Exaltone (=Cyclopentadecanone) from Isomuscone (=Cyclohexadecanone), a one-C-atom ring-contraction methodology via a stereospecific favorskii rearrangement: Regioselective application to (-)-(R)-muscone

Article abstract of DOI:10.1002/hlca.201100398

Treatment of cyclohexadecanone (1g; with I₂ (2.2 mol-euqiv.) and KOH in MeOH) furnished the unsaturated (Z)-ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3-chloroperbenzoic acid (m-CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone (=cyclopentadecanone; 1f) with NaOH in MeOH/H₂O and then HCl at 65°. This methodology was similarly extended to higher (C₁₇) and lower (C₁₅ to C₁₁) cyclic ketone analogues, as well as regioselectively to (-)-(R)-muscone (5c) and homomuscone (5f) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1-oxaspiro[2,n]alkanes and -alkenes 4 and 8, resulting from a Coreyi-Chaykovsky oxiranylation, are also presented. Copyright

Full text of DOI:10.1002/hlca.201100398

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Helvetica Chimica Acta – Vol. 95 (2012)
Exaltoneꢀ (¼Cyclopentadecanone) from Isomusconeꢀ
(¼Cyclohexadecanone), a One-C-Atom Ring-Contraction Methodology via a
Stereospecific Favorskii Rearrangement: Regioselective Application to
(ꢀ)-(R)-Muscone
by Christian Chapuis*, Fabrice Robvieux, Carole Cantatore, Christine Saint-Le´ger, and
Laurent Maggi
Firmenich SA, Corporate R&D Division, P.O. Box 239, CH-1211 Geneva 8
(phone: þ 41-22-7803610; fax: þ 41-22-7803334; e-mail: christian.chapuis@firmenich.com)
1
Lately dedicated to Prof. J. Jurczak on the occasion of his 70th birthday )
Treatment of cyclohexadecanone (1g; with I2 (2.2 mol-euqiv.) and KOH in MeOH) furnished the
unsaturated (Z)-ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further
treatment with 3-chloroperbenzoic acid (m-CPBA) afforded the unreported epoxy ester 3g (88% yield),
which was cleaved in 33% yield to Exaltoneꢀ (¼cyclopentadecanone; 1f) with NaOH in MeOH/H2O and
then HCl at 658. This methodology was similarly extended to higher (C17) and lower (C15 to C11) cyclic
ketone analogues, as well as regioselectively to (ꢀ)-(R)-muscone (5c) and homomuscone (5f)
(Scheme 2). Olfactive properties of the corresponding macrocyclic 1-oxaspiro[2,n]alkanes and -alkenes
4 and 8, resulting from a CoreyꢀChaykovsky oxiranylation, are also presented.
Introduction. – Among the historical nitro and polycyclic aromatic musks2) and a
new class of musk-like aliphatic esters, more recently explored [2] by modifying BASFꢀs
Cyclomuskꢀ3) [3], macrocyclic musks occupy a preponderant place4). The synthesis of
these macrocyclic ketones or lactones relies principally on two distinc-
tive methodologies, namely ring expansion or contraction, and macrocyclization.
The latter are exemplified by macrolactonization [5]5) or various reactions leading
to CꢀC bond formation, such as intramolecular variants of the Dieckmann condensa-
tion [9], alkylation [10], either McMurry [11], Wittig [12], or metathesis reactions
[13][9e], ketene dimerization [14], as well as RambergꢀBꢁcklund rearrangement
1
)
In early 2011. For patent reasons, this manuscript (2008) was kept for several years prior to
submission.
For a recent review, see [1].
3-(5-Isopropenyl-2-methyl-cyclopent-1-en-1-yl)-2,2-dimethylpropyl propanoate.
For a specific review, see [4].
2
3
4
5
)
)
)
)
For supported conditions, see, e.g., [6]; for enzymatic lactonization, see, e.g., [7]; for a recent review,
see [8].
ꢁ 2012 Verlag Helvetica Chimica Acta AG, Zꢂrich

Helvetica Chimica Acta – Vol. 95 (2012)
429
[15]6) or radical cyclizations [21]. Besides the heterogeneous acyloin condensation
[22], the Story synthesis [23], Carothersꢃ depolymerization reaction [24], or Collaudꢃs
macrolactonization [25], almost all these approaches face the same entropic drawback,
which necessitates high-dilution conditions to favor intra- vs. intermolecular reactions.
This aspect massively reduces their industrial interest due to poor productivity and
large quantities of solvent to recycle7). For this reason, the first strategy is by far the
most economical, and in contrast to BaeyerꢀVilliger oxidation [29] or ring expansion
[30], the macrocycle contraction methodology has been much less studied [31]8). We
thus present here our results, combining and extending methodologies previously
reported for aliphatic linear ketones [34a] and for C12 or C11 medium-sized-ring ketones
[35].
Results and Discussion. – First of all, starting from helvetone (¼cyclododecanone;
1c), we repeated the initial work of Schank and Eistert [35b][35c] by performing,
according to Wohllebe and Garbisch [35d – f], the Favorskii rearrangement in MeOH
rather than in H2O, and by using the one-pot I2 procedure of Zacuto and Cai [34a],
instead of isolating the Br2 adduct (Scheme 1). We thus directly obtained in 61% yield
the known a,b-unsaturated methyl ester 2c [36] possessing the (Z)-configuration9) as
shown by 1H-NMR analyses of the olefinic H-atom10). This result is noteworthy, since
6
)
Treatment of the known 1,3-dioxolane-2,2-dioctanol (Ia) [16] with CBr4 and Ph3P (see Scheme 3 in
the Exper. Part) afforded the unreported corresponding dibromide Ib (yield 65%), which was then
cyclized (Na2S, EtOH [17]) to the new cyclic thioether IIa (61%), prior to oxidation (H2O2,
NaHCO3, MnSO4, MeCN [18]) to sulfone IIb (95%). When treated under RambergꢀBꢁcklund
conditions (KOH, Al2O3, EtOH, CCl4 or CBr2F2, 608 [19]), this sulfone IIb afforded, in 70 – 82%
yield, a 3:7 (E)/(Z) mixture of unsaturated macrocyclic acetal III, a known precursor in the
synthesis of civetone (IVa) by Stoll and co-workers [20]. Similarly, hydrolysis of acetals IIa or IIb
(HCl, THF/H2O) furnished the corresponding macroheterocyclic ketones Va or Vb (58 – 60%)
respectively, both devoid of olfactive character. Acylation of Ia (AcCl, DMAP, Et3N, CH2Cl2)
afforded diacetate Ic (60%). Quantitative hydrolysis of acetals I to ketones VI (HCl, THF/H2O)
allowed to access 9-hydroxynonanoic acid (VIIb), after BayerꢀVilliger oxidation of VIc 3-
chloroperbenzoic acid (m-CPBA), CHCl3, 508; yield 85%) and saponification (NaOH, EtOH, 788;
yield 89%).
7
8
9
)
)
)
In this context, the vapor phase is technically by far the most economical, with, e.g., intramolecular
acid salt variants of the Piria reaction [26] or Dieckmann condensation [27]. For an example of high-
dilution loop techniques, see [28].
This is understandable, as the starting material is already a macrocycle, and only the ones with an
even number of C-atoms are efficiently accessible by dimeric metathesis of a medium-sized
unsaturated ring [32] or by buta-1,3-diene Wilke catalytic trimerization [33].
For the stereospecific Favorskii rearrangement of diastereoisomeric cyclic a,a’-dibromo ketones,
see [35e]. Merck chemists reported the alkoxide-promoted isomerization of a,a-diiodo ketones to
their a,a’-isomers, and their observed (Z)-configuration was rationalized on the basis of an
alkoxide-promoted disrotatory electrocyclic cyclopropanone opening, with concerted expulsion of
iodide [34a]. For a recent theoretical study of this mechanism, see [34b]. Ester 2c was also obtained
as a 5:1 (Z)/(E) isomer mixture in 91% yield from the a,a’-dibromo ketone, according to [35f].
The d(H) of the olefinic H-atom of the (E)-isomers are at lower field (by ca. 0.6 ppm) than those of
the (Z)-isomers. This is in agreement with empirical observations [36][37a]. This distinction may
also be made on the basis of a comparison of the allylic methylene H-atoms [37b]. We
unambiguously attributed the (Z)-configuration on the basis of NOESY experiments.
10
)

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 1
i) I2 (2.2 mol-equiv.), KOH, MeOH, 08. ii) m-CPBA, CH2Cl2. iii) NaOH, MeOH/H2O, then HCl, 658. iv)
Me3S(O)I, tBuOH, tBuOK, 508.
a) GC Yield.
Merck chemists obtained a-hydroxy ketals when they applied their I2/KOH/MeOH
conditions to small-ring ketones [34a]. Previous degradations of 2c to 1b made use of
the Curtius rearrangement [35], which is industrially not acceptable due to both the
high toxicity and instability of hydrazoic acid. We thus preferred to apply the known 3-
chloroperbenzoic acid (m-CPBA) oxidation to afford epoxy ester 3c [38] in 70% yield.
Saponification with NaOH in refluxing MeOH/H2O, followed by acidification with HCl
[39], afforded undecanone 1b in 32% yield11). Encouraged by these preliminary
results, we applied our sequence to cyclotridecanone (1d). The corresponding
unsaturated methyl ester (Z)-2d12) was isolated in 56% yield, and its glycidic acid
ester or ester 3d in 65% yield. Subsequent de(methoxycarbonyl)ation furnished
cyclododecanone 1c in 34% yield. As the efficiency of the Favorskii rearrangement may
strongly depend on the ring size [35i], we were very interested to pursue our approach
with larger macrocyclic ketones. Thus, cyclotetradecanone (1e) afforded methyl ester
2e in only 2%. This illustrates the cyclic strain of the cyclotetradecane system, reluctant
to form the transient intermediate [42]13). When Exaltoneꢀ (1f) was submitted to the
original Favorskii conditions, we isolated 2f in 83% yield, and epoxy ester 3f (53%
11
)
For an alternative LiAlH4, then NaIO4 sequence, see [38a]. For an unexpected regioselectivity in
the cleavage of a glycidic acid ester (¼oxiranecarboxylate), see [39b]. Thus, reduction of 3d,
resulting in 1-(hydroxymethyl)cyclododecan-1-ol [40], potentially gives access to the olfactory
interesting 1-oxaspiro[2.11]tetradecane 4c [30v], possessing cashmeran, musky, camphoraceous,
woody, earthy, and mouldy notes [40b]. Alternatively, the other unreported oxaspiro compounds 4
were obtained by a direct CoreyꢀChaykovsky oxiranylation of ketones 1 [30v].
For (E)-2d, with an olefinic H-atom at d(H) 6.72, see [41].
Preliminary calculations at the B3LYP/6-31G** level [43] suggest a much higher transition state for
the formation of the transient trisubstituted cyclopropanone derived from ketone 1e, as compared
to 1b, 1c, 1d, 1f, 1g, and 1h. This drawback precludes the preparative synthesis of either 3e (47% GC
yield) or 1d (44% GC yield).
12
13
)
)

