Synthesis of the 2-alkenyl-4-alkylidenebut-2-eno-4-lactone (=α-alkenyl-γ-alkylidenebutenolide) core structure of the carotenoid pyrrhoxanthin via the regioselective dihydroxylation of hepta-2,4-diene-5-ynoic acid esters

Article abstract of DOI:10.1002/hlca.200590149

A new strategy for the stereoselective synthesis of 4-alkylidenebut-2-eno- 4-lactones (= γ-alkylidenebutenolides) with (Z)-configuration of the exocyclic C=C bond at C(4) was developed. It is exemplified by the synthesis of 4-alkylidenebutenolactone 31 (Scheme 4), which constitutes a substructure of the carotenoids pyrrhoxanthin (1) and peridinin. The formation of the precursor 4-(1-hydroxyalkyl)butenolactone 29 was accomplished either by cyclocarbonylation of the prop-2-yn-1-ol moiety of 27 (→ 29) or by hydrostannylation of the isopropylidene-protected alkynoic acid ester 26 (->28) followed by transacetalization/transesterification (→ 30). The 4- alkylidenebutenolactone was formed by the ami-selective Mitsunobu dehydration 29 → 31.

Full text of DOI:10.1002/hlca.200590149

Helvetica Chimica Acta Vol.88 (2005)
1943
Synthesis of the 2-Alkenyl-4-alkylidenebut-2-eno-4-lactone (ˆa-Alkenyl-g-
alkylidenebutenolide) Core Structure of the Carotenoid Pyrrhoxanthin via the
Regioselective Dihydroxylation of Hepta-2,4-diene-5-ynoic Acid Esters
by Joachim Schmidt-Leithoff and Reinhard Br¸ckner*
Institut f¸r Organische Chemie and Biochemie, Albert-Ludwigs-Universit‰t, Albertstr.21, D-79104 Freiburg
(fax: ‡ 49-761-2036100; e-mail: reinhard.brueckner@organik.chemie.uni-freiburg.de)
Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthday
A new strategy for the stereoselective synthesis of 4-alkylidenebut-2-eno-4-lactones (ˆ g-alkylidenebu-
tenolides) with (Z)-configuration of the exocyclic CˆC bond at C(4) was developed.It is exemplified by the
synthesis of 4-alkylidenebutenolactone 31 (Scheme 4), which constitutes a substructure of the carotenoids
pyrrhoxanthin (1) and peridinin.The formation of the precursor 4-(1-hydroxyalkyl)butenolactone 29 was
accomplished either by cyclocarbonylation of the prop-2-yn-1-ol moiety of 27 (!29) or by hydrostannylation of
the isopropylidene-protected alkynoic acid ester 26 (!28) followed by transacetalization/transesterification
(! 30).The 4-alkylidenebutenolactone was formed by the anti-selective Mitsunobu dehydration 29 ! 31.
Introduction. Carotenoids have attracted and continue to attract the interest of
organic chemists, biochemists, and medicinal chemists alike [1].This is due to the
diversity of their functions which include their being colorants, anti-oxidants,
progenitors of secondary metabolites (vitamin A, odorants), antitumor agents, or
light-harvesting agents [2].Usually, carotenoids are C
entities.However, a few
40
carotenoids possess a skeleton of no more than 37 C-atoms.One of the latter is
pyrrhoxanthin (1; Scheme 1), a mono-acetate of pyrrhoxanthinol (C37H48O6).Pyr-
rhoxanthin was first isolated from Gyrodinium resplendens [3].Its structure was
elucidated by Liaaen-Jensen and co-workers [4]1).Pyrrhoxanthin features seven
conjugated CˆC bonds.One of these double bonds is conjugated with a C ꢀCÀCˆC
moiety.Another C ˆC bond of pyrrhoxanthin is incorporated into a but-2-enolactone
ring.This makes up a 2-alkenyl-4-alkylidenebut-2-enolactone substructure (in which
the exocyclic CˆC bond at C(4) displays a (Z)-configuration).A single total synthesis
of pyrrhoxanthin has been accomplished to date, namely in 1993 by Yamano and Ito
[5]2).Concomitantly, these workers reported the total synthesis of the structurally
related [6]3) carotenoid butenolactone peridinin [7]4).In fact, several C 37 carotenoids
1
)
For the second isolation (two-dimensional structure), see [4a]; for the re-isolation (three-dimensional
structure), see [4b].
For the total syntheses of pyrrhoxanthin and enantiomerically pure peridinin, see [5]; continued previous
studies which were reported in [7].
For the two-dimensional structure, see [6a]; for the three-dimensional structure, see [6b,c].
Synthesis of a racemic mixture of peridinin and diastereoisomers.
2
)
3
4
)
)
¹ 2005 Verlag Helvetica Chimica Acta AG, Z¸rich

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Helvetica Chimica Acta Vol.88 (2005)
containing a 2-alkenyl-4-alkylidenebut-2-eno-4-lactone moiety are known5).Synthetic
efforts towards such compounds have been resumed recently, culminating in the second
total synthesis of peridinin [9] and a total synthesis of epiperidinin [10].
Scheme 1. Synthetic Strategy for the Butenolactone Core of Pyrrhoxanthin (1)
Given the general [11] and our group×s specific [11c] interests in carotenoid (vide
supra) and noncarotenoid6) 4-alkylidenebut-2-eno-4-lactone syntheses, we now report
a new access to the 4-(1-hydroxyalkyl)but-2-eno-4-lactone ! 4-alkylidenebut-2-eno-4-
lactone route towards such target structures.It allows for the first time to prepare the
desired 4-(1-hydroxyalkyl)butenolactones from 4,5-dihydroxyhept-2-ene-6-ynates 3, as
demonstrated by a stereoselective synthesis of a 4-alkylidenebutenolactone 2b
(Scheme 1; R ˆ CF3CH2, X ˆ H).It is likely that the same strategy could lead to the
hydroxy-containing but otherwise analogous 4-alkylidenebutenolactone 2a (X ˆ OH).
Conceivably, compound 2a is a novel building block for the total synthesis of
pyrrhoxanthin (1).
Scheme 2 juxtaposes the current study×s C1 extension of 4,5-dihydroxyhept-2-ene-6-
ynoates 3 to 4-(1-hydroxyalkyl)butenolactones 7 with our previous accesses to this key
intermediate en route to type-10 4-alkylidenebutenolactones.These included the
elaboration of sugar lactones 4 [13], the diastereoselective vinylogous Mukaiyama
aldol addition 5 ‡ 6 ! 7 [14], successive manipulation of the three CÀHal bonds of the
trihalodienediol 8 [15], and most recently, the desymmetrization of tartrate 9 [16].The
5
)
)
Peridinol [4], anhydroperidinol [8a], pyrrhoxanthinol [4], hydratopyrrhoxanthinol [8b], uriolide [8c],
deepoxyuriolide [8d], anhydrouriolide [8d], 3'-dehydrouriolide [8d], and unnamed carotenoids [8e,f].
See, e.g., freelingyne (revised structure) [12a,b], lissoclinolide [12c], and xerulinic acid, xerulin, and
dihydroxerulin [12d].
6

Helvetica Chimica Acta Vol.88 (2005)
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diversity and complementariness of these approaches underlines the versatility of our
b-elimination strategy 4-(1-hydroxyalkyl)butenolactone 7 ! 4-alkylidenebutenolac-
tone 10 [11c].
Scheme 2. Ways to the 4-(1-Hydroxyalkyl)butenolactone Precursor 7
Results and Discussions.
Methyl heptadienynoate 18 and the analogous
trifluoroethyl ester 19 were precursors of choice for the desired type-3 esters 20 and
21, respectively (Scheme 3).Heptadienynoates 18 and 19 were obtained by Stille
couplings [17] between the (2E)-3-stannylbut-2-enoates 16 (methyl ester) or 17
(trifluoroethyl ester) and bromoenyne 12.This bromoenyne, in turn, resulted from the
chemoselective C,C-coupling between bromoiodoethene 10 [18] and the (tert-
butyl)dimethylsilylated ethyne 11 [19], following the procedure of Negishi et al. [18].
The 3-(tributylstannyl)butenoates 16 and 17 were obtained as pure (E)-isomers by the
(tributylstannyl)cupration [20] of methyl but-2-yonate (13)7) and trifluoroethyl but-2-
ynoate (15)8), respectively; optimizing yields and stereoselectivies, we found
(Bu3Sn)BuCu(CN)Li2 [23] the best reagent for effecting the conversion of ester 13
(100% yield) and (Bu3Sn)Cu ¥ SMe2 ¥ LiBr9) the best reagent for transforming ester 15
7
)
)
)
Ester 13 was prepared by treating prop-1-ynyllithium (generated in situ [21a,b]) with methyl
carbonochloridate [21c].
Ester 15 was prepared from but-2-yonic acid (14), which was obtained by the Jones oxidation of but-2-yn-
1-ol [22].
8
9
For the reagent and stannylcupration of ethyl pentynoate with it, see [24].

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Scheme 3. Synthesis of 2,2,2-Trifluoroethyl Dihydroxyenynoate 22
a) 11, MeMgBr (1.1 equiv.), THF, r.t., 3 h; ZnBr2 (1.3 equiv.), 08, 30 min; 10 (1.1 equiv.), [Pd(PPh3)4] (2 mol-
%), r.t., 18 h; 83%; ([14]: 70%). b) BuLi (2.4 equiv.), CuCN (1.2 equiv.), THF, À 788, 15 min; Bu3SnH
(2.4 equiv.), À 788, 10 min; MeOH (1.2 equiv.), À 788, 3 min; addition of 13, À 788, 90 min; 100%. c)
CF3CH2OH (10 equiv.), H2SO4 (cat.), benzene, Dean Stark trap filled with MgSO4, reflux, 24 h; 81%. d)
Bu3SnSnBu3 (1.3 equiv.), BuLi (1.3 equiv.), THF, À 208, 20 min; addition of CuBr¥ SMe2 (1.3 equiv.), À 788,
25 min; addition of 15, À 788, 12 h; 96% (separated from 4% of the (Z)-isomer). e) CuI (1.5 equiv.),
[Pd(PPh3)4] (5 mol-%), DMF, 608, 1 h; 84%. f) CuI (1.5 equiv.), [Pd(PPh3)4] (3 mol-%), DMF, 258, 8 h; 100%.
g) K2OsO2(OH)4 (1 mol-%), K3Fe(CN)6 (3.0 equiv.), (DHQ)2PHAL (5 mol-%), K2CO3 (3.0 equiv.),
MeSO2NH2 (1.0 equiv.), tBuOH/H2O 1:1, 258, 24 h; 65% (inseparable mixture of regioisomers 20 and iso-20).
h) K2OsO2(OH)4 (1 mol-%), K3Fe(CN)6 (3.0 equiv.), (DHQ)2PHAL (5 mol-%), K2CO3 (3.0 equiv.),
t
MeSO2NH2 (1.0 equiv.), BuOH/H2O 1 :1, 258, 24 h; 76%. i) Bu4NF (1.5 equiv.), THF, 4 h, 08; 76%.

