FLAVOUR AND FRAGRANCE JOURNAL
Flavour Fra`r[ J[ 1999^ 04] 182Ð187
Synthesis of (10R)-(E)-acora-3,7(11)-dien-12-al, a new
fragrant sesquiterpene aldehyde
Peter Weyerstahl and Peter Degenkolb
Institut für Organische Chemie, Technische Universität Berlin, Strasse des 17 Juni 135, D-10623 Berlin, Germany
Received 02 January 1999
Revised 02 March 1999
Accepted 03 March 1999
ABSTRACT] The synthesis of "09R#!"E#!acora!2\6"00#!dien!01!al "0# is described starting from the enanti!
omerically pure "¦#!pulegenic acid "3# via the Diels!Alder adducts 7a\b[ The odour of the new sesquiterpene
aldehyde was typically aldehydic\ fruity and leathery[ Copyright Þ 1999 John Wiley + Sons\ Ltd[
KEY WORDS] "09R#!"E#!acora!2\6"00#!dien!01!al^ synthesis^ sesquiterpene^ vetiver oil^ odorous compounds
Introduction
Vetiver oil\ the commercially available oil from Veti!
veria zizanioides "L[# Nash "Gramineae#\ is one of the
most complex essential oils[ It contains about 199 con!
stituents\ mostly functionalized bicyclic and tricyclic
sesquiterpenes[ For a long time\ many research groups
have contributed to the analysis of vetiver oil[0 Due
to the pleasant sweet\ woody\ root!like odour\ highly
appreciated in perfumery\ and due to the intellectual
challenge\ we tried to identify further constituents of
this oil[1
In the course of the separation process\ we obtained
a medium polar fraction containing 79) of the new
oppositadienal 2[ This fraction smelled strongly woody
with a rhubarb note\ typical of vetiver oil[ To give
the _nal evidence of the structure and for an olfactory
evaluation\ we recently synthesized aldehyde 2[2 The
polar main fraction containing mostly sesquiterpene
alcohols was only partially separable by ~ash chro!
matography "FC#[ Therefore\ it was transformed on the
one hand to the methyl ethers3 and on the other hand
by MnO1 oxidation to give a mixture of a\b!unsaturated
aldehydes "from the corresponding primary allyl alco!
hols#\ ketones and unchanged alcohols\ more easily sep!
arable by FC[ One of these FC fractions containing
aldehydes "NMR# smelled pleasantly sweetÐwoody[
However\ its main component could be puri_ed only
up to 39)\ since repeated FC led to oxidation and
decomposition[ The structure elucidation by NMR
spectroscopy resulted in formula 0\ an acorane deriva!
tive[ For the same reasons as described above for com!
pound 2\ the presumed acorane 0 should be synthesized[
 Correspondence to] P[ Weyerstahl\ Institut fur Organische Chemie\ Technische
Universitat Berlin\ Strasse des 06 Juni 024\ D!09512 Berlin\ Germany[
Copyright Þ 1999 John Wiley + Sons\ Ltd[
The key compound for an enantioselective synthesis
of 0 is the spiroketone 7 prepared previously by Marx
et al[4 by Diels!Alder reaction of the methylene ketone
6 with isoprene[ Enone 6 was obtained in a seven step
synthesis from "R#!pulegone[
Experimental
0
H!NMR] Bruker AM 399[ 02C!NMR "CDCl2#] Bruker
AC 199 with DEPT program[ GCÐMS] MAT 84 SC\
29 m DB 4 column "Fa[ J + W#\ carrier gas He[ HRÐ
MS] MAT 84 SC\ direct inlet "69 eV#[ GC] Packard 322\
14 m CP Sil 4 CB column\ carrier gas N1[ IR "CCl3#]
Perkin!Elmer 770[ Optical rotation "CHCl2#] Perkin!
