Synthesis of C37-Alkenones for Past Climate Reconstructions

Article abstract of DOI:10.1002/ejoc.202000145

The total syntheses of three C₃₇ methyl-alkenones with different degrees of unsaturation and of their ¹³C-labelled analogues from commercially available starting materials are presented herein for the first time. These molecules are important to improve the reliability of the measurements and reconstructions of the sea surface temperature and salinity.

Full text of DOI:10.1002/ejoc.202000145

A Journal of
Accepted Article
Title: Synthesis of C37-Alkenones for Past Climate Reconstructions
Authors: Giacomo Berton, Sarah Pizzini, Fabrizio Fabris, Tommaso
Bertolin, Eugenia Pafumi, Leonardo Ceccon, Jonas
Daelemans, Giuseppe Borsato, Alessandro Scarso, Rossano
Piazza, and Patrizia Ferretti
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000145
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
Synthesis of C37-Alkenones for Past Climate Reconstructions
Giacomo Berton,[a] Sarah Pizzini,[b],[c] Fabrizio Fabris, [a],* Tommaso Bertolin,[a] Eugenia Pafumi,[a]
Leonardo Ceccon,[a] Jonas Daelemans,[d] Giuseppe Borsato,[a] Alessandro Scarso,[a] Rossano Piazza,[b]
Patrizia Ferretti[b],[c]
Dedicated to Prof. Ottorino De Lucchi with respect and gratitude.
[a]
Prof. F. Fabris, G. Berton, T. Bertolin, E. Pafumi, L, Ceccon, G. Borsato and Prof. A. Scarso
Dipartimento di Scienze Molecolari e Nanosistemi
Università Ca’ Foscari Venezia
Via Torino 155, 30172 Mestre VE (ITALY)
E-mail: fabrisfa@unive.it
https://www.unive.it/data/people/5592325
Prof. R. Piazza, S. Pizzini, P. Ferretti
Dipartimento di Scienze Ambientali, Informatica e Statistica
Università Ca’ Foscari Venezia
Via Torino 155, 30172 Mestre VE (ITALY)
E-mail: piazza@unive.it
S. Pizzini, P. Ferretti
Istituto per la Dinamica dei Processi Ambientali, Consiglio Nazionale delle Ricerche (CNR-IDPA)
Università Ca’ Foscari Venezia
Via Torino 155, 30172 Mestre VE (ITALY)
E-mail: sarah.pizzini@idpa.cnr.it
[b]
[c]
[d]
J. Daelemens
Department of Chemistry, Faculty of Science
Antwerpen University
Groenenborgerlaan 17, 2020 Antwerpen (BELGIUM).
E-mail: jonas.daelemans@gmail.com
Supporting information for this article is given via a link at the end of the document.
The total syntheses of three C37 methyl-alkenones with different
degrees of unsaturation and of their 13C-labelled analogues
from commercially available starting materials are presented
herein for the first time. These molecules are important to
Uk′
=
(Equation 2)[5]
C
37:2
37
C
+C
37:2
37:3
improve
the
reliability
of
the
measurements
and
C37:2 represents the concentration of the heptatriaconta-
15E,22Edien-2-one (E,E-3), C37:3 the concentration of the
heptatriaconta-8E,15E,22E-trien-2-one (E,E,E-2), and C37:4 the
concentration of the heptatriaconta-8E,15E,22E,29E-tetraen-2-
one (E,E,E,E-1) (Figure 1).
reconstructions of the sea surface temperature and salinity.
Introduction
The reconstruction of ocean surface temperatures in the
geological past is central to assessing the climate history and
understanding what affects climate changes, as the oceans play
a fundamental role in the evolution of the Earth’s climate. One of
the most powerful tools for reconstructing sea surface
temperature (SST) is represented by the alkenone unsaturation
indices (Uk37 and Uk’37), extensively used in palaeoclimate and
palaeoceanography research.
Alkenones are biosynthesised by a few species of haptophyte
algae which prefer the upper photic zone (e.g., Emiliania huxleyi,
Lohmann 1902; Gephyrocapsa oceanica, Kamptner 1943),[1-2]
and the indices reported above are based on the observation
that the extent of unsaturation of the 37-carbon chain length
alkenones (C37) varies with the temperature of the water in
which the algae grew.[3] The numerical expression of this
relationship gave rise to the compilation of two indices, which
are linearly correlated with SST, as reported in Equations 1 and
2.
Figure 1. The structures of alkenones E,E,E,E-1, E,E,E-2 and E,E-3.
In Equation 2, the abundance of the tetra-unsatured alkenone
C37:4 was omitted, due to its insignificant contribution to SST.
However, the C37:4 remains an important proxy index of climate
change, being linked to low-salinity water masses,[6] and often
employed to infer the surface advection of iceberg-bearing water
C
37:2
−C
37:3
Uk
=
(Equation 1)[3-4]
37
C
37:2
+C +C
37:3 37:4
1
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
masses together with their living arctic alkenone producers.[7]
The discovery in the mid 1980’s that the alkenone unsaturation
indices recovered in sediments could provide insights into past
acetal.[18] The key-reagent 7 was obtained in a reproducible 86%
overall yield in 3 steps, in a ten gram scale.
changes in SST represented
a
major breakthrough in
palaeoclimate research. Since then, stratigraphic variations in
the Uk37 and Uk’ recorded in ocean sediment have provided
37
time series records of past SST change on a variety of
timescales,[8-9] spanning the Cenozoic, at least since the Eocene.
As with any palaeoceanographic proxy, there are still some
questions that need to be addressed in order to improve the
confidence in the data and enhance the reliability of the SST
reconstruction. To our knowledge, one of them is related to the
commercial unavailability of standard compounds which
Scheme 1. Preparation of key-reagent 7. Reagents and conditions. a: 48% aq
HBr, toluene, 120 °C, 48 h (98%); b: NaOCl, TEMPO (cat.), NaHCO3,
H2O/DCM, 25 °C, 1 h (98%); c: 1,2-ethanediol, PTSA (cat.), cyclohexane, 3 Å
MS, 90 °C, 18 h (96%).
represent
a fundamental and inescapable requirement to
develop and validate an analytical method, as well as to
optimize its analytical results. The synthesis of compounds 1-3
was briefly presented in an early article by Rechka and
Maxwell,[10] in which detailed description of the methods was
postponed to a future article, so far not published, although the
mass properties of these compounds were described in a
second article of the same year.[11] Herein we present our
methodology, that takes advantage of the synthetic
improvements occurred in the meantime, allowing in most cases
a safer and environmentally friendly alternative, like the use of
photoisomerisation of Z-double bonds versus the use of E-
selective, but potentially noxious, chromium-based coupling
reactions. Furthermore, the syntheses were extended to the
preparation of the 13C-labelled analogous compounds, that could
greatly improve the analytical accuracy of the measurement of
alkenone concentrations, with respect to the use of the n-alkane
hexatriacontane which is usually employed as an internal
standard for this kind of determinations.[12-15] Here we report on
the synthesis of heptatriaconta-15E,22Edien-2-one (E,E-3),
The Wittig reaction turned out to be particularly troublesome,
requiring an in-depth screening of the operative conditions
(solvents, bases and temperatures; Scheme 2). Eventually, the
best methodology turned out to be the preparation of the
alkylphosphonium salt 8[19] in acetonitrile (ACN). This solvent
was finally replaced by a mixture of DMPU/THF for the reaction
of formation of the phosphorus ylide, that was accomplished with
n-butyllithium at 0 °C.[20] This temperature resulted a good
compromise to limit the reactivity of the base and, at the same
time, to avoid the precipitation of the reagent, that in some cases
caused a decrease of the yields. The Wittig reaction produced
the desired alkene moiety with remarkable Z-selectivity (more
than 95:5, according to H NMR integrals),§ although the double
1
bonds in natural occurring alkenones 1-3 are all with E
configuration. This issue was not considered crucial, since a
photoisomerisation of all the alkenes in the late stage of the
syntheses was planned. Hydrolyses to restore the aldehydic
moieties required for the following Wittig reactions were
achieved refluxing the acetals in moistened acetic acid, which
resulted mild and effective (Scheme 2).
heptatriaconta-8E,15E,22E-trien-2-one
(E,E,E-2),
and
heptatriaconta-8E,15E,22E,29E-tetraen-2-one (E,E,E,E-1; Fig.
1), in order to provide compounds of high degree of purity,
suitable to be used as calibration standards for analytical
methods and help to ascertain the deviation in the results
between laboratories. We also synthesised their 13C-labelled
methyl-ketone analogous compounds, which allow quality
assurance and quality control procedures, reducing bias that
might occur before the instrumental analysis.
Results and Discussion
The syntheses of compounds 1-3 consist in a series of Wittig
reactions, starting from the suitable linear aliphatic aldehyde (i.e.
octanal and pentadecanal) with a common synthon, bearing a
terminal bromide and a protected aldehyde. The latter reagent
has been obtained from commercially available 1,7-heptanediol
in three steps (Scheme 1). The monobromination was
successfully achieved in very good yields according to the
methodology reported by Chong and coworkers.[16] The
oxidation of the residual alcoholic moiety was obtained with a
simple, efficient and environmentally friendly methodology, using
commercial bleach in the presence of a catalytic amount of
TEMPO.[17] The aldehyde was finally protected as 1,3-dioxolane,
since conspicuous loss of material was observed in the following
phosphonation step, if the aldehyde was protected as dimethyl
Scheme 2. First Wittig reaction for the syntheses of 1 and 2. Reagents and
conditions. a: PPh3, ACN, 100 °C, 72 h (98%); b: i) n-BuLi, DMPU/THF, -5-
0 °C, 2 h; ii) C7H15CHO or C14H29CHO, 25 °C, 30 min (73 and 87%); c: H2O,
AcOH, 110 °C, 24 h (67% and 99%).
Starting from aldehyde 11, a sequential repetition for three times
of the Wittig reaction with the ylide derived from phosphonium
salt 8 and deprotection of the resulting acetal moieties afforded
aldehyde 22, which only requires one methyl to complete the C37
final linear chain (Scheme 3). Similarly, starting from aldehyde
12, a sequential repetition for two times of the Wittig reaction
2
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
with the ylide derived from 7 and deprotection of the resulting
acetal moieties[21] afforded aldehyde 20, which only requires one
methyl to complete the C37 final linear chain (Scheme 3).
Scheme 3. Second and third Wittig reaction for the syntheses of 1 and 2 and additional fourth one for 2. Reagents and conditions. a: i) 7, PPh3, ACN, 100 °C, 72
h; ii) n-BuLi, DMPU/THF, -5-0 °C, h; iii) indicated reagent, 25 °C, 30 min (indicated yields); b: H2O, AcOH, 110 °C, 24 (indicated yields).
2
h
Scheme 4. Preparation of key-reagent 28. Reagents and conditions. a: TBSCl,
Et3N, ACN/cyclohexane, 25 °C, 24 (63%); b: NaOCl, TEMPO (cat.),
NaHCO3, H2O/DCM, 25 °C, 1 h (94%); c: i) 7, PPh3, ACN, 100 °C, 72 h; ii) n-
BuLi, DMPU/THF, -5-0 °C, 2 h; iii) indicated reagent, 25 °C, 30 min (66%); d:
H2 (0.1 MPa), 5% Pd/C, AcOEt, 25 °C, 5 h (94%); e: NH4F, MeOH, 90 °C, 10 h
(95%); f: CBr4, PPh3, ACN, from 0 to 25 °C, 24 h (89%).
