CHEMISTRY & BIODIVERSITY – Vol.

5 (2008) 1083

The Search for Innovative Fragrant Molecules

by Caroline Plessis
Mane S.A., Chemistry Research Center, 620 route de Grasse, F-06620 Le Bar-sur-Loup
(phone: þ 33 4 9309 7000; fax: þ 33 4 9342 5425; e-mail: [email protected])

An overview of the recent research subjects in the perfumery field and, more precisely the synthesis
of novel compounds for the hesperidic family of odorants, is presented. The new derivatives possess very
different structures; nevertheless, they all share an aldehydic odor, but with diverse nuances, which make
them all attractive for different purposes.

Introduction. – Discovering interesting new fragrance ingredients in each family of

odorants, and being highly innovative in an extremely competitive environment is a real
challenge for small companies today [1]. Yet, it still proves possible, and an overview of
the recent research products developed at Mane is presented.
In this contribution, we mainly focus on molecules of the aldehydic family of
odorants, but this also will lead us to interesting new insights into the fruity and floral
families. Work on new norbornyl derivatives [2] in the context of the woody family will
be described in the following article. The different topics that are discussed here include
derivatives of campholenic aldehyde with unexpected non-woody odors [3], deriva-
tives of 5,7-dimethylocta-1,6-diene, especially an intense and pleasant smelling
aldehyde obtained by hydroformylation [4], and new d-lactones and tetrahydropyrans
with interesting citrus and fruity odors [5].

Campholenic Aldehyde Derivatives. – Compounds derived from campholenic

aldehyde ( ¼ 2,2,3-trimethylcyclopent-3-ene-1-acetaldehyde) usually exhibit sandal-
wood-type notes [1], and this was also initially the aim of our work when we began the
synthesis of new derivatives of this class. It is of course well-known that certain
prerequisites need to be met to obtain a sandalwood odor [1] [6], such as an optimal
distance between a bulky group and the osmophore, the most polar functional group,
which, in most cases, bears an O-atom, which in the sandalwood family most often is a
OH function. It was thus proposed to prepare, via a simple and elegant pathway, the
new compounds 1 (Scheme 1), although these structures do not possess the ideal
requirements to emanate sandalwood odors. Two close examples, 1a and the isomeric
1a’, had previously been described for use in perfumery, and 1a had been mentioned to
possess a sandalwood-floral odor [7].
Our synthesis consisted in preparing the new compounds 1 (Scheme 1) from the
corresponding alcohols 2, obtained by reaction of campholenic aldehyde with suitable
Grignard reagents. The alcohols 2 were converted into the required vinyl ethers, which
easily underwent Claisen rearrangement to afford aldehydes 3. These aldehydes 3 were

B 2008 Verlag Helvetica Chimica Acta AG, ZDrich

1084 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

Scheme 1

then further reduced to the alcohols 1. Following this reaction scheme, alcohols 1b and
1c were obtained, using vinylmagnesium bromide and isopropenylmagnesium bromide,
respectively (Scheme 2).

Scheme 2

However, this elegant synthesis was not so easy to perform. It was essential to avoid
methods involving Hg to obtain the intermediate vinyl ethers, and the alternative
methods with Pd catalysts required well-purified alcohols 2. Unfortunately, whereas the
Grignard reactions proceeded cleanly with total conversion, the purification by
distillation happened to be difficult, leading to by-products (presumably due to
polymerization of the allylic alcohols), lowering the yield dramatically. At that point, it
was actually found that the alcohols 1 were not very interesting, possessing only slightly
sandalwood or vague woody odors. However, the intermediate aldehydes 3 were found
to be far more interesting, emanating intense aldehydic, floral, non-woody odors.
It was, therefore, necessary to investigate this substance class further, and to
prepare other aldehydes of that kind, but other routes needed to be developed to
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1085

achieve an easy access to the differently substituted target molecules. Finally, two
rather simple routes with possible industrial scale-up were found interesting to obtain
the desired compounds. The first one of them involved a Wittig reaction, and the first
compound prepared that way was aldehyde 3b (FleurenalH ; Scheme 3). The ylide of
phosphonium salt 4, easily obtained from commercially available 4-chlorobutanenitrile,
was condensed with campholenic aldehyde to provide intermediate nitrile 5b, as a 9 : 1
(Z)/(E)-mixture. The nitrile 5b was further reduced by diisobutylaluminum hydride
(DIBAL-H) to furnish aldehyde 3b in 36% overall yield. Compound (þ)-3b has also
been prepared from (þ)-(R)-campholenic aldehyde with a similar yield, without
significant change in the power or character of the odor.

Scheme 3

Half-hydrogenated nitrile 5’b and its corresponding aldehyde 3’b, derived from
hydrogenated campholenic aldehyde were also prepared with similar yields. Starting
from the same phosphonium salt 4, the methylated aldehyde 3c was prepared in a
similar manner. Prior to the Wittig reaction, phosphonium salt 4 was alkylated with
MeI, and 3c was obtained as a 1 : 1 (Z)/(E)-mixture in 30% overall yield (Scheme 4).

Scheme 4

The alternative pathway consisted in preparing fully hydrogenated nitriles 5’’ via
malonic ester synthesis with cyanoacetic acid and a suitable carbonyl compound 6,
obtained by aldolization from campholenic aldehyde (Scheme 5). Prior to reduction
with DIBAL-H to the target aldehydes, the intermediate diene nitriles were fully
1086 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

Scheme 5

reduced to 5’’. Thus were obtained saturated aldehydes 3’’ in overall yields between 20
and 25%.
Starting from aldehydes 3, a variety of other derivatives were also prepared. Thus,
diethyl acetals 7b and 7’’d (see below) were obtained from 3b and 3’’d, respectively.
Aldehyde 3’’c was methylated by known methods to give 3’’e [8], and ketone 8 was
synthesized by reacting MePh3PBr with nitrile 5b (Scheme 6) [9].

Scheme 6

Finally, although we did not achieve an interesting sandalwood odorant, this project
afforded many new molecules, from nitriles to aldehydes and their acetals, with a wide
odor range, from typically aldehydic odorants to derivatives with floral, marine, or even
animalic aspects (see Table 1).

5,7-Dimethylocta-1,6-diene Derivatives. – 5,7-Dimethylocta-1,6-diene (9) was

described and used as a starting material for fragrance ingredients already 40 years
ago. Hydroboration and hydration were employed to prepare alcohol and ester
derivatives [10]. Astonishingly, we found that hydroformylation was never attempted
with this diene, and we speculated that the products of such reactions could possess
interesting olfactory properties for application in perfumery.
During the course of the hydroformylation reaction, which is mediated by
transition-metal catalysts, a H-atom and a CHO group are formally added across the
(usually terminal) C¼C bond of an alkene. The recent development of Rh catalysts, as
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1087

Table 1. Odor Descriptions of Campholenic Aldehyde Derivatives

Compound R1 R2 R3 Y C¼C Bonds Odor description

1b H H H CH2OH C(3’)¼C(4’), Slightly woody (sandalwood)
C(3)¼C(4)
3b H H H CHO C(3’)¼C(4’), Floral (lily of the valley), green,
C(3)¼C(4) very Powerful
3’b H H H CHO C(3)¼C(4) Powerful, floral (lily of the valley), green
3c Me H H CHO C(3’)¼C(4’), Floral (lily of the valley), LilialH, LyralH
C(3)¼C(4)
3’’c Me H H CHO None Slightly woody, green, lactonic (wax),
plastic
3’’d Et H H CHO None Sweet (furaneol), animalic (costus, goat),
a bit metallic
3’’a H Me H CHO None Marine, ozonic, transparent (MelonalH )
3’’e Me H Me CHO None None
5b H H H CN C(3’)¼C(4’), Slightly woody (cedarwood), floral
C(3)¼C(4)
5’b H H H CN C(3)¼C(4) Not powerful, floral ( HelionalH,
FloralozoneH )
5c Me H H CN C(3’)¼C(4’), Slightly anisic, fruity
C(3)¼C(4)
5’’c Me H H CN None Sweet, gourmand, not powerful
5’’d Et H H CN None Iris, carrot, powdery, plastic
5’’’c Me H H CN C(2)¼C(3) Woody (sandalwood), lactonic,
a bit animalic
7b H H H CH(OEt)2 C(3’)¼C(4’), Plastic, not powerful
C(3)¼C(4)
7’’d Et H H CH(OEt)2 None Fruity (apple), alcoholic, animal, cresolic
8 H H H C(O )Me C(3’)¼C(4’), Green (fig leaves), sweet
C(3)¼C(4)

well as the design of new phosphine ligands, allow relatively mild reaction conditions
and provide excellent chemo- and regioselectivities in this highly atom-efficient
process. Thus, the terminal C¼C bond of 9 should undergo hydroformylation with
introduction of a valuable CHO function.
Hence, 5,7-dimethylocta-1,6-diene (9) was treated under a CO/H2 atmosphere in
the presence of a Rh catalyst and a suitable ligand to give a mixture of aldehydes 10
(NoreenalH ) and 11 (Scheme 7).
By tuning the catalyst or the ligand, the ratio of linear vs. branched aldehyde (10/11
ratio) could be modified, and using, for instance, bis-(h4-cycloocta-1,5-diene)di-m-
methoxydirhodium(I) as catalyst and XantphosH as ligand, under 30 bars of syngas
(equimolar CO/H2 mixture) at 70 – 808, gave almost exclusively the linear derivative
10 in 75% yield. This aldehyde has a very intense aldehydic odor in the mandarin
range.
1088 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

Scheme 7

When using monophosphine ligands such as Ph3P, the selectivity towards the linear
products was reduced, and a mixture enriched in 11 was obtained. Fine distillation
furnished purely the branched isomer 11, which was found greener in smell, reminiscent
of citronella and parsley. Other derivatives were then prepared from NoreenalH (10)
and its hydrogenation product 10’ (obtained in 96% yield by hydrogenation over Pd/C),
including alcohols, esters, and acetals (Scheme 8). Thus, alcohols 12 and 12’ were
obtained by reduction of 10 and 10’, respectively, with NaBH4 in 73 and 54% yield.

