Stille coupling reactions in the preparation of substituted trienic systems

Article abstract of DOI:10.1055/s-1998-5936

The formation of the tetraenoate 2 was envisaged during a synthetic approach to the decalin system 1. The iododiene 3 was obtained in high yield from the corresponding stannyl derivative. The right hand fragment 13a was synthesized from propionate 8 using, during this sequence, a condensation of (E)-1-lithio-2-tributylstannylethene with aldehyde 10. The Pd(0)-catalyzed Stille coupling reaction between 3 and 13a was then realized in 75% yield to deliver the expected triene 23 which was then transformed into the expected tetraenoate 2.

Full text of DOI:10.1055/s-1998-5936

SYNTHESIS
Papers
522
Stille Coupling Reactions in the Preparation of Substituted Trienic Systems
Jean-François Betzer, Jean-Yves Lallemand, Ange Pancrazi*
Laboratoire de Synthèse Organique, DCSO, Ecole Polytechnique, F-91128, Palaiseau, France
Fax +33(1)69333010; E-mail: pancrazi@poly.polytechnique.fr
Received 9 September 1997
Abstract: The formation of the tetraenoate 2 was envisaged dur-
ing a synthetic approach to the decalin system 1. The iododiene 3
was obtained in high yield from the corresponding stannyl deriva-
tive. The right hand fragment 13a was synthesized from propi-
onate 8 using, during this sequence, a condensation of (E)-1-
lithio-2-tributylstannylethene with aldehyde 10. The Pd(0)-cata-
lyzed Stille coupling reaction between 3 and 13a was then real-
ized in 75% yield to deliver the expected triene 23 which was then
transformed into the expected tetraenoate 2.
The strategy we wanted to develop for an approach to the
bottom part 1 was based on an intramolecular Diels–Alder
reaction5 performed on the tetraenoate 2 while its prepa-
ration was envisaged via a Pd(0)-catalyzed Stille coupling
reaction between iododiene 3 and stannyl derivative 4.
In a preceding work,6 we described an efficient prepara-
tion of the stannyldiene 7. Methylation of commercial
enynol 5 gave 6 which was treated with the homocuprate
Key words: Stille coupling reaction, Pd(0)-catalyzed hydrostan-
nylation, stannylcupration, (E)-lithio-2-tributylstannylethene
7
(Bu3Sn)2CuCNLi2 in THF/MeOH (2:1) at –10˚C for
12 hours to deliver the dienylstannane 7 in 77% yield as
the only stereomer (Scheme 2). A halogen-metal
exchange8 then furnished the expected iodo compound 3
in 89% yield.
Total synthesis of the macrocyclic antibiotics chlorothri-
cine, tetrocarcine and kijamicin (Scheme 1)1 have been re-
ported in the literature since 1986.1,2 Due to their
biological interest3 and their particular structures, work in
this field remained important.4
During a screening program, a new macrocyclic deriva-
tive which presents some interesting antibiotic properties,
was isolated. Spectroscopic data did not give us at this
time the complete structure of this new compound but its
bottom half was tentatively assigned to be analogous to
the tetrocarcine and kijamicin ones. Therefore the prepa-
ration of 1 was undertaken, as depicted in Scheme 1, in or-
der to corroborate this new structure.
Scheme 2
The diol derivative 9 was obtained from the commercial
methyl propionate 8, as described,9 in 74% overall yield
for six steps (Scheme 3). Swern oxidation of the primary
alcohol 9 led to the expected aldehyde 10 in 97% yield.
After reaction of lithium trimethylsilylacetylide with alde-
hyde 10 (96% yield), a basic treatment (K2CO3, MeOH)
furnished the propargyl derivative 11a as a 1:1 mixture
(99% yield) of two diastereomers at C-7. The correspond-
ing benzoate derivative 11b was prepared by esterification
of 11a. The unsaturated ethyl esters 12a and 12b were
then obtained in respectively 50% and 63% overall yields
from 11b.
At this stage, the synthesis of the corresponding vinylstan-
nanes 13a and 16a,b was attempted using either
stannylcupration10 or Pd(0)-catalyzed hydrostannylation
reactions.11,12 Pd(0)-catalyzed reaction of the propargylic
alcohol 11a was carried out in 72% yield and the distal
and proximal stannyl isomers 13a and 14a were obtained
in a 80:20 ratio (Entry 1, Table 1).
Under stannylcupration conditions [(Bu3Sn)2CuCNLi2,
THF, –40˚C to –30˚C, 2 h] reaction of 11a gave a
19:25:56 mixture of the two regioisomers 13a and 14a and
the bis-stannyl derivative 15a (Entry 2, Table 1) in 86%
yield. Formation of the latter compound could result from
a reductive elimination of the stannylcuprate intermedi-
ate; a stabilization of the cuprate by the oxygen function
of the side chain could be involved, the Cu atom reacting
Scheme 1

SYNTHESIS
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523
Table 2. Stannylation Reactions of Propargyl Derivatives 12
Entry R Method Reaction Conditions
Product
Ratio
Yielda
(%)
16 17 18
1
2
3
4
5
H
A
B
C
A
C
BuSnH/(Ph3P)2PdCl2/
THF, 20°C
(Bu3Sn)2CuCNLi2/THF
–40 to –30°C, 2 h
(Bu3Sn)2CuCNLi2/THF/
MeOH, –40 to –30°C, 2 h
Bu3SnH/(Ph3P)2PdCl2/
THF, 20°C
(Bu3Sn)2CuCNLi2/THF/ 100
MeOH, –40 to –30°C, 2 h
100
0
0
34
H
0 20 80 38
H
75 25
60 40
0
0
0
46
57
37
Bz
Bz
0
Scheme 3
a
Yields refer to purified products after column chromatography on
silica gel.
Table 1. Stannylation Reactions of Propargyl Derivative 11a
Table 2). Stannylcupration of 12a using (Bu3Sn)2-
CuCNLi2 in THF also led to the formation of a bis(stan-
nyl) compound 18a (Entry 2, Table 2), whereas in the
presence of methanol, the reaction led to a 75:25 mixture
of 16a and 17a (46% yield, Entry 3, Table 2). When these
conditions were applied to ester 12b, only 16b was
isolated in 37% yield (Entry 5, Table 2).
Entry Method Reaction Conditions
Product Ratio
Yielda
(%)
72
As these stannylation reactions appeared to run in fair to
modest yields to deliver the expected vinylstannanes 13a
or 16a,b, we decided to generate them directly by reaction
of the (E)-1-lithio-2-tributylstannylethene13 with the cor-
responding aldehydes 10 and 20. The aldehyde 20 was
prepared from 9 in five steps and 45% overall yield as de-
picted in Scheme 4.
13a 14a 15a
1
2
3
4
A
B
C
C
Bu3SnH/(Ph3P)2PdCl2/
THF, 20°C
(Bu3Sn)2CuCNLi2/THF, 19 25 56
–40 to –30°C, 2 h
(Bu3Sn)2CuCNLi2/THF/ 63 37
MeOH, –40 to –30°C, 2 h
(Bu3Sn)2CuCNLi2/THF/ 75 25
MeOH, 0°C, 2 h
80 20
0
86
0
61
0
81
When aldehyde 10 was reacted with 1.7 equivalents of the
(E)-1-lithio-2-tributylstannylethene [prepared by the ad-
dition of 1.7 equivalents of BuLi to 2 equivalents of the
(E)-1,2-bis(tributylstannyl)ethene14], the expected pure
(E)-vinylstannane 13a was obtained in 95% yield
(Scheme 5).
a
Yields refer to purified products after column chromatography on
silica gel.
then as a transition metal.12 Nevertheless this reaction
could be inhibited when the stannylcupration reaction was
performed in a 2:1 mixture of THF/MeOH (methanol was
used in this case as a proton source to trap the stannylcu-
prate intermediate). The best result under these conditions
was the formation of the two distal and proximal isomers
13a and 14a in a 75:25 ratio and 81% yield when 11a was
reacted at 0˚C (Entries 3,4, Table 1).
When the Pd(0)-catalyzed hydrostannylation was per-
formed on the unsaturated esters 12a, only distal stannyl
derivative 16a was obtained but in poor yield (34%, Entry
1, Table 2). However,the reaction with the benzoate deriv-
ative 12b gave a better yield (57%) but the two regioiso-
mers 16b and 17b were obtained in 60:40 ratio (Entry 4,
Scheme 4

SYNTHESIS
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524
Scheme 6
Table 3. Coupling Reactions Between 13a and 3
Entry Pd(O)-Catalyst
Reaction Conditions Product Yielda
Ratio
Scheme 5
Sol- Time Temp
vent (h)
(°C)
23/24 (%)
However, using the same conditions, treatment of the al-
dehyde 20 led to a mixture of 16a (40%), 21 (9%), and 22
(7%). Compounds 21 and 22 resulted in a second addi-
tion-substitution of the (E)-1-lithio-2-tributylstan-
nylethene onto the carbonyl ester function. Using 1.2
equivalents of the (E)-1,2-bis(tributylstannyl)ethene and
1 equivalent of BuLi, 16a was obtained as the only prod-
uct in 62% yield (Scheme 5).
1
2
3
4
5
6
7
8
9
(Ph3P)4Pdb
THF 12
THF 12
DMF 12
DMF 12
DMF 12
20
reflux
20
20
40
20
40
20
40
–
–
–
–
100:0 32
100:0 34
100:0 20
100:0 26
100:0 22
100:0 21
100:0 18
60:40 74
75:25 37
100:0 75
(dba)3Pd2/Ph3P/CuIc
(dba)3Pd2/(2-furyl)3P/CuIc DMF 12
DMF 12
NMP 12
NMP 12
DMF 12
NMP 12
DMF 36
10
11
12
(dba)3Pd2/Ph3As/CuIc
20
20
20
Having resolved the stereospecific preparation of the vi-
nylstannyl compounds 13a and 16a and iodo derivative 3,
we then turned our efforts to the Stille coupling reaction.15
This coupling reaction was first realized with Pd(PPh3)4,
prepared as described by Hegedus,16 and triene 23 was ob-
tained in 30% yield as the best result when DMF was used
as solvent instead of THF (Scheme 6 and Entries 1–3, Ta-
ble 3). Under the same conditions, coupling reaction be-
tween 16a and 3 did not work and tetraenoate 2 was not
isolated.
d
(MeCN)2PdCl2
a
Yields refer to purified products after column chromatography on silica
gel.
Prepared as described by Hegedus16 and used in 10 mol%.
Pd(0) = 5 mol%, ligand = 20 mol%, CuI = 10 mol%.
Commercially available catalyst was used in 12 mol% (see Ref. 22 for
typical procedures).
b
c
d
Formation of an “abnormal” Stille coupling product such
as 24 was first described by Busacca and co-workers,19
and involves a Heck mechanism and a palladium carbene
intermediate. It was interesting to note that formation of
such abnormal coupling was observed only when triphe-
nylarsine was used as the palladium ligand. As a last at-
tempt when PdCl2(MeCN)2 was used in DMF at 20˚C
(Entry 12, Table 3), the cross-coupling reaction furnished
the expected triene 23 as a pure isomer in 75% yield; no
trace of compound 24 was detected.
The Stille reaction was also tested using Pd2(dba)3/Ph3P
and CuI17 for coupling 13a and 3 in DMF (Entries 4,5, Ta-
ble 3) but no change for the formation of 23 (20 to 34%
yield) and no “copper effect” were observed in this case.
As described by Farina18 we also tried to use tri(2-fur-
yl)phosphine as palladium ligand but no rate acceleration
was observed and triene 23 was prepared in a range of
18–26% yield (Entries 6–9, Table 3). However, counter-
part using triphenylarsine and CuI in DMF at 20˚C, the re-
action gave a 60:40 mixture of isomeric trienes 23 and 24
in 74% yield (Entries 10,11, Table 3).
Final preparation of tetraenoate 2 was executed from the
triene 23. After protection of the two alcohol functions by
esterification (BzCl, CH2Cl2, Et3N, DMAP), the diben-

SYNTHESIS
April 1998
525
zoate 25 was treated under acidic conditions (TsOH, CuI/DMF (74% yield, 23/24 = 60:40). Pure triene 23 was
MeOH) to remove the THP group (Scheme 7). At ambient obtained in 75% yield when PdCl2(MeCN)2/DMF condi-
temperature reaction led to the expected alcohol 26 in tions were employed. Tetraenoate 2 was finally prepared
80% yield after 2.5 hours. As an interesting result, when in 15 steps from the commercial derivative 8 in 20% over-
the same reaction was performed during 5 hours, com- all yield.
pounds 26 and 27 (single diastereomer) were obtained in
Compound 2 is now ready for the intramolecular
90% yield and in a 38:62 ratio .
Diels–Alder reaction envisaged for the preparation of the
southern part of 1. Work in this area is in progress.
All air and/or water sensitive reactions were carried out under argon
atmosphere with anhydrous, freshly distilled solvents using standard
syringe-cannula/septa techniques. THF and Et2O were distilled from
sodium/benzophenone and MeOH from Mg(OMe) . All glasswares
2
were oven dried (110°C) and/or carefully dried with a flameless heat
gun, unless otherwise stated. Petroleum ether used refers to the frac-
tion with bp 50°C.
1H NMR spectra were recorded in CDCl3 on a Bruker WP 200
(200 MHz) or on a Bruker AM 400 (400 MHz) instrument. The chem-
ical shifts are expressed in parts per million (ppm) referenced to re-
sidual CHCl3 (δ = 7.27). Data are reported as follows: δ, chemical
shift; multiplicity (recorded as s, singlet; d, doublet; t, triplet; q, quad-
ruplet and m, multiplet), coupling constants (J in Hertz, Hz), integra-
tion and assignment. H,H-COSY and H,H-NOESY experiments were
routinely carried out to ascertain H-H connections and configuration
assignments, respectively. 13C NMR spectra were recorded on the
same instruments at 50.3 MHz and 100.6 MHz, respectively. 13C
NMR chemical shifts are expressed in parts per million (ppm), report-
ed from the central peak of CDCl3 (δ = 77.14). J-modulated spin-echo
technique (J-mod) experiments were used for evaluating CH multi-
plicities. For Sn - 1H or Sn - 13C coupling constants the central signal
is normally associated with two close pairs of satellites corresponding
to both 117Sn (7.5%) and 119Sn (8.6%) isotopes. When detected for
large coupling constants (250–300 Hz), the two different coupling
constants are reported whereas in other cases (generally for small
ones, < 100 Hz) average values are reported. Mass spectra were ob-
tained on a Hewlett-Packard HP 5989B spectrometer via either direct
introduction (chemical ionization, CI, NH3) or GC/MS coupling with
a Hewlett-Packard HP 5890 chromatograph. Infrared spectra were
obtained on a Perkin-Elmer FT 1600 instrument using NaCl salt
plates (film). Microanalyses were performed by the Service de Mi-
croanalyse, Institut de Chimie des Substances Naturelles, C.N.R.S.,
F-91198, Gif sur Yvette. Flash chromatography was performed on E.
Merck silica gel Si 60 (40–63 mm).
Scheme 7
Oxidation of the primary alcohol 26 using Swern condi-
tions led to the corresponding aldehyde which was sub-
mitted to a Wittig reaction. Removal of the benzoate
functions (EtONa, EtOH, 20˚C) then delivered the expect-
ed tetraenoate 2 in a 32% overall yield from 23 (43% yield
for the three steps, Scheme 8).
(2E,4E)-5-Iodo-3-methylhexa-2,4-dien-1-ol (3):
To a solution of vinylstannane 7 (202 mg, 0.503 mmol) in CH2Cl2
(1 mL) at 0°C was slowly added a solution of I2 (134 mg,
0.528 mmol) in CH2Cl2 (1.5 mL). After 15 min the solvent was re-
moved under pressure and the residue was taken up in a mixture of
Et2O (2 mL), aq 1 M KF solution (1.4 mL, 1.40 mmol) and satd aq
Na2S2O3 solution (5 mL). After stirring for 3 h at r.t., the solution was
filtered on a pad of Celite. The organic layer was decanted, dried
(MgSO4) and concentrated in vacuo. Purification by flash chromatog-
raphy on silica gel (Et2O/petroleum ether, 50:50) gave 3 (107 mg,
89.9%) as a pale yellow colorless oil (Chromatography must be ef-
fected quickly due to the great instability of 3).
1H NMR (400 MHz, CDCl3): δ = 1.75 (s, 3 H, CH3-3), 2.06 (br s, 1
H, OH), 2.56 (d, 3 H, J = 1.4 Hz, CH3, H3-6), 4.18 (dq, 2 H, J = 6.7,
1.5 Hz, H2-1), 5.49 (t, 1 H, J = 6.7 Hz, H-2), 6.62 (s, 1 H, H-4).
13C NMR (50 MHz, CDCl3): δ = 16.6 (CH3-3), 29.6 (CH3, C-6), 59.2
(C-1), 97.6 (C-5), 129.6 (C-2), 135.4 (C-3), 143.7 (C-4).
Scheme 8
In conclusion, we were able to prepare, in a stereoselec-
tive way, iododiene 3 and vinylstannane 11a, in 62 and
68% yield, respectively. The Stille coupling reaction be-
tween 3 and 11a gave the expected triene 23 and the
anomalous coupling product 24 using Pd2(dba)3/AsPh3/
IR (film): ν = 3332, 2954, 2918, 2869, 2853, 1651, 1615, 1434, 1377,
1066, 1000, 879, 679 cm–1.
MS (DI, CI, NH3): m/z = 256 (MH+ + NH3), 238 (MH+ + NH3 –
H2O), 221, 175, 128, 111, 94.