Helvetica Chimica Acta – Vol. 95 (2012)
431
yield) afforded the cyclotetradecanone (1e) in 52% yield14). Potentially of highest
interest, treatment of Isomusconeꢀ (1g) furnished the unsaturated ester 2g15) in 83%
yield. Treatment with m-CPBA led to the unreported epoxy ester 3g (88%), which
afforded, in 33% yield, Exaltoneꢀ (1f). Finally, cycloheptadecanone (1h) gave 2h in
50% yield. This latter was epoxidized (53%) to afford Isomusconeꢀ (1g) in 52% yield
after saponification and acidic decarboxylation.
We then extended this methodology to nonsymmetric macrocyclic ketones16) and
were pleased to observe, with (ꢀ)-(R)-muscone (5c) (Scheme 2), a complete
regioselectivity in favor of 6c (56%)17
)
18). Similarly, starting from the musky (ꢀ)-
(R)-homomuscone (5f) [45], we only isolated 6f (48%)19)20)21).
Conclusion. – For the preparation of either odd- or even-numbered macrocyclic
ketones of olfactive interest, we combined a one-pot Favorskii process, reported to
produce (Z)-prop-2-enoates from linear ketones, with a one-C-atom ring-contraction
methodology, earlier applied to the preparation of medium-sized-ring ketones22).
Most of the intermediate (Z)-unsaturated or epoxy methyl esters are new. This
approach uses very simple scalable conditions and avoids high-dilution techniques, and
may be regioselectively extended to b-substituted analogues. With either C14, or a-
14
)
)
)
For alternative industrial conditions (maleic anhydride, H2O2), see [39b].
15
16
Ester 2g of undefined configuration was independently obtained by an earlier method [44].
When 2-methylcyclopentadecanone [29b] was treated under the present Favorskii conditions, we
isolated mainly 2-methoxy-2-methylcyclopentadecanone. IR: 2925, 2853, 1713, 1459, 1400, 1370,
1
1194, 1167, 1120, 1068, 903, 715. H-NMR: 3.22 (s, 3 H); 2.94 – 2.87 (m, 1 H); 2.31 – 2.23 (m, 1 H);
1.74 – 1.61 (m, 2 H); 1.39 – 1.29 (m, 14 H); 1.29 – 1.19 (m, 8 H); 1.24 (s, 3 H). 13C-NMR: 215.2 (s); 85.0
(s); 51.9 (q); 37.8 (t); 36.1 (t); 27.6 (2t); 27.2 (t); 26.8 (t); 26.7 (t); 26.4 (t); 26.3 (t); 26.1 (t); 25.9 (t); 22.6
.
(t); 22.1 (t); 18.9 (q). MS: 268 (5, Mþ ), 240 (12), 141 (7), 85 (100), 72 (60), 55 (17).
17
18
)
)
The intermediate cyclopropanone with the halide at the C-atom bearing the unsubstituted side
chain is the more easily formed (see Footnote 9).
Further epoxidation (m-CPBA, CH2Cl2; ! 7c (82%)) followed by de(methoxycarbonyl)ation
(NaOH, MeOH/H2O, then HCl, 658), furnished the musky (R)-normuscone (5a; 8%), besides the
main (þ)-(2R)-2-methyl cyclotetradecanone (55%, [a]2D0 ¼ þ7.5 (c ¼ 1.6, MeOH)). 13C-NMR: 215.5
(s); 45.6 (d); 38.4 (t); 33.0 (t); 26.3 (2t); 26.1 (t); 25.5 (t); 25.3 (t); 24.9 (t); 24.8 (t); 24.7 (t); 24.5 (t); 21.7
(t); 17.2 (q)), both already described as racemates [29b][30f][30v] (see Footnote 11).
Further epoxidation (m-CPBA, CH2Cl2; ! 7f (79%)) followed by de(methoxycarbonyl)ation
(NaOH, MeOH/H2O, then HCl, 658), furnished (ꢀ)-(R)-muscone (5c; 12%), besides the main (þ)-
(2R)-2-methylcyclopentadecanone (66%) [46] (see Footnote 11).
19
)
20
21
)
)
To determine their olfactive properties, we also prepared, by CoreyꢀChaykovsky reaction, the
unreported oxaspiro compounds 8a – 8j.
Finally, even the unsaturated (þ)-(R)-muscenone (5d) was prone to regioselective Favorskii
reaction and afforded 6d, albeit in a poor 3% yield. Addition of I2 across the C¼C bond was not
exploited to regenerate a cycloalkynyl functionality. Similarly, a potential access to (3R,5Z)-
t
configured 5b (LiAlH4, THF; [VO(acac)2], BuOOH, toluene; LiAlH4, THF; NaIO4, THF/H2O)
was not attempted.
22
)
In this series, the methyl ester 2b is the smallest reported medium-sized ring with a (Z)-
configuration [35e]. Epoxidation with m-CPBA afforded directly 3b (63%), and de(methoxycarbo-
nyl)ation gave cyclodecanone 1a in 47% yield. Further ring contraction was unsuccessfully
attempted (for the (E)-isomer of cyclonon-1-ene-1-carboxylic acid methyl ester, with the signal of
an olefinic H-atom at d(H) 6.85, see [36]).

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Helvetica Chimica Acta – Vol. 95 (2012)
substituted, or unsaturated macrocyclic ketones, the isolated yields become deceiv-
ing23).
We are indebted to Dr. J.-Y. De Saint Laumer for B3LYP/6-31G** preliminary calculations.
Experimental Part
General. See [52]. Starting cyclic ketones24) were purchased from Aldrich (1b, 1c, 1d, and 1f) and
PfaltzꢀBauer (1h). Ketones 1e and 1g were obtained from 1f and 1h, resp., by the methodology described
herein. The other unsaturated or methylated ketones 5b (Givaudan SA), 5c ([a]2D0 ¼ ꢀ7.4 (c ¼ 2.8,
MeOH); Firmenich SA), 5d ([a]2D0 ¼ þ6.3 (c ¼ 4.0 MeOH); Firmenich SA), 5e (Firmenich SA), 5f
([a]2D0 ¼ ꢀ6.9 (c ¼ 1.0 MeOH); [45]), 5g (Symrise GmbH), 5h (Symrise GmbH), 5i (BASF GmbH), 5j
(BASF GmbH), and IVa (Firmenich SA) are industrially available.
Transformations of 1 ! 2 and 5 ! 6: General Procedure A (G.P.A). The macrocyclic ketone 1 or 5
(1.0 mol-equiv.) was added dropwise/portionwise to a soln. of I2 (2.2 mol-equiv.) in MeOH (3.9 ml/
mmol) at ꢀ 58, and after 15 min, a soln. of KOH (5.0 mol-equiv.) in MeOH (3.6 ml/mmol) was added
dropwise at 08. After 1 h at 08, the mixture was concentrated, diluted with Et2O, washed with 15% aq.
NaHSO3 soln., dried (Na2SO4), and concentrated and the residue purified.
Methyl (1Z)-Cyclodec-1-ene-1-carboxylate (2b). According to G.P.A. After CC (SiO2, cyclohexane/
AcOEt 98 :2), yield 57%. IR: 2927, 2860, 1708, 1638, 1461, 1440, 1378, 1247, 1231, 1195, 1146, 1123, 1104,
1032, 897, 806, 774, 708. 1H-NMR: 6.25 (t, J ¼ 8, 1 H); 3.76 (s, 3 H); 2.54 (br. q, J ¼ 7, 2 H); 2.36 (t, J ¼ 6,
2 H); 1.64 – 1.58 (m, 2 H); 1.56 – 1.51 (m, 2 H); 1.46 – 1.40 (m, 2 H); 1.32 – 1.26 (m, 3 H); 1.25 – 1.18 (m,
3 H). 13C-NMR: 168.5 (s); 145.7 (d); 129.8 (s); 51.1 (q); 34.7 (t); 29.4(t); 27.9 (t); 26.3 (t); 24.7 (t); 24.5 (t);
24.0 (t); 23.0 (t). MS: 196 (77, Mþ), 165 (18), 153 (77), 137 (21), 135 (22), 125 (19), 95 (72), 81 (100), 79
(42), 67 (56), 55 (45), 53 (30), 41 (54).
23
)
When these conditions were applied to the commercially available heptane-3,5-dione, we isolated
the already reported 2-methyl-4-oxohexanoic acid methyl ester [47] in 48% yield (13C-NMR: 209.5
(s); 176.5 (s); 51.7 (q); 45.4 (t); 36.3 (t); 34.8 (d); 17.3 (q); 7.7 (q). MS: 158 (1, Mþ), 129(47), 127 (15),
101 (14), 59 (100), 57 (94), 41 (29), 29 (58), 27 (30)). For an analogous multi-step sequence via a Cs-
symmetric monohalide, see [48] as a single example. Similarly, treatment of cycloheptane-1,3-dione
afforded, after chromatographic purification (SiO2, cyclohexane/AcOEt 97:3 ! 60:40), a) the
commercially available 3-oxocyclohexanecarboxylic acid methyl ester (4% yield), b) hexanedioic
acid dimethyl ester (2% yield), c) the reported 3-oxocyclohex-1-ene-1-carboxylic acid methyl ester
(11% yield) [49], d) 2-iodo-3-oxocyclohex-1-ene-1-carboxylic acid methyl ester (5% yield. IR: 2951,
1
1730, 1687, 1607, 1434, 1288, 1250, 1224, 1176, 1132, 1098, 1040, 977, 910, 800, 727, 647. H-NMR:
3.90 (s, 3 H); 2.70 (t, J ¼ 6.2, 2 H); 2.67 (t, J ¼ 6.2, 2 H); 2.14 (quint., J ¼ 6.2, 2 H). 13C-NMR: 197.6 (s);
167.2 (s); 156.8 (s); 94.2 (s); 52.3 (q); 36.8 (t); 25.6 (t); 21.1 (t). MS: 280 (100, Mþ), 252 (19), 249 (11),
224 (12), 221 (7), 165 (16), 121 (8), 93 (12), 66 (48), 55 (23)), e) 2,4-diodo-3-methoxycyclohexa-1,3-
diene-1-carboxylic acid methyl ester (14% yield. IR: 2947, 2830, 1717, 1602, 1546, 1432, 1362, 1278,
1241, 1191, 1155, 1135, 1078, 999, 977, 911, 866, 808, 793, 763, 728, 627. 1H-NMR: 3.82 (s, 3 H); 3.62
(s, 3 H); 2.75 (dd, J ¼ 7, 9.8, 2 H); 2.59 (dd, J ¼ 7, 9.8, 2 H). 13C-NMR: 167.0 (s); 153.6 (s); 136.8 (s);
97.4 (s); 85.9 (s); 60.0 (q); 52.1 (q); 35.9 (t); 29.1 (t). MS: 420 (0, Mþ), 389 (10), 278 (8), 261 (19), 234
(62), 219 (27), 203 (8), 191 (18), 181 (9), 166 (100), 151 (12), 135 (35), 127 (10), 123 (17), 107 (20), 95
(18), 92 (23), 77 (41), 64 (29), 59 (32), 51 (16)), and f) the known cyclopent-2-ene-1,2-dicarboxylic
acid dimethyl ester [50] (16% yield. 13C-NMR: 173.4 (s); 165.2 (s); 139.7 (d); 138.7 (s); 52.2 (q); 51.7
(q); 51.0 (d); 31.1 (t); 26.6 (t)). We are actually extending and exploring in more detail this
particularly rare version of the Favorskii rearrangement to other substrates [51], with only 1.0 mol-
equiv. of I2.
24
)
Most of them are naturally occurring in musk rat (1d, 1f, 1g, and 1h [53]), civet cat (1e, 1f, 1g, 1h, and
IVa [54][9b]), and musk deer (tincture of Tonkin musk, 1e, and 5c [55]).

Helvetica Chimica Acta – Vol. 95 (2012)
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Scheme 2
i) I2 (2.2 mol-equiv.), KOH, MeOH, 08. ii) m-CPBA, CH2Cl2. iii) NaOH, MeOH/H2O, then HCl, 658. iv)
Me3S(O)I, tBuOH, tBuOK, 508.
Methyl (1Z)-Cycloundec-1-ene-1-carboxylate (2c). According to G.P.A. After CC (SiO2, cyclo-
hexane/AcOEt 98 :2), yield 61%. IR: 2927, 2858, 1714, 1639, 1463, 1437, 1376, 1345, 1323, 1231, 1191,
1163, 1115, 1054, 1031, 1010, 989, 939, 909, 882, 866, 838, 807, 788, 762, 736, 722. 1H-NMR: 6.10 (t, J ¼ 10,
1 H); 3.76 (s, 3 H); 2.53 (dt, J ¼ 5, 8, 2 H); 2.32 (t, J ¼ 5.5, 2 H); 1.61 – 1.51 (m, 4 H); 1.43 – 1.34 (m, 4 H);
1.34 – 1.25 (m, 4 H); 1.23 – 1.18 (m, 2 H). 13C-NMR: 169.0 (s); 143.6 (d); 131.7 (s); 51.2 (q); 35.7 (t); 29.9
(t); 27.0 (t); 26.3 (t); 25.9 (2t); 25.8 (t); 25.6 (t); 25.2 (t). MS: 210 (100, Mþ), 179 (20), 167 (18), 153 (96),
149 (22), 109 (24), 95 (69), 81 (62); 67 (48), 55 (33), 41 (42). Weak, very vaguely woody, cedar.
Methyl (1Z)-Cyclododec-1-ene-1-carboxylate (2d). According to G.P.A. After CC (SiO2, cyclo-
hexane/AcOEt 98 :2), yield 56%25). IR: 2926, 2859, 1715, 1637, 1461, 1439, 1377, 1231, 1193, 1152, 1121,
1106, 1057, 1004, 942, 918, 894, 852, 818, 730, 700. 1H-NMR: 6.11 (t, J ¼ 8, 1 H); 3.75 (s, 3 H); 2.48 (dt, J ¼
5, 8, 2 H); 2.35 (t, J ¼ 6.5, 2 H); 1.68 – 1.62 (m, 2 H); 1.54 – 1.50 (m, 2 H); 1.48 – 1.42 (m, 2 H); 1.39 – 1.23
(m, 10 H). 13C-NMR: 168.4 (s); 145.0 (d); 130.3 (s); 51.1 (q); 33.8 (t); 29.6 (t); 27.3 (t); 26.6 (t); 26.1 (t);
25.7 (t); 25.2 (t); 24.4 (t); 24.1 (t); 23.7 (t). MS: 224 (100, Mþ), 193 (35), 167 (31), 153 (50), 109 (52), 95
(78), 81 (88), 67 (62), 55 (60), 41 (62).
25
)
If the reaction time and/or the temperature exceeded the prescription, methyl (1Z)-2-iodo-
cyclododec-1-ene-1-carboxylate was also isolated as a by-product. H-NMR: 3.80 (s, 3 H); 2.58 (t,
1
J ¼ 7, 2 H); 2.45 (t, J ¼ 6, 2 H); 1.68 (quint., J ¼ 6, 2 H); 1.49 (quint., J ¼ 7, 2 H); 1.41 – 1.30 (m, 12 H).
13C-NMR: 170.3 (s); 142.3 (s); 106.0 (s); 52.0 (q); 36.7 (t); 28.7 (t); 27.2 (t); 25.6 (t); 24.3 (t); 24.2 (2t);
24.1 (t); 22.9 (t); 22.3 (t). MS: 350 (40, Mþ), 319 (10), 223 (23), 163 (63), 121 (28), 107 (21), 95 (55), 81
(100), 67 (47).