Scheme 8
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1089

Compounds 12 and 12’ were further esterified to provide in 76% the acetates 13a and
13’a, respectively, and the propanoate 13b was prepared from 12 in 71% yield. The
different acetals 14 and 14’ were also obtained in good yields from 10 and 10’,
respectively. The saturated acetals 14’ have also been prepared by hydrogenation of the
corresponding acetals 14 in quantitative yields.
Similarly, derivatives of the branched aldehyde 11 were synthesized, such as 2,5,7-
trimethyloct-6-en-1-ol and 2,5,7-trimethyloct-6-en-1-yl acetate [11]. All those novel
derivatives possess various interesting and nice aldehydic odors, with green, floral, or
fruity aspects as compiled in Table 2.

Table 2. Odor Descriptions of the 6,8-Dimethylnon-7-ene Derivatives

Compound Odor description

10 Aldehydic, mandarin, very powerful
10’ Aldehydic, bigarade orange, fruity
11 Aldehydic, green, citronella, parsley
12 Aldehydic, rosy, green
12’ Aldehydic, fruity (peach), rosy
13a Aldehydic, nitrile, cinnamic
13b Aldehydic, fruity (pear, dry fruits), cinnamic, floral
14a Green (peas), grapefruit
14’a Fruity (apple, pineapple), green, hesperidic
14’b Peach, apricot (juice)

New d-Lactones and Tetrahydropyrans. – New d-lactones and tetrahydropyrans

were also found to possess interesting citrus and fruity notes. The unknown g-
substituted d-lactones 15 were prepared along with their parent tetrahydropyrans 16 on
a convergent route (Scheme 9). Michael addition of the morpholino enamine of a
suitable starting aldehyde to methyl acrylate provided 17. The aldehyde function could
be selectively reduced to the alcohol 18 to provide either the lactone 15, or, by further
reduction via the diol 19, the tetrahydropyrans 16. Different derivatives were prepared
in good overall yields, displaying mostly fruity, citrus odor profiles (Table 3).

Table 3. Odor Descriptions of the New d-Lactones and Pyrans

Compound Odor description

H
15a ( Figolide ) Lactonic, fig leaves, coconut
15b ( VerbenolideH ) Lemony, nitrile, green, lactonic
16c (CilandraneH ) Mandarin, coriander, green, lactonic
16d ( BetahydraneH ) Metallic, nitrile, rhubarb

So, this project gave also birth to unexpected interesting aldehydic odorants with
green or fruity aspects. These derivatives have a major advantage over the common
aldehydes perfumery raw materials: they are less fragile than the latter.
1090 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

Scheme 9

In conclusion, the aldehydic family of odorants has been enriched with new
interesting compounds possessing very different structures – a valuable benefit to the
field of perfumery. These compounds are likely to find their way into many different
applications, as, furthermore, their novel nuances make them very attractive in
enhancing floral, marine, or fruity compositions.

Experimental Part
General. All reagents and solvents were commercially available, and were used without any further
purification, unless otherwise mentioned. GC: HP 6890 with a polar DBWAX-FF column. IR Spectra:
Biorad fts-155 spectrophotometer. NMR Spectra: Bruker 200 MHz instrument in CDCl3 . MS: Normag
quadrupole RIO-IC spectrometer.
6-(2,2,3-Trimethylcyclopent-3-enyl)hex-4-enenitrile (5b). A suspension of (3-cyanopropyl)triphenyl-
phosphonium chloride (365.8 g, 1 mol; readily prepared by reaction between Ph3P and 4-chlorobuta-
nenitrile), K2CO3 (276 g, 2 mol), commercial campholenic aldehyde (180 g, 1.02 mol), and a cat. amount
of PhCOOH (6.1 g, 0.05 mol) in toluene (1.5 l) was refluxed for 24 h. The mixture was then cooled down
and filtered. The filtrate was washed twice with warm H2O, dried (MgSO4 ), and the solvents were
evaporated to afford an oily crude product, which was triturated with t-BuOMe to precipitate most of the
phosphine oxide. After filtration, the solvents were evaporated, and the crude oil was distilled.
Compound 5b (136 g, 0.67 mol, 67%) was obtained as a 9 : 1 (Z)/(E)- mixture of isomers. B.p. 98 – 1008/
0.76 – 0.79 Torr. IR (neat): 798m, 1013w, 1360m, 1444m, 1463m, 1653w, 2246w, 2835m, 2866s, 2895s, 2930s,
2956s, 3013w, 3035w.
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1091