SYNTHESIS
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(4S)-4-Methyl-5-[(tetrahydropyran)-2-yloxy]pentan-1-ol (9):
To a solution of commercial methyl (R)-(–)-β-hydroxyisobutyrate (8;
10.0 g, 84.7 mmol) in Et2O (90 mL) and 3,4-dihydro-2H-pyran
(9.3 mL, 101.6 mmol, 1.2 equiv) at 0°C was added TsOH (177 mg,
0.93 mmol, 0.01 equiv). The cold bath was removed and the mixture
left to stand overnight at r.t. The mixture was then diluted with Et2O
and the organic layer was washed with satd aq NaHCO3 solution,
dried (MgSO4), filtered and concentrated in vacuo. Purification by
flash chromatography on silica gel (Et2O/petroleum ether, 0:100 to
20:80) gave methyl (2R)-2-methyl-3-[(tetrahydropyran)-2-yloxy]-
propanoate (16.8 g, 98%) as a colorless oil.
IBX Oxidation: To a solution of IBX (53.2 g, 189.9 mmol, 2.2 equiv)
in DMSO (400 mL) (dissolution of IBX in DMSO requires 1–1.5 h)
at r.t. was added dropwise a solution of (2R)-2-methyl-3-[(tetrahydro-
pyran)-2-yloxy]propan-1-ol (15.0 g, 86.3 mmol) in DMSO (100 mL).
The resulting slurry was stirred for 2 h. H2O was then added at 0°C
and the mixture was diluted with Et2O (2 L). The organic layer was
washed with H2O (5 × 200 mL), dried (MgSO4), filtered and concen-
trated in vacuo. The crude (2R)-2-methyl-3-[(tetrahydropyran)-2-
yloxy]propanal thus obtained was used in the next step without fur-
ther purification.
1H NMR (400 Hz, CDCl3), two diastereomers: δ = 1.13 (d, 1.5 H, J
= 7.1 Hz, CH3-2), 1.15 (d, 1.5 H, J = 7.0 Hz, CH3-2), 1.48–1.65 (m, 4
H, Hb-3' + Ha-4' + H2-5'), 1.65–1.75 (m, 1 H, Ha-3'), 1.75–1.85 (m, 1
H, Ha-4'), 2.61–2.72 (m, 1 H, H-2), 3.47–3.58 (m, 1 H, Hb-6'), 3.57
(t, 1 H, J = 9.9 Hz, Hb-3), 3.59 (t, 0.5 H, J = 9.9 Hz, Hb-3), 3.77–3.88
(m, 1 H, Ha-6'), 3.94 (t, 0.5 H, J = 10.0 Hz, Ha-3), 3.96 (dd, 0.5 H, J
= 10.0, 9.9 Hz, Ha-3), 4.60 (t, 0.5 H, J = 4.3 Hz, H-2'), 4.61 (t, 0.5 H,
J = 3.5 Hz, H-2'), 9.28 (d, 1 H, J = 1.9 Hz, CHO).
1H NMR (400 Hz, CDCl3), two diastereomers: δ = 1.18 (d, 1.5 H, J
= 7.5 Hz, CH3-2), 1.19 (d, 1.5 H, J = 7.0 Hz, CH3-2), 1.45–1.62 (m, 4
H, Hb-3' + Hb-4' + H2-5'), 1.63–1.71 (m, 1 H, Ha-3'), 1.72–1.83 (m,
1 H, Ha-4'), 2.77 (sext, 1 H, J = 6.8 Hz, H-2), 3.45 (dd, 0.5 H, J = 8.9,
5.8 Hz, Hb-3), 3.48–3.56 (m, 1 H, Hb-6'), 3.60 (t, 0.5 H, J = 8.1 Hz,
Hb-3), 3.69 (s, 1.5 H, OCH3), 3.70 (s, 1.5 H, OCH3), 3.76 (t, 0.5 H, J
= 9.7 Hz, Ha-3), 3.86–3.78 (m, 1 H, Ha-6'), 3.91 (t, 0.5 H, J = 9.7 Hz,
Ha-3), 4.60 (t, 0.5 H, J = 3.1 Hz, H-2'), 4.62 (t, 0.5 H, J = 3.3 Hz, H-
2').
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 10.8 (CH3-2),
19.3, 19.4 (C-5'), 25.5 (C-4'), 30.5 (C-3'), 46.7, 46.8 (C-2), 62.1, 62.2
(C-6'), 67.4, 67.6 (C-3), 98.8, 99.2 (C-2'), 203.7, 203.8 (C-1).
IR (film): ν = 2942, 1725, 1454, 1352, 1202, 1035 cm–1.
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 14.0 (CH3-2),
19.3, 19.4 (C-5'), 25.5 (C-4'), 30.5, 30.6 (C-3'), 40.2, 40.4 (C-2), 51.4
(OCH3), 61.9, 62.1 (C-6'), 69.2, 69.4 (C-3), 98.7, 99.1 (C-2'), 173.7
(C-1).
MS (GC, CI, NH3): m/z = 190 (MH+ + NH3), 173 (MH+), 102, 85.
IR (film): ν = 2945, 2875, 1742, 1455, 1262, 1124, 1078, 1060, 1034
Horner–Emmons Reaction of Swern Oxidation's Crude Product: To
a solution of NaH (powder, 80% in oil, 25 mg, 0.83 mmol, 1.2 equiv)
in anhyd THF (2 mL) at 0°C was added dropwise a solution of methyl
diethylphosphonoacetate (152 µL, 0.83 mmol, 1.2 equiv) in anhyd
THF (4 mL) over 5 min. The solution was stirred at r.t. for 15 min (un-
til H2 evolution had stopped). Then the mixture was cooled to –78°C
and a solution of the freshly prepared crude aldehyde (2R)-2-methyl-
3-[(tetrahydropyran)-2-yloxy]propanal by Swern oxidation (see
above) in anhyd THF (2 mL) was added via a cannula. After stirring
for 50 min, the mixture was allowed to warm to r.t. The mixture was
stirred for another 1 h and was then quenched by the addition of H2O
(5 mL). The aqueous layer was separated and extracted with Et2O
(2 × 20 mL). The combined organic extracts were washed with brine,
dried (MgSO4), filtered and concentrated in vacuo. Purification by
flash chromatography on silica gel (Et2O/petroleum ether, 0:100
to 20:80) gave methyl (2E,4S)-4-methyl-5-[(tetrahydropyran)-2-
yloxy]pent-2-enoate (110 mg, 70% for two steps) as a colorless oil.
cm–1.
MS (GC, CI, NH3): m/z = 220 (MH++ NH3), 203 (MH+), 169, 136,
119, 102, 85.
To a solution of LiAlH4 (powder, 95%, 1.25 g, 31.2 mmol, 0.8 equiv)
in anhyd Et2O (80 mL) at 0°C was added dropwise a solution of me-
thyl (2R)-2-methyl-3-[(tetrahydropyran)-2-yloxy]propanoate (7.90 g,
39.1 mmol) in anhyd Et2O (40 mL) over 30 min. The cold bath was
removed and the mixture was stirred at r.t. for 3 h and cooled at 0°C.
The excess of LiAlH4 was decomposed by successive addition of H2O
(1.5 mL), 15% aq NaOH solution (1.5 mL) and H2O (4.5 mL). After
1.5 h at r.t., the mixture was filtered on a pad of Celite and the solid
was washed with Et2O. The combined filtrate and washings were
dried (K2CO3), filtered and concentrated in vacuo. Purification by
flash chromatography on silica gel (Et2O/petroleum ether, 40:60 to
70:30) gave (2R)-2-methyl-3-[(tetrahydropyran)-2-yloxy]propan-1-
ol (6.41 g, 94%) as a colorless oil.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.89 (d, 1.5 H,
J = 6.9 Hz, CH3-2), 0.90 (d, 1.5 H, J = 6.9 Hz, CH3-2), 1.48–1.63 (m,
4 H, Hb-3' + Hb-4' + H2-5'), 1.68–1.74 (m, 2 H, Ha-3' + Ha-4'),
1.98–2.09 (m, 1 H, OH), 2.73–2.84 (m, 1 H, H-2), 3.34 (t, 0.5 H, J =
9.4 Hz, Hb-3), 3.47–3.83 (m, 3.5 H, 0.5 Ha-3 + Hb-3 + H2-6'),
3.82–3.91 (m, 2 H, H2-1), 4.57 (t, 1 H, J = 4.0 Hz, H-2').
Horner–Emmons Reaction of IBX Oxidation's Crude Product: To a
solution of NaH (powder, 80% in oil, 3.05 g, 101.7 mmol, 1.2 equiv)
in anhyd THF (40 mL) at 0°C was added dropwise a solution of me-
thyl diethylphosphonoacetate (19.2 mL, 104.5 mmol, 1.2 equiv) in
anhyd THF (200 mL) over 30 min. The solution was stirred at r.t. for
30 min (until H2 evolution had stopped). Then the mixture was cooled
to –78°C and a solution of the freshly prepared crude aldehyde (2R)-
2-methyl-3-[(tetrahydropyran)-2-yloxy]propanal by IBX oxidation
(see above) in anhyd THF (160 mL) was added via a cannula. After
stirring for 1.4 h, the mixture was allowed to warm to r.t. The mixture
was stirred for another 1 h and was then quenched by the addition of
H2O (100 mL). The aqueous layer was separated and extracted with
Et2O (2 × 1 L). The combined organic extracts were washed with
brine, dried (MgSO4), filtered and concentrated in vacuo. Purification
by flash chromatography on silica gel (Et2O/petroleum ether, 0:100
to 20:80) gave methyl (2E,4S)-4-methyl-5-[(tetrahydropyran)-2-
yloxy]pent-2-enoate (17.4 g, 88% for two steps) as a colorless oil.
1H MNR: (400 Hz, CDCl3), two diastereomers: δ = 1.10 (d, 3 H, J =
6.8 Hz, CH3-4), 1.48–1.63 (m, 4 H, Hb-3' + Hb-4' + H2-5'), 1.68–1.75
(m, 1 H, Ha-3'), 1.77–1.86 (m, 1 H, Ha-4'), 2.59–2.70 (m, 1 H, H-4),
3.32 (dd, 0.5 H, J = 9.6, 9.5 Hz, Hb-5), 3.33 (dd, 0.5 H, J = 9.4, 8.9
Hz, Hb-5), 3.47–3.54 (m, 1 H, Hb-6'), 3.67 (dd, 0.5 H, J = 9.4, 9.0 Hz,
Ha-5), 3.70 (dd, 0.5 H, J = 9.6, 9.5 Hz, Ha-5), 3.73 (s, 3 H, OCH3),
3.28–3.38 (m, 1 H, Ha-6'), 4.58 (t, 0.5 H, J = 3.9 Hz, H-2'), 4.59 (t, 0.5
H, J = 3.4 Hz, H-2'), 5.87 (dd, 0.5 H, J = 15.6, 1.8 Hz, H-2), 5.88 (dd,
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 13.5, 13.6 (CH3-
2), 19.7 (C-5'), 25.5 (C-4'), 30.7 (C-3'), 35.6, 35.8 (C-2), 62.5, 62.6
(C-6'), 67.5 (C-1), 72.2, 72.1 (C-3), 99.5, 99.2 (C-2').
IR (film): ν = 3406, 2941, 1454, 1353, 1201, 1120, 1032 cm–1.
MS (GC, CI, NH3): m/z = 192 (MH+ + NH3), 175 (MH+), 108, 102,
91, 85.
Swern Oxidation: To a solution of oxalyl chloride (72 mL,
0.83 mmol, 1.2 equiv) in anhyd CH2Cl2 (5 mL) at –55°C was added
DMSO (128 mL, 1.65 mmol, 2.4 equiv). This was followed 5 min lat-
er with the addition via cannula of a solution of (2R)-2-methyl-3-[(tet-
rahydropyran)-2-yloxy]propan-1-ol (120 mg, 0.69 mmol) in anhyd
CH2Cl2 (1 mL). The resulting slurry was stirred for 1 h and Et3N
(480 mL, 3.44 mmol, 5.0 equiv) was added. After 5 min, the mixture
was warmed to r.t. The mixture was diluted with CH2Cl2 (20 mL) and
washed with an ice-cold 0.5 M HCl solution (7 mL) and H2O (7 mL).
The aqueous phases were extracted with CH2Cl2 (20 mL). The organ-
ic layers were combined, dried (MgSO4), filtered and concentrated in
vacuo. The crude aldehyde (2R)-2-methyl-3-[(tetrahydropyran)-2-
yloxy]propanal thus obtained was used without further purification.

