The first synthesis of geranyllinalool enantiomers

Article abstract of DOI:10.1135/cccc20020083

(3R)-(-)-Geranyllinalool and its (3S)-(+)-isomer were synthesized in 7 steps starting from both enantiomers of citramalic acid and geranyl bromide. The synthetic sequence established the absolute configurations of naturally occurring geranyllinalools for

Full text of DOI:10.1135/cccc20020083

Geranyllinalool Enantiomers
83
THE FIRST SYNTHESIS OF GERANYLLINALOOL ENANTIOMERS
1,
2
3
Aleš SVATOŠ *,+, Klára URBANOVÁ and Irena VALTEROVÁ
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
1
Flemingovo nám. 2, 166 10 Prague 6, Czech Republic; e-mail: svatos@uochb.cas.cz,
2
3
urbanova@uochb.cas.cz, irena@uochb.cas.cz
Received Novem ber 5, 2001
Accepted Jan uary 4, 2002
Dedicated to the memory of Dr Václav Černý.
(3R)-(–)-Geran yllin alool an d its (3S)-(+)-isom er were syn th esized in 7 steps startin g from
both en an tiom ers of citram alic acid an d geran yl brom ide. Th e syn th etic sequen ce estab-
lish ed th e absolute con figuration s of n aturally occurrin g geran yllin alools for th e first tim e.
Keyw ord s: Terpen oids; Diterpen es; Alcoh ols; Absolute con figuration ; Markin g ph erom on es;
Bum blebees; Cuprates; Cross-couplin g reaction s; Carbom etallation .
Geran yllin alool (1) is a diterpen e alcoh ol widely distributed in biological
m aterials. It can be foun d in oleoresin s1, in plan ts (“Absolue de Jasm in ”)2,
an d it is also an im portan t in sect sem ioch em ical3. Ch iral diterpen ic alco-
h ols such as geran ylcitron ellol or geran yllin alool are rath er com m on com -
pon en ts of m arkin g ph erom on es of bum blebee an d cuckoo-bum blebee
m ales4. On e of th e im portan t ch aracteristics of th ose sign als is th e in form a-
tion about th e absolute con figuration s of ch iral ph erom on e com pon en ts5.
However, up-today on ly ach iral syn th eses of geran yllin alool h ave been de-
veloped6 an d th e absolute con figuration of n aturally occurrin g geran yl-
lin alool rem ain s to be establish ed. In th is paper, we are reportin g th e first
syn th esis of both en an tiom ers of geran yllin alool (Sch em e 1) establish in g
th e absolute con figuration s of n aturally occurrin g com poun ds.
+
Presen t address: Max Plan ck In stitute for Ch em ical Ecology, Win zerlaer Str. 10, 7745 Jen a,
Germ an y.
Collect. Czech. Chem. Commun. (Vol. 67) (2002)
doi:10.1135/cccc20020083

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Svatoš, Urbanová, Valterová:
EXPERIMENTAL
All air-sen sitive organ ic tran sform ation s were run in an oven -dried (120 °C) glassware.
Solven ts were dried an d distilled prior to use: tetrah ydrofuran (THF) an d dieth yl eth er from
ben zoph en on e/Na ketyl, aceton e with dry potassium carbon ate in an argon atm osph ere.
Oth er reagen ts an d solven ts were purch ased from com m ercial sources an d used with out fur-
th er purification . NMR spectral data were recorded in CDCl3 solution on
a Varian
UNITY-500 spectrom eter at 500 MHz for 1H an d 128.2 MHz for 13C, respectively. TMS was
used as th e in tern al stan dard an d ch em ical sh ifts (in ppm ) were plotted on th e δ-scale.
Couplin g con stan ts (J) are given in Hz. In frared spectra (waven um bers in cm –1) were m ea-
sured in CCl4 solution on a Bruker IFS 88FT-IR spectrom eter. Optical rotation s were recorded
in CHCl3 or eth er on a Perkin –Elm er 241 polarim eter at 20 °C; [α]D values are given in
10–1 deg cm 2/g.