In the case of compound 3, after the first Wittig-hydrolysis
sequence affording aldehyde 12, a new reagent was required to
introduce the saturated C14 linear chain. The synthesis of the
acetal-protected 14-bromotetradecanal 28 started from the
commercially available 1,7-heptanediol 4 (Scheme 4), which
was partially protected as tert-butyldimethylsilyl ether. In order to
avoid a statistical distribution of mono-, di- and un-protected diol,
a combination of a biphasic solvent system[22] was employed in
combination with a very slow addition of the silylating reagent.
The alcoholic moiety was oxidised with the previously described
methodology,[17] although in low yields, presumably for an over
oxidation caused by the presence of an excess of bleach. The
resulting aldehyde was reacted with the ylide derived from 7 and
the Wittig reaction afforded the unsaturated C14 functionalised
alkyl chain Z>E-25, that was hydrogenated to remove the double
bond. The TBS moiety was easily and efficiently removed with
ammonium fluoride,[23] and the resulting alcohol was replaced in
one step under the neutral conditions of Appel reaction, although
the use of ACN was crucial for the success of the reaction.[24-26]
In conclusion, the second key-reagent 28 was obtained in 31%
overall yield in 6 steps.
h
Reagent 28 was used to generate under the previously
described methodology[20] the phosphorus ylide, that reacted
with Z>E-12 to complete the C36 linear chain containing two
double bonds Z>E-29. The acetal moiety was removed
according to the usual hydrolytic methodology to afford the
aldehyde 30 (Scheme 5).
Scheme 5. Last Wittig reaction for the synthesis of 3. Reagents and conditions.
a: i) 28, PPh3, ACN, 100 °C, 48 h; ii) n-BuLi, DMPU/THF, -5-0 °C, 2 h; iii)
indicated reagent, 25 °C, 30 min (51%); b: H2O, AcOH, 110 °C, 24 h (65%).
The three aldehydes Z>E-22, Z>E-20 and Z>E-30 were reacted
with Grignard reagents CH3MgI and 13CH3MgI in diethyl ether to
afford the corresponding alcohols, eventually isotopically marked
at the methyl substituent (Scheme 6).
3
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
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double bonds, affording the final ketones all-E-1-3(*), whose
stereochemical purity was largely improved by
crystallisation from hot methanol.
a
final
Scheme 6. Addition of the last fragment of the C37 chain (eventually 13C-
labelled). Reagents and conditions. a: i) CH3I or 13CH3I, Mg, Et2O, 40 °C, 15
min; ii) indicated reagent, 25 °C, 30 min (indicated yields).
Before oxidising compounds Z>E-31-33(*) to the corresponding
ketones, that could suffer some Norrish I or II rearrangements,
the obtained alcohols were subjected to the photoisomerisation
to obtain the all-E isomers. The reaction was accomplished with
a 500 W high pressure mercury lamp in cyclohexane, in the
Scheme 8. Final oxidative step for the syntheses of 1, 2, 3. Reagents and
conditions. a: i) Me2SO, (COCl)2, DCM, -78 to -40 °C, 1 h; ii) Et3N, -40 to 25 °C,
1 h (indicated yields).
presence of
a
radical scavenger (Scheme 7).[27-28] The
Conclusion
effectiveness of the reaction was confirmed by the 0.03 ppm
1
down-field shifts of the main vinyl resonances in the H NMR of
In conclusion, compounds E,E,E,E-1, E,E,E-2 and E,E-3 were
obtained in 11%, 5% and 5% yields after 11, 9 and 7 steps,
starting from octanal in the first case and from pentadecanal in
the latter cases. These compounds will be used as standards for
accurate analytical measurements of their concentrations in
oceanic sediments, in order to reconstruct palaeotemperature
and salinity records. Furthermore, the 13C-labelled analogues
compounds E,E,E,E-1*, E,E,E-2* and E,E-3* were obtained in
4%, 9% and 3% yields. These compounds will improve the
reliability of such measurements, in virtue of the isotopic dilution
procedures.
the crude material (analogues 0.3 ppm down-field shifts were
observed in 13C NMR). More significantly, the resonances of the
allylic carbons experienced a down-field shift of ca. 5 ppm, from
nearly 27 to 32 ppm.[29]
Experimental Section
The reactions were followed with TLC Polygram Sil G/UV254, 0.25 mm
thickness. 1H NMR, 13C NMR, and 2D spectra were recorded with a
Bruker Avance 300 and Ascend 400 spectrometers, working at 300-400
and 75-100 MHz respectively. Resonance frequencies are referred to
tetramethylsilane. IR spectra were recorded with
a Perkin Elmer
Spectrum One spectrophotometer. Masses of the intermediate new
products were obtained with a Bruker Compact (ESI-TOF) spectrometer.
Source type: ESI Ion Polarity Positive. Set Nebuliser: 0.3 Bar. Focus
Active Set Capillary: 4500 V. Set Dry Heater: 200 °C. Scan begins at 50
m/z and ends at 800 m/z. Set End Plate Offset: -500 V. Set Dry Gas: 3.5
L/min. Set Collision Cell RF: 2500.0 Vpp. A 1 mg/mL solution of sample
in DCM was diluted 1:1000 into i-PrOH containing 0.1% trifluoroacetic
acid and the solution injected by syringe pump. Masses of final products
were analysed by single quadrupole GC/LRMS (Hewlett Packard-Agilent
6890 Series GC System, coupled with an Agilent 5973 inert Mass
Selective Detector) operating in Electron Impact mode (EI, 70 eV)
equipped with a 30 m long column (HP-5ms, 0.25 mm I.D., 0.25 μm film
thickness). The MS source and analyser were set to 230 °C and 150 °C
Scheme 7. Photoisomerisation of the precursors of 1, 2, 3. Reagents and
conditions. a: PhSSPh, cyclohexane, Ar, 25 °C, 1 h (indicated yields).
The final oxidation of the alcohols 31-33(*) was accomplished by
a mild Swern oxidation (Scheme 8), that does not affect the
4
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
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respectively, while the transfer line was set to 300 °C. The operating
conditions of the GC were optimised and set as follows. Helium 5.5
(99.9995%) was used as carrier gas at a constant flow rate of 1.0 mL
min-1. The splitless mode inlet was set to 300 °C. The oven was
programmed from 90 °C to 315 °C at 30 °C min-1 with 17.5 min hold, for a
total run time of 25 min. Acquisition was performed in Full Scan mode
and perfluorotributylamine (PFTBA) was chosen as reference compound.
GC/HRMS characterisation was carried out by Hewlett Packard-Agilent
6890 Series GC System, coupled with a Thermo Finnigan MAT 95 XP
operating in EI mode (45 eV; R ≥ 10,000) equipped with a 15 m long
column of the same type, for a total run time of 12 min. Acquisition was
performed in Multiple Ion Detection (MID) mode. The MS source was set
to 290 °C and the transfer line to 300 °C. PFK was selected as reference
compound to provide the inherent lock (504.9691) and cali (554.9659)
masses. Reagents and solvents with high purity degree purchased by the
providers were used as given. Otherwise, they were purified following the
procedures reported in literature.[30] Anhydrous solvents were prepared
by adding activated 3 Å molecular sieves to the solvent under inert
atmosphere. Molecular sieves were activated shortly before the use by
continuous heating under vacuum. Flash chromatography were
performed with silica gel Merk 60, 230-400 mesh, following procedures
reported in literature.[31]
× 110 mL). The organic phase was dried over MgSO4, filtered and dried
in vacuum. The crude product was purified by flash chromatography.
General Procedure to Grignard Reaction (GP4)
In a flame-dried 50 mL Schlenk-tube, Mg (0.21 g, 8.5 mmol) was dry-
stirred for 18 h under argon. To the resulting solid anhydrous Et2O (0.5
mL) and a solution of MeI (1.0 g, 7.1 mmol) in anhydrous Et2O (5 mL)
were added dropwise, keeping a steady flow in order to maintain the
mixture under reflux. The resulting suspension was refluxed for an
additional 0.5 h, cooled to room temperature and decanted, obtaining a
fresh solution of MeMgI (nearly 1.4 M in Et2O). The solution was rapidly
transferred via syringe (equipped with a PE filter) to a 50 mL round-
bottomed two-necked flask with argon inlet and septum containing a
solution of aldehyde (2.9 mmol) in anhydrous Et2O (2 mL). The mixture
was stirred at room temperature for 1 h. The reaction was quenched with
saturated aqueous NH4Cl (150 mL) and the resulting mixture was
extracted with Et2O (3 × 50 mL). The combined organic phases were
dried over MgSO4, filtered and dried in vacuum. The crude product was
purified by flash chromatography.
General Procedure to Alcohol Isomerisation (GP5)
General Procedure to Primary Alcohols Oxidation (GP1)
In a 500 mL photochemical reactor, a solution of the secondary alcohol
isomers (0.34 mmol, 1 eq.) and diphenyl disulphide (2 eq. for each
double bond of the secondary alcohol) in cyclohexane (280 mL) was
bubbled with argon for 0.5 h. The bubbling was maintained while the
solution was irradiated from inside with a 500 W high pressure mercury-
vapor lamp (Helios-Italquartz) in a quartz cooling jacket (a picture of the
home-made photochemical apparatus is reported in the Supporting
Information). The reaction was followed via 1H NMR, observing the vinylic
signals shifting up-field. The resulting solution was concentrated in
vacuum and the crude product was purified by flash chromatography.
In a 250 mL round bottomed flask, primary alcohol (22 mmol, 1 eq.) and
TEMPO (0.01 eq.) were dissolved in DCM (45 mL). A solution composed
by aqueous 5% NaOCl (1.4 eq) and saturated aqueous NaHCO3 (25 mL)
was then poured in the flask and the resulting mixture was vigorously
stirred at room temperature for 45 min, checking the reaction through
TLC. The reaction was then quenched with saturated aqueous Na2S2O3
(90 mL). The mixture was decanted and the organic phase collected. The
aqueous layer was extracted with DCM (4 × 50 mL) and the combined
organic phases were washed with saturated aqueous NaHCO3 (2 × 50
mL), dried over MgSO4, filtered and concentrated in vacuum. The
recovered product was pure enough for the following steps.
General Procedure to Swern Oxidation (GP6)
In a 250 mL round bottomed two necked flask, dried following Schlenk
technique and equipped with argon inlet and septum, DMSO (3 eq.) was
dissolved in anhydrous DCM (10 mL) and the solution was cooled to -
78 °C. Oxalyl chloride (2 eq.) was added dropwise and the resulting
solution was stirred for 20 min at -78 °C. A solution of secondary alcohol
(2.5 mmol, 1 eq.) in anhydrous DCM (6 mL) was added dropwise, and
the resulting solution was stirred for 1 hour, allowing the temperature to
rise to -40 °C. Triethylamine (2.6 mL) was added and the solution was
allowed to reach room temperature. The reaction was quenched in water
(60 mL). The organic phase was separated and the aqueous layer was
extracted with DCM (3 × 20 mL). The combined organic phases were
dried over MgSO4, filtered and concentrated in vacuum to afford crude
product that was purified by flash chromatography and recrystallized from
methanol.
General Procedure to Wittig Reaction (GP2)
In a 250 mL round bottomed flask, alkyl bromide (25.3 mmol, 1 eq.) and
triphenylphosphine (1.2 eq.) were suspended in anhydrous ACN (63 mL).
The flask was topped with a reflux condenser and an argon inlet, then the
suspension was refluxed for 72 h, checking the reaction through TLC.