SYNTHESIS
April 1998
527
0.5 H, J = 15.6, 1.8 Hz, H-2), 6.96 (dd, 0.5 H, J = 15.8, 12.8 Hz, H-
3), 6.98 (dd, 0.5 H, J = 15.7, 12.7 Hz, H-3).
equiv) was added. After 5 min, the mixture was warmed to r.t. The
mixture was diluted with CH2Cl2 (100 mL) and was washed with an
ice-cold 1M HCl solution (123 mL) and H2O (123 mL). The aqueous
phases were extracted with CH2Cl2 (200 mL). The organic layers were
combined, dried (MgSO4), filtered and concentrated in vacuo. Purifica-
tion by flash chromatography on silica gel (Et2O/petroleum ether,
20:80 to 30:70) gave the aldehyde 10 (4.75 g, 97%) as a colorless oil.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.91 (d, 1.5 H,
J = 6.7 Hz, CH3-4), 0.92 (d, 1.5 H, J = 6.7 Hz, CH3-4), 1.84–1.42 (m,
9 H, H2-3 + H-4 + H2-3' + H2-4' + H2-5'), 2.47 (td, 2 H, J = 6.5, 1.8
Hz, H2-2), 3.18 (t, 0.5 H, J = 9.6 Hz, Hb-5), 3.19 (dd, 0.5 H, J = 9.6,
9.5 Hz, Hb-5), 3.52–3.44 (m, 1 H, Hb-6'), 3.56 (dd, 1 H, J = 9.8, 9.5
Hz, Ha-5), 3.57 (dd, 0.5 H, J = 10.0, 9.5 Hz, Ha-5), 3.82 (td, 1 H, J =
8.7, 2.1 Hz, Ha-6'), 4.53 (t, 0.5 H, J = 3.9 Hz, H-2'), 4.54 (t, 0.5 H, J
= 2.9 Hz, H-2'), 9.27 (t, 1 H, J = 1.8 Hz, H-1).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 16.1 (CH3-4),
19.4 (C-5'), 25.6 (C-4'), 30.6 (C-3'), 36.7, 36.8 (C-4), 51.1 (OCH3),
62.1, 62.2 (C-6'), 71.1, 71.2 (C-5), 98.8, 99.0 (C-2'), 120.7 (C-2),
151.4 (C-3), 166.9 (C-1).
IR (film): ν = 2948, 1726, 1659, 1436, 1273, 1122, 1039 cm–1.
MS (GC, CI, NH3): m/z = 246 (MH+ + NH3), 229 (MH+), 162, 145,
102, 85.
To a solution of methyl (2E,4S)-4-methyl-5-[(tetrahydropyran)-2-
yloxy]pent-2-enoate (2.11 g, 9.24 mmol) in EtOAc (30 mL) was add-
ed 5% Pd/C (1.97 g, 0.94 mmol, 0.1 equiv) and the mixture was
stirred vigorously at r.t. under H2 for 1 h. The catalyst was removed
by filtration through a pad of Celite and the filtrate was concentrated
in vacuo. Purification of the residue by flash chromatography on sili-
ca gel (Et2O/petroleum ether, 0:100 to 20:80) gave methyl (4S)-4-me-
thyl-5-[(tetrahydropyran)-2-yloxy]pentanoate (2.11 g, quantitative
yield) as a colorless oil.
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 17.0 (CH3-4),
19.7 (C-5'), 25.6 (C-4'), 26.2 (C-3), 30.8 (C-3'), 33.2 (C-4), 41.7 (C-
2), 62.3 (C-6'), 72.5 (C-5), 99.1, 99.2 (C-2'), 202.2 (C-1).
IR (film): ν = 2940, 1725, 1453, 1122, 1063, 1033 cm–1.
MS (GC, CI, NH3): m/z = 218 (MH+ + NH3), 201 (MH+), 200, 183,
134, 116, 102, 85.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.90 (d, 1.5 H,
J = 6.5 Hz, CH3-4), 0.91 (d, 1.5 H, J = 6.7 Hz, CH3-4), 1.43–1.84 (m,
9 H, H2-3 + H-4 + H2-3' + H2-4' + H2-5'), 2.28–2.42 (m, 2 H, H2-2),
3.17 (dd, 0.5 H, J = 9.7, 9.6 Hz, Hb-5), 3.18 (dd, 0.5 H, J = 9.6, 9.4
Hz, Hb-5), 3.43–3.51 (m, 1 H, Hb-6'), 3.55 (dd, 0.5 H, J = 9.4, 8.8 Hz,
Ha-5), 3.56 (dd, 0.5 H, J = 9.4, 8.7 Hz, Ha-5), 3.64 (s, 3 H, OCH3),
3.81 (td, 1 H, J = 8.1, 2.8 Hz, Ha-6'), 4.52–4.57 (m, 1 H, H-2').
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 16.9 (CH3-4),
19.6 (C-5'), 25.7 (C-4'), 29.2 (C-3), 30.8 (C-3'), 32.0 (C-2), 33.3 (C-
4), 51.3 (OCH3), 62.2 (C-6'), 72.6 (C-5), 99.1 (C-2'), 174.1 (C-1).
IR (film): ν = 2950, 1740, 1437, 1120, 1033 cm–1.
Anal. calc. for C11H20O3 (201.9): C, 65.97; H, 10.07; found C, 65.15;
H, 10.11.
(3R/S,6S)-6-Methyl-7-[(tetrahydropyran)-2-yloxy]hept-1-yn-3-ol
(11a):
To a solution of commercial (trimethylsilyl)acetylene (368 mg, 3.74
mmol, 2.0 equiv) in anhyd THF (10 mL) at –78°C was added BuLi
(1.6 M solution in hexane, 1.4 mL, 2.25 mmol, 1.2 equiv). The mix-
ture was stirred at 0°C for 1.5 h and cooled to –78°C. Then a solution
of freshly prepared aldehyde 10 (375 mg, 1.87 mmol) in anhyd THF
(2 mL) was added via cannula. After stirring for 50 min, the mixture
was quenched by the addition of satd aq NH4Cl solution. The mixture
was allowed to warm to r.t. and then extracted with Et2O (1 × 30 mL).
The combined extracts were washed with brine, dried (MgSO4), fil-
tered and concentrated in vacuo. Purification by flash chromatogra-
phy on silica gel (Et2O/petroleum ether, 40:60 to 50:50) gave (3R/S,6S)-
6-methyl-7-[(tetrahydropyran)-2-yloxy]-1-(trimethylsilyl)hept-1-yn-
3-ol (537 mg, 96%) as a colorless oil.
MS (GC, CI, NH3): m/z = 248 (MH+ + NH3), 231 (MH+), 164, 147,
129, 115, 102, 85.
To a solution of LiAlH4 (powder, 95%, 1.58 g, 39.5 mmol, 1.2 equiv)
in Et2O (40 mL) at 0°C was added dropwise a solution of methyl (4S)-
4-methyl-5-[(tetrahydropyran)-2-yloxy]pentanoate (7.59 g, 33.0
mmol) in Et2O (100 mL) over 30 min. The cold bath was removed and
the mixture was stirred at r.t. for 4 h and cooled at 0°C. Then the ex-
cess of LiAlH4 was decomposed by successive addition of H2O
(1 mL), 15% aq NaOH solution (1 mL) and H2O (1.5 mL). After 1.5 h
at r.t., the mixture was filtered on a pad of Celite and the solid was
washed (Et2O). The combined filtrate and washings were dried
(K2CO3), filtered and concentrated in vacuo. Purification by flash
chromatography on silica gel (Et2O/petroleum ether, 50:50 to 80:20)
gave (4S)-4-methyl-5-[(tetrahydropyran)-2-yloxy]pentan-1-ol (9)
(6.19 g, 93%) as a colorless oil.
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.17 [s, 9 H,
Si(CH3)3], 0.92 (d, 1.5 H, J = 6.8 Hz, CH3-6), 0.93 (d, 1.5 H, J = 6.8
Hz, CH3-6), 1.86–1.48 (m, 11 H, H2-4 + H2-5+ H-6 + H2-3' + H2-4' +
H2-5'), 2.32–2.37 (m, 1 H, OH), 3.18 (dd, 0.5 H, J = 10.0 Hz, 9.4 Hz,
Hb-7), 3.23 (t, 0.5 H, J = 9.5 Hz, Hb-7), 3.48–3.54 (m, 1 H, Hb-6'),
3.58 (dd, 0.5 H, J = 10.8, 9.5 Hz, Ha-7), 3.59 (dd, 0.5 H, J = 10.6, 9.5
Hz, Ha-7), 3.85 (td, 1 H, J = 8.3, 2.9 Hz, Ha-6'), 4.29–4.38 (m, 1 H,
H-3), 4.58 (t, 1 H, J = 3.9 Hz, H-2').
9:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.93 (d, 1.5 H,
J = 6.7 Hz, CH3-4), 0.95 (d, 1.5 H, J = 6.7 Hz, CH3-4), 1.28–1.17 (m,
1 H, OH), 1.89–1.48 (m, 11 H, H2-2 + H2-3 + H-4 + H2-3' + H2-4' +
H2-5'), 3.20 (dd, 0.5 H, J = 9.4, 6.2 Hz, Hb-5), 3.25 (dd, 0.5 H, J = 9.6,
6.2 Hz, Hb-5), 3.79–3.48 (m, 4 H, H2-1 + Ha-5 + Hb-6'), 3.86 (td, 1
H, J = 9.3, 3.6 Hz, Ha-6'), 4.58 (t, 1 H, J = 3.2 Hz, H-2').
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 17.0 (CH3-4),
19.6 (C-5'), 25.6 (C-4'), 29.9 (C-3), 30.3 (C-2), 30.8 (C-3'), 33.2 (C-
4), 62.2 (C-6'), 63.0 (C-1), 73.0 (C-5), 99.0 (C-2').
IR (film): ν = 3397, 2938, 1453, 1352, 1200, 1120, 1061, 1032 cm–1.
MS (GC, CI, NH3): m/z = 220 (MH+ + NH3), 203 (MH+), 136, 120,
119, 102, 85.
13C NMR (50 MHz, CDCl3), four diastereomers: δ = –0.3 [Si(CH3)3],
17.1, 17.2 (CH3-6), 19.6 (C-5'), 25.6 (C-4'), 29.2, 29.3 (C-5), 30.8 (C-
3'), 33.2 (C-6), 35.2, 35.3 (C-4), 62.2 (C-6'), 63.1 (C-3), 72.8, 72.9 (C-
7), 89.2, 89.3 (C-2), 99.0, 98.9 (C-2'), 107.1 (C-1).
IR (film): ν = 3418, 2953, 2169, 1454, 1353, 1250, 1120, 1032, 843,
808, 760 cm–1.
MS (GC, CI, NH3): m/z = 316 (MH+ + NH3), 299 (MH+), 281, 232,
215, 197, 102, 85.
A solution of (3R/S,6S)-6-methyl-7-[(tetrahydropyran)-2-yloxy]-1-
(trimethylsilyl)hept-1-yn-3-ol (486 mg, 1.63 mmol) and anhyd
K2CO3 (338 mg, 2.44 mmol, 1.5 equiv) in anhyd MeOH (9 mL) was
stirred 1 h at r.t. Then the mixture was extracted with Et2O and
washed with H2O and brine. The organic layer was dried (MgSO4),
filtered and concentrated in vacuo. Purification by flash chromatogra-
phy on silica gel (Et2O/petroleum ether, 30:70) gave 11a (368 mg,
99%) as a colorless oil.
Anal. calc. for C11H20O3 (201.9): C, 65.31; H, 10.96; found C, 65.37;
H, 11.05.
(4S)-4-Methyl-5-[(tetrahydropyran)-2-yloxy]pentanal (10):
To a solution of oxalyl chloride (2.6 mL, 29.7 mmol, 1.2 equiv) in
CH2Cl2 (80 mL) at –55°C was added DMSO (4.6 mL, 59.3 mmol, 2.4
equiv). This was followed 5 min later with the addition via cannula of
a solution of the alcohol 9 (5.0 g, 24.7 mmol) in CH2Cl2 (40 mL). The
resulting slurry was stirred for 1 h and Et3N (17.2 mL, 123.6 mmol, 5
11a:
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.93 (d, 1.5 H,
J = 6.2 Hz, CH3-6), 0.94 (d, 1.5 H, J = 6.3 Hz, CH3-6), 1.81–1.48 (m,

SYNTHESIS
Papers
528
12 H, H2-4 + H2-5 + H-6 + H2-3' + H2-4' + H2-5' + OH), 2.45 (s, 0.5
H, H-1), 2.46 (s, 0.5 H, H-1), 3.18 (dd, 0.5 H, J = 9.6, 9.4 Hz, Hb-7),
3.24 (dd, 0.5 H, J = 9.5, 9.4 Hz, Hb-7), 3.48–3.52 (m, 1 H, Hb-6'),
3.56 (dd, 0.5 H, J = 12.0, 9.7 Hz, Ha-7), 3.60 (dd, 0.5 H, J = 9.6, 9.3
Hz, Ha-7), 3.85 (td, 1 H, J = 7.7, 2.9 Hz, Ha-6'), 4.32–4.39 (m, 1 H,
H-3), 4.57 (t, 0.5 H, J = 3.3 Hz, H-2'), 4.58 (t, 0.5 H, J = 3.3 Hz, H-2').
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 17.2, 17.3
(CH3-6), 19.6 (C-5'), 25.6 (C-4'), 29.1 (C-5), 30.7 (C-3'), 33.1, 33.2
(C-6), 35.2 (C-4), 62.2 (C-6'), 62.4, 62.5 (C-3), 76.49 (C-1), 85.2 (C-
2), 99.0, 99.1 (C-2').
11b:
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.98 (d, 1.5
H, J = 6.4 Hz, CH3-6), 0.99 (d, 1.5 H, J = 6.7 Hz, CH3-6), 1.51–2.03
(m, 11 H, H2-4 + H2-5 + H-6 + H2-3' + H2-4' + H2-5'), 2.49 (s, 0.5 H,
H-1), 2.50 (s, 0.5 H, H-1), 3.23 (dd, 1 H, J = 9.6, 9.3 Hz, Hb-7), 3.26
(dd, 0.5 H, J = 9.7, 9.2 Hz, Hb-7), 3.47–3.52 (m, 1 H, Hb-6'), 3.59 (t,
0.5 H, J = 9.5 Hz, Ha-7), 3.63 (dd, 0.5 H, J = 9.6, 9.5 Hz, Ha-7),
3.83–3.88 (m, 1 H, Ha-6'), 4.59 (t, 1 H, J = 3.5 Hz, H-2'), 5.61 (t, 0.5
H, J = 6.3 Hz, H-3), 5.62 (t, 0.5 H, J = 6.3 Hz, H-3), 7.47 (t, 2 H, J =
7.5 Hz, H-arom), 7.59 (t, 1 H, J = 7.4 Hz, H-arom), 8.08 (d, 2 H, J =
8.3 Hz, H-arom).
IR (film): ν = 3407, 3308, 2947, 2872, 2361, 1456, 1261, 1119,
1062, 1025 cm–1.
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 17.1 (CH3-6), 19.5
(C-5'), 25.6 (C-4'), 29.1 (C-5), 30.8 (C-3'), 32.5 (C-4), 33.2 (C-6), 62.0,
62.1 (C-6'), 64.7 (C-3), 72.7 (C-7), 73.7 (C-1), 81.5 (C-2), 99.0 (C-2'),
128.4 (C-arom), 129.8 (C-arom), 133.1 (C-arom), 165.4 [OC(O)Ph].
IR (film): ν = 3293, 2940, 2870, 2359, 1723, 1601, 1451, 1266,
1106, 1031, 868, 814, 712 cm–1.
MS (GC, CI, NH3): m/z = 244 (MH+ + NH3), 227 (MH+), 160, 143,
102, 85.
Anal. calc. for C13H22O3 (226.3): C, 68.99; H, 9.80; found C, 68.84;
H, 9.72.
(3R/S,6S)-3-(Benzoyloxy)-6-methyl-7-[(tetrahydropyran)-2-
yloxy]hept-1-yne (11b):
MS (GC, CI, NH3): m/z = 348 (MH+ + NH3), 331 (MH+), 264, 247,
102, 85.
To a solution of (3R/S,6S)-6-methyl-7-[(tetrahydropyran)-2-yloxy]-
1-(trimethylsilyl)hept-1-yn-3-ol (see preparation of 11a, 100 mg,
0.34 mmol) and DMAP (0.02 equiv) in anhyd CH2Cl2 (5 mL) at
–30°C were added Et3N (280 µL, 2.01 mmol, 6.0 equiv) and benzoyl
chloride (117 µL, 1.01 mmol, 3.0 equiv). The cold bath was removed
and the mixture was stirred at 0°C for 2 h. Then the mixture was di-
luted with Et2O. The organic layer was washed with H2O and brine,
dried (MgSO4), filtered and concentrated in vacuo. Purification by
flash chromatography on silica gel (Et2O/petroleum ether, 0:100 to
30:70) gave (3R/S,6S)-3-(benzoyloxy)-6-methyl-7-[(tetrahydropy-
ran)-2-yloxy]-1-(trimethylsilyl)hept-1-yne (110 mg, 82%) as a color-
less oil.
Anal. calc. for C20H26O4 (330.4): C, 72.70; H, 7.93; found C, 72.57;
H, 7.88.
Ethyl (2E,4S,7R/S)-2,4-Dimethyl-7-hydroxynon-2-en-8-ynoate
(12a):
A solution of 12b (see below, 440 mg, 1.34 mmol) and anhyd K2CO3
(278 mg, 2.01 mmol, 1.5 equiv) in anhyd EtOH (10 mL) was stirred
at r.t. overnight. Then the mixture was extracted with Et2O and
washed with H2O and brine. The organic layer was dried (MgSO4),
filtered and concentrated in vacuo. Purification by flash chromatogra-
phy on silica gel (Et2O/petroleum ether, 40:60 to 50:50) gave 12a
(231 mg, 77%) as a colorless oil.
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.19 [s, 9 H,
Si(CH3)3], 0.97 (d, 1.5 H, J = 6.7 Hz, CH3-6), 0.98 (d, 1.5 H, J = 6.6
Hz, CH3-6), 1.51–2.01 (m, 11 H, H2-4 + H2-5 + H-6 + H2-3' + H2-4'
+ H2-5'), 3.21 (dd, 0.5 H, J = 10.0, 9.7 Hz, Hb-7), 3.25 (t, 0.5 H, J =
9.4 Hz, Hb-7), 3.47–3.53 (m, 1 H, Hb-6'), 3.58 (t, 0.5 H, J = 9.4 Hz,
Ha-7), 3.61 (dd, 0.5 H, J = 9.6, 9.4 Hz, Ha-7), 3.828–3.88 (m, 1 H,
Ha-6'), 4.59 (t, 1 H, J = 3.3 Hz, H-2'), 5.6 (t, 0.5 H, J = 6.3 Hz, H-3),
5.65 (t, 0.5 H, J = 6.3 Hz, H-3), 7.42–7.50 (m, 2 H, H-arom),
7.62–7.53 (m, 1 H, H-arom), 8.04–8.13 (m, 2 H, H-arom).
13C NMR (50 MHz, CDCl3), four diastereomers: δ = –0.05
[(CH3)3Si], 17.2 (CH3-6), 19.4 (C-5'), 25.8 (C-4'), 29.4 (C-5), 30.9
(C-3'), 32.9 (C-4), 33.4 (C-6), 62.3 (C-6'), 65.4 (C-3), 72.9 (C-7), 90.8
(C-2), 99.1, 99.2 (C-2'), 103.3 (C-1), 128.5 (C-arom), 130.0 (C-
arom), 130.7 (C-arom), 133.1 (C-arom), 165.3 [OC(O)Ph].
IR (film): ν = 2954, 2871, 2177, 1724, 1600, 1584, 1452, 1265,
1105, 1034, 843, 760, 712 cm–1.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.99 (d, 3 H, J
= 6.6 Hz, CH3-4), 1.26 (t, 3 H, J = 7.1 Hz, CH3CH2O), 1.41–1.67 (m,
4 H, H2-5 + H2-6), 1.80 (s, 3 H, CH3-2), 2.43 (s, 0.5 H, H-9), 2.44 (s,
0.5 H, H-9), 2.44–2.52 (m, 1 H, H-4), 2.77 (d, 1 H, J = 5.3 Hz, OH),
4.14 (q, 2 H, J = 7.1 Hz, CH3CH2O), 4.27–4.33 (m, 1 H, H-7), 6.49
(d, 1 H, J = 10.1 Hz, H-3).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 12.5
(CH3CH2O), 14.2 (CH3-4), 20.0 (CH3-2), 32.0, 32.1 (C-5), 32.9, 33.0
(C-4), 35.4 (C-6), 60.6 (CH3CH2O), 61.9, 62.0 (C-7), 72.9 (C-9), 85.0
(C-8), 126.9 (C-2), 147.3 (C-3), 168.5 [C(O)OEt].
IR (film): ν = 3442, 3301, 2929, 2870, 2361, 1706, 1647, 1456,
1368, 1260, 1191, 1127, 1093, 1028, 751 cm–1.
MS (DI, CI, NH3): m/z = 242 (MH+ + NH3), 225 (MH+), 207, 196,
179, 161, 151, 133, 86.
Anal. calc. for C13H20O3 (224.3): C, 69.61; H, 8.99; found C, 69.07;
H, 8.94.
MS (DI, CI, NH3): m/z = 420 (MH+ + NH3), 403 (MH+), 336, 319,
214, 197, 102.
Ethyl (2E,4S,7R/S)-7-(Benzoyloxy)-2,4-dimethylnon-2-en-8-yno-
ate (12b):
To a solution of (3R/S,6S)-3-(benzoyloxy)-6-methyl-7-[(tetrahydro-
pyran)-2-yloxy]-1-(trimethylsilyl)hept-1-yne (908 mg, 2.26 mmol) in
THF (10 mL) at r.t. was added in one portion TBAF•3H2O (powder,
1.42 g, 4.52 mmol, 2 equiv). The resulting mixture was stirred for 1 h
at 20°C, treated with satd aq NaHCO3 solution and extracted with
CH2Cl2. The organic layer was washed with H2O, dried (MgSO4), fil-
tered and concentrated in vacuo. Purification by flash chromatogra-
phy on silica gel (Et2O/petroleum ether, 0:100 to 20:80) gave 11b
(347 mg, 47%) as a colorless oil.
To a solution of 11b (528 mg, 1.60 mmol) in MeOH (50 mL) at r.t.
was added TsOH (98 mg, 0.48 mmol, 0.3 equiv) and the mixture was
stirred at r.t. for 2 h. Then it was quenched by the addition of Et3N
(134 µL, 0.96 mmol, 0.6 equiv). After 5 min the MeOH was removed
under reduced pressure and the residue was taken up in CH2Cl2. The
CH2Cl2 layer was washed with H2O and the aqueous layer was sepa-
rated and extracted with CH2Cl2 (2 × 50 mL). The combined organic
extracts were washed with brine, dried (MgSO4), filtered and concen-
trated in vacuo. Purification by flash chromatography on silica gel
(Et2O/petroleum ether, 50:50 to 80:20) gave (2S,5R/S)-5-(benzoyl-
oxy)-2-methylhept-6-yn-1-ol, as a colorless oil (361 mg, 92%) .
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.98 (d, 3 H, J
= 6.5 Hz, CH3-2), 1.37–1.44 (m, 2 H, H2-3), 1.67–1.75 (m, 2 H, H-2
+ OH), 1.90–2.07 (m, 2 H, H2-4), 2.51 (s, 0.5 H, H-7), 2.52 (s, 0.5 H,
H-7), 3.48–3.55 (m, 2 H, H2-1), 5.60–5.64 (m, 1 H, H-5), 7.47 (t, 2 H,
J = 7.7 Hz, H-arom), 7.60 (t, 1 H, J = 7.7 Hz, H-arom), 8.08 (d, 2 H,
J = 7.7 Hz, H-arom).
To a solution of 11a (500 mg, 2.2 mmol) and DMAP (15 mg, 0.05
equiv) in anhyd CH2Cl2 (20 mL) at –30°C were added Et3N (2 mL,
13.2 mmol, 6.0 equiv) and benzoyl chloride (7.7 mL, 6.6 mmol,
3.0 equiv). The cold bath was removed and the mixture was stirred at
0°C for 12 h. Then the mixture was diluted with Et2O. The organic
layer was washed with H2O and brine, dried (MgSO4), filtered and
concentrated in vacuo. Purification by flash chromatography on silica
gel (Et2O/petroleum ether, 0:100 to 20:80) gave 11b (695 mg, 96%)
as a colorless oil.