Elmer polarimeter 030[ TLC] Silica gel 59 F 143 "Merck
no[ 4443#[ Flash chromatography "FC#] ICN Biome!
dicals silica 21Ð52\ elution with light petroleum ether
"b[p[ 39Ð59>C# and increasing amounts of methyl tbutyl
ether "MTBE#[ For numbering see Schemes 0 and 1[
Preparation of Precursor 7
"0S\4R# ! 0 ! "1!Isopropylidene ! 4 ! methylcyclopentane#
methanol "4#
A solution of "¦#!pulegenic acid "3\ 6[0 g\ 39 mmol#5 in
dry Et1O "39 ml# was added dropwise with stirring at
9>C to a slurry of LiAlH3 "2[1 g\ 73 mmol# in dry Et1O
"69 ml# within 0 h[ Then the mixture was quenched with
saturated NH3Cl solution at 9>C and worked up as
usual to give 4 "5[14 g\ 85)#[ IR] n 2539 cm−0 "OH#[
0
H!NMR "CDCl2#] d 9[84 "d\ J  6 Hz\ 4!Me#\ 0[17
"dddd\ J  02[4\ 7\ 4\ 4 Hz\ 3!H#\ 0[54\ 0[69 "1 s\ br[\
Me1C1#\ 0[74 "dddd\ J  02[4\ 7[4\ 2\ 2 Hz\ 3?!H#\ 1[91Ð
1[06 "m\ 2!\ 4!H#\ 1[21 "ddd\ br[\ J  05\ 6\ 6 Hz\ 2?!
183 P[ WEYERSTAHL AND P[ DEGENKOLB
Scheme 1.
H#\ 1[30 "t\ br[\ J  6 Hz\ 0!H#\ 2[37 "mc\ CH1OH#^ in
agreement with the data given in reference 6[ 02C!NMR]
d 19[3\ 10[9\ 10[3 "2 q\ 4!Me\ Me1C1#\ 17[6\ 20[4 "1 t\
C!2\ !3#\ 25[0 "d\ C!4#\ 41[5 "d\ C!0#\ 53[2 "t\ CH1O#\
013[7 "s\ C!Me1#\ 024[1 "s\ C!1#^ in agreement with the
data given in reference 6[ GCÐMS] m:z ")# 043 "06\
M¦#\ 026 "08#\ 012 "099#\ 84 "05#\ 82 "04#\ 80 "04#\ 70
"62#\ 68 "12#\ 56 "04#[
Odour "GC] 88[8)#] harsh\ mossy\ leathery\ cam!
phoraceous\ woody\ with a tonality of oakmoss[
"1S\2R#!1!Hydroxymethyl!2!methylcyclopentanone "5#
Ozone was bubbled into a mixture of 4 "4[3 g\ 24 mmol#\
2 drops of a saturated solution of sudan red in CH1Cl1
and a spatula tip of NaHCO2 in CH1Cl1 "69 ml# at
−67>C until the colour disappeared "ca[ 0 h#[ Then
dimethyl sul_de "DMS\ 22 ml\ 33 mmol# was added and
the mixture was allowed to warm to room temperature
overnight[ The solvent was evaporated at 14>C:4 Torr
and the residue was worked up as usual to yield crude
5 "3[33 g\ 88)#\ which was used for the next step[ IR] n
2349 "OH#\ 0639 cm−0 "CO#[ 0H!NMR "C5D5 ðCDCl2Ł#]
d 9[79 ð0[06Ł "d\ J  5[4 Hz\ 2!Me#\ 9[71 "dddd\ J  01\
01\ 00\ 7[4 Hz\ 3!H#\ 0[27 ð0[76Ł "ddd\ J  00[4\ 5[4\ 3
Hz\ 1!H#\ 0[43 "dddd\ J  01\ 8\ 5\ 0[4 Hz\ 3?!H#\ 0[5Ð
0[6 "m\ 2!H#\ 0[61 "ddd\ J  07\ 01\ 8 Hz# and 0[84 ð1[27Ł
"ddd\ J  07\ 7[4\ 0[4 Hz\ 4!H1#\ 2[49 ð2[58Ł "dd\ J  00\
5[4 Hz# and 2[68 ð2[76Ł "dd\ J  00\ 3 Hz\ CH1OH#^
reference 4^ d "CDCl2# 0[06 "d#\ 0[3Ð1[3 "m#\ 2[61 "dd#[
Copyright Þ 1999 John Wiley + Sons\ Ltd[
02
C!NMR] d 07[7 "q\ 2!Me#\ 18[2 "t\ C!3#\ 22[2 "d\ C!2#\
27[1 "t\ C!4#\ 47[0 "d\ C!1#\ 48[1 "t\ CH1O#\ 110[2 "s\ C!