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Helvetica Chimica Acta – Vol. 95 (2012)
Methyl (1Z)-Cyclotridec-1-ene-1-carboxylate (2e). According to G.P.A. After CC (SiO2, cyclo-
hexane/AcOEt 98 :2), yield 2%26). IR (GC): 2925, 2858, 1715, 1638, 1460, 1440, 1375, 1233, 1195, 1153,
1
1124, 1106, 1057. H-NMR: 5.89 (t, J ¼ 7.7, 1 H); 3.74 (s, 3 H); 2.44 (dt, J ¼ 5, 6.3, 2 H); 2.35 (t, J ¼ 7.5,
2 H); 1.68 – 1.23 (m, 18 H). 13C-NMR (deduced from impurities): 168.7 (s); 141.3 (d); 131.3 (s); 51.1 (q);
33.3 (t); 28.9 (t); 27.9 (t); 27.0 (t); 26.6 (t); 26.4 (t); 25.6 (t); 25.4 (t); 24.7 (t); 24.4 (t); 23.7 (t). MS: 238 (57,
Mþ), 207 (5); 178 (9), 164 (15), 153 (21), 149 (17), 141 (16), 135 (24), 127 (20), 125 (27), 123 (22), 121
(24); 113 (35), 111 (32), 109 (43), 107 (23), 101 (23), 97 (50), 95 (79), 87 (37), 81 (100), 69 (40), 67 (85),
55 (89), 41 (96).
Methyl (1Z)-Cyclotetradec-1-ene-1-carboxylate (2f). According to G.P.A. After distillation, yield
83%27). B.p. 1208/0.2 mbar. IR: 2925, 2856, 1715, 1640, 1457, 1440, 1373, 1349, 1321, 1234, 1196, 1169,
1154, 1138, 1125, 1105, 1057, 1025, 997, 948, 904, 805, 768, 748, 716. 1H-NMR: 5.82 (t, J ¼ 7.5, 1 H); 3.73 (s,
3 H); 2.47 (dt, J ¼ 5, 7, 2 H); 2.31 (t, J ¼ 7, 2 H); 1.49 – 1.42 (m, 2 H); 1.40 – 1.22 (m, 18 H). 13C-NMR:
168.8 (s); 143.2 (d); 131.7 (s); 51.1 (q); 33.6 (t); 28.5 (t); 27.7 (t); 27.0 (t); 26.8 (t); 26.0 (t); 25.6 (t); 25.4 (t);
24.8 (t); 24.5 (t); 23.8 (t); 23.7 (t). MS: 252 (88, Mþ), 221 (21), 113 (25), 109 (38), 95 (69), 81 (85), 67
(78), 55 (91), 41 (100).
Methyl (1Z)-Cyclopentadec-1-ene-1-carboxylate (2g). According to G.P.A. After CC (SiO2,
cyclohexane/Et2O 97:3 to 1:1), yield 83%. B.p. 1808/0.1 mbar. IR: 2924, 2855, 1716, 1640, 1458, 1437,
1375, 1323, 1195, 1154, 1028, 1000, 903, 809, 718. 1H-NMR: 5.86 (t, J ¼ 6, 1 H); 3.73 (s, 3 H); 2.47 (dt, J ¼ 5,
7, 2 H); 2.32 (t, J ¼ 6, 2 H); 1.52 – 1.43 (m, 4 H); 1.38 – 1.22 (m, 18 H). 13C-NMR: 168.7 (s); 143.6 (d);
131.7 (s); 51.2 (q); 33.9 (t); 28.9 (t); 28.6 (t); 27.5 (t); 27.3 (t); 27.2 (t); 27.1 (2t); 26.9 (t); 26.8 (2t); 26.6 (t);
25.6 (t). MS: 266 (100, Mþ), 235 (18), 109 (18), 95 (32), 81 (38), 67 (29), 55 (34), 41 (30).
Methyl (1Z)-Cyclohexadec-1-ene-1-carboxylate (2h). According to G.P.A. After CC (SiO2, cyclo-
hexane/Et2O 97:3), yield 50%. B.p. 2008/0.1 mbar. IR: 2923, 2854, 1717, 1640, 1459, 1435, 1376, 1325,
1192, 1154, 1029, 1003, 901, 811, 720. 1H-NMR: 5.85 (t, J ¼ 6, 1 H); 3.73 (s, 3 H); 2.46 (dt, J ¼ 5, 7, 2 H);
2.30 (t, J ¼ 6, 2 H); 1.48 – 1.41 (m, 4 H); 1.35 – 1.24 (m, 20 H). 13C-NMR: 168.7 (s); 143.0 (d); 131.5 (s);
51.1 (q); 34.3 (t); 29.0 (t); 28.9 (t); 27.9 (t); 27.7 (t); 27.6 (t); 27.4 (t); 27.2 (2t); 27.1 (t); 26.7 (t); 25.9 (t); 25.7
(t); 25.4 (t). MS: 280 (100, Mþ); 249 (12); 109 (18); 95 (30); 81 (32); 67 (24); 55 (27); 41 (25).
Epoxidation to 3 or 8: General Procedure B (G.P.B). A mixture of unsaturated ester 2 or 6 (1.0 mol-
equiv.) and m-CPBA (1.0 mol-equiv.) in CH2Cl2 (2.7 ml/mmol) was stirred at 208 for 24 h. The mixture
was diluted, extracted with 15% aq. NaHSO3 soln., washed with sat. aq. NaHCO3 soln. and brine, dried
(Na2SO4), and concentrated and the residue purified.
Methyl cis-11-Oxabicyclo[8.1.0]undecane-1-carboxylate (3b). According to G.P.B. After CC (SiO2,
cyclohexane/AcOEt 98 :2), yield 63%. IR: 2935, 2871, 1749, 1448, 1278, 1193, 1129, 1006. 1H-NMR: 3.80
(s, 3 H); 3.43 (dd, J ¼ 4, 10, 1 H); 2.56 – 2.50 (m, 1 H); 2.13 – 2.07 (m, 1 H); 1.83 – 1.76 (m, 1 H); 1.73 – 1.66
(m, 2 H); 1.62 – 1.44 (m, 9 H); 1.36 – 1.25 (m, 2 H). 13C-NMR: 173.8 (s); 64.6 (d); 64.6 (s); 52.3 (q); 34.1
(t); 27.5 (t); 26.8 (t); 26.0 (t); 24.4 (2t); 23.4 (t); 24.3 (t). MS: 212 (0, Mþ), 153 (12), 135 (100), 109 (18), 95
(23), 93 (27), 81 (35), 71 (39), 69 (45), 67 (52), 55 (70), 41 (47).
Methyl cis-12-Oxabicyclo[9.1.0]dodecane-1-carboxylate (3c). According to G.P.B. After CC (SiO2,
cyclohexane/AcOEt 98 :2), yield 70%. IR: 2937, 2870, 1745, 1447, 1352, 1268, 1199, 1164, 1134, 999, 854,
26
)
The main by-product was methyl (1Z)-2-iodocyclotridec-1-ene-1-carboxylate (64%): IR: 2937, 2867,
1746, 1437, 1267, 1155, 1121, 1027. 1H-NMR: 3.79 (s, 3 H); 2.60 (t, J ¼ 7.5, 2 H); 2.37 (t, J ¼ 7.5, 2 H);
1.70 – 1.64 (m, 2 H); 1.57 – 1.49 (m, 2 H); 1.43 – 1.32 (m, 12 H); 1.30 – 1.23 (m, 2 H). 13C-NMR: 170.1
(s); 144.4 (s); 106.1 (s); 52.1 (q); 39.4 (t); 29.9 (t); 26.5 (t); 26.1 (t); 26.0 (t); 25.9 (t); 25.8 (2t); 25.6 (2t);
.
25.5 (t). MS: 364 (18, Mþ ), 333 (6), 237 (28), 177 (22), 135 (18), 121 (23), 109 (21), 95 (100), 81 (67),
67 (42), 55 (35), 41 (35).
27
)
Methyl (1Z)-2-iodocyclotetradec-1-ene-1-carboxylate was also isolated in 14% yield. IR: 2926,
2856, 1727, 1627, 1460, 1443, 1431, 1350, 1270, 1248, 1206, 1190, 1168, 1145, 1124, 1103, 1062, 1043,
1
1031, 831, 806, 775, 750, 717. H-NMR: 3.79 (s, 3 H); 2.56 (t, J ¼ 9, 2 H); 2.35 (t, J ¼ 7, 2 H); 1.61
(quint., J ¼ 7.5, 2 H); 1.46 – 1.40 (m, 2 H); 1.38 – 1.30 (m, 16 H). 13C-NMR: 170.3 (s); 141.4 (s); 105.2
(s); 52.1 (q); 39.8 (t); 30.9 (t); 27.2 (t); 26.5 (t); 26.3 (t); 26.2 (t); 25.6 (t); 25.2 (t); 25.1 (t); 24.9 (t); 23.9
.
(t); 23.8 (t). MS: 378 (33, Mþ ), 347 (11), 251 (52), 191 (38), 135 (25), 109 (82), 95 (100), 81 (68), 67
(67), 55 (58), 41 (70).