SYNTHESIS
April 1998
529
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 16.5 (CH3-2),
28.5 (C-3), 32.3, 32.4 (C-4), 35.4 (C-2), 64.7 (C-5), 67.9 (C-1), 73.9,
74.0 (C-7), 81.3 (C-6), 128.4 (C-arom), 129.8 (C-arom), 129.9 (C-
arom), 133.2 (C-arom), 165.6 [OC(O)Ph].
PdCl2(PPh3)2 (0.02 equiv) was added Bu3SnH (1.2 equiv) over a pe-
riod of ca 1–2 min. Towards the end of the addition, the originally
light yellow solution abruptly turned orange-brown, and H2 evolution
was observed, signaling the formation of (Bu3Sn)2. After stirring at
20°C for 10 min, the dark brown mixture was concentrated in vacuo.
The crude product was purified by flash chromatography on basic sil-
ica gel (Et2O/petroleum ether, 0:100 to 50:50).
Method B, Stannylcupration with (Bu3Sn)2CuCNLi2 (Homocuprate):
To a solution of (Bu3Sn)2 (8.0 equiv) in anhyd THF (0.1 to 0.3 M) was
added BuLi (1.6 M solution in hexane, 8.0 equiv) at –78°C. The so-
lution was stirred 30 min at –40°C. Then the mixture was added via
cannula to a suspension of CuCN (4.0 equiv) in anhyd THF (1 M) at
–78°C. The mixture was stirred at –40°C until a yellow solution was
obtained and cooled to –78°C. Then a solution of alkyne in anhyd
THF was added via cannula. The mixture was allowed to warm to the
appropriate temperature and when the starting material had been con-
sumed, the mixture was quenched by addition of brine. The mixture
was diluted with Et2O and the organic layer was washed with brine,
dried (MgSO4), filtered and concentrated in vacuo. The crude product
was purified by flash chromatography on basic silica gel (Et2O/petro-
leum ether, 0:100 to 50:50).
Method C, Stannylcupration with (Bu3Sn)2CuCNLi2 and internal
quenching with MeOH (Homocuprate/MeOH): To a solution of
(Bu3Sn)2 (8.0 equiv) in anhyd THF (0.1 to 0.3 M) was added BuLi
(1.6 M solution in hexane, 8.0 equiv) at –78°C. The solution was
stirred 30 min at –40°C. Then the mixture was added via cannula to a
suspension of CuCN (4.0 equiv) in anhyd THF (1 M) at –78°C. The
mixture was stirred at –40°C until a yellow solution was obtained and
cooled to –78°C. Then anhyd MeOH (110 equiv) was added and the
yellow solution turned to a red gel. The temperature was allowed to
warm to –40°C for 15 min until the gel was converted to a red solu-
tion. The red solution was cooled to –78°C before the addition via
cannula of a solution of alkyne in THF. The mixture was allowed to
warm to the appropriate temperature and when the starting material
had been consumed, the mixture was quenched by addition of brine.
The mixture was diluted with Et2O and the organic layer was washed
with brine, dried (MgSO4), filtered and concentrated in vacuo. The
crude product was purified by flash chromatography on basic silica
gel (Et2O/petroleum ether, 0:100 to 50:50).
IR (film): ν = 3296, 2956, 2874, 2361, 1722, 1602, 1491, 1316,
1270, 1108, 1070, 1026, 712 cm–1.
MS (DI, CI, NH3): m/z = 264 (MH+ + NH3), 247 (MH+), 229, 160,
142, 125, 105, 94.
To a solution of oxalyl chloride (320 µL, 3.66 mmol, 2.5 equiv) in an-
hyd CH2Cl2 (20 mL) at –55°C was added DMSO (567 µL,
7.33 mmol, 5.0 equiv). This was followed 5 min later with the addi-
tion of a solution of (2S,5R/S)-5-(benzoyloxy)-2-methylhept-6-yn-1-
ol (361 mg, 1.47 mmol) in anhyd CH2Cl2 (4 mL). The resulting slurry
was stirred for 1 h and Et3N (2.66 mL, 19.1 mmol, 13.0 equiv) was
added. After stirring for 5 min, the mixture was warmed to r.t. The
mixture was diluted with CH2Cl2 (40 mL) and was washed with an
ice-cold 1M HCl solution (19 mL) and H2O (19 mL). The aqueous
phases were extracted with CH2Cl2 (40 mL), the organic layers were
combined, dried (MgSO4), filtered and concentrated in vacuo. The
crude aldehyde (2S,5R/S)-5-(benzoyloxy)-2-methylhept-6-ynal thus
obtained was used in the next step without further purification.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 1.17 (d, 3 H, J
= 7.2 Hz, CH3-2), 1.36–1.44 (m, 2 H, H2-3), 1.95–2.04 (m, 2 H, H2-
4), 2.41–2.48 (m, 1 H, H-2), 2.52 (s, 0.5 H, H-7), 2.53 (s, 0.5 H, H-7),
5.60–5.63 (m, 1 H, H-5), 7.46 (t, 2 H, J = 7.7 Hz, H-arom), 7.60 (t, 1
H, J = 7.7 Hz, H-arom), 8.06 (d, 2 H, J = 7.7 Hz, H-arom), 9.65 (s, 1
H, H-1).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 13.0 (CH3-2),
25.3 (C-3), 31.7 (C-4), 45.3 (C-2), 63.7 (C-5), 74.2 (C-7), 80.5 (C-6),
128.2 (C-arom), 129.4 (C-arom), 133.0 (C-arom), 164.9 [OC(O)Ph],
203.7 (C-1).
IR (film): ν = 2933, 2360, 1721, 1451, 1316, 1266, 1177, 1107,
1070, 1025, 713 cm–1.
MS (DI, CI, NH3): m/z = 262 (MH+ + NH3), 245 (MH+), 215, 123,
105, 94.
A solution of the crude aldehyde (2S,5R/S)-5-(benzoyloxy)-2-methyl-
hept-6-ynal (520 mg, see above) and (ethoxycarbonyleth-
ylidene)triphenylphosphorane (2.23 g, 6.15 mmol, 4.2 equiv) in
anhyd toluene (10 mL) was warmed at 45°C for 8 h. Then the toluene
was removed under reduced pressure. The residue was dissolved in
Et2O, filtered on a pad of Celite and the solid was washed with Et2O.
The combined filtrate and washings were concentrated in vacuo. Pu-
rification by flash chromatography on silica gel (Et2O/petroleum
ether, 0:100 to 20:80) gave 12b (335 mg, 69% for two steps) as a col-
orless oil.
Stannylations of 11a; (1E,3R/S,6S)-6-Methyl-7-[(tetrahydropy-
ran)-2-yloxy]-1-[(tributyl)stannyl]hept-1-en-3-ol (13a), (3R/
S,6S)-6-Methyl-7-[(tetrahydropyran)-2-yloxy]-2-[(tributyl)stan-
nyl]-hept-1-en-3-ol (14a) and (1Z,3R/S,6S)-1,2-{Bis[(tribu-
tyl)stannyl]}-6-methyl-7-[(tetrahydropyran)-2-yloxy]hept-1-en-3-
ol (15a):
Entry 1, Table 1 : Method A, Pd Stannylation: From 11a (100 mg,
0.44 mmol), stannane 13a (132 mg, 58%) and stannane 14a (33 mg,
14%) were obtained (72% , 13a/14a = 80:20).
12b:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 1.06 (d, 3 H, J
= 6.5 Hz, CH3-4), 1.29–1.34 (m, 3 H, CH3CH2O), 1.55–1.66 (m, 2 H,
H2-5), 1.85–1.90 (m, 5 H, H2-6 + CH3-2), 2.50 (s, 0.5 H, H-9), 2.51
(s, 0.5 H, H-9), 2.54–2.59 (m, 1 H, H-4), 4.22 (q, 2 H, J = 7.1 Hz,
CH3CH2O), 5.58–5.62 (m, 1 H, H-7), 6.55 (br d, 1 H, J = 9.9 Hz, H-
3), 7.47 (t, 2 H, J = 7.7 Hz, H-arom), 7.60 (t, 1 H, J = 7.7 Hz, H-arom),
8.07 (d, 2 H, J = 7.6 Hz, H-arom).
Entry 2, Table 1 : Method B, Homocuprate: From 11a (80 mg,
0.35 mmol), stannane 13a (30 mg, 16%), stannane 14a (40 mg, 22%),
vicinal bis(stannane) 15a (134 mg, 48%) and starting material 11a
(11 mg, 14%) were obtained (86%, 13a/14a/15a = 19:25:56).
Entry 3, Table 1 : Method C, Homocuprate/MeOH: From 11a (80 mg,
0.35 mmol), stannane 13a (68 mg, 38%), stannane 14a (41 mg, 23%)
and starting material 11a (24 mg, 30%) were obtained (61%, 13a/14a
= 63:37).
Entry 4, Table 1 : Method C, Homocuprate/MeOH: From 11a (80 mg,
0.35 mmol), stannane 13a (108mg, 61%), stannane 14a (36 mg, 20%)
and starting material 11a (8 mg, 10%) were obtained (81%, 13a/14a
= 75:25).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 12.5
(CH3CH2O), 14.3 (CH3-4), 19.9 (CH3-2), 32.1 (C-6), 32.8 (C-5), 32.9
(C-4), 60.4 (CH3CH2O), 64.3 (C-7), 74.0 (C-9), 81.1 (C-8), 127.3 (C-
2), 128.7 (C-arom), 129.8 (C-arom), 133.2 (C-arom), 146.7 (C-3),
165.4 [OC(O)Ph], 168.2 [C(O)OEt].
IR (film): ν = 2958, 2930, 2869, 2359, 1722, 1650, 1451, 1367,
1266, 1192, 1096, 1070, 1026, 750, 713 cm–1.
MS (DI, CI, NH3): m/z = 346 (MH+ + NH3), 329 (MH+), 285, 279,
164, 102.
13a:
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.92–0.85 [m,
18 H, CH3-6 + 3 CH2 + 3 CH3, Sn(CH2CH2CH2CH3)3], 1.34–1.27 [m,
7 H, OH + 3 CH2, Sn(CH2CH2CH2CH3)3], 1.42–1.92 [m, 17 H, H2-4
+ H2-5+ H-6+ H2-3'+ H2-4'+ H2-5' + 3 CH2, Sn(CH2CH2CH2CH3)3],
Stannylations of Alkynes 11a, 12a and 12b; General Procedure:
Method A, Palladium(0)-catalyzed hydrostannylation (Pd Stannyla-
tion): To a solution of alkyne derivative in THF (0.1 to 0.3 M) and

