Stereospecific synthesis of (E,Z)- and (Z,Z)-hexadeca-10,12-dienal. Sex pheromone components of Diaphania hyalinata

Article abstract of DOI:10.1055/s-1999-3666

Isomeric (E,Z)- and (Z,Z)-hexadeca-10,12-dienal were prepared, stereospecifically, in 51% and 43% overall yields from dec-1-yne.

Full text of DOI:10.1055/s-1999-3666

PAPER
107
Stereospecific Synthesis of (E,Z)- and (Z,Z)-Hexadeca-10,12-dienal.
Sex Pheromone Components of Diaphania hyalinata
Jorge A. Cabezas,1a Allan C. Oehlschlager*1b
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada
Fax: JAC: +1(506)253-5020; ACO: +1(506)261-5397; E-mail: JAC: jcabezas@cariari.ucr.ac.cr; ACO: chemtica@sol.racsa.co.cr
Received 1 March 1998; revised 2 July 1998
per reaction6 before protection of the alcohol of 5 as the
tert-butyldimethylsilyl ether (92%). This protecting group
is stable to subsequent conditions used to build the diene
systems and is removed under nonacidic conditions with-
out isomerization of the double bonds.
Abstract: Isomeric (E,Z)- and (Z,Z)-hexadeca-10,12-dienal were
prepared, stereospecifically, in 51% and 43% overall yields from
dec-1-yne.
Key words: (E,Z)-hexadeca-10,12-dienal, (Z,Z)-hexadeca-10,12-
dienal, dec-1-yne, stereospecific reaction
To transform acetylene 6 into enyne 7 we used methodol-
ogy developed by Negishi7 for the synthesis of trans-
enynes. Thus, we reacted 6 sequentially, with disiamyl-
borane, pent-1-ynyllithium, iodine and sodium acetate. In
our hands, the desired enyne 7 was obtained in low yield
and was contaminated with an unidentified product. A
successful transformation of 6 into 7 was performed using
SuzukiÕs8 stereospecific palladium cross-coupling of 1-
alkenylboranes with 1-alkynyl halides. Thus, acetylene 6
was treated with disiamylborane, sodium methoxide and
1-bromopent-1-yne under palladium catalysis, to produce
(E)-enyne 7 in 87%. Enyne 7, was converted to the corre-
sponding (E,Z)-diene 8, in 92%, by hydroboration with di-
siamylborane at low temperature (Ð20¡C to 0¡C)
followed by protonolysis with acetic acid. GC analysis of
the crude reaction mixture revealed that reduction yielded
only one product. Diene 8 was treated with Bu4NF in THF
at 0¡C to remove the protecting group. Silyl impurities
were removed by Kugelrohr distillation and the residue
filtered through a small pad of silica gel. The alcohol thus
obtained was oxidized to 1, using Py2CrO3, in 76% yield
from 8. The 1H NMR spectrum (400 MHz) indicated that
this compound was obtained free from other stereoiso-
mers (isomeric purity >99%) (Figure 1). The overall yield
from dec-1-yne was 51%.
Diaphania hyalinata and Diaphania nitidalis are pyralid
species that exhibit similar life cycles and habits. The
former feeds upon the foliage of pumpkin and other cu-
curbits,2 whereas the latter is particularly destructive to
cantaloupe, cucumber and muskmelon.3 The damage
caused make these crops unsuitable for marketing. The
isomers (E,Z)-hexadeca-10,12-dienal (1) and (Z,Z)-hexa-
deca-10,12-dienal (2) were isolated, as minor compo-
nents, from the extracts of ovipositors of female
melonworm, D. hyalinata,2 while trace amounts of 1 were
found in extracts from pickleworm adults of D. nitidalis.3
These compounds, along with others, represent essential
components of the sex pheromones of these species.
