Efficient homologation of aldehydes to 2,4,6-alkatrienals by means of an α-(1,3-dioxenylallyl)boronate

Article abstract of DOI:10.1055/s-2000-8720

The α-dioxenyl-allylboronate 4 allows the direct conversion of aldehydes into the 7-hydroxy-2,4-dienals (6). The latter compounds can be dehydrated to 2,4,6-alkatrienals 7 by means of the Burgess reagent or methanesulfonyl anhydride/Hunig Base.

Full text of DOI:10.1055/s-2000-8720

2060
PAPER
Efficient Homologation of Aldehydes to 2,4,6-Alkatrienals by means of an
a-(1,3-Dioxenylallyl)boronate
Reinhard W. Hoffmann,* Frank Schäfer, Eckart Haeberlin, Thorsten Rohde, Karsten Körber
Fachbereich Chemie der Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany
Fax +49(0)6421288917; E-mail: rwho@ps1515.chemie.uni-marburg.de
Received 19 June 2000; revised 24 August 2000
OH
O
O
Abstract: The a-dioxenyl-allylboronate 4 allows the direct conver-
sion of aldehydes into the 7-hydroxy-2,4-dienals (6). The latter
compounds can be dehydrated to 2,4,6-alkatrienals 7 by means of
the Burgess reagent or methanesulfonyl anhydride/Hünig Base.
O
O
O
B
+
R
R
O
Key words: allylboration reaction, polyenals
4
5
7
O
OH
O
O
Intensive efforts have been devoted in recent years to the
synthesis of the polyene-macrolide antibiotics1 such as
amphotericin 1. In this context several strategies evolved
to generate 1,3,5-polyol sequences in a highly stereoselec-
tive manner.1,2 Yet, the synthesis of the polyene segment
of 1 and related compounds is by no means routine.
R
R
6
Scheme 1
Hitherto, mostly Wittig/Horner reagents have been ap-
plied to the synthesis of the polyene part of the polyene
macrolides, allowing the introduction of four to six double
bonds at one time. Alternatively, iterative processes have
been applied with reagents that introduce three or two
double bonds at a time (Table 1). Thus, the synthesis of
triene esters generally relies on the homologation of alde-
hydes with the Wittig/Horner reagents 2 and 3.12,13 When
trienals are desired, the reagents shown in Table 2 involv-
ing those of the Wittig/Horner type14,15 or vinylmetal spe-
cies developed by Wollenberg,16 Duhamel17 and Suzuki9
are employed. For recent aldol-type homologation reac-
tions see ref.18,19
HO
TosO
KOtBu
O
O
O
O
O
O
TosCl
Py
8
83 %
9
+
+
OH
O
OTos
O
O
tBuLi
Et2O
O
O
O
O
Li
O
B
B
10
Cl
Et2O
O
O
O
92 %
4
We were interested in testing whether an aldehyde/trienal
homologation can be developed on the basis of the allylb-
oration reaction. We envisaged the use of the allylbor-
onate 4,23 which carries a dioxenyl unit at the a-position
as a latent enal function (Scheme 1).24 Reaction of 4 with
an aldehyde should generate the chain extended dioxene
5. Funk has shown that dioxenes can thermally be cleaved
to enals.24 Hence, heating of 5 should give rise to the hy-
droxy-dienal 6. In order to complete the synthesis of trie-
nal 7, water is to be eliminated in a concluding step. In the
following we describe our efforts to realize this plan.
O
Scheme 2
1,3-Dioxene (9) is generally prepared from commercial
glycerolformal by tosylation, selective crystallization of
the tosylate 8, and subsequent base-induced elimination
(Scheme 2).25,26 The yield of the dioxene 9 could be im-
proved to over 80% by carrying out the elimination reac-
tion with potassium tert-butoxide in triethyleneglycol.
The dioxene 9 was lithiated24 at -78 °C with either sec-
butyl- or tert-butyllithium in diethyl ether, a solvent,
which allowed for a clean reaction with the a-chloroallyl-
boronate 1027 to give the desired reagent 4 in 92% yield.
Reagent 4 was obtained as a diastereomeric mixture. The
diastereomers may be separated by chromatography, but
this is not necessary in the present context.
OH
OH
O
OH
H
HO
O
OH
OH
OH
OH
O
COOR
The reaction of the allylboronate 4 with aldehydes pro-
ceeded readily at room temperature in petroleum ether as
solvent. Thus, reaction with benzaldehyde generated a 2:1
Osugar
Amphotericin B
1
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Efficient Homologation of Aldehydes to 2,4,6-Alkatrienals by means of an a-(1,3-Dioxenylallyl)boronate
2061
Table 1 Representative Polyene Syntheses
Transformation
Reagent
References
COOEt
(EtO)2(O)P
COOEt
3
R
O
R
COOEt
COOEt
4
R
R
O
O
R
R
(EtO)2(O)P
COOEt
COOEt
5,6
2
(EtO)2(O)P
COOEt
"
7
R
R
O
O
3
Ph3P
Li
O
OEt
5,8
R
O
9
R
R
O
R
R
Cp2Zr(Cl)
OMe
SiMe3
ZnX
COOEt
10
Br
Li
11
R
O
R
OMe
O
Table 2 Common Reagents for the Conversion of Aldehydes into
Alkatrienals
mixture (92%) of the homoallylic alcohols (E)-11a and
(Z)-11a Likewise, reaction with isobutyraldehyde fur-
nished a 1.7:1 mixture of (E)-11b and (Z)-11b (94%). Re-
action with crotonaldehyde provided 91% of a 2:1 mixture
of (E)-11c and (Z)-11c (Scheme 3).
R
Reagent
O
O
R
O
Ref.
Yield (%)
The geometric isomers of 11 may be separated by flash
chromatography, but this is not necessary in the present
context. On heating in toluene under reflux the dioxene
ring of 11 undergoes cyclo-reversion with loss of formal-
dehyde. The hydroxy-dienals (E,E)-6 and (Z,E)-6 were
formed with retention of the olefin geometry present in
the precursor molecules (E)-11 and (Z)-11. The double
bond generated by the cyclo-reversion has uniform E-geo-
metry.24 The (E,E)- and (Z,E)-isomers are readily distin-
guished by the characteristic 13C NMR-signals, (E,E):
193, 152, 143, 130, 130 ppm; (Z,E): 193, 146, 139, 132,
128 ppm.
O
14
P
65 - 70
35 - 75
35 - 75
O
(EtO)2
20
Ph3P
Li
O
15,21
OEt
OEt
21
22
65 - 90
70 - 90
Li
OEt
Me3Si
In view of the desired synthesis of all-(E)-trienals, an
isomerization of (Z,E)-isomers to the (E,E)-isomers had to
be accomplished. This was attained most readily by treat-
ment with a small quantity of iodine for 30 minutes in tol-
uene at room temperature (Scheme 4).
N
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

2062
R. W. Hoffmann et al.
PAPER
Table 3 One Pot Conversion of Aldehydes into Hydroxydienals
OH
O
OH
O
O
OH
4
O
R
+
R
R
Toluene
2d, r.t.
