Synthesis, Absolute Configurations, and Biological Activities of Floral Scent Compounds from Night-Blooming Araceae

Floral Scent Compounds from Night-Blooming Araceae

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Synthesis, Absolute Conﬁgurations, and Biological Activities of

Patrick Stamm, Florian Etl, Artur Campos D. Maia, Stefan D ö tterl, and Stefan Schulz*

Cite This: J. Org. Chem. 2021, 86, 5245 −5254

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sı Supporting Information

ABSTRACT: The uncommon jasmone derivatives dehydrojas-

mone, isojasmol, and isojasmyl acetate, ﬂoral scent compounds

from night-blooming Araceae, were synthesized in a scalable

synthesis employing conjugate addition with a selenoacetal as the

key step. The stereoselective strategy with subsequent enzymatic

kinetic resolution allowed determining the absolute conﬁguration

of the natural compounds by GC on a chiral phase. The

homoterpene (E)-4,8-dimethyl-1,3,7-nonatrien-5-yl acetate, anoth-

er uncommon scent compound, was obtained by α-regioselective

aldehyde prenylation. The biological activities of dehydrojasmone

and isojasmol were investigated in ﬁeld assays, showing that these

unique volatiles are able to selectively attract speciﬁc cyclocepha-

line scarab beetle pollinators.

INTRODUCTION

Night-blooming neotropical angiosperms of diﬀerent plant

lineages rely on single or simple combinations of speciﬁc ﬂoral

volatile organic compounds to selectively attract certain

species of specialized cyclocephaline scarab beetle pollinators,

a mechanism assumed to play a key role in the reproductive

isolation and species diversiﬁcation of these plants. In 2019, we

reported the discovery of three new ﬂoral scent compounds

and one related compound from headspace extracts of the

South American scarab beetle-pollinated Araceae species

another common plant volatile known to be involved in

3,6

■

pollinator attraction and chemical defense.

Herein, we report the synthesis of the jasmone derivatives

2−4 and homoterpene 6 by a scalable synthesis, the

assignment of their absolute conﬁgurations, and results of

ﬁeld tests of their activities as attractants for scarab beetle

pollinators.

RESULTS AND DISCUSSION

■

Synthesis of Jasmone Derivatives 2−4. Flowers and

inﬂorescences of tropical plants pollinated by cyclocephaline

scarab beetles emit large amounts of volatiles. Therefore, we

Thaumatophyllum mello-barretoanum, Xanthosoma hylaeae,

and Philodendron squamiferum. After isolation by preparative

gas chromatography, their structures were elucidated using

high-resolution mass spectrometry and NMR spectroscopy,

with their relative and absolute conﬁgurations still to be

assigned (Scheme 1). The new compounds were found to be

derived from more common ﬂoral scents, likely through

biosynthetic “post-processing”: isojasmol (3, isolated from T.

mello-barretoanum, also produced by X. hylaeae, and Ludovia

assumed that about 40 mg of material would be required for

testing the attractiveness of these compounds in the ﬁeld.

Consequently, we were looking for a synthesis that could

reliably yield the target compounds in the 100 mg range. Initial

attempts using alkylation reactions starting from 1,3-cyclo-

pentanedione were hampered by sometimes low yields and

isomerizations. Subsequently, we opted for a late introduction

of the double-bonds and 2-cyclopentenone as the starting

material.

lancifolia ) and isojasmyl acetate (4, isolated from X. hylaeae)

are reduction products of (Z)-jasmone (1), a widespread plant

volatile produced from linolenic acid along the jasmonic acid

cascade, which plays a role in attracting pollinators,

antiherbivore defense, and intra- and interspeciﬁc control of

Similar to the classic three-component coupling prostaglan-

din synthesis developed by Noyori et al., a conjugate addition-

gene expression. The dienone dehydrojasmone (2, isolated

Received: January 19, 2021

Published: March 16, 2021

from T. mello-barretoanum) is an oxidation product of (Z)-

jasmone (1), with the endocyclic double-bond being shifted to

the semicyclic position in all three compounds. The fourth

compound, (E)-4,8-dimethyl-1,3,7-nonatrien-5-yl acetate (6,

isolated from P. squamiferum), is an oxidation product of the

homoterpene (E)-4,8-dimethyl-1,3,7-nonatriene (DMNT, 5),

2021 American Chemical Society

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Scheme 1. Structures, Source Plants, and Assumed

Biosynthetic Precursors of the Floral Scent Compounds

Dehydrojasmone (2), Isojasmol (3), Isojasmyl Acetate (4),

and (E)-4,8-Dimethyl-1,3,7-nonatrien-5-yl acetate (6).

Scheme 2. Synthesis of Key Intermediate 10 by Conjugate

Addition of Selenium-Stabilized Organolithium Reagents 8/

11 Followed by Enolate Trapping

Photos from Top to Bottom by A. Maia, E. G. Gonc a̧ lves,

and D. Scherberich

From ketone 10, racemic dehydrojasmone (rac-2) was

smoothly obtained by α-selenylation of the keto group (LDA,

(

PhSe) /Br ) followed by oxidative elimination of both selenyl

2 2

16,17

groups using mCPBA (Scheme 3).

En route to isojasmol

Scheme 3. Synthesis of Racemic Dehydrojasmone (rac-2),

Isojasmol (rac-3), and epi-Isojasmol (rac-epi-3) via

Oxidative and Reductive Transformations of Ketone 10

enolate trapping strategy was anticipated to allow for an

eﬃcient construction of the carbon skeleton of jasmone

derivatives 2−4. The nucleophile used thereby should be

suitably functionalized to later enable the facile introduction of

the semicyclic double-bond. Organolithium reagents bearing

an α-phenylselenyl group caught our interest as heterosub-

stituted organometallics of this kind are known to selectively

undergo conjugate addition to α,β-unsaturated carbonyl

systems in the presence of polar-aprotic co-solvents like

−11

HMPA or DMPU.

Unlike the enolates typically obtained

from copper-based conjugate additions, the resulting lithium

enolates are reactive enough to be directly alkylated.

Thus, (PhSe)CH Li (8), which can be generated via

selenium-lithium exchange from selenoacetal 7, itself readily

available from diphenyl diselenide and dibromomethane, was

selected as the nucleophile of ﬁrst choice (Scheme 2). Despite

extensive optimization attempts, its reaction with 2-cyclo-

pentenone and allylic iodide 9, accessible by iodination of the

respective commercially available alcohol, produced only low

and variable yields of the desired coupling product 10. As

expected, the presence of excess HMPA was observed to

suppress 1,2-addition but presumably also promotes compet-

ing deprotonation of the enone by exalting the basicity of

organolithium reagent 8. However, when treated with LDA

instead of n-BuLi, selenoacetal 7 is deprotonated to yield the

alternative nucleophile (PhSe) CHLi (11), which compared to

exhibits a lower basicity and higher tendency toward

(3), the reduction of ketone 10 produced two chromato-

graphically separable diastereomers rac-13 and rac-14. Like

known for analogous substrates, sodium borohydride was

conjugate addition due to stabilization of the carbanionic

center by the second PhSe-group. This nucleophile proved to

be better suited for the addition, enabling the synthesis of the

respective coupling product 12 in a fair yield on a 15 g scale.

Compound 12 could then be eﬃciently transformed into the

originally targeted key intermediate 10 by short-term

protection of the keto group as the diethyl acetal followed

by removal of one PhSe-group via selenium-lithium exchange.

observed to exhibit a moderate 2:1 diastereoselectivity toward

the 1,2-trans-product rac-14, while the addition of cerium

trichloride promotes the 4:1 formation of 1,2-cis-product rac-

13 (NaBH , CeCl ·7H O, EtOH, −10 °C). Complete 1,2-cis-

selectivity was obtained by the use of the hindered reducing

agent L-selectride, in which case the oxidative workup generally

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Scheme 4. Enantioselective Synthesis of Target Compounds 2−4 via Lipase-Catalyzed Kinetic Resolution

necessary for this reagent caused the concomitant oxidation of

the PhSe-group, oﬀering the possibility to perform the

reduction of the keto group and selenoxide elimination

eﬃciently as a one-pot reaction. Finally, the PhSe-group of

Synthesis of Homoterpene 6. The construction of the

carbon skeleton of homoterpene 6 is eﬃciently accomplished

via prenylation of the unsaturated aldehyde 16, itself accessible

from commercially available 3-ethoxymethacrolein and vinyl-

,2-trans-diastereomer rac-14 was eliminated in high yield

magnesium bromide (Scheme 5). Typically, unsymmetrically

under high-dilution conditions (mCPBA, hexane/NEt , Δ).

Comparison of the two synthetic epimers rac-3 and rac-epi-3

with natural isojasmol by GC/MS, TLC, and NMR spectros-

copy showed the natural relative conﬁguration to be trans.

To give access to the enantioenriched target compounds and

allow for the assignment of their natural absolute conﬁg-

Scheme 5. Synthesis of Homoterpene 6 via α-Regioselective

Prenylation

urations, a lipase-catalyzed kinetic resolution of rac-3

(

Amano lipase PS, vinyl acetate) was employed (Scheme 4).

After approximately 50% conversion (∼4 days), both the

product acetate and starting alcohol were obtained in high

enantiomeric excess (98%). By synthesis and analysis of the

Mosher esters (see the Supporting Information), the slower

acetylated enantiomer of isojasmol was shown to possess the

(

1S,2S)-conﬁguration, conﬁrming the selectivity predicted by

Kazlauskas’ rule. By comparing the synthetic and natural

samples via GC on a chiral stationary phase, (1S,2S) was

revealed to be the conﬁguration of both natural isojasmol (3)

Figure S2) and its acetate (4) (Figure S4). (1S,2S)-Isojasmyl

acetate ((1S,2S)-4) was ﬁnally obtained via acetylation with

acetic anhydride from (1S,2S)-3.