Helvetica Chimica Acta Vol.88 (2005)
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(96% yield)10).We noticed an interesting additive effect upon the stereochemical
outcome of the stannylcupration of the trifluoroethyl ester 15: Modifying (Bu3Sn)Bu-
Cu(CN)Li2 with an equimolar amount of methanol which is the general procedure
given in [20] , we obtained 65% of a 97:3 (mol ratio) mixture of 17 and its
methanolysis product 16, plus separately 4% of the (Z)-isomer of 17.However, when
we added an equimolar amount of trifluoroethanol to the (Bu3Sn)BuCu(CN)Li2 before
combining the resulting mixture with ester 15, we isolated only the (Z)-isomer 17
(60%) of the resulting trifluoroethyl ester.This is a remarkable observation in its own
right because in [20], solely −clean cis-additions of the stannylcuprate× are reported.
Cu-Assisted [26] [Pd(PPh3)4]-catalyzed Stille couplings between (tributylstannyl)-
butenoates 16 and 17 on the one side and bromoenyne 12 on the other side under
conditions gleaned from [27] furnished methyl heptadienynoate 18 in 83% and
trifluoroethyl heptadienynoate 19 in 100% yield.Next, we required a vicinal cis-
dihydroxylation of the C(4)ˆC(5) bond of these compounds which left their respective
C(2)ˆC(3) bond unaffected.Yet, starting from methyl ester 18, such a regioselectivity
remained elusive.Adopting Sharpless× −improved× asymmetric dihydroxylation proto-
col [28]11) because it gave the best yield (65%), we obtained an 85 :15 mixture of diols
20 (desired) and iso-20 (undesired and inseparable by flash chromatography on silica
gel [29]).In contrast, Sharpless× standard asymmetric dihydroxylation procedure (for
the first description, see [30a]; for a review, see [30b]) allowed only a very sluggish
dihydroxylation 18 ! 20/iso-20.From these observations we concluded that a C ꢀC
substituent deactivates CˆC bonds towards attack by [OsO4L].Accordingly, the
undesired attack of [OsO4L] upon the C(2)ˆC(3) bond should be suppressed if we
dihydroxylated trifluoroethyl dienynoate 19 rather than methyl dienynoate 18.This is
because the stronger electron demand of the CF3CH2O2C vs.CH 3O2C substituent was
expected to slow down osmylation of the C(2)ˆC(3) bond in the former substrate
compared to the latter.Indeed, our adaptation of the −improved× asymmetric
dihydroxylation protocol [28], when applied to trifluoroethyl ester 19, provided a
single dihydroxyenynoate, namely compound 21 (76% yield).Desilylation with Bu 4NF
in THF gave the unprotected dihydroxyenynoate 22 also with 76% yield.
The right-hand moiety of model butenolactone 2b (Scheme 1) was introduced by
means of building block 25 (Scheme 4).The preparation of 25 began with known well-
yielding (83 98%) transformations: 1) Ozonolysis of b-ionone (23) gave the a,b-
unsaturated aldehyde [31]; 2) C1 extension of the CHˆO function led to the
homologated enyne [32]12); 3) epoxidation of the CˆC bond provided epoxyalkyne 24
[33]13); 4) Pd-catalyzed regio- and stereoselective hydrostannylation of the CꢀC bond
delivered a trans-configured alkenylstannane [16].In the terminating new reaction, the
stannane, treated with I214), rendered the (epoxycyclohexyl) alkenyl iodide 25.
10
)
)
For an analogous preparation of the tert-butyl analog of ester 16, see [25].
Bennani and Sharpless [28a] increased the normal amounts of K2OsO2(OH)4 and (DHQ)2PHAL by a
factor of 5 (as we did), while Blundell et al. [28b] increased them by a factor of 10.
The alkynylation method is described in [32b].
Epoxidation of 1-chloro-2-(2,6,6-trimethylcyclohex-1-enyl)ethene leads in 99% yield to 1-chloro-2-(1,2-
epoxy-2,6,6-trimethylcyclohexyl)ethene [33b].
11
12
13
)
)
14
)
We followed a protocol published for a related transformation [34].

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Helvetica Chimica Acta Vol.88 (2005)
Scheme 4. Synthesis of 2-Alkenyl-4-alkylidenebut-2-eno-4-lactone 31
a) O3, MeOH, À 788, 2.5 h; Zn (1.5 equiv.), AcOH/H2O 1 :1; 93% ([31a]: 90%; [31b]: 64% combined yield for
this step and an ensuing acetalization). b) Lithium diisopropylamide (1.2 equiv.), Me3SiCHN2 (1.2 equiv.),
THF, À 788, 90 min; 89% ([32a]: 74%). c) 3-Chloroperbenzoic acid (1.2 equiv.), CH2Cl2, 16 h, 258; 98% ([33a]:
64%). d) [Pd(PPh3)4] (5 mol-%), Bu3SnH (1.2 equiv.), THF, 3 h, 258; 73% ([16]: 83%). e) I2 (1.0 equiv.),
CH2Cl2, 3 h, 08; 91%. f) TsOH (10 mol-%), Me2C(OMe)2 (1.5 equiv.), CH2Cl2, 3 h, r.t.; 97%. g) Lithium
hexamethyldisilazanide (1.3 equiv.), THF, À 788, 30 min; ClCO2Me (4.0 equiv.), 45 min; 85%. h) 25
(1.05 equiv.), [Pd(PPh3)2Cl2] (5 mol-%), CuI (15 mol-%), THF, Et3N (21 equiv.), 258, 50 min; 76%. i) Bu3SnH
(1.05 equiv.), [Pd(PPh3)4] (5 mol-%), THF, 08, 60 min; 88%. j) CO (42 bar), H2 (8 bar), [Pd2dba3] ¥ CHCl3
(10 mol-%), Ph2P(CH2)4PPh2 (20 mol-%), CH2Cl2, 508, 24 h; 32% including the subsequent step. k) TsOH
(20 mol-%), MeOH, reflux, 8 h; 64%. l) 25 (1.1 equiv.), [Pd(PPh3)4] (5 mol-%), CuI (1.2 equiv.), DMF, 3 h, r.t.;
96% of a presumed 86 :14 mixture 29/epi-29. m) PPh3 (6.0 equiv.), diethyl diazenenedicarboxylate (DEAD;
6.0 equiv.), THF, À 308, 1 h; 70% of an inseparable 97.3 :2.7 (Z)/(E)-mixture 31.

Helvetica Chimica Acta Vol.88 (2005)
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Proceeding towards the target butenolactone, we initially combined building block
25 and the unsaturated dihydroxy ester 22 by virtue of its HÀCꢀC moiety via a
SonogashiraÀHagihara coupling (for the original report, see [35a]; reviews in [35b
d]) (Scheme 4, left side).It yielded 76% of the (8 E)-enynoate 27.The latter, we hoped,
would lend itself to butenolactone formation through incorporation of carbon
monoxide and lactonization.This transformation has been described for simple
primary and secondary alcohols of the prop-2-yn-1-ol type [36]15) but none of which,
however, was functionalized nearly as much as our substrate.Nonetheless, following
descriptions by Alper, co-workers, and others [36a,b], the one-step carbonylative
lactonization of the prop-2-yn-1-ol type alcohol 27 was achieved in the presence of
10 mol-% [Pd2(dba)3] ¥ CHCl3 (dba ˆ dibenzylideneacetone ˆ 1,5-diphenylpenta-1,4-
dien-3-one) and 20 mol-% Ph2P(CH)4PPh2 (dppb) under 50 atmospheres of CO and
H2 (ca.5 :1).Workup after 24 h at 50 8 yielded a mixture of the butenolactone 29 and
unreacted starting material 27.These constituents could neither be separated nor
completely liberated from impurities.Accordingly, the mixture was directly dehydrated
under Mitsunobu conditions [37]16), i.e., by treatment with 6 equiv.each of
triphenylphosphine and diethyl diazenedicarboxylate at À 308.To avoid loss of
configurational integrity at the stereogenic CˆC bonds of the desired product, we
applied the same protective measures which had preserved the CˆC geometries in the
analogous methyl ester [16]: 1) We excluded light during reaction and chromatography,
2) employed degassed THFas a solvent and degassed cyclohexane/AcOEt as an eluent,
and 3) added 2,6-di(tert-butyl)cresol to the solvent as a radical scavenger.This
completed the generation of 4-alkylidenebutenolactone 31 in 32% overall yield from
alcohol 2717).
In quest for an improved yield, we established a second set of reactions from the
dihydroxy ester 22 to the target structure 31 (Scheme 4, right side).They started with
acetonide formation (97% yield) and continued with consecutive treatments by lithium
hexamethyldisilazanide and methyl carbonochloridate.This provided ester 26 with a
but-2-ynoate moiety in 85% yield.Its C ꢀC bond was hydrostannylated with Bu3SnH/
cat.[Pd(PPh )4] [39]18).Because of the presence of the neighboring isopropylidene-
3
dioxy group (see below), this reaction was completely regio- and stereoselective.
Consequently, it gave the (2E)-2-stannylprop-2-enoate 28 (88% yield) and none of the
isomers.Ester derivative 28 was subjected to a one-pot transacetalization/trans-
15
)
Conditions: Prop-2-yn-1-ol, CO/H2, and cat.[PdL x] (for the original report, see [36a]; for applications, see
[36b,c]).A variant for tertiary 3-(trimethylsilyl)prop-2-yn-1-ols, with CO/H 2 and cat.[Rh 4(CO)12] has been
described in [36d].
16
17
)
)
For related applications in our group, see [10][13b][14][16].
It should be noted that other methods for the conversion of prop-2-yn-1-ol type alcohols into
butenolactones are known (for hydromagnesation followed by carboxylation, see [38a,b]; for i)
hydroalumination followed by iodinolysis, ii) CO, cat.[PdL x], see [38c i]; for i) hydrozirconation, ii)
CO, see [38j]; for i) mesylation, ii) CO, H2O, cat.PdL x, iii) cat.AgNO 3, see [38k p]).Whether they are or
are not applicable to 4-alkylidenebutenolactone syntheses as exemplified by our two-step sequence 27 !
¾
29 ! 31 has not yet been studied in depth.At least, Stille×s method [39b]
reduction by RedAl ,
iodinolysis, carbonylation of the resulting 3-iodoallyl alcohol failed when tried with 27.Of course, this
may be less an inherent problem than due to the reducible CO2CH2CF3 group.
18
)
For [Pd(PPh3)4] as a catalyst, see [39a,b]; for [Mo(CO)3(NCÀtBu)3] as a catalyst, see [39c].

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Helvetica Chimica Acta Vol.88 (2005)
esterification reaction in refluxing MeOH in the presence of 20 mol-% TsOH.This
treatment copied from a similar transformation by Hanisch in our group [15] gave
rise to the formation of the 2-(tributylstannyl)-4-(1-hydroxyalkyl)butenolactone 30 in
64% yield.The latter compound and ethenyl iodide 25 containing the epoxycyclohex-
ane moiety then were Stille-coupled under the conditions of [27].This provided the 2-
substituted 4-(1-hydroxyalkyl)butenolactone 29 as the major constituent of what we
interpreted as a 86 :14 mixture with the 4-epimer epi-29, the yield of 29 thus being 83%.
In any event, the presumed 29 epi-29 mixture was converted into the 2-substituted 4-
alkylidenebutenolactone 31 (inseparable 97:3 (E)/(Z)-mixture with respect to the
exocyclic CˆC bond) in 70% yield when we applied the Mitsunobu elimination
protocol already described above.
Comparing the three-step synthesis of butenolactone 31 from ester 22 (via
intermediates 27 and 29) with the six-step route from 22 (via a non-depicted
intermediate followed by compounds 26 and 28 29), the overall yields of 24 and 31%,
respectively, make the second access the more recommendable.It is somewhat more
laborious, yet which is again a benefit does not necessitate handling CO at high
pressure.
Scheme 5 depicts the model hydrostannylations, which led us to choose to
hydrostannylate the acetonide-protected diester 26 containing a prop-2-ynoate moiety
(see Scheme 4) and not the corresponding unprotected dihydroxy diester.The presence
of hydroxy groups in alkyl alk-2-ynoates may lower the regio-selectivity of the
[Pd(PPh3)4]-catalyzed hydro(tributylstannylation) reaction: While being completely a-
selective in the absence of such OH groups [39] and exhibiting a 86 :14 a vs. b
preference for SnÀC bond-formation in the presence of a 4-OH group (under slightly
Scheme 5. Regioselective Hydrostannylation of 4,5-Dioxygenated Alk-2-ynoic Acid Esters