Silica gel Merck 60 (0.040–0.063 m m ) or Florisil (200–300 m esh , Merck) were used for col-
um n ch rom atograph y. Th e purity of syn th esized com poun ds was ch ecked both by TLC on
silica gel Merck 60 an d usin g GC-MS with a Fison s MD 800 in strum en t. Th e capillary col-
um n used for separation was a DB-5m s (5% ph en yl m eth yl silicon e, 30 m × 0.25 m m , film
th ickn ess 0.25 µm ). Th e tem perature program started at 50 °C, wh ile after 2 m in th e tem per-
ature was in creased to 300 °C at a rate of 10 °C/m in . In jector tem perature was 220 °C, h e-
lium flow 0.94 m l/m in .
(+)-(S)-2,2,4-Trim eth yl-1,3-dioxolan -4-eth an ol ((S)-4)
(+)-(S)-2-Hydroxy-2-m eth ylbutan edioic acid {citram alic acid, 2; 2.96 g, 20 m m ol, [α ]2D0 23
(c 3, H2O)} was dissolved in THF (20 m l). Th e solution was cooled to 0 °C an d a boran e–
dim eth yl sulfide com plex (10 M, 5 m l) was added dropwise. Meth an ol was added in two por-
tion s (2 × 0.6 m l) after 20 m in of stirrin g an d subsequen tly after 80 m in . After 30 m in of
furth er stirrin g th e reaction m ixture was h eated to 60 °C for 1 h . Th e solven ts were evapo-
rated an d th e residue was ch rom atograph ed on a silica gel colum n (elution with 10, 30, 60%
of dieth yl eth er in ligh t petroleum an d fin ally n eat eth er). Th e target product (S)-3 was
eluted from th e colum n with m eth an ol. After rem oval th e solven t in vacuum dry aceton e
(142 m l), CuSO4 (4.6 g) an d p-toluen esulfon ic acid (5 m g, 0.029 m m ol) were added. After
3 h on e m ajor product was form ed (ch ecked by TLC, RF 0.38, ligh t petroleum –eth yl acetate
7 : 3). Th e reaction m ixture was filtered an d evaporated to dryn ess. Dieth yl eth er (60 m l)
was added to th e residue, an d th e solution was extracted with a saturated aqueous solution
of NaHCO3 (1 × 20 m l) an d th en with brin e (1 × 20 m l). Th e organ ic ph ase was dried over
an h ydrous MgSO4. After evaporation of th e solven t, 1.540 g (52%) of th e 4 were obtain ed.
[α ]2D0 +4.66 (c 1.0, dieth yl eth er). 1H NMR: 1.34 (3 H, s, H-1); 1.410 an d 1.414 (6 H, 2 × s,
H-2, H-3); 1.77 (2 H, t, J = 1.8, H-5); 2.70 (1 H, t, J = 2.7, H-7); 3.79 (4 H, m , H-4, H-6). MS,
m/z (%): 145 (M – 15; 31), 115 (M – 45; 24), 97 (6), 85 (32), 72 (72), 67 (13), 61 (5), 59 (12),
57 (49), 55 (32), 53 (4), 43 (100), 42 (25), 41 (22), 39 (13), 31 (14).
Sim ilarly, (–)-(R)-citram alic acid {3.94 g, 32.8 m m ol, [α ]2D0 23 (c 3, H2O)} yielded (R)-4
(1.82 g, 43%). [α ]2D0 –4.33 (c 0.8, dieth yl eth er).