Attempts to transform (1S,2S)-3 into enantioenriched

dehydrojasmone (2) via oxidation to the corresponding ketone

followed by α-selenylation/selenoxide elimination were un-

successful, owing to the high tendency of the semicyclic

double-bond to migrate into conjugation to the newly formed

keto group. This could be overcome by performing the kinetic

resolution before the formation of the semicyclic double-bond,

although in this case the enzymatic reaction proceeded

considerably slower (57% alcohol recovered after 8 days).

Cyclopentanol (1S,2S,3R)-14 was obtained with an enantio-

meric excess of 72% and readily transformed into (S)-

dehydrojasmone ((S)-2, ee = 68%) via oxidation to the ketone

with Dess−Martin periodinane (DMP) followed by α-

selenylation/selenoxide elimination. GC analysis on a chiral

phase revealed (S) to be the natural conﬁguration of

dehydrojasmone, although the enantiomeric excesses observed

in natural samples were low (29% in a sample from

Dieﬀenbachia aurantiaca, 4% in a sample from T. mello-

barretoanum), hinting toward a high tendency of 2 to racemize

substituted allylic organometallics, e.g., prenyl Grignard

reagents, add to carbonyl compounds with the higher

substituted terminus (γ-addition), thus necessitating special

methods for the synthesis of the desired α-addition product

8. Methods successfully used in the synthesis of the related

natural product rosiridol include the BCl -mediated addition of

a prenyl stannane and a Ti(III)-catalyzed Barbier-type

prenylation; however, in the present synthesis, these

procedures led to mixtures of α- and γ-isomers in low yields.

Eventually, satisfactory yields of alcohol 18 were obtained by

the addition of prenylzinc bromide to aldehyde 16. This

method, used for the synthesis of rosiridol by Hong et al. and

6,27

then further developed by Zhao et al.,

involves the primary

formation of the γ-addition product 17 followed by an in situ

rearrangement to the thermodynamically more stable α-isomer

induced by heating in polar-aprotic solvents such as HMPA or

(Figure S3).

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DMPU. From alcohol 18, the racemic target compound rac-6

was uneventfully obtained by acetylation with acetic anhydride.

Analogous to the synthesis of jasmone derivatives 2−4, a

lipase-catalyzed kinetic resolution was tested to synthesize

natural product 6 in enantioenriched form; however, alcohol

headspace sample collected from P. grandipes. Scents from

inﬂorescences of D. aurantiaca and P. grandipes were collected at La

Gamba, Costa Rica, on adsorbent tubes ﬁlled with Tenax TA/

Carbotrap B (both Supelco, USA). To obtain the samples ﬁnally used

for the present work, adsorbent tubes were eluted with 1 mL of

acetone (p.a., Sigma-Aldrich, USA) (for more details, see else-

18 showed little reactivity in the presence of various screened

where ).

lipases (Amano lipase PS, lipase B from Candida antarctica

immobilized on Immobead 150, Novozym 435, lipase from C.

rugosa). Hence, the strategy used in the rosiridol synthesis by

Schottner et al., involving the IBX-oxidation of the racemic

alcohol to the respective ketone 19 and subsequent

Commercially available chemicals were purchased from Sigma-

Aldrich, TCI, Fisher Scientiﬁc, and abcr and were used without

further puriﬁcation unless stated otherwise. Water- and air-sensitive

reactions were carried out in heat-dried glassware under a nitrogen

atmosphere. Solvents were dried by conventional methods. A silicone

oil bath was used as a heat source for reactions that require heating. A

enantioselective reduction with diisopinocampheylchlorobor-

Kugelrohr distillation apparatus (Buchi GKR-51) was used for the

ane (DIP-Cl), was adopted. Although the reduction did not

proceed in synthetically useful yield, a highly enantioenriched

sample of acetate 6 was obtained that was used as reference in

GC experiments on a chiral stationary phase (see the

Supporting Information ). Based on the transition-state model

distillation of compound 16. Flash column chromatography was

performed using silica gel 60 (Fluka, particle size 0.040−0.063 mm,

mesh 230−440 ASTM) as the stationary phase and redistilled

technical solvents (pentane, diethyl ether) as eluents. TLC was

performed on Polygram-SIL-G/UV254 silica plates (Macherey-

Nagel). Molybdatophosphoric acid (10% in EtOH) was used for

staining. NMR spectra were recorded on Avance III HD 300 N and

Avance III 400 instruments (Bruker) at room temperature using

tetramethylsilane as an internal standard (0 ppm). Signal multiplicities

are denominated as singlet (s), doublet (d), triplet (t), quartet (q), or

multiplet (m). Structural assignments were made with additional

information from gCOSY, gHSQC, gNOESY, and gHMBC experi-

ments.

by Brown et al. and the selectivity reported by Schottner et

al., we tentatively assign the (S)-conﬁguration to the product

obtained via the reduction with (−)-DIP-chloride. However,

GC analysis on a chiral phase revealed that the natural

compound is a racemic mixture or, at the most, might possess a

low enantiomeric excess of the presumed (S)-enantiomer

Figure S5).

Biological Activities. In ﬁeld bioassays in Costa Rica, the

EI-MS spectra (70 eV) were obtained by GC/MS on HP 6890/

MSD 5973 and HP 7890A/MSD 5975 combinations (Agilent) using

helium as carrier gas and HP-5MS fused-silica capillary columns

(Agilent, 30 m × 250 μm × 0.25 μm). EI-HRMS spectra were

obtained by GC/MS under the following conditions: An Agilent 6890

gas chromatograph was equipped with a 30 m analytical column

two compounds rac-dehydrojasmone (rac-2) and (1S,2S)-

isojasmol ((1S,2S)-3) were highly speciﬁc attractants, each to a

single distinct species of pollinating cyclocephaline scarab

beetle. When tested on ﬁlter paper against ﬁlter paper alone (n

3 each), 40 mg of isojasmol attracted overall 12 individuals

(

Phenomenex ZB1-MS, 30 m × 0.25 mm ID, tf = 0.25 μm). A split

of Cyclocephala amblyopsis Bates, 1888, while the same amount

of dehydrojasmone attracted three individuals of C. gravis

Bates, 1888. No other species of cyclocephaline scarab beetle

responded to the scented baits. The negative control did not

attract insects.

injection port at 270 °C was used for sample introduction, and the

split ratio was set to 10:1. The temperature program was 50 °C (3

min)−10 °C/min−310 °C (3 min). Helium was used as carrier gas

and was set to a 1.0 mL/min ﬂow rate (constant ﬂow mode). The

transfer line was kept at 270 °C. A JMS-T100GC (GCAccuTOF,

JEOL, Japan) time-of-ﬂight mass spectrometer in electron ionization

(EI) mode at 70 eV was used as the detector together with JEOL

MassCenter workstation software. The source and transfer line

temperatures were set at 200 and 270 °C, respectively. The detector

voltage was set at 2050 V. The acquisition range was from m/z 41 to

The speciﬁcity of each substance was further conﬁrmed by

paired testing (n = 2). Again, isojasmol speciﬁcally attracted C.

amblyopsis (six individuals) and dehydrojasmone, C. gravis

(

three individuals). The lower number of C. gravis attracted to

the scented baits appears to represent a natural trend as this

species is less abundant at the study location than C. amblyopsis

600 with a spectrum recording interval of 0.4 s. The system was tuned

with PFK to achieve a resolution of 6000 (FWHM) at m/z 292.9824.

CI-HRMS spectra were obatined by GC/MS under the following

conditions: A TRACE 1310 Series GC coupled to an Exactive GC

Orbitrap mass spectrometer (Thermo Scientiﬁc) was used. Samples

were injected (1 μL) in the gas chromatograph system with a split

inlet of 1:20 and an injector temperature of 270 °C. The system was

equipped with a ZB5MS capillary column (30 m × 25 mm ID × 0.25

μm f.t.; Phenomenex, Aschaﬀenburg, Germany), and helium was used

as carrier gas at a ﬂow rate of 1.0 mL/min. The temperature gradient

used was 50 °C (3 min)−10 °C/min−310 °C (3 min). Mass spectral

data were acquired in full scan mode (40−650 m/z), and the

automatic gain control (AGC) was set to 1E6. The ion source and

transfer line temperatures were set at 250 and 290 °C, respectively.

The analyzer resolution settings were 60,000 at m/z 200 (full width at

half-maximum (FWHM)) and 2 microscans averaging. For positive

chemical ionization (CI) high-purity methane (99.995%; Westfalen

AG) as CI-reagent gas was used at a ﬂow rate of 1.7 mL/min. Internal

lock masses (149.02332 or 207.03235) were used for spectrum mass

correction. Xcalibur software V 4.4 (Thermo Scientiﬁc) was used for

data processing. ESI-HRMS spectra were obtained using a linear ion

trap coupled with an Orbitrap mass analyzer (LTQ-Orbitrap Velos,

ThermoFisher Scientiﬁc (Bremen, Germany)) at a resolution of

100,000 FWHM at m/z 400. The acquisition range was m/z 130−

2000 resulting in an acquisition time of 1.6 s per cycle. Electrospray

measurements were performed in direct infusion mode using a

(

Etl et al., unpublished data). Overall, these results show that

both dehydrojasmone and isojasmol are bioactive and involved

in the chemical communication between night-blooming

Araceae and their speciﬁc pollinators. We expect that further

studies will elucidate the role of these substances in the

reproductive isolation of syntopic species through scent-

mediated pollinator partitioning.