Helvetica Chimica Acta Vol.88 (2005)
1951
different conditions [40]19), the a/b bias of the hydrostannylation of ethyl 4,5-
dihydroxyalk-2-ynoate 32 was only 79 :21 with [Pd(PPh3)4] as the catalyst (Scheme 5);
with [PdCl2(PPh3)2], the a/b ratio decreased to 58 :42.In contrast, the analogous
acetonide-protected ethyl alk-2-ynoate 34 was hydrostannylated with nearly perfect
namely 98 :2 a-selectivity in the presence of [Pd(PPh3)4].Catalysis by [PdCl 2(PPh3)2]
gave rise to a 75 :25 mixture of a- (! 35) and b-tributylstannylated (! iso-35)
products.
In summary, we turned a novel route to 4-(1-hydroxyalkyl)but-2-eno-4-lactones 2
into practice as exemplified by two variants of synthesizing compound 29.Through an
anti-selective Mitsunobu elimination, we completed the 4-alkylidenebutenolactone
core 31 of the carotenoid pyrrhoxanthin with good control of the stereochemistry.
Besides, we noticed that the stannylcupration of but-2-ynoate 15 with (Bu3Sn)Bu-
Cu(CN)Li2 switches from cis- to trans-addition upon modification of the reagent with
CF3CH2OH rather than MeOH.In addition, we could make a C ˆCCO2R group inert
towards osmylation by exchanging a CˆCCO2Me for a CˆCCO2CH2CF3 group.
Experimental Part
General.All reactions were performed in oven-dried (80 8) glassware under Ar or N2.Reactions with light-
sensitive compounds were performed in brown glassware or in ordinary glassware in a fume hood lined with a
UV protection foil.THF was freshly distilled from K, CH Cl2 was distilled from CaH2.Flash chromatography
2
(FC) [29]: Merck silica gel 60.Yields refer to anal.pure samples.Isomer ratios were derived from suitable
1H-NMR integrals.Mp. .: Tottoli apparatus (B¸chi); uncorrected.IR Spectra: Perkin-Elmer Paragon-1000; nÄ in
.
cmÀ1 1H- and 13C-NMR Spectra: Varian Mercury VX-300, Bruker AM-400, and Bruker DRX-500; d in ppm,
coupling constants J in Hz, integrals in accordance with assignments; CHCl3 (d 7.26) as internal standard in
CDCl3, C6HD5 (d 7.16) as internal standard in C6D6, or (HD2C)(D3C)SˆO (d 2.49) as internal standard in
(D6)DMSO for 1H; CDCl3 (center peak of t at d 77.0 ppm) as internal standard in CDCl3 or C6D6 (d 128.0) as
internal standard in C6D6 for 13C.MS: performed by Dr. J. Wˆrth and C. Warth, Institut f¸r Organische Chemie
and Biochemie, Universit‰t Freiburg; in m/z (rel.int.).Combustion analyses: performed by E. Hickl, Institut f¸r
Organische Chemie and Biochemie, Universit‰t Freiburg.
2,2,2-Trifluoroethyl But-2-ynoate (15).To a soln.of but-2-ynoic acid ( 14; 1.86 g, 20.0 mmol) in benzene
(20 ml), CF3CH2OH (14.6 ml, 20.0 g, 200 mmol, 10 equiv.) and H2SO4 (conc., 0.2 ml) were added. The soln. was
heated under reflux for 36 h in a Soxhlet extractor charged with MgSO4.Benzene and CF 3CH2OH were
removed by distillation under atmospheric pressure.The residue was washed with aq.NaHCO 3 soln.(3 Â 30 ml)
and dried (Na2SO4).Distillation (bp. .60 67 8/50 mbar) afforded 15 (2.79 g, 84%). Colorless liquid. n2D0 1.3815.
IR (film): 2980, 2320, 2250, 1735, 1440, 1410, 1290, 1235, 1170, 1090, 990, 965, 885. 1H-NMR (499.9 MHz,
CDCl3): 2.04 (s, Me(4)); 4.52 (q, J(H,F) ˆ 8.3, CF3CH2). 13C-NMR (125.7 MHz, CDCl3): 3.91 (C(4)), 60.96 (q,
2J(C,F) ˆ 37.0, CF3CH2); 70.97 (C(2)); 88.84 (C(3)); 122.56 (q, 1J(C,F) ˆ 277.3, CF3CH2); 151.70 (C(1)).
13C-NMR (125.7 MHz, CDCl3; gated-decoupled): 3.91 (q, 1J(C,H) ˆ 133.1, C(4)); 60.96 (tq, 1J(C,H) ˆ 151.4,
2J(C,F) ˆ 37.0, CF3CH2); 70.97 (q, 3J(C,CH3(4)) ˆ 4.7, C(2)); 88.84 (q, 2J(C,CH3(4) ˆ 10.8, C(3)); 122.56 (qt,
‡
‡
2J(C,H) ˆ 4.7, 1J(C,F) ˆ 277.3, CF3CH2); 151.70 (C(1)). HR-EI-MS (70 eV): 166.0242 (M ), C6H5F3O2 ; calc.
166.0242).
2,2,2-Trifluoroethyl (2E)-3-(Tributylstannyl)but-2-enoate (17).At À 208, 2. 4m BuLi (13.5 ml, 32.5 mmol,
1.3 equiv.) was added to a soln. of hexabutyldistannane (16.4 ml, 18.6 g, 32.5 mmol, 1.3 equiv.) in THF (100 ml).
After 20 min, the soln.was cooled to À 788, and CuBr¥ SMe2 (6.68 g, 32.5 mmol, 1.3 equiv.) was added in one
portion.After 30 min, 15 (4.19 g, 25.0 mmol) was added. The mixture was stirred at À 788 for 8 h.The reaction
was terminated by the addition of aq.NH 4Cl soln.(100 ml) and brine (100 ml).After warming gradually to rt..,
the aq.phase was extracted with Et O (5 Â 100 ml), the combined org.phase dried (Na 2SO4) and evaporated,
2
and the obtained colorless liquid purified by FC (11-cm column, cyclohexane/AcOEt 30 :1): 17 (10.7 g, 94%)
and (Z)-isomer (0.8 g, 6%).
19
)
With [PdCl2(PPh3)2] as the catalyst.

1952
Helvetica Chimica Acta Vol.88 (2005)
Data of 17: IR (film): 2930, 2855, 1740, 1725, 1595, 1465, 1410, 1375, 1345, 1290, 1250, 1165, 1105, 1050, 980,
860. 1H-NMR (499.9 MHz, CDCl3): 0.90 (t, 3J ˆ 7.3, 3 MeCH2CH2CH2); 0.99 (m, 3 MeCH2CH2CH2, flanked by
Sn-isotope satellites as dm, 2J(H,119Sn) ˆ 52.1, 2J(H,117Sn) ˆ 49.8); 1.32 (qt, 3J ˆ 7.8, 7.8, 3 MeCH2CH2CH2);
1.43 1.59 (m, 3 MeCH2CH2CH2); 2.43 (d, 4J(4,2) ˆ 1.9, each peak flanked by Sn-isotope satellites as 2 d,
3J(4,119Sn) ˆ 43.8, 3J(4,117Sn) ˆ 42.0, Me(4)); 4.48 (q, 3J(H,F) ˆ 8.6, CF3CH2); 6.03 (q, 4J(2,4) ˆ 1.9, each peak
flanked by Sn-isotope satellites as interlocked q, 3J(2,119Sn) ˆ 64.0, 3J(2,117Sn) ˆ 57.3, HÀC(2)). 13C-NMR
(125.7 MHz, CDCl3): 9.53 (flanked by Sn-isotope satellites as 2 d, 1J(C,119Sn) ˆ 336.7, 1J(C,117Sn) ˆ 321.8,
3 MeCH2CH2CH2); 13.62 (3 MeCH2CH2CH2); 22.76 (C(4)); 27.29 (flanked by Sn-isotope satellites as d,
3J(C,Sn) ˆ 56.6, 3 MeCH2CH2CH2); 28.94 (flanked by Sn-isotope satellites as d, 2J(C,Sn) ˆ 20.6,
3 MeCH2CH2CH2); 59.59 (q, 2J(C,F) ˆ 36.4, CF3CH2); 123.39 (incompletely resolved q, 1J(C,F) ˆ 148.5,
CF3CH2); 125.71 (flanked by Sn-isotope satellites as d, 2J(C,Sn) ˆ 35.4, C(2)); 161.77 (C(3)); 174.79 (C(1)).
edHSQC (C,H-COSY, 125.7/499.9 MHz, CDCl3): 9.53 (CH3CH2CH2CH2) $ 0.99 (CH3CH2CH2CH2); 13.62
(CH3CH2CH2CH2) $ 0.90 (CH3CH2CH2CH2); 22.76 (C(4)) $ 2.43 (CH3(4)); 27.29 (MeCH2CH2CH2) $ 1.32
(MeCH2CH2CH2); 28.94 (MeCH2CH2CH2) $ 1.43 1.59 (MeCH2CH2CH2); 59.59 (CF3CH2) $ 4.48
‡
‡
(CF3CH2); 125.71 (C(2)) $ 6.03 (HÀ(2)).HR-EI-MS (70 eV): 4010.750 ([ M À Bu] , C14H24F3O2Sn ; calc.
458.1455). Anal. calc. for C18H33F3O2Sn (457.2): C 47.29, H 7.28; found: C 47.37, H 7.10.
Data of (Z)-Isomer of 17: 1H-NMR (300.1 MHz, CDCl3): 0.88 (t, 3J ˆ 7.2, 3 MeCH2CH2CH2); 0.98 (m,
3 MeCH2CH2CH2 , flanked by Sn-isotope satellites as m, 2J(H,Sn) ˆ 51.9); 1.32 (qt, 3J ˆ 7.2, 7.2,
4
3 MeCH2CH2CH2); 1.42 1.52 (m, 3 MeCH2CH2CH2); 2.18 (d, J(4,2) ˆ 1.8, each peak flanked by Sn-isotope
satellites as 2 d, 3J(4,Sn) ˆ 38.0, Me(4)); 4.51 (q, 3J(H,F) ˆ 8.5, CF3CH2); 6.48 (q, 4J(2,4) ˆ 1.6, each peak
3
3
flanked by Sn-isotope satellites as interlocked q, J(2,119Sn) ˆ 101.7, J(2,117Sn) ˆ 97.9, HÀC(2)).
2,2,2-Trifluoroethyl (2E,4E)-7-[(tert-Butyl)dimethylsilyl]-3-methylhepta-2,4-dien-6-ynoate (19).To a soln.
of [Pd(PPh3)4] (241 mg, 209 mmol, 3 mol-%) in degassed DMF (50 ml) were added first bromoenyne 12 (1.88 g,
7.65 mmol, 1.1 equiv.), then CuI (1.99 g, 10.4 mmol, 1.6 equiv.), and finally dropwise 17 (3.18 g, 6.96 mmol).
t
After stirring at r.t. for 90 min, the soln. was diluted with BuOMe (20 ml), aq.NH Cl soln.(50 ml), and aq.
4
NaCl soln.(50 ml).The aq.phase was extracted with Et 2O (4 Â 100 ml), the extract concentrated to 50 ml, and
20% aq.KF soln.(50 ml) added.After stirring for 30 min at rt.,. the aq.phase was extracted with Et
2O (3 Â
50 ml) once more.The combined org.phase was dried (Na 2SO4) and evaporated, and the residue purified by FC
(11.0-cm column, cyclohexane, cyclohexane/AcOEt 20 :1): 19 (2.31 g, 100%). IR (film): 2955, 2930, 2890, 2860,
1735, 1610, 1470, 1465, 1440, 1410, 1360, 1285, 1250, 1230, 1170, 1140, 1095, 1060, 980, 955. 1H-NMR (499.9 MHz,
t
CDCl3): 0.15 (s, Me2Si); 0.96 (s, BuSi); 2.27 (d, 4J(Me,2) ˆ 1.2, MeÀC(3)); 4.50 (q, 3J(H,F) ˆ 8.5, CF3CH2);
4
5
5.87 (m, presumably a partly unresolved qdd, 4J(2,Me) ꢁ J(2,4) ꢁ J(2,5) ꢁ 0.9, HÀC(2)); 6.09 (dd, J(5,4) ˆ
16.1, 5J(5,2) ˆ 0.5, HÀC(5) (see edHSQC)); 6.67 (dd, J(4,5) ˆ 16.0, 4J(4,2) ˆ 0.8, HÀC(4) (see edHSQC)).
13C-NMR (125.7 MHz, CDCl3): À 4.75 (flanked by 29Si-isotope satellites as d, 1J(C,Si) ˆ 55.1, (Me2Si); 13.38
(MeÀC(3)); 16.66 (lower intensity than preceding signal, Me3CSi); 26.07 (Me3CSi); 59.91 (q, 2J(C,F) ˆ 36.5,
CF3CH2); 100.21, 103.94 (C(6), C(7)); 115.39 (C(5)20); 118.57 (C(2)); 123.11 (q, 1J(C,F) ˆ 277.2, CF3CH2);
144.32 (C(4)20)); 153.60 (C(3)); 164.52 (C(1)). edHSQC (C,H-COSY, 125.7/499.9 MHz, CDCl3): À 4.75
((CH3)2Si) $ 0.15 ((CH3)2Si); 13.38 (CH3ÀC(3) $ 2.27 (CH3ÀC(3)); 26.07 ((CH3)3CSi) $ 0.96 ((CH3)3CSi);
59.91 (CF3CH2) $ 4.50 (CF3CH2); 115.39 (C(5)) $ 6.09 (HÀC(5)); 118.57 (C(2)) $ 5.87 (HÀC(2)); 144.32
‡
‡
(C(4)) $ 6.67 (HÀC(4)).HR-EI-MS (70 eV): 3321.417 ( M , C16H23F3O2Si ; calc.3321.419).Anal.calc.for
C16H23F3O2Si (332.4): C 57.81, H 6.97; found: C 57.99, H 6.88.
2,2,2-Trifluoroethyl (2E,4S,5S)-7-[(tert-Butyl)dimethylsilyl]-4,5-dihydroxy-3-methylhept-2-en-6-ynoate
t
(21).To a soln.of 19 (332 mg, 1.00 mmol) in BuOH/H2O 1 :1 (2 ml), K2CO3 (414 mg, 3.00 mmol, 3.0 equiv.),
K3[Fe(CN)6] (988 mg, 3.00 mmol, 3.0 equiv.), MeSO2NH2 (95 g, 1.0 mmol, 1.0 equiv.), and (DHQ)2PHAL
(39 mg, 50 mmol, 5 mol-%) were added.The mixture was cooled to 0 8 and K2OsO2(OH)4 (3.7 mg, 10 mmol,
1 mol-%) was added.After stirring for 20 h, aq.Na 2S2O3 soln.(10 ml) was added and stirring continued at r.t.for
1 h.The aq.phase was extracted with AcOEt (4 Â 25 ml), the combined org.phase dried (Na 2SO4), and
evaporated, and the residue purified by FC (4.5-cm column, cyclohexane/AcOEt 2 :1): 21 (0.265 g, 72%). IR
(film): 3320, 2955, 2935, 2890, 2860, 1745, 1650, 1470, 1465, 1445, 1410, 1395, 1365, 1285, 1255, 1210, 1170, 1140,
1060, 1005, 980. 1H-NMR (499.9 MHz, CDCl3): 0.11 (s, Me2Si); 0.92 (s, tBuSi); 2.22 (d, 4J(Me,2) ˆ 1.4,
MeÀC(3)); 2.31 2.34 (m, OHÀC(5) (see DQF-COSY)); 2.76 (m, (ˆ−dd× with a strong −roof-effect× towards
higher field), J(OH,4) ˆ J(OH,?) ˆ 2.7, OHÀC(4) (see DQF-COSY)); 4.17 (br. dd, J(4,5) ˆ 6.2, 3J(4,OH) ˆ
20
)
Assignments analogous to those given in [41] for ethyl 8,8-dimethylnona-2,4-dien-6-ynoate (d(C) 137.4
(C(4)) and 120.4 (C(5))).