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771. 1H-NMR: 3.79 (s, 3 H); 3.38 (dd, J ¼ 2, 9, 1 H); 2.50 – 2.43 (m, 1 H); 2.09 – 2.01 (m, 1 H); 1.83 – 1.73
(m, 1 H); 1.69 – 1.58 (m, 2 H); 1.55 – 1.23 (m, 13 H). 13C-NMR: 170.8 (s); 63.6 (d); 62.6 (s); 52.2 (q); 34.4
(t); 28.9 (t); 26.8 (t); 26.5 (t); 26.3 (t); 25.8 (t); 23.7 (t); 23.0 (t); 22.0 (t). MS: 226 (1, Mþ), 210 (12), 167
(13), 149 (100), 95 (43), 81 (79), 71 (54), 67 (69), 55 (83), 41 (53).
Methyl cis-13-Oxabicyclo[10.1.0]tridecane-1-carboxylate (3d). According to G.P.B. After CC (SiO2,
cyclohexane/AcOEt 98 :2), yield 65%. IR: 2926, 2860, 2842, 1740, 1471, 1433, 1326, 1308, 1289, 1257,
1243, 1217, 1197, 1135, 1102, 1059, 1034, 1004, 978, 962, 918, 877, 816, 753, 720, 703. 1H-NMR: 3.77 (s, 3 H);
3.22 (dd, J ¼ 3, 10, 1 H); 2.47 – 2.40 (m, 1 H); 2.11 – 2.05 (m, 1 H): 1.90 – 1.86 (m, 1 H); 1.61 – 1.58 (m,
1 H); 1.53 – 1.24 (m, 16 H). 13C-NMR: 170.6 (s); 64.0 (d); 62.0 (s); 52.2 (q); 33.1 (t); 28.0 (t); 27.0 (t); 26.9
(t); 25.1 (t); 25.0 (t); 24.6 (t); 24.0 (t); 23.2 (t); 23.1 (t). MS: 240 (1, Mþ), 181 (15), 163 (42), 121 (23), 109
(27), 95 (83), 81 (92), 71 (77), 67 (62), 55 (100), 41 (67).
Methyl cis-14-Oxabicyclo[11.1.0]tetradecane-1-carboxylate (3e). According to G.P.B. After CC
(SiO2, cyclohexane/AcOEt 98 :2), GC yield 47%. IR (GC): 2937, 2868, 1745, 1448, 1351, 1263, 1198,
1159, 1132. 1H-NMR: 3.77 (s, 3 H); 3.18 (dd, J ¼ 3.5, 10.2, 1 H); 2.44 – 2.39 (m, 1 H); 2.06 – 1.98 (m, 1 H);
1.72 – 1.65 (m, 1 H); 1.52 – 1.46 (m, 2 H); 1.44 – 1.20 (m, 17 H). 13C-NMR (deduced from impurities):
170.4 (s); 63.1 (d); 62.6 (s); 52.1 (q); 33.5 (t); 28.2 (t); 27.0 (t); 26.3 (t); 26.1(t); 25.0 (t); 24.9 (t); 24.7 (t);
24.17 (t); 23.9 (t); 23.0 (t). MS: 254 (3, Mþ), 239 (4), 195 (9), 177 (6), 166 (6), 138 (8), 135 (12), 123 (11),
121 (13), 109 (27), 95 (64), 82 (68), 71 (79), 69 (44), 67 (53), 55 (100), 43 (28), 41 (75), 28 (50).
Methyl cis-15-Oxabicyclo[12.1.0]pentadecane-1-carboxylate (3f). According to G.P.B. After distil-
lation, yield 53%. Bp. 1508/0.2 mbar. IR: 2926, 2858, 1733, 1458, 1440, 1349, 1323, 1250, 1195, 1152, 1129,
1076, 1016, 989, 923, 862, 757, 716. 1H-NMR: 3.77 (s, 3 H); 3.06 (dd, J ¼ 3.8, 8.9, 1 H); 2.38 – 2.32 (m, 1 H);
1.97 – 1.91 (m, 1 H); 1.63 – 1.56 (m, 1 H); 1.52 – 1.46 (m, 2 H); 1.44 – 1.26 (m, 19 H). 13C-NMR: 170.3 (s);
62.8 (d); 62.8 (s); 52.1 (q); 32.1 (t); 27.7 (t); 26.9 (t); 26.5 (2t); 26.0 (t); 25.8 (t); 25.4 (t); 25.0 (t); 24.3 (2t);
24.0 (t). MS: 268 (5, Mþ), 252 (31), 221 (10), 209 (13), 109 (40), 95 (62), 82 (72), 71 (62), 67 (58), 55
(100), 41 (70).
Methyl cis-16-Oxabicyclo[13.1.0]hexadecane-1-carboxylate (3g). According to G.P.B. After distil-
lation, yield 88%. B.p. 1308/0.1 mbar. IR: 2925, 2857, 1733, 1458, 1440, 1350, 1325, 1254, 1195, 1150, 1129,
988, 924, 758, 716. 1H-NMR: 3.77 (s, 3 H); 3.05 (dd, J ¼ 3.5, 8, 1 H); 2.29 (dt, J ¼ 13, 7, 1 H); 1.91 – 1.84 (m,
1 H); 1.55 (quint., J ¼ 7, 2 H); 1.49 – 1.29 (m, 22 H). 13C-NMR: 170.5 (s); 62.7 (s); 62.2 (d); 52.1 (q); 32.7
(t); 28.0 (t); 27.7 (t); 27.3 (t); 27.0 (t); 26.9 (t); 26.8 (t); 26.6 (t); 26.5 (t); 26.4 (t); 26.1 (t); 25.3 (t); 24.9 (t).
MS: 282 (10, Mþ), 266 (10), 223 (22), 123 (27), 109 (34), 96 (58), 82 (88), 71 (81), 67 (53), 55 (100), 41 (68).
Methyl cis-17-Oxabicyclo[14.1.0]heptadecane-1-carboxylate (3h). According to G.P.B. After distil-
lation, yield 53%. B.p. 1508/0.1 mbar. IR: 2924, 2855, 1733, 1458, 1439, 1352, 1328, 1260, 1194, 1149, 1130,
988, 925, 784, 759, 717. 1H-NMR: 3.77 (s, 3 H); 3.00 (dd, J ¼ 4, 9, 1 H); 2.24 (dt, J ¼ 13, 6, 1 H); 1.92 – 1.85
(m, 1 H); 1.56 – 1.44 (m, 4 H); 1.42 – 1.28 (m, 22 H). 13C-NMR: 170.3 (s); 63.0 (s); 62.5 (d); 52.1 (q); 32.8
(t); 27.8 (t); 27.5 (t); 27.4 (2t); 27.1 (t); 27.0 (t); 26.9 (t); 26.4 (t); 26.2 (2t); 26.1 (t); 25.3 (t); 24.2 (t). MS: 296
(10, Mþ), 280 (85), 249 (15), 237 (19), 123 (21), 109 (35), 95 (68), 81 (75), 71 (58), 67 (62), 55 (100), 41
(70).
Hydrolytic Decarboxylation of 3 to 1 or 7 to 5: General Procedure C (G.P.C). A mixture of epoxy
ester 3 or 7 (1.0 mol-equiv.), NaOH (2.1 mol-equiv.), and MeOH/H2O 1:1 (5.6 ml/mmol) was heated
under reflux for 5 h. The cold mixture was then acidified with a soln. of 10n HCl (0.25 ml/mmol) in
MeOH/H2O 1:1 (2.1 ml/mmol) and then heated under reflux. After 1 h, the cold mixture was poured into
sat. aq. NaHCO3 soln. and extracted with Et2O. The org. phase was washed with brine, dried (Na2SO4),
and concentrated and the residue purified by distillation: pure ketone 1 or 5 in the yields reported in
Schemes 1 and 2.
Oxiranylation to 4 or 8: General Procedure D (G.P.D). To a suspension of tBuOK (2.8g, 25 mmol) and
t
trimethylsulfoxonium iodide (5.5 g, 25 mmol) in BuOH (42 ml) at 508, the macrocyclic ketone 1 or 5
(21 mmol) was added dropwise, and the mixture was kept at 508 for 6 to 18 h. After completion, the cold soln.
was diluted. with Et2O and washed twice with sat. aq. NaHCO3 soln., then to neutrality with brine. The org.
phase was dried (MgSO4) and concentrated and the residue purified by CC (SiO2, cyclohexane/AcOEt 9 :1).
1-Oxaspiro[2.9]dodecane (4a). According to G.P.D. Yield 74%. IR: 2920, 2870, 1475, 1443, 1353,
1
1309, 1183, 1148, 1098, 1030, 988, 904, 851, 784, 763, 731. H-NMR: 1.6 – 1.5 (m, 14 H); 1.75 – 1.65 (m,
2 H); 1.85 (t, J ¼ 5.8, 1 H); 1.88 (t, J ¼ 7.8, 1 H); 2.61 (s, 2 H). 13C-NMR: 59.5 (s); 54.9 (t); 32.9 (2t); 25.1

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Helvetica Chimica Acta – Vol. 95 (2012)
(2t); 24.8 (t); 24.2 (2t); 22.6 (2t). MS: 168 (7, Mþ), 139 (27), 125 (100), 111 (97), 97 (50), 95 (60), 85 (45),
83 (46), 81 (65), 72 (57), 69 (38), 67 (67), 55 (82), 41 (65). Metallic, naphthalenic. Citrus, lime, green and
mango flavor.
1-Oxaspiro[2.10]tridecane (4b). According to G.P.D. Yield 74%. IR: 3028, 2918, 2862, 1473, 1443,
1393, 1346, 1276, 1231, 1211, 1187, 1153, 1106, 1081, 1029, 973, 957, 921, 895, 878, 842, 796, 767, 723, 702,
661. 1H-NMR: 2.61 (s, 2 H); 1.85 – 1.78 (m, 2 H); 1.64 – 1.40 (m, 18 H). 13C-NMR: 60.1 (s); 54.2 (t); 33.7
(2t); 26.7 (2t); 26.2 (2t); 25.6 (2t); 23.1 (2t). MS: 182 (2, Mþ), 139 (70), 125 (100), 111 (43), 97 (45), 95
(30), 85 (62), 81 (33), 72 (72), 67 (52), 55 (64), 41 (65). Woody, grapefruit, moos, earthy.
1-Oxaspiro[2.12]pentadecane (4d). According to G.P.D. Yield 84%. IR: 3030, 2917, 2849, 1462, 1445,
1395, 1347, 1269, 1176, 1147, 1104, 1052, 975, 934, 898, 872, 822, 802, 753, 727, 711. 1H-NMR: 2.57 (s, 2 H);
1.69 – 1.61 (m, 2 H); 1.55 – 1.46 (m, 4 H); 1.41 – 1.36 (m, 18 H). 13C-NMR: 59.6 (s); 53.5 (t); 33.0 (2t); 27.0
(2t); 26.2 (2t); 25.7 (2t); 25.4 (2t); 22.8 (2t). MS: 210 (3, Mþ), 195 (6), 125 (17), 111 (22), 97 (50), 85 (91),
72 (100), 55 (49), 41 (51). Fatty, costus with slightly pine aspects28).
1-Oxaspiro[2.13]hexadecane (4e). According to G.P.D. Yield 70%. IR: 3030, 2925, 2856, 1460, 1395,
1
1146, 1102, 900, 710. H-NMR: 2.56 (s, 2 H); 1.62 – 1.54 (m, 2 H); 1.48 – 1.42 (m, 2 H); 1.42 – 1.24 (m,
22 H). 13C-NMR: 59.6 (s); 53.8 (t); 32.7 (2t); 29.8 (2t); 26.3 (2t); 25.7 (2t); 24.7 (t); 23.9 (2t); 21.8 (2t). MS:
224 (4, Mþ), 209 (9), 125 (14), 111 (22), 97 (48), 85 (93), 72 (100), 69 (21), 67 (30), 55 (54), 41 (50).
1-Oxaspiro[2.14]heptadecane (4f). According to G.P.D. Yield 72%. IR: 3030, 2924, 2855, 1458, 1396,
1349, 1287, 1145, 1099, 1064, 933, 901, 805, 746, 709. 1H-NMR: 2.57 (s, 2 H); 1.64 – 1.56 (m, 2 H); 1.52 –
1.43 (m, 4 H); 1.40 – 1.32 (m, 22 H). 13C-NMR: 59.8 (s); 53.8 (t); 33.8 (2t); 27.5 (2t); 26.8 (2t); 26.7 (2t);
26.6 (2t); 26.5 (2t); 23.5 (2t). MS: 238 (4, Mþ), 223 (6), 125 (11), 111 (22), 97 (40), 85 (93), 72 (100), 67
(25), 55 (52), 41 (51). Vaguely woody, fruity, pear, ambrette, weak.
1-Oxaspiro[2.15]octadecane (4g). According to G.P.D. Yield 86%. IR: 3030, 2924, 2855, 1459, 1397,
1350, 1291, 1163, 1140, 1103, 939, 903, 808, 711. 1H-NMR: 2.56 (s, 2 H); 1.63 – 1.56 (m, 2 H); 1.52 – 1.46 (q,
J ¼ 7, 2 H); 1.45 – 1.40 (m, 4 H); 1.38 – 1.30 (m, 22 H). 13C-NMR: 59.6 (s); 53.7 (t); 33.7 (2t); 27.4 (2t); 27.1
(2t); 26.7 (2t); 26.5 (4t); 26.4 (t); 23.5 (2t). MS: 252 (5, Mþ), 237 (7), 141 (8), 125 (9), 111 (19), 97 (34), 85
(92), 72 (100), 67 (24), 55 (52), 41 (51). Vaguely musky, heavy, weak.
1-Oxaspiro[2.16]nonadecane (4h). According to G.P.D. Yield 91%. Alternatively, a soln. of (11Z)-1-
oxaspiro[2.16]nonadec-11-ene (IVb; 132 mg, 0.5 mmol) in AcOEt (3 ml) was hydrogenated in the
presence of 5% Pd/C (13 mg). After absorption of 1.0 equiv. of H2, the mixture was filtered, the filtrate
concentrated, and the residue bulb-to bulb distilled: 4h (58 %)29). IR: 2922, 2853, 1458, 1396, 1350, 1295,
1144, 1100, 1033, 933, 904, 803, 734, 718. 1H-NMR: 2.57 (s, 2 H); 1.63 – 1.57 (m, 2 H); 1.51 – 1.45 (q, J ¼ 7,
2 H); 1.45 – 1.40 (m, 4 H); 1.40 – 1.27 (m, 24 H). 13C-NMR: 59.9 (s); 53.8 (t); 34.0 (2t); 28.2 (2t); 27.8 (2t);
27.7 (2t); 27.5 (2t); 27.1 (2t); 27.0 (2t); 23.9 (2t). MS: 266 (2, Mþ), 135 (6), 121 (8), 111 (13), 97 (28), 83
(31), 69 (41), 55 (95), 41 (100), 29 (36). Woody, sawdust, weak.
(þ)-(1Z,3R)-Methyl 3-Methylcyclotetradec-1-ene-1-carboxylate (6c). According to G.P.A. After
bulb-to-bulb distillation, yield 56%. B.p. 1008/0.21 mbar. [a]2D0 ¼ þ24.5 (c ¼ 3.0, CCl4). IR: 2926, 2857,
1715, 1640, 1456, 1440, 1370, 1228, 1192, 1171, 1126, 1099, 1067, 1031, 1002, 905, 820, 765, 718. 1H-NMR:
5.51 (d, J ¼ 7.5, 1 H); 3.72 (s, 3 H); 3.11 – 3.03 (m, 1 H); 2.68 – 2.62 (m, 1 H); 1.91 (dt, J ¼ 2.8, 12.0, 1 H);
1.52 – 1.32 (m, 9 H); 1.28 – 1.18 (m, 8 H); 1.14 – 1.05 (m, 3 H); 0.96 (d, J ¼ 7, 3 H ) . 13C-NMR: 168.9 (s);
148.7 (d); 130.4 (s); 51.1 (q); 37.0 (t); 34.1 (t); 33.7 (d); 27.1 (t); 26.8 (t); 26.0 (t); 25.6 (2t); 24.5 (t); 24.4 (t);
23.4 (2t); 21.4 (q). MS : 266 (77, Mþ), 235 (29), 141 (40), 128 (43), 109 (55), 95 (100), 81 (87), 67 (82), 55
(91), 41 (86).
(þ)-(1Z,3R,5Z)-Methyl 3-Methylcyclotetradeca-1,5-diene-1-carboxylate (6d). According to G.P.A.
After CC (SiO2, cyclohexane/AcOEt 95 :5), yield 3%. B.p. 1008/0.22 mbar. [a]2D0 ¼ þ47.4 (c ¼ 1.9,
CHCl3). IR: 3009, 2927, 2857, 1712, 1643, 1456, 1435, 1378, 1239, 1195, 1157, 1123, 1105, 1058, 1007, 831,
28
)
)
Compound 4d was already submitted to our perfumers in 1975 by W. K. Giersch (Firmenich SA).
In EtOH, over reduction produced methylcycloheptadecane in 38% yield. IR: 2921, 2852, 1458,
1375, 1350, 1294, 1110, 1066, 727. 1H-NMR: 1.46 – 1.42 (m, 1 H); 1.36 – 1.26 (m, 28 H); 1.19 – 1.11 (m,
4 H); 0.85 (d, J ¼ 7, 3 H). 13C-NMR: 35.3 (2t); 31.3 (d); 28.2 (2t); 27.9 (2t); 27.6 (6t); 27.3 (2t); 25.5
29
.
(2t); 20.9 (q). MS: 252 (10, Mþ ), 125 (11), 111 (24), 97 (48), 83 (59), 69 (61), 57 (51), 55 (97), 43 (65),
41 (100), 29 (33).