(+)-(S)-2-(2,2,4-Trim eth yl-1,3-dioxolan -4-yl)eth yl Tosylate (5)
Th e protected triol (S)-4 (0.56 g, 3.5 m m ol) was dissolved in THF (4 m l). p-Toluen esulfon yl
ch loride (1.58 g, 8.32 m m ol) was added, an d th e reaction m ixture was kept at –10 °C. Pow-
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Geranyllinalool Enantiomers
85
dered KOH (1.3 g) was added in portion s to th e m ixture durin g th e n ext 30 m in . Th e m ix-
ture was furth er kept at –10 °C for 1.5 h un der stirrin g. Brin e (2 m l) was added an d th e
tem perature in creased to 20 °C. Dieth yl eth er (20 m l) was added, an d th e separated organ ic
layer was dried over an h ydrous MgSO4 (3 g). Th e filtrate was evaporated in vacuo an d th e
residue was ch rom atograph ed on Florisil in ligh t petroleum –dieth yl eth er m ixture (5, 10,
an d 20%). Tosylate (S)-5 (0.685 g, 62%) was obtain ed after evaporation of th e solven ts. [α ]D20
+7.06, (c 0.6, dieth yl eth er). 1H NMR: 1.24 an d 1.27 (6 H, 2 × s, H-2, H-3); 1.4 (1 H, s, H-1);
1.91 (2 H, t, J = 1.95, H-5); 2.45 (3 H, s, H-8); 3.74 (2 H, q, J = 3.75, H-4); 4.16 (2 H, t, J =
4.18, H-6); 7.5 (4 H, m , H-7). 13C NMR: 21.6 (C-13), 24.8 (C-7), 26.81 (C-8), 26.84 (C-5),
38.5 (C-3), 67.0 (C-4), 74.2 (C-1), 79.2 (C-2), 109.3 (C-6), 127.9 (C-10), 129.9 (C-11), 133.0
(C-12), 144.8 (C-9). MS, m/z (%): 299 (M – 15; 44), 291 (9), 281 (4), 239 (7), 207 (7), 155
(48), 127 (36), 115 (26), 107 (5), 97 (8), 91 (74), 85 (100), 83 (13), 72 (65), 65 (30), 59 (14),
57 (20), 55 (12), 43 (92), 41 (16), 39 (11).
Sim ilarly, (R)-4 (0.60 g) yielded (R)-5 (0.539 g, 46%). [α ]2D0 –7.42 (c 0.4, dieth yl eth er).
(E)-6,10-Dim eth ylun deca-5,9-dien -1-yn e4a (7)
Th e title com poun d was prepared usin g a sligh tly m odified procedure4a. Allen e (7 m l) pre-
pared from 1,2-dich loroprop-1-en e (18 m l, 195 m m ol) was treated with butyllith ium (2.5 M,
20 m l, 50 m m ol) to form dilith iated allen e an d th e reaction m ixture was subsequen tly
treated at –30 °C with geran yl brom ide (6; 3.27 m l, 16.4 m m ol). After distillation , 1.629 g
(46%) of pure 7 (b.p. 105 °C/15 torr) was obtain ed.
(1E,5E)-1-Iodo-2,6,10-trim eth ylun deca-1,5,9-trien e4a (8)
Th e com plex, [ZrCl2(η5-cyclopen tadien yl)2] (0.55 g, 1.87 m m ol), was dissolved in dry di-
ch lorom eth an e (30 m l). Th e flask was cooled to –25 °C, an d a solution of trim eth yl-
alum in ium in toluen e (1 M, 13.2 m l, 13.2 m m ol) was added. After 30 m in , water (240 µl)
was added dropwise. Coolin g to –20 °C was con tin ued for an oth er 30 m in wh en acetylen e 7
(1.56 g, 8.8 m m ol) dissolved in dich lorom eth an e (10 m l) was added. Th e reaction m ixture
was stirred at –20 °C for 20 m in . Th en , iodin e (2.68 g, 10.6 m m ol) dissolved in THF (10 m l)
was added at –45 °C. Th e tem perature was th en in creased to –5 °C an d kept for 5 m in . A sat-
urated solution of Na2CO3 (2 m l) an d MgSO4 (4 g) was added at room tem perature, an d in -
organ ic salts were filtered off. After evaporation of th e solven ts, a ch rom atograph ically pure
product (RF 0.44, ligh t petroleum –eth yl acetate 9 : 1) was obtain ed. After distillation (b.p.
95–110 °C/150 Pa), 2.498 g (89.3%) of 8 were obtain ed. Measured spectral data on th is sam -
ple were in full accord with th ose of th e previously prepared sam ple4a
.