0#[ GCÐMS] m:z ")# 018 "67\ M¦¦H#\ 017 "06\ M¦#\
009 "51#\ 84 "01#\ 72 "49#\ 71 "39#\ 58 "44#\ 56 "41#\ 46
"27#\ 44 "099#[
"2R#!1!Methylene!2!methylcyclopentanone "6#
A mixture of 5 "1[6 g\ 10 mmol#\ dicyclohexyl!
carbodiimide "DCCI\ 5[2 g\ 20 mmol# and Cu1Cl1 "19
mg# in dry Et1O "29 ml# was re~uxed for 1 h[ After
_ltration and evaporation the residue was distilled rap!
idly at 39Ð49>C:9[91 Torr "kugelrohr# to yield 6 "0[6 g\
62)#[ IR] n 0629\ 0539 cm−0 "C1C0CO#[ 0H!NMR
"C5D5#] d 0[12 "d\ J  6 Hz\ 2!Me#\ 0[30 "dddd\ J  00\
00\ 09\ 7 Hz# and 1[08 "dddd\ J  00\ 7\ 6\ 2 Hz\ 3!H1#\
1[16 "ddd\ J  07\ 00\ 7 Hz# and 1[39 "ddd\ br[\ J  07\
7\ 2 Hz\ 4!H1#\ 1[65 "ddddq\ J  09\ 6\ 2\ 2\ 6 Hz\ 2!H#\
4[12\ 5[99 "1 d\ br[\ J  2 Hz\ CH1#^ reference 4] d "CCl3#
0[04 "d#\ 0[7Ð1[7 "m#\ 3[78\ 4[47[ 02C!NMR] d 07[8 "q\
2!Me#\ 17[8 "t\ C!3#\ 25[0 "d\ C!2#\ 26[3 "t\ C!4#\ 004[8
"t\ CH1#\ 049[2 "s\ C!1#\ 196[3 "s\ C!0#[
"3R\4S#!"7a# and "3R\4R#!3\7!Dimethylspiroð3[4Łdec!
6!en!0!one "7b#
A solution of 6 "3[4 g\ 30 mmol# in benzene "4 ml# was
added dropwise with stirring at 9>C to a slurry of AlCl2
"49 mg\ 9[3 mmol# in benzene "4 ml# within 19 min[
Then isoprene "01[3 ml\ 019 mmol# was added dropwise[
Stirring was continued at room temperature for 0 h\
Flavour Fra`r[ J[ 1999^ 04] 182Ð187
 SYNTHESIS OF A NEW FRAGRANT SESQUITERPENE ALDEHYDE 184

Scheme 2.

then the mixture was cooled to 9>C[ AlCl2 "9[43 g\ 3 Usual work!up and FC "PE:MTBE 85 ] 3# gave 7a\b
mmol# was added\ the mixture was allowed to warm to "5[56 g\ 81)#\ GC] 79 ] 19[ ðaŁD!43[4> "c  2#[ IR] n 0624
room temperature and stirring was continued overnight[ cm−0 "CO#[ 0H!NMR "C5D5\ from the mixture# 7a] d

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Flavour Fra`r[ J[ 1999^ 04] 182Ð187
185 P[ WEYERSTAHL AND P[ DEGENKOLB

Table 1. 13C-NMR (d, CDCl3)a values of compounds 1, 8, 9, 03[4 mmol# in a mixture of freshly distilled tetra!