R
R
O
R =
Ph
O
E-11
Z-11
a
b
c
d
O
Me2CH
Me-CH=CH-
Ph-(CH=CH)3-
R =
Ph-
Yield (%)
Toluene, Rf.
O
TBDMSO
e
92
90
OH
OH
Me2CH-
R
R
95
82
35
80
40
Me-CH=CH-
OH
E,E-6
Z,E-6
93 %
91 %
O
Scheme 3
OH
Ph
a)
a)
b)
OH
OH
Ph
cat. I2
O
TBDMSO
93
Benzene, r.t.
O
Z,E-6c
E,E-6c
aThe products are contaminated with pinacol, which could not be
removed by simple chromatography.
Scheme 4
b6:1 syn/anti-mixture
O
O
OH
R
80 - 95 %
R
When the starting aldehyde for the preparation of the hy-
droxydienals is chiral, asymmetric induction from the ste-
reogenic centers resident in the aldehyde may lead to high
diastereoselectivities in the formation of the new stereo-
genic center. This is demonstrated by the last entry in Ta-
ble 3. If the diastereoselectivity reached in this manner is
not high enough, asymmetric induction could be assisted
by use of an enantiomerically pure reagent 4. Its synthesis
would not be a problem, since the required enantiomeri-
cally pure a-chloroallylboronates are readily accessible.31
aq. Na2S2O3
E,E-6
4
O
O
B
B
O
O
O
O
O
O
O
R
R
O
B
The hydroxydienals 6 are by themselves of interest in nat-
ural product synthesis. There are several natural products
such as 12,28 and 13,29 which contain partial structures that
can obviously be derived from hydroxydienals. More-
over, all members of the leukomycin class of macrolide
antibiotics 30 contain a substructure 14 that can be access-
ed via hydroxydienals.
110 o
C
I2
O
O
O
R
Scheme 5
Based on these findings the following one-pot procedure
for the conversion of aldehydes into (E,E)-hydroxydienals
was established: First, the allylboration of the aldehydes
was carried out in toluene, then the reaction mixture was
heated to reflux in order to effect the cyclo-reversion, and
finally a small quantity of iodine was added to achieve the
Z/E-isomerization. The iodine was ultimately removed by
a Na2S2O3-wash on workup (Scheme 5). The one-pot
transformation of aldehydes to the hydroxy-dienals 6
could thus be attained in up to 90% yield. Examples are
given in Table 3.
OH
O
OH
OH
12
OH
O
O
O
13
14
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Efficient Homologation of Aldehydes to 2,4,6-Alkatrienals by means of an a-(1,3-Dioxenylallyl)boronate
2063
Table 4 Dehydration of Hydroxydienals to Trienals
Table 5 Dehydration of Hydroxydienals to Trienals
OH
OH
R
Ph
O
O
R
O
O
Ph
7
7a
Solvent Temp. (oC) Yield (%)
6
6a
a)
Reagent
Reference
33
R =
Method
B
Yield (%)
85
CuSO4, SiO2
CCl4
76
≈20
a
b
Ph
-
PyH+ Cl
A
B
80
90
Me2CH
110
34
35
36
37
Toluene
CHCl3
40 - 60
50 - 80
50 - 70
20 - 75
B
82
c
d
Me-CH=CH-
P2O5, SiO2
56
40
80
B
40
Martins sulfurane
Burgess Reagent
CH2Cl2
Benzene
Ph
TBDMSO
A
80
e
Polymer supported
Burgess Reagent
38
Benzene
CH2Cl2
80
25
≈50
aMethod A: Burgess-reagent, benzene, reflux; Method B: methane-
sulfonyl anhydride, ethyl-diisopropylamine, CH2Cl2, reflux
(MeSO2)2O,
Hünig-Base
75 - 90
4
OH
OH
O
120 o
C
0.25 eq I2
O
Toluene
R
O
(MeSO2)2O
O
74%
17
Hünig-Base
15
Scheme 7
R
80 %
78 %
16
a
b
R =
Ph-
CH3-CH=CH-
Scheme 6
O
B
O
O
O
O
DBU
The dehydration of the hydroxy-dienals 6 to the trienals 7
appeared to be a straightforward transformation. Never-
theless, many common methods failed completely, such
as SOCl2/pyridine, POCl3/pyridine, tosyl chloride/pyri-
dine, CCl4/triphosphine, triphenylphosphine/diethyl azo-
dicarboxylate.32 The methods by which we could success-
fully achieve the desired dehydration are listed in Table 4.
R
R
Toluene
25 °C
18
7
20 - 60 %
Scheme 8
Some of these methods were, however, unreliable, when While the two-stage operation, conversion of an aldehyde
reproducibility or scaleup were addressed.
to a hydroxydienal 6 and separate elimination of water is
a viable route to the desired trienals, we nevertheless test-
ed whether a true one-pot procedure is possible. For in-
stance, in the reaction of crotonaldehyde with 4 the
tetraenal 17 was obtained directly in 74% yield, when
0.25 equivalents of iodine were used to effect Z/E-isomer-
ization. Probably adventitious hydrogen iodide induced
the conversion of the intermediate hydroxydienal to the
tetraenal 17 (Scheme 7). This method worked, however,
only with a,b-unsaturated aldehydes.
Eventually the Burgess reagent33 (method A) and meth-
anesulfonyl anhydride/Hünig base (method B, for a relat-
ed method see ref.19) were applied to the dehydration of a
series of hydroxydienals (Table 5). With simple hydroxy-
dienals yields in the order of ≥ 80% are frequently at-
tained.
The reaction leading to hexa- and heptadienals was less
clean, partly because the starting hydroxy-dienals were
contaminated with residual pinacol, which appeared to in-
terfere with the elimination reaction. The hexa- and hep-
taenals 16 could be obtained in somewhat better yields by
a simultaneous elimination of two equivalents of water
from the dihydroxy-polyenals 15 (Scheme 6).
For other aldehydes, we explored a route by which the
mixed borate ester 18 was subjected to treatment with
base. After addition of DBU to the crude E/Z-mixture
of 18, stirring overnight at room temperature led indeed
directly to the desired trienals 7 (Scheme 8). However, as
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

2064
R. W. Hoffmann et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 21.6, 68.6, 70.6, 93.4, 127.8,
130.0, 145.2.
Table 6 One Pot Conversion of Aldehydes into Trienals by
Sequential Reaction with 4, Heating and Treatment with DBU
Anal. Calcd for C11H14O5S (258.3): C, 51.15; H, 5.46. Found: C,
51.03; H, 5.44.