(+)-(5E,9E)-(S)-1,2-O-Isopropyliden e-2,6,10,14-tetram eth ylpen tadeca-
5,9,13-trien e-1,2-diol (10)
A solution of 2-th ien yllith ium in THF (1 M, 1 m l, 1 m m ol) was added dropwise to a suspen -
sion of CuCN (89.6 m g, 1.4 m m ol) in THF (0.5 m l) at –80 °C. Th e tem perature was th en in -
creased to 0 °C un der form ation of a brown solution of dilith ium cyan o(2-th ien yl)cuprate.
Iodide 8 (398 m g, 1.25 m m ol) was dissolved in THF (1 m l) in a separate flask an d cooled to
–90 °C in an eth er/CO2 (s) bath . A solution of t-BuLi (1.7 M, 1.25 m l, 2.1 m m ol) in pen tan e
was added an d th e reaction m ixture was stirred for 20 m in . Th is m ixture was th en tran s-
ferred in to th e flask with th e cuprate solution usin g stain less tubin g an d an argon over-
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Svatoš, Urbanová, Valterová:
pressure. Th e solution of th e form ed 2-th ien yl(vin yl)cuprate (9) was stirred at ca –30 °C for
an oth er 10 m in . Th e tem perature of th e reaction m ixture was decreased to –70 °C, an d a so-
lution of tosylate 5 (0.251 g, 0.8 m m ol) in THF (1 m l) was added. Th e reaction was com -
pleted at 20 °C after 2 days. Ice (3 g) was added to th e m ixture, followed by addin g a
saturated solution of NH4Cl an d NH4OH (2 : 1, 10 m l) an d eth er (10 m l). After 10 m in stir-
rin g, th e product was extracted with eth er (2 × 10 m l). Th e com bin ed organ ic ph ases were
wash ed with a saturated solution of NH4Cl an d NH4OH (2 : 1, 10 m l) an d dried over an h y-
drous MgSO4. After evaporation of th e solven ts th e product was purified on Florisil (0, 5, 10,
20, an d 50% eth er in ligh t petroleum ). Com poun d 10, obtain ed in 45% yield (0.12 g), was
im m ediately used for th e n ext reaction . MS, m/z (%): 334 (M+; 1), 319 (M+ – 15; 1), 291 (1),
276 (7), 265 (1), 250 (2), 189 (4), 175 (4), 161 (3), 149 (7), 136 (14), 121 (19), 115 (13), 109
(14), 107 (14), 95 (24), 93 (24), 81 (63), 69 (100), 57 (19), 41 (26).
Sim ilarly, (R)-5 (0.251 g, 0.8 m m ol) yielded 0.1685 g (63%) of crude (R)-10.
(+)-(5E,9E)-(S)-2,6,10,14-Tetram eth ylpen tadeca-5,9,13-trien e-1,2-diol (11)
Pyridin ium (4-toluen e)sulfon ate (108 m g, 0.43 m m ol) an d m eth an ol (9 m l) were added
to 10 (0.12g, 0.36 m m ol). After 44 h of stirrin g at th e room tem perature th e reaction was
term in ated sin ce n o addition al 11 was form ed (TLC, RF 0.67, ligh t petroleum –eth yl acetate
9 : 1). Colum n ch rom atograph y on Florisil (elution system 30, 50, 70, an d 100% dieth yl
eth er in ligh t petroleum ) afforded 76.2 m g (67%) of diol 11. A substan tial am oun t of
un reacted 10 (19.2 m g) was recovered. [α ]2D0 +2.52 (c 0.3, CHCl3). 1H NMR: 1.29 (3 H, s); 1.56
(3 H, s); 1.59 (3 H, s); 1.60 (3 H, s); 1.65 (3 H, s); 1.60–2.08 (6 × 2 H, m ); 3.24 (2 H, s); 3.7
(2 H, bs); 5.00 (1 H, bd, J = 10.2); 5.10 (2 H, bt, J = 6.6); 5.17 (1 H, bt, J = 6.6). MS, m/z (%):
294 (M+; 2), 276 (M+ – 18; 1), 245 (4), 210 (5), 189 (4), 163 (6), 152 (5), 136 (22), 121 (42),
109 (26), 95 (55), 93 (61), 81 (100), 79 (25), 75 (11), 69 (91), 67 (28), 55 (32), 41 (49).