CONCLUSIONS

■

In summary, we establisehd an eﬃcient strategy for the scalable

synthesis of the new jasmone derivatives 2, 3, and 4 and

determined their absolute conﬁgurations. These speciﬁc

jasmone derivatives exhibit high and selective attractivity to

specialized pollinating cyclocephaline scarab beetles.

EXPERIMENTAL SECTION

General Information. Natural dehydrojasmone (2) and natural

■

(

E)-4,8-dimethyl-1,3,7-nonatrien-5-yl acetate (6) were available in

samples of T. mello-barretoanum and P. squamiferum, respectively,

both from our previous work. Natural dehydrojasmone (2) was also

obtained from a dynamic headspace sample of D. aurantiaca. Natural

isojasmol (3) and isojasmyl acetate (4) were available in a dynamic

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Article

custom-made microspray device mounted on a Proxeon nanospray

ion source. The microspray device allows for the sample infusion

through a stainless steel capillary (90 μm ID). The typical spray

voltage was 2.3−2.8 kV in positive mode. Accurate mass measure-

ments in the Orbitrap were performed using the lock mass option of

the instrument control software using the cation of tetradecyltrime-

thylammonium bromide (256.29988 amu) as internal mass reference.

Enantiomer separation of isojasmol (3) and dehydrojasmone (2)

was achieved by GC/FID on 7890A and 7820A gas chromatographs

7 (19.5 g, 60 mmol, 1 equiv.) in THF (20 mL) was added, and the

reaction mixture was stirred at −80 °C for another 1 h. DMPU (4.0

mL, 4.2 g, 33 mmol, 0.55 equiv.) and 2-cyclopentenone (5.0 mL, 4.9

g, 60 mmol, 1 equiv.) were added dropwise in short succession (2

min). After an additional 2 min, allylic iodide 9 (12.4 g, 63 mmol,

1.05 equiv.) was added. The mixture was warmed to −40 °C and

stirred for 2 h at this temperature. The reaction was quenched by the

addition of 1 M aq. HCl. The layers were separated, and the aqueous

layer was extracted two times with diethyl ether. The combined

organic layers were successively washed with a mixture of sat. aq.

NaHCO /sat. aq. Na S O , sat. aq. NaCl and dried over MgSO . The

(Agilent) using hydrogen as carrier gas and a β-DEX 225 capillary

column (Supelco, 30 m × 0.25 mm × 0.25 μm ﬁlm thickness). In a

typical temperature program, a starting temperature of 90 °C was held

for 45 min. Then, the temperature was raised at a rate of 20 °C/min

to 220 °C. Enantiomeric separation of homoterpene alcohol 18 was

achieved by GC/FID on a 7820A gas chromatograph (Agilent) using

hydrogen as carrier gas and a hydrodex β-6TBDM capillary column

solvent was removed under reduced pressure, and the crude product

was puriﬁed by column chromatography on silica (pentane/diethyl

ether 10:1) to yield cyclopentanone 12 as a yellowish oil (14.5 g, 30.4

mmol, 51%).

R (pentane/diethyl ether 10:1) = 0.27; H NMR (300 MHz,

(

Macherey-Nagel, 25 m × 0.25 mm ID). A starting temperature of 65

CDCl ): δ [ppm] = 7.56−7.50 (m, 4H), 7.33−7.22 (m, 6H), 5.24−

C was held for 150 min. Then, the temperature was raised at a rate of

5.14 (m, 1H), 4.97−4.87 (m, 1H), 4.71 (d, J = 2.8 Hz, 1H), 2.57−

.8 °C/min to 85 °C and eventually at a rate of 40 °C/min to 230 °C.

2.49 (m, 1H), 2.46−2.26 (m, 3H), 2.16−1.99 (m, 3H), 1.85−1.63

IR spectra were recorded on a Bruker Tensor 27 (diamond ATR).

Deviating from this, the IR spectrum of compound 6 was obtained

using a GC/IR instrument, consisting of an Agilent 7890B gas

chromatograph coupled to a Dani DiscovIR-GC. The band intensities

are denominated as strong (s), medium (m), weak (w), and broad

(m, 3H), 0.84 (t, J = 7.5 Hz, 3H); C{ H} NMR (75 MHz, CDCl ):

δ [ppm] = 218.3 (C ), 134.7 (CH), 134.2 (CH), 133.6 (CH), 130.7

(C ), 130.1 (C ), 129.2 (CH), 129.1 (CH), 128.2 (CH), 128.1 (CH),

124.9 (CH), 52.9 (CH), 50.4 (CH), 47.2 (CH), 37.3 (CH ), 25.0

(CH ), 24.4 (CH ), 20.3 (CH ), 14.1 (CH ); HRMS (EI-TOF) m/z:

(

br). Optical rotation values were measured on an MCP150 Modular

[M] Calcd for C H OSe : 478.0314; Found 478.0297; EI-MS (70

23 26 2

Circular Polarimeter (Anton Paar).

eV): m/z (%) = 478 (5, [M] ), 476 (4), 321 (22), 319 (12), 253

(55), 251 (30), 163 (100), 157 (28), 155 (17), 145 (16), 135 (32),

121 (26), 119 (37), 96 (50), 91 (36), 79 (29), 77 (36), 69 (22), 67

Bis(phenylselenyl)methane (7). Using a modiﬁed procedure by

Ribaudo et al., sodium borohydride (6.3 g, 167 mmol, 2.6 equiv.) was

slowly added in portions to a suspension of diphenyl diselenide (20.0

g, 64 mmol, 1 equiv.) in abs. EtOH (700 mL) at 0 °C. The reaction

mixture was stirred at 0 °C for 30 min, giving a clear decolorized

solution, and dibromomethane (4.5 mL, 11.1 g, 64 mmol, 1 equiv.)

was added. The solution was stirred at room temperature for 20 h.

The solvent was removed under reduced pressure, and the residue

was partitioned between water and diethyl ether. The aqueous layer

was extracted with diethyl ether, and the combined organic layers

−1

(13), 55 (18), 41 (28); IR (ATR, neat): ν∼ [cm ] = 3060 (w), 2962

(m), 2870 (w), 1736 (s), 1576 (m), 1470 (m), 1439 (m), 1266 (w),

1149 (m), 1066 (m), 1021 (m), 910 (m), 805 (m), 733 (s), 687 (s).

(2RS,3SR)-2-((Z)-2-Penten-1-yl)-3-((phenylselenyl)methyl)-

cyclopentan-1-one (10). p-Toluenesulfonic acid monohydrate (56

mg, 0.3 mmol, 1 mol %) was added at room temperature to a solution

of cyclopentanone 12 (14.1 g, 29.7 mmol, 1 equiv.) in abs. EtOH

(200 mL). After dissolution, triethyl orthoformate (21 mL, 18.7 g,

126 mmol, 4.4 equiv.) was added, and the reaction mixture was stored

in a refrigerator overnight. The solvent was removed under reduced

pressure, and the crude diethyl acetal was dried in high vacuum.

The acetal was dissolved in THF (250 mL), and n-butyllithium

(1.6 M in hexanes, 44 mL, 70 mmol, 2.4 equiv.) was added dropwise

at −80 °C. After stirring for 50 min at −80 °C, EtOH (10 mL) was

added, and the reaction mixture was warmed to room temperature. 1

M aq. HCl (150 mL) was added, and the biphasic mixture was stirred

vigorously for 1 h. The layers were separated, and the aqueous layer

was extracted with diethyl ether. The combined organic layers were

were dried over MgSO . After removal of the solvent under reduced

pressure, selenoacetal 7 was obtained as a yellow oil/low-melting solid

(

19.7 g, 60.4 mmol, 94%).

H NMR (300 MHz, CDCl ): δ [ppm] = 7.52−7.45 (m, 4H),

.24−7.19 (m, 6H), 4.16 (s, 2H); C{ H} NMR (75 MHz, CDCl ):

δ [ppm] = 132.7 (CH), 130.7 (C ), 129.0 (CH), 127.3 (CH), 20.9

(

CH ); EI-MS (70 eV): m/z (%) = 328 (25, [M] ), 326 (23), 324

14), 173 (15), 171 (73), 169 (41), 167 (17), 157 (14), 93 (21), 91

−

100), 77 (23), 65 (13), 51 (19); IR (ATR, neat): ν∼ [cm ] = 3056

w), 1574 (m), 1472 (m), 1433 (m), 1130 (m), 1065 (m), 1020 (m),

728 (s), 681 (s), 620 (m).

washed with sat. aq. NaHCO and dried over MgSO , and the solvent

3 4

(

Z)-1-Iodo-2-pentene (9). Using a modiﬁed procedure by

was removed under reduced pressure. The crude product was puriﬁed

by column chromatography on silica (pentane/diethyl ether 10:1) to

Kurashina et al., (Z)-2-penten-1-ol (7.3 mL, 6.2 g, 72 mmol, 1

equiv.) was added at 0 °C to a solution of sodium iodide (21.6 g, 144

mmol, 2 equiv.) in acetonitrile (150 mL). The boron triﬂuoride-

diethyl ether-complex (18.2 mL, 20.4 g, 144 mmol, 2 equiv.) was

added dropwise, and the dark solution was stirred at 0 °C for 35

min. The reaction mixture was poured into a mixture of sat. aq.

NaHCO and sat. aq. Na S O , and the aqueous and acetonitrile

layers were extracted two times with pentane. The combined pentane

yield cyclopentanone 10 as a yellowish oil (8.94 g, 27.8 mmol, 94%).