O
one-pot
R
R
O
1,3-Dioxene (9)
KOH (98.0 g, 1.75 mol) was suspended in triethylene glycol (600
mL) and stirred at 100 °C until a homogenous solution was ob-
tained. The mixture was allowed cool to 50 °C and 5-tosyloxy-1,3-
dioxane (8) (180 g, 0.70 mol) was added in one portion. The result-
ing mixture was heated slowly to 200 °C under stirring, the H2O and
dioxene formed were condensed in a cold trap (0 °C). n-Decane
(100 mL) was added to the condensate, the phases were separated
and the aqueous phase was extracted with n-decane (2 ¥ 30 mL).
The combined organic phases were dried (MgSO4) and the product
9 was carefully distilled from the decane solution. The crude diox-
ene was once more distilled at slightly reduced pressure from a bath
of 40-50 °C into a trap cooled with liquid N2 to give 9 (49.9 g, 83%)
as a colorless liquid. Compound 9 (Lit.26 bp: 78 °C) was stored over
solid K2CO3 in a refrigerator.
R =
Ph-
Yield (%)
32
60
53
Me2CH-
Me2C=CH-
TBDMSO
20
1H NMR (200 MHz, CCl4): d = 4.13 (dd, 2H, J = 2.5, 1.9 Hz), 4.79
(dt, 1H, J = 6.4, 2.6 Hz), 4.94 (s, 2H), 6.45 (dt, 1H, J = 6.4, 1.9 Hz).
the data in Table 6 show, the yields remained inferior to
the two stage reaction sequence described above.
The 1H NMR data correspond to those given in ref.26
13C NMR (75 MHz, CDCl3): d = 64.6, 90.5, 102.7, 143.6.
In conclusion, the reagent 4 was found to convert a variety
of aldehydes to hydroxydienals 6 in yields which reach
90%. Dehydration of the latter may be effected with the
Burgess-reagent or more reliably with methanesulfonyl 2-[1-(1,3-Diox-4-en-6-yl)-2-propenyl]-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane (4)
A solution of t-BuLi in pentane (1.7 N, 1.47 mL, 2.50 mmol) was
anhydride/Hünig base to generate the fully conjugated
trienals 7 in yields around 80%. Therefore, the overall ef-
added at -78 °C into a solution of 1,3-dioxene (9) (215 mg, 2.50
ficiency of converting aldehydes to trienals with the meth-
mmol) in anhyd Et2O (5 mL) under a N2 atm. After stirring for 15
od described here is equivalent to or slightly better than
min, a pre-cooled (-78 °C) solution of 2-(1-chloroprop-2-enyl)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (10)27 (506 mg, 2.50
mmol) in anhyd Et2O (5 mL) was added via cannula. Stirring was
continued for 20 min at -78 °C. After the mixture reached r.t., Et2O
(20 mL) was added. The mixture was extracted quickly with sat.
NaHCO3 (5 mL), the phases were separated, and the organic phase
was dried (MgSO4). The solution was concentrated in vacuo and the
residue was filtered through a 4 cm layer of silica gel with petro-
leum ether/Et2O (3:1), containing 1% Et3N to furnish the product 4
(580 mg, 92%) as an approx. 1:1 mixture of diastereomers. The di-
astereomers may be separated by MPLC with petroleum ether/
EtOAc (9:1). The stereostructures of the diastereomers have not
been assigned.
the methods used previously, see Table 2. The advantage
is that some of the necessary steps are transferred to the
synthesis of the reagent 4 giving the syntheses of poly-
enals a higher level of convergency. Our method has since
been successfully applied to a synthesis of phenalamide
34
A2.
1
All temperatures quoted are uncorrected. H NMR, 13C NMR:
Bruker ARX200, AC-300, and AMX-500. Boiling range of petro-
leum ether: 40-60 °C. Flash chromatography: Silica gel Si 60, E.
Merck AG, Darmstadt, 40-63 mm. Medium pressure liquid chroma-
tography: Silica gel Lichroprep Si 60, E. Merck AG, Darmstadt,
15-12 mm, 10 bar, detection by differential refractometry (Knaur,
Berlin).
Diastereomer A
Eluted first.
5-Tosyloxy-1,3-dioxolane (8)
1H NMR (300 MHz, CDCl3): d = 1.24 (s, 12H), 2.19 (dd, 1H,
J = 8.6, 8.5 Hz), 4.48 (d, 1H, J = 8.0 Hz), 4.96 (dd, 1H, J = 6.5, 1.8
Hz), 5.01-5.12 (m, 4H), 5.77 (ddd, 1H, J = 17.2, 10.0, 9.5 Hz), 6.51
(dd, 1H, J = 6.4, 1.5 Hz).
13C NMR (75 MHz, CDCl3): d = 24.6, 73.7, 83.5, 89.7, 106.0,
116.5, 134.6, 143.4.
To a solution of glycerolformal (Aldrich, 250 g, 2.40 mol) and p-
toluenesulfonyl chloride (477 g, 2.50 mol) in CHCl3 (500 mL) was
added anhyd pyridine (242 mL, 3.0 mol) at 0 °C over 1 h and finally
4-(dimethylamino)pyridine (approx. 20 mg). After stirring for 12 h,
the mixture was partitioned between H2O (300 mL) and CHCl3 (300
mL). The phases were separated and the aqueous phase was extract-
ed with CHCl3 (300 mL). The combined organic phases were dried
(MgSO4) and concentrated in vacuo. The residue was crystallized
from a mixture of petroleum ether (300 mL) and Et2O (300 mL).
The product obtained was washed with cold (0 °C) Et2O (5 mL) and
recrystallized twice with the same solvent mixture to give 8 (180 g,
58%).
Anal. Calcd for C13H21BO4 (252.2): C, 61.93; H, 8.40. Found: C,
62.06; H, 8.40.
Diastereomer B
Eluted second.
1H NMR (300 MHz, CDCl3): d = 1.23 (s, 6H), 1.24 (s, 6H), 2.18 (t,
1H, J = 9.1 Hz), 4.52 (dt, 1H, J = 9.4, 1.8 Hz), 4.86 (dd, 1H, J = 6.4,
2.0 Hz), 5.01-5.12 (m, 4H), 5.83 (ddd, 1H, J = 17.1, 10.3, 9.0 Hz),
6.51 (dd, 1H, J = 6.4, 1.7 Hz).
13C NMR (75 MHz, CDCl3): d = 24.5, 24.7, 73.4, 83.6, 88.9, 106.3,
116.1, 135.4, 143.7.
Mp: 86 °C [Lit.25 mp: 90-91 °C (C6H6)].
1H NMR (300 MHz, CDCl3): d = 2.44 (s, 3H), 3.77 (dd, 2H,
J = 12.0, 3.8 Hz), 3.96 (dd, 2H, J = 12.0, 3.5 Hz), 4.41-4.47 (m,
1H), 4.73 (d, 1H, J = 6.3 Hz), 4.78 (d, 1H, J = 6.3 Hz), 7.34 (d, 2H,
J = 8.1 Hz), 7.80 (d, 2H, J = 8.4 Hz).
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Efficient Homologation of Aldehydes to 2,4,6-Alkatrienals by means of an a-(1,3-Dioxenylallyl)boronate
2065
Anal. Calcd for C13H21BO4 (252.1): C, 61.93; H, 8.40. Found: C,
61.68; H, 8.42.