SYNTHESIS
Papers
530
3.15 (dd, 0.5 H, J = 11.5, 9.1 Hz, Hb-7), 3.23 (t, 0.5 H, J = 9.4 Hz, Hb-
7), 3.46–3.54 (m, 1.5 H, Hb-6' + 0.5Ha-7), 3.60 (t, 0.5 H, J = 9.5 Hz,
Ha-7), 3.84 (td, 1 H, J = 7.9, 2.8 Hz, Ha-6'), 3.99–4.18 (m, 1 H, H-3),
4.56 (t, 1 H, J = 3.0 Hz, H-2'), 6.00 (dm, 1 H, J = 19.1 Hz, H-2), 6.12
(d, 1 H, J = 19.1 Hz, J 1H - 117Sn = J 1H - 119Sn = 71.2 Hz, H-1).
13C NMR (100 MHz, CDCl3), four diastereomers: δ = 9.4 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = 326.8 Hz, J 13C - 119Sn = 341.2
Hz], 13.6 [3 CH3, Sn(CH2CH2CH2CH3)3], 17.2 (CH3, CH3-6), 19.5
(C-5'), 25.5 (C-4'), 27.2 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C -119Sn = 56.5 Hz], 27.7
[3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 61.8
Hz], 29.3 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn
= 19.7 Hz], 29.5 [C-5, 3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn =
J
13C - 119Sn = 17.7 Hz], 30.9 (C-3'), 33.5 (C-6), 34.9 (C-4), 62.3 (C-
6'), 73.2 (C-7), 84.0 (C-3, J 13C - 117Snb = J 13C - 119Snb = 90.9 Hz, J
13C - 117Sna = J 13C - 119Sna = 46.2 Hz), 99.02, 99.2 (C-2'), 140.3 (C-
1, J 13C - 117Sna = J 13C - 119Sna = 61.8 Hz), 172.2 (C-2, J 13 C - 117Snb
= J 13C - 119Snb = 30.3 Hz).
= J 13C - 119Sn = 52.8 Hz], 29.1 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13
C
IR (film): ν = 3614, 3459, 2954, 2870, 2853, 1538, 1463, 1376,
-
117Sn = J 13C - 119Sn = 19.5 Hz], 29.3, 29.4 (C-5), 30.7 (C-3'), 33.3,
1120, 1063, 1025, 865, 666 cm–1.
33.4 (C-6), 34.4 (C-4), 61.9 (C-6'), 72.4 (C-7), 75.5 (C-3, J 13C - 117Sn
= J 13C - 119Sn = 60.9 Hz), 75.7 (C-3, J 13C - 117Sn = J 13C - 119Sn =
60.8 Hz), 98.7, 98.9 (C-2'), 127.3 (C-1, J 13C - 117Sn = J13C - 119Sn =
367.0 Hz), 151.3 (C-2).
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 597,
595, 507, 443, 308, 291, 244, 160, 102, 85.
Anal. calc. for C37H76O3Sn2 (806.4): C, 55.11; H, 9.50; found C,
54.92; H, 9.59.
IR (film): ν = 3444, 2925, 2870, 2852, 1601, 1463, 1376, 1200,
1120, 1062, 1032, 904, 868, 668 cm–1.
Stannylations of 12a; Ethyl (2E,4S,7R/S,8E)-2,4-Dimethyl-7-hy-
droxy-9-[(tributyl)stannyl]non-2,8-dienoate (16a), Ethyl (2E,4S,
7R/S)-2,4-Dimethyl-7-hydroxy-8-[(tributyl)stannyl]non-2,8-di-
enoate (17a) and Ethyl (2E,4S,7R/S,8Z)-8,9-{Bis[(tributyl)stan-
nyl]}-2,4-dimethyl-7-hydroxynon-2,8-dienoate (18a):
Entry 1, Table 2: Method A Pd Stannylation: From 12a (65 mg,
0.29 mmol), stannane 16a (54 mg, 37%) was obtained.
Entry 2, Table 2: Method B Homocuprate: From 12a (50 mg,
0.22 mmol), stannane 17a (9 mg, 8%), vicinal bis(stannane) 18a (50
mg, 30%), and starting material 12a (20 mg, 40%) were obtained
(38%, 17a/18a = 20:80).
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 501
(MH+ –H2O), 461 (M+ – 57, C4H9), 359, 308, 291, 244, 229, 162, 102,
85.
Anal. calc. for C25H50O3Sn (517.4): C, 58.04; H, 9.74; found C,
58.17; H, 9.88.
14a:
1
H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.87–0.97 [(m,
18 H, CH3-6 + 3 CH2 + 3 CH3, Sn(CH2CH2CH2CH3)3], 1.38–1.23 [m,
7 H, OH + 3 CH2, Sn(CH2CH2CH2CH3)3], 1.41–1.82 [m, 17 H, H2-4
+
H2-5
+
H-6
+
H2-3'
+
H2-4'
+
H2-5'
+
3
CH2,
Entry 3, Table 2: Method C Homocuprate/MeOH: From 12a (50 mg,
0.22 mmol), stannane 16a (40 mg, 35%), stannane 17a (13 mg, 11%)
and starting material 12a (13 mg, 26%) were obtained (46%, 16a/17a
= 75:25).
Sn(CH2CH2CH2CH3)3], 3.18 (dd, 0.5 H, J = 9.4, 9.3 Hz, Hb-7), 3.25
(t, 0.5 H, J = 9.3 Hz, Hb-7), 3.48–3.57 (m, 1.5 H, 0.5 Ha-7 + Hb-6'),
3.62 (dd, 0.5 H, J = 9.4 , 9.2 Hz, Ha-7), 3.87 (td, 1 H, J = 8.3, 3.4 Hz,
Ha-6'), 4.16–4.21 (m, 1 H, H-3), 4.57–4.59 (m, 1 H, H-2'), 5.22 (s, 1
H, J 1H - 117Sn = J 1H - 119Sn = 63.1 Hz, Ha-1), 5.79 (s, 1 H, J 1H -
117Sn = J 1H - 119Sn = 132.0 Hz, Hb-1).
16a:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.82–0.99 [m,
15 H, 3 CH2 + 3 CH3, Sn(CH2CH2CH2CH3)3], 1.02 (d, 3 H, J = 6.8
13C NMR (100 MHz, CDCl3), four diastereomers: δ = 10.3 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = 321.1 Hz, J 13C - 119Sn = 335.5
Hz], 13.8 [3 CH3, Sn(CH2CH2CH2CH3)3], 17.3, 17.4 (CH3, CH3-6),
19.7 (C-5'), 25.7 (C-4'), 27.5 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13C -
117Sn = J 13C - 119Sn = 58.5 Hz], 29.2 [3 CH2, Sn(CH2CH2CH2CH3)3,
Hz, CH3-4), 1.29–1.35 [m,
9 H, CH3CH2O + 3 CH2,
Sn(CH2CH2CH2CH3)3], 1.47–1.59 [m, 11 H, H2-5 + H2-6 + OH + 3
CH2, Sn(CH2CH2CH2CH3)3], 1.85 (d, 3 H, J = 1.4 Hz, CH3-2),
2.48–2.57 (m, 1 H, H-4), 4.02–4.17 (m, 1 H, H-7), 4.20 (q, 2 H, J =
7.1 Hz, CH3CH2O), 5.98 (dd, 1 H, J = 19.1, 5.4 Hz, H-8), 6.18 (d, 1
H, J = 19.1 Hz, J 1H - 117Sn = J 1H - 119Sn = 69.7 Hz, H-9), 6.54 (dq,
1 H, J = 10.1, 1.4 Hz, H-3).
J
13C - 117Sn = J 13C - 119Sn = 18.4 Hz], 29.8, 29.9 (C-5), 30.8 (C-3'),
33.5, 33.6 (C-6), 35.1 (C-4), 62.2, 62.3 (C-6'), 73.0, 73.1 (C-7), 79.9
(C-3, J 13C - 117Sn = J 13C - 119Sn = 32.1 Hz), 99.0, 99.1 (C-2'), 123.9
(C-1, J 13C - 117Sn = J13C - 119Sn = 21.2 Hz), 124.1 (C-1, J 13C - 117Sn
= J 13C - 119Sn = 21.0 Hz), 159.4, 159.6 (C-2).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 9.56 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = 342.3 Hz, J 13C - 119Sn = 327.1
Hz], 12.5 (CH3CH2O), 13.6 [3 CH3, Sn(CH2CH2CH2CH3)3], 14.3
(CH3, CH3-4), 19.9 (CH3-2), 27.2 [3 CH2, Sn(CH2CH2CH2CH3)3, J
IR (film): ν = 3462, 2926, 2870, 2852, 1463, 1376, 1120, 1062,
1025, 978, 919, 904, 867, 806, 666 cm–1.
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 501
(MH+ – H2O), 359, 308, 291, 145, 102, 85.
13C 117Sn 13C 119Sn
- = J - = 53.1 Hz], 29.1 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 19.4 Hz], 32.5,
32.6 (C-5), 33.2, 33.3 (C-4), 34.9 (C-6), 60.3 (CH3CH2O), 75.5 (C-7),
126.8 (C-2), 127.8 (C-9), 147.4 (C-3), 151.2 (C-8), 168.3 [C(O)OEt].
IR (film): ν = 3432, 2956, 2926, 2870, 2853, 1711, 1647, 1601, 1457,
1375, 1260, 1177, 1122, 1096, 1024, 990, 873, 794, 750, 689, 663 cm–1.
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 517
(MH+), 499 (MH+ – H2O), 459, 443, 308, 291, 227, 209, 181, 135,
112, 72.
Anal. calc. for C25H50O3Sn (517.4): C, 58.04; H, 9.74; found C,
58.24; H, 9.98.
15a:
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.87–1.01 [m,
33 H, CH3-6 + 6 CH2 + 6 CH3, 2 Sn(CH2CH2CH2CH3)3], 1.28–1.39
[m, 13 H, OH + 6 CH2, 2 Sn(CH2CH2CH2CH3)3], 1.42–1.87 [m, 23
H, H2-4 + H2-5 + H-6 + H2-3' + H2-4' + H2-5' + 6 CH2, 2
Sn(CH2CH2CH2CH3)3], 3.16 (dd, 0.5 H, J = 9.4, 9.3 Hz, Hb-7), 3.24
(dd, 0.5 H, J = 9.4z, 9.3 Hz, Hb-7), 3.47–3.55 (m, 1.5 H, Ha-7 + Hb-
6'), 3.63 (dd, 0.5 H, J = 9.4, 9.3 Hz, Ha-7), 3.87 (td, 1 H, J = 8.3, 3.4
Hz, Ha-6'), 4.00–4.09 (m, 1 H, H-3), 4.57–4.59 (m, 1 H, H-2'), 6.75
(s, 1 H, J 1H - 117Sna = J 1H - 119Sna = 132.0 Hz, J 1H - 117Snb = J 1H
Anal. calc. for C25H48O3Sn (515.4): C, 58.27; H, 9.39; C, 58.68, H,
9.52.
17a:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.89–0.96 [m,
15 H, 3 CH2 + 3 CH3, Sn(CH2CH2CH2CH3)3], 1.02 (d, 3 H, J = 6.6
Hz, CH3-4), 1.29–1.35 [m, 10 H, CH3CH2O + OH + 3 CH2,
Sn(CH2CH2CH2CH3)3], 1.43–1.53 [m, 11 H, H-4 + H2-5 + H2-6 + 3
CH2, Sn(CH2CH2CH2CH3)3], 1.85 (s, 3 H, CH3-2), 2.46–2.55 (m, 1
H, H-4), 4.12–4.18 (m, 1 H, H-7), 4.19 (q, 2 H, J = 7.2 Hz,
-
119Snb = 66.5 Hz, H-1).
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 11.1 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = 318.4 Hz, J 13C - 119Sn = 333.5
Hz], 11.4 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13C -117Sn = 309.3 Hz, J
13C - 119Sn = 324.1 Hz], 13.8 [6 CH3, Sn(CH2CH2CH2CH3)3], 17.4
(CH3, CH3-6), 19.7 (C-5'), 25.7 (C-4'), 27.5 [3 CH2,
1
1
CH3CH2O), 5.22 (d, 1 H, J = 1.9 Hz, J H - 117Sn = J H - 119Sn =
62.5 Hz, Ha-9), 5.79 (d, 1 H, J = 1.9 Hz, J 1H - 117Sn = J 1H - 119Sn =

SYNTHESIS
April 1998
531
131.3 Hz, Hb-9), 6.53 (d, 1 H, J = 10.2 Hz, H-3).
Hz], 32.4 (C-5 + C-6), 33.2, 33.3 (C-4), 60.5 (CH3CH2O), 77.4, 77.5
(C-7), 126.4 (C-2), 127.3 (C-9), 128.4 (C-arom), 129.8 (C-arom),
132.8 (C-arom), 146.0 (C-8), 147.1 (C-3), 165.9 [OC(O)Ph], 168.4
(C-1).
IR (film): ν = 2956, 2926, 2870, 1716, 1648, 1602, 1451, 1366,
1314, 1268, 1175, 1109, 1069, 1026, 988, 864, 749, 711 cm–1.
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 638
(MH+ + NH3), 621 (MH+), 499, 497, 348, 308, 291, 226, 209, 122.
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 10.7 [3 CH2,
Sn(CH2CH2CH2CH3)3], 12.7 (CH3, CH3CH2O), 13.7 [3 CH3,
Sn(CH2CH2CH2CH3)3], 14.4 (CH3-4), 20.1 (CH3-2), 27.5 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 51.5 Hz], 29.3
[3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn =
19.4 Hz], 33.1, 33.2 (C-5), 33.5 (C-4), 35.8 (C-6), 60.5 (CH3CH2O),
79.5 (C-7), 124.0 (C-9, J 13C - 117Sn = J 13C - 119Sn = 16.7 Hz), 127.1
(C-2), 147.5 (C-3), 159.8 (C-8), 168.4 [C(O)OEt].
IR (film): ν = 3497, 2956, 2927, 2870, 2853, 1711, 1696, 1648, 1375,
17b:
1257, 1180, 1119, 1080, 1024, 920, 874, 750 cm–1.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.83–0.95 [m,
15 H, 3 CH2 + 3 CH3, Sn(CH2CH2CH2CH3)3], 1.02 (d, 3 H, J = 6.5
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 499
(MH+ – H2O), 457, 391, 364, 308, 291, 242, 209, 181, 135, 96.
Hz, CH3-4), 1.24–1.35 [m,
Sn(CH2CH2CH2CH3)3], 1.42–1.53 [m,
9
H, CH3CH2O
H, H2-5
+
3
CH2,
CH2,
8
+ 3
18a:
Sn(CH2CH2CH2CH3)3], 1.68–1.87 (m, 2 H, H2-6), 1.85 (s, 3 H, CH3-
2), 2.48–2.59 (m, 1 H, H-4), 4.19 (q, 2 H, J = 7.0 Hz, CH3CH2O), 5.24
(s, 1 H, J 1H - 117Sn = J 1H - 119Sn = 61.0 Hz, Ha-9), 5.56–5.62 (m, 1
H, H-7), 5.93 (s, 1 H, J 1H - 117Sn = J 1H - 119Sn = 125.0 Hz, Hb-9),
6.53 (d, 1 H, J = 9.9 Hz, H-3), 7.46 (t, 2 H, J = 7.1 Hz, H-arom), 7.58
(t, 1 H, J = 7.2 Hz, H-arom), 8.07 (t, 2 H, J = 8.3 Hz, H-arom).
1H NMR (200 MHz, CDCl3), two diastereomers: δ = 0.87–0.97 (m,
30 H, 6 CH2 + 6 CH3, 2 Sn(CH2CH2CH2CH3)3], 1.01 (d, 3 H, J = 6.6
Hz, CH3-4), 1.23–1.85 [m, 33 H, H-4 + H2-5 + H2-6 + OH + 6 CH2,
2 Sn(CH2CH2CH2CH3)3 + 6 CH2, 2 Sn(CH2CH2CH2CH3)3
+
CH3CH2O], 1.85 (s, 3 H, CH3-2), 2.42–2.58 (m, 1 H, H-4), 3.97–4.06
(m, 1 H, H-7), 4.18 (q, 2 H, J = 7.1 Hz, CH3CH2O), 6.53 (d, 1 H, J =
10.1 Hz, H-3), 6.74 (s, 1 H, J 1H - 117Sna = J 1H - 119Sna = 176.4 Hz,
J 1H - 117Snb = J 1H - 119Snb = 66.2 Hz, H-9).
13
C NMR (50 MHz, CDCl3), two diastereomers: δ = 9.9 [(3 CH2,
Sn(CH2CH2CH2CH3)3], 12.7 (CH3CH2O), 13.7 [3 CH3,
Sn(CH2CH2CH2CH3)3], 14.4 (CH3-4), 20.0 (CH3-2), 27.3 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 51.0 Hz), 29.2
[3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 21.0
Hz], 32.4 (C-5 + C-6), 33.2, 33.3 (C-4), 60.5 (CH3CH2O), 81.8 (C-7),
126.4 (C-9), 132.8, 132.7, 132.4, 131.4, 131.3, 129.8, 128.7, 128.4
(C-arom + C-8 + C-2), 147.1 (C-3), 165.9 [OC(O)Ph], 168.4 (C-1).
IR (film): ν = 2956, 2926, 2870, 1716, 1648, 1602, 1451, 1366, 1314,
1268, 1175, 1109, 1069, 1026, 988, 864, 749, 711 cm–1.
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 11.3 [3 CH2,
Sn(CH2CH2CH2CH3)3], 11.7 [3 CH2, Sn(CH2CH2CH2CH3)3], 12.6
(CH3CH2O), 13.6 [6 CH3, 2 Sn(CH2CH2CH2CH3)3], 14.6 (CH3-4),
20.1 (CH3-2), 27.4 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J
13C - 119Sn = 55.2 Hz], 27.6 [3 CH2, Sn(CH2CH2CH2CH3)3, J 13C -
117Sn = J 13C - 119Sn = 60.8 Hz], 29.4 [3 CH2, Sn(CH2CH2CH2CH3)3],
29.5 [3 CH2, Sn(CH2CH2CH2CH3)3], 33.4 (C-5), 33.5 (C-4), 35.4 (C-
6), 60.4 (CH3CH2O), 83.8, 84.0 (C-7), 127.0 (C-2), 140.6-140.9 (C-
9), 147.5 (C-3), 168.4 (C-1), 172.1, 172.2 (C-8).
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 499
(MH+ – 122, PhCO2H), 497, 348, 308, 291, 226, 209, 122.
IR (film): ν = 3505, 2955, 2923, 2870, 2853, 2360, 1712, 1696,
1648, 1463, 1375, 1258, 1180, 1124, 1072, 1022, 960, 863, 750, 666
cm–1.
Ethyl (2E,4S)-7-(Benzoyloxy)-2,4-dimethylhept-2-enoate (19):
To a solution of 9 (4.55 g, 22.5 mmol) and DMAP (0.05 equiv) in an-
hyd CH2Cl2 (100 mL) at –30°C were added Et3N (18.8 mL,
135.0 mmol, 6.0 equiv) and benzoyl chloride (7.8 mL, 67.5 mmol,
3.0 equiv). The cold bath was removed and the mixture was stirred at
0°C for 2 h. Then the mixture was diluted with Et2O. The organic lay-
er was washed with H2O and brine, dried (MgSO4), filtered and con-
centrated in vacuo. Purification by flash chromatography on silica gel
(Et2O/petroleum ether, 0:100 to 20:80) gave (2S)-5-(benzoyloxy)-2-
methyl-1-[(tetrahydropyran)-2-yloxy]pentane (6.89 g, quantitative
yield) as a colorless oil.
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 789
(MH+ – H2O), 787, 745, 597, 515, 457, 441, 308, 291, 209, 179, 135.
Anal. calc. for C37H74O3Sn2 (804.4): C, 55.25; H, 9.27; found C,
54.65; H, 9.29.
Stannylations of 12b; Ethyl (2E,4S,7R/S,8E)-2,4-Dimethyl-7-
(benzoyloxy)-9-[(tributyl)stannyl]non-2,8-dienoate (16b) and
Ethyl
(2E,4S,7R/S)-2,4-Dimethyl-7-(benzoyloxy)-8-[(tributyl)-
stannyl]non-2,8-dienoate (17b):
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.98 (d, 1.5 H,
J = 6.6 Hz, CH3-2), 0.99 (d, 1.5 H, J = 6.6 Hz, CH3-2), 1.27–1.33 (m,
1 H, Hb-3), 1.50–1.86 (m, 10 H, H-2 + Ha-3 + H2-4 + H2-3' + H2-4' +
H2-5'), 3.22 (dd, 0.5 H, J = 9.5, 9.4 Hz, Hb-1), 3.26 (dd, 0.5 H, J = 9.5,
9.4 Hz, Hb-1), 3.48–3.53 (m, 1 H, Hb-6'), 3.61 (dd, 0.5 H, J = 9.6, 9.4
Hz, Ha-1), 3.63 (dd, 0.5 H, J = 9.6, 9.4 Hz, Ha-1), 3.83–3.89 (m, 1 H,
Ha-6'), 4.33 (t, 2 H, J = 6.6 Hz, H2-5), 4.59 (t, 1 H, J = 3.1 Hz, H-2'),
7.44 (t, 2 H, J = 8.0 Hz, H-arom), 7.50–7.58 (m, 1 H, H-arom), 8.06
(d, 2 H, J = 8.0 Hz, H-arom).
Method A, Pd Stannylation: From 12b (1.05 g, 3.20 mmol), stannane
16b (677 mg, 34%) and stannane 17b (452 mg, 23%) were obtained
(57%, 16b/17b = 60:40).
Method C, Homocuprate/MeOH: From 12b (50 mg, 0.15 mmol),
stannane 16b (35 mg, 37%) and starting material 12b (11 mg, 22%)
were obtained.
16b:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.83–0.95 [m,
15 H, 3 CH2 + 3 CH3, Sn(CH2CH2CH2CH3)3], 1.02 (d, 3 H, J = 6.5
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 17.1, 17.2 (CH3-
2), 19.6 (C-5'), 25.6 (C-4'), 26.3 (C-4), 30.1 (C-3), 30.8 (C-3'), 33.3
(C-2), 62.2 (C-6'), 65.4 (C-5), 72.8 (C-1), 99.1 (C-2'), 128.4 (C-arom),
129.6 (C-arom), 130.7 (C-arom), 132.9 (C-arom), 166.7 [OC(O)Ph].
IR (film): ν = 3063, 2949, 2871, 1790, 1719, 1601, 1584, 1452,
1382, 1314, 1275, 1212, 1174, 1116, 1072, 1033, 904, 867, 712 cm–1.
MS (DI, CI, NH3): m/z = 324 (MH+ + NH3), 307 (MH+), 240, 223,
205, 184, 154, 118, 102, 85.
Hz, CH3-4), 1.24–1.35 [m,
Sn(CH2CH2CH2CH3)3], 1.42–1.53 (m,
9
H, CH3CH2O
H, H2-5
+
+ 3
3
CH2,
CH2,
8
Sn(CH2CH2CH2CH3)3], 1.68–1.87 (m, 2 H, H2-6), 1.85 (s, 3 H, CH3-
2), 2.48–2.59 (m, 1 H, H-4), 4.19 (q, 2 H, J = 7.0 Hz, CH3CH2O),
5.42–5.49 (m, 1 H, H-7), 5.98 (dd, 1 H, J = 19.1, 5.8 Hz, H-8), 6.25
(d, 1 H, J = 19.1 Hz, J 1H - 117Sn = J 1H - 119Sn = 68.6 Hz, H-9), 6.53
(d, 1 H, J = 9.9 Hz, H-3), 7.46 (t, 2 H, J = 7.1 Hz, H-arom), 7.58 (t, 1
H, J = 7.2 Hz, H-arom), 8.07 (t, 2 H, J = 8.3 Hz, H-arom).
To a solution of (2S)-5-(benzoyloxy)-2-methyl-1-[(tetrahydropyran)-
2-yloxy]pentane (7.0 g, 22.8 mmol) in MeOH (200 mL) at r.t. was
added TsOH (1.30 g, 6.85 mmol, 0.3 equiv) and the mixture was
stirred at r.t. for 1 h. Then it was quenched by the addition of Et3N (1.9
mL, 13.7 mmol, 0.6 equiv). After 5 min, the MeOH was removed un-
der reduced pressure and the residue was taken up in CH2Cl2. The res-
13
C NMR (50 MHz, CDCl3), two diastereomers: δ = 9.9 [3 CH2,
Sn(CH2CH2CH2CH3)3], 12.7 (CH3CH2O), 13.7 [3 CH3,
Sn(CH2CH2CH2CH3)3], 14.4 (CH3-4), 20.0 (CH3-2), 27.3 [3 CH2,
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 51.0 Hz], 29.2
[3 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn = 21.0