R (pentane/diethyl ether 10:1) = 0.23; H NMR (400 MHz,

CDCl ): δ [ppm] = 7.55−7.48 (m, 2H), 7.30−7.23 (m, 3H), 5.44−

5.36 (m, 1H), 5.22−5.14 (m, 1H), 3.32 (dd, J = 12.2 Hz, 3.9 Hz, 1H),

2.90 (dd, J = 12.2 Hz, 8.4 Hz, 1H), 2.40−1.94 (m, 9H), 1.58−1.49

(m, 1H), 0.92 (t, J = 7.5 Hz, 3H); C{ H} NMR (100 MHz,

CDCl ): δ [ppm] = 219.2 (C ), 133.9 (CH), 132.7 (CH), 130.3

extracts were dried over MgSO , and the solvent was removed under

(C ), 129.1 (CH), 127.0 (CH), 125.1 (CH), 54.7 (CH), 41.8 (CH),

reduced pressure to yield crude allylic iodide 9 as a colorless liquid

37.7 (CH ), 33.1 (CH ), 27.4 (CH ), 25.4 (CH ), 20.5 (CH ), 14.1

(12.4 g, 63.2 mmol, 88%). During synthesis and handling, this

(CH ); HRMS (EI-TOF) m/z: [M] Calcd for C H OSe:

sensitive and lachrymatory compound was protected from light to

avoid decomposition/isomerization. It was used immediately in the

next step or stored in the freezer for short time periods.

322.0836; Found 322.0849; EI-MS (70 eV): m/z (%) = 322 (46,

[M] ), 320 (24), 254 (22), 252 (11), 172 (100), 170 (50), 165 (33),

158 (25), 157 (28), 151 (42), 147 (16), 135 (23), 123 (18), 109

(38), 97 (91), 95 (33), 93 (30), 91 (53), 83 (35), 81 (62), 79 (42),

77 (46), 69 (29), 67 (48), 55 (56), 41 (61); IR (ATR, neat): ν∼

EI-MS (70 eV): m/z (%) = 196 (8, [M] ), 127 (14), 70 (7), 69

(

100), 67 (7), 54 (13), 53 (10), 41 (71), 39 (23); H and C{ H}

−1

NMR data: see elsewhere.

[cm ] = 3062 (w), 3006 (w), 2962 (m), 2927 (w), 2872 (w), 1736

(

2RS,3SR)-3-(Bis(phenylselenyl)methyl)-2-((Z)-2-penten-1-

(s), 1578 (m), 1470 (m), 1437 (m), 1409 (w), 1157 (m), 1070 (m),

1022 (m), 914 (w), 805 (w), 733 (s), 690 (s).

rac-4-Methylene-5-((Z)-2-penten-1-yl)-2-cyclopenten-1-one

(rac-2). At −80 °C, n-butyllithium (1.6 M in hexanes, 5.6 mL, 9.0

mmol, 1.2 equiv.) was added to a solution of diisopropylamine (1.36

yl)cyclopentan-1-one (12). A solution of n-butyllithium (1.6 M in

hexanes, 41 mL, 66 mmol, 1.1 equiv.) was added at −80 °C to a

solution of diisopropylamine (9.6 mL, 6.9 g, 69 mmol, 1.15 equiv.) in

abs. THF (300 mL). After stirring for 5 min, a solution of selenoacetal

249

J. Org. Chem. 2021, 86, 5245−5254

The Journal of Organic Chemistry

Article

mL, 0.98 g, 9.7 mmol, 1.3 equiv.) in abs. THF (50 mL). After 3 min,

cyclopentanone 10 (2.40 g, 7.47 mmol, 1 equiv.) in THF (5 mL) was

added dropwise, and the reaction mixture was stirred for 1 h at −80

(CH), 130.9 (C ), 129.0 (CH), 127.3 (CH), 126.6 (CH), 74.8 (CH),

51.4 (CH), 42.3 (CH), 33.8 (CH ), 33.1 (CH ), 29.8 (CH ), 25.7

(CH ), 20.6 (CH ), 14.2 (CH ); EI-MS (70 eV): m/z (%) = 324 (39,

C. In a separate ﬂask, bromine (0.25 mL, 0.78 g, 4.9 mmol, 0.65

[M] ), 322 (19), 172 (100), 170 (51), 167 (36), 158 (51), 153 (88),

149 (44), 119 (30), 107 (55), 93 (71), 91 (70), 81 (93), 79 (72), 77

(54), 69 (73), 67 (59), 55 (74), 41 (88); IR (ATR, neat): ν∼ [cm ]

= 3403 (br), 3064 (w), 2957 (m), 1578 (w), 1470 (m), 1437 (m),

1303 (w), 1213 (w), 1070 (m), 1025 (m), 936 (w), 886 (w), 732 (s),

688 (s).

equiv.) was added dropwise to a solution of diphenyl diselenide (1.52

g, 4.86 mmol, 0.65 equiv.) in THF (5 mL). The resulting dark

PhSeBr-solution was rapidly added to the enolate solution

−

(

decoloration). The reaction mixture was transferred to a separation

funnel and partitioned between diethyl ether and 1 M aq. HCl. The

aqueous layer was extracted with diethyl ether, and the combined

1,2-trans-Diastereomer rac-14. R (pentane/diethyl ether 2:1) =

organic layers were washed with sat. aq. NaHCO and sat. aq. NaCl

0.32; H NMR (300 MHz, CDCl ): δ [ppm] = 7.51−7.45 (m, 2H),

and dried over MgSO₄.

7.28−7.18 (m, 3H), 5.50−5.31 (m, 2H), 3.93−3.85 (m, 1H), 3.19

(dd, J = 11.7 Hz, 4.8 Hz, 1H), 2.90 (dd, J = 11.8 Hz, 8.5 Hz, 1H),

2.22−1.98 (m, 4H), 1.92−1.78 (m, 3H), 1.75 (s, 1H), 1.67−1.51 (m,

The solvent was removed under reduced pressure, and the crude

α,δ-bis(phenylselenyl)ketone was dissolved in DCM (50 mL). At −60

C, mCPBA (70−75%, 4.27 g, 17.3−18.6 mmol, 2.3−2.5 equiv.) in

3H), 0.95 (t, J = 7.5 Hz, 3H); C{ H} NMR (75 MHz, CDCl ): δ

DCM (20 mL) was added dropwise, and the reaction mixture was

[ppm] = 133.5 (CH), 132.3 (CH), 130.8 (C ), 129.0 (CH), 126.7

stirred at −60 °C for 30 min. Triethylamine (6.2 mL, 4.5 g, 45 mmol,

(CH), 126.6 (CH), 78.7 (CH), 54.3 (CH), 43.7 (CH), 34.3 (CH₂),

33.2 (CH ), 30.2 (CH ), 29.4 (CH ), 20.6 (CH ), 14.2 (CH );

equiv.) was added, and the mixture was poured into reﬂuxing DCM

(

400 mL). After 5 min in reﬂux, the solution was cooled to room

HRMS (EI-TOF) m/z: [M] Calcd for C H OSe: 324.0992; Found

17 24

temperature and washed with sat. aq. NaHCO . The aqueous layer

324.1009; EI-MS (70 eV): m/z (%) = 324 (16, [M] ), 322 (8), 306

(9), 158 (29), 149 (100), 135 (9), 133 (10), 119 (25), 107 (41), 93

(52), 91 (41), 81 (57), 79 (46), 69 (50 ), 67 (38), 55 (44), 41 (57);

was extracted with DCM, and the combined organic layers were dried

over MgSO . The solvent was removed under reduced pressure, and

−

the residue was puriﬁed by column chromatography on silica

IR (ATR, neat): ν∼ [cm ] = 3350 (br), 3064 (w), 2957 (m), 1578

(w), 1470 (m), 1437 (m), 1342 (w), 1214 (w), 1072 (m), 1023 (m),

973 (m), 909 (w), 731 (s), 688 (s).

(

pentane/diethyl ether 20:1 → 10:1) to yield rac-dehydrojasmone

(rac-2, 0.89 g, 5.49 mmol, 73%) as a yellowish liquid with a fruity

odor. The compound is best stored in solution in a freezer. When left

(1RS,2SR)-3-Methylene-2-((Z)-2-penten-1-yl)cyclopentan-1-

ol (rac-epi-3). L-Selectride (1 M in THF, 1.0 mL, 1.0 mmol, 1.3

equiv.) was added dropwise to a solution of cyclopentanone 10 (246

mg, 0.77 mmol, 1 equiv.) in abs. THF (15 mL) at −80 °C. The

reaction mixture was allowed to warm to −25 °C over the course of

1.5 h. Then, a solution of mCPBA (70−75%, 1.04 g, 4.22−4.52 mmol,

5.5−5.9 equiv.) in THF (5 mL) was added dropwise, and the mixture

was allowed to warm to −10 °C over the course of 1 h. The solution

was poured into a reﬂuxing mixture of hexane (100 mL) and

triethylamine (10 mL). After 5 min in reﬂux, the reaction mixture was

neat at room temperature, it decomposes overnight.