Previous syntheses of the (E,Z)-isomer 1 have involved
Wittig condensation of butyltriphenylphosphorane with
(E)-12-(2-tetrahydropyranyloxy)dodec-2-enal,4 followed
by oxidation. The major drawback of this procedure is the
generation of a mixture of E and Z isomers in the Wittig
reaction. The (Z,Z)-isomer has been prepared by the Ca-
diotÐChodkiewicz coupling of pent-1-yne with undec-10-
yn-1-ol, followed by reduction of the triple bond with di-
cyclohexylborane to the corresponding dienol.2 The alco-
hols (E,Z)- and (Z,Z)-hexadeca-10,12-dien-1-ol have been
synthesized stereospecifically, by the palladium-cata-
lyzed cross-coupling reaction between an hydroxyalke-
nylborane and the appropriate haloalkene in the presence
of a base.5 The overall %yields reported for the syntheses
of these alcohols, from undec-10-en-1-ol, are 41 and 27%
respectively.5
Synthesis of (Z,Z)-hexadeca-10,12-dienal (2) involved the
palladium cross-coupling of acetylene 6, with (Z)-1-iodo-
pent-1-ene (10) prepared by the cis-addition of Gilman
cuprate 9 to acetylene followed by quenching with iodine
(Scheme 2). GC analysis of the cross-coupling reaction
mixture evidenced the formation of only one product and
total consumption of reagents 6 and 10. 1H NMR analysis
corroborated the stereochemistry of the (Z)-enyne 11,
which was obtained with an isomeric purity of 96% (75%
isolated yield). The (Z)-enyne 11, was stereospecifically
reduced to the (Z,Z)-diene 12, by hydroboration with di-
siamylborane followed by protonolysis (94% yield). Di-
ene 12 was deprotected with Bu4NF and oxidized with
Py2CrO3 to yield dienal 2 in 72% yield from 12. The over-
In this paper we report stereospecific syntheses of the iso-
meric dienals 1 and 2 in 51 and 43% overall yields from
dec-1-yne (3).
The syntheses utilized the common precursor tert-bu-
tyldimethylsilyl undec-10-ynyl ether (6) which was pre-
pared from dec-1-yne (3) by coupling of its lithium
acetylide with paraformaldehyde, at low temperature, to
give undec-2-yn-1-ol (4) in 93% (Scheme 1). The latter
was isomerized to undec-10-yn-1-ol (5) in 98% by a zip-
1
all yield from dec-1-yne was 43%. H NMR spectrum
showed that dienal 2 was obtained without contamination
with other stereoisomers and with an isomeric purity high-
er than 99% (Figure 2).
Synthesis 1999, No. 1, 107Ð111 ISSN 0039-7881 © Thieme Stuttgart á New York

108
J. A. Cabezas, A. C. Oehlschlager
PAPER
Obtention of a highly pure synthetic sample of 1, allowed
observation in the 1H NMR spectrum of long range con-
stant couplings (4J) for olefinic hydrogen H11 (Figure 1).
Thus, H11 shows a multiplicity of a doublet, doublet, doub-
let, of triplets (dddt) (or ddtd) as a result of couplings with
H10 (3J), H12 (3J), H9 (4J), and H13 (4J) with coupling con-
stants of 15, 11, 1.5 and 1.5 Hz respectively. This signal
had been previously reported5 with a multiplicity of a doub-
let of doublets (dd), because in the earlier spectrum long
1
range coupling (4J) was not observed. Likewise, the H
NMR spectrum (400 MHz) of dienal 2 (and its precursor
12) showed a complex pattern for olefinic hydrogens H10,
H13 (Figure 2, d = 5.43) and H11, H12 (Figure 2, d = 6.25),
as a result of 3J, and probably 4J, coupling. These signals
were previously reported,5 for the corresponding dienols
as a doublet of doublets (dd) for both H10 and H13, and a
doublet (d) for H11 and H13.
Glassware and syringes were dried overnight in an oven at 140¡C
and flushed with argon immediately prior to use. Transfers of liq-
uids were performed with syringes equipped with stainless-steel
needles. CrO3, KH, TBDMSCl, CuI and Pd(PPh3)4 were weighed in
a glove bag under N2. Reactions were carried out under positive
pressure of argon. THF was refluxed and freshly distilled from K/
benzophenone ketyl under argon. 1H and 13C NMR spectra were re-
corded on
a Bruker AMX-400 spectrometer, operating at
400.13 MHz and 100.62 MHz respectively. GC analyses were con-
ducted on a HewlettÐPackard 5892 instrument equipped with a
flame ionization detector.