HR-MS: for C19H34O2 calculated 294.2559; foun d: 294.2580.
Sim ilarly, (R)-10 (0.1355 g, 0.41 m m ol) yielded 0.0673 g (56%) of (R)-11. [α ]2D0 –2.63 (c 0.4,
CHCl3).
(+)-(5E,9E)-(S)-2-Hydroxy-2,6,10,14-tetram eth ylpen tadeca-5,9,13-trien al (12)
A) Oxidation with pyridinium dichromate (PDC). Dich lorom eth an e (0.5 m l) an d PDC
(17.3 m g, 0.06 m m ol) were added to diol 11 (10 m g, 0.034 m m ol). After 10-m in stirrin g at
room tem perature, th e products form ed were ch ecked by TLC an d GC-MS. It was foun d th at
un desired farn esyl aceton e h ad been form ed predom in an tly. MS, m/z (%): 262 (M+; 0.5), 219
(M+ – 43; 0.8), 193 (M+ – 69; 1), 178 (3), 161 (3), 136 (17), 125 (9), 121 (8), 107 (24), 95
(15), 93 (17), 81 (34), 79 (10), 69 (98), 67 (23), 55 (9), 53 (49), 43 (100), 41 (62).
B) Swern oxidation. Eth yl(diisopropyl)am in e (160 µl), dim eth yl sulfoxide (150 µl), an d di-
ch lorom eth an e (500 µl) were added to diol 11 (40 m g, 0.136 m m ol). Un der in ten sive
stirrin g, sulfuryltrioxypyridin ium com plex (64 m g, 0.4 m m ol) was th en added. After 3 m in ,
12 was form ed as th e on ly product (ch ecked by TLC, RF 0.4, ligh t petroleum –eth yl acetate
9 : 1). No traces of th e startin g diol 11 were detected. Ice (0.5 g) an d dieth yl eth er (0.5 m l)
were added, an d th e m ixture was stirred for 10 m in . Th e organ ic layer was extracted with
eth er an d ligh t petroleum (1 : 1, 2 × 1 m l). Th e organ ic ph ase was dried over an h ydrous
MgSO4, filtered th rough a Florisil colum n an d evaporated to dryn ess, yieldin g 24 m g (60%)
of un stable h ydroxyaldeh yde 12, wh ich was im m ediately used for th e n ext reaction . MS,
m/z (%): 292 (M+; 0.5), 249 (M+ – 43; 1), 231 (0.8), 191 (1), 187 (1), 177 (1), 161 (3), 136
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Geranyllinalool Enantiomers
87
(20), 121 (12), 109 (10), 107 (11), 95 (25), 93 (20), 81 (51), 69 (100), 67 (21), 55 (12), 45
(16), 43 (29), 41 (44).
Sim ilarly, (R)-11 (24 m g, 0.0816 m m ol) yielded 28.3 m g (65%) of crude (R)-12, wh ich was
subm itted to Wittig reaction with out purification .
(+)-(6E,10E)-(S)-3,7,11,15-Tetram eth ylh exadeca-1,6,10,14-tetraen -3-ol,
[(+)-(S)-geran yllin alool; (S)-1]
Meth yl(triph en yl)ph osph on ium brom ide (240 m g, 0.7 m m ol) was suspen ded in THF (1 m l).
Th e suspen sion was cooled to –70 °C, an d BuLi (2.5 M, 280 µl, 0.7 m m ol) was added. Th e
tem perature was th en in creased to –10 °C (30 m in ), th en decreased again to –55 °C. Subse-
quen tly, a solution of th e h ydroxyaldeh yde (S)-12 (24 m g) in THF (1 m l) was added. Th e re-
action tem perature was kept at 0 °C. After 1.5 h , a saturated solution of NH4Cl (1 m l) was
added. Th e m ixture was extracted with dieth yl eth er an d ligh t petroleum (1 : 1, 2 × 1 m l).