R (pentane/diethyl ether 10:1) = 0.26; H NMR (400 MHz,

CDCl ): δ [ppm] = 7.72 (d, J = 5.6 Hz, 1H), 6.27 (dd, J = 5.5 Hz, 1.4

Hz, 1H), 5.45−5.38 (m, 1H), 5.40−5.39 (m, 1H), 5.35−5.34 (m,

H), 5.26−5.19 (m, 1H), 2.87−2.83 (m, 1H), 2.59−2.47 (m, 2H),

13 1

.07−2.00 (m, 2H), 0.93 (t, J = 7.5 Hz, 3H); C{ H} NMR (100

MHz, CDCl ): δ [ppm] = 208.6 (C ), 159.0 (CH), 148.8 (C ), 134.2

(

CH), 134.0 (CH), 124.0 (CH), 113.0 (CH ), 47.7 (CH), 27.1

CH ), 20.6 (CH ), 14.1 (CH ); ); HRMS (EI-TOF) m/z: [M]

Calcd for C H O: 162.1045; Found 162.1060; EI-MS (70 eV): m/z

cooled to room temperature and washed with sat. aq. NaHCO . The

(

%) = 162 (17, [M] ), 147 (10), 133 (50), 119 (18), 115 (9), 107

11), 105 (25), 103 (7), 94 (100), 91 (36), 79 (15), 77 (23), 69 (7),

aqueous layer was extracted two times with ethyl acetate, and the

combined organic layers were washed with sat. aq. NaCl and dried

5 (12), 55 (13), 51 (11), 41 (19), 39 (17); GC: I = 1300 (HP-

MS); IR (ATR, neat): ν∼ [cm ] = 3009 (w), 2965 (w), 2876 (w),

704 (s), 1639 (w), 1546 (m), 1455 (w), 1267 (w), 1166 (m), 1075

over MgSO , and the solvent was removed under reduced pressure.

−

The crude product was puriﬁed by column chromatography on silica

(pentane/diethyl ether 10:1 → 5:1) to yield epi-isojasmol (rac-epi-3)

as a yellowish liquid (100 mg, 0.60 mmol, 78%).

(w), 901 (m), 837 (m), 726 (w), 689 (w).

^Rf ⁽^p^eⁿ^t^aⁿ^e^/^dⁱ^e^t^h^y^l^e^t^h^e^r²^:¹⁾⁼⁰^.⁴⁵^;¹H NMR (400 MHz,

(

1RS,2SR,3RS)-2-((Z)-2-Penten-1-yl)-3-((phenylselenyl)-

methyl)cyclopentan-1-ol (rac-13) and (1RS,2RS,3SR)-2-((Z)-2-

Penten-1-yl)-3-((phenylselenyl)methyl)cyclopentan-1-ol (rac-

CDCl ): δ [ppm] = 5.51−5.42 (m, 2H), 5.00−4.98 (m, 1H), 4.90 (q,

J = 2.3 Hz, 1H), 4.26 (q, J = 3.2 Hz, 1H), 2.61−2.50 (m, 1H), 2.47−

2.33 (m, 3H), 2.28−2.19 (m, 1H), 2.15−2.08 (m, 2H), 1.81−1.76

4). Variant A (NaBH ). At room temperature, sodium borohydride

(21 mg, 0.55 mmol, 1.5 equiv.) was added to a solution of

(m, 2H), 0.98 (t, J = 7.5 Hz, 3H); C{ H} NMR (100 MHz,

CDCl ): δ [ppm] = 153.1 (C ), 132.9 (CH), 127.2 (CH), 106.2

cyclopentanone 10 (116 mg, 0.361 mmol, 1 equiv.) in abs. MeOH (5

mL). After stirring for 40 min, the solvent was removed under

reduced pressure, and the residue was puriﬁed by column

chromatography on silica (pentane/diethyl ether 4:1) to yield 1,2-

trans-cyclopentanol rac-14 (75.5 mg, 0.234 mmol, 65%) and 1,2-cis-

cyclopentanol rac-13 (39 mg, 0.12 mmol, 33%) as colorless oils.

Variant B (NaBH /CeCl ). At −10 °C, sodium borohydride (3.1

(CH ), 74.1 (CH), 49.7 (CH), 32.4 (CH ), 29.5 (CH ), 25.0 (CH ),

20.6 (CH ), 14.2 (CH ); EI-MS (70 eV): m/z (%) = 165 (6, [M−

H] ), 148 (13), 137 (11), 133 (15), 122 (28), 119 (100), 109 (22),

105 (31), 96 (31), 93 (46), 91 (97), 83 (32), 81 (46), 80 (90), 79

(85), 77 (42), 69 (39), 67 (48), 55 (29), 53 (23), 41 (87); GC: I =

−

1304 (HP-5MS); IR (ATR, neat): ν∼ [cm ] = 3373 (br), 3073 (w),

3006 (w), 2961 (s), 2932 (m), 1654 (m), 1456 (m), 1299 (w), 1255

(w), 1153 (m), 1077 (m), 1022 (m), 976 (m), 877 (s), 794 (m), 735

(s), 675 (m), 607 (w).

mg, 0.081 mmol, 1.1 equiv.) was added to a solution of

cyclopentanone 10 (23.6 mg, 0.073 mmol, 1 equiv.) and cerium

trichloride heptahydrate (30.1 mg, 0.081 mmol, 1.1 equiv.) in abs.

EtOH (2 mL). The reaction mixture was warmed to room

temperature over the course of 2 h. The reaction was quenched by

(1RS,2RS)-3-Methylene-2-((Z)-2-penten-1-yl)cyclopentan-1-

ol (rac-3). At 0 °C, mCPBA (70−75%, 3.79 g, 15.4−16.5 mmol, 1.0−

1.1 equiv.) was added to a solution of 1,2-trans-cyclopentanol rac-14

(4.97 g, 15.4 mmol, 1 equiv.) in DCM (50 mL). After stirring for 15

min at 0 °C, the reaction mixture was poured into a reﬂuxing mixture

of hexane (1.5 L) and triethylamine (50 mL). After 1 h in reﬂux, the

reaction mixture was cooled to room temperature and washed with

the addition of sat. aq. NaHCO , and the aqueous layer was extracted

two times with diethyl ether. The combined organic layers were dried

over MgSO . GC analysis of the crude product showed the

diastereomeric ratio 14/13 to be 1:4.

,2-cis-Diastereomer rac-13. R (pentane/diethyl ether 2:1) =

.46; H NMR (300 MHz, CDCl ): δ [ppm] = 7.51−7.46 (m, 2H),

.28−7.18 (m, 3H), 5.47−5.30 (m, 2H), 4.23 (td, J = 4.8 Hz, 2.0 Hz,

H), 3.21 (dd, J = 11.6 Hz, 3.9 Hz, 1H), 2.82 (dd, J = 11.6 Hz, 8.5

sat. aq. NaHCO . The aqueous layer was extracted two times with

diethyl ether. The combined organic layers were dried over MgSO₄,

and the solvent was removed under reduced pressure. The crude

product was puriﬁed by column chromatography on silica (pentane/

diethyl ether 4:1 → 2:1) to yield rac-isojasmol (rac-3) as a yellowish

liquid (2.41 g, 14.5 mmol, 94%).

Hz, 1H), 2.23−2.00 (m, 6H), 1.95−1.82 (m, 1H), 1.67−1.49 (m,

H), 1.47 (s, 1H), 1.46−1.33 (m, 1H), 0.96 (t, J = 7.5 Hz, 3H);

C{ H} NMR (75 MHz, CDCl ): δ [ppm] = 132.8 (CH), 132.3

250

J. Org. Chem. 2021, 86, 5245−5254

The Journal of Organic Chemistry

Article

R_f(pentane/diethyl ether 2:1) = 0.31; ¹H NMR (400 MHz,

mg, 0.18 mmol, 4 equiv.), (1S,2S)-isojasmol ((1S,2S)-3, 7.4 mg, 0.045

mmol, 1 equiv.), and DMAP (3 mg, 0.02 mmol, 0.5 equiv.) were

added successively. The mixture was stirred overnight at room

temperature and then directly subjected to column chromatography

on silica (pentane/diethyl ether 20:1) to yield the (S)-Mosher ester

(12.3 mg, 0.032 mmol, 72%) as a colorless oil/solid.

CDCl ): δ [ppm] = 5.54−5.44 (m, 2H), 4.94−4.91 (m, 1H), 4.90−

.87 (m, 1H), 3.91 (q, J = 6.1 Hz, 1H), 2.54−2.45 (m, 1H), 2.35−

.95 (m, 7H), 1.75 (br s, 1H), 1.67−1.57 (m, 1H), 0.98 (t, J = 7.5 Hz,

H); ¹³C{ H} NMR (100 MHz, CDCl ): δ [ppm] = 152.8 (C ),

33.5 (CH), 126.8 (CH), 106.7 (CH ), 77.9 (CH), 52.3 (CH), 32.5

(

CH ), 29.8 (CH ), 29.2 (CH ), 20.7 (CH ), 14.2 (CH ); HRMS

In an analogous experiment, the (R)-Mosher ester (19.9 mg, 0.052

mmol, 93%) was obtained from (R)-Mosher’s acid (26.2 mg, 0.112

mmol) and (1S,2S)-isojasmol ((1S,2S)-3, 9.3 mg, 0.056 mmol).