Data of (Z)-5b: 1H-NMR (CDCl3 ): 0.83 (s, 3 H); 1.03 (s, 3 H); 1.6 – 1.65 (m, 3 H); 1.75 – 1.95 (m,
2 H); 1.95 – 2.4 (m, 3 H); 2.4 – 2.55 (m, 4 H); 5.2 – 5.3 (m, 1 H); 5.35 – 5.7 (m, 2 H). 13C-NMR (CDCl3 ):
13.02; 17.93; 20.13; 23.76; 26.28; 28.32; 35.93; 47.15; 50.66; 119.82; 212.99; 125.57; 133.51; 148.83.
Data of (E)-5b: 1H-NMR (CDCl3 ; selected data): 0.80 (s, 3 H); 1.01 (s, 3 H). 13C-NMR (CDCl3 ):
18.14; 28.81; 33.69; 50.41; 122.08; 126.41; 134.25; 148.89. EI-MS (70 eV): 203 (10, M þ ), 188 (100), 171
(38), 160 (19), 147 (35), 133 (19), 121 (31), 109 (83), 108 (91), 107 (26), 105 (24), 95 (26), 94 (31), 93
(44), 91 (44), 81 (19), 79 (40), 77 (33), 55 (36), 53 (27), 41 (72), 39 (26). Odor description: slightly
woody (cedarwood), floral.
(þ)-6-[(1R)-2,2,3-Trimethylcyclopent-3-enyl]hex-4-enenitrile ((þ)-5b). Prepared from (þ)-(R)-
campholenic aldehyde (152 g, 1 mol) in 62% yield as described for 5b. [a]D ¼ þ 1.92 (neat).
6-(2,2,3-Trimethylcyclopentyl)hex-4-enenitrile (5’b). Prepared from 2H-dihydrocampholenic alde-
hyde (25 g, 0.163 mol) in 56% yield as described for 5b. The product was obtained as a 9 : 1 (Z)/(E)-
mixture. B.p. 828/0.02 Torr. IR (neat): 1367m, 1388w, 1428m, 1453m, 1465m, 1660w, 1710w, 1727w, 2247m,
2870s, 2955s, 3013m.
Data of (Z)-5’b: 1H-NMR (CDCl3 ): 0.53 (s, 3 H); 0.82 (d, J ¼ 6.7, 3 H); 0.88 (s, 3 H); 1.05 – 1.25 (m,
2 H); 1.25 – 1.55 (m, 2 H); 1.55 – 1.90 (m, 3 H); 2.05 – 2.25 (m, 1 H); 2.27 – 2.47 (m, 4 H); 5.20 – 5.40 (m,
1 H); 5.45 – 5.65 (m, 1 H). 13C-NMR (CDCl3 ): 13.82; 14.33; 17.47; 23.24; 25.60; 28.13; 28.27; 29.85; 44.97;
50.89; 119.34; 124.67; 133.30.
Data of (E)-5’b: 1H-NMR (CDCl3 , selected data): 0.50 (s, 3 H); 0.84 (s, 3 H). 13C-NMR (CDCl3 ):
12.54; 17.67; 19.65; 25.80; 27.84; 28.01; 33.69; 35.45; 50.18; 50.52; 119.34; 125.05; 133.03. EI-MS (70 eV):
205 (1, M þ ), 190 (7), 188 (4), 162 (8), 148 (13), 134 (8), 120 (6), 111 (72), 109 (18), 95 (24), 84 (33), 70
(22), 69 (100), 67 (25), 55 (38), 41 (41). Odor description: not powerful, floral (HelionalH,
FloralozoneH ).
4-Methyl-6-(2,2,3-trimethylcyclopent-3-enyl)hex-4-enenitrile (5c). To a suspension of (3-cyanopro-
pyl)triphenylphosphonium chloride (180 g, 0.49 mol) in THF (0.6 l) was added portionwise t-BuOK
(60.8 g, 0.54 mol). After stirring at r.t. for 30 min, the mixture was cooled down (ice bath) before slowly
adding MeI (34 ml, 0.54 mol). The mixture was stirred for a further h, and another equiv. of t-BuOK
(60.8 g, 0.54 mol) was added portionwise. After stirring at r.t. for another h, campholenic aldehyde (97 g,
0.55 mol) was added, and the mixture was further stirred overnight. The mixture was poured into 1 : 1
H2O/t-BuOMe (600 ml). The separated aq. layer was acidified and extracted three times with t-BuOMe
(200 ml). The combined org. layers were washed twice with H2O (200 ml), then with sat. aq. NaHCO3
(250 ml) and with brine (250 ml). After drying (MgSO4 ), the solvents were evaporated, and the crude
product was purified by distillation. B.p. 104 – 1068/0.7 – 0.8 Torr. Compound 5c was obtained as a 1 : 1
(Z)/(E)-mixture (52 g, 42%). IR (neat): 799m, 1013w, 1356m, 1382w, 1445m, 1462m, 1691w, 2246w,
2835m, 2866m, 2930s, 2956s, 3036w. 1H-NMR (CDCl3 ): 0.79 (s, 3 H); 0.99 (s, 3 H); 1.58 – 1.63 (m, 3 H);
1.63 – 2.53 (m, 12 H); 2.41 (s, 3 H); 5.2 – 5.25 (m, 1 H); 5.25 – 5.38 (m, 1 H). 13C-NMR (CDCl3 ): 12.57;
15.64/15.84; 16.31/22.72; 19.68; 25.84/25.87; 27.56; 28.36/28.5; 35.07; 35.48/35.52; 46.68; 50.34/50.53;
119.47/119.52; 121.56/121.69; 127.43/128.48; 130.79/130.9; 148.41/148.49. EI-MS (70 eV): (Z)-5c: 217 (12,
M þ ), 202 (19), 185 (13), 146 (12), 122 (45), 121 (93), 109 (100), 108 (93), 107 (83), 95 (31), 93 (48), 91
(48), 81 (63), 79 (54), 77 (35), 67 (76), 55 (37), 53 (34), 41 (66), 39 (23). (E)-5c: 217 (15, M þ ), 202 (27),
185 (5), 146 (10), 122 (54), 121 (100), 109 (99), 108 (100), 107 (90), 95 (33), 93 (48), 91 (50), 81 (64), 79
(53), 77 (35), 67 (75), 55 (35), 53 (33), 41 (61), 39 (22). Odor description: slightly anisic, fruity.
4-Methyl-6-(2,2,3-trimethylcyclopentyl)hexanenitrile (5’’c). 2-Methyl-4-(2,2,3-trimethylcyclopent-3-
enyl)but-2-enal (83 g, 0.43 mol) was reacted at r.t. with CNCH2COOH (36.7 g, 0.43 mol) in the presence
of 2,6-lutidine (4.6 g, 0.043 mol) and ammonium acetate (2 g, 0.026 mol) to provide 4-methyl-6-(2,2,3-
trimethyl-cyclopent-3-enyl)hexa-2,4-dienenitrile (76% crude yield). After removal of the less-volatile
by-products, a soln. of 4-methyl-6-(2,2,3-trimethylcyclopent-3-enyl)hexa-2,4-dienenitrile was hydro-
genated in EtOH under H2 pressure (P(H2 ) ¼ 20 bars; r.t.) over 5% Pd/C (10 g) to provide 5’’c (55 g,
55%). B.p. 958/0.07 Torr. IR (neat): 1365m, 1385w, 1427w, 1465m, 2246w, 2869s, 2955s. 1H-NMR
(CDCl3 ): 0.49 (s, 3 H); 0.82 (d, J ¼ 6.7, 3 H); 0.85 (s, 3 H); 0.91 (2d, J ¼ 6.3, 3 H); 1.0 – 1.8 (m, 13 H); 2.25 –
2.42 (m, 2 H). 13C-NMR (CDCl3 ): 13.91/14.43; 14.93/15.0; 18.77/19.06; 25.68/25.72; 27.5/27.69; 28.24/
28.38; 30.13; 32.1/32.27; 32.55; 35.35/35.65; 42.32; 45.24; 50.85/51.17. EI-MS (70 eV): 221 (3, M þ ), 206
1092 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

(6), 204 (9), 178 (18), 84 (100), 83 (26), 70 (56), 69 (83), 55 (58), 41 (45). Odor description: Sweet,
gourmand, not powerful.
4-Ethyl-6-(2,2,3-trimethylcyclopentyl)hexanenitrile (5’’d). Prepared as described for 5’’c, from 2-
ethyl-4-(2,2,3-trimethylcyclopent-3-enyl)but-2-enal (41 g, 0.2 mol, prepared from campholenic aldehyde
and propanal). Compound 5’’d was obtained as a 7 : 3 mixture of isomers (20 g, 40%). B.p. 1128/0.03 Torr.
IR (neat): 1118w, 1244w, 1367m, 1384w, 1461m, 1738w, 2247w, 2869s, 2956s. 1H-NMR (CDCl3 ; common
signals): 0.46 (s, 3 H); 0.7 – 0.9 (m, 9 H); 0.9 – 1.5 (m, 12 H); 1.5 – 1.85 (m, 3 H); major isomers: 2.27 (t, J ¼
7.4, 2 H); minor isomers: 2.54 (t, J ¼ 7.2, 2 H). 13C-NMR (CDCl3 ): Major isomers: 10.18/10.52; 13.73/
13.76; 14.27; 14.52/14.66; 24.72/25.16; 25.54/25.58; 27.0/27.27; 28.19/28.23; 28.58/28.83; 29.97/30.04; 31.31/
31.39; 38.05/38.25; 42.12/42.15; 45.08/45.11; 50.93/51.14; 119.89; minor isomers (selected data): 10.55/
10.88; 25.46/25.92; 26.97/27.05; 30.68/31.02; 39.12/39.23; 50.99. EI-MS (70 eV): 235 (1, M þ ), 220 (3), 192
(10), 84 (162), 83 (26), 70 (67), 69 (89), 55 (49), 41 (43). Odor description: orris, carrot, powdery, plastic.
4-Methyl-6-(2,2,3-trimethylcyclopentyl)hex-3-enenitrile. (5’’’c). Prepared as described for 5’’c from 2-
methyl-4-(2,2,3-trimethylcyclopentyl)butanal (60 g, 0.306 mol, obtained from 2-methyl-4-(2,2,3-trime-
thylcyclopent-3-enyl)but-2-enal by hydrogenation (5% Pd/C, EtOH, 40 bars H2 )). Compound 5’’’c was
obtained as a 4 : 6 mixture of isomers (31.5 g, 47%). B.p. 958/0.03 Torr. IR (neat): 920w, 1049w, 1366m,
1386m, 1418w, 1453m, 1466m, 1669w, 1754w, 2250w, 2869s, 2954s. 1H-NMR (CDCl3 ): 0.49 (s, 3 H); 0.75 –
0.9 (m, 6 H); 0.9 – 1.4 (m, 5 H); 1.4 – 1.6 (m, 2 H); 1.6 – 2.1 (m, 3 H); 1.65 (s, 3 H); 3.03 (d, J ¼ 6.9, 2 H);
5.1 – 5.2 (m, 1 H); minor isomer (selected data): 1.73 (d, J ¼ 1.3, 3 H). 13C-NMR (CDCl3 ): Major isomer:
13.82; 14.37; 16.16; 16.39; 25.56; 28.04; 28.46; 30.05; 38.4; 42.25; 45.11; 50.29; 111.11; 118.63; 142.96.
Minor isomer: 13.82; 14.37; 16.02; 16.39; 23.13, 28.15; 28.25; 28.46; 31.13, 38.4; 42.31; 45.19; 50.61; 111.72;
118.63; 143.09. EI-MS (70 eV): Major isomer: 219 (1, M þ ), 204 (5), 179 (8), 124 (9), 109 (26), 95 (16), 84
(67), 83 (32), 81 (17), 70 (44), 69 (100), 67 (26), 55 (40), 41 (49); minor isomer: 219 (1, M þ ), 204 (7), 124
(15), 109 (69), 95 (23), 84 (49), 83 (26), 82 (36), 81 (20), 70 (35), 69 (100), 67 (30), 55 (39), 41 (48).
Odor description: Woody (sandalwood), lactonic, a bit animalic.
6-(2,2,3-Trimethylcyclopent-3-enyl)hex-4-enal (3b, FleurenalH ). A 1m soln. of DIBAL-H in toluene
(355 ml, 0.355 mol) was added dropwise to a soln. of 5b (60 g, 0.295 mol) in toluene (100 ml) at such a
rate that the temp. remained under 408. After complete addition, the soln. was heated at 808 for 2 h. The
hydrolysis was carefully performed pouring the reaction soln. into a mixture of AcOH (60 g) and ice
(400 g). The aq. layer was extracted twice with t-BuOMe (200 ml), and the combined org. layers were
washed twice with H2O (250 ml), with sat. aq. NaHCO3 (250 ml), and finally with brine (250 ml). After
drying (MgSO4 ), the solvents were evaporated to furnish a crude oil, which was purified by bulb-to-bulb
prior to conventional distillation (42% yield). B.p. 76 – 788/0.2 Torr. IR (neat): 798m, 1013w, 1360m,
1384w, 1409w, 1444m, 1463m, 1727s, 2719w, 2833m, 2866m, 2894s, 2930s, 2955s, 3010m, 3035w. 1H-NMR
(CDCl3 ): (Z)-3b): 0.8 (s, 3 H); 1.1 (s, 3 H); 1.55 – 1.65 (m, 3 H); 1.65 – 2.6 (m, 9 H); 5.15 – 5.25 (m, 1 H);
5.25 – 5.55 (m, 2 H); 9.78 (t, J ¼ 1.5, 1 H). 13C-NMR (CDCl3 ): 12.58; 19.67; 20.11; 25.85; 27.77; 35.52;
43.76; 46.69; 50.31; 121.6; 127.2; 131.09; 148.49; 202.15. 1H-NMR (CDCl3 ): (E)-3b (selected data): 0.76 (s,
3 H); 0.97 (s, 3 H); 9.66 (m, 1 H). EI-MS (70 eV): 206 (8, M þ ), 191 (19), 173 (12), 147 (28), 121 (30), 109
(48), 108 (100), 107 (45), 105 (20), 97 (21), 95 (36), 93 (52), 91 (36), 81 (27), 79 (65), 77 (30), 69 (36), 67
(76), 55 (46), 53 (21), 43 (24), 41 (80), 39 (26). Odor description: floral (lily of the valley), green, very
powerful.
(þ)-6-[(1R)-2,2,3-Trimethylcyclopent-3-enyl]hex-4-enal ((þ)-3b). Prepared from (þ)-5b (35 g,
0.173 mol) in 48% yield, as described above for 3b. [a]D ¼ þ 2 (neat).
6-(2,2,3-Trimethylcyclopentyl)hex-4-enal (3’b). Prepared as described for 3b in 37% yield from 5’b
(14.5 g, 0.072 mol) as a 9 : 1 (Z)/(E)-mixture. IR (neat): 1366m, 1388m, 1409w, 1453m, 1466m, 1728s,
2719m, 2870s, 2955s, 3010m.
Data of (Z)-3’b: 1H-NMR (CDCl3 ): 0.51 (s, 3 H); 0.80 (d, J ¼ 6.7, 3 H); 0.86 (s, 3 H); 1.05 – 1.25 (m,
2 H); 1.25 – 1.90 (m, 5 H); 2.02 – 2.20 (m, 1 H); 2.25 – 2.52 (m, 4 H); 5.12 – 5.50 (m, 2 H); 9.74 (t, J ¼ 1.5,
1 H). 13C-NMR (CDCl3 ): 13.82; 14.24; 20.03; 25.60; 28.15; 29.87; 42.18; 43.74; 44.99; 50.97; 126.75;
131.28; 202.01.
Data of (E)-3’b: 1H-NMR (CDCl3 ; selected data): 0.47 (s, 3 H); 0.97 (s, 3 H); 9.72 (t, J ¼ 1.6, 1 H).
13
C-NMR (CDCl3 ): 12.52; 13.24; 25.13; 25.79; 27.72; 35.48; 42.09; 43.41; 45.10; 50.28; 127.16; 130.99;
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1093