The resulting solution was dried in vacuum, then DMPU (28 mL) was
added. The solution was stirred under vacuum at 80 °C for 0.5 h, then
cooled to room temperature. The flask was topped with a septum and
purged with argon. Anhydrous THF (114 mL) was added, then the
solution was cooled to -5 °C. n-Butyllithium (1.6 M in hexane, 19 mL, 1.2
eq.) was added dropwise with a syringe over a period of 2 h, keeping the
temperature between -5 and -1 °C to avoid the formation of a precipitate.
The resulting red solution was allowed to return to room temperature,
then pure aldehyde (or a solution in 10 mL of cyclohexane) (0.9 eq.) was
injected rapidly. The resulting solution was stirred for 15 min at room
temperature. Water (60 mL) was added and the resulting mixture was
extracted with cyclohexane (3 × 30 mL). The combined organic phases
were washed with water (2 × 50 mL), dried over MgSO4, filtered and
dried in vacuum. The crude product was purified by flash
chromatography.
7-Bromoheptan-1-ol (5): In a 500 mL round bottomed flask, 1,7-
heptandiol (10 g, 76 mmol) was dissolved in toluene (230 mL). Aqueous
48% HBr (19 mL) was added, the flask was topped with a reflux
condenser and the mixture was refluxed for 48 h. The mixture was
cooled to room temperature, decanted and the organic phase was
collected, washed with saturated aqueous NaHCO3 (2 × 100 mL), dried
over MgSO4, filtered and concentrated in vacuum. The product was
obtained as a colourless oil (13.8 g, 93% yield). Rf = 0.58 (silica gel,
Et2O); 1H NMR (400 MHz, CDCl3): δ 3.65 (2H, t, J = 6.6 Hz), 3.41 (2H, t,
J = 6.8 Hz), 1.91-1.82 (2H, m), 1.62-1.54 (2H, m), 1.49-1.27 (6H, m).
Further spectroscopic data (13C, IR, MS) are in accordance with the
literature.16
General Procedure to Acetal Removal (GP3)
In a 250 mL round bottomed flask, acetal (22 mmol, 1eq.) was dissolved
in acetic acid (170 mL) and water (30 mL) was added. The system was
purged with argon and the solution was stirred overnight at 100 °C. The
resulting solution was cooled to room temperature and poured over
saturated aqueous NaHCO3 (160 mL) and cyclohexane (300 mL). The
aqueous layer was extracted with cyclohexane (3 × 100 mL) and the
collected organic layers were washed with saturated aqueous NaHCO3 (3
7-Bromoheptanal (6): GP1 was applied to 5. Yellow oil (12.0 g, 95%
yield). Rf = 053 (silica gel, 2:8 AcOEt/cyclohexane); 1H NMR (400 MHz,
CDCl3): δ 9.77 (1H, t, J = 1.7 Hz), 3.41 (2H, t, J = 6.7 Hz), 2.45 (2H, td, J
5
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
= 7.3, 1.7 Hz), 1.92-1.81 (2H, m), 1.73-1.58 (2H, m), 1.53-1.29 (4H, m).
Further spectroscopic data (13C, IR, MS) are in accordance with the
literature.17
2-(Octacosa-6,13,20-trien-1-yl)-1,3-dioxolane (Z>E-17): GP2 was
applied to Z>E-15 and 7, eluent 5:95 AcOEt/cyclohexane, colourless oil
(81% yield). Rf = 0.46 (silica gel, 5:95 AcOEt/cyclohexane); 1H NMR (400
MHz, CDCl3): δ 5.43-5.28 (6H, m), 4.84 (1H, t, J = 4.8 Hz), 4.00-3.79 (4H,
m), 2.07-1.91 (12H, m), 1.71-1.59 (2H, m), 1.47-1.20 (28H, m), 0.87 (3H,
t, J = 6.7 Hz); 13C{1H} NMR (100 MHz): δ 130.1 (CH), 130.1 (CH), 130.0
(CH, 2C), 129.9 (CH), 129.9 (CH), 104.8 (CH), 65.0 (CH2, 2C), 34.1
(CH2), 32.04 (CH2), 29.9 (CH2), 29.8 (CH2, 5C), 29.4 (CH2), 29.4 (CH2,
2C), 29.1 (CH2, 2C), 27.4 (CH2), 27.3 (CH2, 4C), 27.3 (CH2), 24.1 (CH2),
22.8 (CH2), 14.3 (CH3); IR (film) νmax 3399, 2926, 2854, 1577, 1543, 1456,
1429, 1251, 1209, 1006, 785, 760 cm-1; HRMS (ESI-TOF) m/z: [M+H+]
calcd for C31H57O2 461.4353; found 461.4342.
2-(6-Bromohexyl)-[1,3]dioxolane (7): In a 250 mL round bottomed flask,
6 (14.2 g, 73.6 mmol), ethylene glycol (5.5 g, 88.7 mmol), and p-
toluensulphonic acid monohydrate (0.01 g, 0.06 mmol) were dissolved in
cyclohexane (140 mL). A pressure-equalizing dropping funnel filled with
activated 3 Å molecular sieves was placed over the flask and topped with
a reflux condenser. The apparatus was purged with argon and the
suspension refluxed overnight for 18 h. The resulting solution was poured
over saturated aqueous NaHCO3 (20 mL), decanted, and the organic
layer was washed again with saturated aqueous NaHCO3 (3 × 20 mL),
dried over MgSO4, filtered and concentrated in vacuum. The product was
obtained as light orange oil (15.4 g, 97% yield). Rf = 053 (silica gel, 2:8
AcOEt/cyclohexane); 1H NMR (300 MHz, CDCl3): δ 4.85 (1H, t, J = 4.8
Hz), 4.04-3.78 (4H, m), 3.41 (2H, td, J = 6.8, 2.0 Hz), 1.92-1.80 (2H, m),
1.72-1.58 (2H, m), 1.56-1.25 (6 H, m). Further spectroscopic data (13C,
IR, MS) are in accordance with the literature.17
Nonacosa-7,14,21-trienal (Z>E-19): GP3 was applied to Z>E-17,
colourless oil (99% yield). Rf = 0.46 (silica gel, 5:95 AcOEt/cyclohexane);
1H NMR (400 MHz, CDCl3): δ 9.77 (1H, t, J = 1.8 Hz), 5.46-5.17 (6H, m),
2.42 (2H, td, J = 7.4, 1.9 Hz), 2.08-1.94 (12H, m), 1.71-1.55 (2H, m),
1.41-1.22 (28H, m), 0.88 (3H, t, J = 6.7 Hz); 13C{1H} NMR (100 MHz): δ
202.9 (CH), 130.4 (CH), 130.1 (CH), 130.0 (CH), 130.0 (CH), 129.9 (CH),
129.6 (CH), 44.0 (CH2), 32.0 (CH2), 29.9 (CH2), 29.8 (CH2, 3C), 29.8
(CH2), 29.6 (CH2), 29.4 (CH2), 29.4 (CH2), 29.1 (CH2, 2C), 28.9 (CH2),
27.4 (CH2), 27.3 (CH2, 4C), 27.1 (CH2), 22.8 (CH2), 22.2 (CH2), 14.3
(CH3); IR (film) νmax 2924, 2850, 1577, 1546, 1465, 1429, 1261, 1209,
1097, 1013, 794, 760 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for
C29H53O 417.4091; found 417.4083.
2-(Tetradec-6-en-1-yl)-1,3-dioxolane (Z>E-9): GP2 was applied to
octanal and 7, eluent 5:95 AcOEt/cyclohexane, colourless oil (73% yield).
Rf = 0.36 (silica gel, 1:9 AcOEt/cyclohexane); 1H NMR (400 MHz, CDCl3):
δ 5.43-5.30 (2H, m), 4.86 (1H, t, J = 4.8 Hz), 4.00-3.84 (4H, m), 2.42-2.29
(2H, m), 2.07-1.98 (4H, m), 1.70-1.62 (2H, m), 1.46-1.29 (14H, m), 0.90
(3H, t, J = 6.5 Hz); 13C{1H} NMR (100 MHz): δ 130.2 (CH), 129.8 (CH),
104.8 (CH), 65.0 (CH2), 34.0 (CH2), 32.0 (CH2), 29.9 (CH2), 29.8 (CH2),
29.4 (CH2), 29.4 (CH2), 27.4 (CH2), 27.2 (CH2), 24.1 (CH2), 22.8 (CH2),
14.2 (CH3); IR (KBr) νmax 3006, 2926, 2849, 1728, 1655, 1580, 1541,
1460, 1434, 1412, 1371, 1353, 1307, 1263, 1200, 1140, 1043, 960, 949,
900, 719, 700 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C17H33O2
269.2448; found 269.2446.
2-(Pentatriaconta-6,13,20,27-tetraen-1-yl)-1,3-dioxolane
(Z>E-21):
GP2 was applied to Z>E-19 and 7, eluent 5:95 AcOEt/cyclohexane,
colourless oil (73% yield). Rf = 0.35 (silica gel, 5:95 AcOEt/cyclohexane);
1H NMR (400 MHz, CDCl3): δ 5.41-5.29 (8H, m), 4.84 (1H, t, J = 4.8 Hz),
4.00-3.81 (4H, m), 2.10-1.91 (16H, m), 1.70-1.60 (2H, m), 1.47-1.24 (34H,
m), 0.87 (3H, t, J = 6.8 Hz); 13C{1H} NMR (100 MHz): δ 130.1 (CH), 130.1
(CH), 130.0 (CH, 3C), 130.0 (CH), 129.9 (CH), 129.9 (CH), 104.8 (CH),
65.0 (CH2, 2C), 34.1 (CH2), 32.7 (CH2), 32.0 (CH2), 29.9 (CH2), 29.8
(CH2, 6C), 29.8 (CH2), 29.7 (CH2), 29.4 (CH2), 29.4 (CH2, 2C), 29.1 (CH2,
2C), 27.4 (CH2), 27.3 (CH2, 5C), 27.3 (CH2), 24.1 (CH2), 22.8 (CH2), 14.3
(CH3); IR (film) νmax 3005, 2926, 2855, 1464, 1432, 1401, 1259, 1141,
1031, 968, 941, 801, 721 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for
C38H68O2 557.5292; found 557.5292.
Pentadec-7-enal (Z>E-11): GP3 was applied to Z>E-9, colourless oil
1
(67% yield). Rf = 0.36 (silica gel, 1:9 AcOEt/cyclohexane); H NMR (400
MHz, CDCl3): δ 9.74 (1H, t, J = 1.8 Hz), 5.39-5.27 (2H, m), 2.40 (2H, td, J
= 7.4, 1.9 Hz), 2.06-1.92 (4H, m), 1.66-1.57 (2H, m), 1.40-1.19 (14H, m),
0.85 (3H, t, J = 6.6 Hz); 13C{1H} NMR (100 MHz): δ 202.7 (CH), 130.4
(CH), 129.4 (CH), 44.0 (CH2), 32.0 (CH2), 29.8 (CH2), 29.5 (CH2), 29.4
(CH2), 29.3 (CH2), 28.9 (CH2), 27.3 (CH2), 27.0 (CH2), 22.8 (CH2), 22.1
(CH2), 14.2 (CH3); IR (film) νmax 3384, 2917, 2849, 1574, 1541, 1465,
1429, 784, 760 cm-1; HRMS (ESI-TOF) m/z: [M+Na+] calcd for
C15H28ONa 247.2032; found 247.2009.