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756, 721. 1H-NMR: 5.56 (d, J ¼ 8.5, 1 H); 5.53 –5.37 (m, 2 H); 3.74 (s, 3 H); 3.28–3.20 (m, 1 H); 2.55–2.48
(m, 1 H); 2.24–2.02 (m, 4 H); 1.95–1.86 (m, 2 H); 1.57–1.48 (m, 1 H); 1.42–1.21 (m, 8 H); 1.17 –1.09 (m,
2 H); 1.02 (d, J¼ 7, 3 H ) . 13C-NMR: 168.9 (s); 147.0 (d); 130.5 (d); 129.8 (s); 128.0 (d); 51.1 (q); 34.8 (t);
33.6 (d); 32.4 (t); 27.8 (t); 26.8 (t); 26.2 (t); 25.9 (t); 25.2 (t); 24.9 (t); 24.0 (t); 21.0 (q). MS: 264 (74, Mþ), 233
(21), 205 (41), 175 (16), 149 (18), 135 (20), 126 (54), 95 (93), 81 (70), 67 (100), 55 (53), 41 (63).
(þ)-(1Z,3R)-Methyl 3-Methylcyclopentadec-1-ene-1-carboxylate (6f). According to G.P.A. After
bulb-to-bulb distillation, yield 48%. B.p. 1108/0.20 mbar. [a]2D0 ¼ þ9.8 (c ¼ 1.8, CCl4). IR: 2923, 2852,
1
1717, 1640, 1449, 1440, 1371, 1350, 1192, 1163, 1106, 903, 861, 830, 761, 719. H-NMR: 5.57 (d, J ¼ 8.5,
1 H); 3.73 (s, 3 H); 3.08 – 3.00 (m, 1 H); 2.65 – 2.59 (m, 1 H); 2.03 – 1.96 (m, 1 H); 1.49 – 1.40 (m, 9 H);
1.43 – 1.13 (m, 13 H); 0.95 (d, J ¼ 7, 3 H ) . 13C-NMR: 169.0 (s); 148.1 (d); 130.6 (s); 51.1 (q); 38.1 (t); 34.2
(t); 33.6 (d); 27.8 (t); 27.7 (t); 27.5 (t); 27.2 (t); 27.1 (t); 27.0 (t); 26.9 (t); 26.7 (t); 26.4 (t); 25.8 (t); 21.8 (q).
MS: 280 (18, Mþ), 249 (9), 141 (16), 128 (14), 125 (14), 121 (11), 111 (18), 109 (26), 95 (49), 81 (49), 79
(32), 69 (43), 67 (54), 55 (85), 43 (40), 41 (100), 29 (35).
(1R,13R,14R)/(1S,13R,14S)-Methyl 13-Methyl-15-oxabicyclo[12.1.0]pentadecane-1-carboxylate
(7c). According to G.P.B. After CC (SiO2, cyclohexane/AcOEt 95 :5), yield 82%; 8 :2 mixture of
stereoisomers. [a]D20 ¼ þ8.43 (c ¼ 3.0, CCl4). IR: 2926, 2858, 1734, 1458, 1441, 1349, 1322, 1251, 1195, 1156,
1136, 1104, 1047, 981, 956, 917, 794, 764, 718. 1H-NMR: 3.77 (s, 3 H); 2.77 (d, J ¼ 9.5, 1 H); 2.44 – 2.37 (m,
1 H); 1.63 – 1.55 (m, 1 H); 1.50 – 1.34 (m, 18 H); 1.29 – 1.22 (m, 3 H); 1.10 (d, J ¼ 7, 3 H ) . 13C-NMR: 170.4
(s); 68.4 (d); 63.7 (s); 52.0 (q); 34.6 (t); 33.2 (d); 32.4 (t); 26.8 (t); 26.7 (t); 26.4 (t); 26.3 (t); 25.8 (t); 24.4
(t); 24.0 (t); 23.7 (t); 23.6 (t); 18.6 (q). MS: major 282 (9, Mþ), 254 (15), 223 (21), 149 (23), 123 (17), 109
(29), 95 (45), 85 (47), 82 (49), 69 (76), 55 (100), 41 (62); minor 282 (10, Mþ), 254 (15), 223 (21), 149 (24),
123 (18), 109 (29), 95 (45), 85 (52), 82 (51), 69 (74), 55 (100), 41 (61).
(1R,14R,15R)/(1S,14R,15S)-Methyl 14-Methyl-16-oxabicyclo[13.1.0]hexadecane-1-carboxylate (7f).
According to G.P.B. After CC (SiO2, cyclohexane/AcOEt 97:3 ! 95 :5), yield 59%; 78 :22 mixture of
stereoisomers. [a]D20 ¼ þ5.8 (c ¼ 2.5, CCl4). IR: 2925, 2855, 1732, 1458, 1440, 1350, 1260, 1194, 1155, 1106,
1032, 790, 765, 729. 1H-NMR: major: 3.77 (s, 3 H); 2.75 (d, J ¼ 9.5, 1 H); 2.37 – 2.28 (m, 1 H); 1.72 – 1.49
(m, 4 H); 1.45 – 1.16 (m, 20 H); 1.10 (d, J ¼ 6.5, 3 H); minor: 3.75 (s, 3 H); 2.93 (d, J ¼ 8, 1 H); 2.45 – 2.36
(m, 1 H); 1.72 – 1.49 (m, 4 H); 1.45 – 1.16 (m, 20 H); 0.93 (d, J ¼ 6.5, 3 H). 13C-NMR (deduced from the
mixture): 170.7 (s); 67.7 (d); 63.6 (s); 52.2 (q); 34.2 (t); 33.7 (d); 32.8 (t); 28.1 (t); 27.7 (t); 27.0 (t); 26.9 (t);
26.8 (t); 26.4 (t); 26.1 (t); 25.9 (t); 25.5 (t); 24.9 (t); 18.1 (q). MS: major: 296 (13, Mþ), 280 (12), 268 (22),
237 (29), 181 (9), 163 (18), 127 (15), 123 (19), 109 (28), 95 (52), 81 (52), 69 (71), 55 (100), 41 (68); minor
296 (13, Mþ), 280 (14), 268 (18), 237 (22), 181 (9), 163 (17), 127 (15), 123 (19), 109 (28), 95 (51), 85 (42),
82 (50), 81 (49), 69 (70), 55 (100), 41 (63).
rac-5-Methyl-1-oxaspiro[2.13]hexadecane (8a). According to C.P.D. After bulb-to-bulb distillation,
72% yield; 75 :25 mixture of stereoisomers. B.p. 1258/0.1 mbar. IR: 2925, 2858, 1461, 1395, 1378, 1277,
1136, 943, 897, 800, 715. 1H-NMR: 2.60 – 2.53 (m, 1 H); 2.44 – 2.42 (m, 1 H); 2.03 – 1.95 (m, 2 H); 1.85 –
1.78 (m, 1 H); 1.5 – 1.34 (m, 16 H); 1.29 – 1.21 (m, 3 H); 1.19 – 1.10 (m, 3 H); 0.97 (d, J ¼ 7, 2.25 H); 0.89
(d, J ¼ 7, 0.75 H). 13C-NMR: major: 58.9 (s); 52.2 (t); 40.9 (t); 34.6 (t); 32.7 (t); 26.6 (d); 26.4 (t); 26.2 (t);
25.5 (t); 24.7 (t); 24.6 (t); 24.4 (t); 24.2 (t); 23.6 (t); 22.4 (t); 20.0 (q); minor: 58.8 (s); 54.8 (t); 40.2 (t); 35.2
(t); 32.8 (t); 27.1 (d); 26.3 (t); 23.7 (t); 24.8 (t); 24.6 (t); 24.3 (t); 24.2 (t); 24.0 (t); 23.6 (t); 21.1 (t); 19.9 (q).
MS: major: 238 (6, Mþ), 223 (36), 195 (12), 139 (22), 125 (18), 111 (100), 99 (41), 85 (51), 83 (33), 81
(31), 72 (55), 69 (38), 67 (30), 57 (22), 55 (68), 43 (27), 41 (58); minor: 238 (6, Mþ), 223 (32), 195 (13),
139 (22), 125 (18), 111 (100), 99 (41), 85 (51), 83 (35), 81 (33), 72 (55), 69 (40), 67 (30), 57 (23), 55 (74),
43 (27), 41 (60). Woody, ambery, cedar, musky.
rac-(7Z)-5-Methyl-1-oxaspiro[2.13]hexadec-7-ene (8b). According to G.P.D. After bulb-to-bulb
distillation, yield 52%; 80 :20 mixture of stereoisomers. B.p. 1208/0.12 mbar. IR: 3028, 2926, 2851, 1456,
1396, 969, 937, 892, 837, 782, 706. 1H-NMR: 5.45–5.36 (m, 1 H); 5.25–5.20 (m, 1 H); 2.45 (s, 2 H); 2.16–
2.07 (m, 4 H); 1.68 –1.58 (m, 2 H); 1.52 –1.33 (m, 11 H); 1.29–1.10 (m, 4 H); 1.06 (d, J¼ 7, 3 H ) . 13C-NMR:
132.0 (d); 130.9 (d); 58.5 (s); 53.4 (t); 41.6 (t); 37.8 (t); 33.3 (t); 30.5 (d); 30.2 (t); 27.7 (t); 27.1 (t); 24.7 (t);
24.1 (t); 23.4 (t); 23.2 (t); 21.6 (q). MS: 236 (32, Mþ), 221 (10), 151 (12), 135 (16), 123 (30), 109 (46), 97
(72), 95 (74), 81 (94), 67 (87), 55 (100), 41 (87). Waxy, candle, musky, nitromusk, animal, woody, good.
(5R)-5-Methyl-1-oxaspiro[2.14]heptadecane (8c). According to G.P.D. After bulb-to-bulb distilla-
tion, yield 77%; 67:33 mixture of stereoisomers. B.p. 1208/0.1 mbar. [a]2D0 ¼ þ12.2 (c ¼ 1.7, CHCl3). IR:

438
Helvetica Chimica Acta – Vol. 95 (2012)
3029, 2923, 2855, 1458, 1395, 1377, 1350, 1284, 1138, 1102, 951, 897, 796, 710. 1H-NMR (deduced from the
mixture): major: 2.54 (d, J ¼ 4, 1 H); 2.46 (d, J ¼ 4, 1 H); 1.96 – 1.60 (m, 9 H); 1.44 – 1.04 (m, 18 H); 0.96
(d, J ¼ 7, 3 H); minor: 2.60 (s, 2 H); 2.12 – 1.60 (m, 9 H); 1.44 – 1.04 (m, 18 H); 0.90 (d, J ¼ 7, 3 H ) .
13C-NMR: 58.9 (s); 52.8 (t); 41.5 (t); 35.7 (t); 33.8 (t); 28.2 (d); 27.5 (t); 27.0 (t); 26.8 (2t); 26.7 (2t); 26.5
(t); 26.2 (t); 25.1 (t); 23.9 (t); 20.6 (q). MS: major: 252 (10, Mþ), 237 (22), 209 (11), 139 (12), 135 (12),
125 (15), 111 (63), 97 (55), 83 (63), 69 (67), 55 (100), 41 (73); minor: 252 (10, Mþ), 237 (22), 209 (10),
139 (12), 135 (13), 125 (15), 111 (60), 97 (54), 83 (63), 69 (67), 55 (100), 41 (72). Rancid, oily, vaguely
musky, candle, weak.
(þ)-(5R,7Z)-5-Methyl-1-oxaspiro[2.14]heptadec-7-ene (8d). According to G.P.D. After bulb-to-bulb
distillation, yield 60%; 60 :40 mixture of stereoisomers. B.p. 1208/0.14 mbar. [a]2D0 ¼ þ15.1 (neat). IR:
3008, 2924, 2855, 1458, 1395, 1376, 1349, 962, 897, 791, 721. 1H-NMR: (deduced from the mixture): major:
5.57 – 5.41 (m, 2 H); 2.55 (d, J ¼ 4.5, 1 H); 2.50 (d, J ¼ 4.5, 1 H); 2.26 – 2.12 (m, 2 H); 1.97 – 1.88 (m, 1 H);
1.75 – 1.62 (m, 2 H); 1.49 – 1.26 (m, 18 H); 1.00 (d, J ¼ 7, 3 H); minor: 5.57 – 5.41 (m, 2 H); 2.58 (s, 2 H);
2.26 – 2.12 (m, 2 H); 1.97 – 1.88 (m, 1 H); 1.75 – 1.62 (m, 2 H); 1.49 – 1.26 (m, 18 H); 0.96 (d, J ¼ 7, 3 H ) .
13C-NMR (deduced from the mixture): major: 131.6 (d); 128.0 (d); 58.6 (s); 53.1 (t); 41.8 (t); 34.5 (t); 33.4
(t); 32.0 (d); 28.0 (t); 27.2 (t); 27.0 (t); 26.6 (t); 26.3 (2t); 26.0 (2t); 22.8 (t); 20.1 (q); minor: 131.8 (d); 128.0
(d); 58.7 (s); 53.9 (t); 41.8 (t); 34.9 (t); 33.4 (t); 32.2 (d); 28.1 (t); 27.3 (t); 27.0 (t); 26.7 (t); 26.2 (t); 26.1 (t);
26.0 (t); 25.6 (t); 22.3 (t); 19.8 (q). MS: major: 250 (19, Mþ), 235 (9), 193 (8), 147 (11), 135 (17), 123 (23),
111 (41), 109 (42), 97 (51), 95 (78), 81 (100), 67 (84), 55 (94), 41 (82); minor: 250 (20, Mþ), 235 (10), 193
(9), 147 (10), 135 (17), 123 (23), 111 (43), 109 (41), 97 (54), 95 (76), 81 (100), 67 (84), 55 (96), 41 (84).
Musky, animal, nitromusk, weak.
rac-(6Z)-1-Oxaspiro[2.14]heptadec-6-ene (8e). According to G.P.D. After bulb-to-bulb distillation,
yield 78%. B.p. 1208/0.21 mbar. IR: 3005, 2924, 2855, 1457, 1397, 1349, 1036, 964, 903, 818, 768, 712.
1H-NMR: 5.46 – 5.33 (m, 2 H); 2.60 (d, J ¼ 5, 1 H); 2.57 (d, J ¼ 5, 1 H); 2.21 – 2.14 (m, 2 H); 2.09 – 1.97
(m, 2 H); 1.70 – 1.57 (m, 2 H); 1.48 – 1.33 (m, 18 H). 13C-NMR: 130.6 (d); 128.9 (d); 59.4 (s); 53.8 (t); 35.0
(t); 33.5 (t); 28.1 (t); 27.2 (t); 27.0 (t); 26.8 (t); 26.5 (t); 26.4 (2t); 26.2 (t); 23.4 (t); 23.2 (t). MS: 236 (11,
Mþ), 207 (10), 135 (12), 123 (26), 109 (50), 95 (77), 81 (89), 67 (100), 55 (88), 41 (83). Waxy, candle,
musky, nitromusk, weak.
(5R)-5-Methyl-1-oxaspiro[2.15]octadecane (8f). According to G.P.D. After bulb-to-bulb distillation,
yield 86%; 69 :31 mixture of stereoisomers. B.p. 1208/0.1 mbar. [a]2D0 ¼ þ2.7 (c ¼ 1.5, CCl4). IR: 3034,
2934, 2865, 1460, 1382, 1354, 953, 745. 1H-NMR (deduced from the mixture): major: 2.54 (d, J ¼ 4.7, 1 H);
2.45 (dd, J ¼ 4.7, 1.5, 1 H); 1.96 – 1.70 (m, 9 H); 1.43 – 1.05 (m, 20 H); 0.96 (d, J ¼ 6.3, 3 H); minor: 2.59 (s,
2 H); 2.12 – 1.70 (m, 9 H); 1.43 – 1.05 (m, 20 H); 0.90 (d, J ¼ 6.3, 3 H). 13C-NMR: 58.9 (s); 52.7 (t); 41.6
(t); 35.6 (t); 33.7 (t); 28.6 (d); 27.5 (2t); 27.2 (t); 27.1 (t); 26.7 (t); 26.5 (t); 26.2 (2t); 26.0 (t); 25.5 (t); 24.1
(t); 20.4 (q). MS: major: 266 (10, Mþ), 251 (19), 223 (8), 208 (7), 149 (8), 139 (10), 135 (12), 125 (17),
121 (11), 111 (51), 97 (55), 95 (49), 83 (60), 81 (48), 69 (67), 67 (38), 57 (55), 55 (100), 43 (42), 41 (78);
minor: 266 (11, Mþ), 251 (12), 248 (8), 223 (6), 208 (5), 166 (5), 149 (9), 139 (9), 135 (12), 125 (13), 121
(12), 111 (43), 97 (52), 95 (44), 83 (61), 81 (46), 69 (67), 67 (38), 57 (60), 55 (100), 43 (42), 41 (71).
rac-1-Oxaspiro[2.15]octadec-7-ene (8g). According to G.P.D. After bulb-to-bulb distillation, yield
78%; 60 :40 (E)/(Z) mixture. B.p. 1008/0.09 mbar. IR: 3028, 2925, 2854, 1458, 1442, 1397, 1368, 1349,
1289, 966, 935, 903, 810, 727, 711. 1H-NMR: major (E): 5.38 – 5.32 (m, 2 H); 2.61 (d, J ¼ 5, 1 H); 2.52 (d,
J ¼ 5, 1 H); 2.07 – 2.01 (m, 4 H); 1.62 – 1.55 (m, 2 H); 1.46 – 1.28 (m, 20 H); minor (Z): 5.47 – 5.37 (m,
2 H); 2.58 (d, J ¼ 5, 1 H); 2.54 (d, J ¼ 5, 1 H); 2.07 – 2.01 (m, 4 H); 1.62 – 1.55 (m, 2 H); 1.46 – 1.28 (m,
20 H). 13C-NMR: (deduced from the mixture): major (E): 131.6 (d); 130.6 (d); 59.6 (s); 53.2 (t); 34.5 (t);
33.7 (t); 32.1 (t); 31.9 (t); 28.1 (t); 27.6 (t); 27.2 (t); 27.1 (t); 26.5 (t); 26.4 (t); 25.4 (t); 24.6 (t); 23.1 (t);
minor (Z): 130.3 (d); 129.4 (d); 59.6 (s); 53.7 (t); 34.5 (t); 32.1 (t); 31.9 (t); 28.6 (t); 27.8 (t); 28.0 (t); 27.6
(t); 27.0 (t); 26.7 (t); 26.3 (t); 25.8 (t); 25.0 (t); 22.2 (t). MS: major (E): 250 (28, Mþ), 232 (11), 137 (13),
135 (15), 123 (23), 121 (21), 109 (43), 98 (58), 95 (79), 81 (83), 67 (94), 55 (100), 41 (87); minor (Z): 250
(30, Mþ), 232 (11), 137 (11), 135 (17), 123 (21), 121 (23), 109 (41), 98 (50), 95 (77), 81 (83), 67 (90), 55
(100), 41 (87). Slightly musky, waxy, candle.
rac-1-Oxaspiro[2.15]octadec-9-ene (8h). According to G.P.D. After CC (SiO2, cyclohexane/AcOEt
9 :1), yield 76%; 57:43 (E)/(Z) mixture. IR: 3030, 2985, 2934, 2864, 1456, 1443, 967, 894, 795, 720.
1H-NMR: 5.37 – 5.33 (m, 2 H); 2.58 – 2.54 (m, 2 H); 2.08 – 2.03 (m, 4 H); 1.60 – 1.27 (m, 22 H). 13C-NMR

Helvetica Chimica Acta – Vol. 95 (2012)
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(deduced from the mixture): major: (E): 131.1 (d); 130.5 (d); 59.3 (s); 53.4 (t); 34.8 (t); 33.9 (t); 33.7 (t);
31.7 (t); 31.3 (t); 28.8 (t); 28.3 (t); 28.0 (t); 27.3 (t); 27.1 (t); 26.3 (t); 24.0 (t); 23.7 (t); minor: (Z): 131.1 (d);
130.9 (d); 59.6 (s); 53.7 (t); 34.5 (t); 33.3 (t); 32.3 (t); 32.1 (t); 32.0 (t); 31.5 (t); 29.3 (t); 27.2 (t); 27.1 (t);
26.7 (t); 26.1 (t); 24.1 (t); 22.6 (t). MS: major (E): 250 (35, Mþ), 232 (9), 175 (6), 161 (7), 147 (10), 135
(20), 121 (26), 109 (38), 95 (77), 81 (87), 67 (93), 55 (100), 41 (89); (Z) 250 (33, Mþ), 232 (9), 175 (5),
161 (7), 147 (11), 135 (18), 121 (24), 109 (36), 95 (76), 81 (84), 67 (94), 55 (100), 41 (90). Musky,
nitromusk, animal, powdery.
rac-1-Oxaspiro[2.15]octadec-10-ene (8i). According to G.P.D. After CC (SiO2, cyclohexane/AcOEt
9 :1), yield 85%; 65 :35 (E)/(Z) mixture. IR: 3028, 2985, 2924, 2852, 1459, 1442, 965, 895, 797, 719.
1H-NMR (deduced from the mixture): major: (E) 5.34 – 5.29 (m, 2 H); 2.55 (d, J ¼ 5, 1 H); 2.51 (d, J ¼ 5,
1 H); 2.08 – 2.03 (m, 4 H); 1.60 – 1.27 (m, 22 H); minor (Z): 5.41 – 5.37 (m, 2 H); 2.55 (d, J ¼ 5, 1 H); 2.52
(d, J ¼ 5, 1 H); 2.08 – 2.03 (m, 4 H); 1.60 – 1.27 (m, 22 H). 13C-NMR (deduced from the mixture): major
(E): 131.5 (d); 130.0 (d); 59.4 (s); 53.8 (t); 33.6 (t); 32.5 (t); 32.3 (t); 29.0 (t); 28.4 (t); 28.1 (t); 28.0 (t); 27.8
(2t); 27.5 (t); 26.9 (t); 24.4 (t); 23.4 (t); minor (Z): 131.0 (d); 130.0 (d); 59.4 (s); 53.9 (t); 33.8 (t); 32.4 (t);
32.2 (t); 28.8 (t); 28.7 (t); 28.0 (t); 27.8 (2t); 27.6 (t); 27.5 (t); 27.1 (t); 23.4 (t); 23.3 (t). MS: major (E): 250
(13, Mþ), 135 (20), 121 (25), 109 (32), 97 (43), 95 (66), 81 (81), 67 (100), 55 (86), 41 (91). minor (Z): 250
(13, Mþ), 135 (16) 121 (22), 109 (28), 97 (43), 95 (62), 81 (82), 67 (100), 55 (85), 41 (88). Vaguely musky,
candel, very weak.
rac-1-Oxaspiro[2.11]tetradeca-6,10-diene (8j). According to G.P.D. After CC (SiO2, cyclohexane/
AcOEt 9 :1), yield 84%; 1:2 (6E,10Z)/(6Z,10E) mixture. IR: 3029, 2985, 2930, 2865, 1458, 1443, 966, 894,
795, 720. 1H-NMR: 5.6 – 5.2 (m, 4 H); 2.5 – 2.65 (m, 1 H); 2.52 – 2.49 (m, 1 H); 2.3 – 2.0 (m, 6 H); 1.8 –
1.55 (m, 4 H); 1.5 – 1.3 (m, 2 H). 13C-NMR (deduced from the mixture): major: 132.4 (d); 131.8 (d);
131.3 (d); 128.1 (d); 59.7 (s); 52.7 (t); 35.5 (t); 31.6 (t); 29.7 (t); 28.2 (t); 28.1 (t); 23.3 (t); 21.3 (t); minor:
130.3 (d); 129.6 (d); 129.4 (d); 129.3 (d); 59.2 (s); 52.6 (t); 34.1 (t); 30.9 (t); 30.8 (t); 29.1 (t); 28.0 (t); 25.7
(t) ; 23.0 (t). MS: major: 192 (2, Mþ), 161 (20), 145 (15), 131 (22), 119 (26), 109 (28), 107 (31), 105 (44),
93 (49), 91 (67), 81 (52), 79 (100), 67 (91), 55 (29), 54 (27), 41 (30); minor: 192 (2, Mþ), 161 (20), 145
(17), 131 (22), 119 (20), 109 (24), 107 (26), 105 (34), 93 (42), 91 (57), 81 (48), 79 (100), 67 (88), 55 (32),
54 (35), 41 (35). Cedar, eucalyptus, woody, pine.
2,2-Bis(8-bromooctyl)-1,3-dioxolane (Ib; Scheme 3). A mixture of diol Ia [16]30) (108.5 g,
330 mmol), CBr4 (217 g, 660 mmol), and Ph3P (190 g, 720 mmol) was heated at 308. The strong
exothermic reaction was then equilibrated at 308 for 6 h, before dilution with Et2O. The Ph3P(O) was
filtered and washed with Et2O, the filtrate concentrated, and the residue purified by CC (SiO2,
cyclohexane/AcOEt 98 :2); Ib (65%).
Alternatively, a soln. of 1,17-dibromoheptadecan-9-one (VIb; 1.0 g, 2.43 mmol) in cyclohexane
(60 ml) was heated under reflux in the presence of TsOH (20 mg) and ethylene glycol (¼ethane-1,2-diol;
3.0 g, 65.2 mmol). After 24 h and collection of the formed H2O with a DeanꢀStark apparatus, the cold
mixture was concentrated and the residue extracted with Et2O. The org. phase was washed to neutrality
with 15% aq. NaHCO3 soln., then brine, dried (Na2SO4), and concentrated: pure Ib (quant.). IR: 2926,
2854, 1495, 1462, 1438, 1371, 1250, 1177, 1077, 1043, 947, 913, 729, 694, 666, 644. 1H-NMR: 3.92 (s, 4 H);
3.40 (t, J ¼ 6, 4 H); 1.84 (quint., J ¼ 5, 4 H); 1.61 – 1.54 (m, 4 H); 1.45 – 1.40 (m, 4 H); 1.36 – 1.26 (m,
16 H). 13C-NMR: 111.8 (s); 64.9 (2t); 37.1 (2t); 34.0 (2t); 32.8 (2t); 29.8 (2t); 29.4 (2t); 28.7 (2t); 28.1 (2t);
23.8 (2t). MS: 454 (0, Mþ), 265 (97), 263 (100), 183 (10), 99 (11), 69 (10), 55 (12).
1,3-Dioxolan-2,2-dioctanol Diacetate (Ic). AcCl (95 g, 1.2 mol) was added dropwise in 1 h at < 308 to
a soln. of Ia (90.0 g, 0.27 mol) and DMAP (11.4 g, 0.09 mol) in Et3N (200 ml) and CH2Cl2 (500 ml). After
3 h, the mixture was poured onto ice, and extracted with Et2O. The org. phase was washed to neutrality
with brine, dried (Na2SO4), and concentrated. The residue was subjected to CC (SiO2, cyclohexane/
AcOEt 7:3): Ic (60%). IR: 2929, 2855, 1737, 1465, 1387, 1365, 1233, 1144, 1116, 1080, 1038, 948, 897, 859,
724, 634, 606. 1H-NMR: 4.05 (t, J ¼ 7, 4 H); 3.92 (s, 4 H); 2.04 (s, 6 H); 1.64 – 1.56 (m, 8 H); 1.37 – 1.25 (m,
IR: 3346, 2925, 2853, 1464, 1372, 1348, 1316, 1209, 1136, 1051, 948, 902, 787, 723, 621. 1H-NMR: 3.92
(s, 4 H); 3.62 (t, J ¼ 7, 4 H); 1.84 (br. s, 2 H); 1.61 – 1.52 (m, 8 H); 1.36 – 1.25 (m, 20 H). 13C-NMR:
111.9 (s); 64.9 (2t); 62.9 (2t); 37.1 (2t); 32.8 (2t); 29.8 (2t); 29.5 (2t); 29.3 (2t); 25.7 (2t); 23.8 (2t). MS:
30
)
.
330 (0, Mþ ), 269 (1), 201 (100), 99 (9), 69 (7), 55 (9).