201.92. EI-MS (70 eV): 208 (1, M þ ), 193 (3), 124 (6), 111 (33), 109 (25), 95 (28), 80 (25), 79 (22), 69
(100), 67 (24), 55 (38), 41 (40). Odor description: powerful, floral (lily of the valley), green.
4-Methyl-6-(2,2,3-trimethylcyclopent-3-enyl)hex-4-enal (3c). Prepared from 5c (36 g, 0.176 mol) in
54% yield, as a 6 : 4 (Z)/(E)-mixture, as described for 3b.
Data of (Z)-3c. 1H-NMR (CDCl3 ): 0.77 (s, 3 H); 0.97 (s, 3 H); 1.55 – 1.65 (m, 3 H); 1.65 – 1.70 (m,
3 H); 1.70 – 2.05 (m, 4 H); 2.05 – 2.25 (m, 2 H); 2.25 – 2.55 (m, 3 H); 5.15 – 5.25 (m, 2 H); 9.77 (t, J ¼ 1.7,
1 H). 13C-NMR (CDCl3 ): 12.57/19.67; 23.09; 24.28; 25.86; 28.31; 35.60; 42.25; 46.66; 50.66; 121.63; 126.41;
132.67; 148.50; 202.28.
Data of (E)-3c: 1H-NMR (CDCl3 ; selected data): 1.57 – 1.60 (m, 3 H); 9.74 (t, J ¼ 1.9, 1 H).
13
C-NMR (CDCl3 ): 12.57/19.67; 16.13; 25.88; 28.45; 31.96; 35.53; 42.13; 46.66; 50.51; 121.68; 125.35;
132.74; 148.50; 202.61. Odor description: floral (lily of the valley), LilialH, LyralH.
4-Methyl-6-(2,2,3-trimethylcyclopentyl)hexanal (3’’c). Prepared from 5’’c (44 g, 0.2 mol) in 88% yield
as described for 3b. IR (neat): 1365w, 1387w, 1465m, 1729s, 2714w, 2869s, 2931s, 2955s. 1H-NMR (CDCl3 ):
0.49 (s, 3 H); 0.74 – 0.91 (m, 6 H); 0.82 (d, J ¼ 6.7, 3 H); 0.91 – 1.56 (m, 10 H); 1.56 – 1.85 (m, 4 H); 2.35 –
2.53 (m, 2 H); 9.78 (t, J ¼ 1.9, 1 H). 13C-NMR (CDCl3 ): 13.92/14.42; 19.29/19.6; 25.71/25.74; 27.66/27.85;
28.28/28.42; 28.69/29.21; 30.17; 32.68/32.93; 35.8/36.08; 41.71/41.83; 42.31; 45.27; 50.95/51.26; 203.04. EI-
MS (70 eV): 224 (2, M þ ), 207 (6), 163 (9), 110 (20), 109 (36), 95 (34), 85 (33), 84 (70), 83 (34), 81 (29),
70 (79), 69 (100), 67 (23), 57 (19), 55 (66), 43 (22), 41 (55). Odor description: slightly woody, green,
lactonic (wax), plastic.
4-Ethyl-6-(2,2,3-trimethylcyclopentyl)hexanal (3’’d). The crude material was obtained from 5’’d
(15 g, 0.064 mol) as described for 3b. Purification by column chromatography (CC) provided pure 3’’d
(8.8 g, 0.037 mol, 58%) as a 1 : 1 mixture of isomers. IR (neat): 1051m, 1103m, 1367m, 1385m, 1461s,
1728s, 2715w, 2869s, 2955s. 1H-NMR (CDCl3 ): 0.45 (s, 3 H); 0.7 – 0.95 (m, 9 H); 0.78 (d, J ¼ 6.7, 3 H);
0.95 – 1.35 (m, 12 H); 1.35 – 1.65 (m, 3 H); 1.65 – 1.85 (m, 3 H); 2.34/2.38 (2td, J ¼ 1.7/1.5, 7.8/7.6, 2 H); 9.73
(t, J ¼ 1.9, 1 H). 13C-NMR (CDCl3 ): 10.45/10.77; 13.78; 14.30; 24.93/25.68; 25.24; 25.58; 27.19/27.21; 28.24;
30.03; 31.87/31.90; 38.55/38.68; 41.20/41.42; 42.18; 45.14; 51.07/51.11; 202.98. EI-MS (70 eV): 238 (1, M þ ),
223 (4), 209 (4), 177 (6), 123 (8), 110 (20), 109 (27), 99 (19), 95 (27), 84 (66), 83 (37), 81 (26), 70 (79), 69
(100), 67 (23), 57 (19), 55 (81), 43 (30), 41 (65). Odor description: sweet (furaneol), animalic (costus,
goat), a bit metallic.
3-Methyl-6-(2,2,3-trimethylcyclopentyl)hexanal (3’’a). The crude material was obtained from 5’’a
(10.3 g, 0.046 mol) as described for 3b. Purification by CC provided pure 3’’a (3.3 g, 0.0147 mol, 32%). IR
(neat): 1127w, 1367m, 1384m, 1464s, 1728s, 2712m, 2869s, 2954s. 1H-NMR (CDCl3 ): 0.47 (s, 3 H); 0.80 (d,
J ¼ 6.7, 1 H); 0.83 (s, 3 H); 0.94 (2d, J ¼ 6.6, 1 H); 1.0 – 1.55 (m, 10 H); 1.55 – 1.85 (m, 2 H); 2.03 (d, J ¼ 6.5,
1 H); 2.18/2.24 (td, J ¼ 2.2, 7.7, 2 H); 2.34/2.42 (td, J ¼ 2, 5.8, 2 H); 9.74 (t, J ¼ 2.2, 1 H). 13C-NMR (CDCl3 ):
13.85; 14.31; 19.86/20.05; 25.63; 26.14/26.22; 28.12/28.25; 28.21; 30.12; 30.47/30.58; 37.28/37.39; 42.20;
45.19; 20.79/50.85; 50.99/51.17; 202.99/203.02. EI-MS (70 eV): 224 (1, M þ ), 109 (13), 95 (21), 84 (61), 83
(28), 81 (22), 70 (86), 69 (100), 67 (18), 55 (52), 43 (23), 41 (51). Odor description: marine, ozonic,
transparent (MelonalH ).
2,4-Dimethyl-6-(2,2,3-trimethylcyclopentyl)hexanal (3’’e). Aldehyde 3’’c (10 g, 0.045 mol) was
alkylated according to [8] with MeI (9.6 g, 0.068 mol) via its diisobutylenamine, obtained with (i-
Bu)2NH (5.8 g, 0.045 mol) by azeotropic removal of H2O with toluene (30 ml). The obtained product
was purified by CC to give recovered 3’’c (12%) and pure 3’’e (4.6 g, 0.019 mol, 43%) as a mixture of
isomers, two observable groups in NMR, ratio 6 : 4, composed each of two diastereoisomers. IR (neat):
1367w, 1380w, 1464m, 1709m, 1729s, 2704w, 2870s, 2956s. Major isomers: 1H-NMR (CDCl3 ): 0.48 (s, 3 H);
0.80 (d, J ¼ 6.7, 3 H); 0.83 (s, 3 H); 0.87 (d, J ¼ 6.5, 3 H); 0.92 – 1.51 (m, 10 H); 1.06 (d, J ¼ 6.9, 3 H); 1.51 –
1.87 (m, 3 H); 9.55 (d, J ¼ 1.6, 1 H); 9.57 (d, J ¼ 1.5, 1 H). 13C-NMR (CDCl3 ): 13.85; 14.10/14.26; 14.35;
19.66/19.99; 25.64; 27.63; 28.20; 30.10; 30.51/30.95; 35.73/36.02; 38.17/38.51; 42.24; 44.13; 45.20; 50.83/
51.17; 205.40. Minor isomers: 1H-NMR (CDCl3 ; selected data): 0.88 (d, J ¼ 6.6, 3 H); 1.05 (d, J ¼ 7.0, 3 H);
9.59 (2d, J ¼ 2.0, 1 H). 13C-NMR (CDCl3 ): 13.24/13.38; 13.85; 14.35; 19.10/19.43; 25.68; 27.42; 28.34;
30.10; 30.41/30.60; 36.40/36.67; 37.33/37.92; 42.24; 44.23; 45.20; 50.88/51.14; 205.35. EI-MS (70 eV): 238
(M þ ), 223 (1), 180 (6), 125 (15), 109 (32), 99 (22), 97 (22), 95 (27), 84 (62), 83 (37), 81 (21), 71 (20), 70
(73), 69 (100), 57 (21), 55 (72), 43 (39), 41 (57). Odorless.
1094 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