Helvetica Chimica Acta Vol.88 (2005)
1953
4
2.1, broadened by unresolved J(4,2), HÀC(4); 4.37 (dd, J(5,4) ˆ 3J(5,OH) ˆ 6.2, no broadening (cf. HÀ(4)),
3
HÀ(5)); 4.47, 4.50 (AB, JAB ˆ 12.8, A and B in addition split to q, J(A,F) ˆ 3J(B,F) ˆ 8.5, CF3CH2); 6.12 (qd,
4J(2,Me) ˆ 4J(2,4) ˆ 1.3, HÀC(2)).DQF-COSY (− H,H-COSY×, 4999. MHz, CDCl 3; only selected signals): 2.33
(OHÀC(5)) $ 4.37 (HÀC(5)); 2.76 (OHÀC(4)) $ 4.17 (HÀC(4), extremely weak); 4.17 (HÀC(4) $ 2.76
(OHÀC(4)), 4.37 (HÀC(5)); 4.37 (HÀC(5) $ 2.33 (OHÀC(5)), 4.17 (HÀC(4)). 13C-NMR (125.7 MHz,
CDCl3): À 4.89 (Me2Si); 15.71 (MeÀC(3)); 16.35 (lower intensity than d 15.71, Me3CSi); 25.92 (much lower
intensity than d 15.71, Me3CSi); 59.88 (q, 2J(C,F) ˆ 36.5, CF3CH2); 64.99 (C(5) (see edHSQC)); 79.32 (C(4) (see
edHSQC)); 91.60 (calc. 97.16, C(7)21); 102.89 (calc. 108.64, C(6)21)); 116.48 (C(2)); 123.10 (incompletely visible
1
q, J(C,F) ˆ 276.7, CF3CH2); 157.88 (C(3)); 164.17 (C(1)). edHSQC (−C,H-COSY×, 125.7/499.7 MHz, CDCl3):
À 4.89 ((CH3)2Si) $ 0.11 ((CH3)2Si); 15.71 (CH3ÀC(3) $ 2.22 (CH3ÀC(3)); 25.92 ((CH3)3CSi) $ 0.92
((CH3)3CSi); 59.88 (CF3CH2) $ 4.47 and 4.50 (CF3CH2); 64.99 (C(5)) $ 4.37 (HÀC(5)); 79.32 (C(4)) $ 4.17
t
‡
‡
(HÀC(4)); 116.48 (C(2)) $ 6.12 (HÀC(2)).HR-EI-MS (70 eV): 3090. 778 ([ M À Bu] , C12H16F3O4Si ; calc.
309.0770). Anal. calc. for C16H25F3O4Si (366.5): C 52.44, H 6.88; found: C 52.14, H 6.52.
2,2,2-Trifluorethyl (2E,4S,5S)-4,5-Dihydroxy-3-methylhept-2-en-6-ynoate (22).At 0 8, 1. 0m Bu4NF in THF
(1.49 ml, 1.49 mmol, 1.5 equiv.) was added to a soln. of 21 (0.25 g, 0.99 mmol) in THF (10 ml). After 50 min
stirring at 08, more 1.0m Bu4NF in THF (1.49 ml, 1.49 mmol, 1.5 equiv.) was added. After another 3 h at 08, H2O
(10 ml) was added.The aq.phase was extracted with AcOEt (4 Â 10 ml), the combined org.layer dried
(Na2SO4) and evaporated, and the residue purified by FC (4.5-cm column, cyclohexane/AcOEt 2 :1,
cyclohexane/AcOEt 1:1): 22 (139 mg, 76%).IR (film): 3400, 3305, 2975, 1730, 1650, 1410, 1285, 1210, 1170,
1145, 1060, 980, 870, 840. 1H-NMR (499.9 MHz, CDCl3): 2.22 (d, 4J(Me,2) ˆ 1.4, MeÀC(3)); 2.45 (br. s,
OHÀC(5) (cf. 21)); 2.57 (d, 4J(7,5) ˆ 2.2, HÀC(7) (see DQF-COSY)); 2.75 (br. s, OHÀC(4) (cf. 21)); 4.22 (br.
d, J(4,5) ˆ 5.2, HÀC(4) (see DQF-COSY)); 4.41 (br. s, surprising, cf. HÀC(4)), HÀC(5) (see DQF-COSY);
4.49, 4.50 (AB, JAB ˆ 12.8, A and B in addition split to q, 3J(H,F) ˆ 8.5, CF3CH2); 6.15 (qd, 4J(2,Me) ˆ 4J(2,4) ˆ
1.4, HÀC(2)).DQF-COSY (−H,H-COSY×, 4999. MHz, CDCl 3): 2.22 (MeÀC(3)) $ 6.15 (HÀC(2)); 2.45
(OHÀC(5)) $ 4.41 (HÀC(5)); 2.57 (HÀC(7)) $ 4.41 (HÀC(5)); 2.75 (OHÀC(4)) $ 4.22 (HÀC(4), weak);
4.22 (HÀC(4)) $ 2.75 (OHÀC(4), weak), 4. 41 (HÀC(5)); 4.41 (HÀC(5)) $ 2.45 (OHÀC(5)); 4.22
(HÀC(4)); 6.15 (HÀC(2)) $ 2.22 (MeÀC(3)). 13C-NMR (125.7 MHz, CDCl3): 16.00 (MeÀC(3)); 59.92 (q,
2J(C,F) ˆ 36.5, CF3CH2); 64.13 (C(5)); 75.57 (C(7)); 78.66 (C(4)); 81.19 (weaker than the two preceding signals,
C(6)); 116.31 (C(2)); 123.09 (q, 1J(C,F) ˆ 277.2, CF3CH2); 157.57 (C(3)); 164.23 (C(1)). edHSQC (−C,H-COSY×,
125.7/499.9 MHz, CDCl3): 16.00 (CH3ÀC(3)) $ 2.22 (CH3ÀC(3)); 59.92 (CF3CH2) $ 4.49 and 4.50 (CF3CH2);
64.13 (C(5)) $ 4.41 (HÀC(5)); 75.57 (C(7)) $ 2.57 (HÀC(7)); 78.66 (C(4)) $ 4.22 (HÀC(4)); 116.31
‡
‡
(C(2)) $ 6.15 (HÀC(2)).HR-EI-MS (70 eV): 1970.420 ([ M À HCꢀCH(OH)] , C7H8F3O3 ; calc.1970.425).
Anal.calc.for C 10H11F3O4 (252.2): C 47.63, H 4.40; found: C 47.90, H 4.52.
(1E)-1-(1,2-Epoxy-2,6,6-trimethylcyclohexyl)-2-iodoethene (ˆ1-[(1E)-2-Iodoethenyl]-2,2,6-trimethyl-7-oxa-
bicyclo[4.1.0]heptane; 25).At 0 8, a soln.of I (0.79 g, 3.13 mmol, 1.0 equiv.) in CH2Cl2 (30 ml) was added via
2
cannula to a soln. of the ethenylstannane (1.42 g, 3.13 mmol; prepared from alkyne 24) in CH2Cl2 (30 ml).After
stirring at 08 for 3 h, the solvent was evaporated.A conc.aq.KF soln.was added to the residue.After stirring for
30 min at r.t., the suspension was diluted with Et2O (40 ml) and filtered through a pad of Celite.The aq.phase
was extracted with Et2O (3Â 100 ml), the combined org.phase was dried (Na 2SO4) and evaporated, and the residue
purified by FC (6.0-cm column, cyclohexane/AcOEt 50 :1): 25 (0.83 g, 91%). IR (film): 2960, 2930, 2870, 1605,
1460, 1455, 1380, 1365, 1285, 1265, 1235, 1175, 1145, 1115, 1080, 1065, 1045, 975, 950, 910. 1H-NMR (499.9 MHz,
CDCl3; s of unknown contamination at d 0.17): 0.94, 1.08, 1.18 (3 s, MeÀC(2), 2 MeÀC(6)); 1.03 1.08 (m,
HaÀC(5)); 1.35 1.43 (m, CH2(4), HbÀC(5)); 1.73 (ddd, Jgem ˆ 15.2, J(3,4) ˆ 5.7, HaÀC(3)), 1.83 1.90 (m,
HbÀC(3)); 6.22 (d, 3J ˆ 14.3, (ICHˆCH (see edHSQC)); 6.75 (d, 3J ˆ 14.3, ICHˆCH (see edHSQC)).DQF-
COSY (− H,H-COSY×, 499.9 MHz, CDCl3): 1.03 1.08 (HaÀC(5)) $ 1.35 1.43 (CH2(4), HbÀC(5)); 1.35 1.43
(inter alia CH2(4)) $ 1.03 1.08 (HaÀC(5)), 1.73 (HaÀC(3)), 1.83 1.90 (HbÀC(3)); 1.73 (HaÀC(3)) $ 1.35
1.43 (inter alia CH2(4)), 1.83 1.90 (HbÀC(3)); 1.83 1.90 (HbÀC(3)) $ 1.35 1.43 (inter alia CH2(4)), 1.73
(HaÀC(3)); 6.22 (ICHˆCH) $ 6.75 (ICHˆCH); 6.75 (ICHˆCH) $ 6.22 (ICHˆCH). 13C-NMR (125.7 MHz,
CDCl3; contamination present as specified below): 16.86 (C(4)); 20.88 25.65, 25.69 (MeÀC(2), 2 MeÀC(6));
29.86 (C(3)); 35.61 (C(5)); 64.95 (calc. 64.29, C(2)21)); 73.51 (calc. 67.52, C(1)21)); 78.94 (calc. 71.92,
ICHˆCH21)); 141.95 (calc. 148.13, ICHˆCH21)); C(6) could not be identified unambiguously among the −extra
peaks× all but one due to the unknown contaminant(s) at d 16.75, 18.49, 22.76, 25.54, 26.23, 28.99, 33.27, and
21
)
Tentative assignment based on increment calculation by ACD/Chem Sketch, Vs.40. 4 (1999); Vs.40. 7 for
26 and 29.