11, 12 and 13 (for numbering see Figure 1) methylene diamine "TMEDA\ 29 ml# and PE "09 ml#[
C No[ 0b 02 01 00 8c 7ad Stirring was continued at −49>C for 09 min and at
room temperature for 1 h[ Then the mixture was cooled
0 s 40[0 38[3 38[5 36[4 35[8 38[6
1 t 23[2 26[5 28[9 28[1 17[1 20[0
to −67>C\ treated with freshly distilled acetaldehyde
2 d 019[4 019[5 008[7 019[7 008[0 007[2 "1[3 ml\ 32 mmol# and stirred for a further 29 min[ The
3 s 023[7 023[0 022[8 028[9 022[4 022[4 mixture was allowed to warm to 9>C within 5 h and
4 t 17[8 17[1 17[9 17[0 16[9 15[5
5 t 29[5 22[2 22[9 25[2 14[4 15[2
quenched with ice:water[ Usual work!up and FC
6 s 069[3 s 038[6 s 049[9 d 028[0 s 060[1 s 111[1 "PE:MTBE 1 ] 0# gave 00 "9[33 g\ 08)# as _rst fraction
7 t 17[8 d 013[4 d 033[1 d 017[5 t 23[0 t 24[9 and 09 "0[35 g\ 38)# as second fraction[
8 t 16[3 15[3 13[4 16[6 13[2 11[4
09 d 28[8 39[7 28[2 31[6 39[4 27[8
00 s 029[6 s 001[0 s 086[6 "3R\4S#\3\7 ! Dimethylspiroð3[4Łdeca ! 0\6 ! dien ! 0 ! yl#
3!Me q 13[1 12[4 12[4 12[4 12[2 12[1
09!Me q 05[3 05[1 05[6 02[4 03[2 03[7 ethanol "09\ 0 ] 0!mixture of C!00 diastereomers#
00!Me q 00[4 02[4 17[1 IR] n 2519\ 2379 cm−0 "OH#[ 0H!NMR "CDCl2#] d
00!Re d 082[3 d 032[5 9[78:9[80 "d\ J  6 Hz\ 09!Me#\ 0[21:0[23 "1 d\ J  6
 Exchangeable values[ Hz\ 00!Me#\ 0[56 "s\ br[\ 3!Me#\ 1[33 "d\ br[\ J  04 Hz\
a
Without 0H02C correlation[ 1!H#\ 3[14 "mc\ 00!H#\ 4[24:4[28 "mc\ 2!H#\ 4[69 "mc\ 7!
b
In C5D5[ Values for the major "0S#!isomer[ The "0R#!isomer shows] d 38[3 "s\
C!0#\ 010[5 "d\ C!2#\ 023[9 "s\ C!3#\ 060[8 "s\ C!6#\ 32[0 "d\ C!09#\ 029[7 "s\ C! H#[ 02C!NMR] d 04[4:04[6 "q\ 09!Me#\ 12[4 "q\ 3!Me#\
00#\ 13[2 "q\ 3!Me#\ 06[7 "q[ 09!Me#\ 01[1 "q\ 00!Me#\ 082[3 "d\ 00!CHO#\ 17[2\ 13[2 "q\ 00!Me#\ 15[1:15[3\ 17[9:17[0\ 22[4:22[6\ 26[3 "3
18[3\ 18[6\ 20[8\ 21[4 "4 t#[
c
Without tosyl values[ t\ C!1\ !4\ !5\ !8#\ 30[9:30[3 "d\ C!09#\ 37[6 "s\ C!0#\
d
Values for the minor isomer 7b] d 49[9 "s\ C!0#\ 007[7 "d\ C!2#\ 021[8 "s\ C!3#\ 53[8:54[0 "d\ C!00#\ 019[3:019[5 "d\ C!2#\ 012[2:012[3 "d\
111[7 "s\ C!6#\ 27[7 "d\ C!09#\ 12[0 "d\ 3!Me#\ 05[5 "09!Me#\ 15[4\ 15[7\ 15[8\
18[2\ 24[2 "4 t#[ C!7#\ 023[0:023[1 "s\ C!3#\ 043[8 "s\ C!6#[ GCÐMS] m:z
e
0] R  CHO^ 02] R  CHOMe^ OMe] q 48[3[ ")# 195 "0\ M¦#\ 077 "41#\ 062 "11#\ 059 "39#\ 027 "38#\
012 "24#\ 098 "26#\ 84 "099#\ 80 "14#\ 68 "11#[
9[61 "d\ J  6 Hz\ 09!Me#\ 0[08 "dddd\ J  02\ 8\ 6\ 6