CI-Orbitrap) m/z: [M + H] Calcd for C H O 167.1436; Found

67.1431; EI-MS (70 eV): m/z (%) = 166 (4, [M] ), 165 (14, [M−

H] ), 151 (11), 148 (13), 137 (25), 133 (15), 122 (32), 119 (91),

09 (42), 107 (25), 105 (25), 97 (45), 96 (71), 95 (47), 93 (63), 91

76), 83 (53), 81 (56), 80 (64), 79 (81), 77 (52), 69 (57), 67 (64),

(1S,2S)-Isojasmyl (S)-Mosher Ester. R (pentane/diethyl ether

20:1) = 0.47; H NMR (400 MHz, CDCl ): δ [ppm] = 7.54−7.50

(

(m, 2H), 7.43−7.36 (m, 3H), 5.52−5.35 (m, 2H), 5.13 (q, J = 4.4 Hz,

1H), 4.97 (q, J = 2.1 Hz, 1H), 4.93 (q, J = 2.1 Hz, 1H), 3.56−3.54

(m, 3H), 2.69−2.62 (m, 1H), 2.50−2.33 (m, 2H), 2.30−1.99 (m,

5 (43), 53 (33), 43 (24), 41 (100), 39 (44); GC: I = 1296 (HP-

MS); IR (ATR, neat): ν∼ [cm ] = 3333 (br), 3073 (w), 2960 (s),

875 (m), 1654 (m), 1442 (m), 1343 (w), 1067 (s), 961 (m), 881

−

5H), 1.79−1.71 (m, 1H), 0.96 (t, J = 7.5 Hz, 3H); C{ H} NMR

(

s), 727 (m), 682 (m).

1S,2S)-3-Methylene-2-((Z)-2-penten-1-yl)cyclopentan-1-ol

(1S,2S)-3) and (1R,2R)-3-Methylene-2-((Z)-2-penten-1-yl)-

(100 MHz, CDCl ): δ [ppm] = 166.1 (C ), 151.3 (C ), 133.7 (CH),

(

132.4 (C ), 129.5 (CH), 128.3 (CH), 127.3 (CH), 125.5 (CH),

(

123.3 (q, J = 288 Hz, CF ), 107.4 (CH ), 84.5 (q, J = 27.5 Hz, C ),

cyclopentyl Acetate ((1R,2R)-4). Amano Lipase PS (2.36 g) was

added to a solution of rac-isojasmol (rac-3, 1.48 g, 8.88 mmol, 1

equiv.) in diethyl ether (50 mL), pentane (50 mL), and vinyl acetate

2.5 (CH), 55.4 (CH ), 49.4 (CH), 30.2 (CH ), 30.0 (CH ), 29.8

(CH ), 20.7 (CH ), 14.2 (CH ).

2 2 3

(

1S,2S)-Isojasmyl (R)-Mosher Ester. R (pentane/diethyl ether

(50 mL). The reaction mixture was stirred vigorously at room

(

0:1) = 0.40; H NMR (400 MHz, CDCl ): δ [ppm] = 7.55−7.50

temperature for 91 h (progress monitored by chiral GC). Then, the

mixture was ﬁltered, and the ﬁlter cake was washed extensively with

diethyl ether. The ﬁltrate was concentrated under reduced pressure,

and the residue was puriﬁed by column chromatography on silica

m, 2H), 7.42−7.36 (m, 3H), 5.47−5.39 (m, 1H), 5.36−5.28 (m,

H), 5.12 (q, J = 4.9 Hz, 1H), 4.95 (q, J = 2.0 Hz, 1H), 4.89 (q, J =

.1 Hz, 1H), 3.54−3.53 (m, 3H), 2.62−2.56 (m, 1H), 2.54−2.34 (m,

H), 2.28−2.10 (m, 3H), 2.01 (quin, J = 7.4 Hz, 2H), 1.86−1.77 (m,

(

pentane/diethyl ether 10:1 → 2:1). After evaporation, the combined

isojasmol fractions were redissolved in diethyl ether/pentane 1:1 and

washed two times with sat. aq. K CO to remove co-eluted acetic acid.

H), 0.95 (t, J = 7.5 Hz, 3H); C{ H} NMR (100 MHz, CDCl ): δ

[

ppm] = 166.1 (C ), 151.0 (C ), 133.6 (CH), 132.3 (C ), 129.5

(CH), 128.3 (CH), 127.4 (CH), 125.4 (CH), 123.3 (q, J = 288 Hz,

CF ), 107.4 (CH ), 84.5 (q, J = 27.7 Hz, C ), 82.2 (CH), 55.3 (CH ),

The organic layer was dried over MgSO , and the solvent was

removed under reduced pressure. (1S,2S)-Isojasmol ((1S,2S)-3, 648

mg, 3.90 mmol, 44%) and (1R,2R)-isojasmyl acetate ((1R,2R)-4, 879

mg, 4.22 mmol, 47%) were obtained as yellowish liquids.

9.2 (CH), 30.1 (CH ), 30.0 (CH ), 29.8 (CH ), 20.7 (CH ), 14.2

2 2 2 2

(CH₃).

(

1S,2S)-3-Methylene-2-((Z)-2-penten-1-yl)cyclopentyl Ace-

To allow for the determination of the enantiomeric excess by GC

on a chiral stationary phase, a sample of (1R,2R)-isojasmyl acetate was

transformed back into isojasmol by deacylation: Sodium ethoxide (21

wt % in EtOH, 1.6 equiv.) was added to a solution of (1R,2R)-4 in

EtOH (0.05 M), and the mixture was left at room temperature for 4 h.

Water was added, and the mixture was extracted two times with

tate ((1S,2S)-4). Acetic anhydride (0.11 mL, 120 mg, 1.2 mmol, 2

equiv.) and DMAP (7 mg, 0.06 mmol, 10 mol %) were added at room

temperature to a solution of (1S,2S)-isojasmol ((1S,2S)-3, 100 mg,

.60 mmol, 1 equiv.) and triethylamine (0.33 mL, 240 mg, 2.4 mmol,

equiv.) in abs. DCM (10 mL). After stirring for 16 h at room

temperature, the reaction mixture was diluted with diethyl ether,

washed with 1 M aq. HCl, sat. aq. NaHCO , and dried over MgSO .

diethyl ether. After drying over MgSO , the crude isojasmol solution

was directly analyzed.

The solvent was removed under reduced pressure, and (1S,2S)-

isojasmyl acetate ((1S,2S)-4, 118 mg, 0.57 mmol, 94%) was obtained

as a yellowish liquid.

(

¹^S^,²^S⁾^-^I^s^o^j^a^s^m^o^l⁽⁽¹^S^,²^S⁾^-³⁾^.^[^α^]D = −54.8 (c 0.93, EtOH); ee =

8% (GC); the spectroscopic data were identical to those reported for

rac-isojasmol (rac-3).

1R,2R)-Isojasmyl Acetate ((1R,2R)-4). R (pentane/diethyl ether

[

α] = −29.3 (c 1.05, EtOH); the spectroscopic data were

(

identical to those reported for (1R,2R)-isojasmyl acetate ((1R,2R)-4).

(1S,2S,3R)-2-((Z)-2-penten-1-yl)-3-((phenylselenyl)methyl)-

cyclopentan-1-ol ((1S,2S,3R)-14) and (1R,2R,3S)-2-((Z)-2-Pent-

en-1-yl)-3-((phenylselenyl)methyl)cyclopentyl Acetate (15).

Amano Lipase PS (0.72 g) was added to a solution of rac-1,2-trans-

cyclopentanol rac-14 (0.87 g, 2.69 mmol, 1 equiv.) in diethyl ether

(15 mL), pentane (15 mL), and vinyl acetate (15 mL). The reaction

mixture was stirred vigorously at room temperature for 7 days. Then,

the mixture was ﬁltered, and the ﬁlter cake was washed extensively

with diethyl ether. The ﬁltrate was concentrated under reduced

pressure, and the residue was puriﬁed by column chromatography on

silica (pentane/diethyl ether 2:1) to yield (1S,2S,3R)-cyclopentanol

(1S,2S,3R)-14 (498 mg, 1.54 mmol, 57%) and (1R,2R,3S)-cyclo-

pentyl acetate 15 (404 mg, 1.11 mmol, 41%) as yellowish oils.

To allow for the determination of the conﬁguration and

enantiomeric excess by GC on a chiral stationary phase, a sample

of (1S,2S,3R)-cyclopentanol (1S,2S,3R)-14 was transformed into

isojasmol by selenoxide elimination analogous to the preparation of

rac-isojasmol (rac-3).

(

0:1) = 0.50; H NMR (400 MHz, CDCl ): δ [ppm] = 5.48−5.33

m, 2H), 4.97−4.95 (m, 1H), 4.93−4.87 (m, 2H), 2.56−2.44 (m,

H), 2.40−2.31 (m, 1H), 2.28−2.12 (m, 2H), 2.09−1.99 (m, 3H),

13 1

.02 (s, 3H), 1.75−1.66 (m, 1H), 0.95 (t, J = 7.5 Hz, 3H); C{ H}

NMR (100 MHz, CDCl ): δ [ppm] = 170.8 (C ), 152.0 (C ), 133.2

(

CH), 125.9 (CH), 106.9 (CH ), 79.8 (CH), 49.5 (CH), 30.02

CH ), 20.99 (CH ), 29.96 (CH ), 21.3 (CH ), 20.6 (CH ), 14.1

CH ); HRMS (ESI-Orbitrap) m/z: [M + Na] Calcd for

C H O Na 231.1361; Found 231.1356; EI-MS (70 eV): m/z (%)

166 (1), 148 (61), 133 (27), 119 (100), 106 (36), 105 (33), 97

(16), 93 (16), 92 (16), 91 (59), 81 (19), 80 (73), 79 (55), 77 (23),

9 (16), 67 (15), 55 (10), 53 (11), 43 (75), 41 (39), 39 (14); GC: I

1410 (HP-5MS); IR (ATR, neat): ν∼ [cm ] = 3074 (w), 2964

−1

(m), 2875 (w), 1736 (s), 1657 (w), 1441 (w), 1369 (m), 1236 (s),

040 (m), 965 (w), 886 (m), 725 (w), 608 (w); [α]_D= +32.5 (c

.07, EtOH); ee = 98% (GC after derivatization).