1954
Helvetica Chimica Acta Vol.88 (2005)
33.82. edHSQC (−C,H-COSY×, 125.7/499.7 MHz, CDCl3): 16.86 (C(4)) $ 1.35 1.43 (inter alia CH2(4)); 20.88,
25.65, 25.69 (3 CH3) $ 0.94, 1.08, 1.18 (3 CH3); 29.86 (C(3)) $ 1.73 (HaÀC(3)), 1.83 1.90 (HbÀC(3)); 35.61
(C(5)) $ 1.03 1.08 (HaÀC(5)), 1.35 1.43 (inter alia HbÀC(5)); 78.94 (ICHˆCH) $ 6.22 (ICHˆCH); 141.95
‡
‡
(ICHˆCH) $ 6.75 (ICHˆCH).HR-EI-MS (70 eV): 2920. 322 ( M , C11H17IO ; calc.2920. 324).
2,2,2-Trifluoroethyl (2E,4S,5S)-4,5-(Isopropylidenedioxy)-3-methylhept-2-en-6-ynoate (ˆ2,2,2-Trifluoro-
ethyl (2E)-3-[(4S,5S)-5-Ethynyl-2,2-dimethyl-1,3-dioxolan-4-yl]but-2-enoate).TsOH (57.mg, 40
mmol,
0.1 equiv.) and 2,2-dimethoxypropane (74.0 ml, 62.0 mg, 595 mmol, 1.5 equiv.) were added to a soln. of 22
(100 mg, 397 mmol) in CH2Cl2 (5 ml).After stirring for 3 h at r.t., aq.NaHCO 3 soln.(10 ml) was added.The aq.
phase was extracted with CH2Cl2 (4 Â 8 ml), the combined org.phase dried (Na 2SO4) and evaporated, and the
crude product purified by FC (3.0-cm column, cyclohexane/AcOEt 1.5 :1): title compound (113 mg, 97%). IR
1
(film): 3460, 3305, 2990, 1740, 1655, 1415, 1385, 1285, 1245, 1220, 1170, 1090, 1060, 980. H-NMR (499.9 MHz,
CDCl3): 1.49, 1.53 (2 incompletely resolved q, 4J(within Me2C) ˆ 0.5, Me2C); 2.23 (d, 4J(Me,2) ˆ 1.3,
4
MeÀC(3)); 2.63 (d, J(7,5) ˆ 2.1, HÀC(7)); 4.34 (dd, J(5,4) ˆ 7.7, 4J(5,7) ˆ 2.1, (>4J(4,2)), HÀC(5)); 4.51 (q,
3J(C,F) ˆ 8.5, CF3CH2); 4.53 (dd, J(4,5) ˆ 7.7, 4J(4,2) ˆ 1.0, (<4J(5,7)), HÀC(4)); 6.17 (dq, 4J(2,4) ˆ 4J(2,Me) ˆ
1.4, HÀC(2)). 13C-NMR (125.7 MHz, CDCl3): 15.28 (MeÀC(3)); 26.15, 26.48 (Me2C); 59.92 (q, 2J(C,F) ˆ 36.5,
CF3CH2); 69.82 (C(5) (see edHSQC)); 75.73 (C(7)); 80.16 (lower intensity than the preceding signal, C(6));
84.65 (C(4) (see edHSQC)); 111.48 (Me2C); 114.51 (C(2)); 123.08 (q, 1J(C,F) ˆ 277.2, CF3CH2); 156.20 (C(3));
164.21 (C(1)). edHSQC (−C,H-COSY×, 125.7/499.9 MHz, CDCl3): 15.28 (CH3ÀC(3)) $ 2.23 (CH3ÀC(3));
26.15, 26.48 ((CH3)C) $ 1.49 and 1.53 ((CH3)C); 59.92 (CF3CH2) $ 4.51 (CF3CH2); 69.82 (C(5)) $ 4.34
(HÀC(5)); 84.65 (C(4)) $ 4.53 (HÀC(4)); 114.51 (C(2)) $ 6.17 (HÀC(2)).Anal.calc.for C 13H15F3O4 (292.3):
C 53.43, H 5.17; found: C 53.61, H 5.11.
2,2,2-Trifluoroethyl (2E,4S,5S)-4,5-(Isopropylidenedioxy)-7-(methoxycarbonyl)-3-methyloct-2-en-6-ynoate
(ˆ2,2,2-Trifluoroethyl (2E)-3-[(4S,5S)-5-(3-Methoxy-3-oxoprop-1-ynyl)-2,2-dimethyl-1,3-dioxolan-4-yl]but-2-
enoate; 26).At À 788, 1. 0m LiHMDS in THF (0.22 mmol, 0.22 ml, 1.3 equiv.) was added dropwise to a soln.
of 2,2,2-trifluoroethyl (2E,4S,5S)-4,5-(isopropylidenedioxy)-3-methylhept-2-en-6-ynoate (50.0 mg, 0.17 mmol)
in THF (5 ml).The resulting soln.was stirred for 30 min before ClCO 2Me (0.053 ml, 64.3 mg, 680 mmol,
4.0 equiv.) was added all at once. After stirring for 45 min at À 788, H2O (10 ml) was added.After warming to
r.t., the aq. phase was extracted with Et2O (4 Â 15 ml), the combined org.phase dried (Na 2SO4) and evaporated,
and the residue purified by FC (3.0-cm column, cyclohexane/AcOEt 3.5 :1): 26 (53.0 mg, 89%). IR (film): 2995,
2245, 1725, 1655, 1440, 1410, 1385, 1375, 1325, 1280, 1260, 1220, 1165, 1145, 1085, 1060, 980, 965. 1H-NMR
(499.9 MHz, CDCl3): 1.50, 1.53 (s and incompletely resolved q, resp., 4J(within Me2C) ˆ 0.5, Me2C); 2.21 (d,
4J(Me,4) ˆ 1.4, MeÀC(3)); 3.81 (s, MeO); 4.45 (d, J(5,4) ˆ 7.4, HÀC(5)); 4.51 (q, 3J(H,F) ˆ 8.5, CF3CH2); 4.61
(br. dd, J(4,5) ˆ 7.4, 4J(4,2) ˆ 0.8, HÀC(4)); 6.17 (qd, 4J(2,Me) ˆ 4J(2,4) ˆ 1.4, HÀC(2)).DQF-TPPI-COSY
(− H,H-COSY×, 499.9 MHz, CDCl3): 2.21 (MeÀC(3)) $ 4.61 (HÀC(4)), 6.17 (HÀC(2)); 4.45 (HÀC(5)) $ 4.61
(HÀC(4)); 4.61 (HÀC(4)) $ 2.21 (MeÀC(3)), 4.45 (HÀC(5)), 6.17 (HÀC(2)); 6.17 (HÀC(2)) $ 2.21
(MeÀC(3)), 4.61 (HÀC(4)). 13C-NMR (125.7 MHz, CDCl3): 15.21 (MeÀC(3)); 25.84, 26.43 (Me2C); 52.98
(MeO); 59.98 (q, 2J(C,F) ˆ 36.6, CF3CH2); 69.38 (C(4) (see edHSQC)); 78.17 (calc. 88.34, C(6)21)); 83.06 (calc.
91.89, C(7)21)); 84.22 (C(5) (see edHSQC)); 112.35 (Me2C); 114.99 (C(2)); 123.04 (incompletely visible q,
1J(C,F) ˆ 277.3, CF3CH2); 153.18 (CO2Me22); 155.38 (C(3)22)); 164.05 (C(1)22)).edHSQC (−C,H-COSY×, 1257. /
499.9 MHz, CDCl3): 15.21 (CH3ÀC(3)) $ 2.21 (CH3ÀC(3)); 25.84, 26.43 ((CH3)2C) $ 1.50, 1.53 ((CH3)2C);
52.98 (CH3O) $ 3.81 (CH3O); 59.98 (CF3CH2) $ 4.51 (CF3CH2); 69.38 (C(4)) $ 4.61 (HÀC(4)); 84.22
‡
(C(5)) $ 4.45 (HÀC(5)); 114.99 (C(2)) $ 6.17 (HÀC(2)).HR-EI-MS (70 eV): 3350.745 ([ M À CH3] ,
‡
C14H14F3O6 ; calc.3350. 742).Anal.calc.for C 15H17F3O6 (350.3): C 51.43, H 4.89; found: C 51.37, H 4.75.
2,2,2-Trifluoroethyl (2E,8E,4S,5S)-9-(1,2-Epoxy-2,6,6-trimethylcyclohexyl)-4,5-dihydroxy-3-methylnona-
2,8-dien-6-ynoate (ˆ2,2,2-Trifluoroethyl (2E,8E,4S,5S)-4,5-Dihydroxy-3-methyl-9-(2,2,6-trimethyl-7-oxabicy-
clo[4.1.0]hept-1-yl)nona-2,8-dien-6-ynoate; 27; 1:1 diastereoisomer mixture if the MeÀC(2') 1H-NMR signal
is correctly interpreted and not split by a 4J(3',MeÀC(2')) coupling).To a suspension of [PdCl 2(PPh3)2]
(94.9 mg, 0.135 mmol, 5 mol-%) in THF (15 ml), CuI (77.2 mg, 0.405 mmol, 15 mol-%) was added. Then a soln.
of 25 (829 mg, 2.84 mmol, 1.05 equiv.) and 22 (681 mg, 2.70 mmol) in THF (10 ml) was added via cannula.After
the dropwise addition of Et3N (8.00 ml, 5.81 g, 57.4 mmol, 21.2 equiv.), the mixture was stirred for 90 min at r.t.
The reaction was terminated by the addition of aq.NH 4Cl soln.(10 ml).The aq.phase was extracted with Et 2O
22
)
Assignment of the Cquat. based on the similarity to the unequivocally assigned Cquat. resonances 156.20
(C(3)) and 164.21 (C(1)) of 2,2,2-trifluoroethyl (2E,4S,5S)-4,5-(isopropylidenedioxy)-3-methylhept-2-en-6-
ynoate (see above); this left d 153.18 (or 179,71 in case of 28) for CO2Me.