7-(2,2,3-Trimethylcyclopent-3-enyl)hept-5-en-2-one (8). A 2.1m soln. of BuLi in hexanes (50 ml,

0.105 mol) was added at 08 to a suspension of MePh3PBr (37 g, 0.103 mol) and KI (7.2 g, 0.051 mol) in
THF (300 ml). After 30 min, 5b (17.5 g, 0.103 mol) was added, and the mixture was refluxed for a further
6 h and, then, allowed to cool to r.t. overnight. The soln. was poured into a 8 : 2 sat. aq. NH4Cl/t-BuOMe,
and the aq. layer was extracted with t-BuOMe (3  50 ml). The combined org. layers were washed with
brine (3  30 ml), dried (MgSO4 ), and the solvents were evaporated. The crude product was purified by
distillation to afford pure 8 (11 g, 56%) as a 95 : 5 (Z)/(E)-mixture. B.p. 76 – 788/0.04 Torr. IR (neat):
578w, 798m, 1013w, 1161m, 1361s, 1412m, 1438s, 1462s, 1654w, 1719s, 2836m, 2867s, 2957s, 3009m, 3036m.
1
H-NMR (CDCl3 ): 0.78 (s, 3 H); 0.98 (s, 3 H); 1.55 – 1.65 (m, 3 H); 1.65 – 1.9 (m, 2 H); 1.9 – 2.4 (m, 5 H);
2.13 (s, 3 H); 2.4 – 2.55 (m, 2 H); 5.15 – 5.25 (m, 1 H); 5.25 – 5.5 (m, 2 H). 13C-NMR (CDCl3 ): 12.59; 19.69;
21.71; 25.86; 27.73; 29.92; 35.52; 43.55; 46.69; 50.38; 121.61; 127.75; 130.65; 148.51; 208.43. EI-MS (70 eV):
220 (2, M þ ), 205 (3), 187 (4), 162 (5), 150 (8), 147 (38), 121 (17), 109 (34), 108 (86), 107 (24), 93 (51),
91 (31), 81 (20), 79 (36), 77 (24), 67 (41), 55 (22), 43 (100), 41 (28). Odor description: green (fig leaves),
sweet.
4-(6,6-Diethoxyhex-2-enyl)-1,5,5-trimethylcyclopentene (7b). Treatment of 3b (16 g, 0.078 mol) with
HC(OEt)3 (23 g, 0.156 mol) and cat. amount of TsOH in EtOH (36 ml) at r.t. provided 7b (15 g, 70%) as
a 9 : 1 (Z)/(E)-mixture of isomers. B.p. 948/0.07 Torr. IR (neat): 798w, 1014w, 1064s, 1130s, 1360w, 1375m,
1444m, 1744w, 2871s, 1931s, 2957s, 3007m, 3037w.
Data of (Z)-7b: 1H-NMR (CDCl3 ): 0.77 (s, 3 H); 0.97 (s, 3 H); 1.17 (t, J ¼ 7.1, 6 H); 1.50 – 1.90 (m,
7 H); 1.90 – 2.35 (m, 5 H); 3.54 (m, 4 H); 4.46 (t, J ¼ 5.7, 1 H); 5.15 – 5.25 (m, 1 H); 5.25 – 5.47 (m, 2 H).
13
C-NMR (CDCl3 ): 12.51; 15.28; 19.63; 22.57; 25.82; 27.69; 33.46; 35.49; 46.65; 50.45; 60.84; 102.33,
121.67; 128.84; 129.89; 148.37.
Data of (E)-7b (selected data): 1H-NMR (CDCl3 ): 0.74 (s, 3 H); 0.95 (s, 3 H). 13C-NMR (CDCl3 ):
129.60; 130.42. Odor description: like plastic, not powerful.
2-(6,6-Diethoxy-3-ethylhexyl)-1,1,5-trimethylcyclopentane (7’’d). Obtained in 75% yield as described
for 7b from 3’’d (8.5 g, 0.036 mol) as a 1 : 1 mixture of isomers. IR (neat): 1016m, 1064s, 1126s, 1345w,
1375m, 1460m, 2870s, 2956s. 1H-NMR (CDCl3 ): 0.47 (s, 3 H); 0.75 – 0.9 (m, 3 H); 0.8 (d, J ¼ 6.7, 3 H); 0.83
(s, 3 H); 0.9 – 1.37 (m, 10 H); 1.19 (t, J ¼ 7.1, 6 H); 1.37 – 1.67 (m, 3 H); 1.67 – 1.85 (m, 2 H); 3.56 (m, 4 H);
4.45 (t, J ¼ 5.7, 1 H). 13C-NMR (CDCl3 ): 10.68/10.99; 13.87; 14.37; 15.33; 25.58/26.02; 25.67; 27.36/27.41;
27.64/28.01; 28.33; 30.15; 30.47/30.74; 32.16/32.20; 38.98/39.05; 42.25; 51.23; 60.67; 103.32. EI-MS (70 eV):
312 (1, M þ ), 268 (1), 103 (100), 95 (9), 75 (31), 69 (22), 55 (15), 47 (14), 41 (9). Odor description: fruity
(apple), alcoholic, animal, cresolic.
6,8-Dimethylnon-7-enal (NoreenalH ; 10). 5,7-Dimethylocta-1,6-diene (9; 138 g, 1 mol) was placed in
an autoclave with bis(h4-cycloocta-1,5-diene)-di-m-methoxydirhodium(I) (232 mg, 0.48 mmol) and
diphenylphosphino-1,8-dimethyl-9,9-xanthene (836 mg, 1.44 mmol) under 30 bar of equimolar CO/H2
pressure. The mixture was then stirred for 12 h at 70 – 808. After cooling, the crude product was purified
by distillation to provide 10 (88.2 g, 0.48 mol, 75%). B.p. 808/9 Torr. IR (neat): 841w, 944w, 1068w, 1378m,
1410w, 1453m, 1727s, 2716w, 2866s, 2929s, 3436w. 1H-NMR (CDCl3 ): 0.88 (d, J ¼ 6.7, 3 H); 1.05 – 1.38 (m,
4 H); 1.50 – 1.66 (m, 2 H); 1.58 (d, J ¼ 1.1, 3 H); 1.66 (d, J ¼ 1.0, 3 H); 2.16 – 2.35 (m, 1 H); 2.40 (dt, J ¼ 1.8,
7.3, 2 H); 4.84 (sept. d, J ¼ 1.3, 9.4, 1 H); 9.74 (t, J ¼ 1.9, 1 H). 13C-NMR (CDCl3 ): 17.89; 21.25; 22.24;
25.73; 27.05; 32.24; 37.47; 43.90; 129.88; 131.16; 202.84. EI-MS (70 eV): 168 (7, M þ ), 124 (12), 109 (14),
83 (100), 69 (24), 55 (49), 41 (25). Odor description: citrus (mandarin), fresh, coriander leaves, fruity
(melon), very powerful.
2,5,7-Trimethyloct-6-enal (11). Compound 9 (35.3 g, 0.256 mol) was placed in an autoclave with
bis(h4-cycloocta-1,5-diene)-di-m-methoxydirhodium(I) (26 mg, 0.054 mmol) and Ph3P (210 mg,
0.362 mmol) under 5 bar of equimolar CO/H2 pressure. The mixture was then stirred 12 h at 908. After
the mixture had cooled to r.t., the crude product was purified by fine distillation to afford 11 (8 g,
48 mmol, 19%, two isomers). B.p. 64 – 658/6 Torr). IR (neat): 842w, 921w, 1071w, 1120w, 1378m, 1454m,
1727s, 2707w, 2810w, 2869s, 2928s, 2964s, 3434w. Major isomer: 1H-NMR (CDCl3 ): 0.85 – 1.05 (m, 1 H);
0.91 (d, J ¼ 6.8, 3 H); 1.06 (d, J ¼ 6.9, 3 H); 1.10 – 1.25 (m, 1 H); 1.25 – 1.37 (m, 2 H); 1.57 – 1.72 (m, 1 H);
1.59 (s, 3 H); 1.67 (s, 3 H); 2.24 – 2.34 (m, 1 H); 4.82 – 4.87 (m, 1 H); 9.58 (d, J ¼ 1.7, 1 H). 13C-NMR
(CDCl3 ): 13.38; 17.95; 21.24; 25.75; 28.47; 32.51; 34.97; 46.45; 130.35; 130.75; 205.36. Minor isomer
(selected data): 1H-NMR (CDCl3 ): 0.90 (d, J ¼ 6.6, 3 H); 1.06 (d, J ¼ 7, 3 H); 9.58 (d, J ¼ 1.5, 1 H).
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1095