Undec-2-yn-1-ol (4)
To a cold (Ð78¡C) THF solution (200 mL) of dec-1-yne (9.0 mL,
50 mmol) was added, over 15 min, 2.45 M BuLi in hexanes
(20.4 mL, 50 mmol), and the resulting solution stirred for 30 min.
After this time dry paraformaldehyde (1.65 g, 55 mmol) was added
in one portion and the mixture warmed overnight to r.t. The mixture
was quenched by addition of sat. NH4Cl and extracted with Et2O (2
× 100 mL). Et2O extracts were dried (MgSO4) and the solvent evap-
orated in vacuo. Kugelrohr distillation (90Ð92¡C/0.9 Torr) gave
7.85 g of product (93% yield). [Chem. Abstr. Reg. No. 34683-71].
Scheme 1
1H NMR (400 MHz, CDCl3): d = 0.88 (t, 3H, J = 7.0 Hz), 1.22Ð1.30
(m, 8H), 1.32Ð1.40 (m, 2H), 1.45Ð1.54 (tt, 2H, J = 7.0, 7.0 Hz), 1.58
(s, 1H), 2.20 (tt, 2H, J = 7.0, 2.5 Hz), 4.24 (t, 2H, J = 2.5 Hz).
13C NMR (100 MHz, CDCl3): d = 14.0, 18.7, 22.6, 28.6, 28.9, 29.1,
29.1, 31.8, 51.4, 78.3, 86.7.
Undec-10-yn-1-ol (5)
KH mineral oil suspension (ca. 7.6 g) was successively washed with
anhyd THF (3 × 30 mL) under argon. Traces of solvent were re-
moved under vacuum and the flask purged with argon. Propane-1,3-
diamine (80 mL) was added to the KH (3.50 g, 87 mmol) and stirred
for 1 h at r.t. After this time undec-2-yn-1-ol (4) was added (4.34 g,
25.8 mmol) and the resulting mixture stirred overnight under argon.
The mixture was slowly added to ~100 g of ice and extracted with
Et2O (4 × 100 mL), the extracts were washed with dil HCl, brine
and dried (MgSO4). Evaporation of solvent in vacuo gave 4.24 g of
product (98%). [Chem. Abstr. Reg. No. 2774-84-7].
1H NMR (400 MHz, CDCl3): d = 1.23Ð1.43 (m, 11H), 1.46Ð1.60
(m, 4H), 1.92 (t, 1H, J = 2.5 Hz), 2.17 (td, 2H, J = 7.5, 2.5 Hz), 3.62
(t, 2H, J = 7.0 Hz).
13C NMR (100 MHz, CDCl3): d = 18.4, 25.7, 28.5, 28.7, 29.0, 29.3,
29.4, 32.8, 63.0, 68.0, 84.7.
The spectroscopic characteristics matched the reported data.5
Scheme 2
Synthesis 1999, No. 1, 107–111 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereospecific Synthesis of (E,Z)- and (Z,Z)-Hexadeca-10,12-dienal
109
Figure 1 Olefinic region of the 1H NMR (400 MHz) spectrum of (E,Z)-hexadeca-10,12-dienal (1).
Figure 2 Olefinic region of the 1H NMR (400 MHz) spectrum of (Z,Z)-hexadeca-10,12-dienal (2).