Hz\ 8!H#\ 0[25 "ddd\ br[\ J  02\ 6\ 5 Hz\ 0 H#\ 0[4Ð1[9 "3R\4S# ! 3\7 ! Dimethylspiroð3[4Łdeca ! 0\6 ! diene
"m\ 6 H#\ 0[56 "s\ br[\ 3!Me#\ 0[80 "ddd\ J  08\ 8\ 6 Hz# "00#
and 1[94 "ddd\ J  08\ 8\ 5 Hz\ 7!H1#\ 4[26 "mc\ 2!H#[ 0
H!NMR "CDCl2#] d 9[83 "d\ J  6 Hz\ 09!Me#\ 0[53 "s\
7b] d 9[64 "d\ J  6 Hz\ 09!Me#\ 0[56 "s\ br[\ 3!Me#\ 4[24 br[\ 3!Me#\ 1[28 "dddd\ J  05\ 7\ 2\ 1 Hz# and 1[44
"mc\ 2!H#[ 02C!NMR] See Table 0[ GCÐMS "7a  7b#] "dddd\ J  05\ 7\ 1\ 1 Hz\ 8!H1#\ 4[27 "mc\ 2!H#\ 4[57
m:z ")# 067 "29\ M¦#\ 052 "39#\ 059 "099#\ 034 "78#\ 025 "dd\ br[\ J  2\ 1 Hz\ 6!H#\ 4[70 "dd\ br[\ J  2\ 1 Hz\ 7!
"66#\ 010 "55#\ 096 "38#\ 82 "88#\ 80 "61#\ 68 "69#\ 66 "41#\ H#[ 02C!NMR] See Table 0[ GCÐMS] m:z ")# 051 "01\
56 "35#[ M¦#\ 036 "29#\ 83 "59#\ 80 "19#\ 68 "099#[
"3R\4S#!3\7!Dimethylspiroð3[4Łdec!6!en!0!one tosyl!
hydrazone "8# "3R\4S# ! 3\7 ! Dimethylspiroð3[4Łdeca ! 0\6 ! dien ! 0 ! yl#
Ketone 7a\b "9[79 g\ 3[4 mmol# was poured into a slurry ethanone "01#
of tosylhydrazine "9[78 g\ 3[7 mmol# in methanol "2 Analogously to reference 7\ tetrapropylammonium per!
ml#[ After addition of glacial acetic acid "7 drops# the ruthenate "TPAP\ 84 mg\ 9[16 mmol# was added to a
solution becomes clear[ After 0 d it was concentrated mixture of N!methylmorpholine N!oxide "NMO\ 9[84
and _ltered[ The white solid was washed with cold meth! g\ 7[0 mmol#\ 09 "0[00 g\ 4[3 mmol# and molecular sieves
anol and dried in vacuo at room temperature over 1 "3 _\ 1[6 g# in CH1Cl1 "09 ml#[ The mixture was stirred
days to yield 8 "0[16 g\ 71)#\ m[ p[ 025>C[ IR] n 2119 for 0 h at room temperature\ then it was _ltered over
cm−0 "C1N#[ 0H!NMR "CDCl2#] d 9[71 "d\ J  6 Hz\ silica gel and washed several times with CH1Cl1[ After
09!Me#\ 0[24Ð0[5 "m\ 2 H#\ 0[53 "s\ br[\ 3!Me#\ 0[6Ð1[94 evaporation and FC "PE:MTBE 2 ] 0# 01 "9[87 g\ 78)#
"m\ 5 H#\ 1[04 "ddd\ J  08\ 8\ 6 Hz# and 1[13 "ddd\ remained[ ðaŁD −19> "c  00#[ IR] n 0569\ 0594 cm−0
J  08\ 09\ 5 Hz\ 7!H1#\ 4[18 "mc\ 2!H#^ NHTs] 1[30 "s\ "C1C0CO#[ 0H!NMR "CDCl2#] d 9[81 "d\ J  6 Hz\
Me!Ar#\ 6[03 "s\ br[\ NH#\ 6[17\ 6[79 "1 d\ br[\ J  8 09!Me#\ 0[45 "dddd\ J  02\ 5\ 1\ 1 Hz\ 5!H#\ 0[54 "s\
Hz\ 3 H!Ar#[ 02C!NMR] See Table 0[ C08H15N1O1S^ br[\ 3!Me#\ 0[69 "d\ br[\ J  07 Hz\ 1!H#\ 0[76 "dd\ br[\
calculated 235[0604\ found 235[0611 "HRÐMS#[ J  06\ 5[4 Hz\ 4!H#\ 0[85 "ddd\ J  07\ 3\ 0[4 Hz\ 8!