Hexatriaconta-7,14,21,28-tetraenal (Z>E-22): GP3 was applied to Z>E-
21, eluent 5:95 AcOEt/cyclohexane, colourless oil (87% yield). Rf = 0.35
(silica gel, 5:95 AcOEt/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 9.76
(1H, t, J = 1.8 Hz), 5.50-5.20 (8H, m), 2.42 (2H, td, J = 7.3, 1.9 Hz), 2.09-
1.94 (16H, m), 1.71-1.59 (2H, m), 1.41-1.20 (32H, m), 0.88 (3H, t, J = 6.8
Hz); 13C{1H} NMR (100 MHz): δ 202.9 (CH), 130.4 (CH), 130.1 (CH),
130.0 (CH, 2C), 130.0 (CH), 130.0 (CH), 130.0 (CH), 129.6 (CH), 44.0
(CH2), 32.0 (CH2), 29.9 (CH2), 29.8 (CH2), 29.8 (CH2, 4C), 29.7 (CH2),
29.6 (CH2), 29.4 (CH2), 29.4 (CH2), 29.1 (CH2, 3C), 28.9 (CH2), 27.4
(CH2), 27.4 (CH2), 27.3 (CH2, 4C), 27.1 (CH2), 22.8 (CH2), 22.2 (CH2),
22.1 (CH2), 14.3 (CH3); IR (film) νmax 3437, 3005, 2926, 2855, 2708, 1729,
1651, 1463, 1434, 1404, 1261, 1094, 1027, 861, 803, 721, 696 cm-1;
HRMS (ESI-TOF) m/z: [M+H+] calcd for C36H65O 513.5030; found
513.5020.
2-(Henicosa-6,13-dien-1-yl)-1,3-dioxolane (Z>E-13): GP2 was applied
to Z>E-11 and 7, eluent 5:95 AcOEt/cyclohexane, colourless oil (80%
yield). Rf = 0.41 (silica gel, 1:9 = AcOEt/cyclohexane); 1H NMR (400 MHz,
CDCl3): δ 5.42-5.29 (4H, m), 4.84 (1H, t, J = 4.9 Hz), 4.02-3.79 (4H, m),
2.09-1.92 (8H, m), 1.75-1.54 (2H, m), 1.47-1.22 (22H, m), 0.88 (3H, t, J =
6.8 Hz); 13C{1H} NMR (100 MHz): δ 130.1 (CH), 130.1 (CH), 129.9 (CH),
129.9 (CH), 104.8 (CH), 65.0 (CH2, 2C), 34.1 (CH2), 32.0 (CH2), 29.9
(CH2), 29.8 (CH2, 3C), 29.4 (CH2), 29.4 (CH2, 2C), 29.1 (CH2), 27.4 (CH2),
27.3 (CH2, 2C), 27.2 (CH2), 24.1 (CH2), 22.8 (CH2), 14.3 (CH3); IR (film)
νmax 3401, 3005, 2927, 2856, 1577, 1542, 1465, 1434, 1407, 1259, 1141,
1039, 965, 784, 760 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for
C24H45O2 365.3387; found 365.3393.
Heptatriaconta-8,15,22,29-tetraen-2-ol (Z>E-31): GP4 was applied to
Z>E-22, colourless oil (98% yield). Rf
= 0.28 (silica gel, 9:1
DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 5.43-5.25 (8H, m),
3.79 (1H, td, J = 6.6, 5.5 Hz), 2.09-1.93 (16H, m), 1.57-1.48 (2H, m),
1.48-1.23 (34H, m), 1.19 (3H, d, J = 6.2 Hz), 0.87 (3H, t, J = 6.7 Hz);
13C{1H} NMR (100 MHz): δ 130.1 (CH), 130.1 (CH), 130.0 (CH, 2C),
130.0 (CH, 2C), 129.9 (CH), 129.9 (CH), 68.2 (CH), 39.5 (CH2), 32.7
(CH2), 32.0 (CH2), 29.9 (CH2), 29.9 (CH2), 29.8 (CH2, 5C), 29.8 (CH2),
29.7 (CH2), 29.4 (CH2, 2C), 29.4 (CH2), 29.1 (CH2, 2C), 29.0 (CH2), 27.4
(CH2), 27.3 (CH2, 4C), 27.3 (CH2), 25.8 (CH2), 23.7 (CH2), 22.8 (CH2),
14.3 (CH3); IR (film) νmax 3005, 2927, 2855, 1577, 1541, 1464, 1260,
1212, 1097, 1009, 971, 784, 757 cm-1.
Docosa-7,14-dienal (Z>E-15): GP3 was applied to Z>E-13, colourless
oil (98% yield). Rf = 0.41 (silica gel, 1:9 AcOEt/cyclohexane); 1H NMR
(400 MHz, CDCl3): δ 9.76 (1H, t, J = 1.9 Hz), 5.41-5.28 (4H, m), 2.42 (2H,
td, J = 7.4, 1.9 Hz), 2.08-1.92 (8H, m), 1.69-1.58 (2H, m), 1.43-1.20 (20H,
m), 0.88 (3H, t, J = 6.7 Hz); 13C{1H} NMR (100 MHz) δ 202.9 (CH), 130.4
(CH), 130.1 (CH), 129.9 (CH), 129.5 (CH), 44.0 (CH2), 32.0 (CH2), 29.9
(CH2), 29.8 (CH2), 29.8 (CH2), 29.6 (CH2), 29.4 (CH2), 29.4 (CH2), 29.1
(CH2), 28.9 (CH2), 27.4 (CH2), 27.3 (CH2), 27.3 (CH2), 27.1 (CH2), 22.8
(CH2), 22.1 (CH2), 14.3 (CH3); IR (film) νmax 3391, 2922, 2851, 1711,
1574, 1543, 1435, 1261, 1105, 1012, 785, 762 cm-1; HRMS (ESI-TOF)
m/z: [M+H+] calcd for C22H41O 321.3152; found 321.3136.
6
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
(8E,15E,22E,29E)-Heptatriaconta-8,15,22,29-tetraen-2-ol
(E>Z-31):
= 14 Hz), 32.8 (CH2), 32.7 (CH2, 3C), 32.5 (CH2), 32.0 (CH2), 30.2 (CH2),
30.1 (CH2), 30.0 (CH2), 30.0 (13CH3), 29.9 (CH2), 29.8 (CH2), 29.8 (CH2),
29.7 (CH2, 3C), 29.6 (CH2), 29.5 (CH2), 29.3 (CH2), 29.3 (CH2), 28.8
(CH2), 28.8 (CH2), 28.8 (CH2), 28.8 (CH2), 23.9 (CH2), 22.8 (CH2), 14.2
(CH3); IR (KBr) νmax 3425, 2954, 2919, 2848, 1712, 1466, 1457, 1435,
1375, 1344, 1163, 1070, 963, 720 cm-1; GC/LRMS (EI, 70 eV) m/z: 527.6
(M+, 0.4), 109.2 (8), 95.2 (15), 86.0 (64), 84.0 (100), 81.1 (16), 67.1 (16),
55.2 (14), 51.1 (36%); GC/HRMS (EI, 45 eV) m/z: [M]+ calcd for
C3613CH66O 527.5147; found 527.5035; Kováts retention index 3876.[32]
GP5 was applied to Z>E-31, eluent 1:9 AcOEt/cyclohexane, white waxy
solid (85% yield). Rf = 0.30 (silica gel, 9:1 DCM/cyclohexane); 1H NMR
(400 MHz, CDCl3): δ 5.44-5.30 (8H, m), 3.84-3.74 (1H, m), 2.08-1.90
(16H, m), 1.59-1.22 (36H, m), 1.18 (3H, d, J = 6.2 Hz), 0.87 (3H, t, J =
6.7 Hz); 13C{1H} NMR (100 MHz): δ 130.6 (CH), 130.6 (CH), 130.5 (CH,
2C), 130.5 (CH, 2C), 130.4 (CH), 130.3 (CH), 68.3 (CH), 39.5 (CH2), 32.8
(CH2), 32.7 (CH2, 6C), 32.7 (CH2), 32.0 (CH2), 29.8 (CH2), 29.8 (CH2),
29.7 (CH2), 29.7 (CH2), 29.7 (CH2, 3C), 29.4 (CH2), 29.3 (CH2), 29.3
(CH2), 29.3 (CH2), 29.0 (CH2), 28.8 (CH2), 28.8 (CH2), 25.8 (CH2), 23.6
(CH2), 22.8 (CH2), 14.3 (CH3); IR (KBr) νmax 3320, 3225, 2922, 2849,
1539, 1458, 1440, 1374, 1131, 1067, 1045, 965, 731, 688 cm-1; HRMS
(ESI-TOF) m/z: [M+H+] calcd for C37H69O 529.5343; found 529.5305.
2-(Henicos-6-en-1-yl)-1,3-dioxolane (Z>E-10): GP2 was applied to 7
and pentadecanal, eluent 65:35 DCM/cyclohexane, waxy yellow solid
1
(87% yield). Rf = 0.35 (silica gel, 1:9 AcOEt:cyclohexane); H NMR (400
MHz, CDCl3): δ 5.39-5.32 (2H, m,), 4.84 (1H, t, J = 4.8 Hz,), 4.00-3.91
(2H, m), 3.89-3.81 (2H, m), 2.07-1.93 (4H, m), 1.71-1.59 (2H, m), 1.54-
1.11 (30H, m), 0.88 (3H, t, J = 6.7 Hz); 13C{1H} NMR (100 MHz): δ 130.0
(CH), 129.6 (CH), 104.7 (CH), 64.8 (CH2, 2C), 33.9 (CH2), 31.9 (CH2),
29.8 (CH2), 29.7 (CH2, 4C), 29.7 (CH2, 3C), 29.6 (CH2), 29.4 (CH2), 29.3
(CH2), 29.2 (CH2), 27.2 (CH2), 27.1 (CH2), 24.0 (CH2), 22.7 (CH2), 14.1
(CH3); IR (KBr) νmax 3004, 2922, 2853, 1730, 1651, 1577, 1540, 1466,
1437, 1409, 1377, 1358, 1305, 1259, 1207, 1141, 1044, 967, 941, 902,
721, 694 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C24H47O2
367.3571; found 367.3567.