13
C-NMR (CDCl3 ): 13.30; 13.94; 21.30; 28.52; 32.55; 46.43; 130.40; 130.80. EI-MS (70 eV): 168 (2, M þ ),
96 (100), 83 (65), 69 (22), 55 (86), 41 (47). Odor description: aldehydic, green, citronella, parsley.
6,8-Dimethylnonanal (10’). A mixture of 10 (41 g, 0.24 mol), 10% Pd/C (4 g) and toluene (200 ml)
was stirred under H2 (1 bar) at r.t. After completion of the reaction, the catalyst was filtered off over a
pad of CeliteH. The solvent was evaporated, and the crude product was purified by distillation to give pure
10’ (38 g, 0.23 mol, 96%). B.p. 708/3 Torr. EI-MS (70 eV): 170 (1, M þ ), 137 (4), 124 (10), 109 (22), 95
(31), 83 (50), 69 (39), 57 (55), 55 (37), 43 (100), 41 (57), 39 (27). Odor description: aldehydic, bigarade
orange, fruity.
6,8-Dimethylnon-7-en-1-ol (12). Compound 10 (18 g, 0.11 mol) was added to a cold stirred
suspension of NaBH4 (2 g, 0.053 mol) in EtOH (100 ml). Stirring of the mixture was continued at r.t. for
16 h, prior to cooling to 108, and addition of acetone (20 g, 1.36 mol) and 10% aq. HCl (20 g). H2O
(40 ml) and toluene (70 ml) were added subsequently, and the separated org. layer was washed with sat.
aq. NaHCO3 (50 ml) and twice with H2O (50 ml). The org. layer was dried (MgSO4 ) and concentrated
under reduced pressure. The crude product was purified by distillation to furnish 12 (13.4 g, 0.08 mol,
73%). B.p. 1058/10 Torr. IR (neat): 844w, 1047m, 1356m, 1412m, 1451m, 2724w, 2872s, 2932s, 2960s, 3334
(br.). 1H-NMR (CDCl3 ): 0.88 (d, J ¼ 6.7, 3 H); 0.95 – 1.42 (m, 6 H); 1.42 – 1.65 (m, 2 H); 1.58 (d, J ¼ 1.1,
3 H); 1.66 (d, J ¼ 1.0, 3 H); 2.0 (br. s, 1 H); 2.15 – 2.4 (m, 1 H); 3.60 (t, J ¼ 6.6, 2 H); 4.85 (sept. d, J ¼ 1.2,
9.4, 1 H). 13C-NMR (CDCl3 ): 17.87; 21.24; 25.72; 25.89; 27.24; 32.32; 32.76; 37.75; 62.92; 129.60; 131.49.
EI-MS (70 eV): 170 (5, M þ ), 109 (4), 96 (8), 83 (100), 69 (12), 55 (32), 41 (19). Odor description:
aldehydic, bergamot, floral (rosy), cinnamic.
6,8-Dimethylnonan-1-ol (12’). Obtained in 54% yield from 10’ (64 g, 0.376 mol) as described for 12.
B.p. 708/1 Torr. 1H-NMR (CDCl3 ): 0.80 (d, J ¼ 6.7, 3 H); 0.82 (t, J ¼ 6.8, 3 H); 0.84 (d, J ¼ 6.9, 3 H); 0.87 –
1.12 (m, 3 H); 1.12 – 1.37 (m, 5 H); 1.37 – 1.72 (m, 4 H); 1.90 (br. s, 1 H); 3.61 (t, J ¼ 6.6, 2 H). 13C-NMR
(CDCl3 ): 19.73; 22.26; 23.40; 25.18; 26.06; 26.75; 30.18; 32.81; 37.32; 46.79; 62.97. Odor description:
aldehydic, fruity (peach), rosy.
2,5,7-Trimethyloct-6-en-1-ol. Obtained in 88% yield from 10 (4.7 g, 0.03 mol) as described for 12.
B.p. 828/1 Torr. IR (neat): 842w, 985w, 1041m, 1336m, 1376m, 1416m, 1453m, 2728w, 2872s, 2926s, 2960s,
3339 (br.). Major isomers: 1H-NMR (CDCl3 ): 0.89 (d, J ¼ 6.7, 6 H); 1.0 – 1.45 (m, 5 H); 1.45 – 1.70 (m,
1 H); 1.58 (s, 3 H); 1.68 (s, 3 H); 2.26 (br. s, 1 H); 3.32 – 3.75 (m, 2 H); 4.86 (d, J ¼ 9.2, 1 H). 13C-NMR
(CDCl3 ): 16.57/16.66; 17.91; 21.20/21.40; 25.76; 30.94; 32.68/32.71; 35.07/35.11; 35.94/35.97; 68.31/68.36;
129.76/129.84; 131.35/131.43. Minor isomers (selected data): 13C-NMR (CDCl3 ): 16.79/16.89; 31.04/31.08;
34.94; 68.26; 129.53/129.60; 131.52/131.60. EI-MS (70 eV): 170 (2), 152, 83 (100), 55 (61), 41 (28).
6,8-Dimethylnon-7-en-1-yl Acetate (13a). A soln. of 12 (13 g, 76 mmol) and Et3N (10.8 g, 107 mmol)
in t-BuOMe (200 ml) was cooled to 58, and AcCl (8.4 g, 107 mmol) in t-BuOMe (20 ml) was added
dropwise. The mixture was stirred to r.t. further for 14 h, and then poured into a cold 10% aq. HCl soln.
(100 ml). The org. layer was separated and washed with sat. aq. NaHCO3 (50 ml) and twice with brine
(50 ml), and then dried (MgSO4 ) and concentrated under reduced pressure. The crude product was
purified by distillation to provide 13a in 76% yield. Bp 588/0.4 Torr. Odor description: aldehydic, nitrile,
cinnamic.
6,8-Dimethylnon-7-en-1-yl Propanoate (13b). Obtained in 71% yield from 12 (13 g, 0.076 mol) and
propanoyl chloride (9.9 g, 0.107 mol) as described for 13a. B.p. 708/0.6 Torr. Odor description: aldehydic,
fruity (pear, dry fruits), cinnamic, floral.
2,5,7-Trimethyl-6-octen-1-yl acetate. Obtained in 72% yield from 12 (3.3 g, 0.033 mol; two isomers) as
described for 13a. IR (neat): 842w, 984w, 1037m, 1237s, 1375m, 1455m, 1743s, 2857m, 2926s, 2963 (s).
1
H-NMR (CDCl3 ): 0.82 – 0.95 (m, 6 H); 1.02 – 1.15 (m, 1 H); 1.15 – 1.35 (m, 3 H); 1.57 (s, 3 H); 1.62 – 1.80
(m, 1 H); 1.66 (s, 3 H); 2.02 (s, 3 H); 2.2 – 2.3 (m, 1 H); 3.8 (m, 1 H); 3.92 (m, 1 H); 4.81 – 4.86 (m, 1 H).
13
C-NMR (CDCl3 ): 16.79/16.95; 17.89; 20.88; 21.15/21.34; 25.71; 31.12; 32.53/32.58; 32.58/32.65; 34.85;
69.40/69.44; 129.80/129.87; 131.19/131.27; 171.17. EI-MS (70 eV): 212 (1, M þ ), 152 (14), 137 (10), 109
(24), 95 (28), 83 (100), 67 (14), 55 (58), 43 (50).
6,8-Dimethylnon-7-enal Dimethyl Acetal (14a). Obtained in quant. yield from 10 (50 g, 0.3 mol),
MeOH (192 g, 6 mol) and HC(OMe)3 (64 g, 0.6 mol) as described for 7b. B.p. 708/1 Torr. 1H-NMR
(CDCl3 ): 0.87 (d, J ¼ 6.7, 3 H); 1.06 – 1.38 (m, 6 H); 1.48 – 1.65 (m, 2 H); 1.58 (d, J ¼ 1.1, 3 H); 1.66 (d, J ¼
1.1, 3 H); 2.16 – 2.40 (m, 1 H); 3.29 (s, 6 H); 4.33 (t, J ¼ 5.7, 1 H); 4.84 (sept. d, J ¼ 1.3, 9.4, 1 H). 13C-NMR
1096 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