(dd, 1H, J = 15.2, 7.9 Hz), 6.35 (dd, 1H, J = 11.3, 11.0 Hz), 7.27-
7.36 (m, 5H), 9.50 (d, 1H, J = 7.9 Hz).
13C NMR (75 MHz, CDCl3): d = 38.0, 73.5, 125.8, 128.0, 128.6,
6-(4-Hydroxy-4-phenylbut-1-enyl)-1,3-diox-4-ene (11a)
Benzaldehyde (0.18 mL, 1.8 mmol) was added dropwise at r.t. to a
solution of 4 (306 mg, 1.21 mmol) in anhyd petroleum ether (4 mL).
TLC indicated that the reaction was complete after stirring for
2 days. Et2O (25 mL) and sat. NaHCO3 (10 mL) were added, the
phases were separated, and the aqueous phase was extracted with
Et2O (2 ¥ 20 mL). The combined organic phases were dried
(MgSO4) and concentrated to give an E/Z-mixture of 11a (258 mg,
92%). The geometric isomers could be separated by flash chroma-
tography with petroleum ether/Et2O (7:1).
129.1, 132.4, 138.2, 143.3, 146.2, 193.8.
Anal. Calcd for C13H14O2 (202.3): C, 77.20; H, 6.98. Found: C,
77.16; H, 7.04.
6-(4-Hydroxy-5-methylhex-1-enyl)-1,3-diox-4-ene (11b)
Compound 4 (256 mg, 1.02 mmol) and isobutyraldehyde (0.14 mL,
1.5 mmol) were allowed to react as described for the synthesis of
11a. Flash chromatography with petroleum ether/Et2O (7:1) fur-
nished (E)-11b (132 mg) and (Z)-11b (58 mg) in a total yield of
94%.
(E)-11a
Eluted first.
(E)-11b
Eluted first.
1H NMR (300 MHz, CDCl3): d = 2.20 (m, 1H), 2.40-2.58 (m, 2H),
4.62-4.74 (m, 2H), 4.81 (dd, 1H, J = 6.5, 2.8 Hz), 4.93 (d, 1H,
J = 5.6 Hz), 4.97 (d, 1H, J = 5.5 Hz), 5.56 (dd, 1H, J = 15.6, 5.4
Hz), 5.64-5.78 (m, 1H), 6.54 (dd, 1H, J = 6.3, 1.8 Hz), 7.24-7.34
(m, 5H).
13C NMR (75 MHz, CDCl3): d = 42.1, 72.2, 73.6, 87.8, 104.8,
125.8, 127.6, 128.4, 130.7, 132.3, 143.6, 143.8.
1H NMR (300 MHz, CDCl3): d = 0.92 (d, 3H, J = 6.8 Hz), 0.93 (d,
3H, J = 6.7 Hz), 1.48 (d, 1H, J = 4.4 Hz), 1.62-1.73 (m, 1H), 2.09-
2.20 (m, 1H), 2.26-2.34 (m, 1H), 3.37-3.44 (m, 1H), 4.73 (m, 1H),
4.87 (dd, 1H, J = 6.4, 2.6 Hz), 5.03 (s, 2H), 5.60 (dd, 1H, J = 15.5,
6.1 Hz), 5.72-5.82 (m, 1H), 6.57 (dd, 1H, J = 6.4, 1.9 Hz).
13C NMR (75 MHz, CDCl3): d = 17.3, 18.7, 33.2, 37.2, 72.3, 75.7,
88.0, 104.9, 131.7, 131.9, 143.6.
Anal. Calcd for C14H16O3 (232.3): C, 72.39; H, 6.94. Found: C,
72.28; H, 6.61.
Anal. Calcd for C11H18O3 (198.3): C, 66.64; H, 9.15. Found: C,
66.77; H, 9.28.
(Z)-11a
Eluted second.
(Z)-11b
Eluted second.
1H NMR (300 MHz, CDCl3): d = 2.19 (d, 1H, J = 3.6 Hz), 2.54-
2.63 (m, 2H), 4.70 (dd, 1H, J = 6.5, 1.1 Hz), 4.73-4.78 (m, 1H),
4.99 (m, 1H), 5.01 (d, 1H, J = 5.6 Hz), 5.06 (d, 1H, J = 5.6 Hz),
5.51-5.67 (m, 2H), 6.52 (dd, 1H, J = 6.3, 1.8 Hz), 7.23-7.33 (m,
5H).
13C NMR (75 MHz, CDCl3): d = 37.4, 68.6, 73.4, 89.0, 105.9,
125.7, 127.6, 128.5, 129.2, 131.6, 143.5, 143.8.
1H NMR (300 MHz, CDCl3): d = 0.91 (d, 3H, J = 6.8 Hz), 0.93 (d,
3H, J = 6.8 Hz), 1.58 (d, 1H, J = 4.7 Hz), 1.62-1.74 (m, 1H), 2.22-
2.34 (m, 2H), 3.41 (m, 1H), 4.83 (dd, 1H, J = 6.3, 2.1 Hz), 5.06 (d,
1H, J = 5.6 Hz), 5.11 (d, 1H, J = 5.6 Hz), 5.57-5.72 (m, 2H), 6.57
(dd, 1H, J = 6.3, 1.8 Hz).
13C NMR (75 MHz, CDCl3): d = 17.5, 18.8, 32.6, 33.3, 68.6, 75.9,
89.1, 106.0, 130.4, 131.2, 143.5.
Anal. Calcd for C14H16O3 (232.3): C, 72.39; H, 6.94. Found: C,
72.03; H, 7.37.
Anal. Calcd for C11H18O3 (198.3): C, 66.64; H, 9.15. Found: C,
66.13; H, 9.13.
7-Hydroxy-7-phenylhepta-2,4-dienal (6a)
7-Hydroxy-8-methylnona-2,4-dienal (6b)
Benzaldehyde (0.13 mL, 1.3 mmol) was added dropwise to a solu-
tion of 4 (243 mg, 0.96 mmol) in anhyd toluene (4 mL). After stir-
ring for 2 days, the mixture was held under reflux for 3 h. After
cooling to r.t., Et2O (25 mL) and sat. NaHCO3 (20 mL) were added,
the phases were separated and the aqueous phase was extracted with
Et2O (2 ¥ 25 mL). The combined organic phases were dried
(MgSO4) and concentrated to give a mixture of the hydroxy-dienals
(178 mg, 92%). The geometric isomers could be separated by flash
chromatography with petroleum ether/Et2O (4:1).
Compound 4 (287 mg, 1.14 mmol) and isobutyraldehyde (0.16 mL,
1.8 mmol) were allowed to react as described for the synthesis of 6a
to give a mixture of the hydroxydienals (178 mg, 93%). This mix-
ture was separated by flash chromatography with petroleum ether/
Et2O (4:1).
(2E,4E)-6b
Eluted first.