H#\ 1[90 "d\ br[\ J  06 Hz\ 4?!H#\ 1[04 "qdd\ J  6\ 6\
"3R\4S#!3\7!Dimethylspiroð3[4Łdeca!0\6!diene!0!yl# 0[4 Hz\ 09!H#\ 1[17 "s\ MeCO#\ 1[17 "d\ br[\ J  07 Hz\
ethanol "09# and "3R\4S#!3\7!dimethylspiroð3[4Łdeca! 1?!H#\ 1[34 "ddd\ J  02\ 01\ 5[4 Hz\ 5?!H#\ 1[53 "ddd\
0\6!diene "00# J  07\ 6\ 2 Hz\ 8?!H#\ 4[29 "dq\ J  2[4\ 0[4 Hz\ 2!H#\
nBuLi "0[5 M in hexane\ 16 ml\ 32 mmol# was added 5[57 "dd\ J  3\ 2 Hz\ 7!H#[ 02C!NMR] See Table 0[
dropwise with stirring at −49>C to a slurry of 8 "4[9 g\ GCÐMS] m:z ")# 193 "32\ M¦#\ 078 "34#\ 075 "07#\ 060

Copyright Þ 1999 John Wiley + Sons\ Ltd[ Flavour Fra`r[ J[ 1999^ 04] 182Ð187
 SYNTHESIS OF A NEW FRAGRANT SESQUITERPENE ALDEHYDE 186
"06#\ 050 "25#\ 046 "19#\ 025 "84#\ 010 "099#\ 094 "20#\ 82
"56#\ 80 "57#\ 66 "41#[
"E#!"3R\4S#!0!"1!Methoxy!0!methylethenyl#!3\7!di!
methylspiroð3[4Łdeca!0\6!diene "02#
Methoxymethylphosphonium chloride "2[32 g\ 09
mmol# in Et1O "14 ml# was treated with nBuLi "0[5 M
in hexane\ 4 ml\ 7 mmol# at room temperature[ A solu!
tion of 01 "9[60 g\ 2[4 mmol# in Et1O "1 ml# was added
dropwise at −29>C to the red solution[ The mixture
was allowed to warm to room temperature and was
stirred overnight[ After _ltration\ evaporation and FC
"PE:MTBE 09 ] 0 : 0 ] 0# 02 "9[50 g\ 65)# was obtained[
0
H!NMR "CDCl2\ typical signals only#] d 9[80 "d\ J  6
Hz\ 09!Me#\ 0[55 "s\ br[\ 3!Me#\ 0[61 "s\ br[\ 00!Me#\
1[34 "ddd\ J  06\ 6\ 1[4 Hz\ 8!H#\ 2[48 "s\ OMe#\ 4[23
"mc\ 2!H#\ 4[31 "dd\ J  1[4\ 1[4 Hz\ 7!H#\ 5[95 "s\ br[\
01!H#[ 02C!NMR] See Table 0[ GCÐMS] m:z ")# 121
"10\ M¦#\ 053 "34#\ 050 "47#\ 038 "099#\ 034 "02#\ 022
"34#\ 006 "04#\ 094 "16#\ 80 "18#[
"09R# ! "E# ! Acora ! 2\6"00#!dien!01!al ð"E#!"3R#!1!