(CDCl3 ): 17.87; 21.25; 24.74; 25.73; 27.29; 32.30; 32.46; 37.69; 52.42; 52.49; 104.5; 129.59; 131.47. EI-MS
(70 eV): 214 ( < 1, M þ ), 182 (12), 135 (11), 109 (11), 107 (10), 97 (33), 95 (23), 84 (26), 83 (64), 81 (12),
75 (100), 71 (20), 69 (13), 67 (13), 55 (32), (41 (20). Odor description: green (peas), grapefruit.
6,8-Dimethylnon-7-enal Diethyl Acetal (14b). Obtained in 88% yield from 10 (33 g, 0.27 mol), EtOH
(120 g, 2.6 mol) and HC(OEt)3 (80 g, 0.54 mol) as described for 7b. B.p. 1068/5 Torr. 1H-NMR (CDCl3 ):
0.86 (d, J ¼ 6.7, 3 H); 1.12 – 1.37 (m, 6 H); 1.17 (t, J ¼ 7.1, 6 H); 1.47 – 1.65 (m, 2 H); 1.57 (d, J ¼ 1.1, 3 H);
1.65 (d, J ¼ 1.0, 3 H); 2.15 – 2.37 (m, 1 H); 3.36 – 3.75 (m, 4 H); 4.44 (t, J ¼ 5.7, 1 H); 4.83 (sept. d, J ¼ 1.3,
9.4, 1 H). 13C-NMR (CDCl3 ): 15.27; 17.84; 21.23; 24.87; 25.70; 27.28; 32.28; 33.55; 37.69; 60.66; 60.72;
102.90; 129.52; 131.48. EI-MS (70 eV): 242 ( < 1, M þ ), 197 (10), 196 (12), 151 (5), 135 (10), 129 (7), 111
(38), 109 (15), 107 (10), 103 (100), 98 (16), 96 (17), 95 (41), 85 (15), 83 (71), 81 (16), 75 (55), 69 (21), 67
(13), 57 (16), 55 (34), 47 (30), 43 (10).
2-(5,7-Dimethyloct-6-enyl)[1,3]dioxolane (14c). Obtained in 88% yield from 10 (45.5 g, 0.27 mol),
ethylene glycol (167.4 g, 2.7 mol) and HC(OEt)3 (80 g, 0.54 mol) as described for 7b. B.p. 678/0.7 Torr.
1
H-NMR (CDCl3 ): 0.86 (d, J ¼ 6.7, 3 H); 1.0 – 1.45 (m, 6 H); 1.45 – 1.7 (m, 2 H); 1.57 (d, J ¼ 1.1, 3 H); 1.64
(d, J ¼ 1.1, 3 H); 2.17 – 2.44 (m, 1 H); 3.75 – 3.87 (m, 2 H); 3.87 – 3.97 (m, 2 H); 4.79 – 4.88 (m, 1 H); 4.81 (t,
J ¼ 4.8, 1 H). 13C-NMR (CDCl3 ): 17.85; 21.20; 24.19; 25.70; 27.34; 32.25; 33.89; 37.65; 64.73; 104.61;
129.56; 131.45. EI-MS (70 eV): 212 (4, M þ ), 155 (7), 135 (8), 127 (14), 107 (9), 99 (43), 86 (13), 83 (69),
81 (6), 73 (100), 69 (9), 67 (9), 55 (32), 45 (14), 43 (7), 41 (16).
6,8-Dimethylnonanal Dimethyl Acetal (14’a). Obtained in 75% yield from 14a as described for 10’.
B.p. 708/1 Torr. 1H-NMR (CDCl3 ): 0.81 (d, J ¼ 6.7, 3 H); 0.82 (d, J ¼ 6.5, 3 H); 0.84 (d, J ¼ 6.7, 3 H); 0.88 –
1.13 (m, 3 H); 1.13 – 1.38 (m, 5 H); 1.38 – 1.51 (m, 1 H); 1.51 – 1.69 (m, 3 H); 3.30 (s, 6 H); 4.35 (t, J ¼ 5.7,
1 H). 13C-NMR (CDCl3 ): 19.72; 22.26; 23.40; 24.90; 25.18; 26.79; 30.15; 32.49; 37.26; 46.78; 52.49; 52.52;
104.52. EI-MS (70 eV): 216 ( < 1, M þ ), 185 (4), 97 (7), 83 (5), 75 (100), 71 (8), 69 (5), 55 (6), 43 (6), 41
(7). Odor description: fruity (apple, pineapple), green, hesperidic.
6,8-Dimethylnonanal Diethyl Acetal (14’b). Obtained in quant. yield from 14b as described for 10’.
B.p. 908/2 Torr. 1H-NMR (CDCl3 ): 0.79 (d, J ¼ 6.6, 3 H); 0.80 (d, J ¼ 6.4, 3 H); 0.83 (d, J ¼ 6.6, 3 H); 0.87 –
1.12 (m, 3 H); 1.18 (t, J ¼ 7.0, 6 H); 1.21 – 1.51 (m, 6 H); 1.51 – 1.70 (m, 3 H); 3.55 (m, 4 H); 4.46 (t, J ¼ 5.7,
1 H). 13C-NMR (CDCl3 ): 15.29; 19.71; 22.23; 23.37; 25.03; 25.15; 26.75; 30.13; 33.56; 37.24; 46.75; 60.73;
102.91. EI-MS (70 eV): 244 ( < 1, M þ ), 199 (7), 103 (100), 97 (15), 75 (22), 57 (10), 47 (16), 43 (9). Odor
description: peach, apricot (juice).
2-(5,7-Dimethyloctyl)[1,3]dioxolane (14’c). Obtained in quant. yield from 14c as described for 10’.
B.p. 678/0.7 Torr. 1H-NMR (CDCl3 ): 0.80 (d, J ¼ 6.7, 3 H); 0.81 (d, J ¼ 6.5, 3 H); 0.83 (d, J ¼ 7.0, 3 H);
0.87 – 1.17 (m, 4 H); 1.17 – 1.50 (m, 5 H); 1.50 – 1.72 (m, 3 H); 3.75 – 3.87 (m, 2 H); 3.87 – 3.97 (m, 2 H);
4.82 (t, J ¼ 4.8, 1 H). 13C-NMR (CDCl3 ): 19.69; 22.24; 23.36; 24.35; 25.15; 26.83; 30.10; 33.89; 37.21;
46.75; 64.75; 104.64. EI-MS (70 eV): 214 ( < 1, M þ ), 73 (100), 45 (6), 43 (5).
Methyl 4-Formylnonanoate (17b). A soln. of morpholine (418.0 g, 4.80 mol) in cyclohexane (344.0 g)
was heated to 65 – 708, and heptanal (444.2 g, 3.89 mol) added over a period of 5 h with removal of the
formed H2O in a trap. After completion of the reaction, the mixture was allowed to cool, and the
cyclohexane as well as the excess morpholine were distilled off under reduced pressure (808/30 Torr). A
soln. of KOH (4.0 g, 0.10 mol) in MeOH (40 ml) was then added, and the mixture was heated to 608.
Then, methyl acrylate (237.5 g, 2.76 mol) was added to the mixture over a period of 4 h, stirring continued
for further 12 h at 608, and methyl acrylate (165.3 g, 1.92 mol) was again added after 2 h 30 min. The
mixture was then stirred at 808 for further 12 h, prior to the addition of a pH 4 buffer soln. within 2 h. The
reaction was quenched, and the mixture was stirred for further 4 h, the aq. layer extracted twice with
cyclohexane (200 ml), and the combined org. layers washed with H2O (100 ml), sat. aq. NaHCO3
(100 ml), and brine (100 ml). After drying (MgSO4 ), the solvents were evaporated. The resulting crude
product was purified by short-path distillation to afford 17b in 83% purity (663 g, 2.74 mol, 70%).
3,4,5,6-Tetrahydro-5-pentyl-2H-pyran-2-one (VerbenolideH ; 15b). At 58, 17b was added slowly to a
suspension of NaBH4 (41.6 g, 1.1 mol) in EtOH (1500 ml), and the mixture was stirred at 58 overnight. A
10% aq. NaOH soln. (1900 ml) was then added dropwise at 108 within 2 h. Stirring was continued until
the colorless precipitate disappeared (2 h). Most of the EtOH was then evaporated, and the aq. layer was
washed twice with toluene/hexane 1 : 1 (200 ml). After cooling the mixture to 08, the aq. layer was further
acidified by adding a 10% aq. HCl soln. (1900 ml) dropwise at 108 over a period of 3 h. Stirring was
 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008) 1097