Helvetica Chimica Acta Vol.88 (2005)
1955
(4 Â 15 ml), the combined phase dried (Na2SO4) and evaporated, and the residue purified by FC (5.5-cm
column, cyclohexane/AcOEt 1:1): 27 (0.859 g, 76%). IR (film): 3420, 2965, 2935, 2875, 1735, 1650, 1450, 1440,
1410, 1380, 1365, 1285, 1205, 1170, 1140, 1065, 1045, 980, 960. 1H-NMR (499.9 MHz, CDCl3; most assignments by
DQF-TPPI-COSY, see below): 0.92, 1.08 (2 br. s, 2 MeÀC(6')); 1.03 1.08 (m, HaÀ(5')); 1.151, 1.153 (2 s,
MeÀC(2')23); 1.37 1.47 (m, CH2(4') (HbÀC(5')); 1.74 (ddd, 2J ˆ 15.3, J(3'a,4') ˆ 5.6, 5.6, HaÀC(3')); 1.89 (ddd,
2J ˆ 15.1, J(3'b,4') ˆ 7.8, 7.8, HbÀC(3)); 2.23 (d, 4J(Me,2) ˆ 1.4, MeÀC(3)); 2.42 (br. d, J(OH,5) ˆ 6.3,
OHÀC(5)); 2.77 (br. d, J(OH,4) ˆ 3.1, OHÀC(4)); 4.22 (br. dd, J(4,5) ˆ 5.2, J(4,OH) ˆ 2.2, HÀC(4)); 4.44
4.55 (m, CF3CH2, HÀC(5)); 5.70 (dd, J(8,9) ˆ 15.7, 5J(8,5) ˆ 1.8 (diagnostic for assignment), HÀC(8)); 6.16
(qd, 4J(2,Me) ˆ 4J(2,4) ˆ 1.3, HÀC(2)); 6.40 (d, J(9,8) ˆ 15.8, HÀC(9)).DQF-TPPI-COSY (H,H-COSY,
499.9 MHz, CDCl3): 0.92 (MeaÀC(6')) $ 1.08 (MebÀC(6')); 1.08 (MebÀC(6')) $ 0.92 (MeaÀC(6')); 1.03 1.08
(HaÀC(5')) $ 1.37 1.47 (CH2(4'), HbÀC(5')); 1.37 1.47 (CH2(4'), HbÀC(5')) $ 1.03 1.08 (HaÀC(5')), 1.74
(HaÀC(3')), 1.89 (HbÀC(3')); 1.74 (HaÀC(3')) $ 1.37 1.47 (inter alia CH2(4')), 1.89 (HbÀC(3')); 1.89
(HbÀC(3')) $ 1.37 1.47 (inter alia CH2(4')), 1.74 (HaÀC(3')); 2.23 (MeÀC(3)) $ 6.16 (HÀC(2)); 2.42
(OHÀC(5)) $ 4.44 4.55 (inter alia HÀC(5)); 2.77 (OHÀC(4)) $ 4.22 (HÀC(4)); 4.22 (HÀC(4)) $ 2.77
(OHÀC(4)), 4.44 4.55 (inter alia HÀC(5)), 6.16 (HÀC(2), very low intensity); 4.44 4.55 (inter alia
HÀC(5)) $ 2.42 (OHÀC(5)), 4.22 (HÀC(4)), 6.40 (HÀC(9), very low intensity); 5.70 (HÀC(8)) $ 4.44 4.55
(very low intensity, inter alia HÀC(5)), 6.40 (HÀC(9)); 6.16 (HÀC(2)) $ 2.23 (MeÀC(3)), 4.22 (very low
intensity, HÀC(4)); 6.40 (HÀC(9)) $ 5.70 (HÀC(8)). 13C-NMR (125.7 MHz, CDCl3): 16.12 (MeÀC(3)); 16.89
(C(4')); 20.69 (MeÀC(2')24)); 25.68, 25.76 (2 MeÀC(6')24); 29.90 (C(3')); 33.45 (low intensity, C(6')); 35.60
(C(5')); 59.87 (incompletely resolved q, 2J(C,F) ˆ 36.5, CF3CH2); 64.94 (C(5)24)); 65.90 (C(2')); 70.97 (C(1'));
78.88 (C(4)24)); 85.65, 86.84 (C(6), C(7)); 111.48 (C(8)24)); 116.05 (C(2)24)); 123.11 (q (only the center signals
are visible), 1J(C,F) ˆ 277.0, CF3CH2); 141.00 (C(9)24)); 158.11 (C(3)); 164.27 (C(1)). edHSQC (−C,H-COSY×,
125.7/499.9 MHz, CDCl3): 16.12 (CH3ÀC(3)) $ 2.23 (CH3ÀC(3)); 16.89 (C(4')) $ 1.37 1.47 (inter alia
CH2(4')); 20.69 (CH3ÀC(2')) $ 1.151, 1.153 (CH3ÀC(2'))); 25.68, 25.76 (2 CH3ÀC(6')) $ 0.92, 1.08
(2 CH3À(6')); 29.90 (C(3'))$ 1.74 ( HaÀC(3')), 1.89 (HbÀC(3')); 35.60 (C(5'))$ 1. 03 1. 08 (HaÀC(5')), 1.37
1.47 (inter alia HbÀC(5')); 59.87 (CF3CH2) $ 4.44 4.55 (inter alia CF3CH2); 64.94 (C(5)) $ 4.44 4.55 (inter
alia HÀC(5)); 78.88 (C(4))$ 4.22 (HÀC(4)); 111.48 (C(8))$ 5.70 (HÀC(8)); 116.05 (C(2)) $ 6.16 (HÀC(2));
141.00 (C(9)) $ 6.40 (HÀC(9)).Anal.calc.for C 21H27F3O5 (416.4): C 60.57, H 6.54; found: C 60.86, H 6.79.
2,2,2-Trifluoroethyl (2E,4S,5S,6E)-4,5-(Isopropylidenedioxy)-7-(methoxycarbonyl)-3-methyl-7-(tributyl-
stannyl)hepta-2,6-dienoate (ˆ2,2,2-Trifluoroethyl (2E)-3-{(4S,5S)-5-[(1E)-3-Methoxy-3-oxo-2-(tributylstan-
nyl)prop-1-enyl]-2,2-dimethyl-1,3-dioxolan-4-yl}but-2-enoate; 28).To a degassed soln.of [Pd(PPh 3)4] (57 mg,
50 mmol, 5 mol-%) in THF (10 ml), a degassed soln.of 26 (347 mg, 0.99 mmol) in THF (2 ml) was added. At 08,
Bu3SnH (0.293 ml, 317 mg, 1.09 mmol, 1.1 equiv.) was added. After stirring for 1 h at 08, H2O (10 ml) and aq.
NaCl soln.(10 ml) were added.The aq.phase was extracted with Et 2O (4 Â 25 ml), the combined org.phase
dried (Na2SO4) and evaporated, and the residue purified by FC (4.5-cm column; cyclohexane, cyclohexane/
AcOEt 10 :1): 28 (558 mg, 88%).IR (film): 2985, 2960, 2930, 2875, 2855, 1740, 1710, 1650, 1615, 1455, 1435,
1415, 1380, 1285, 1240, 1220, 1200, 1170, 1140, 1080, 1065, 980, 960, 865. 1H-NMR (499.9 MHz, CDCl3): 0.89 (t,
2
3J ˆ 7.3, 3 MeCH2CH2CH2); 1.00 (m, probably each peak flanked by Sn-isotope satellites as 2 d, J(H,119Sn) ˆ
53.2, 2J(H,117Sn) ˆ 51.0, 3 MeCH2CH2CH2); 1.31 (qt, 3J ˆ 7.3, 7.3, 3 Me CH2CH2CH2); 1.46 1.53 (m,
3 MeCH2CH2CH2), superimposing 1.479 and 1.483 (2 s, Me2C); 2.16 (d, 4J(Me,2) ˆ 1.4, MeÀC(3)); 3.63 (s,
4
MeO); 4.10 (dd, J(4,5) ˆ 8.2, J(4,2) ˆ 0.8, HÀC(4)); 4.46, 4.51 (AB, JAB ˆ 12.4, A and B in addition split to q,
3J(A,F) ˆ 3J(B,F) ˆ 8.4, CF3CH2); 4.83 (dd, J(5,6) ˆ J(5,4) ˆ 8.1, each peak flanked by Sn-isotope satellites as d,
4J(5,Sn) ˆ 5.7, HÀC(5)); 5.97 (d, J(6,5) ˆ 8.0, each peak flanked by Sn-isotope satellites as 2 d, 3J(6,119Sn) ˆ 55.9,
3J(6,117Sn) ˆ 53.5, HÀC(6)); 6.01 (dq, 4J(2,4) ˆ 4J(2,Me) ˆ 1.3, HÀC(2)).DQF-COSY (H,H-COSY,
499.9 MHz, CDCl3): 0.89 (MeCH2CH2CH2) $ 1.31 (MeCH2CH2CH2); 1.00 (MeCH2CH2CH2) $ 1.46 1.53
(MeCH2CH2CH2); 1.31 (MeCH2CH2CH2) $ 0.89 (MeCH2CH2CH2), 1.46 1.53 (MeCH2CH2CH2); 1.46 1.53
(MeCH2CH2CH2) $ 1.00 (MeCH2CH2CH2), 1.31 (MeCH2CH2CH2); 2.16 (MeÀC(3)) $ 6.01 (HÀC(2)); 4.10
(HÀC(4)) $ 4.83 (HÀC(5)); 4.83 (HÀC(5)) $ 4.10 (HÀC(4)), 5.97 (HÀC(6)); 5.97 (HÀC(6)) $ 4.83
(HÀC(5)); 6.01 (HÀC(2)) $ 2.16 (MeÀC(3)). 13C-NMR (125.7 MHz, CDCl3): 10.46 (flanked by Sn-isotope
satellites as 2 d, 1J(C,119Sn) ˆ 349.4, 1J(C,117Sn) ˆ 333.9, 3 MeCH2CH2CH2); 13.61 (3 MeCH2CH2CH2), 15.11
(MeÀC(3)); 26.70 (Me2C); 27.16 (flanked by Sn-isotope satellites as d, 3J(C,Sn) ˆ 57.8, 3 MeCH2CH2CH2);
23
)
)
The splitting of this signal could be caused by the existence of a 1:1 mixture of diastereoisomers.
Assignments of MeÀC(2') vs. 2 Me ÀC(6'), C(4) vs.C(5), and C(2) vs.C(8) vs.C(9) based on edHSQC
cross-peaks.
24