1H NMR (300 MHz, CDCl3): d = 0.90 (d, 3H, J = 6.8 Hz), 0.91 (d,
3H, J = 6.7 Hz), 1.68 (septet, 1H, J = 6.7 Hz), 1.99 (m, 1H), 2.23-
2.43 (m, 2H), 3.45 (ddd, 1H, J = 8.6, 5.5, 3.9 Hz), 6.04 (dd, 1H,
J = 15.4, 8.0 Hz), 6.26-6.41 (m, 2H), 7.07 (dd, 1H, J = 15.3, 9.9
Hz), 9.48 (d, 1H, J = 8.0 Hz).
13C NMR (75 MHz, CDCl3): d = 17.3, 18.6, 33.5, 38.0, 75.7, 130.4,
130.6, 143.6, 152.2, 193.8.
(2E,4E)-7-Hydroxy-7-phenylhepta-2,4-dienal [(E,E)-6a]
Eluted first.
1H NMR (300 MHz, CDCl3): d = 2.25 (m, 1H), 2.56-2.68 (m, 2H),
4.81 (t, 1H, J = 6.3 Hz), 6.05 (dd, 1H, J = 15.3, 8.0 Hz), 6.26 (ddd,
1H, J = 15.2, 7.1, 6.8 Hz), 6.36 (dd, 1H, J = 15.4, 10.4 Hz), 7.28-
7.36 (m, 5H), 9.48 (d, 1H, J = 8.0 Hz).
Anal. Calcd for C10H16O2 (168.2): C, 71.39; H, 9.59. Found: C,
71.36; H, 9.43.
13C NMR (75 MHz, CDCl3): d = 42.7, 73.5, 125.7, 127.9, 128.6,
130.8, 131.2, 141.9, 143.5, 151.9, 193.8.
(2E,4Z)-6b
Eluted second.
Anal. Calcd for C13H14O2 (202.3): C, 77.20; H, 6.98. Found: C,
76.92; H, 7.10.
1H NMR (300 MHz, CDCl3): d = 0.93 (d, 3H, J = 6.9 Hz), 0.95 (d,
3H, J = 6.7 Hz), 1.70 (septet, 1H, J = 6.7 Hz), 1.82 (m, 1H), 2.45-
2.49 (m, 2H), 3.34-3.50 (m, 1H), 6.09 (dt, 1H, J = 10.7, 7.8 Hz),
6.13 (dd, 1H, J = 15.1, 7.9 Hz), 6.37 (dd, 1H, J = 11.3, 10.9 Hz),
7.42 (ddd, 1H, J = 15.2, 11.5, 0.9 Hz), 9.57 (d, 1H, J = 7.9 Hz).
(2E,4Z)-7-Hydroxy-7-phenylhepta-2,4-dienal [(E,Z)-(6a)]
Eluted second.
1H NMR (300 MHz, CDCl3): d = 2.15 (m, 1H), 2.68-2.89 (m, 2H),
4.82 (dd, 1H, J = 6.5, 6.2 Hz), 6.03 (dt, 1H, J = 10.7, 7.9 Hz), 6.11
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

2066
R. W. Hoffmann et al.
PAPER
13C NMR (75 MHz, CDCl3): d = 17.3, 18.7, 33.3, 33.5, 75.9, 128.7,
132.3, 140.0, 146.4, 193.9.
13C NMR (75 MHz, CDCl3): d = 17.6, 36.1, 72.0, 127.8, 128.8,
132.3, 133.0, 138.7, 146.5, 193.9.
Anal. Calcd for C10H16O2 (168.2): C, 71.39; H, 9.59. Found: C,
71.24; H, 9.50.
Anal. Calcd for C10H14O2: C, 72.26; H, 8.49. Found: C, 72.40; H,
8.49.
6-(4-Hydroxyhepta-1,5-dienyl)-1,3-diox-4-ene (11c)
Compound 4 (430 mg, 1.7 mmol) and crotonaldehyde (0.20 ml, 2.2
mmol) were allowed to react as described for the synthesis of 11a
to give an E/Z-mixture of the dioxene 11c (303 mg, 91%). The geo-
metric isomers could be separated by flash chromatography with
pentane/t-BuOMe (4:1).
Isomerization of (Z)-6c to (2E,4E,8E)-7-Hydroxy-2,4,8-decatri-
enal [(E)-6c]
To a solution of (2E,4Z,8E)-7-hydroxydecatrienal [(Z)-6c, 48 mg,
0.29 mmol] in anhyd benzene (3 mL) were added some crystals of
iodine (approx. 10 mg). On completion of the reaction (30 min,
TLC), t-BuOMe was added (10 mL) and the mixture was washed
with sat. Na2S2O3 (10 mL). The phases were separated and the aque-
ous phase was extracted with t-BuOMe (3 ¥ 10 mL). The combined
organic phases were dried (MgSO4) and concentrated. Flash chro-
matography with pentane/t-BuOMe (4:1) furnished 44 mg (92%) of
(2E,4E,8E)-6c.
(E)-11c
Eluted first.
1H NMR (300 MHz, CDCL3): d = 1.68 (ddd, 3H, J = 6.3, 1.5, 0.7
Hz), 1.86 (br s, 1H), 2.28 (t, 2H, J = 6.6 Hz), 4.08 (q, 1H, J = 6.05
Hz), 4.69-4.73 (m, 1H), 4.85 (dd, 1H, J = 6.6, 2.6 Hz), 5.01 (s, 2H),
5.47 (ddq, 1H, J = 15.3, 6.6, 1.3 Hz), 5.57 (ddt, 1H, J = 0 15.7, 6.0,
0.7 Hz), 5.66 (ddd, 1H, J = 15.3, 6.45, 0.9 Hz), 5.72 (ddd, 1H,
J = 15.4, 7.0, 0.7 Hz), 6.56 (dd, 1H, J = 6.3, 1.8 Hz).
(2E,4E)-7-Hydroxyalka-2,4-dienals ; One-Pot Procedure
(1-2 mmol scale, cf. Table 3, Scheme 5)
The reagent 4 (1 equiv) and the aldehyde (1 equiv) were allowed to
react in anhyd toluene (3-5 mL) at r.t. until TLC indicated complete
reaction. The mixture was held under reflux for 2 h. After cooling
to r.t., iodine (20-50 mg) was added and the mixture was stirred for
approx. 30 min until TLC indicated complete isomerization. Et2O
was added (25 mL) and the mixture was washed with sat. Na2S2O3
(20 mL). The phases were separated and the aqueous phase was ex-
tracted with Et2O (3 ¥ 20 mL). The combined organic phases were
dried (MgSO4) and concentrated. The crude products were purified
by flash chromatography.
13C NMR (75 MHz, CDCl3): d = 17.6, 40.3, 72.0, 72.2, 87.8, 104.9,
127.1, 130.8, 131.9, 133.4, 143.6.
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 67.17; H,
8.21.
(Z)-11c
Eluted second.