Synthesis 1999, No. 1, 107–111 ISSN 0039-7881 © Thieme Stuttgart · New York

110
J. A. Cabezas, A. C. Oehlschlager
PAPER
Alcohol 5 was transformed into silyl ether 6 according to the proce-
through a small pad of Florisil. Concentration in vacuo gave 0.5 g
of 1 (76% from 8). [Chem. Abstr. Reg. No. 69977-23-7].
dure of Corey and Venkateswarlu.9
1H NMR (400 MHz, CDCl3): d = 0.90 (t, 3H, J = 7.0 Hz), 1.20Ð1.48
(m, 12H), 1.55Ð1.65 (m, 2H), 2.08 (td, 2H, J = 7.0, 7.5 Hz), 2.14
(tdd, 2H, J = 7.0, 7.0, 1.5 Hz), 2.41 (td, 2H, J = 7.0, 1.5 Hz), 5.30
(br dt, 1H, J = 11.0, 7.5 Hz), 5.65 (dt, 1H, J = 15.0, 7.0 Hz), 5.95
(br dd, 1H, J = 11.0, 11.0 Hz), 6.29 (ddtd, 1H, J = 15.0, 11.0, 1.5,
1.5 Hz), 9.75 (t, 1H, J = 1.5 Hz).
13C NMR (100 MHz, CDCl3): d = 13.7, 22.1, 22.9, 29.2, 29.3, 29.4,
29.8, 32.8, 43.9, 125.8, 128.8, 129.9, 134.5, 202.7.
MS: m/z (%) = 236 (M+, 11), 109 (13), 95 (25), 81 (61), 67 (100),
55 (26), 41 (40).
tert-Butyldimethylsilyl (E)-Hexadeca-10-en-12-ynyl Ether (7)
To a dry round-bottom flask, maintained at Ð10¡C under argon, was
¥
added 1 M BH3 THF solution (3.9 mL, 3.9 mmol) followed by the
dropwise addition of 2 M 2-methylbut-2-ene in THF (3.9 mL,
7.8 mmol), and the resulting mixture stirred at 0¡C, under argon, for
2 h. After this time, a THF solution (3 mL) of acetylene 6 (1.0 g,
3.55 mmol) was added and the mixture stirred at ¡C for 3 h. Dry
NaOMe (0.22 g, 4.13 mmol) was then added and the reaction stirred
for an additional hour. After this time the solvent was removed un-
der vacuum, the system purged with argon and the vinylborate thus
obtained, dissolved in benzene (5 mL).
The NMR spectra are in agreement with the reported data.5
In a different flask, equipped with a reflux condenser were dis-
solved 1-bromopent-1-yne (0.52 g, 3.55 mmol) and Pd(PPh3)4
(0.100 g, 0.08 mmol) in benzene (6 mL). The resulting solution was
stirred at r.t. for 30 min. To this solution was added, under argon,
the borate solution previously prepared and the mixture refluxed for
3 h. The residual organoborane was oxidized [3 M NaOH (0.5 mL)
and 30% H2O2 (0.5 mL)] for 1 h at r.t. The mixture was extracted
with Et2O, dried (MgSO4) and the solvent evaporated in vacuo. The
residue was dissolved in pentane and filtered through a pad of Flo-
risil, and eluted with Et2O/hexane 5:95. Evaporation of solvent in
vacuo, gave 1.08 g of product (87%).
(Z)-1-Iodopent-1-ene (10)
Propyllithium, prepared from 1-bromopropane and lithium accord-
ing to Brandsma12 was titrated according to the method of Watson
and Easthman.13
Gilman cuprate, 9, was prepared from propyllithium and CuI. Its
addition to acetylene was performed according to standard proce-
dures.14
1H NMR (400 MHz, CDCl3): d = 0.95 (t, 3H, J = 7.0 Hz), 1.46 (qt,
2H, J = 7.0, 7.0 Hz), 2.12 (m, 2H), 6.13Ð6.20 (m, 2H).
13C NMR (100 MHz, CDCl3): d = 13.6, 21.3, 36.7, 82.2, 141.2.