1956
Helvetica Chimica Acta Vol.88 (2005)
28.77 (flanked by Sn-isotope satellites as d, 2J(C,Sn) ˆ 20.6, 3 MeCH2CH2CH2); 51.42 (CO2Me); 59.78 (q,
2J(C,F) ˆ 36.5, CF3CH2); 78.03 (flanked by Sn-isotope satellites as d, 3J(C,Sn) ˆ 41.2, C(5) (see edHSQC));
84.65 (C(4) (see edHSQC)); 110.35 (low intensity, Me2C); 114.67 (C(2) (see edHSQC)); 123.12 (q (only three
peaks visible), 1J(C,F) ˆ 277.2, CF3CH2); 143.28 (C(7)); 145.01 (flanked by Sn-isotope satellite as d, 2J(C,Sn) ˆ
13.9, C(6) (see edHSQC)); 157.25 (C(3)22)); 164.17 (C(1)22)); 170.71 (CO2Me22).edHSQC (C,H-COSY, 1257. /
499.9 MHz, CDCl3): 10.46 (CH3CH2CH2CH2) $ 1.00 (CH3CH2CH2CH2); 13.61 (CH3CH2CH2CH2) $ 0.89
(CH3CH2CH2CH2); 15.11 (CH3ÀC(3)) $ 2.16 (CH3ÀC(3)); 26.70 ((CH3)2C) $ 1.479, 1.483 ( (CH3)2 C); 27.16
(CH3CH2CH2CH2) $ 1.31 (CH3CH2CH2CH2); 28.77 (CH3CH2CH2CH2) $ 1.46 1.53 (CH3CH2CH2CH2); 51.42
(CO2CH3) $ 3.63 (CO2CH3); 59.78 (CF3CH2) $ 4.46, 4.51 (CF3CH2); 78.03 (C(5)) $ 4.83 (HÀC(5)); 84.65
(C(4)) $ 4.10 (HÀC(4)); 114.67 (C(2)) $ 6.01 (HÀC(2)); 145.01 (C(6)) $ 5.97 (HÀC(6)).HR-EI-MS
‡
‡
(70 eV): 585.1500 ([M À Bu] , C23H36F3O6Sn ; calc.5851. 486).Anal.calc.for C
27H45F3O6Sn (641.4): C 50.56,
H 7.07; found: C 51.04, H 7.27.
(5S)-3-[(1E)-2-(1,2-Epoxy-2,6,6-trimethylcyclohexyl)ethenyl]-5-{(1S,2E)-1-hydroxy-2-methyl-3-[(2,2,2-tri-
fluoroethoxy)carbonyl]prop-2-enyl}-furan-2(5H)-one (ˆ2,2,2-Trifluoroethyl (2E,4S)-4-{(2S)-2,5-Dihydro-5-
oxo-4-[(1E)-2-(2,2,6-trimethyl-7-oxabicyclo[4.1.0]hept-1-yl)ethenyl]furan-2-yl}-4-hydroxy-3-methylbut-2-
enoate; 29; should be a 1:1 mixture with respect to the epoxide moiety, but there was no spectral evidence;
tentatively assigned to represent a 86 :14 mixture with its diastereoisomer epi-29 (ˆ(5R)-isomer)). Method A:
To a soln.of [Pd 2dba3] ¥ CHCl3 (7.7 mg, 7.5 mmol, 10 mol-%) in CH2Cl2 (40 ml), butane-1,4-diyl-bis[diphenyl-
phosphine] (7.7 mg, 15 mmol, 20 mol-%) was added.The soln.was stirred for 30 min (red ! yellow).A soln.of
27 (31 mg, 74 mmol) in CH2Cl2 (10 ml) was added via cannula.The resulting soln.was transferred into an
autoclave, which was pressurized with H2 (8 bar) and CO (42 bar).Under stirring, the mixture was heated at 50 8
for 24 h.After cooling and release of the gases, the solvent was evaporated and the residue passed through a
short chromatography column (1.5 cm  15 cm, cyclohexane/AcOEt 2 :1): 7:3-mixture (19.9 mg) of 29/epi-29
(14.2 mg, 43%) and re-isolated 27 (5.7 mg, 19%).
Method B: A degassed soln.of 30 (347 mg, 610 mmol) in DMF (5 ml) was transferred via cannula to a
degassed soln.of [Pd(PPh 3)4] (35 mg, 30 mmol, 5 mol-%) and iodoalkene 25 (196 mg, 0.671 mmol, 1.1 equiv.) in
DMF (5 ml). CuI (139 mg, 0.732 mmol, 1.2 equiv.) was then added and the resulting suspension stirred for 3 h at
r.t. After dilution with tBuOMe (5 ml), aq.NH 4Cl soln.(10 ml), and H 2O (10 ml), the aq.phase was extracted
with Et2O (4 Â 25 ml), the combined org.phase dried (Na 2SO4) and evaporated, and the residue purified by FC
(6.0-cm column, cyclohexane/AcOEt 2 :1): 29/epi-29 (260 mg, 96%).IR (film): 3445, 2960, 2930, 2875, 2855,
1
1740, 1655, 1455, 1410, 1380, 1365, 1350, 1280, 1260, 1205, 1170, 1145, 1100, 1070, 980, 870, 840, 800. H-NMR
(499.9 MHz, CDCl3; postulated 86 :14 mixture 29/epi-29): 29: 0.93, 1.14, 1.15 (3 s, MeÀC(2''), (2 MeÀC(6''));
3
1.06 1.11 (m, HaÀC(5'')); 1.40 1.49 (m, CH2(4''), HbÀC(5'')); 1.76 (m, (ˆ−ddd×, Jgem ˆ 15.0, J(3''a,4'') ˆ 5.5,
5.5, HaÀC(3'')); 1.90 (m, (−ddd×, Jgem ˆ 15.2, 3J(3''b,4'') ˆ 7.8, 7.8 ) , H bÀC(3'')); 2.26 (d, 4J(Me,3''') ˆ 1.2,
MeÀC(2''')); 2.54 (very br. d, J(OH,1''') ˆ 2.5, OH); 4.25 (very br. d, J(1''',OH) ˆ 3.2, HÀC(1''')); 4.50, 4.52,
(AB, JAB ˆ 12.7, A and B in addition split to q, 3J(H,F) ˆ 8.5, CF3CH2); 5.04 (dd, J(5,1'') ˆ 5.4, J(5,4) ˆ 2.0,
HÀC(5)); 6.10 (qd, 4J(3''',Me) ˆ 4J(3''',1''') ˆ 1.3, HÀC(3''')); 6.31 (d, J(1',2') ˆ 15.7, HÀC(1') (see edHSQC));
7.00 (d, J(4,5) ˆ 2.0, HÀC(4)); 7.234 (d, J(2',1') ˆ 15.8, HÀC(1') (see edHSQC)); epi-29: 0.92, 1.16 (MeÀC(2''),
4
4
2 MeÀC(6'')); 2.25 (d, J(Me,3''') ˆ 1.4, MeÀC(2''')); 6.08 (qd, J(3''',Me) ˆ 4J(3''',1''') ˆ 1.3, HÀC(3''')); 7.228
(d, J(1',2') ˆ 15.7, HÀC(1')).DQF-COSY (H,H-COSY, 4999. MHz, CDCl 3): 1.06 1.11 (HaÀC(5'')) $ 1.40
1.49 (CH2(4''), HbÀC(5'')); 1.40 1.49 (CH2(4''), HbÀC(5'')) $ 1.06 1.11 (HaÀC(5'')), 1.76 (HaÀC(3'')), 1.90
(HbÀC(3'')); 1.76 (HaÀC(3'')) $ 1.40 1.49 (inter alia CH2(4''); 1.90 (HbÀC(3'')); 1.90 (HbÀC(3'') $ 1.40 1.49
(inter alia CH2(4'')), 1.76 (HaÀC(3'')); 2.26 (MeÀC(2''')) $ 6.10 (HÀC''')); 2.54 (br. s, OH) $ 4.25 (HÀC(1'''));
4.25 (HÀC(1''')) $ 2.43 (br. s, OH), 5. 04 (HÀC(5)), 6.10 (HÀC(3''')), very weak); 5.04 (HÀC(5)) $ 4.24
(HÀC(1''')), 6.99 (HÀC(4)); 6.10 (HÀC(3''')) $ 2.26 (MeÀC(2''')), 4.24 (HÀC(1'''), very weak); 6.31
(HÀC(1')) $ 7.234 ( H ÀC(2')); 7.00 (HÀC(4)) $ 5.04 (HÀC(5)); 7.234 (HÀC(2')) $ 6.31 (HÀC(1')).
13C-NMR (125.7 MHz, CDCl3): 29: 15.97 (MeÀC(2''') (see edHSQC)), 16.96 (C(4'') (see edHSQC)); 20.82,
25.82, 25.89 (MeÀC(2''), 2 MeÀC(6'')), 29.98 (C(3'')); 33.59 (lower intensity than preceding and following
signal, C(6'')); 35.65 (C(5'')); 60.01 (q, 3J(C,F) ˆ 36.6, CF3CH2), 65.90 (calc. 66.63, C(2'')21)); 71.33 (calc. 73.72,
C(1'')21)); 76.79 (C(1''')); 81.53 (C(5)); 116.60 (C(3''')); 120.65 (C(1'); cf.C(8) of 27); 123.02 (incompletely
visible q, 1J(C,F) ˆ 277.2, CF3CH2); 130.29 (C(3); d(C(3)) < d(C(2)); 134.63 (C(2'); cf.C(9) of 27); 143.41
(C(4)); 157.35 (C(2'''); cf.C(2 ') of 30); 163.94 (CO2Tfe; cf.C(1) of 22), 170.74 (C(2); d(C(3)) < d(C(2))); epi-
29: 20.89 (MeÀC(2'')); 29.69 (C(3'')); 33.57 (C(6'')); 35.63 (C(5'')); 143,46 (C(4)).edHSQC (C,H-COSY, 125.7/
499.9 MHz, CDCl3): 15.97 (CH3ÀC(2''')) $ 2.26 (CH3ÀC(2''')); 16.96 (C(4'')) $ 1.40 1.49 (inter alia CH2(4''));
20.82, 25.82, 25.89 (CH3ÀC(2''), 2 CH3ÀC(6'')) $ 0.93, 1.14, 1.15 (CH3ÀC(2''), 2 CH3ÀC(6'')); 29.98 (C(3'')) $
signal of very low intensity 1.76 (HaÀC(3'')), signal of normal intensity 1.90 (HbÀC(3'')); 35.65 (C(5'')) $ signal