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Helvetica Chimica Acta – Vol. 95 (2012)
Scheme 3
a) CBr4, PPh3. b) Na2S, EtOH. c) H2O2, NaHCO3, MnSO4, MeCN. d) KOH Al2O3, EtOH, CBr2F2, 608.
e) HCl, H2O/THF. f) AcCl, N,N-dimethylpyridin-4-amine (DMAP), Et3N, CH2Cl2. g) Ethylene glycol,
t
TsOH, cyclohexane, 858. h) m-CPBA, CHCl3, 508. i) NaOH, EtOH/H2O, 788. j) Me3S(O), BuOK,
tBuOH, 508. k) I2 (2.2 mol-equiv.), KOH, MeOH. l) H2, Pd/C, AcOEt.
20 H). 13C-NMR; 171.2 (2s); 111.8 (s); 64.9 (2t); 64.6 (2t); 37.1 (2t); 29.8 (2t); 29.5 (2t); 29.2 (2t); 28.6 (2t);
25.9 (2t); 23.8 (2t); 21.0 (2q). MS: 414 (0, Mþ), 243 (100), 99 (9), 87 (8), 43 (7).
1,4-Dioxa-14-thiaspiro[4.17]docosane (IIa). To refluxing EtOH (1.0 l) were added simultaneously a
soln. of dibromide Ib (8.0 g, 17 mmol) in EtOH (150 ml) and Na2S (2.7 g, 35 mmol) in EtOH (150 ml).
After 1.5 h, the solvent was evaporated and the mixture diluted with pentane, before extraction with H2O.
The residue of the concentrated org. phase was purified by CC (SiO2, hexane/CH2Cl2 9 :1 ! 1:1) and

Helvetica Chimica Acta – Vol. 95 (2012)
441
recrystallization from EtOH: pure IIa (61%). M.p. 44 – 45.58. IR: 2919, 2851, 1471, 1415, 1379, 1226, 719,
1
648. H-NMR: 3.91 (s, 4 H); 2.48 (t, J ¼ 8, 4 H); 1.64 – 1.56 (m, 8 H); 1.43 – 1.31 (m, 20 H). 13C-NMR:
112.1 (s); 64.4 (2t); 35.4 (2t); 30.1 (2t); 28.7 (2t); 28.5 (2t); 27.8 (4t); 27.4 (2t) ; 23.3 (2t). MS: 328 (25, Mþ),
285 (17), 283 (19), 267 (13), 215 (62), 183 (78), 155 (20), 141 (18), 99 (100), 86 (21), 55 (25).
1,4-Dioxa-14-thiaspiro[4.17]docosane 14,14-Dioxide (IIb). A mixture of 30% aq. H2O2 soln. (3 ml)
and 0.2m aq. NaHCO3 (103 ml) was added dropwise at 208 to a soln. of IIa (2.0 g, 1.5 mmol) and MnSO4 ·
H2O (12 mg) in MeCN (138 ml). After 0.5 h, sat. aq. NaCl soln. (50 ml) was added, the mixture extracted
with AcOEt, and the extract concentrated: IIb (95%). IR: 2920, 2855, 1461, 1415, 1371, 1350, 1315, 1290,
1270, 1218, 1184, 1152, 1125, 1077, 1050, 1033, 952, 906, 825, 719. 1H-NMR: 3.92 (s, 4 H); 2.81 (sept., J ¼ 8,
2 H); 2.75 (sept., J ¼ 8, 2 H); 1.71 (quint., J ¼ 8, 4 H); 1.61 – 1.55 (m, 4 H); 1.52 – 1.46 (m, 4 H); 1.38 – 1.32
(m, 16 H). 13C-NMR: 112.0 (s); 64.5 (2t); 49.6 (2t); 35.4 (2t); 28.2 (2t); 27.5 (2t); 27.4 (2t); 27.0 (2t); 23.2
(2t); 20.7 (2t). MS : 360 (5, Mþ), 317 (35), 183 (85), 155 (20), 141 (19), 99 (100), 86 (21), 55 (16).
(13Z)-1,4-Dioxaspiro[4.16]henicos-13-ene (III). A suspension of KOH/Al2O3 1:3 (by wt.; 2.7 g) in
EtOH (10 ml) was heated at 608, and IIb (100 mg, 0.2 mmol) was added, followed by dropwise addition
of CBr2F2 (2 ml). After 6 h the solvent was evaporated and the residue dissolved in CH2Cl2. The org.
phase was washed with brine, dried (Na2SO4), and concentrated and the residue purified by CC (SiO2,
hexane/AcOEt 2 :1): pure III (82%); 3 :7 mixture of (E)/(Z) isomers. Both the (E)/(Z) ratio and the
chemical yield depend on the source of halogen (KOH/Al2O3, EtOH, CCl4: (E)/(Z) 3 :7, 70%), the
solvent (KOH/Al2O3, tBuOH, CBr2F2: (E)/(Z) 6 :4, 91%), and the base (NaOH, tBuOH, CBr2F2: (E)/
(Z) 45 :55, 75%; tBuOK, THF, CBr2F2: (E)/(Z) 9 :1, 86%). IR: 3000, 2923, 2853, 1495, 1458, 1353, 1292,
1
1210, 1189, 1178, 1073, 945, 915, 728, 694. H-NMR: 5.33 (t, J ¼ 5, 2 H); 3.90 (s, 4 H); 2.04 (dt, J ¼ 5, 7,
4 H); 1.60 – 1.50 (m, 4 H); 1.40 – 1.21 (m, 20 H). 13C-NMR: 130.1 (2d); 112.2 (s); 64.3 (2t); 35.8 (2t); 32.4
(2t); 29.2 (2t); 28.7 (2t), 27.8 (2t); 27.1 (2t), 22.9 (2t). MS: 294 (3, Mþ), 251 (5), 155 (32), 142 (11), 99
(100), 86 (14), 67 (10), 55 (19).
For the hydrolysis of III to civetone (IVa), see [20]31).
31
)
When civetone (IVa; (E)/(Z) < 5:95 ) was treated under Favorskii conditions, we isolated the
macrocyclic methoxycarbonyl derivative VIII (7%). Furthermore, when civetone IVa was treated
under CoreyꢀChaykovsky conditions, (11Z)-1-oxaspiro[2.16]nonadec-11-ene (IVb) was isolated in
94% yield (Scheme 3). Its hydrogenation afforded the corresponding saturated 1-oxaspiro
compound 4h. Earlier treatment of 3c with BF3 · Et2O afforded, after a three-step sequence, a
complex mixture of the conjugated/deconjugated cycloundecenones [38a]. (2E)-Cyclopentadec-2-
en-1-one (IXa; Scheme 4) may be readily obtained from cyclopentadecanone (1f), either in a single
step according to Nicolaouꢃs protocol [56a – c] (o-iodoxybenzoic acid, PhF, DMSO, 658, yield 83%),
or in a two-step low-temperature lithium diisopropylamide (LDA) deprotonation with Me3SiCl
quenching, followed by oxidation with stoichiometric [Pd(OAc)2] according to either Schꢁfer and
co-workers [57a] (yield 80%) or Rꢂedi and Hansen [57b] (yield 85%), or via an efficient four-step
sequence (Scheme 4) comprising acetalization to Xa [58] (ethylene glycol, cyclohexane, TsOH, yield
98%), bromination to XIa [58b][58c] (PhMe3NþBr3ꢀ, THF, yield 98%; 13C-NMR: 22.2 (t); 25.9 (t);
26.4 (2t); 26.5 (2t); 26.6 (t); 26.8 (2t); 26.9 (t); 27.4 (t); 32.3 (t); 35.4 (t); 61.1 (d); 65.6 (t); 66.1 (t); 111.0
(s)), elimination to XIIa (MeOK (see [58d] for MeONa as base), DMSO, yield 99%; 13C-NMR: 23.4
(t); 25.9 (t); 26.8 (t); 26.9 (2t); 27.1 (2t); 27.2 (t); 28.0 (t); 28.3 (t); 31.1 (t); 38.7 (t); 64.2 (2t); 109.6 (s);
130.1 (d); 132.5 (d)), and deprotection to IXa [58] (10% aq. HCl soln., acetone, yield 90%), by
analogy with Mookherjeeꢃs report [58b]. For alternative syntheses, see [59]. We applied this
sequence also to cyclohexadecanone (1g), via the uncharacterized acetal Xb [60] and its unreported
intermediates XIb and XIIb, for the preparation of the musk-like (2E)-cyclohexadecenone IXb
[44][61] (m.p. 30 – 328, 13C-NMR: 25.1 (t); 26.2 (t); 26.4 (t); 26.5 (t); 26.7 (t); 26.9 (t); 27.0 (t); 27.1 (t);
.
27.3 (t); 27.4 (2t); 31.6 (t); 38.9 (t); 131.3 (d); 148.2 (d); 201.7 (s); MS: 236 (79, Mþ ), 178 (15), 137
(18), 135 (17), 123 (20), 121 (18), 109 (82), 96 (100), 81 (91), 68 (48), 55 (87), 41 (56)). (ꢀ)-(R)-5f was
obtained in 35% yield (62% ee) from IXb, after 24 h at 208, by analogy with [62]. (2E,14E)-
Cyclopentadeca-2,14-dien-1-one was isolated in only 12% yield from 1f, under HIO3/DMSO/
cyclohexene conditions [56d].

