106, 6837. (c) Yamamoto, K.; Deguchi, R.; Ogimura,
Y.; Tsuji, J. Chem. Lett. 1984, 1657. (d) Takahashi, T.;
Jinbo, Y.; Kitamura, K.; Tsuji, J. Tetrahedron Lett. 1984, 25,
(
(
35) Tsuji, J. Pure Appl. Chem. 1989, 61, 1673.
36) (a) Szabó, K. J. Chem. Soc. Rev. 2001, 30, 136.
5921. (e) Hayashi, T.; Yamamoto, A.; Hagihara, T. J. Org.
(b) Branchadell, V.; Moreno-Mañas, M.; Pleixats, R.
Chem. 1986, 51, 723. (f) Granberg, K. L.; Bäckvall, J. E.
J. Am. Chem. Soc. 1992, 114, 6858. (g) Dvorak, D.; Stary,
I.; Kocovsky, P. J. Am. Chem. Soc. 1995, 117, 6130.
Organometallics 2002, 21, 2407. (c) Branchadell, V.;
Moreno-Mañas, M.; Pleixats, R.; Thorimbert, S.;
Commandeur, C.; Boglio, C.; Malacria, M. J. Organomet.
Chem. 2003, 687, 337. (d) Commandeur, C.; Thorimbert,
S.; Malacria, M. J. Org. Chem. 2003, 68, 5588.
(
h) Hayashi, T.; Yamane, M.; Ohno, A. J. Org. Chem. 1997,
2, 204.
14) (a) Mohr, J. T.; Stoltz, B. M. Chem. Asian J. 2007, 2, 1476.
b) Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Angew. Chem.
6
(
(
(
(
37) Wolinsky, J.; Erickson, K. L. J. Org. Chem. 1965, 30, 2208.
38) Lawrence, N. J.; Muhammad, F. Tetrahedron 1998, 54,
(
Int. Ed. 2005, 44, 4442. (c) Michelet, V.; Genêt, J. P.;
Savignac, M. In Handbook of Organopalladium Chemistry
for Organic Synthesis, Vol. 2; Negishi, E., Ed.; Wiley: New
York, 2002, Chap. V.2.6. (d) Trost, B. M.; Crawley, M. L.
Chem. Rev. 2003, 103, 2921.
1
5361.
39) Salmond, W. G.; Barta, M. A.; Havens, J. L. J. Org. Chem.
978, 43, 790.
(
(
(
(
1
40) Maryanoff, B. E.; Reitz, A. B.; Duhlemswiler, B. A. J. Am.
Chem. Soc. 1985, 107, 217.
41) Fukuzawa, A.; Sato, H.; Masamune, T. Tetrahedron Lett.
15) (a) Lloyd-Jones, G. C.; Stephen, S. C. Chem. Eur. J. 1998, 4,
2539. (b) Gouriou, L.; Lloyd-Jones, G. C.; Vyskocil, S.;
Kocovsky, P. J. Organomet. Chem. 2003, 687, 525.
1987, 28, 4303.
42) Neumann, H.; Seebach, D. Chem. Ber. 1978, 111, 2785.
Synthesis 2009, No. 16, 2778–2784 © Thieme Stuttgart · New York