Helvetica Chimica Acta Vol.88 (2005)
1957
of normal intensity 1.06 1.11 (m, HaÀC(5'')), signal of very low intensity 1.40 1.49 (inter alia CH2(5'')); 60.01
(CF3CH2) $ 4.50, 4.52 (CF3CH2); 76.79 (C(1''')) $ 4.25 (HÀC(1''')); 81.53 (C(5)) $ 5.04 (HÀC(5)); 116.60
(C(3''')) $ 6.10 (HÀC(3''')); 120.65 (C(1')) $ 6.31 (HÀC(1')); 134.63 (C(2')) $ 7.234 (HÀC(2')); 143.42
‡
‡
(C(4)) $ 7.00 (HÀC(4)).HR-EI-MS (70 eV): 4441.750 ( M , C22H27F3O6 , calc.4441.760).Anal.calc.for
C22H27F3O6 (444.4): C 59.45, H 6.12; found: C 59.76, H 6.89.
(5S)-5-{(2E,1S)-1-Hydroxy-2-methyl-3-[(2,2,2-trifluoroethoxy)carbonyl]prop-2-enyl}-3-(tributylstannyl)-
furan-2(5H)-one (ˆ2,2,2-Trifluoroethyl (2E,4S)-4-[(2S)-2,5-Dihydro-5-oxo-4-(tributylstannyl)furan-2-yl]-4-hy-
droxy-3-methylbut-2-enoate; 30). TsOH (37 mg, 0.19 mmol, 0.2 equiv.) was added to a soln. of 28 (616 mg,
960 mmol) in MeOH (15 ml).The resulting soln.was heated under reflux for 8 h.After dilution with tBuOMe
(10 ml), aq.NaHCO soln.(10 ml), and H 2O (5 ml), the aq.phase was extracted with Et 2O (4 Â 25 ml), the
3
combined org.phase dried (Na 2SO4) and evaporated, and the residue purified by FC (3.5-cm column,
cyclohexane/AcOEt 5 :1): 30 (347 mg, 64%).IR (film): 3410, 2955, 2925, 2855, 1735, 1650, 1580, 1455, 1410,
1285, 1165, 1140, 980, 1065, 870. 1H-NMR (499.9 MHz, CDCl3; unknown contaminant with s at d 0.07): 0.89 (t,
3J ˆ 7.4, 3 MeCH2CH2CH2); 1.10 (m, each peak flanked by Sn-isotope satellites as 2 d, 2J(H,119Sn) ˆ 54.6,
2J(H,117Sn) ˆ 52.1, 3 MeCH2CH2CH2); 1.32 (qt, 3J ˆ 7.4, 7.4, 3 MeCH2CH2CH2); 1.43 1.61 (m,
3 MeCH2CH2CH2); 2.24 (d, 4J(Me,3') ˆ 1.4, MeÀC(2')); 2.34 (d, J(OH,1) ˆ 4.9, OH); 4.20 (dd, J(1',OH) ˆ
J(1',5) ˆ 4.8, HÀC(1')); 4.49, 4.51 (JAB ˆ 12.7, A and B in addition split to q, 3J(H,F) ˆ 8.5, CF3CH2); 5.08 (dd,
J(5,1') ˆ 5.3, J(5,4) ˆ 1.5, each peak flanked by Sn-isotope satellites as d, 4J(5,Sn) ˆ 7.4, HÀC(5)); 6.07 (qd,
4J(3',Me) ˆ 4J(3',1') ˆ 1.2, HÀC(3')); 7.36 (d, J(4,5) ˆ 1.5, each peak flanked by Sn-isotope satellites as d,
3J(4,Sn) ˆ 21.6, HÀC(4)).DQF-COSY (H,H-COSY, 4999.MHz, CDCl 3): 0.89 (MeCH2CH2CH2) $ 1.32
(MeCH2CH2CH2); 1.10 (MeCH2CH2CH2) $ 1.43 1.61 (MeCH2CH2CH2); 1.32 (MeCH2CH2CH2) $ 0.89
(MeCH2CH2CH2), 1.43 1.61 (MeCH2CH2CH2); 1.43 1.61 (MeCH2CH2CH2) $ 1.10 (MeCH2CH2CH2), 1.32
(MeCH2CH2CH2); 2.24 (MeÀC(2')) $ 6.07 (HÀC(3'), low intensity); 2.34 (OHÀC(1')) $ 4.20 (HÀC(1'));
4.20 (HÀC(1')) $ 2.24 (MeÀC(2')), 5.08 (HÀC(5)); 5.08 (HÀC(5)) $ 4.20 (HÀC(1')); 6.07 (HÀC(3')) $ 2.24
(MeÀC(2'), low intensity); no cross-peak HÀC(4) $ HÀC(5). 13C-NMR (125.7 MHz, CDCl3; unknown
contaminant at d 29.69): 9.85 (flanked by Sn-isotope satellites as 2 d, 1J(C,119Sn) ˆ 361.5, 1J(C,117Sn) ˆ 345.1,
3 MeCH2CH2CH2); 13.60 (3 MeCH2CH2CH2); 16.13 (MeÀC(2')); 27.13 (flanked by Sn-isotope satellites as d,
3J(C,Sn) ˆ 59.0, 3 MeCH2CH2CH2); 28.88 (flanked by Sn-isotope satellites as d, 2J(C,Sn) ˆ 21.8,
3 MeCH2CH2CH2); 59.98 (q, 2J(C,F) ˆ 36.5, CF3CH2); 76.86 (C(1') see edHSQC)); 85.62 (flanked by Sn-
isotope satellites as d, 3J(5,Sn) ˆ 33.0, C(5) (see edHSQC)); 116.23 (C(3') (see edHSQC)); 123.03
(incompletely resolved q, 1J(C,F) ˆ 277.0, CF3CH2); 138.18 (C(3)); 157.83 (C(2')22)); 161.07 (more intense
than the 2 preceding and the 2 following signals and thus not Cquat, flanked by Sn-isotope satellites as d,
2J(C,Sn) ˆ 15.8, C(4); cf.C(3 ')); 163.98 (CO2Tfe22)); 176.89 (C(2)22)). edHSQC (C,H-COSY, 125.7/499.9 MHz,
CDCl3):
9.85
(CH3CH2CH2CH2) $ 1.10
(CH3CH2CH2CH2);
13.60
(CH3CH2CH2CH2) $ 0.89
(CH3CH2CH2CH2); 16.13 (CH3ÀC(2')) $ 2.24 (CH3ÀC(2')); 27.13 (CH3CH2CH2CH2) $ 1.32
(CH3CH2CH2CH2); 28.88 (CH3CH2CH2CH2) $ 1.43 1.61 (CH3CH2CH2CH2); 59.98 (CF3CH2) $ 4.49, 4.51
(CF3CH2); 76.86 (C(1')) $ 4.20 (HÀC(1')); 85.62 (C(5)) $ 5.08 (HÀC(5)); 116.23 (C(3')) $ 6.07 (HÀC(3')).
‡
‡
HR-EI-MS (70 eV): 513.0931 ([M À Bu] , C19H28F3O5Sn ; calc.5130. 911).
(5Z)-3-[(1E)-2-(1,2-Epoxy-2,6,6-trimethylcyclohexyl)ethenyl]-5-{(2E)-3-[(2,2,2-trifluoroethoxy)carb-
onyl]prop-2-enyliden}furan-2(5H)-one (ˆ2,2,2-Trifluoroethyl (2E,4Z)-3-Methyl-4-{5-oxo-4-[(1E)-2-(2,2,6-tri-
methyl-7-oxabicyclo[4.1.0]hept-1-yl)ethenyl]furan-2(5 H)-ylidene}but-2-enoate; 31).At À 308 and excluding
light, DEAD (0.112 ml, 123 mg, 0.707 mmol, 6 equiv.) was added to a soln. of 29 (52.4 mg, 0.118 mmol) in
degassed THF (8 ml; containing 250 mg/l of 2,6-di-(tert-butyl)cresol).After 10 min of stirring, PPh (186 mg,
3
0.707 mmol, 6 equiv.) was added in one portion. After 1 h, the solvent was removed at À 308 in vacuo.The
remaining crude product was purified by FC (3.5-cm column, degassed cyclohexane/AcOEt 10 :1, with 0.9%
Et3N): 31 (35.3 mg, 70%). Yellow solid. IR (film): 3080, 2960, 2930, 2870, 2855, 1780, 1730, 1600, 1570, 1445,
1410, 1380, 1365, 1285, 1255, 1220, 1170, 1140, 1065, 1045, 980, 955, 940, 890, 845, 815, 765. 1H-NMR (499.9 MHz,
C6D6; sample containing 2.7 wt.-% of (5E)-isomer, determined by its d at 7.46 (J(2',1') ˆ 15.7, HÀC(2'))): 0.93
(ddd, Jgem ˆ 13.2, J(5'',4''a) ˆ 7.1, J(5'',4''b) ˆ 3.1, HaÀC(5'')); 1.05, 1.08, 1.09 (3 s, MeÀC(2''), 2 MeÀC(6''));
1.17 1.27 (m, HaÀC(4'')); 1.30 1.37 (m, HbÀC(4'')); 1.49 (m, HaÀC(3''), HbÀC(5'')); 1.81 (ddd, Jgem ˆ 15.2,
J(3'',4''a) ˆ 8.6, J(3'',4''b) ˆ 6.6, HbÀC(3'')); 2.54 (d, 4J(Me,3''') ˆ 1.4, MeÀC(2''')); 4.07 (q, 3J(H,F) ˆ 8.7,
CF3CH2); 4.75 (s, HÀC(1''')); 5.76 (dq, 4J(3''',1''') ˆ 4J(3''',Me) ˆ 1.2, HÀC(3''')); 5.86 (s, HÀC(4)); 6.49 (d,
J(1',2') ˆ 15.5, HÀC(1')); 7.55 (d, J(2',1') ˆ 15.5, HÀC(2')).DQF-COSY (H,H-COSY, 4999. MHz, C 6D6): 0.93
(HaÀC(5'')) $ 1.30 1.37 (HbÀC(4'')), 1.49 (inter alia HbÀC(5'')); 1.17 1.27 (HaÀC(4'')) $ 1.30 1.37
(HbÀC(4'')), 1.49 (HaÀC(3''), HbÀC(5'')), 1.81 (HbÀC(3'')); 1.30 1.37 (HbÀC(4'')) $ 0.93 (HaÀC(5'')),
1.17 1.27 (HaÀC(4'')), 1.49 (HaÀC(3''), HbÀC(5'')), 1.81 (HbÀC(3'')); 1.49 (HaÀC(3''), HbÀC(5'')) $ 0.93

1958
Helvetica Chimica Acta Vol.88 (2005)
(HaÀC(5'')), 1.17 1.27 (low intensity, HaÀC(4'')), 1.30 1.37 (low intensity, HbÀC(4'')), 1.81 (HbÀC(3'')); 1.81
(HbÀC(3'')) $ 1.17 1.27 (HaÀC(4'')), 1.30 1.37 (HbÀC(4'')), 1.49 (HaÀC(3''), HbÀC(5'')); 2.54
(MeÀC(2''')) $ 5.76 (HÀC(3''')); 5.76 (HÀC(3''')) $ 2.54 (MeÀC(2''')); 6.49 (HÀC(1')) $ 7.55 ( H ÀC(2'));
7.55 ( H ÀC(2')) $ 6.49 (HÀC(1')). 13C-NMR (125.7 MHz, C6D6): 17.30 (C(4'') or MeÀC(2''')); 17.37
(MeÀC(2''') or C(4'')); 20.80, 25.96, 26.17 (MeÀC(2''), 2 MeÀC(6'')); 30.32 (C(3'')); 33.88 (lower intensity
than preceding and following signal, C(6'')); 36.07 (C(5'')); 59.64 (q, 2J(C,F) ˆ 36.1, CF3CH2); 65.96 (C(2''));
71.31 (C(1'')); 114.42 (C(1''')); 120.56 (C(3''')); 121.81 (C(1')); 123.83 (incompletely visible q, 1J(C,F) ˆ 277.6,
CF3CH2); 128.06 (C(3), tentative; lower intensity than d 128.29 of solvent C6D5H); 135.98 (C(4)); 137.13
(C(2')); 151.16, 152.69 (C(5), C(2'''); d(olef.C) < d(C(2) and CO2Tfe)); 163.97, 167.31 (C(2) and CO2Tfe)).
edHSQC (C,H-COSY, 125.7/499.9 MHz, C6D6): 17.30, 17.37 (C(4''), CH3ÀC(2''')) $ 1.17 1.27 (HaÀC(4'')),
1.30 1.37 (HbÀC(4'')), 2.54 (CH3ÀC(2''')); 20.80, 25.96, 26.17 (CH3ÀC(2''), 2 CH3ÀC(6'')) $ 1.05, 1.08, 1.09
(CH3ÀC(2''), 2 CH3ÀC(6'')); 30.32 (C(3'')) $ 1.49 (inter alia HaÀC(3'')), 1.81 (HbÀC(3'')); 36.07 (C(5'')) $
0.93 (HaÀC(5'')), 1.49 (inter alia HbÀC(5'')); 59.64 (CF3CH2) $ 4.07 (CF3CH2); 114.42 (C(1''')) $ 4.75
(HÀC(1''')); 120.56 (C(3''')) $ 5.76 (HÀC(3''')); 121.81 (C(1')) $ 6.49 (HÀC(1')); 135.98 (C(4)) $ 5.86
(HÀC(4)); 137.13 (C(2')) $ 7.55 (HÀC(2')).ROESY (499.9 MHz, C 6D6): 4.75 (HÀC(1''')) $ 5.76 (HÀC(3''')),
5.86 (HÀC(4)); 5.76 (HÀC(3''')) $ 4.75 (HÀC(1''')); 5.86 (HÀC(4)) $ 4.75 (HÀC(1''')), 6.49 (HÀC(1')); 6.49
(HÀC(1')) $ 5.86 (HÀC(4), 7.55 (HÀC(2')); 7.55 (HÀC(2')) $ 6.49 (HÀC(1')).HR-EI-MS (70 eV): 426.1653
‡
‡
(M , C22H25F3O5 ; calc.4261. 654).
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Received February 28, 2005