(8E,15E,22E,29E)-Heptatriaconta-8,15,22,29-tetraen-2-one (E,E,E,E-
1): GP6 was applied to E,E,E,E-31, eluent 5:95 AcOEt/cyclohexane,
white waxy solid (from hot methanol) (65% yield). Rf = 0.30 (silica gel,
DCM); 1H NMR (400 MHz, CDCl3): δ 5.46-5.30 (8H, m), 2.41 (2H, t, J =
7.5 Hz), 2.13 (3H, s), 2.05-1.85 (16H, m), 1.63-1.45 (2H, m), 1.41-1.21
(32H, m), 0.88 (3H, t, J = 6.6 Hz); 13C{1H} NMR (100 MHz): δ 209.4 (C),
130.8 (CH), 130.6 (CH), 130.5 (CH, 2C), 130.5 (CH, 2C), 130.4 (CH),
130.1 (CH), 43.9 (CH2), 32.8 (CH2), 32.7 (CH2, 6C), 32.5 (CH2), 32.0
(CH2), 30.0 (CH2), 29.8 (CH2), 29.7 (CH2, 6C), 29.5 (CH2), 29.3 (CH2),
29.3 (CH2), 28.9 (CH2), 28.8 (CH2), 28.8 (CH2), 28.8 (CH2), 23.9 (CH2),
22.8 (CH2), 14.3 (CH3); IR (KBr) νmax 3445, 2954, 2919, 2848, 1712,
1632, 1467, 1466, 1457, 1435, 1376, 1167, 1070, 963, 720 cm-1;
GC/LRMS (EI, 70 eV) m/z: 526.7 (M+, 1), 508.5 (0.3), 109.2 (16), 95.2
(31), 86.0 (62), 84.0 (100), 81.2 (31), 67.1 (31), 55.1 (27), 51.1 (36%);
GC/HRMS (EI, 45 eV) m/z: [M]+ calcd for C37H66O 526.5114; found
526.5108; Kováts retention index 3877.[32]
Docos-7-enal (Z>E-12): GP3 was applied to Z>E-10, pale yellow oil
1
(99% yield). Rf = 0.35 (silica gel, 1:9 AcOEt/cyclohexane); H NMR (400
MHz, CDCl3): δ 9.76 (1H, t, J = 1.8 Hz), 5.45-5.24 (2H, m), 2.42 (2H, td, J
= 7.3, 1.9 Hz), 2.11-1.91 (4H, m), 1.70-1.58 (2H, m), 1.47-1.15 (28H, m),
0.87 (3H, t, J = 7.0 Hz); 13C{1H} NMR (100 MHz): δ 202.8 (CH), 130.3
(CH), 129.3 (CH), 43.9 (CH2), 31.9 (CH2), 29.7 (CH2), 29.7 (CH2, 4C),
29.6 (CH2, 2C), 29.6 (CH2), 29.4 (CH2), 29.4 (CH2), 29.3 (CH2), 28.8
(CH2), 27.2 (CH2), 26.9 (CH2), 22.7 (CH2), 22.0 (CH2), 14.1 (CH3); IR
(KBr) νmax 3000, 2922, 2852, 2713, 1729, 1577, 1540, 1465, 1437, 1115,
875, 721 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C22H43O
323.3308; found 323.3296.
Labelled heptatriaconta-8,15,22,29-tetraen-2-ol (Z>E-31*): GP4 was
applied to Z>E-22 using 13C-labelled iodomethane, eluent 5:95
AcOEt/cyclohexane, pale yellow waxy solid (85% yield). Rf = 0.28 (silica
gel, 9:1 DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 5.43-5.27 (8H,
m), 3.85-3.72 (1H, m), 2.11-1.90 (16H, m), 1.48-1.24 (36H, m), 1.18 (3H,
dd, J = 125.1, 6.2 Hz), 0.88 (3H, t, J = 7.1 Hz); 13C{1H} NMR (100 MHz):
δ 130.1 (CH), 130.1 (CH), 130.0 (CH, 2C), 130.0 (CH, 2C), 130.0 (CH),
129.9 (CH), 68.3 (CH, d, J = 38 Hz), 39.5 (CH2), 32.7 (CH2), 32.0 (CH2),
29.9 (CH2), 29.9 (CH2), 29.8 (CH2, 2C), 29.8 (CH2), 29.7 (CH2), 29.4
(CH2), 29.4 (CH2, 6C), 29.1 (CH2), 27.4 (CH2), 27.3 (CH2, 2C), 27.3 (CH2),
25.8 (CH2), 25.8 (CH2), 23.7 (13CH3), 22.8 (CH2), 22.5 (CH2), 19.7 (CH2),
14.3 (CH3); IR (KBr) νmax 3350, 3005, 2927, 2855, 1540, 1464, 1401,
1365, 1115, 968, 786, 762 cm-1.
2-(Octacosa-6,13-dien-1-yl)-1,3-dioxolane (Z>E-14): GP2 was applied
to Z>E-12 and 7, eluent 1:1 DCM/petroleum ether, pale yellow waxy solid
(75% yield). Rf = 0.36 (silica gel, 6:4 DCM:PE); 1H NMR (400 MHz,
CDCl3): δ 5.46-5.25 (4H, m), 4.84 (1H, t, J = 4.8 Hz,), 4.06-3.91 (2H, m),
3.90-3.76 (2H, m), 2.11-1.92 (8H, m), 1.74-1.59 (2H, m), 1.50-1.11 (36H,
m), 0.88 (3H, t, J = 6.7 Hz); 13C{1H} NMR (100 MHz): δ 130.0 (CH), 129.9
(CH), 129.8 (CH), 129.7 (CH), 104.7 (CH), 64.8 (CH2, 2C), 33.9 (CH2),
31.9 (CH2), 29.8 (CH2), 29.7 (CH2, 4C), 29.7 (CH2, 5C), 29.6 (CH2), 29.4
(CH2), 29.2 (CH2), 29.0 (CH2), 27.2 (CH2), 27.2 (CH2), 27.2 (CH2), 27.1
(CH2), 26.9 (CH2), 24.0 (CH2), 22.7 (CH2), 14.1 (CH3); IR (KBr) νmax 3004,
2922, 2853, 1731, 1651, 1577, 1540, 1465, 1437, 1407, 1377, 1360,
1308, 1259, 1209, 1140, 1043, 966, 941, 902, 721, 694 cm-1; HRMS
(ESI-TOF) m/z: [M+1+] calcd for C31H59O2 463.4510; found 463.4493.
Labelled
(8E,15E,22E,29E)-heptatriaconta-8,15,22,29-tetraen-2-ol
(E>Z-31*): GP5 was applied to Z>E-31*, eluent 1:9 AcOEt/cyclohexane,
white waxy solid (85% yield). Rf = 0.30 (silica gel, 9:1 DCM/cyclohexane);
1H NMR (400 MHz, CDCl3): δ 5.41-5.33 (8H, m), 3.84- 3.74 (1H1H, m),
2.05-1.91 (16H, m), 1.47-1.21 (36H, m),1.18 (3H, dd, J = 125.2, 6.2 Hz),
0.88 (3H, t, J = 7.1 Hz); 13C{1H} NMR (100 MHz): δ 130.6 (CH), 130.6
(CH), 130.5 (CH, 2C), 130.5 (CH, 2C), 130.4 (CH), 130.3 (CH), 68.3 (CH,
d, J = 38 Hz), 39.5 (CH2), 32.8 (CH2), 32.7 (CH2, 4C), 32.7 (CH2), 32.0
(CH2), 29.8 (CH2), 29.8 (CH2), 29.7 (CH2), 29.7 (CH2), 29.7 (CH2, 2C),
29.4 (CH2), 29.4 (CH2, 6C), 29.3 (CH2), 28.8 (CH2), 23.7 (CH2), 23.7
(CH2), 23.6 (13CH3), 22.8 (CH2), 14.3 (CH3); IR (KBr) νmax 3401, 2925,
2850, 1577, 1541, 1464, 1434, 1253, 1215, 1006, 971, 784, 757 cm-1;
HRMS (ESI-TOF) m/z: [M+H+] calcd for C3613CH69O 530.5376; found
530.5361.
Nonacosa-7,14-dienal (Z>E-16): GP3 was applied to Z>E-14, pale
yellow oil (99% yield). Rf = 0.36 (silica gel, 6:4 DCM/PE); 1H NMR (400
MHz, CDCl3): δ 9.76 (1H, t, J = 1.8 Hz), 5.41-5.28 (4H, m), 2.42 (2H, td, J
= 7.4, 1.9 Hz), 2.11-1.92 (8H, m), 1.74-1.54 (2H, m), 1.47-1.15 (34H, m),
0.87 (3H, t, J = 7.0 Hz); 13C{1H} NMR (100 MHz): δ 202.7 (CH), 130.2
(CH), 130.0 (CH), 129.7 (CH), 129.4 (CH), 43.9 (CH2), 31.9 (CH2), 29.8
(CH2), 29.7 (CH2, 4C), 29.7 (CH2, 3C), 29.6 (CH2), 29.6 (CH2), 29.4 (CH2),
29.4 (CH2), 29.3 (CH2), 29.0 (CH2), 28.8 (CH2), 27.2 (CH2), 27.2 (CH2),
27.2 (CH2), 26.9 (CH2), 22.7 (CH2), 22.0 (CH2), 14.1 (CH3); IR (KBr) νmax
3004, 2922, 2852, 2712, 1729, 1651, 1578, 1541, 1465, 1437, 1407,
1344, 1305, 1198, 1182, 1119, 1026, 967, 872, 853, 740, 721, 695, 542
cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C29H55O 419.4247; found
419.4208.
Labelled (8E,15E,22E,29E)-heptatriaconta-8,15,22,29-tetraen-2-one
(E,E,E,E-1*): GP6 was applied to E,E,E,E-31*, eluent 5:95
AcOEt/cyclohexane, white waxy solid (from hot methanol) (30% yield). Rf
= 0.30 (silica gel, DCM); 1H NMR (400 MHz, CDCl3): δ 5.43-5.33 (8H, m),
2.41 (2H, t, J = 7.5 Hz), 2.13 (3H, d, J = 127.0 Hz), 2.05-1.88 (16H, m),
1.61-1.52 (2H, m,), 1.41-1.21 (32H, m), 0.87 (3H, t, J = 7.1 Hz); 13C{1H}
NMR (100 MHz): δ 209.4 (C, d, J = 40 Hz), 130.8 (CH), 130.8 (CH),
130.5 (CH, 2C), 130.5 (CH, 2C), 130.4 (CH), 130.1 (CH), 43.9 (CH2, d, J
2-(Pentatriaconta-6,13,20-trien-1-yl)-1,3-dioxolane (Z>E-18): GP2 was
applied to Z>E-16 and 7, eluent 85:15 DCM/cyclohexane, pale yellow oil
(97% yield). Rf = 0.48 (silica gel, 85:15 DCM/cyclohexane); 1H NMR (400
MHz, CDCl3): δ 5.44-5.25 (6H, m), 4.84 (1H, t, J = 4.8 Hz), 4.03-3.90 (2H,
7
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
m), 3.90-3.77 (2H, m), 2.10- 1.92 (12H, m), 1.71-1.60 (2H, m), 1.51-1.13
(42H, m), 0.88 (3H, t, J = 6.7 Hz); 13C{1H} NMR (100 MHz): δ 130.0 (CH),
129.9 (CH), 129.8 (CH, 2C), 129.8 (CH), 129.7 (CH), 104.7 (CH), 64.8
(CH2, 2C), 33.9 (CH2), 31.9 (CH2), 29.8 (CH2), 29.7 (CH2, 5C), 29.7 (CH2,
6C), 29.6 (CH2), 29.4 (CH2), 29.3 (CH2), 29.2 (CH2), 29.0 (CH2), 29.0
(CH2), 27.2 (CH2), 27.2 (CH2, 2C), 27.2 (CH2, 2C), 27.1 (CH2), 24.0 (CH2),
22.7 (CH2), 14.1 (CH3); IR (KBr) νmax 3004, 2912, 2852, 1728, 1654,
1577, 1541, 1464, 1437, 1404, 1377, 1358, 1305, 1259, 1141, 1038, 967,
938, 721, 694 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C38H71O2
559.5449; found 559.5463.