Mosher Esters of (1S,2S)-Isojasmol ((1S,2S)-3). Following the

procedure by Ward and Rhee for the microscale preparation of

Mosher’s acid chloride, oxalyl chloride (0.04 mL, 57 mg, 0.45 mmol,

(1S,2S,3R)-Cyclopentanol (1S,2S,3R)-14. [α] = −45.1 (c 0.97,

10 equiv.) was added dropwise to a solution of (S)-Mosher’s acid

DCM); ee = 72% (GC after derivatization); the spectroscopic data

(

20.9 mg, 0.089 mmol, 2 equiv.) and DMF (7 μL, 6.5 mg, 0.089

were identical to those reported for rac-1,2-trans-cyclopentanol rac-

mmol, 2 equiv.) in abs. hexane (5 mL). After stirring for 1 h at room

temperature, the mixture was decanted, and the solvent and excess

oxalyl chloride were removed under reduced pressure. The residue

was dissolved in abs. DCM (2 mL), and triethylamine (0.02 mL, 18

14.

(1R,2R,3S)-Cyclopentyl Acetate 15. R (pentane/diethyl ether 2:1)

= 0.67; H NMR (300 MHz, CDCl ): δ [ppm] = 7.51−7.45 (m, 2H),

7.28−7.20 (m, 3H), 5.46−5.36 (m, 1H), 5.33−5.23 (m, 1H), 4.83

251

J. Org. Chem. 2021, 86, 5245−5254

The Journal of Organic Chemistry

Article

(

dt, J = 8.0 Hz, 3.1 Hz, 1H), 3.17 (dd, J = 11.7 Hz, 4.8 Hz, 1H), 2.88

liquid. The compound is best stored in a freezer to avoid rapid

dd, J = 11.7 Hz, 8.4 Hz, 1H), 2.22−1.47 (m, 10H), 2.01 (s, 3H),

degradation.

.92 (t, J = 7.5 Hz, 3H); C{ H} NMR (75 MHz, CDCl ): δ [ppm]

(E)/(Z) = 93:7 (NMR); H NMR (300 MHz, CDCl ): δ [ppm] =

170.6 (C ), 133.4 (CH), 132.4 (CH), 130.6 (C ), 128.9 (CH),

9.48 (s, 1H), 6.92−6.77 (m, 2H), 5.78−5.48 (m, 2H), 1.88−1.85 (m,

26.6 (CH), 125.8 (CH), 80.6 (CH), 51.3 (CH), 43.5 (CH), 33.9

3H); C{ H} NMR (75 MHz, CDCl ): δ [ppm] = 195.1 (CH),

(

CH ), 31.0 (CH ), 30.3 (CH ), 29.8 (CH ), 21.3 (CH ), 20.5

148.5 (CH), 138.4 (C ), 131.9 (CH), 126.2 (CH ), 9.5 (CH ); EI-

MS (70 eV): m/z (%) = 96 (83, [M] ), 95 (37), 67 (100), 65 (30),

63 (10), 53 (43), 51 (11), 41 (48), 39 (18).

CH ), 14.2 (CH ); HRMS (EI-TOF) m/z: [M] Calcd for

C H O Se 366.1098; Found 366.1073; EI-MS (70 eV): m/z (%)

366 (17, [M] ), 364 (9), 306 (19), 304 (10), 238 (9), 171 (9), 157

(E)-4,8-Dimethyl-1,3,7-nonatrien-5-ol (18). Zinc was activated

(

19), 149 (100), 135 (8), 133 (12), 119 (32), 107 (49), 93 (57), 91

according to Knochel et al. 1,2-Dibromoethane (0.30 mL, 0.66 g,

3.5 mmol, 0.15 equiv.) was added to a suspension of zinc powder

(5.88 g, 90 mmol, 3.9 equiv.) in abs. THF (50 mL), and the mixture

was brieﬂy heated to reﬂux. Trimethylsilyl chloride (0.37 mL, 0.31 g,

2.9 mmol, 0.13 equiv.) was added, and the mixture was stirred at

room temperature for 15 min. The mixture was cooled to 0 °C, and

prenyl bromide (5.2 mL, 6.7 g, 45 mmol, 1.9 equiv.) was slowly added

over the course of 30 min. After stirring for 1 h at room temperature,

the excessive zinc was removed by ﬁltration through a glass frit, and

dienal 16 (2.23 g, 23.2 mmol, 1 equiv.) in THF (3 mL) was added

dropwise. After 30 min, DMPU (40 mL) was added and THF was

removed under reduced pressure (Schlenk line). The reaction mixture

was heated to 100 °C for 5 h. After cooling to room temperature, the

50), 81 (55), 79 (56), 77 (32), 69 (30), 67 (33), 55 (24), 43 (81),

−

1 (44); IR (ATR, neat): ν∼ [cm ] = 3063 (w), 3006 (w), 2961

(m), 2930 (w), 2872 (w), 1732 (s), 1578 (w), 1470 (w), 1437 (m),

367 (m), 1239 (s), 1022 (s), 970 (w), 734 (s), 690 (m), 607 (w);

[α] = +39.3 (c 1.17, DCM).

(

S)-4-Methylene-5-((Z)-2-penten-1-yl)-2-cyclopenten-1-one

(

(S)-2). (2S,3R)-2-((Z)-2-Penten-1-yl)-3-((phenylselenyl)methyl)-

cyclopentan-1-one ((2S,3R)-10). Dess−Martin periodinane (354

mg, 0.84 mmol, 2 equiv.) was added to a solution of (1S,2S,3R)-

cyclopentanol (1S,2S,3R)-14 (135 mg, 0.42 mmol, 1 equiv.) in DCM

(

8 mL). The turbid reaction mixture was stirred for 2 h at room

temperature. Then, a mixture of sat. aq. NaHCO₃and sat. aq.

Na S O was added. After stirring for 5 min, the phases became clear.

The mixture was extracted two times with diethyl ether. The

combined organic layers were washed with sat. aq. NaHCO , dried

over MgSO , and concentrated under reduced pressure. The residue

mixture was partitioned between dil. aq. NH Cl and diethyl ether.

The aqueous layer was extracted two times with diethyl ether, and the

combined organic layers were washed with water and dried over

MgSO . The solvent was removed under reduced pressure, and the

was puriﬁed by ﬁltering through a short column of silica (pentane/

diethyl ether 2:1). (2S,3R)-Cyclopentanone (2S,3R)-10 (90 mg, 0.28

mmol, 67%) was obtained as a colorless oil and directly used in the

next step.

residue was puriﬁed by column chromatography on silica (pentane/

diethyl ether 10:1 → 4:1) to yield homoterpene alcohol 18 (2.76 ,

16.6 mmol, 71%) as a colorless liquid.

R (pentane/diethyl ether 10:1) = 0.12; H NMR (300 MHz,

(

S)-4-Methylene-5-((Z)-2-penten-1-yl)-2-cyclopenten-1-one ((S)-

). At −80 °C, LiHMDS (1 M in THF, 0.34 mL, 0.34 mmol, 1.2

equiv.) was added dropwise to a solution of (2S,3R)-cyclopentanone

2S,3R)-10 (90 mg, 0.28 mmol, 1 equiv.) in abs. THF (5 mL). After

stirring for 1 h at −80 °C, phenylselenyl chloride (70 mg, 0.36 mmol,

.3 equiv.) in THF (2 mL) was added. Then, the reaction mixture was

CDCl ): δ [ppm] = 6.59 (ddd, J = 16.8 Hz, 10.8 Hz, 10.2 Hz, 1H),

.08 (d, J = 11.0 Hz, 1H), 5.20 (dd, J = 16.9 Hz, 1.9 Hz, 1H), 5.15−

.07 (m, 2H), 4.04 (t, J = 6.5 Hz, 1H), 2.31−2.24 (m, 2H), 1.77 (d, J

(

1.1 Hz, 3H), 1.73 (d, J = 1.3 Hz, 3H), 1.65 (s, 3H); C{ H} NMR

(75 MHz, CDCl ): δ [ppm] = 140.0 (C ), 135.1 (C ), 132.7 (CH),

125.6 (CH), 119.8 (CH), 116.9 (CH ), 76.6 (CH), 34.2 (CH ), 25.8

transferred to a separation funnel and partitioned between diethyl

ether and 1 M aq. HCl. The aqueous layer was extracted with diethyl

ether, and the combined organic layers were washed with sat. aq.

NaHCO and dried over MgSO .

(CH ), 17.9 (CH ), 12.5 (CH ); HRMS (EI-TOF) m/z: [M] Calcd

3 3 3

for C H O 166.1358; Found 166.1353; EI-MS (70 eV): m/z (%) =

166 (2, [M] ), 148 (7), 133 (4), 105 (9), 97 (100), 79 (19), 77 (11),

70 (16), 69 (22), 55 (17), 53 (11), 43 (27), 41 (45), 39 (17); IR

−

The solvent was removed under reduced pressure, and the crude

(ATR, neat): ν∼ [cm ] = 3372 (br), 3084 (w), 2972 (m), 2918 (m),

1649 (w), 1600 (w), 1444 (m), 1379 (m), 1042 (s), 987 (s), 901 (s),

838 (w), 660 (m), 569 (m).