"3\7!dimethylspiroð3[4Łdec!6!ylidene!0!#propanal\ 0Ł
A solution of 02 "9[08 g\ 9[71 mmol#\ pyridinium p!
toluenesulfonate "PPTS\ 9[4 g# in acetone "01 ml# was
re~uxed for 19 min[ After usual work!up and FC "hex!
ane:Et1O\ 09 ] 0# a diastereomeric mixture "19 mg\ 00)#
of the "0S#!isomer "0\ GC] 56)\ RI Sil 4] 0683# and of
the "0R#!isomer "GC] 16)\ RI Sil 4] 0665# was isolated[
ðaŁD −15[1> "c  02#[ IR] n 0569\ 0519 cm−0
"C1C0CO#[
Odour "GC] 83)#] aldehydic\ aqueous\ fruity\ leath!
ery[
0 08) of the readily separable alkene 00[ Oxidation of
H!NMR "C5D5 ðCDCl2Ł\ from the mixture#] "0S#!
isomer] "0# d 9[60 ð9[82Ł "d\ J  6 Hz\ 09!Me#\ 0[54 ð0[58Ł
"s\ br[\ 3!Me#\ 0[63 "mc\ 1!H#\ 0[80 ð0[71Ł "dd\ J  1\ 1
Hz\ 00!Me#\ 1[90 "mc\ 1?!H#\ 1[35 "mc\ 7!H1#\ 4[16 ð4[21Ł
"mc\ 2!H#\ 09[91 ð09[94Ł "s\ CHO#[
02
C!NMR] See Table 0[ GCÐMS] m:z ")# 107 "19\
¦ fore\ an unambiguous assignment of the con_guration
M #\ 192 "09#\ 199 "4#\ 078 "01#\ 050 "56#\ 049 "39#\ 024
"099#\ 010 "29#\ 096 "07#\ 094 "05#\ 80 "08#\ 68 "02#[
C04H11O] calculated 107[0560\ found 107[0560 "HRÐ
MS#[
"0R#!isomer] d 9[68 ð9[80Ł "d\ J  6 Hz\ 09!Me#\ 0[52
ð0[56Ł "s\ br[\ 3!Me#\ 0[70 "mc\ 1!H#\ 0[81 ð0[72Ł "dd\
J  1\ 1 Hz\ 00!Me#\ 1[21 "mc\ 1?!H#\ 1[15 "ddq\ J  06\
7\ 1 Hz# and 1[45 "dddq\ J  06\ 6\ 6\ 1 Hz\ 7!H1#\ 4[23
ð4[30Ł "mc\ 2!H#\ 09[92 ð09[94Ł "s\ CHO#[ 02C!NMR] See
Table 0[ GCÐMS] Nearly identical with that of 0[
Results and Discussion
The synthesis of enone 6 could be improved[ "¦#!Pule!
genic acid "3#\ readily available from "R#!pulegone\ or
Copyright Þ 1999 John Wiley + Sons\ Ltd[
directly from pennyroyal oil\5 was reduced with LiAlH3
to give the alcohol 4[ The odour of this monoterpene
derivative 4 "GC] 88[8)# was harsh\ mossy\ leathery\
camphoraceous\ woody\ with a tonality of oakmoss[
Ozonolysis of which yielded the labile hydroxyketone
5[ Subsequent dehydration of 5 with DCCI a}orded
compound 6 which is prone to undergo polymerization[
The thermal Diels!Alder reaction of 6 with isoprene
to give the spiroketone 7 is not very diastereoselective
since by {para| vs[ {meta| attack and by trans vs[ cis
position of the methyl group of the cyclopentane ring
to the double bond of the six!membered ring\ all the
four diastereomers were formed[ By addition of Lewis
acids\ the trans:cis selectivity was improved a little and
the genesis of the undesired {meta| isomers was
suppressed[4 We studied the in~uence of various Lewis
acids to optimize this Diels!Alder reaction[ By addition
of AlCl2 in two successive parts to the reaction mixture
"0 mol) at 9>C\ then 09 mol) after 0 h#\ a 3 ] 0 mixture
of 7a\b was obtained in 81) total yield[ Such a dias!
tereomeric ratio of about 3 ] 0 was maintained also in
the following steps up to compound 02[ However\ for
reasons of simplicity\ we have looked only at the main
isomers of 8Ð02[
The introduction of the side chain at the sterically
hindered keto function is quite di.cult[ After some
preliminary experiments "Wittig!Horner reaction\ alk!