Labelled heptatriaconta-8,15,22-trien-2-ol (Z>E-32*): GP4 was applied
to Z>E-20 using 13C-labelled methyl iodide, eluent DCM, white waxy solid
(78% yield). Rf = 0.37 (silica gel, DCM); 1H NMR (400 MHz, CDCl3): δ
5.40-5.30 (6H, m), 3.84-3.75 (1H, m), 2.08-1.93 (12H, m), 1.46-1.24 (45H,
m), 1.18 (3H, dd, J = 125.2, 6.2 Hz), 0.87 (3H, t, J = 6.7 Hz); 13C{1H}
NMR (100 MHz): δ 130.1 (CH), 130.1 (CH), 130.0 (CH), 130.0 (CH),
129.9 (CH), 129.9 (CH), 68.3 (CH, d, J = 39 Hz), 39.5 (CH2), 32.7 (CH2),
32.1 (CH2), 29.9 (CH2), 29.8 (CH2, 2C), 29.8 (CH2, 4C), 29.7 (CH2, 2C),
29.5 (CH2, 2C), 29.4 (CH2, 2C), 29.1 (CH2), 29.0 (CH2), 27.4 (CH2), 27.3
(CH2, 5C), 25.8 (CH2, 2C), 23.7 (13CH3), 22.8 (CH2), 19.7 (CH2), 14.3
(CH3); IR (KBr) νmax 3395, 2924, 2852, 1574, 1540, 1465, 1251, 1113,
1067, 1009, 784, 765 cm-1.
Hexatriaconta-7,14,21-trienal (Z>E-20): GP3 was applied to Z>E-18,
pale yellow oil (98% yield). Rf
=
0.48 (silica gel, 85:15
DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 9.77 (1H, t, J = 1.8 Hz),
5.44-5.26 (6H, m), 2.42 (2H, td, J = 7.4, 1.9 Hz), 2.10-1.92 (12H, m),
1.72-1.58 (2H, m), 1.47-1.15 (40H, m), 0.88 (3H, t, J = 6.7 Hz); 13C{1H}
NMR (100 MHz): δ 202.9 (CH), 130.4 (CH), 130.1 (CH), 130.0 (CH),
130.0 (CH), 129.9 (CH), 129.5 (CH), 44.0 (CH2), 32.1 (CH2), 29.9 (CH2),
29.85 (CH2, 4C), 29.82 (CH2, 5C), 29.7 (CH2, 2C), 29.6 (CH2), 29.5 (CH2,
2C), 29.1 (CH2), 29.0 (CH2), 28.9 (CH2), 27.4 (CH2, 5C), 27.1 (CH2), 22.8
(CH2), 22.2 (CH2), 14.3 (CH3); IR (KBr) νmax 3004, 2921, 2852, 2713,
1729, 1651, 1577, 1541, 1464, 1435, 1305, 1259, 1182, 1119, 1089,
1067, 1027, 993, 965, 743, 721, 695, 542 cm-1; HRMS (ESI-TOF) m/z:
[M+H+] calcd for C36H67O 515.5186; found 515.5148.
Labelled (8E,15E,22E)-heptatriaconta-8,15,22-trien-2-ol (E>Z-32*):
GP5 was applied to Z>E-32*, eluent 9:1 DCM/cyclohexane, white waxy
solid (75% yield). Rf = 0.38 (silica gel, DCM); 1H NMR (400 MHz, CDCl3):
δ 5.43-5.32 (6H, m), 3.84-3.74 (1H, m), 2.08-1.93 (12H, m), 1.48-1.21
(45H, m), 1.18 (3H, dd, J = 125.1, 6.1 Hz), 0.87 (1H, t, J = 6.7 Hz);
13C{1H} NMR (100 MHz): δ 130.6 (CH), 130.6 (CH), 130.5 (CH), 130.5
(CH), 130.4 (CH), 130.3 (CH), 68.3 (CH, d, J = 39 Hz), 39.5 (CH2), 32.8
(CH2), 32.7 (CH2), 32.7 (CH2, 4C), 32.1 (CH2, 2C), 29.8 (CH2, 2C), 29.8
(CH2, 2C), 29.7 (CH2), 29.7 (CH2), 29.7 (CH2), 29.5 (CH2), 29.4 (CH2),
29.3 (CH2), 28.8 (CH2), 28.8 (CH2), 25.8 (CH2), 23.7 (CH2, 4C), 23.6
(13CH3), 22.8 (CH2), 19.7 (CH2), 14.3 (CH3); IR (KBr) νmax 3296, 3203,
3000, 2956, 2919, 2849, 1470, 1458, 1364, 1128, 965, 726 cm-1; HRMS
(ESI-TOF) m/z: [M+H+] calcd for C3613CH71O 532.5533; found 532.5566.
Heptatriaconta-8,15,22-trien-2-ol (Z>E-32): GP4 was applied to Z>E-20,
pale yellow waxy solid (58% yield). Rf = 0.37 (silica gel, DCM); 1H NMR
(400 MHz, CDCl3): δ 5.42-5.28 (6H, m), 3.86 3.73 (1H, m), 2.02 (12H, q,
J = 6.4, 5.4 Hz), 1.61-1.20 (44H, m), 1.19 (3H, d, J = 6.2 Hz), 0.87 (3H, t,
J = 6.7 Hz); 13C{1H} NMR (100 MHz): δ 130.0 (CH), 129.9 (CH), 129.9
(CH), 129.8 (CH), 129.8 (CH), 129.7 (CH), 68.1 (CH), 39.3 (CH2), 31.9
(CH2), 29.8 (CH2), 29.7 (CH2, 5C), 29.7 (CH2, 6C), 29.6 (CH2), 29.4 (CH2),
29.3 (CH2), 29.3 (CH2), 29.0 (CH2, 2C), 27.2 (CH2), 27.2 (CH2), 27.2
(CH2, 3C), 27.1 (CH2), 25.7 (CH2), 23.5 (CH2), 22.7 (CH2), 14.1 (CH3); IR
(KBr) νmax 3350, 3005, 2921, 2852, 1651, 1577, 1541, 1464, 1404, 1376,
1347, 1259, 1123, 1094, 966, 941, 720 cm-1.
Labelled (8E,15E,22E)-heptatriaconta-8,15,22-trien-2-one (E,E,E-2*):
GP6 was applied to E,E,E-32*, eluent 4:6 DCM/cyclohexane, white waxy
solid (from hot methanol) (25% yield). Rf
= 0.34 (silica gel,
1
DCM/cyclohexane 6:4); H NMR (400 MHz, CDCl3): δ 5.43-5.32 (6H, m),
2.41 (2H, t, J = 7.4 Hz), 2.13 (3H, d, J = 126.9 Hz), 2.04-1.91 (12H, m),
1.63-1.51 (2H, m), 1.40-1.20 (40H, m), 0.87 (3H, t, J = 6.7 Hz); 13C{1H}
NMR (100 MHz): δ 209.4 (C, d, J = 40 Hz), 130.8 (CH), 130.6 (CH),
130.5 (CH), 130.5 (CH), 130.4 (CH), 130.1 (CH), 43.9 (CH2, d, J = 14 Hz),
32.8 (CH2), 32.7 (CH2, 3C), 32.7 (CH2), 32.5 (CH2), 32.1 (CH2), 30.1
(CH2, 2C), 30.0 (13CH2), 29.8 (CH2, 4C), 29.8 (CH2, 2C), 29.7 (CH2), 29.7
(CH2, 2C), 29.6 (CH2), 29.5 (CH2, 2C), 29.3 (CH2), 28.8 (CH2), 28.8 (CH2),
28.8 (CH2), 23.9 (CH2), 22.8 (CH2), 14.3 (CH3); IR (KBr) νmax 2955, 2918,
2848, 1712, 1466, 1456, 1435, 1375, 1163, 963, 719 cm-1; GC/LRMS (EI,
70 eV) m/z: 529.6 (M+, 6), 511.6 (5), 109.1 (53), 96.1 (72), 95.1 (100),
84.0 (75), 83.1 (58), 81.1 (99), 67.1 (92), 55.1 (78%); GC/HRMS (EI, 45
eV) m/z: [M]+ calcd for C3613CH68O 529.5304; found 529.5192; Kováts
retention index 3887.[32]
(8E,15E,22E)-Heptatriaconta-8,15,22-trien-2-ol (E>Z-32): GP5 was
applied to Z>E-32, eluent 12:88 AcOEt/cyclohexane, white waxy solid
(33% yield). Rf = 0.38 (silica gel, DCM); 1H NMR (400 MHz, CDCl3): δ
5.38 (6H, td, J = 3.8, 1.9 Hz), 3.86-3.73 (1H, m), 2.02 (12H, q, J = 6.4,
5.4 Hz), 1.61-1.20 (44H, m), 1.19 (3H, d, J = 6.2 Hz), 0.87 (3H, t, J = 6.7
Hz); 13C{1H} NMR (100 MHz): δ 130.5 (CH), 130.4 (CH), 130.3 (CH),
130.3 (CH), 130.3 (CH), 130.2 (CH), 68.2 (CH), 39.3 (CH2), 32.6 (CH2),
32.6 (CH2, 2C), 32.5 (CH2), 31.9 (CH2), 29.7 (CH2, 3C), 29.7 (CH2, 3C),
29.6 (CH2), 29.5 (CH2, 6C), 29.5 (CH2), 29.4 (CH2, 2C), 29.2 (CH2), 29.1
(CH2), 28.7 (CH2), 28.7 (CH2), 25.6 (CH2), 23.5 (CH2), 22.7 (CH2), 14.1
(CH3); IR (KBr) νmax 3302, 3219, 2956, 2918, 2848, 1632, 1500, 1470,
1458, 1443, 1432, 1412, 1371, 1292, 1256, 1149, 1131, 1105, 1067,
1042, 1017, 965, 927, 845, 727 cm-1; HRMS (ESI-TOF) m/z: [M+H+]
calcd for C37H71O 531.5499; found 531.5534.
7-((tert-Butyldimethylsilyl)oxy)heptan-1-ol (23): In a 500 mL round
bottomed flask, 1,7-heptandiol (4.76 g, 36 mmol), tert-butyldimethylsilyl
chloride (5.43 g, 36 mmol), triethylamine (4.40 g, 43 mmol), acetonitrile
(90 mL) and n-hexane (270 mL) were added and the system was purged
with argon. The resulting biphasic system was vigorously stirred at room
temperature for 24 h. The reaction was quenched with saturated
aqueous NH4Cl (360 mL) and the resulting mixture was extracted with
AcOEt (3 × 100 mL). The united organic layers were washed with water
(2 × 200 mL) and dried in vacuum. The residue was purified by flash
chromatography, eluting with AcOEt/cyclohexane from 1:9 to 3:7,
affording the product as a colourless oil (4.31 g, 17.5 mmol, 63% yield).