α,δ-bis(phenylselenyl)ketone was dissolved in DCM (3 mL). At −60

C, mCPBA (70−75%, 166 mg, 0.67−0.72 mmol, 2.4−2.6 equiv.) in

DCM (2 mL) was added dropwise, and the reaction mixture was

(E)-4,8-Dimethyl-1,3,7-nonatrien-5-yl Acetate (rac-6). Acetic

anhydride (0.05 mL, 56 mg, 0.55 mmol, 2 equiv.) was added to a

solution of homoterpene alcohol 18 (45 mg, 0.28 mmol, 1 equiv.) and

triethylamine (0.15 mL, 111 mg, 1.1 mmol, 4 equiv.) in DCM (1

mL). Then, DMAP (7 mg, 0.06 mmol, 0.2 equiv.) was added. After 30

min, the reaction mixture was diluted with diethyl ether, washed

stirred at −60 °C for 30 min. N,N-Diisopropylethylamine (0.29 mL,

20 mg, 1.7 mmol, 6 equiv.) was added, and the mixture was diluted

with warm DCM (40 mL) and brieﬂy heated to reﬂux. Then, the

solution was cooled to room temperature, successively washed with 1

M aq. HCl and sat. aq. NaHCO , and dried over MgSO . The solvent

was removed under reduced pressure, and the residue was puriﬁed by

column chromatography on silica (pentane/diethyl ether 10:1) to

yield (S)-dehydrojasmone ((S)-2, 39 mg, 0.24 mmol, 85%) as a

yellowish liquid.

successively with 1 M aq. HCl, sat. aq. NaHCO , and dried over

MgSO . After removal of the solvent under reduced pressure,

homoterpene acetate rac-6 (51 mg, 0.25 mmol, 89%) was obtained

as a yellowish liquid.

R (pentane/diethyl ether 10:1) = 0.39; H NMR (400 MHz,

[

α] = −16.5 (c 0.97, DCM); ee = 68% (GC); the remaining

spectroscopic data were identical to those reported for rac-

CDCl ): δ [ppm] = 6.55 (ddd, J = 16.8 Hz, 10.9 Hz, 10.2 Hz, 1H),

dehydrojasmone (rac-2).

6.05 (dm, J = 10.9 Hz, 1H), 5.22 (dd, J = 16.8 Hz, 2.0 Hz, 1H), 5.16−

5.11 (m, 2H), 5.01 (tm, J = 7.2 Hz, 1H), 2.44−2.35 (m, 1H), 2.33−

2.25 (m, 1H), 2.04 (s, 3H), 1.76 (d, J = 1.3 Hz, 3H), 1.68 (d, J = 1.0

(

E)-2-Methyl-2,4-pentadienal (16). A modiﬁed procedure by

Spangler et al. was used. At 0 °C, a solution of vinylmagnesium

bromide (1 M in THF, 63 mL, 63 mmol, 1.3 equiv.) was added to

abs. diethyl ether (100 mL), forming a turbid mixture. 3-

Ethoxymethacrolein (5.8 mL, 5.6 g, 49 mmol) was added dropwise,

and the clear yellow solution was stirred for 30 min at room

temperature. Then the solution was poured into a mixture of crushed

Hz, 3H), 1.61 (br s, 3H); C{ H} NMR (100 MHz, CDCl ): δ

[ppm] = 170.2 (C ), 135.8 (C ), 134.4 (C ), 132.3 (CH), 127.7

(CH), 118.9 (CH), 117.7 (CH ), 78.5 (CH), 31.7 (CH ), 25.7

(CH ), 21.2 (CH ), 17.9 (CH ), 12.7 (CH ); HRMS (CI-Orbitrap)

m/z: [M + H] Calcd for C H O 209.1542; Found 209.1536; EI-

MS (70 eV): m/z (%) = 208 (<1, [M] ), 166 (3), 148 (4), 139 (21),

97 (100), 91 (6), 79 (16), 69 (12), 43 (37), 41 (18); GC: I = 1381

(HP-5MS); IR (GC-IR): ν∼ [cm ] = 3085 (w), 2975 (m), 2920

(m), 1734 (s), 1447 (m), 1368 (m), 1239 (s), 1020 (m), 903 (m).

(E)-4,8-Dimethyl-1,3,7-nonatrien-5-one (19). Homoterpene

alcohol 18 (100 mg, 0.60 mmol, 1 equiv.) in DMSO (1 mL) was

added to a solution of IBX (252 mg, 0.90 mmol, 1.5 equiv.) in DMSO

ice and sat. aq. NH Cl, 3 M aq. HCl (7 mL) was added, and the

mixture was stirred vigorously for 5 min. The layers were separated,

and the aqueous layer was extracted two times with diethyl ether. The

combined organic layers were washed with water and dried over

−

MgSO . The solvent was removed under reduced pressure, and the

residue was puriﬁed by short-path distillation (32 mbar, 100−125 °C

oven temp.) to yield dienal 16 (2.72 g, 28.3 mmol, 58%) as a colorless

252

J. Org. Chem. 2021, 86, 5245−5254

The Journal of Organic Chemistry

Complete contact information is available at:

Article

(

3 mL). After stirring for 1.5 h at room temperature, the reaction

Florian Etl − Department of Botany and Biodiversity Research,

University of Vienna, 1030 Vienna, Austria

mixture was poured into an aq. pH 7 buﬀer solution (KH PO /

Na HPO ). The turbid mixture was extracted three times with

pentane/diethyl ether 2:1. The combined organic layers were dried

over Na SO , and the solvent was removed under reduced pressure.

Artur Campos D. Maia − Department of Systematics and

Ecology, Federal University of Paraíba, 58051-900 Joao

Pessoa, Brazil

The residue was puriﬁed by column chromatography on silica

pentane/diethyl ether 20:1) to yield homoterpene ketone 19 (52.6

Stefan Dötterl − Department of Biosciences, Paris-Lodron

University of Salzburg, 5020 Salzburg, Austria

(

mg, 0.32 mmol, 53%) as a colorless liquid.

^Rf ⁽^p^eⁿ^t^aⁿ^e^/^dⁱ^e^t^h^y^l^e^t^h^e^r⁵^:¹⁾⁼⁰^.⁵⁹^;¹H NMR (300 MHz,

https://pubs.acs.org/10.1021/acs.joc.1c00145

CDCl ): δ [ppm] = 7.03 (d, J = 10.9 Hz, 1H), 6.75 (dt, J = 16.7 Hz,

0.5 Hz, 1H), 5.61 (d, J = 16.7 Hz, 1H), 5.50 (d, J = 10.0 Hz, 1H),

.37−5.29 (m, 1H), 3.42 (d, J = 6.9 Hz, 2H), 1.91 (s, 3H), 1.75 (s,

Author Contributions

H), 1.67 (s, 3H); C{ H} NMR (75 MHz, CDCl ): δ [ppm] =

The manuscript was written through contributions of all

authors, i.e., the chemistry part by P.S. and S.S., the bioassay

part by A.C.D.M., F.E., and S.D. The syntheses were

performed by P.S., and the behavioral assays were performed

by F.E.. All authors commented on previous versions of the

manuscript. The concept of the study was developed by all

authors, which also gave approval to the ﬁnal version of the

manuscript.

00.4 (C ), 138.4 (CH), 136.5 (C ), 134.8 (C ), 132.8 (CH), 124.5

(CH ), 117.0 (CH), 37.4 (CH ), 25.6 (CH ), 18.1 (CH ), 11.8

2 2 3 3

(

CH ); HRMS (EI-TOF) m/z: [M] Calcd for C H O 164.1201;

11 16

Found 164.1194; EI-MS (70 eV): m/z (%) = 164 (4, [M] ), 96 (8),

5 (100), 67 (61), 65 (15), 53 (4), 51 (3), 41 (37), 39 (17); IR

(

−1

ATR, neat): ν∼ [cm ] = 3088 (w), 2972 (w), 2922 (m), 1662 (s),

627 (w), 1586 (w), 1445 (m), 1354 (m), 1267 (m), 1238 (m), 1139

(

m), 1063 (m), 988 (s), 922 (s), 846 (m), 788 (m), 653 (m), 606

w).

Notes

(

S,E)-4,8-Dimethyl-1,3,7-nonatrien-5-yl Acetate ((S)-6).

(

−)-Diisopinocampheylchloroborane (81 mg, 0.25 mmol, 1.5

The authors declare no competing ﬁnancial interest.

equiv.) was rinsed with abs. diethyl ether (1 mL) into a solution of

E)-4,8-dimethyl-1,3,7-nonatrien-5-one (27.5 mg, 0.17 mmol, 1

(

ACKNOWLEDGMENTS

We thank the staﬀ of the Tropical Field Station La Gamba for

logistic support.

■

equiv.) in 0.4 mL diethyl ether. After stirring for 6 h at room

temperature, the reaction mixture was cooled to 0 °C, and

acetaldehyde (redistilled, 21 μL, 0.37 mmol, 2.2 equiv.) was

added. The solution was allowed to warm to room temperature

overnight. Then, the solution was diluted with diethyl ether, 1 M aq.

NaOH was added, and the mixture was stirred vigorously for 10 min.

The layers were separated, and the aqueous layer was extracted with

diethyl ether. The combined organic layers were dried over MgSO₄,

and the solvent was removed under reduced pressure. After column

chromatography on silica (pentane/diethyl ether 5:1), homoterpene

alcohol (S)-18 was obtained in low yield and purity. The

enantiomeric excess was determined to be >90% by GC on a chiral

stationary phase.

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■

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ASSOCIATED CONTENT

sı Supporting Information

■

The Supporting Information is available free of charge at

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TIC chromatograms, and ﬁeld bioassays (PDF)

AUTHOR INFORMATION

■

Corresponding Author

Stefan Schulz − Institute of Organic Chemistry, Technische

Universität Braunschweig, 38106 Braunschweig, Germany;

orcid.org/0000-0002-4810-324X; Email: stefan.schulz@

tu-bs.de

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