SYNTHESIS
Papers
532
idue was washed with H2O and the aqueous layer was separated and
extracted with CH2Cl2 (2 × 200 mL). The combined organic extracts
were washed with brine, dried (MgSO4), filtered and concentrated in
vacuo. Purification by flash chromatography on silica gel (Et2O/
petroleum ether, 50:50 to 80:20) gave (2S)-5-(benzoyloxy)-2-methyl-
pentan-1-ol (4.10 g, 81%) as a colorless oil.
IR (film): ν = 2959, 1718, 1650, 1602, 1452, 1367, 1314, 1274,
1201, 1175, 1112, 1070, 1026, 712 cm–1.
MS (GC, CI, NH3): m/z = 322 (MH+ + NH3), 305 (MH+), 276, 259,
231, 199, 182, 154, 136, 122, 105, 94.
Anal. calc. for C18H24O4 (304.4): C, 71.03; H, 7.95; found C, 70.85;
H, 7.84.
1H NMR (400 MHz, CDCl3): δ = 0.98 (d, 3 H, J = 6.7 Hz, CH3-2),
1.26–1.36 (m, 1 H, Hb-3), 1.58–1.65 (m, 1 H, Ha-3), 1.67–1.76 (m, 1
H, H-2), 1.76–1.82 (m, 1 H, Hb-4), 1.84–1.93 (m, 1 H, Ha-4),
3.47–3.55 (m, 3 H, H2-1 + OH), 4.34 (t, 2 H, J = 6.7 Hz, H2-5), 7.46
(t, 2 H, J = 7.6 Hz, H-arom), 7.57 (t, 1 H, J = 7.6 Hz, H-arom), 8.05
(d, 2 H, J = 7.6 Hz, H-arom).
Ethyl (2E,4S)-2,4-Dimethyl-7-oxohept-2-enoate (20):
A solution of 19 (4.37 g, 14.3 mmol) and anhyd K2CO3 (2.97 mg, 21.5
mmol, 1.5 equiv) in anhyd MeOH (70 mL) was stirred for 8 h at 40°C.
Then the mixture was extracted with Et2O and washed with H2O and
brine. The organic layer was dried (MgSO4), filtered and concentrated
in vacuo. Purification by flash chromatography on silica gel (Et2O/pe-
troleum ether, 50:50 to 60:40) gave ethyl (2E,4S)-2,4-dimethyl-7-hy-
droxyhept-2-enoate (2.49 g, 87%) as a colorless oil.
13C NMR (50 MHz, CDCl3): δ = 16.6 (CH3-2), 26.6 (C-4), 29.9 (C-
3), 35.8 (C-2), 65.4 (C-5), 68.3 (C-1), 128.5 (C-arom), 129.7 (C-
arom), 131.0 (C-arom), 132.9 (C-arom), 166.8 [OC(O)Ph].
IR (film): ν = 3420, 2954, 1718, 1602, 1451, 1387, 1315, 1276,
1176, 1113, 1070, 1026, 711 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.03 (d, 3 H, J = 6.5 Hz, CH3-4),
1.31 (t, 3 H, J = 6.9 Hz, CH3CH2O), 1.37–1.42 (m , 2 H, Hb-5 + OH),
1.47–1.58 (m, 3 H, H2-6 + Ha-5), 1.85 (d, 3 H, J = 1.4 Hz, CH3-2),
2.51–2.55 (m, 1 H, H-4), 3.63 (t, 2 H, J = 6.2 Hz, H2-7), 4.20 (q, 2 H,
J = 6.9 Hz, CH3CH2O), 6.55 (dq, 1 H, J = 10.2, 1.4 Hz, H-3).
MS (DI, CI, NH3): m/z = 240 (MH+ + NH3), 223 (MH+), 240, 221,
139, 122, 101, 78, 61.
Anal. calc. for C13H18O3 (222.3): C, 70.25; H, 8.16; found C, 70.01;
H, 8.24.
13C NMR (50 MHz, CDCl ): δ = 12.6 (CH3CH2O), 14.4 (CH3-4),
3
20.0 (CH3-2), 30.9 (C-6), 33.3 (C-5), 33.4 (C-4), 60.5 (CH3CH2O),
63.1 (C-7), 127.1 (C-2), 147.4 (C-3), 168.5 (C-1).
IR (film): ν = 3405, 2931, 2870, 1708, 1647, 1456, 1367, 1254,
1188, 1130, 1094, 1056, 1030, 750 cm–1.
To a solution of oxalyl chloride (6.4 mL, 73.6 mmol, 4.0 equiv) in
anhyd CH2Cl2 (200 mL) at –55°C was added DMSO (11.4 mL,
147.2 mmol, 8.0 equiv). This was followed 5 min later with the addi-
tion via cannula of a solution of alcohol (2S)-5-(benzoyloxy)-2-meth-
yl-pentan-1-ol (4.09 g, 18.4 mmol) in anhyd CH2Cl2 (50 mL). The
resulting slurry was stirred for 1 h and Et3N (53.9 mL, 386.4 mmol,
21.0 equiv) was added at this point and after 5 min, the mixture was
warmed to r.t. The mixture was diluted with CH2Cl2 (200 mL) and
washed with an ice-cold 2 M HCl solution (193 mL) and H2O (193
mL). The aqueous phases were extracted with CH2Cl2 (300 mL), the
organic layers were combined, dried (MgSO4), filtered and concen-
trated in vacuo. The crude aldehyde (2S)-5-(benzoyloxy)-2-methyl-
pentanal thus obtained was used without further purification.
1H NMR (200 MHz, CDCl3): δ = 1.16 (d, 3 H, J = 7.1 Hz, CH3-2),
1.40–1.48 (m, 1 H, Hb-3), 1.51–1.61 (m, 1 H, Ha-3), 1.77–1.90 (m, 2
H, H2-4), 2.40–2.47 (m, 1 H, H-2), 4.36 (t, 2 H, J = 6.7 Hz, H-5), 7.46
(t, 2 H, J = 7.6 Hz, H-arom), 7.58 (t, 1 H, J = 7.6 Hz, H-arom), 8.06
(d, 2 H, J = 7.5 Hz, H-arom), 8.95 (d, 1 H, J = 1.7 Hz, H-1).
13C NMR (50 MHz, CDCl3): δ = 13.5 (CH3-2), 26.3 (C-4), 27.0 (C-
3), 46.0 (C-2), 64.7 (C-5), 128.5 (C-arom), 129.6 (C-arom), 130.3 (C-
arom), 133.1 (C-arom), 166.7 [OC(O)Ph], 204.6 (C-1).
MS (GC, CI, NH3): m/z = 218 (MH+ + NH3), 201 (MH+), 172, 155,
137, 109, 95, 85, 58.
Anal. calc. for C11H20O3 (200.3): C, 65.97; H, 10.07; found C, 65.81;
H, 9.95
To a solution of oxalyl chloride (785 µL, 8.99 mmol, 1.2 equiv) in
anhyd CH2Cl2 (25 mL) at –55°C was added DMSO (1.4 mL,
18.0 mmol, 2.4 equiv). This was followed 5 min later with the addi-
tion via cannula of a solution of ethyl (2E,4S)-2,4-dimethyl-7-
hydroxyhept-2-enoate (1.50 g, 7.49 mmol) in anhyd CH2Cl2 (10 mL).
The resulting slurry was stirred for 1 h and Et3N (5.2 mL, 37.5 mmol,
5.0 equiv) was then added and 5 min later the mixture was warmed to
r.t. The solution was diluted with CH2Cl2 (80 mL) and was washed
with an ice-cold 1 M HCl solution (38 mL) and H2O (38 mL). The
aqueous phases were extracted with CH2Cl2 (80 mL). The organic
layers were combined, dried (MgSO4), filtered and concentrated in
vacuo. Purification by flash chromatography on silica gel (Et2O/
petroleum ether, 10:90 to 40:60) gave 20 (1.18 g, 80%) as a colorless oil.
IR (film): ν = 2960, 1718, 1602, 1452, 1387, 1315, 1275, 1176,
1113, 1070, 1026, 713 cm–1.
20:
MS (GC, CI, NH3): m/z = 238 (MH+ + NH3), 221 (MH+), 105, 99.
1H NMR (400 MHz, CDCl3): δ = 1.06 (d, 3 H, J = 6.6 Hz, CH3-4),
1.31 (t, 3 H, J = 7.1 Hz, CH3CH2O), 1.59–1.66 (m, 1 H, Hb-5),
1.75–1.83 (m, 1 H, Ha-5), 1.84 (d, 3 H, J = 1.2 Hz, CH3-2), 2.42 (t, 2
H, J = 8.0 Hz, H2-6), 2.52–2.58 (m, 1 H, H-4), 4.20 (q, 2 H, J = 7.1
Hz, CH3CH2O), 6.49 (dq, 1 H, J = 10.2, 1.2 Hz, H-3), 9.25 (s, 1 H, H-
7).
A solution of preceding crude aldehyde (see above) and (ethoxycar-
bonylethylidene)triphenylphosphorane (14.1 g, 38.9 mmol, 2.1 equiv)
in anhyd toluene (80 mL) was warmed at 50°C for 9 h. Then toluene
was removed under reduced pressure, the residue taken up in Et2O,
filtered on a pad of Celite and the solid was washed with Et2O. The
combined filtrate and washings were concentrated in vacuo. Purifica-
tion of the residue by flash chromatography on silica gel (Et2O/petro-
leum ether, 0:100 to 30:70) gave 19 (4.37 g, 78% for two steps) as a
colorless oil.
13C NMR (50 MHz, CDCl3): δ = 12.4 (CH3CH2O), 14.2 (CH3-4),
19.7 (CH3-2), 28.9 (C-5), 32.6 (C-4), 41.7 (C-6), 60.3 (CH3CH2O),
127.8 (C-2), 145.8 (C-3), 167.9 (C-1), 201.1 (C-7).
IR (film): ν = 2961, 2930, 2871, 2720, 1709, 1649, 1458, 1389,
1367, 1257, 1194, 1132, 1094, 1031, 751 cm–1.
MS (GC, CI, NH3): m/z = 216 (MH+ + NH3), 199 (MH+), 187, 170,
153, 142, 125, 109, 95, 81, 69.
19:
1H NMR (400 MHz, CDCl3): δ = 1.06 (d, 3 H, J = 6.6 Hz, CH3-4),
1.32 (t, 3 H, J = 7.1 Hz, , CH3CH2O), 1.42–1.50 (m, 1 H, Hb-5),
1.53–1.62 (m, 1 H, Ha-5), 1.71–1.79 (m, 2 H, H2-6), 1.86 (d, 3 H, J =
1.3 Hz, CH3-2), 2.54–2.62 (m, 1 H, H-4), 4.21 (q, 2 H, J = 7.1 Hz,
CH3CH2O), 4.32 (t, 2 H, J = 6.5 Hz, H2-7), 6.56 (d, 1 H, J = 10.1 Hz,
H-3), 7.46 (t, 2 H, J = 7.5 Hz, H-arom), 7.58 (t, 1 H, J = 7.5 Hz, H-
arom), 8.05 (d, 2 H, J = 7.5 Hz, H-arom).
Anal. calc.for C11H18O3 (198.3): C, 66.64; H, 9.15; found C, 66.51; H
9.07.
Addition of (E)-1-Lithio-2-[(tributyl)stannyl]ethene to Aldehyde
10; (1E,3R/S,6S)-6-Methyl-7-[(tetrahydropyran)-2-yloxy]-1-
[(tributyl)stannyl]hept-1-en-3-ol (13a):
To a solution of (E)-1,2-{bis[(tributyl)stannyl]ethene (9.12 g,
15.0 mmol, 2.0 equiv) in anhyd THF (80 mL) at –78°C was added
BuLi (1.6 M solution in hexane, 8.0 mL, 12.8 mmol, 1.7 equiv). The
mixture was stirred for 2 h at –40 to –15°C. Then the mixture was
13C NMR (50 MHz, CDCl3): δ = 12.7 (CH3CH2O), 14.4 (CH3-4),
20.2 (CH3-2), 26.9 (C-6), 33.1 (C-4), 33.2 (C-5), 60.6 (CH3CH2O),
65.0 (C-7), 127.1 (C-2), 128.5 (C-arom), 129.7 (C-arom), 130.5 (C-
arom), 133.0 (C-arom), 147.2 (C-3), 166.8 [OC(O)Ph], 168.5 (C-1).

