Some applications of ring-closing metathesis to the synthesis of trans- fused oxepane polyethers

Article abstract of DOI:10.1055/s-2000-6265

The synthesis of transfused oxepane systems was achieved via tandem ring-closing metathesis/allylstannane-alde-hyde cyclizations. Repetition of this process in one or two directions provides a reiterative synthesis of trans-fused polyoxepanes.

Full text of DOI:10.1055/s-2000-6265

SPECIAL TOPIC
883
Some Applications of Ring-Closing Metathesis to the Synthesis of trans-Fused
Oxepane Polyethers
Ignacio Brouard, Liu Hanxing, Julio D. Martín*
Instituto de Investigaciones Químicas, Américo Vespucio s/n, Isla de la Cartuja, E-41092 Seville, Spain
Fax +34(95)4460565; E-mail: jdelgado@cica.es
Received 18 January 2000
This article is dedicated to Professor José Barluenga on the occasion of his 60th birthday.
Over the last few years various new synthetic methodolo-
Abstract: The synthesis of trans-fused oxepane systems was
gies have been developed for the specific construction of
achieved via tandem ring-closing metathesis/allylstannane-alde-
hyde cyclizations. Repetition of this process in one or two directions
provides a reiterative synthesis of trans-fused polyoxepanes.
ortho-condensed polyether systems by carbon-carbon and
carbon-oxygen bond-forming reactions.4,5 More recently,
ring-closing metathesis (RCM)6 has been introduced as an
Key words: ring-closing metathesis, oxepanes, trans-fused poly-
ethers, synthetic methods, cyclizations, ruthenium, silicon
efficient methodology for the synthesis of fused-poly-
ethers by intramolecular formation of carbon-carbon dou-
7
ble bonds. Rutheniumbenzylidene catalyst 18 has been
shown to be highly effective in these reactions mostly be-
cause of its high stability, mildness and tolerance to a
wide variety of functional groups. We published recently
an application of the RCM strategy to the synthesis of
trans-fused oxabicyclic systems.7g,o The initial objective
of our efforts in this area was the development of a cy-
clization reaction that would assemble ether rings of vari-
ous sizes from simple acyclic dienes in the trans-
relationship that is found in natural polyethers. Thus, in
our models we considered only terminal olefins on an ox-
ane ring, and we changed chain lengths to explore the in-
fluence on ring size and steric environment of reacting
olefins. Herein we report on the application of RCM tech-
nology to the synthesis of A-C, F-H and K-M fragments
suitable for a convergent approach to the highly flexible
natural mimetic oxepanyl polyether 2 (Scheme 1). We
also explore the possibility to incorporate RCM into con-
vergent synthetic schemes.9
The unique ability of polyoxygenated compounds to se-
lectively interact with charged and neutral molecules has
attained major prominence in chemistry and biology. Nat-
ural polyethers of marine origin1 provide many of the
most striking examples, particularly in terms of their spec-
ificity. Examples of interest in our group include the con-
formationally constrained polyethers: brevetoxins
(BTXs) and ciguatoxins (CTXs), which are selective acti-
vators of voltage-sensitive sodium channels in nerves,
heart and muscle.2 The binding of both groups of trans-
fused polyethers induces a conformational change in the
organization of the protein which tends to stabilize a mul-
tiplicity of different open and/or preopened states of the
channel. In consequence, BTXs and CTXs shift the volt-
age dependence of the activation process in the hyperpo-
larizing direction, slow down the activation kinetics, and
eliminate the inactivation of the Na+ current, inducing a
persisting activation of the channel.2,3
Scheme 1
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