Th e organ ic ph ase was wash ed with a saturated solution of NaCl (1 m l) an d dried over an -
h ydrous MgSO4. After evaporation of th e solven ts, on e dom in an t product was foun d (RF
0.72, ligh t petroleum –eth yl acetate 9 : 1). Th e crude product was ch rom atograph ed on silica
gel (elution with 2, 3, 5, 10, 20, 50% of dieth yl eth er in ligh t petroleum ) providin g (S)-(+)-1
in 41% yield (9.8 m g). [α ]2D0 +18.2 (c 0.06, CHCl3). 1H NMR: 1.28 (3 H, s); 1.56 (3 H, s); 1.59
(3 H, s); 1.60 (3 H, s); 1.68 (3 H, s); 1.60–2.06 (12 H, 6 × m ); 5.07 (1 H, bd, J = 10.7); 5.10
(2 H, bt, J = 6.6); 5.17 (1 H, bt, J = 6.6); 5.21 (1 H, bd, J = 17.3); 5.92 (1 H, dd, J = 10.7,
17.3). 13C NMR: 15.98 (C-19), 16.01 (C-20), 17.7 (C-17), 22.7 (C-5), 25.7 (C-16), 26.6 (C-9),
26.8 (C-13), 27.9 (C-18), 39.69 (C-8), 39.71 (C-12), 42.1 (C-4), 73.5 (C-3), 111.7 (C-1), 124.2
(C-10), 124.3 (C-14), 124.4 (C-6), 131.2 (C-15), 135.6 (C-11), 135.7 (C-7), 1 145.1 (C-2). MS,
m/z (%): 290 (M+; 1), 272 (M+ – 18; 2), 256 (2), 239 (1), 229 (2), 203 (4), 189 (4), 175 (3),
161 (10), 147 (8), 135 (12), 121 (15), 107 (31), 93 (52), 81 (11), 79 (17), 69 (100), 55 (22), 41
(23). HR-MS: for C20H34O calculated 290.2610; foun d 290.2602. IR: 3 430 (OH); 2 962,
2 922, 2 852 (C–H); 1 645 (C=C); 1 457, 1 378 (C–H); 1 126, 1 115 (C–O); 922 (CH=CH2).
Sim ilarly, (R)-12 (28 m g, 0.053 m m ol) yielded 4 m g (27%) of (R)-1. [α ]2D0 –17.0 (c 0.1,
CHCl3). HR-MS: for C20H34O calculated 290.2610; foun d 290.2587; oth er spectral data were
iden tical to (S)-1 en an tiom er.
RESULTS AND DISCUSSION
For th e preparation of both en an tiom ers of geran yllin alool (1) we used
2-h ydroxy-2-m eth ylbutan edioic acid (citram alic acid, 2), com m ercially
available in both en an tiom eric form s (Aldrich , 98% e.e.).
(+)-(S)-2-Hydroxy-2-m eth ylbutan edioic acid [(+)-(S)-citram alic acid, (S)-2]
was reduced7 usin g boran e–dim eth yl sulfide com plex in THF at room tem -
perature for 24 h affordin g triol7 (S)-3. Triol (S)-3 was protected with ace-
ton e8 to afford aceton ide (S)-4 in 43% overall yield. Ketal 4 was con verted
to th e tosylate (S)-5 usin g TsCl/powdered KOH/THF/–20 °C (ref.9) to pre-
ven t poten tial deprotection of 4. Acid (R)-(–)-2 was con verted to th e
tosylate (R)-5 by usin g a sim ilar reaction s sequen ce. Iodide 8 was prepared
from lith iated dian ion of allen e an d geran yl brom ide4a,10 6. Th e in itially
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88
Svatoš, Urbanová, Valterová:
form ed dien yn e 7 was carbom etallated with trim eth ylalum in ium catalyzed
by ZrCp2Cl2 com plex an d in th e presen ce of 1.5 eqivalen t of water11. Th e
form ed vin ylallan e was con verted to vin yliodide 8 with iodin e (in 89%
yield based on 7).