enyllithium\ acetylide anion#\ the Shapiro reaction8 was
successful[ Treatment of the tosyl hydrazone 8 with 2
equivalents of nBuLi in TMEDA:hexane followed by
addition of acetaldehyde gave the secondary alcohol 09
in 38) yield as a 0 ] 0 mixture of two diastereomers by
forming a new stereogenic centre at C!00\ together with
allyl alcohol 09 with MnO1 furnished the ketone 01 in
55) yield[ By means of the oxidation system\
TRAP:NMO\7 the yield could be improved to 78)[
The 0H!NMR spectrum of the main isomer of 01
showed clearly separated signals for all protons[ There!
was possible by the NOED spectra[ 09!Me gave a NOE
with 5!Ha\ 09!H showed a NOE with 1!Ha\ hence\ the
methyl group at C!09 "cyclopentane ring# is trans orien!
tated to the double bond "cyclohexene ring#[
For the homologation of 01 to the aldehyde 0\ a
Wittig reaction via the corresponding enol ether 02 was
chosen[ Due to the sterical hindrance of the keto group
of 01\ the Wittig reaction was di.cult[ After several
experiments under various conditions\ reaction of 01
with 2 equivalents of triphenylmethoxymethyl!
phosphonium chloride in presence of 1[2 equivalents of
nBuLi gave the "E#!enol ether 02 in 65) yield[ Hydroly!
sis of 02 should provide the free aldehyde group\ and
under these reaction conditions the 6\7!double bond
should be shifted in conjugation to the 6\00!position[
Several well!known reagents for the enol cleavage failed
Flavour Fra`r[ J[ 1999^ 04] 182Ð187
187 P[ WEYERSTAHL AND P[ DEGENKOLB
or led to decomposition[ The only method we found\
treatment of 02 with PPTS in re~uxing aqueous acetone\
a}orded the acoradienal 0 in a non!optimized yield of
00) after FC[ In addition\ starting from the 4 ] 0 iso!
meric mixture of 02\ this ratio decreased to 1[4 ] 0[ This
result indicated that the major "0S#!isomer 0 is even
more sensitive than its minor "0R#!isomer[ However\
the con_guration of both products was proven again
by the NOED spectra similar to those of ketone 01[
Furthermore\ the NOEs con_rmed the "E#!con!
_guration of the aldehyde\ as expected for sterical
reasons[ The 0H!NMR data of 0 are similar to those of
the compound isolated from the oxidized polar fraction
of vetiver oil\ but not identical[ Meanwhile\ after
extended NMR studies\ the structure of this aldehyde
was assigned to be 1\ a spirovetivane derivative[09
Thus\ acoradienal is an enantioselectively synthesized
sesquiterpene aldehyde\ not yet found in nature[ The
odour of the mixture "GC] 83)# of 0 and its "0R#!
Copyright Þ 1999 John Wiley + Sons\ Ltd[
epimer was evaluated as typically aldehydic\ fruity and
leathery[
Acknowled`ement * We thank Dr S[ Sonnenberg\ Haarmann +
Reimer GmbH\ D!26590 Holzminden\ for the olfactory evaluations[
References
0[ Smadja J[ Riv[ Ital[ EPPOS[ 0883^ 04[
1[ Weyerstahl P\ Marschall H\ Splittgerber U\ Wolf D\ Surburg H[
Flavour Fra`r[ J[\ in press[
2[ Weyerstahl P\ Marschall H\ Degenkolb P\ Lebada P[ Eur[ J[ Or`[
Chem[ 0888^ 564[
3[ Weyerstahl P\ Marschall H\ Splittgerber U\ Wolf D[ Flavour
Fra`r[ J[\ in press[
4[ Marx JN\ Norman LR[ J[ Or`[ Chem[ 0864^ 39] 0591[
5[ Weyerstahl P\ Brendel J[ Liebi`s Ann[ Chem[ 0881^ 558[
6[ Nangia A\ Prasuna G[ Tetrahedron 0885^ 21] 2324[
7[ Ley SV\ Norman J\ Gri.th WP\ Marsden SP[ Synthesis 0883^
528[
8[ Chamberlin AR\ Bloom SH[ Or`[ React[ 0889^ 28] 0[
09[ Weyerstahl P\ Marschall H\ Splittgerber U\ Wolf D[ Flavour
Fra`r[ J[ 1999^ 04] 50[
Flavour Fra`r[ J[ 1999^ 04] 182Ð187