1H NMR (300 MHz, CDCl3): d = 1.64 (ddd, 3H, J = 6.2, 1.4, 0.7
Hz), 1.72 (br s, 1H), 2.29 (t, 2H, J = 6.1 Hz), 4.06 (1H, J = 6.2 Hz),
4.76 (dd, 1H, J = 6.4, 2.1 Hz), 4.99-5.06 (m, 3H), 5.54 (ddq, 1H,
J = 15.5, 6.7, 1.5 Hz), 5.50-5.62 (m, 2H), 5.65 (ddd, 1H, J = 13.4,
6.4, 0.9 Hz), 6.61 (dd, 1H, J = 6.3, 1.8 Hz).
13C NMR (75 MHz, CDCl3): d = 17.7, 35.7, 68.8, 72.1, 89.1, 106.0,
127.2, 129.3, 131.3, 133.4, 143.6.
(2E,4E,8E,10E,12E)-7-Hydroxy-13-phenyltrideca-2,4,8,10,12-
pentaenal (6d)
1H NMR (300 MHz, CDCl3): d = 2.43 (t, 2H, J = 6.3 Hz), 4.23-
4.29 (m, 1H), 5.65-5.81 (m, 1H), 6.01 (dd, 1H, J = 15.6, 7.8 Hz),
6.10 (dd, 1H, J = 15.2, 7.9 Hz), 6.22-6.38 (m, 4H), 6.48 (d, 1H,
J = 15.6 Hz), 6.74 (dd, 1H, J = 15.5, 9.8 Hz), 7.02 (dd, 1H, J = 15.2,
10.3 Hz), 7.12-7.37 (m, 5H), 9.50 (d, 1H, J = 8.0 Hz).
Anal. Calcd for C11H16O3: C, 67.32; H, 8.22. Found: C, 67.51; H,
8.09.
13C NMR (75 MHz, CDCl3): d = 41.0, 71.6, 126.4, 127.7, 128.6,
128.6, 130.8, 131.3, 131.4, 131.8, 133.3, 134.1, 134.7, 137.2, 141.6,
152.0, 193.9.
7-Hydroxy-2,4,8-decatrienal (6c)
A solution of E-11c (56 mg, 0.29 mmol) in anhyd toluene (3 mL)
was heated to 120 °C in a tightly sealed flask for 2 h. After the mix-
ture had cooled to r.t., silica gel (approx. 50 mg) was added, and the
mixture was evaporated to dryness. Flash chromatography with
pentane/t-BuOMe (4:1) furnished 46 mg of (E)-6c (97%).
HRMS: m/z calcd for C19H20O2 (M+): 280.1463. Found: 280.1458.
(2E,4E,8E,10E)-7,13-Dihydroxy-13-phenyltrideca-2,4,8,10-tet-
raenal (15a)
(E)-6c
1H NMR (300 MHz, CDCl3): d = 2.38 (t, 2H, J = 6.4 Hz), 2.45 (t,
2H, J = 6.9 Hz), 4.18 (pd, 1H, J = 6.2, 6.1 Hz), 4.64 (t, 1H, J = 6.3
Hz), 5.54 (dd, 1H, J = 14.4, 6.5 Hz), 5.63 (dd, 1H, J = 14.6, 7.3 Hz),
5.91-6.38 (m, 5H), 6.99 (dd, 1H, J = 15.3, 10.3 Hz), 7.17-7.30 (m,
5H), 9.45 (d, 1H, J = 8.0 Hz).
1H NMR (300 MHz, CDCl3): d = 1.69 (ddd, 3H, J = 6.3, 1.5, 0.7
Hz), 2.43 (t, 2H, J = 6.3 Hz), 4.18 (q, 1H, J = 6.4 Hz), 5.49 (ddq,
1H, J = 15.4, 7.0, 1.5 Hz), 5.69 (dqd, 1H, J = 15.2, 6.3, 0.6 Hz), 6.07
(ddd, 1H, J = 15.6, 8.3, 0.6 Hz), 6.25 (dd, 1H, J = 15.4, 7.0 Hz),
6.38 (ddq, 1H, J = 15.1, 10.3, 0.7 Hz), 7.08 (dd, 1H, J = 15.4, 10.3
Hz), 9.51 (d, 1H, J = 8.1 Hz).
13C NMR (75 MHz, CDCl3): d = 40.9, 42.5, 71.4, 73.6, 125.7,
127.5, 128.4, 130.6. 130.9, 131.1, 132.3, 133.4, 141.9, 143.8, 146.5,
152.1, 193.9.
13C NMR (75 MHz, CDCl3): d = 17.6, 41.0, 71.8, 127.6, 130.5,
130.9, 133.1, 142.3, 152.2, 193.9.
MS: The sample gave no suitable M+ peak..
Anal. Calcd for C10H14O2: C, 72.26; H, 8.49. Found: C, 72.30; H,
8.68.
(2E,4E,7R,8S,9S)-9-tert-Butyldimethylsilyloxy-7-hydroxy-8-
methylundeca-2,4-dienal (6e)
(Z)-6c
(Z)-11c (59 mg, 0.30 mmol) was converted as above into (Z)-6c (48
mg, 96%).
Diastereomeric mixture, starting from (2R,3S)-3-tert-Butyldimeth-
ylsilyloxy-2-methylpentanal.35
1H NMR (300 MHz, CDCl3): d = 1.71 (ddd, 3H, J = 6.3, 1.5, 0.7
Hz), 2.57 (mc, 2H), 4.20 (q, 1H, J = 6.4 Hz), 5.52 (ddq, 1H,
J = 15.2, 6.8, 1.2 Hz), 5.72 (ddq, 1H, J = 15.4, 0.6, 6.5 Hz), 6.05
(mc, 1H), 6.16 (dd, 1H, J = 15.1, 8.1 Hz), 6.38 (t, 1H, J = 11.2 Hz),
7.43 (ddd, 1H, J = 15.4, 11.5, 1.0 Hz), 9.60 (d, 1H, J = 8.1 Hz).
1H NMR (500 MHz, CDCl3): d = 0.09 (s, 3H), 0.10 (s, 3H), 0.80 (t,
3H, J = 7.5 Hz), 0.88 (s, 9H), 0.91 (d, 3H, J = 7.0 Hz), 1.53-1.60
(m, 3H), 2.29-2.35 (m, 1H), 2.45-2.51 (m, 1H), 3.01 (s, 1H), 3.78
(ddd, 1H, J = 8.5, 5.8, 2.7 Hz), 3.89 (m, 1H), 6.08 (dd, 1H, J = 15.4,
8.0 Hz), 6.33 (ddd, 1H, J = 15.2, 7.0, 6.8 Hz), 6.39 (dd, 1H,
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Efficient Homologation of Aldehydes to 2,4,6-Alkatrienals by means of an a-(1,3-Dioxenylallyl)boronate
2067
J = 15.3, 10.5 Hz), 7.09 (dd, 1H, J = 15.3, 10.4 Hz), 9.53 (d, 1H,
J = 8.0 Hz).