Rf = 0.26 (silica gel, 2:8 AcOEt/cyclohexane); 1H NMR (400 MHz, CDCl3):
δ 3.64 (2H, t, J = 6.6 Hz), 3.60 (2H, t, J = 6.6 Hz), 1.61-1.47 (4H, m), 1.43
(1H, s), 1.44-1.23 (6H, m), 0.89 (9H, s), 0.05 (6H, s). Further
spectroscopic data (13C, IR, MS) are in accordance with the literature.[33]
(8E,15E,22E)-Heptatriaconta-8,15,22-trien-2-one (E,E,E-2): GP6 was
applied to E,E,E-32, eluent 6:4 DCM/cyclohexane, white waxy solid (from
hot methanol) (41% yield). Rf = 0.34 (silica gel, 6:4 DCM/cyclohexane);
1H NMR (400 MHz, CDCl3): δ 5.52-5.26 (6H, m), 2.41 (2H, t, J = 7.5 Hz),
2.21-1.84 (15H, m), 1.64-1.49 (2H, q, J = 8.7, 8.0 Hz), 1.29 (2H, m), 1.28-
1.18 (38H, m), 0.88 (3H, t, J = 6.6 Hz); 13C{1H} NMR (100 MHz): δ 209.2
(C), 130.6 (CH), 130.4 (CH), 130.3 (CH), 130.3 (CH), 130.3 (CH), 130.0
(CH), 43.8 (CH2), 32.6 (CH2), 32.6 (CH2, 2C), 32.5 (CH2), 32.4 (CH2),
31.9 (CH2), 29.8 (CH3), 29.7 (CH2, 4C), 29.7 (CH2, 4C), 29.5 (CH2), 29.5
(CH2, 3C), 29.5 (CH2), 29.4 (CH2, 2C), 29.2 (CH2), 28.7 (CH2), 28.7 (CH2),
28.7 (CH2), 23.7 (CH2), 22.7 (CH2), 14.1 (CH3); IR (KBr) νmax 3004, 2922,
2852, 1721, 1654, 1577, 1541, 1464, 1437, 1357, 1259, 1159, 965, 720
cm-1; GC/LRMS (EI, 70 eV) m/z: 528.5 (M+, 2), 510.5 (2), 109.1 (52), 96.1
(60), 95.1 (99), 84.0 (95), 81.1 (100), 69.1 (60), 67.0 (85), 55.1 (80%);
GC/HRMS (EI, 45 eV) m/z: [M]+ calcd for C37H68O 528.5270; found
528.5265; Kováts retention index 3887.[32]
7-((tert-Butyldimethylsilyl)oxy)heptanal (24): GP1 was applied to 23,
yellow oil (94% yield). Rf = 0.60 (silica gel, 2:8 AcOEt/cyclohexane); 1H
NMR (400 MHz, CDCl3): δ 9.77 (1H, t, J = 1.8 Hz), 3.60 (2H, t, J = 6.5
Hz), 2.42 (2H, td, J = 7.4, 1.8 Hz), 1.69-1.59 (2H, m), 1.56-1.48 (2H, m),
1.40-1.30 (4H, m), 0.89 (9H, s), 0.06 (6H, s). Further spectroscopic data
(13C, IR, MS) are in accordance with the literature.[33]
8
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
((13-(1,3-Dioxolan-2-yl)tridec-7-en-1-yl)oxy)(tert-butyl)dimethylsilane
(Z>E-25): GP2 was applied to 7 and 24, eluent 15:85 AcOEt/cyclohexane
(66% yield). Rf = 0.20 (silica gel, 3:7 DCM/cyclohexane); 1H NMR (400
MHz, CDCl3): δ 5.40-5.31 (2H, m), 4.84 (1H, t, J = 4.8 Hz), 4.03-3.78 (4H,
m), 3.60 (2H, t, J = 6.6 Hz), 2.05-1.94 (4H, m), 1.70-1.60 (2H, m), 1.56-
1.24 (20H, m), 0.90 (9H, s), 0.06 (6H, s); 13C{1H} NMR (100 MHz): δ
130.1 (CH), 129.9 (CH), 104.8 (CH), 65.5 (CH2, 2C), 63.5 (CH2), 34.1
(CH2), 33.0 (CH2), 29.9 (CH2, 2C), 29.3 (CH2, 2C), 27.3 (CH2, 2C), 26.2
(CH3, 3C), 25.9 (CH2), 24.1 (CH2), 18.5 (C), -5.1 (CH3, 2C); IR (film) νmax
3423, 2929, 2857, 2453, 1891, 1476, 1463, 1410, 1388, 1358, 1254,
1138, 1099, 1039, 1001, 973, 946, 836, 809, 775, 707, 661, 475, 466,
459 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C22H45O3Si 385.3132;
found 385.3119.
(51% yield). Rf = 0.30 (silica gel, 6:4 DCM/cyclohexane); 1H NMR (400
MHz, CDCl3): δ 5.41-5.29 (4H, m), 4.84 (1H, t, J = 4.8 Hz), 4.02-3.79 (4H,
m), 2.09-1.95 (8H, m), 1.70-1.54 (2H, m), 1.44-1.19 (50H, m), 0.88 (3H, t,
J = 6.6 Hz); 13C{1H} NMR (100 MHz): δ 130.0 (CH, 2C), 129.8 (CH, 2C),
104.7 (CH2), 64.8 (CH2, 2C), 34.0 (CH2), 31.9 (CH2), 29.8 (CH2, 2C), 29.7
(CH2, 4C), 29.7 (CH2, 5C), 29.6 (CH2, 3C), 29.6 (CH2, 3C), 29.4 (CH2,
2C), 29.3 (CH2, 2C), 29.00 (CH2), 27.2 (CH2, 2C), 27.2 (CH2, 2C), 24.1
(CH2), 22.7 (CH2), 14.1 (CH3); IR (film) νmax 2917, 2849, 1577, 1540,
1471, 491, 477 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C38H73O2
561.5605; found 561.5554.
Hexatriaconta-14,21-dienal (Z>E-30): GP3 was applied to Z>E-29,
eluent 3:7 DCM/cyclohexane, pale yellow oil (65% yield). Rf = 0.30 (silica
gel, 6:4 DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 9.76 (1H, t, J =
1.9 Hz), 5.40-5.30 (4H, m), 2.41 (2H, td, J = 7.4, 1.9 Hz), 2.06-1.96 (8H,
m), 1.68-1.58 (2H, m), 1.40-1.21 (48H, m), 0.87 (3H, t, J = 7.0 Hz);
13C{1H} NMR (100 MHz): δ 203.1 (CH), 130.11 (CH), 130.10 (CH), 130.0
(CH, 2C), 44.1 (CH2), 32.1 (CH2), 29.9 (CH2), 29.8 (CH2, 4C), 29.8 (CH2,
4C), 29.8 (CH2, 2C), 29.7 (CH2), 29.7 (CH2, 2C), 29.6 (CH2), 29.5 (CH2,
2C), 29.5 (CH2, 2C), 29.3 (CH2), 29.1 (CH2), 27.4 (CH2, 2C), 27.3 (CH2,
2C), 22.8 (CH2, 2C), 22.3 (CH2), 14.3 (CH3); IR (KBr) νmax 3000, 2921,
2851, 1725, 1467 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C36H69O
518.5377; found 518.5368.
((13-(1,3-Dioxolan-2-yl)tridecyl)oxy)(tert-butyl)dimethylsilane (26): A
mixture of Z>E-25 (1.75 g, 4.7 mmol) and Pd/C 5% (20 mg) in AcOEt (50
mL) was stirred under H2 atmosphere (1 atm, balloon) at room
temperature for 18 h. The resulting mixture was filtered on a celite plug
and washed with AcOEt. The resulting solution was concentrated in
vacuum, to afford the product as colourless oil (1.65 g, 4.4 mmol, 94%
yield). Rf = 0.30 (silica gel, 1:1 DCM/cyclohexane); 1H NMR (400 MHz,
CDCl3): δ 4.84 (1H, t, J = 4.8 Hz), 4.02-3.78 (4H, m), 3.59 (2H, t, J = 6.7
Hz), 1.68-1.19 (24H, m), 1.54-1.19 (9H, m), 0.98-0.83 (6H, m); 13C{1H}
NMR (100 MHz): δ 104.9 (CH2), 65.0 (CH2), 63.5 (CH2), 34.1 (CH2), 33.5
(CH2), 29.8 (CH2, 2C), 29.7 (CH2, 2C), 26.1 (CH3, 3C), 25.9 (CH2), 24.2
(CH2), 18.5 (C), -5.1 (CH3, 2C); IR (film) νmax 2927, 2855, 1728, 1463,
1437, 1407, 1388, 1360, 1254, 1144, 1100, 1038, 1006, 940, 835, 812,
775, 721, 661, 542, 461 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for
C22H47O3Si 387.3289; found 387.3278.
Heptatriaconta-15,22-dien-2-ol (Z>E-33): GP4 was applied to Z>E-30,
eluent DCM, white waxy solid (45% yield). Rf = 0.40 (silica gel, DCM); 1H
NMR (400 MHz, CDCl3): δ 5.41-5.30 (4H, m), 3.84-3.75 (1H, m), 2.09-
1.96 (8H, m), 1.49-1.22 (52H, m), 1.19 (3H, d, J = 6.2 Hz), 0.87 (3H, t, J
= 6.8 Hz); 13C{1H} NMR (100 MHz): δ 130.1 (CH, 2C), 130.0 (CH, 2C),
68.4 (CH), 39.5 (CH2), 32.1 (CH2), 30.0 (CH2), 29.9 (CH2, 2C), 29.8 (CH2,
11C), 29.7 (CH2, 2C), 29.5 (CH2, 2C), 29.5 (CH2, 2C), 29.1 (CH2), 27.4
(CH2, 2C), 27.3 (CH2, 2C), 25.9 (CH2), 23.6 (CH3), 22.8 (CH2), 14.3
(CH3); IR (KBr) νmax 3400, 3340, 3003, 2918, 2850, 1469, 1345, 1136,
826, 720, 687 cm-1.
13-(1,3-Dioxolan-2-yl)tridecan-1-ol (27): In a 100 mL round bottomed
flask, 26 (1.65 g, 4.4 mmol), methanol (40 mL) and NH4F (1.13 g, 30.5
mmol) were added. The system was purged with argon and kept under
reflux conditions for 10 h. The resulting solution was concentrated in
vacuum and the crude product was purified by flash chromatography,
eluting with 7:3 cyclohexane/AcOEt, affording the product as a white
solid (1.13 g, 4.2 mmol, 95% yield), m.p. 72 °C. Rf = 0.22 (silica gel, 2:8
AcOEt/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 4.84 (1H, t, J = 4.8
Hz), 4.04-3.77 (4H, m), 3.64 (2H, t, J = 6.6 Hz), 1.72-1.51 (4H, set of m),
1.47-1.20 (20H, m); 13C{1H} NMR (100 MHz): δ 104.8 (CH), 64.9 (CH2,
2C), 63.1 (CH2), 34.0 (CH2), 32.9 (CH2), 29.7 (CH2, 2C), 29.6 (CH2), 29.6
(CH2), 29.6 (CH2), 29.5 (CH2), 29.5 (CH2), 25.8 (CH2), 24.1 (CH2); IR
(KBr) νmax 3434, 3384, 2918, 2850, 1469, 1411, 1354, 1157, 1121, 1056,
1029, 999, 956, 916, 877, 839, 801, 718, 608 cm-1; HRMS (ESI-TOF)
m/z: [M+Na+] calcd for C16H32O3Na 295.2244; found 295.2238.
(15E,22E)-Heptatriaconta-15,22-dien-2-ol (E>Z-33): GP5 was applied
to Z>E-33, eluent DCM, white waxy solid (66% yield). Rf = 0.43 (silica gel,
9:1 DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 5.40-5.33 (4H, m),
3.84-3.74 (1H, m), 2.07-1.89 (8H, m), 1.85-1.72 (2H, m), 1.66-1.21 (50H,
m), 1.19 (3H, d, J = 6.2 Hz), 0.87 (3H, t, J = 6.7 Hz); 13C{1H} NMR (100
MHz): δ 130.6 (CH, 2C), 130.5 (CH, 2C), 68.4 (CH), 39.5 (CH2), 32.8
(CH2, 2C), 32.7 (CH2, 2C), 32.1 (CH2, 2C), 29.8 (CH2, 15C), 29.7 (CH2,
3C), 29.5 (CH2), 29.3 (CH2), 25.9 (CH2), 23.6 (CH3), 22.8 (CH2), 14.3
(CH3); IR (KBr) νmax 3429, 2981, 2849, 2346, 1626, 1462, 1133, 964, 721,
666 cm-1; HRMS (ESI-TOF) m/z: [M+H+] calcd for C37H73O 533.5656;
found 533.5647.