SYNTHESIS
April 1998
533
cooled at –78°C and a solution of freshly prepared aldehyde 10
(1.51 g, 7.52 mmol) in anhyd THF (10 mL) was added via cannula.
After stirring for 20 min, the mixture was quenched by the addition of
satd aq NH4Cl solution. The mixture was allowed to warm to r.t. and
then extracted with Et2O (300 mL). The combined extracts were
22:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.86–0.93 [m,
30 H, 6 CH2 + 6 CH3, 2 Sn(CH2CH2CH2CH3)3], 1.04 (d, 3 H, J = 6.8
Hz, CH3, CH3-6), 1.28–1.34 [m, 12 H,
6
CH2,
2
Sn(CH2CH2CH2CH3)3], 1.47–1.53 [m, 16 H, H2-7 + H2-8 + 6 CH2, 2
Sn(CH2CH2CH2CH3)3], 1.80 (s, 3 H, CH3-4), 2.53–2.64 (m, 1 H, H-
6), 3.35–3.40 (m, 1 H, OH), 3.99–4.18 (m, 1 H, H-9), 5.98 (dd, 0.5 H,
J = 19.1, 5.5 Hz, H-10), 5.99 (dd, 0.5 H, J = 19.1, 5.5 Hz, H-10), 6.07
(d, 1 H, J = 19.3 Hz, H-1 or H-2), 6.15 (d, 1 H, J = 19.1 Hz, H-11),
6.29 (d, 1 H, J = 19.3 Hz, J 1H - 117Sn = J 1H - 119Sn = 71.9 Hz, H-1
or H-2), 6.40 (d, 1 H, J = 9.6 Hz, H-5).
washed with brine, dried (MgSO ), filtered and concentrated in vac-
4
uo. Purification by flash chromatography on silica gel (Et2O/petro-
leum ether, 0:100 to 50:50) gave 13a (3.70 g, 95%) as a colorless oil.
Addition of (E)-1-Lithio-2-[(tributyl)stannyl]ethene to Aldehyde
20; Ethyl (2E,4S,7R/S,8E)-2,4-Dimethyl-7-hydroxy-9-[(tribu-
tyl)stannyl]non-2,8-dienoate (16a), [2R/S(9E),3E,5S,8R/S(11E)]-
2,8-{Bis[(tributyl)stannylethenyl]}-3,5-dimethyl-2-hydroxy-oxa-
cyclooct-3-ene (21) and Ethyl (1E,4E,6S,9R/S,10E)-1,11-
{Bis[(tributyl)stannyl]}-4,6-dimethyl-9-hydroxy-3-oxaundeca-
1,4,10-trienoate (22):
13C NMR (50 MHz, CDCl3): two diastereomers: δ = 9.9 [6 CH2, 2
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = 326.1 Hz, J 13C - 119Sn = 322.8
Hz], 11.2, 11.9 (CH3-6), 13.7 [6 CH3, 2 Sn(CH2CH2CH2CH3)3], 20.1
(CH3-4), 27.3 [6 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C -
119Sn = 52.0 Hz], 29.3 [6 CH2, 2 Sn(CH2CH2CH2CH3)3], 32.8 (C-7),
33.8 (C-6), 35.1, 36.8 (C-8), 75.6 (C-9, J 13C - 117Sn = J 13C - 119Sn =
48.0 Hz), 128.3 (C-11), 131.4 (C-2), 135.9 (C-4), 147.9 (C-5), 151.2
(C-10), 151.5 (C-1), 200.3 (C-3).
To
a solution of (E)-1,2-{bis[(tributyl)stannyl]ethene (3.46 g,
5.71 mmol, 2.0 equiv) in anhyd THF (30 mL) at –78°C was added
BuLi (1.6 M solution in hexane, 3.03 mL, 4.85 mmol, 1.7 equiv). The
mixture was stirred for 2 h at –40 to –25°C, then cooled to –78°C and
a solution of freshly prepared aldehyde 20 (566 mg, 2.85 mmol) in an-
hyd THF (5 mL) was added via cannula. After stirring for 15 min, the
mixture was quenched by the addition of satd aq NH4Cl solution. The
mixture was allowed to warm to r.t. and then extracted with Et2O
(200 mL). The combined extracts were washed with brine, dried
(MgSO4), filtered and concentrated in vacuo. Purification by flash
chromatography on silica gel (Et2O/petroleum ether, 0:100 to 50:50)
gave 16a (590 mg, 40%), 21 (202 mg, 9%) and 22 (157 mg, 7%) as
colorless oils.
IR (film): ν = 3424, 2956, 2925, 2870, 2852, 1668, 1635, 1376,
1070, 990, 874 cm–1.
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 597,
595, 525, 467, 345, 308, 291, 235, 207, 199, 125, 72.
Coupling Reactions Between the Iodo Derivative 3 and Stannane
13a; General Procedures:
Method 1, (Ph3P)4Pd in THF or DMF: To a flame-dried flask under
a purge of argon was added the vinyl iodide 3 (1 equiv).18 The appro-
priate solvent was added and the mixture was degassed 3 times by
evacuating to 0.06 Torr and flushing with argon. (Ph3P)4Pd
(0.1 equiv) was then added and 5 min later a deoxygenated (vide in-
fra) solution of the vinyl stannane 13a (1 equiv) was added via can-
nula. The mixture was then stirred at r.t. overnight, then taken up in
Et2O (30 mL). The organic layer was washed with H2O (3 × 10 mL)
and concentrated in vacuo. The residue was dissolved in Et2O (5 mL)
and treated with aq 1 M KF solution (4 equiv). After stirring for 2 h
at r.t., the mixture was filtered on a pad of Celite. The organic layer
was decanted, dried (MgSO4), filtered, and concentrated in vacuo. Pu-
rification was performed by flash chromatography on silica gel (Et2O/
petroleum ether, 40:60 to 100:0).
To
a solution of (E)-1,2-{bis[(tributyl)stannyl]ethene (1.63 g,
2.69 mmol, 1.3 equiv) in anhyd THF (30 mL) at –78°C was added
BuLi (1.6 M solution in hexane, 1.3 mL, 2.07 mmol, 1.0 equiv). The
mixture was stirred for 2 h at –40 to –25°C, then cooled to –78°C and
a solution of freshly prepared aldehyde 20 (410 mg, 2.07 mmol) in an-
hyd THF (5 mL) was added via cannula. After stirring for 10 min, the
mixture was quenched by the addition of satd aq NH4Cl solution. The
mixture was allowed to warm to r.t. and then extracted with Et2O
(200 mL). The combined extracts were washed with brine, dried
(MgSO4), filtered and concentrated in vacuo. Purification by flash
chromatography on silica gel (Et2O/petroleum ether, 0:100 to 50:50)
gave 16a (661 mg, 62%) as a colorless oil.
Method 2, PdL4 prepared from tris(dibenzylideneacetone)dipalladi-
um(0), PPh3, or PFu3, or AsPh3 as ligands, and CuI in DMF or NMP:
To a flame-dried flask under a purge of argon were added tris(diben-
zylideneacetone)dipalladium(0) (0.05 equiv) and the appropriate
ligand (0.2 equiv). The corresponding solvent was added and the mix-
ture was degassed 3 times by evacuating to 0.06 Torr and flushing
with argon. A solution of deoxygenated (vide infra) vinyl iodide 3 (1
equiv) was added via cannula and 5 min later a solution of deoxygen-
ated (vide infra) vinyl stannane 13a (1 equiv) was added via cannula.
Then, solid CuI (0.1 equiv) was added to the mixture, which was
stirred at r.t. for overnight. The mixture was dissolved in Et2O
(30 mL) and washed with H2O (3 × 10 mL). The organic layer was
concentrated in vacuo and the residue was dissolved in Et2O (5 mL)
and treated with aq 1M KF solution (4 equiv). After stirring for 2 h
at r.t., the mixture was filtered on a pad of Celite. The organic layer
was decanted, dried (MgSO4), filtered, and concentrated in vacuo. Pu-
rification was performed by flash chromatography on silica gel (Et2O/
petroleum ether, 40:60 to 100:0).
21:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 0.85–0.96 [m,
30 H, 6 CH2 + 6 CH3, 2 Sn(CH2CH2CH2CH3)3], 0.99 (d, 3 H, J = 6.7
Hz, CH3-4), 1.27–1.36 [m, 12 H, 6 CH2, 2 Sn(CH2CH2CH2CH3)3],
1.47–1.55 [m, 17 H, H2-6
+ H2-7 + OH + 6 CH2, 2
Sn(CH2CH2CH2CH3)3], 1.61 (d, 3 H, J = 1.3 Hz, CH3-3), 2.33–2.44
(m, 1 H, H-5), 4.00–4.06 (m, 1 H, H-8), 5.32 (d, 1 H, J = 9.3 Hz, H-
4), 5.99 (dd, 0.5 H, J = 19.1, 5.5 Hz, H-11), 6.00 (dd, 0.5 H, J = 19.1,
5.5 Hz, H-11), 6.07 (d, 1 H, J = 19.3 Hz, H-9 or H-10), 6.13 (d, 1 H,
J = 19.1 Hz, H-12), 6.20 (d, 1 H, J = 19.3 Hz, J 1H - 117Sn = J 1H -
119Sn = 72.8 Hz, H-9 or H-10).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 9.95 [6 CH2, 2
Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = 326.1 Hz, J 13C - 119Sn = 340.2
Hz], 13.0 (CH3-5), 13.7 [6 CH3, 2 Sn(CH2CH2CH2CH3)3], 20.9 (CH3-
3), 27.3 [6 CH2, Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J 13C - 119Sn
= 51.9 Hz], 29.3 [6 CH2, 2 Sn(CH2CH2CH2CH3)3, J 13C - 117Sn = J
13C - 119Sn = 19.9 Hz], 32.7, 32.8 (C-5), 33.3, 33.5 (C-6), 35.1, 35.3
(C-7), 75.7, 75.9 (C-8), 82.3 (C-2, J 13C - 117Sn = J 13C - 119Sn = 56.1
Hz), 126.1 (C-10), 127.8 (C-12), 133.2 (C-4), 136.8 (C-3), 151.6,
151.7 (C-9 + C-11).
Method 3, PdCl2(MeCN)2, DMF, 20˚C: To a flame-dried flask under
a purge of argon were added the vinyl stannane 13a (1 equiv) and vi-
nyl iodide 3 (1.3 equiv). DMF was added and the mixture was de-
gassed 3 times by evacuating to 0.06 Torr and flushing with argon.
Then PdCl2(MeCN)2 (0.04 equiv) was added and the mixture stirred
at r.t. After 12 h and 24 h additional portions of the palladium catalyst
(0.02 equiv) were added. After 36 h, the mixture was dissolved in
Et2O (30 mL) and washed with H2O (3 × 10 mL). The organic layer
was concentrated in vacuo and the residue was taken up in Et2O
IR (film): ν = 3440, 2955, 2924, 2870, 2852, 1668, 1588, 1463,
1376, 1182, 1071, 992, 874, 666 cm–1.
MS (DI, CI, NH3): m/z calculated from major 120Sn isotope = 757
(MH+ – 32), 597, 595, 525, 478, 401, 308, 291, 235, 207, 72.

SYNTHESIS
Papers
534
(5 mL) and treated with aq 1 M KF solution (4 equiv). After stirring
for 2 h at r.t., the mixture was filtered on a pad of Celite. The organic
layer was decanted, dried (MgSO4), filtered, and concentrated in vac-
uo. Purification was performed by flash chromatography on silica gel
(Et2O/petroleum ether, 40:60 to 100:0).
(2E,4E,6E,8R/S,11S)-1,8-[Bis(benzoyloxy)]-12-[(tetrahydropyr-
an)-2-yloxy]-3,5,11-trimethyldodeca-2,4,6-triene (25):
To a solution of 23 (5.0 g, 14.9 mmol) and DMAP (0.02 equiv) in an-
hyd CH2Cl2 (80 mL) at –30°C was added Et3N (24.9 mL,
178.3 mmol, 12.0 equiv) and benzoyl chloride (10.3 mL, 89.2 mmol,
6.0 equiv). The cold bath was removed and the mixture was stirred at
0°C for 2 h and at r.t. for 6 h. Then the mixture was diluted with Et2O,
the organic layer washed with H2O and brine, dried (MgSO4), filtered
and concentrated in vacuo. Purification by flash chromatography on
silica gel (Et2O/petroleum ether, 0:100 to 40:60) gave 25 (6.74 g,
83%) as a colorless oil.
(2E,4E,6E,8R/S,11S)-12-[(Tetrahydropyran)-2-yloxy]-3,5,11-trime-
thyldodeca-2,4,6-triene-1,8-diol (23):
Entry 12, Table 3, Method 3, [PdCl2(MeCN)2, DMF, 20°C]: from vi-
nyl iodide 3 (6.6 g, 27.7 mmol) and stannane 13a (10.7 g, 20.7 mmol),
triene 23 (5.2 g, 75%) was obtained after 36 h at 20°C.
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.96 (d, 1.5 H, J
= 6.5 Hz, CH3-11), 0.97 (d, 1.5 H, J = 6.5 Hz, CH3-11), 1.21–1.38 (m,
1 H, Hb-10), 1.44–1.62 (m, 5 H, Ha-10 + H2-4' + H2-5'), 1.63–1.75 (m,
1 H, H-11), 1.76–1.91 (m, 4 H, H2-9 + H2-3'), 1.91 (s, 3 H, CH3-3 or
CH3-5), 1.93 (s, 3 H, CH3-3 or CH3-5), 3.20 (dd, 0.5 H, J = 9.5, 6.2 Hz,
Hb-12), 3.24 (dd, 0.5 H, J = 9.5, 6.2 Hz, Hb-12), 3.48–3.54 (m, 1 H, Hb-
6'), 3.56 (dd, 0.5 H, J = 9.0, 6.2 Hz, Ha-12), 3.60 (dd, 0.5 H, J = 9.5, 6.6
Hz, Ha-12), 3.68–3.88 (m, 1 H, Ha-6'), 4.53–4.59 (m, 1 H, H-2'), 4.95
(d, 2 H, J = 7.0 Hz, H2-1), 5.57 (dt, 1 H, J = 7.2, 6.6 Hz, H-8), 5.63 (t,
1 H, J = 7.0 Hz, H-2), 5.73 (dd, 1 H, J = 15.6, 7.2 Hz, H-7), 5.97 (s, 1
H, H-4), 6.39 (d, 1 H, J = 15.6 Hz, H-6), 7.45 (t, 2 H, J = 7.6 Hz, H-
arom), 7.46 (t, 2 H, J = 7.3 Hz, H-arom), 7.55 (t, 1 H, J = 7.2 Hz, H-
arom), 7.57 (t, 1 H, J = 7.4 Hz, H-arom), 8.05 (d, 2 H, J = 6.8 Hz, H-
arom), 8.08 (d, 2 H, J = 6.8 Hz, H-arom).
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.94 (d, 1.5 H,
J = 6.7 Hz, CH3-11), 0.95 (d, 1.5 H, J = 6.7 Hz, CH3-11), 1.26–1.79
(m, 13 H, 2 OH + H2-9 + H2-10 + H-11 + H2-3' + H2-4' + H2-5'), 1.81
(s, 3 H, CH3-3), 1.91 (s, 3 H, CH3-5), 3.17 (t, 0.5 H, J = 9.4 Hz, Hb-
12), 3.22 (dd, 0.5 H, J = 9.4, 9.3 Hz, Hb-12), 3.47–3.54 (m, 1.5 H,
0.5Ha-12 + Hb-6'), 3.60 (dd, 0.5 H, J = 9.5, 9.4 Hz, Ha-12), 3.83–3.87
(m, 1 H, Ha-6'), 4.12–4.18 (m, 1 H, H-8), 4.26 (d, 2 H, J = 6.6 Hz, H2-
1), 4.52–4.60 (m, 1 H, H-2'), 5.57 (t, 1 H, J = 6.7 Hz, H-2), 5.66 (dd,
1 H, J = 15.6, 6.6 Hz, H-7), 5.68 (dd, 1 H, J = 15.6, 6.6 Hz, H-7), 5.89
(s, 1 H, H-4), 6.24 (d, 1 H, J = 15.6 Hz, H-6).
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 14.0 (CH3-5),
17.0 (CH3-3), 17.1 (CH3-11), 19.6 (C-5'), 25.6 (C-4'), 29.7 (C-10),
30.8 (C-3'), 33.6 (C-11), 35.2 (C-9), 59,7 (C-1), 62.4 (C-6'), 73.0, 73.1
(C-12), 73.5 (C-8), 99.1, 99.2 (C-2'), 129.7 (C-2), 131.9 (C-7), 133.9
(C-5), 134.6 (C-4), 135.0 (C-3), 135.8, 136.2(C-6).
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 13.9 (CH3-5),
17.0 (CH3-11), 17.3 (CH3-3), 19.5 (C-5'), 25.6 (C-4'), 29.3, 29.4 (C-
10), 30.8 (C-3'), 32.4 (C-9), 33.4 (C-11), 61.7 (C-1), 62.0 (C-6'), 72.7
(C-12), 75.6, 75.7 (C-8), 98.9 (C-2'), 124.4 (C-2), 127.1 (C-7), 128.2
(C-arom), 129.5 (C-arom), 132.7 (C-arom), 134.1 (C-3 or C-5), 135.1
(C-4), 137.8, 138.0 (C-6), 165.8, 166.4 [OC(O)Ph].
IR (film): ν = 3425, 2934, 2871, 1669, 1455, 1378, 1200, 1121, 1061,
1031, 976, 904, 868, 815 cm–1.
MS (DI, CI, NH3): m/z = 356 (MH+ + NH3), 321 (MH+ – H2O), 303,
291, 237, 219, 201, 169, 118, 102, 85, 58.
Anal. calc. for C20H34O4 (338.5): C, 70.97, H, 10.12; found C, 71.10;
H, 10.35.
IR (film): ν = 2937, 1789, 1722, 1599, 1451, 1272, 1213, 1037,
1017, 996, 703 cm–1.
MS (DI, CI, NH3): m/z = 564 (MH+ + NH3), 527, 480, 442, 425, 358,
341, 303, 256, 219, 191, 139, 102, 78.
(2E,4E,7R/S,10S)-6-Methylene-11-[(tetrahydropyran)-2-yloxy]-
3,5,10-trimethylundeca-2,4-diene-1,7-diol (24):
Anal. calc. for C34H42O6 (546.7): C, 74.70; H, 7.74; found C, 74.58;
H, 7.58.
Entry 10, Table 3, Method 2, via PdL4 prepared from tris(dibenzyli-
deneacetone)dipalladium(0), AsPh3 as ligand in DMF at 20°C and
CuI (10% mol): from vinyl iodide 3 (330 mg, 1.4 mmol) and stannane
13a (535 mg, 1.04 mmol), a mixture of trienes 23 and 24 (260 mg,
74%, 23/24 = 60:40) was obtained after 12 h at 20°C.
(2S,5R/S,6E,8E,10E)-5,12-[Bis(benzoyloxy)]-2,8,10-trimethyl-
dodeca-6,8,10-trien-1-ol (26) and [2R(1E,3E,5E),5S]-2-[7-(Ben-
zoyloxy)-3,5-dimethylhepta-1,3,5-trien-1-yl]-5-methyl-
oxaclyclohexane (27):
To a solution of 25 (417 mg, 0.76 mmol) in MeOH (15 mL) at r.t. was
added TsOH (834 mg, 0.23 mmol, 0.3 equiv). The mixture was stirred
at r.t. for 2.5 h and then quenched by the addition of Et3N (64 µL,
0.46 mmol, 0.6 equiv). After 5 min the MeOH was removed under re-
duced pressure and the residue was dissolved in CH2Cl2. The organic
layer was washed with H2O and the aqueous layer separated and ex-
tracted with CH2Cl2 (2 × 100 mL). The combined organic extracts were
washed with brine, dried (MgSO4), filtered and concentrated in vacuo.
Purification by flash chromatography on silica gel (Et2O/petroleum
ether, 50:50 to 60:40) gave 26 (269 mg, 80%) as a colorless oil.
24 :
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.93 (d, 1.5
H, J = 6.7 Hz, CH3-10), 0.96 (d, 1.5 H, J = 6.7 Hz, CH3-10), 1.83–1.18
(m, 13 H, 2 OH + H2-8 + H2-9 + H-10 + H2-3' + H2-4' + H2-5'), 1.81
(s, 3 H, CH3-3), 1.96 (s, 3 H, CH3-5), 3.17 (dd, 0.5 H, J = 9.5, 9.4 Hz,
Hb-11), 3.25 (dd, 0.5 H, J = 9.4, 9.3 Hz, Hb-11), 3.49–3.57 (m, 1.5 H,
Hb-6', 0.5 Ha-11), 3.62 (dd, 0.5 H, J = 9.6, 9.5 Hz, Ha-11), 3.84 –3.89
(m, 1 H, Ha-6'), 4.27 (t, 2 H, J = 6.9 Hz, H2-1), 4.43–4.51 (m, 1 H, H-
7), 4.53–4.59 (m, 1 H, H-2'), 5.18 (s, 1 H, Hb-12), 5.25 (d, 1 H, J =
3.2 Hz, Ha-12), 5.55 (t, 1 H, J = 6.9 Hz, H-2), 6.00 (s, 1 H, H-4).
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 13.7 (CH3-5),
17.2, 17.5 (CH3-10), 17.6 (CH3-3), 18.4 (C-5'), 26.9 (C-4'), 30.2 (C-
9), 30.9 (C-3'), 33.6 (C-10), 34.3, 34.4 (C-8), 59.7 (C-1), 62.4 (C-6'),
72.6, 72.8 (C-7), 73.1, 73.2 (C-11), 99.2, 99.3 (C-2'), 110.8 (C-12),
128.9 (C-2), 130.4 (C-4), 134.8 (C-5), 135.8 (C-3), 153.8, 154.0 (C-
6).
To a solution of 25 (7.99 g, 14.6 mmol) in MeOH (200 mL) at r.t. was
added TsOH (834 mg, 4.38 mmol, 0.3 equiv). The mixture was stirred
at r.t. for 5 h and then quenched by the addition of Et3N (650 µL,
4.68 mmol, 0.32 equiv). After 5 min the MeOH was removed under
reduced pressure and the residue was taken up in CH2Cl2. The organic
layer was washed with H2O and the aqueous layer was separated and
extracted with CH2Cl2 (2 × 300 mL). The combined organic extracts
were washed with brine, dried (MgSO4), filtered and concentrated in
vacuo. Purification by flash chromatography on silica gel (Et2O/pe-
troleum ether, 50:50 to 60:40) gave 26 (1.68g, 34%) and 27 (2.76 g,
56%) as colorless oils.
IR (film): ν = 3395, 2942, 2870, 1652, 1599, 1454, 1378, 1353, 1261,
1200, 1137, 1120, 1076, 1062, 1024, 903, 867, 809 cm–1.
MS (DI, CI, NH3): m/z = 356 (MH+ + NH3), 338 (MH+ + NH3–
H2O), 321 (MH+ – H2O), 303, 293, 254, 237, 219, 205, 183, 149, 132,
102, 85.
MS (DI, CI, NH3, negative ion): m/z = 337 (MH+), 336, 319, 291,
277, 269, 235, 221, 199, 179, 161, 148, 127, 119, 89.
Anal. calc. for C20H34O4 (338.5): C, 70.97; H, 10.12; found C, 71.22;
H, 10.48.
26:
1H NMR (400 MHz, CDCl3), four diastereomers: δ = 0.96 (d, 3 H,
J = 6.8 Hz, CH3-2), 1.21–1.33 (m, 2 H, Hb-3 + OH), 1.52–1.62 (m, 1