13C NMR (75 MHz, CDCl3): d = -4.6, -3.6, 5.3, 9.9, 18.0, 25.8,
27.4, 38.8, 39.2, 74.6, 79.2, 130.42, 130.44, 143.6, 152.4, 193.9.
(2E,4E,6E,8S,9S)-8-Methyl-9-tert-butyldimethylsilyloxy-
undeca-2,4,6-trienal (7e)
1H NMR (300 MHz, CDCl3): d = 0.02 (s, 3H), 0.03 (s, 3H), 0.83 (t,
3H, J = 7.4 Hz), 0.88 (s, 9H), 0.99 (d, 3H, J = 6.8 Hz), 1.32-1.48
(m, 2H), 2.40-2.52 (m, 1H), 3.49 (dt, 1H, J = 6.4, 5.1 Hz), 6.04 (dd,
1H, J = 15.3, 7.0 Hz), 6.13 (dd, 1H, J = 15.0, 7.9 Hz), 6.18 (dd, 1H,
J = 15.3, 10.2 Hz), 6.35 (dd, 1H, J = 14.8, 11.1 Hz), 6.64 (dd, 1H,
J = 14.9, 10.1 Hz), 7.10 (dd, 1H, J = 15.2, 11.1 Hz), 9.53 (d, 1H,
J = 8.0 Hz).
Anal. Calcd for C18H34O3Si (326.6): calcd. C, 66.21; H, 10.50;
found C, 65.79; H, 10.15.
(7S,8S,9S)-Diastereomer of 6e
The following signals could be recorded:
13C NMR (75 MHz, CDCl3): d = -4.4, -4.3, 9.7, 14.7, 18.2, 25.9,
1H NMR (300 MHz, CDCl3): d = 0.08 (s, 3H), 0.10 (s, 3H), 0.79 (d,
3H, J = 7.1 Hz), 0.90 (s, 9H), 0.93 (t, 3H, J = 7.3 Hz), 1.50-1.60
(m, 1H), 1.61 (s, 1H), 1.75 (ddd, 1H, J = 9.8, 5.1, 2.8 Hz), 2.20-
2.31 (m, 1H), 2.47 (ddd, 1H, J = 14.7, 4.7, 3.9 Hz), 3.67 (ddd, 1H,
J = 7.8, 5.7, 3.0 Hz), 3.76-3.81 (m, 1H), 4.41 (s, 1H), 6.08 (dd, 1H,
J = 15.3, 8.0 Hz), 6.33-6.43 (m, 2H), 7.08 (dd, 1H, J = 15.3, 10.0
Hz), 9.52 (d, 1H, J = 8.0 Hz).
26.7, 41.9, 76.9, 128.0, 129.0, 130.7, 143.4, 145.4, 152.3, 193.5.
A correct elemental analysis was not obtained.
Method B
Methanesulfonic anhydride (86 mg, 0.49 mmol) was added at r.t.
into a solution of (2E,4E)-7-hydroxy-7-phenylheptadienal (6a,
77 mg, 0.38 mmol) in CH2Cl2 (1 mL). After addition of i-Pr2NEt
(144 ml, 0.84 mmol), the solution was stirred until TLC indicated
complete consumption of the starting material (approx. 2 days). Sil-
ica gel (0.5 g) was added and the suspension was concentrated. The
residue was purified by flash chromatography with pentane/t-
BuOMe (1:1) to give (2E,4E,6E)-7-phenylheptatrienal (7a) (58 mg,
85%) as yellow crystals; mp: 116 °C (Lit. 36 mp: 115-116 °C).
13C NMR (75 MHz, CDCl3): d = -4.6, -4.4, 11.3, 13.5, 17.9, 24.1,
25.8, 39.0, 42.1, 73.2, 79.5, 130.3, 130.5, 143.6, 152.6, 194.0.
(2E,4E,8E,10E,14E)-7,13-Dihydroxyhexadecapentaenal (15b)
1H NMR (300 MHz, CDCl3): d = 1.52 (br s, 2H), 1.64 (d, 3H,
J = 6.2 Hz), 2.25 (t, 2H, J = 6.8 Hz), 2.42 (t, 2H, J = 6.2 Hz), 4.05
(q, 1H, J = 6.5 Hz), 4.24 (q, 1H, J = 6.7 Hz), 5.41 (dd, 1H, J = 15.9,
7.3 Hz), 5.54-5.70 (m, 3H), 6.00-6.11 (m, 2H), 6.13-6.25 (m, 2H),
6.34 (dd, 1H, J = 15.5, 11.3 Hz), 7.06 (dd, 1H, J = 15.4, 10.0 Hz),
9.48 (d, 1H, J = 7.9 Hz).
(2E,4E,6E,8E)-decatetraenal (7c)
Yellow crystals; mp: 103 °C (Lit.37 mp: 105 °C).
13C NMR (50 MHz, CDCl3): d = 17.6, 40.7, 40.9, 71.4, 72.0, 127.0,
(2E,4E,6E,8E,10E,12E)-13-phenyl-2,4,6,8,10,12-tridecahexae-
nal (16a)
130.0, 130.6, 130.7, 131.2, 133.1, 133.2, 135.4, 141.8, 152.0, 193.8.
1H NMR (400 MHz, CDCl3): d = 6.00-6.33 (m, 3H), 6.37 (dd, 1H,
J = 14.4, 10.4 Hz), 6.40-6.67 (m, 4H), 6.69-6.94 (m, 2H), 7.14 (dd,
1H, J = 15.3, 10.5 Hz), 7.20-7.23 (m, 1H), 7.31 (t, 3H, J = 7.3 Hz),
7.39 (td, 2H, J = 8.4, 1.1 Hz), 9.55 (d, 1H, J = 8.0 Hz).
HRMS: m/z calcd for C16H21O3 (M+-H): 261.1491. Found:
261.1441; m/z calcd for (M+-2H): 260.1412. Found: 260.1442.
Dehydration of 7-Hydroxyalka-2E,4E-dienals to alka-
2E,4E,6E-trienals (1-2 mmol scale, cf. Tables 4 and 5)
Method A
13C NMR (100 MHz, CDCl3): d = 126.5 (2C), 127.2, 128.7 (2C),
129.9, 131.5, 132.2, 132.6, 133.0, 134.0, 135.6, 136.7, 137.1, 138.9,
139.1, 142.6, 151.7, 193.5.
Burgess reagent33 (freshly recrystallized from toluene, mp 70 °C, 1
equiv), was suspended in anhyd C6H6 (5 mL). A solution of the hy-
droxydienal (1 equiv) in benzene (3 mL) was added dropwise over
15 min. The mixture was heated in a closed vessel to 85 °C for 2 h.
After cooling to r.t., H2O (10 mL) was added and the phases were
separated. The aqueous phase was extracted with EtOAc (2 ¥ 15
mL), the combined organic phases were dried (MgSO4), and con-
centrated. The resulting trienal was purified by flash chromatogra-
phy with t-BuOMe/pentane (1:1).
HRMS: m/z calcd for C19H18 O (M+): 262.1358. Found: 262.1351.