884
I. Brouard et al.
SPECIAL TOPIC
H
H
H
H
H
H
H
In Scheme 2 we report on a combination of the Yamamoto
allylstannane-aldehyde cyclization strategy10 and RCM to
provide ready access to trans-fused oxatricyclic deriva-
tive 25 (A-C fragment). The intramolecular addition of a
stable g-alkoxy-substituted allylstannane to an aldehyde
carbonyl group has been shown to be of particular interest
in the context of trans-fused oxepanyl synthesis since the
resulting cyclization product is a latent version of what
one starts with.4a That is, if one inspects compound 13 re-
sulting from the application of this cyclization method, it
can be readily seen that protection of the free hydroxyl
group followed by one-carbon homologation of the vinyl
appendage regenerates the initial conditions for continu-
ing with the cyclization process. Two different approach-
es for homologation based on RCM are described in
Scheme 2. In one approach, silicon was chosen as a tem-
porary connecting atom between the two olefins since its
derivatives could be readily prepared and the silicon atom
could be easily removed under oxidative conditions.
Thus, allyldimethylsilyl ethers 4 (or 15), prepared by sily-
lation of alkenols 3 (or 13), were submitted to RCM using
Ru-catalyst 1 giving seven-membered silyloxy olefins 5
(or 17).11 Hydrogenation and cleavage of the saturated si-
lyloxy heterocycle using the oxidative conditions devel-
oped by Tamao12 efficiently afforded one-carbon
homologated diols 7 (or 19). Alternatively, conducting
RCM on the acrylic ester derivative 14 gave the a,b-unsat-
urated lactone 16. Hydrogenation followed by reduction
of the saturated lactone with LiAlH4 gave the diol 19.
Both RCM cyclizations proceed well and deliver the de-
sired homologated diols in good yields. It is, however, in-
teresting to note that the rate of ring closure is
significantly slower in the case of the cyclization conduct-
ed on the acrylic ester derivative 14 and that a higher cat-
alyst loading is required to achieve conversion to lactone
16. In this case the reactivity of the carbene may be atten-
uated by the formation of a chelate structure with the ox-
ygen atom of the carbonyl function and the ruthenium
atom.13 In contrast, silyl ether dienes tested in this study
were efficiently cyclized in CH2Cl2 at 25 ºC within 2-3
hours, producing the cyclized silyloxy olefins in essential-
ly quantitative yield. 11
O
O
O
O
a
c
b
Si
Si
Si
O
O
OH
O
H
5
6
3
4
d
R
H
H
H
H
H
O
O
O
H
j
OR1
h
OR
SnBu3
OR2
O
O
H
H
11, R=H, OH
7, R1=R2=H
8, R1=TBS, R2=H
i
e
f
12, R1=O
13, R=H
H
O
H
9, R1=TBS, R2=CH2CH=CH2
10, R1=H, R2=CH2CH=CH2
k
O
g
O
l
14, R=COCH=CH2
a
O
H
H
Si
15, R =
16
b
m
H
H
H
H
H
H
O
O
O
O
OR2
Si
SnBu3
O
h
OR1
O
O
H
17
O
H
H
H
H
H
R
23, R = H, OH
24, R1= O
i
d
19, R1=R2=H
20, R1=TBS, R2=H
c
e
f
j
H
H
21, R1=TBS, R2=CH2CH=CH2
22, R1=H, R2=CH2CH=CH2
O
O
H
H
H
Si
g
O
O
O
H
H
OH
O
H
H
H
18
25
Reagents and conditions: (a) 2.2 equiv of allylchloromethylsilane,