2-(13-Bromotridecyl)-1,3-dioxolane (28): In a 100 mL round-bottomed
flask, 27 (0.89 g, 3.3 mmol) and triphenylphosphine (1.1 g, 4.4 mmol)
were dissolved in dry ACN (18.4 mL). The system was purged with argon
and the temperature was lowered to 0 °C with an ice bath. A solution
CBr4 (1.43 g, 4.4 mmol) in dry ACN (4 mL) was added to the cold
reaction mixture. The reaction was stirred for 24 h, allowing it to warm to
room temperature. The mixture was extracted with cyclohexane (3 × 20
mL). The combined cyclohexane layers were washed with water (3 × 50
mL). The organic phase was dried over anhydrous MgSO4, filtered and
dried in vacuum, to afford the product as yellow oil (89% yield). Rf = 0.49
(silica gel, 1:9 AcOEt/cyclohexane); 1H NMR (400 MHz, CDCl3): δ = 4.86
(1H, t, J = 4.8 Hz), 4.01-3.84 (4H, m), 3.43 (2H, t, J = 6.9 Hz), 1.90-1.82
(2H, m), 1.71-1.64 (2H, m), 1.36-1.28 (20H, m); 13C{1H} NMR (100 MHz):
δ 104.9 (CH), 65.0 (CH2, 2C), 34.2 (CH2), 34.1 (CH2), 33.0 (CH2), 29.7
(CH2), 29.7 (CH2), 29.7 (CH2), 29.7 (CH2), 29.7 (CH2), 29.7 (CH2), 29.6
(CH2), 28.9 (CH2), 28.3 (CH2), 24.2 (CH2); IR (KBr) νmax 2917, 2847,
1467, 1437, 1415, 1160, 1138, 1124, 1045, 1026, 935, 908, 721 cm-1;
HRMS (ESI-TOF) m/z: [M+H+] calcd for C16H32BrO2 335,1580; found
335.1577.
(15E,22E)-Heptatriaconta-15,22-dien-2-one (E,E-3): GP6 was applied
to E,E-33, white waxy solid (from hot methanol) (60% yield). Rf = 0.34
(silica gel, 6:4 DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 5.44-
5.33 (4H, m), 2.41 (2H, t, J = 7.4 Hz), 2.13 (3H, s), 2.05-1.89 (8H, m),
1.66-1.47 (2H, m), 1.45-1.16 (48H, m), 0.87 (3H, t, J = 6.6 Hz); 13C{1H}
NMR (100 MHz): δ 209.5 (C, d, J = 40 Hz), 130.6 (CH2), 130.6 (CH2),
130.4 (CH2, 2C), 44.0 (CH2), 32.8 (CH2, 2C), 32.7 (CH2, 2C), 32.1 (CH2,
2C), 31.1 (CH2), 30.0 (CH3), 29.8 (CH2, 12C), 29.7 (CH2, 3C), 29.6 (CH2,
2C), 29.5 (CH2), 29.3 (CH2), 28.8 (CH2), 24.0 (CH2), 22.8 (CH2), 14.3
(CH3); IR (KBr) νmax 2919, 2849, 1712, 1470, 1462, 1374, 1166, 963, 729,
716 cm-1; GC/LRMS (EI, 70 eV) m/z: 530.6 (M+, 12), 512.6 (2), 109.1 (36),
96.1 (66), 95.1 (62), 85.9 (63), 83.9 (100), 82.1 (46), 81.1 (60), 55.1
(52%); GC/HRMS (EI, 45 eV) m/z: [M]+ calcd for C37H73O 530.5427;
found 530.5421; Kováts retention index 3899.[32]
Labelled heptatriaconta-15,22-dien-2-ol (Z>E-33*): GP4 was applied to
Z>E-30 using 13C-labelled iodomethane, eluent 5:95 AcOEt/cyclohexane,
pale yellow waxy solid (61% yield). Rf = 0.40 (silica gel, DCM); 1H NMR
(400 MHz, CDCl3): δ 5.40-5.30 (4H, m), 3.84-3.75 (1H, m), 2.07-1.93 (8H,
m), 1.40-1.21 (52H, m), 1.18 (3H, dd, J = 125.1, 6.2 Hz), 0.87 (3H, t, J =
7.1 Hz); 13C{1H} NMR (100 MHz): δ 130.1 (CH), 130.1 (CH), 129.9 (CH,
2-(Pentatriaconta-13,20-dien-1-yl)-1,3-dioxolane (Z>E-29): GP2 was
applied to Z>E-12 and 28, eluent 1:1 DCM/cyclohexane, pale yellow oil
9
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
2C), 68.4 (CH, d, J = 38 Hz), 39.5 (CH2), 32.1 (CH2), 29.9 (CH2), 29.8
(CH2, 3C), 29.8 (CH2), 29.8 (CH2, 5C), 29.8 (CH2), 29.7 (CH2), 29.7 (CH2),
29.5 (CH2), 29.5 (CH2), 29.4 (CH2, 6C), 29.1 (CH2), 27.4 (CH2), 27.3
(CH2), 25.9 (CH2), 25.9 (CH2), 23.6 (13CH3), 22.8 (CH2), 19.7 (CH2), 14.3
(CH3); IR (KBr) νmax 3379, 2920, 2850, 1540, 1465, 1135, 962, 725, 670
cm-1.
[4]
S. C. Brassell, R. G. Brereton, G. Eglinton, J. O. Grimalt, G. Liebezeit, I.
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649-660.
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F. G. Prahl, S. G. Wakeham, Nature 1987, 330, 367-369.
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T. D. Herbert in Treatise on Geochemistry, Vol. 6 (Eds.: H. D. Holland
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Paleoceanography (Eds.: C. Hillaire-Marcel and A. de Vernal), Elsevier,
Oxford, 2007, pp. 441-490.
Labelled (15E,22E)-heptatriaconta-15,22-dien-2-ol (E>Z-33*): GP5
was applied to Z>E-33*, white waxy solid (77% yield). Rf = 0.43 (silica gel,
9:1 DCM/cyclohexane); 1H NMR (400 MHz, CDCl3): δ 5.44-5.32 (4H, m),
3.84-3.75 (1H, m), 2.05-1.90 (8H, m), 1.37-1.22 (52H, m), 1.18 (3H, dd, J
= 125.1, 6.2 Hz), 0.87 (3H, t, J = 7.1 Hz); 13C{1H} NMR (100 MHz): δ
130.6 (CH2), 130.6 (CH2), 130.4 (CH2, 2C), 68.4 (CH, d, J = 38 Hz), 39.5
(CH2), 32.8 (CH2, 2C), 32.7 (CH2, 2C), 32.1 (CH2), 29.9 (CH2, 3C), 29.8
(CH2, 5C), 29.8 (CH2, 2C), 29.7 (CH2, 2C), 29.5 (CH2), 29.4 (CH2, 5C),
29.3 (CH2), 29.0 (CH2), 28.8 (CH2), 25.9 (CH2, 2C), 23.6 (13CH3), 22.8
(CH2), 14.3 (CH3); IR (KBr) νmax 3437, 2919, 2849, 1654, 1635, 1470,
1462, 1382, 1127, 1089, 987, 965, 869, 842, 724 cm-1; HRMS (ESI-TOF)
m/z: [M+H+] calcd for C3613CH73O 534.5689; found 534.5676.
[10] J. A. Rechka, J. R. Maxwell, Tetrahedron Lett. 1988, 29, 2599-2600.
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[13] A. Filippova, M. Kienast, M. Frank, R. R. Schneider, Geochem.,
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720.
Labelled (15E,22E)-heptatriaconta-15,22-dien-2-one (E,E-3*): GP6
was applied to E,E-33*, eluent cyclohexane/AcOEt 9:1, white waxy solid
(from hot methanol) (22% yield). Rf = 0.34 (silica gel, DCM/cyclohexane
6:4); 1H NMR (400 MHz, CDCl3): δ 5.43-5.32 (4H, m), 2.41 (2H, t, J = 7.5
Hz), 2.13 (3H, d, J = 127.0 Hz), 2.4-1.92 (8H, m), 1.61-1.52 (2H, m),
1.38-1.19 (48H, m), 0.88 (3H, t, J = 6.8 Hz); 13C{1H} NMR (100 MHz,
CDCl3): δ 209.5 (C, d, J = 40 Hz), 130.6 (CH), 130.5 (CH), 130.4 (CH,
2C), 44.0 (CH2, d, J = 14 Hz), 32.8 (CH2, 2C), 32.7 (CH2, 2C), 32.1 (CH2),
30.0 (13CH3), 29.9 (CH2, 4C), 29.8 (CH2, 10C), 29.7 (CH2, 2C), 29.6 (CH2,
2C), 29.5 (CH2), 29.3 (CH2), 28.8 (CH2, 2C), 24.0 (CH2), 23.6 (CH2), 22.8
(CH2), 14.3 (CH3); IR (KBr) νmax 2918, 2848, 1711, 1472, 1459, 1374,
1344, 1160, 1067, 963, 729, 718 cm-1; GC/LRMS (EI, 70 eV) m/z: [M]+
531.7 (1), 109.2 (9), 96.1 (23), 95.2 (15), 86.0 (65), 84.0 (100), 81.1 (15),
55.2 (15), 51.1 (36%); GC/HRMS (EI, 45 eV) m/z: [M]+ calcd for
C3613CH70O 531.5460; found 531.5348; Kováts retention index 3898.[32]
[16] J. M. Chong, M. A. Heuft, P. Rabbat, J. Org. Chem. 2000, 65, 5837-
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17269.
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Synthesis, Fourth Edition, John Wiley & Son, 2006.
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55, 3248-3253.
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Acknowledgements
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2329-2340 (with hexane and dodecane homologues, in DCM:
ineffective in our case).
The authors acknowledge MIUR and Università Ca’ Foscari di
Venezia.
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Authors are grateful to Thomas Bassano for the graphical
artwork of Table of Contents.
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Keywords: total synthesis • long chain alkenones • paleoclimate
indicators • paleosalinity indicators • labelled compounds
§
This diastereoselection was considered constant for all the
following Wittig reactions, that are reasonably not affected by the
configuration of the previously formed double bond. The
following configurations of the compounds containing two, three,
and four double bonds were labelled simply as Z>E, since the
contemporary presence of these double bonds led to the
formation of 4, 8 or 16 diastereomers, with a high prevalence of
the all-Z-isomer (90%, 86% and 81% respectively).
[1]
[2]
H. Lohmann, Arch. Protistenkunde, 1902, 1, 89-165.
E. Kamptner, Anzeiger der Kaiserlichen Akademie der Wissenschaften,
Mathematisch-Naturwissenschaftliche Classe 1943, 80, 49-73.
S. C. Brassell, G. Eglinton, I. T. Marlowe, U. Pflaumann, M. Sarnthein,
Nature 1986, 320, 129-133.
[3]
10
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10.1002/ejoc.202000145
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
Key Topic: Palaeoclimate and Palaeosalinity Proxies
The total syntheses of three C37 methyl-alkenones with different degrees of unsaturation and their 13C-labelled analogues are
presented herein. The products are important to improve the reliability of the measurements and estimations of the temperature and
salinity of the oceans during the Cenozoic Era.
11
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