The NMR spectra are in agreement with the reported data.10
1H NMR (400 MHz, CDCl3): d = 0.05 (s, 6H), 0.90 (s, 9H), 0.97 (t,
3H, J = 7.0 Hz), 1.25Ð1.40 (m, 12H), 1.45Ð1.58 (m, 4H), 2.0 (br td,
2H, J = 7.0, 7.0 Hz), 2.25 (td, 2H, J = 7.0, 1.7 Hz), 3.58 (t, 2H, J =
6.7 Hz), 5.45 (dt, 1H, J = 15.0, 1.7 Hz), 6.05 (dt, 1H, J = 15.0,
7.0 Hz).
13C NMR (100 MHz, CDCl3): d = Ð5.2, 13.5, 18.7, 21.4, 22.3, 25.8,
26.0, 28.9, 29.1, 29.4, 29.6, 32.9, 63.3, 79.6, 88.6, 109.9, 143.3.
tert-Butyldimethylsilyl (Z)-Hexadec-12-en-10-ynyl Ether (11)
Enyne 11 was prepared, in 75% isolated yield, by the palladium
cross-coupling reaction between 1-iodopent-1-ene (10) and acety-
lene 6, according to Ratovelama and Linstrumelle.15
The NMR spectra are in agreement with previously reported data.10
1H NMR (400 MHz, CDCl3): d = 0.05 (s, 6H), 0.88 (s, 9H), 0.92 (t,
3H, J = 7.0 Hz), 1.25Ð1.60 (m, 16H), 2.26 (tdd, 2H, J = 7.5, 7.5,
1.0 Hz), 2.33 (td, 2H, J = 8.0, 2.0 Hz), 3.59 (t, 2H, J = 6.5 Hz), 5.44
(m, 1H), 5.81 (dt, 1H, J = 11.0, 7.5 Hz).
13C NMR (100 MHz, CDCl3): d = Ð5.3, 13.7, 18.4, 19.5, 22.2, 26.0,
28.8, 28.9, 29.1, 29.4, 29.5, 32.1, 32.9, 63.3, 77.5, 94.4, 109.6,
142.2.
tert-Butyldimethylsilyl (E,Z)-Hexadeca-10,12-dienyl Ether (8)
A THF solution (3 mL) of enyne 7 (1.06 g, 3.0 mmol) was added
via cannula, under argon, to a disiamylborane solution (4.2 mmol)
(prepared as described above and cooled to Ð20¡C). The resulting
solution was allowed to warm to 0¡C over 5 h. HOAc was added to
the cold solution (0¡C) and the mixture stirred overnight. After ox-
idation of the remnant borane, as above, the solution was extracted
with Et2O and the organic phase dried (MgSO4). Evaporation of the
solvent gave 0.97 g of product (92%).
1H NMR (400 MHz, CDCl3): d = 0.05 (s, 6H), 0.87 (s, 9H), 0.92 (t,
3H, J = 7.0 Hz), 1.20Ð1.32 (m, 12H), 1.34Ð1.55 (m, 4H), 2.08 (td,
2H, J = 7.0, 7.5 Hz), 2.14 (tdd, 2H, J = 7.0, 7.0, 1.5 Hz), 3.59 (t, 2H,
J = 6.75 Hz), 5.30 (br dt, 1H, J = 11.0, 7.5 Hz), 5.65 (dt, 1H, J =
15.0, 7.0 Hz), 5.95 (br dd, 1H, J = 11.0, 11.0 Hz), 6.29 (ddtd, 1H, J
= 15.0, 11.0, 1.5, 1.5 Hz).
The NMR are in agreement with the previously reported data.10
(Z,Z)-Hexadeca-10,12-dienal (2)
Diene 12, was treated with Bu4NF and PDC as described above for
1. [Chem. Abstr. Reg. No. 96348-46-8].
1H NMR (400 MHz, CDCl3): d = 0.90 (t, 3H, J = 7.0 Hz), 1.20Ð1.50
(m, 12H), 1.60 (m, 2H), 2.15 (m, 4H), 2.41 (td, 2H, J = 7.0, 1.5 Hz),
5.43 (m, 2H), 6.25 (m, 2H), 9.75 (t, 1H, J = 1.5 Hz).
13C NMR (100 MHz, CDCl3): d = 13.7, 22.1, 22.8, 27.4, 29.1, 29.3,
29.5, 29.6, 43.9, 123.7, 123.8, 131.8, 131.9, 202.6.