SYNTHESIS
April 1998
535
H, Ha-3), 1.65–1.73 (m, 1 H, H-2), 1.82–1.88 (m, 1 H, Hb-4),
1.89–1.96 (m, 1 H, Ha-4), 1.91 (s, 3 H, CH3-8 or CH3-10), 1.93 (s, 3
H, CH3-8 or CH3-10), 3.44–3.56 (m, 2 H, H2-1), 4.95 (d, 2 H, J =
7.0 Hz, H2-12), 5.61–5.65 (m, 1 H, H-5), 5.64 (t, 1 H, J = 7.0 Hz, H-
11), 5.72 (dd, 0.5 H, J = 15.6, 7.2 Hz, H-6), 5.73 (dd, 0.5 H, J = 15.6,
7.3 Hz, H-6), 5.97 (s, 1 H, H-9), 6.40 (d, 1 H, J = 15.6 Hz, H-7), 7.45
(t, 2 H, J = 7.9 Hz, H-arom), 7.46 (t, 2 H, J = 7.9 Hz, H-arom), 7.57
(t, 1 H, J = 7.6 Hz, H-arom), 7.58 (t, 1 H, J = 7.4 Hz, H-arom), 8.06
(d, 2 H, J = 6.8 Hz, H-arom), 8.08 (d, 2 H, J = 6.9 Hz, H-arom).
13C NMR (50 MHz, CDCl3), four diastereomers: δ = 13.9 (CH3-8),
16.5 (CH3-2), 17.3 (CH3-10), 28.8 (C-3), 33.4 (C-4), 35.7 (C-2), 61.7
(C-12), 67.9 (C-1), 75.2, 75.8 (C-5), 124.3 (C-12), 126.9 (C-6), 128.3
(C-arom), 129.3 (C-arom), 132.8 (C-arom), 134.0 (C-8 or C-10),
135.2 (C-9), 137.9, 138.0 (C-7), 165.9, 166.4 [OC(O)Ph].
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 13.5 (CH3-2),
14.1 (CH3-8), 17.6 (CH3-10), 26.2 (C-3), 32.3 (C-4), 46.0, 46.1 (C-2),
61.7 (C-12), 75.3 (C-5), 124.5 (C-11), 126.5 (C-6), 128.5 (C-arom),
129.7 (C-arom), 133.1 (C-arom), 134.0 (C-8 or C-10), 135.7 (C-9),
138.5 (C-7), 166.0, 166.7 [OC(O)Ph], 204.6 (C-1).
IR (film): ν = 2917, 1717, 1653, 1437, 1316, 1269, 1020, 953 cm–1.
MS (DI, CI, NH3): m/z = 478 (MH+ + NH3), 448, 391, 356, 339, 311,
279, 217, 199, 147, 122, 96, 58.
A solution of the preceding crude aldehyde (2S,5R/S,6E,8E,10E,2S)-
5,12-[bis(benzoyloxy)]-2,8,10-trimethyldodeca-6,8,10-trienal (see
above) and (ethoxycarbonylethylidene)triphenylphosphorane (4.32 g,
11.9 mmol, 2.0 equiv) in anhyd toluene (40 mL) was warmed at 50°C
for 5 h. Then the toluene was removed under reduced pressure. The
residue was dissolved in Et2O, filtered on a pad of Celite and the solid
was washed with Et2O. The combined filtrate and washings were con-
centrated in vacuo. Purification by flash chromatography on silica gel
(Et2O/petroleum ether, 30:70) gave ethyl (2E,4S,7R/S8E,10E,12E)-
7,14-[bis(benzoyloxy)]-2,4,10,12-tetramethyltetradeca-2,8,10,12-
tetraenoate (2.63 g, 81% for two steps) as a colorless oil.
IR (film): ν = 3501, 2924, 2854, 1715, 1652, 1602, 1451, 1377,
1315, 1272, 1177, 1113, 1026, 966, 909, 734, 713 cm–1.
MS (DI, CI, NH3): m/z = 480 (MH+ + NH3), 463 (MH+), 445 (MH+
– H2O), 411, 391, 341, 323, 219, 201, 161, 145, 99, 78.
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 1.04 (d, 3 H, J
= 6.5 Hz, CH3-4), 1.30 (tm, 3 H, J = 6.9 Hz, CH3CH2O), 1.37–1.58
(m, 2 H, H2-5), 1.68–1.93 (m, 2 H, H2-6), 1.85 (d, 1.5 H, J = 1.3 Hz,
CH3-2), 1.86 (d, 1.5 H, J = 1.3 Hz, CH3-2), 1.91 (s, 3H, CH3-10 or
CH3-12), 1.93 (s, 3 H, CH3-10 or CH3-12), 2.49–2.58 (m, 1 H, H-4),
4.21 (qm, 2 H, J = 6.9 Hz, CH3CH2O), 4.95 (d, 2 H, J = 7.0 Hz, H2-
14), 5.52–5.59 (m, 1 H, H-7), 5.64 (t, 1 H, J = 7.0 Hz, H-13), 5.69 (dd,
1 H, J = 15.6, 7.4 Hz, H-8), 5.97 (s, 1 H, H-11), 6.38 (d, 1 H, J = 15.6
Hz, H-9), 6.54 (d, 1 H, J = 10.0 Hz, H-3), 7.45 (t, 2 H, J = 7.6 Hz, H-
arom), 7.47 (t, 2 H, J = 7.5 Hz, H-arom), 7.53–7.59 (m, 2 H, H-arom),
8.05 (d, 2 H, J = 6.7 Hz, H-arom), 8.07 (d, 2 H, J = 6.6 Hz, H-arom).
13C NMR (50 MHz, CDCl3), two diastereomers: δ = 12.6
(CH3CH2O), 14.0 (CH3-10), 14.3 (CH3-4), 17.4 (CH3-12), 17.4 (CH3-
12), 32.4 (C-5 or C-6), 32.8 (C-5 or C-6), 33.1 (C-4), 60.4
(CH3CH2O), 61.7 (C-14), 75.4 (C-7), 124.5 (C-13), 127.0 (C-8),
127.2 (C-2), 128.3 (C-arom), 129.6 (C-arom), 132.8 (C-arom), 134.0
(C-10 or C-12), 135.3 (C-11), 138.1 (C-9), 147.3 (C-3), 165.8, 166.4,
[OC(O)Ph], 168.2 (C-1).
27:
1H NMR (400 MHz, CDCl3): δ = 0.82 (d, 3 H, J = 6.6 Hz, CH3-5),
1.21 (qd, 1 H, J = 11.2, 3.9 Hz, Hax-4), 1.47 (qd, 1 H, J = 11.2, 3.9
Hz, Hb-3), 1.62–1.82 (m, 2 H, Ha-3 + H-5), 1.93–1.96 (m, 1H, Heq-
4), 1.91 (s, 3 H, CH3-3' or CH3-5'), 1.92 (s, 3 H, CH3-3' or CH3-5'),
3.09 (t, 1 H, J = 11.2 Hz, Hax-6), 3.82 (dd, 1 H, J = 11.2, 6.3 Hz, H-
2), 3.93 (ddd, 1 H, J = 11.2, 4.3, 2.1 Hz, Heq-6), 4.95 (d, 2 H, J = 7.1
Hz, H2-7'), 5.63 (t, 1 H, J = 7.1 Hz, H-6'), 5.71 (dd, 1 H, J = 15.8, 6.2
Hz, H-1'), 5.94 (s, 1 H, H-4'), 6.29 (d, 1 H, J = 15.8 Hz, H-2'), 7.45 (t,
2 H, J = 7.5 Hz, H-arom), 7.57 (t, 1 H, J = 8.0 Hz, H-arom), 8.06 (d,
2 H, J = 7.2 Hz, H-arom).
13C NMR (50 MHz, CDCl3): δ = 13.7 (CH3-3'), 17.0 (CH3-5), 17.3
(CH3, CH3-5'), 30.6 (C-5), 32.1 (C-3 or C-4), 32.2 (C-3 or C-4), 61.5
(C-7'), 74.5 (C-6), 77.6 (C-2), 123.8 (C-6'), 128.1 (C-arom), 129.4 (C-
arom), 129.9 (C-1'), 130.3 (C-arom), 132.6 (C-arom), 133.9 (C-4'),
134.5 (C-3' or C-5'), 135.1 (C-2'), 135.3 (C-3' or C-5'), 166.1
[OC(O)Ph].
IR (film): ν = 2928, 1716, 1602, 1585, 1452, 1375, 1315, 1268,
1176, 1093, 1026, 966, 868, 712 cm–1.
IR (film): ν = 2927, 1716, 1652, 1450, 1366, 1269, 1176, 1107,
MS (DI, CI, NH3): m/z = 358 (MH+ + NH3), 341 (MH+), 313, 287,
269, 236, 219, 201, 165, 161, 121, 99, 78, 61.
1026, 713 cm–1.
MS (DI, CI, NH3): m/z = 562 (MH+ + NH3), 534, 478, 440, 423, 356,
315, 301, 255, 227, 159, 122, 105, 78.
Anal. calc. for C22H28O3 (340.5): C, 77.61; H, 8.29; found C, 77.48;
H, 8.31.
A solution of ethyl (2E,4S,7R/S8E,10E,12E)-7,14-[bis(benzoyloxy)]-
2,4,10,12-tetramethyltetradeca-2,8,10,12-tetraenoate (2.63 g, 4.83
mmol) in NaOEt/EtOH (0.01 M NaOEt in EtOH, 150 mL, 1.50 mmol,
0.3 equiv) was stirred for 24 h at r.t. Then the mixture was extracted
with Et2O and washed with H2O and brine. The organic layer was
dried (MgSO4), filtered and concentrated in vacuo. Purification by
flash chromatography on silica gel (Et2O/petroleum ether, 40:60 to
80:20) gave 2 (1.2 g, 76%) as a colorless oil.
Ethyl (2E,4S,7R/S,8E,10E,12E)-7,14-Dihydroxy-2,4,10,12-tetra-
methyltetradeca-2,8,10,12-tetraenoate (2):
To a solution of oxalyl chloride (1.1 mL, 11.9 mmol, 2.0 equiv) in
anhyd CH2Cl2 (60 mL) at –55°C was added DMSO (1.9 mL,
23.9 mmol, 4.0 equiv) . This was followed 5 min later with the addi-
tion via cannula of a solution of 26 (2.76 g, 5.97 mmol) in anhyd
CH2Cl2 (20 mL). The resulting slurry was stirred for 1 h and Et3N
(6.9 mL, 49.5 mmol, 8.3 equiv) was added and after 5 min, the mix-
ture was warmed to r.t. The mixture was diluted with CH2Cl2 (20 mL)
and washed with ice-cold aq 1M HCl (50 mL) and H2O (50 mL). The
aqueous phases were extracted with CH2Cl2 (100 mL), the organic
layers were combined, dried (MgSO4), filtered and concentrated in
vacuo. The crude aldehyde (2S,5R/S,6E,8E,10E,2S)-5,12-[bis(ben-
zoyloxy)]-2,8,10-trimethyldodeca-6,8,10-trienal thus obtained was
used without further purification.
2:
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 1.02 (d, 3 H, J
= 6.7 Hz, CH3-4), 1.30 (t, 3 H, J = 7.2 Hz, CH3CH2O), 1.38–1.65 (m,
5 H, H-4 + H2-5 + 2 OH), 1.64–1.74 (br s, 1 H, OH), 1.82 (s, 3 H, CH3-
10 or CH3-12), 1.83 (d, 1.5 H, J = 1.3 Hz, CH3-2), 1.84 (d, 1.5 H, J =
1.2 Hz, CH3-2), 1.92 (s, 3 H, CH3-10 or CH3-12), 2.47–2.50 (m, 1 H,
H-4), 4.12–4.18 (m, 1 H, H-7), 4.19 (q, 2 H, J = 7.2 Hz, CH3CH2O),
4.28 (d, 2 H, J = 6.8 Hz, H2-14), 5.58 (t, 1 H, J = 6.8 Hz, H-13), 5.70
(dd, 1 H, J = 15.6, 7.1 Hz, H-8), 5.90 (s, 1 H, H-11), 6.24 (d, 1 H, J =
15.6 Hz, H-9), 6.52 (d, 1 H, J = 10.1 Hz, H-3).
1H NMR (400 MHz, CDCl3), two diastereomers: δ = 1.15 (d, 3 H, J
= 7.1 Hz, CH3-2), 1.42–1.58 (m, 2 H, H2-3), 1.76–1.93 (m, 2 H, H2-
4), 1.91 (s, 3 H, CH3-8 or CH3-10), 1.93 (s, 3 H, CH3-8 or CH3-10),
2.43–2.38 (m, 1 H, H-2), 4.95 (d, 2 H, J = 7.0 Hz, H2-12), 5.58–5.62
(m, 1 H, H-5), 5.64 (t, 1 H, J = 7.0 Hz, H-11), 5.71 (dd, 1 H, J = 15.4,
7.2 Hz, H-6), 5.98 (s, 1 H, H-9), 6.40 (d, 1 H, J = 15.4 Hz, H-7), 7.43
(t, 2 H, J = 7.4 Hz, H-arom), 7.46 (t, 2 H, J = 7.7 Hz, H-arom),
7.54–7.58 (m, 2 H, H-arom), 8.05 (d, 2 H, J = 6.7 Hz, H-arom), 8.07
(d, 2 H, J = 6.4 Hz, H-arom), 9.37 (s, 1 H, H-1).
13
C NMR (50 MHz, CDCl3), two diastereomers: δ = 12.6
(CH3CH2O), 14.2 (CH3-10), 14.4 (CH3-4), 17.2 (CH3-12), 19.9 (CH3-
2), 32.7, 32.8 (C-5), 33.45, 33.5 (C-4), 35.6 (C-6), 59.6 (C-14), 60.5
(CH3CH2O), 75.4, 75.6 (C-7), 127.1 (C-2), 129.7 (C-13), 131.6 (C-8),
133.9 (C-10), 135.0 (C-11), 135.8 (C-12), 136.2 (C-9), 147.4 (C-3),
168.5 (C-1).

SYNTHESIS
Papers
536
IR (film): ν = 3366, 2930, 2868, 1707, 1647, 1448, 1368, 1260,
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