(2E,4E,6E,8E,10E,12E,14E)-Hexadecaheptaenal (16b)
The preparation was carried out with complete exclusion of light.
The crude material was purified by flash chromatography with pen-
tane/t-BuOMe (4:1).
1H NMR (400 MHz, CDCl3): d = 1.55 (d, 3H, J = 6.1 Hz), 6.18 (dd,
1H, J = 14.2, 9.8 Hz), 6.39 (dd, 1H, J = 14.3, 9.1 Hz), 6.40-6.58
(m, 5H), 6.63 (m, 1H), 6.88 (dd, 1H, J = 15.3, 10.5 Hz), 7.30-7.45
(m, 5H), 9.57 (d, 1H, J = 8.0 Hz).
(2E,4E,6E)-7-Phenylhepta-2,4,6-trienal (7a)
1H NMR (300 MHz, CDCl3): d = 6.17 (dd, 1H, J = 15.2, 8.0 Hz),
6.55 (dd, 1H, J = 13.9, 11.3 Hz), 6.89 (dd, 1H, J = 13.6, 11.3 Hz),
6.93 (d, 1H, J = 13.9 Hz), 7.00 (dd, 1H, J = 14.5, 9.8 Hz), 7.18 (dd,
1H, J = 15.2, 11.2 Hz), 7.29-7.46 (m, 5H), 9.59 (d, 1H, J = 7.9 Hz),
cf. the data in ref.13,15
13C NMR (125 MHz, CDCl3): d = 28.7, 125.5, 126.9, 127.9, 128.9,
128.9, 130.7, 131.6, 132.1, 133.0, 134.6, 135.7, 137.9, 141.7, 150.7,
192.4.
HRMS: m/z calcd for C16H18O (M+): 226.1358. Found: 226.1356.
13C NMR (75 MHz, CDCl3): d = 127.0, 127.7, 128.8, 130.1, 131.2,
136.3, 138.3, 142.7, 151.6, 193.4, cf. the data in ref.13
2,4,6,8-Decatetraenal (17); One-Pot Procedure
Dioxenylallylboronic acid ester 4 (297 mg, 1.2 mmol) and crotonal-
dehyde (0.15 mL, 1.8 mmol) were allowed to react in anhyd toluene
(2 mL) at r.t. for approx. 2 days until TLC indicated complete con-
sumption of the boronate. The mixture was heated to 120 °C in a
tightly sealed flask for 2 h. After the mixture had cooled to r.t., io-
dine (150 mg, 0.25 equiv) was added (Scheme 7). After stirring at
r.t. for 30 min, t-BuOMe was added (10 mL) and the mixture was
washed with sat. Na2S2O3 (10 mL). The phases were separated and
the aqueous phase was extracted with t-BuOMe (3 ¥ 10 mL). To the
combined organic phases was added silica gel (approx. 50 mg), and
the mixture was evaporated to dryness. Flash chromatography with
(2E,4E,6E)-8-Methylnonatrienal (7b)
1H NMR (300 MHz, CDCl3): d = 1.04 (d, 6H, J = 6.8 Hz), 2.40 (m,
1H), 6.00 (dd, 1H, J = 15.3, 6.6 Hz), 6.07-6.18 (m, 2H), 6.35 (dd,
1H, J = 14.9, 11.1 Hz), 6.63 (dd, 1H, J = 14.9, 10.4 Hz), 7.10 (dd,
1H, J = 15.3, 11.2 Hz), 9.54 (d, 1H, J = 8.1 Hz), cf. the data in ref.
15
.
13C NMR (75 MHz, CDCl3): d = 21.9, 31.5, 126.9, 128.0, 130.6,
143.4, 149.1, 152.3, 193.5, cf. the data in ref. 15
Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York

2068
R. W. Hoffmann et al.
PAPER
pentane/t-BuOMe (1:1) furnished 130 mg of 17 (74%) as yellow
needles, mp: 103 °C.
(14) Duhamel, L.; Guillemont, J.; Le Gallic, Y.; Plé, G.; Poirier, J.;
Ramondenc, Y.; Chabardes, P. Tetrahedron Lett. 1990, 31,
3129.
(15) Ramondenc, Y.; Plé, G. Tetrahedron 1993, 49, 10855.
(16) Wollenberg, R. H. Tetrahedron Lett. 1978, 717.
(17) Contreras, B.; Duhamel, L.; Plé, G. Synth. Commun. 1990, 20,
2983.
Si-Fodil, M.; Ferreira, H.; Gralak, J.; Duhamel, L.
Tetrahedron Lett. 1998, 39, 8975; and references therein.
(18) Cahard, D.; Poirier, J. -M.; Duhamel, P. Tetrahedron Lett.
1998, 39, 7093.
Saito, S.; Shiozawa, M.; Ito, M.; Yamamoto, H. J. Am. Chem.
Soc. 1998, 120, 813.
(19) Saito, S.; Shiozawa, M.; Yamamoto, H. Angew. Chem., Int.
Ed. 1999, 38, 1769; and references therein.
(20) Hemming, K.; Taylor, R. J. K. J. Chem. Soc., Chem. Commun.
1993, 1409.
Conversion of Aldehydes into 2,4,6-Alkatrienals (0.5-2 mmol
scale, cf. Table 6); One-Pot Procedure
The reagent 4 (1 equiv) and the aldehyde (1 equiv) were combined
in anhyd toluene (5 mL). The mixture was stirred at r.t. for approx.
2 days or at 50 °C until TLC indicated complete consumption of the
starting materials. The mixture was then held for 3 h at 110 °C. Af-
ter cooling to r.t., 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1
equiv) was added and the solution was stirred for 12 h at r.t.
(Scheme 8). The mixture was partitioned between CH2Cl2 (50 mL)
and sat. NaHCO3 (10 mL). The phases were separated and the aque-
ous phase was extracted with CH2Cl2 (2 ¥ 10 mL), the combined or-
ganic phases were dried (MgSO4), and concentrated . The residue
was purified by flash chromatography with petroleum ether/Et2O
(3:1).
(21) Duhamel, L.; Ple, G.; Ramondenc, Y. Tetrahedron Lett. 1989,
30, 7377.
Acknowledgement
(22) Bellassoued, M.; Reboul, E.; Salemkour, M. Synth. Commun.
1995, 25, 3097.
This work was supported by the Deutsche Forschungsgemeinschaft
(SFB 260) and the European Community (HCM-Network CHRX-
CT94-0620). We thank Dr. Steven Stanway for exploratory experi-
ments towards the dehydration of hydroxydienals.
(23) We originally aimed at the silylated allylboronate i, which
would allow the conversion of an aldehyde into a trienal via a
tandem allylboration, Peterson olefination,38 and cyclo-
reversion. Unfortunately attempts at the synthesis of i were
met with failure or unattractive low yields.
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Article Identifier:
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Synthesis 2000, No. 14, 2060–2068 ISSN 0039-7881 © Thieme Stuttgart · New York