continued for further 4 h at r.t., the org. layer was then separated, and the aq. one was extracted twice
with toluene (200 ml). The combined org. layers were washed twice with H2O (100 ml) and brine
(200 ml), and dried (MgSO4 ). The solvents were evaporated under reduced pressure, and the crude
material purified by distillation to provide 15b (289 g, 1.7 mol, 61% yield). B.p. 90 – 928/27 Pa. IR (neat):
1055m, 1097w, 1183m, 1245w, 1342w, 1402w, 1460w, 1739s, 2858m, 2928s, 2957s. 1H-NMR (CDCl3 ): 0.88 (t,
J ¼ 4, 3 H); 1.2 – 1.4 (m, 8 H); 1.4 – 1.6 (m, 1 H); 1.8 – 1.95 (m, 1 H); 1.95 – 2.05 (m, 1 H); 2.48 (ddd, J ¼ 7.18,
9.4, 17.8, 1 H); 2.61 (ddd, J ¼ 4.7, 7.0, 17.8, 1 H); 3.94 (dd, J ¼ 9.7, 11.1, 1 H); 4.32 (ddd, J ¼ 1.9, 4.5, 11.1,
1 H). 13C-NMR (CDCl3 ): 14.01; 22.51; 25.53; 26.46; 29.11; 31.52; 31.82; 32.84; 73.73; 171.63. EI-MS
(70 eV): 170 (2, M þ ), 128 (32), 112 (60), 111 (25), 97 (22), 94 (22), 84 (69), 83 (32), 70 (80), 69 (69), 68
(60), 56 (97), 55 (100), 43 (65), 42 (49), 41 (92), 39 (32). Odor description: lemon, nitrile, green, lactonic.
3,4,5,6-Tetrahydro-5-propyl-2H-pyran-2-one (FigolideH ; 15a). Obtained from valeraldehyde as
described for 15b. Bp 808/0.8 Torr. 1H-NMR (CDCl3 ): 0.93 (t, J ¼ 6.7, 3 H); 1.2 – 1.43 (m, 4 H); 1.43 –
1.65 (m, 1 H); 1.92 – 2.10 (m, 2 H); 2.38 – 2.72 (m, 2 H); 3.96 (dd, J ¼ 9.6, 11.1, 1 H); 4.34 (ddd, J ¼ 2.0, 4.4,
11.1, 1 H). 13C-NMR (CDCl3 ): 13.58; 19.43; 24.91; 28.55; 32.01; 33.19; 73.10; 171.11. EI-MS (70 eV): 142
(5, M þ ), 112 (9), 94 (10), 84 (93), 70 (32), 69 (30), 56 (69), 55 (100), 42 (55), 41 (45), 39 (24). Odor
description: Lactonic, coconut, fig leaves.
3,4,5,6-Tetrahydro-3-heptyl-2H-pyran (CilandraneH ; 16c). To a suspension of NaBH4 (22.4 g,
0.59 mol) in iPrOH (400 ml) was added dropwise with stirring over a period of 1 h the formyl-ester
17c (0.59 mol, obtained from nonanal as described for 17b). The mixture was stirred at r.t. overnight.
After cooling to 108, acetone (8.6 g, 0.15 mol) was added at 108 and then over 1 h concentrated HCl
(240 g). H2O was added (250 ml), and the aq. layer was extracted twice with toluene (200 ml). The
combined org. layers were washed with H2O (100 ml) and with brine (100 ml), and then dried (MgSO4 ).
The solvents were evaporated, and the crude diol (118 g, 0.42 mol) was treated with 85% H3PO4 (52.6 g).
The mixture was then stirred at 1208 for 4 h. After cooling to r.t., H2O (150 ml) was added. The aq. layer
was extracted with t-BuOMe (100 ml), and the combined org. layers were washed twice with sat. aq.
NaHCO3 (50 ml) and once with brine (50 ml), dried (MgSO4 ), and concentrated under reduced
pressure. The crude product was purified by distillation to provide 16c (28 g, 0.18 mol, 73%). B.p. 1008/
7 Torr. 1H-NMR (CDCl3 ): 0.8 – 0.95 (m, 3 H); 0.95 – 1.17 (m, 3 H); 1.17 – 1.4 (m, 10 H); 1.42 – 1.70 (m,
3 H); 1.85 (dtdd, J ¼ 1.6, 3.5, 5.3, 12.8, 1 H); 3.02 (dd, J ¼ 10.2, 11.0, 1 H); 3.25 – 3.42 (m, 1 H); 3.80 – 3.94
(m, 2 H). 13C-NMR (CDCl3 ): 14.08; 22.65; 25.99; 26.61; 29.24; 29.82; 30.07; 31.85; 32.53; 36.02; 68.49;
73.64. EI-MS (70 eV): 184 (1, M þ ), 166 (4), 123 (17), 109 (29), 95 (18), 81 (48), 71 (74), 68 (71), 55 (67),
43 (52), 41 (100), 39 (24). Odor description: lactonic, green, aldehydic (mandarin), coriander leaves.
3-Benzyltetrahydro-2H-pyran (BetahydraneH ; 16d). Obtained from 3-phenylpropanal as described
for the preparation of 16c. B.p. 748/0.4 Torr. 1H-NMR (CDCl3 ): 1.15 – 1.30 (m, 1 H); 1.51 – 1.67 (m, 2 H);
1.77 – 1.99 (m, 2 H); 2.44 (dd, J ¼ 7.6, 13.6, 1 H); 2.56 (dd, J ¼ 7.2, 13.6, 1 H); 3.16 (dd, J ¼ 9.6, 11.1, 1 H);
3.36 – 3.46 (m, 1 H); 3.82 – 3.93 (m, 2 H). 13C-NMR (CDCl3 ): 25.67; 29.61; 37.80; 38.99; 68.42; 73.09;
125.90; 128.22; 128.92; 139.86. EI-MS (70 eV): 176 (21, M þ ), 143 (5), 130 (8), 117 (16), 104 (10), 98 (19),
92 (100), 91 (54), 84 (28), 71 (10), 65 (16), 57 (10), 41 (15). Odor description: rosy (geranium), metallic,
nitrile, rhubarb.
I would like to thank Piotr Jaunky and Martin Schrçder for their contributions to this paper by the
results of their research projects. I also would like to thank Yvan Klimkowicz for his helpful laboratory
work in connection with my own projects. The analytical team is also acknowledged, in particular
Christian Ozog for the mass spectra, as are the perfumers who have evaluated the different compounds,
especially Rolph Gasparian, Jean-Paul Pons, and Fabrice Pellegrin. Finally, I would like to thank Jean-
Jacques Chanot and Jean Mane for giving me the opportunity to present this overview of the chemistry
research at Mane during the F&F conference in London, last September.

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1098 CHEMISTRY & BIODIVERSITY – Vol. 5 (2008)

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Received December 18, 2007