O
H3C OH
HO2C
H3C OH
O
H3C
(i)
H3C
(iii)
(ii)
O
O
OH
TsO
CO2H
HO
HO
(S)-5
(S)-2
(S)-3
(S)-4
(iv)
(v)
I
Br
6
7
8
2-
H3C
O
(vi)
(vii)
S
Li+
Cu
O
2
CN
(S)-10
(S)-1
9
(viii)
H3C OH
R
(x)
H3C OH
R = CH2OH (S)-11
R = CH=O (S)-12
(ix)
(i - x)
HO CH3
HO CH3
HO2C
CO2H
(R)-2
(R)-1
(i) BH3·Me2S, THF; (ii) acetone, CuSO4, TsOH; (iii) TsCl, KOH powder, THF, –20 oC; (iv) Li2C3H2,
–35 oC; (v) Me3Al, [ZrCp2Cl2], H2O (0.5 eq.), CH2Cl2, –20 oC, (vi) 1. t-BuLi (2 eq.), –80 oC, 2.
Li(CN)Cu(2-thienyl), –70 oC to r.t.; (vii) –70 oC, 5, –70 oC to r.t.; (viii) TsOH, MeOH, (ix) Me2SO,
(i-Pr)2N-Et, pyridine·SO3, CH2Cl2, r.t.; (x) H2C=PPh3 (5 eq.), 0 o
C
SCHEME 1
Em ployin g h igh er order cuprate ch em istry12, com poun ds 5 an d 8 were
coupled to yield th e protected diol 10. Iodide 8 reacted at –90 °C with
t-BuLi an d th e in situ form ed vin yllith ium com poun d was treated with
dilith ium cyan o(2-th ien yl)cuprate to form th e cuprate 9. Th e latter reacted
at 0 to 20 °C with th e tosylates (S)- an d (R)-5 form in g (S)- or (R)-10. After
deprotection with pyridin ium (4-toluen e)sulfon ate in m eth an ol, diols (S)-
an d (R)-11 were obtain ed in 56 an d 67% yields, respectively. Th e en an tio-
Collect. Czech. Chem. Commun. (Vol. 67) (2002)

Geranyllinalool Enantiomers
89
m eric diols 11 were oxidized usin g Swern oxidation 13 providin g pure
α-h ydroxyaldeh ydes 12 in ca 5 m in . Wh en pyridin ium dich rom ate oxida-
tion 14 was used, farn esylaceton e was th e m ain product resultin g from
1,2-diol cleavage of 11. Th e aldeh ydes 12 were con verted to 1 with an ex-
cess of CH2=PPh 3 ylide15. In frared an d 1H NMR data of prepared en an tio-
m ers of 1 were iden tical with th ose reported for both isolated1a an d
syn th esized6g com poun ds.
Our approach usin g en an tiopure n atural com poun d pool an d carbo-
m etallation /vin yl cuprate sequen ce was n ot previously used to con struct
en an tiopure 4-akyl-3-m eth ylbut-1-en -3-ols. Publish ed routes for th eir prep-
aration s relayed on th e en an tioselective Sh arpless epoxidation of 4-alkyl-
3-m eth yl-but-2-en -1-ols an d a reductive elim in ation of th e correspon din g
2,3-epoxybutan -1-iodide16
.
Kn owin g th e optical rotation of geran yllin allool we can establish th e ab-
solute con figuration s of previously isolated sam ples from n atural m aterials.
Th us (–)-1 previously isolated from Picea abies1a an d from Picea obovata1c
h as th e (R)-absolute con figuration in accord with th e suggested absolute
con figuration 1a. Un fortun ately, so far we were n ot able to separate th e en -
an tiom ers of 1 on ch iral GC colum n s (Lipodex E, dipen tyl butyryl γ-cyclo-
dextrin , an d Cyclodex B, perm eth ylated β-cyclodextrin ) an d to determ in e
th e absolute con figuration s of 1 foun d in labial glan ds of several bum ble-
bees3d. However, furth er in vestigation s in th is direction are in progress.
This work was financially supported by the Ministry of Education, Youth and Sports of the Czech
Republic (COST project No. 828.20) and IOC research project Z4 055 905, which are gratefully ac-
knowledged. We are indebted to Dr D. Šaman for the measurement and interpretation of some NMR
spectra.
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