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(11Z)-1-Oxaspiro[2.16]nonadec-11-ene (IVb). According to G.P.D. Yield 94%. IR: 3000, 2920,
1
2853, 1459, 1398, 1367, 990, 903, 715. H-NMR: 5.34 (t, J ¼ 5, 2 H); 2.55 (s, 2 H); 2.10 – 2.03 (m, 4 H);
1.65 – 1.56 (m, 2 H); 1.46 – 1.27 (m, 22 H). 13C-NMR: 130.2 (2d); 59.4 (s); 53.8 (t); 34.5 (2t); 29.3 (2t); 28.8
(2t); 28.2 (2t); 27.8 (2t); 27.0 (2t); 24.0 (2t). MS: 264 (20, Mþ), 246 (10), 149 (12), 135 (28), 121 (35), 109
(42), 95 (81), 81 (93), 67 (94), 55 (100), 41 (83). Fruity, marmalade, green, geranium leaf, weak.
Thiacyclooctadecan-10-one (Va). A soln. of acetal IIa (1.0 g, 3.04 mmol) in THF (5 ml) and H2O
(5 ml) was hydrolyzed at 208 for 18 h in the presence of conc. HCl soln. (1 ml). The mixture was diluted
with Et2O, neutralized with sat. NaHCO3 soln., and then extracted 3 times with Et2O. The org. phase was
washed with H2O, dried (Na2SO4), and concentrated. Recrystallization from EtOH afforded Va (58%).
M.p. 72 – 73.58. IR: 2918, 2850, 1700, 1471, 1415, 1379, 1310, 1256, 1226, 1112, 1064, 966, 718, 680, 646.
1H-NMR: 2.51 (t, J ¼ 7.7, 4 H); 2.41 (t, J ¼ 6, 4 H); 1.63 (quint., J ¼ 8, 4 H); 1.58 (quint., J ¼ 7, 4 H); 1.42
(quint., J ¼ 6.7, 4 H); 1.35 – 1.28 (m, 12 H). 13C-NMR: 212.3 (s); 42.1 (2t); 31.4 (2t); 28.8 (2t); 28.2 (2t);
28.1 (2t); 28.0 (2t); 27.3 (2t); 23.8 (2t). MS: 284 (28, Mþ), 201 (8), 153 (11), 129 (35), 96 (21), 87 (43), 81
(24), 69 (44), 55 (100), 41 (74).
Thiacyclooctadecan-10-one 1,1-Dioxide (Vb)32). As described for Va : Vb (60%). IR: 2920, 2855,
1702, 1461, 1289, 1270, 1125, 1077, 825. 1H-NMR: 2.96 (t, J ¼ 8, 4 H); 2.41 (t, J ¼ 6, 4 H); 1.81 (quint., J ¼ 7,
4 H); 1.62 (quint., J ¼ 7, 4 H); 1.48 (quint., J ¼ 6, 4 H); 1.39 – 1.27 (m, 12 H). 13C-NMR: 212.1 (s); 51.4
(2t); 42.1 (2t); 28.0 (2t); 27.9 (2t); 27.6 (2t); 27.2 (2t); 23.5 (2t); 21.8 (2t). MS: 316 (45, Mþ), 259 (18), 229
(9), 163 (63), 155 (59), 111 (20), 97 (97), 69 (53), 55 (100), 41 (50).
1,17-Dihydroxyheptadecan-9-one (VIa). As described for Va : VIa (quant.). IR: 3259, 2916, 2883,
2849, 1704, 1487, 1472, 1461, 1407, 1379, 1343, 1323, 1285, 1270, 1243, 1202, 1119, 1060, 1030, 1012, 993,
967, 942, 922, 882, 848, 809, 762, 731, 719, 680. 1H-NMR : 3.63 (t, J ¼ 6.5, 4 H); 2.38 (t, J ¼ 7.7, 4 H); 1.62
(br. s, 2 H); 1.56 (quint., J ¼ 6.5, 8 H); 1.36 – 1.26 (m, 16 H). 13C-NMR: 211.9 (s); 63.0 (t); 42.8 (t); 32.8 (t);
29.3 (t); 29.2 (t); 29.1 (t); 25.7 (t); 23.8 (t). MS: 286 (5, Mþ), 207 (14), 172 (46), 157 (14), 139 (20), 129
(19), 111 (28), 97 (39), 71 (41), 69 (87), 58 (37), 55 (100), 41 (41).
1,17-Dibromoheptadecan-9-one (VIb). As described for Va : VIb (quant.). IR: 2958, 2913, 2887,
2850, 1700, 1471, 1415, 1378, 1310, 1262, 1254, 1243, 1224, 1112, 1067, 1055, 998, 974, 967, 718, 645.
1H-NMR: 3.40 (t, J ¼ 8, 4 H); 2.39 (t, J ¼ 7, 4 H); 1.85 (quint., J ¼ 7, 4 H); 1.56 (quint., J ¼ 8, 4 H); 1.45 –
1.38 (m, 4 H); 1.33 – 1.26 (m, 12 H). 13C-NMR: 211.5 (s); 42.8 (2t); 34.0 (2t); 32.8 (2t); 29.2 (2t); 29.1 (2t);
28.6 (2t); 28.1 (2t); 23.8 (2t). MS: 412 (2, Mþ), 333 (7), 331 (6), 249 (13), 247 (14), 236 (33), 234 (31), 221
(67), 219 (69), 176 (30), 155 (49), 137 (20), 69 (99), 55 (100), 41 (65).
9-Oxoheptadecane-1,17-diyl Diacetate (¼1,17-Bis(acetyloxy)heptadecan-9-one; VIc). As described
for Va : VIc (quant.). IR: 2947, 2926, 2912, 2850, 1731, 1702, 1479, 1462, 1418, 1396, 1371, 1295, 1243, 1122,
1053, 1023, 965, 892, 757, 729, 718, 682, 646, 608. 1H-NMR: 4.05 (t, J ¼ 8, 4 H); 2.39 (t, J ¼ 7, 4 H); 2.05 (s,
6 H); 1.63 – 1.54 (m, 8 H); 1.36 – 1.25 (m, 16 H). 13C-NMR: 211.5 (s); 171.2 (2s); 64.6 (2t); 42.8 (2t); 29.3
(2t); 29.2 (2t); 29.1 (2t); 28.6 (2t); 25.9 (2t); 23.8 (2t), 21.0 (2q). MS: 370 (1, Mþ), 227 (15), 214 (75), 157
(62), 154 (36), 139 (66), 111 (41), 97 (100), 69 (71), 55 (84), 43 (80).
8-(Acetyloxy)octyl 9-(Acetyloxy)nonanoate (VIIa). A mixture of VIc (28.0 g, 63.4 mmol) and m-
CPBA (70%; 35.0 g, 140 mmol) in CHCl3 (200 ml) was heated at 508 for 48 h. The solvent was
evaporated and replaced by Et2O. The soln. was washed with NaHSO3 soln., H2O, 30% aq. NaHCO3
soln., and brine to neutrality, dried (Na2SO4) and concentrated: pure VIIa (85%). IR: 2945, 2920, 2910,
1728, 1370, 730. 1H-NMR: 4.06 (t, J ¼ 7, 2 H); 4.05 (t, J ¼ 7, 2 H); 4.04 (t, J ¼ 7, 2 H); 2.3 (t, J ¼ 8, 2 H); 2.05
(s, 6 H); 1.66 – 1.59 (m, 8 H); 1.40 – 1.30 (m, 16 H). 13C-NMR: 173.9 (s); 171.2 (2s); 64.6 (2t); 64.3 (t); 34.4
(t); 29.1 (5t); 28.6 (3t); 25.9 (3t); 25.0 (t); 21.0 (2q). MS: 386 (0, Mþ), 217 (10), 199 (100), 157 (60), 148
(32), 110 (50), 69 (50), 43 (48).
32
)
In some instances, a partial oxidation allowed the isolation of traces of the corresponding odorless
thiacyclooctadecan-10-one 1-oxide: 1H-NMR: 2.74 (t, J ¼ 6, 4 H); 2.48 – 2.34 (m, 4 H); 1.87 – 1.77 (m,
2 H); 1.77 – 1.66 (m, 2 H); 1.66 – 1.55 (m, 4 H); 1.48 (quint., J ¼ 7, 4 H); 1.37 – 1.25 (m, 12 H).
13C-NMR: 211.9 (s); 51.6 (t); 42.1 (t); 28.0 (t); 27.9 (t); 27.6 (t); 27.2 (t); 23.5 (t); 21.8 (t). MS: 300 (12,
.
M
þ ), 255 (10), 251 (8), 217 (11), 183 (20), 143 (28), 139 (24), 111 (50), 94 (36), 69 (70), 55 (100), 41
(42).

Helvetica Chimica Acta – Vol. 95 (2012)
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9-Hydroxynonanoic Acid (VIIb). A soln. of VIIa (42.0 g, 109 mmol) and NaOH (17.2 g, 430 mmol)
in EtOH (500 ml) was heated under reflux for 15 h. The solvent was evaporated and, replaced by Et2O
and the soln. washed with H2O. After acidification (pH 2) of the aq. phase with 15% HCl, and extraction
with Et2O, the org. phase was washed with brine to neutrality, dried (Na2SO4), and concentrated: pure
VIIb (89%). IR: 3240; 2912, 1710, 728. 1H-NMR: 7.08 (br s, 2 H); 3.63 (t, J ¼ 7, 2 H); 2.33 (t, J ¼ 7, 2 H ) ;
1.66 – 1.52 (m, 4 H); 1.36 – 1.29 (m, 8 H). 13C-NMR: 179.0 (s); 62.7 (t); 34.1 (t); 32.4 (t); 29.2 (t) ; 29.1 (t) ;
29.0 (t) ; 25.6 (t); 24.7 (t). MS: 174 (0, Mþ), 144 (18), 110 (18), 97 (28), 84 (30), 73 (53), 69 (33), 60 (50),
55 (100), 41 (51).
(1Z,9Z)-Methyl Cyclohexadeca-1,9-diene-1-carboxylate VIII. According to G.P.A. Yield
7%. B.p. 1308/0.25 mbar. IR: 3000, 2924, 2854, 1717, 1641, 1459, 1434, 1376, 1348, 1191, 1162, 1030, 969,
907, 810, 776, 718. 1H-NMR: 5.86 (t, J ¼ 7.8, 1 H); 5.45 – 5.30 (m, 2 H); 3.74 (s, 3 H); 2.5 – 2.44 (m, 2 H);
2.35 – 2.28 (m, 2 H); 2.07 – 1.97 (m, 4 H); 1.51 – 1.41 (m, 4 H); 1.39 – 1.24 (m, 12 H). 13C-NMR: 168.8 (s);
143.0 (d); 131.4 (s); 130.1 (d); 129.9 (d); 51.1 (q); 34.1 (t); 29.6 (t); 29.2 (2t); 28.9 (t); 27.8 (2t); 27.7 (t); 27.3
(t); 26.8 (t); 26.1 (t); 25.5 (t). MS: 278 (37, Mþ), 247 (24), 219 (24), 161 (12), 149 (19), 135 (34), 121 (40),
109 (40), 95 (83), 81 (100), 67 (94), 55 (66), 41 (70).
1,4-Dioxaspiro[4.15]icosane (Xb; Scheme 4). In a DeanꢀStark apparatus, a soln. of ketone 1g (66.6 g,
280 mmol), ethylene glycol (25 g, 400 mmol), and TsOH (1 g, 9.8 mmol), in cyclohexane (600 ml) was
heated under reflux for 48 h, and H2O was collected. The cold soln. was extracted with H2O/Et2O, washed
with NaHCO3 soln. and then brine to neutrality, dried (Na2SO4), and concentrated and the residue
distilled through a Vigreux column: Xb (91%). B.p. 125 – 1278/0.1 mbar. M.p. 35 – 368. IR: 2924, 2855,
1459, 1348, 1287, 1188, 1146, 1069, 945, 892, 831, 711. 1H-NMR: 3.91 (s, 4 H); 1.61 – 1.57 (t, J ¼ 10.9, 4 H);
1.4 – 1.25 (m, 26 H). 13C-NMR: 112.2 (s); 64.3 (2t); 35.4 (2t); 27.2 (2t); 26.9 (2t); 26.6 (2t); 26.3 (t); 26.3
(2t); 25.8 (2t); 22.7 (2t). MS: 282 (18, Mþ), 239 (29), 155 (29), 99 (100), 86 (16), 55 (23), 41 (22). Without
character.
Scheme 4
a) PhMe3NþBrꢀ3 , THF. b) MeOK, DMSO. c) 10% aq. HCl soln., acetone.
6-Bromo-1,4-dioxaspiro[4.15]icosane (XIb). PhMe3NBr3 (10.2 g, 270 mmol) was added portionwise
to a soln. of Xb (70 g, 250 mmol) in THF (2 l) at 08. After 3 h at 08, sat. NaHCO3 soln. (500 ml) was
added, and the solvent was evaporated. The aq. soln. was extracted with Et2O, and the org. phase was
washed with NaHCO3 soln. and then brine to neutrality, dried (Na2SO4), and concentrated: XIb
1
(quant.). IR: 2924, 2854, 1105, 710. H-NMR: 4.24 – 4.14 (m, 1 H); 4.01 – 3.96 (m, 1 H); 3.76 – 3.73 (m,
2 H); 3.46 (t, J ¼ 8, 1 H); 2.0 – 1.92 (m, 2 H); 1.88 – 1.83 (m, 2 H); 1.77 – 1.69 (m, 4 H); 1.55 – 1.2 (m,
20 H). 13C-NMR: 111.0 (s); 68.0 (t); 65.7 (t); 60.9 (d); 35.4 (t); 32.7 (t); 29.2 (t); 27.3 (t); 26.8 (t); 26.7 (t);
26.6 (2t); 26.4 (2t); 26.3 (t); 26.1 (t); 25.8 (t); 22.3 (t). MS: 362 (4), 360 (4, Mþ), 319 (10), 317 (10), 281
(49), 155 (23), 99 (100), 55 (16).
(6E)-1,4-Dioxaspiro[4.15]icos-6-ene (XIIb). MeOK (53 g, 760 mmol) was added in one portion to a
soln. of XIb (98 g, 250 mmol) in DMSO (360 ml). After 3 h at 208, the mixture was poured onto brine and
extracted with pentane, the extract dried (Na2SO4) and concentrated, and the residue distilled through a
Vigreux column: pure XIIb (65%). B.p. 120 – 1288/0.2 mbar. IR: 2923, 2854, 1459, 1337, 1257, 1184, 1121,

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Helvetica Chimica Acta – Vol. 95 (2012)
1
1045, 973, 945, 909, 805, 723. H-NMR: 5.71 (dt, J ¼ 9, 19.2, 1 H); 5.3 (d, J ¼ 19.2, 1 H); 3.95 – 3.85 (m,
4 H); 2.11 (q, J ¼ 7.7, 2 H); 1.70 – 1.65 (m, 2 H); 1.4 – 1.2 (m, 22 H). 13C-NMR: 132.2 (d); 129.8 (d); 109.5
(s); 64.2 (2t); 38.9 (t); 31.7 (t); 28.4 (t); 28.0 (2t); 27.4 (t); 27.3 (2t); 26.2 (t); 25.8 (t); 25.2 (t); 25.0 (t); 23.7
(t); MS : 280 (12, Mþ), 237 (22), 183 (27), 125 (100), 99 (40), 55 (15). Vaguely woody, very weak.
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