MS: m/z (%) = 236 (M+, 5), 109 (15), 95 (30), 81 (69), 67 (100), 54
(22).
13C NMR (100 MHz, CDCl3): d = Ð5.2, 13.7, 18.7, 22.9, 25.8, 26.0,
29.2, 29.4, 29.6, 29.8, 32.8, 32.9, 63.3, 125.7, 128.9, 129.8, 134.6.
The NMR spectra are in agreement with the reported data.5
The NMR spectra are in agreement with previously reported data.5
(E,Z)-Hexadeca-10,12-dienal (1)
The crude diene 8, obtained in the previous reaction, was dissolved
in THF (~7 mL), cooled to 0¡C and 1 M Bu4NF in THF (9.0 mL)
added dropwise. The resulting solution was stirred for 4 h and
worked-up according to standard procedures. The silyl impurities
present in the crude mixture were removed by Kugelrohr distilla-
tion. The residue was filtered through a pad of silica gel and eluted
with mixtures pentane/Et2O. The oil obtained after evaporation of
solvent in vacuo (assumed to be ~2.7 mmol) was dissolved
(CH2Cl2), added in one portion to PDC (20 mmol) in CH2Cl211 and
stirred at r.t. for 1 h. The mixture was diluted with Et2O and filtered
Acknowledgement
We wish to thank the Natural Sciences and Engineering Research
Council of Canada for a Research Grant to A.C.O.
References
(1) (a) Present Address: Escuela de Qu’mica, Universidad de
Costa Rica, San JosŽ, 2060, Costa Rica.
Synthesis 1999, No. 1, 107–111 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Stereospecific Synthesis of (E,Z)- and (Z,Z)-Hexadeca-10,12-dienal
111
(b) Present Address: ChemTica Internacional S. A., Apdo.
159-2150, San JosŽ, Costa Rica.
(9) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94,
6190.
(2) Raina, A. K.; Klun, J. A.; Schwarz, M.; Day, A.; Leonhardt,
B. A.; Douglass, L. W. J. Chem. Ecol. 1986, 12, 229.
(3) Klun, J. A.; Leonhardt, B. A.; Schwarz, M.; Day, A.; Raina,
A. K. J. Chem. Ecol. 1986, 12, 239.
(10) Stille, J. K.; Simpson, J. H. J. Am. Chem. Soc. 1987, 109,
2138.
(11) Ratcliffe, R.; Rodehorst, R. J. Org. Chem. 1970, 35, 4000.
(12) Brandsma, L.; Verkruijsse, H. Preparative Polar Organo-
metallic Chemistry 1; Springer-Verlag: Berlin, 1987.
(13) Watson, S. C.; Easthman, J. F. J. Organomet. Chem. 1967, 9,
165.
(14) Alexakis, A.; Normant, J. F.; Villieras, J. Tetrahedron Lett.
1976, 3461.
(4) Reed, D. W.; Underhill, E. W.; Giblin, E. M. J. Chem. Ecol.
1987, 13, 931.
(5) Miyaura, N.; Suginome, H.; Suzuki, A. Tetrahedron 1983, 39,
3271.
(6) Brown, C. A; Yamashita, A. J. Am. Chem. Soc. 1975, 97, 891.
Brown, C.A.; Yamashita, A. J. Chem. Soc., Chem. Commun.
1981, 11, 917.
(7) Negishi, E.; Lew, G.; Yoshida, T. J. Chem. Soc., Chem. Com-
mun. 1973, 874. Negishi, E.; Abramovitch, A. Tetrahedron
Lett. 1977, 411.
Normant, J. F.; Bourgain, M. Tetrahedron Lett. 1971, 2583.
Normant, J. F.; Cahiez, C.; Chuit, C.; Villieras, J. J. Organo-
met. Chem. 1974, 77, 269.
(15) Ratovelama, V.; Linstrumelle, G. Synth. Commun. 1981, 11,
917.
(8) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett. 1979,
3437.
Synthesis 1999, No. 1, 107–111 ISSN 0039-7881 © Thieme Stuttgart · New York