3.0 equiv of Et3N, DMAP catalyst, CH2Cl2, 0-25ºC, 3 h (90%); for
15 (92%); (b) 0.2 mmol diene, 10% of 1, CH2Cl2, 25ºC, 4 h (95%);
for 17 (93%); (c) H2, PtO2 catalyst, EtOAc, 25ºC, 30 min (92%), for
18 (96%); (d) 24.0 equiv of H2O2, 5.0 equiv of KF, 2.0 equiv of
KHCO3, MeOH/THF (1:1), reflux, 12 h (60%); for 19 (66%); (e) 1.5
equiv of t-BuMe2SiCl, 3.0 equiv of imidazole, DMAP catalyst,
CH2Cl2, 0-25ºC, 10 h (80%); for 20 (82%); (f) 2.2 equiv of allyl bro-
mide, 2.2 equiv of KH, Bu4NI catalyst, THF, 0ºC, 8 h, (90%), for 21
(93%); (g) 2.0 equiv of Bu4NF, THF, 25ºC, 6 h (95%); for 22 (98%);
(h) 2.2 equiv of sec-BuLi, THF, -78ºC, 20 min, then add 1.2 equiv
of Bu3SnCl, THF, -78ºC, 10 min (50%); for 23 (58%); (i) 5.0 equiv
of SO3•Py complex, 10.0 equiv. of Et3N, 15.0 equiv of DMSO,
CH2Cl2, 0ºC, 2 h (88%); for 24 (91%); (j) 2.0 equiv of BF3•OEt2,
CH2Cl2, -78ºC, 10 min (98%); for 25 (87%); (k) 2.2 equiv of acry-
loyl chloride, 1.5 equiv of Et3N, CH2Cl2, 20ºC, 4 h (75%); (l) 30
mol% of 1, CH2Cl2, 45ºC, 12 h, (82%); (m) (i) H2, 10% Pd/C catalyst,
3 atm, EtOAc, 25ºC, 4 h (96%); (ii) 3.2 equiv of LiAlH4, Et2O, 0ºC,
4 h (92%)
Scheme 2
HO
H
OH
H
H
H
H
H
O
OR
OR
O
ref. 14
a
SnBu3
Bu3Sn
O
O
O
O
H
H
H
H
H
H
26
27
28, R=H
b
H
H
H
H
O
O
O
d
O
O
29, R=CCH=CH2
c
O
O
O
H
H
H
H
f
H
H
H
H
O
R
1O
OR1
31
H
H
H
H
O
O
H
O
O
O
Si
H
H
H
e
Si
g
30, R=
Si
O
O
OR2
33, R1 = R2=H
34, R1 = H, R2 = TES
R2O
H
H
H
H
As an extension of this methodology in a two-directional
way, we describe in Scheme 3 the synthesis of tetrol 33
(F-H fragment). The readily available oxatricyclic oxepa-
nyl derivative 28 obtained from (E,E,Z)-cyclododecatri-
ene (26) via double cyclization of the bis-allylstannane
2714 was derivatized to tetraenes 29 and 30 and submitted
to RCM using 1 as the catalyst. In these processes, two
rings and two carbon-carbon double bonds are formed in
a single step to yield the unsaturated bis-lactone 31 and
bis-silyloxy ether 32, respectively. Both compounds, 31
and 32, were converted in a two-step sequence into the
tetrol 33 following the above described method. Selective
protection of the primary alcohol groups in 33 followed
by allylation of the secondary hydroxyl groups gave, after
desilylation, compound 36.
32
h
i
j
35, R1 = CH2CH=CH2, R2 = TES
36, R1 = CH2CH=CH2, R2=H
Reagents and conditions: (a) 2.0 equiv of Bu4NIO4, CH2Cl2, 25ºC, 3.5
h then add 4.0 equiv of BF3•OEt2, CH2Cl2, -78 ºC, 5 min, (85%); (b)
3.0 equiv of acryloyl chloride, 2.5 equiv of DMAP, CH2Cl2, 0∞C, 12
h, (76%); (c) 2.3 equiv of allylchlorodimethylsilane, 4.5 equiv of
Et3N, DMAP catalyst, CH2Cl2, 0-25 ºC, 12 h (98%); (d) 30 mol% of
1, CH2Cl2, 25 ºC, 12 h, (83%); (e) 10 mol% of 1, CH2Cl2, 25 ºC, 4 h
(93%); (f) (i) H2, 10%Pd(C) catalyst, EtOAc, 3 atm, 6 h (93%); (ii)
6.0 equiv of LiAlH4, Et2O, 0 ºC, 12 h (92%); (g) (i) H2, PtO2 catalyst,
EtOAc, 25 ºC, 12 h (98%); (ii) 50.0 equiv of H2O2, 12.5 equiv of KF,
8.5 equiv KHCO3, MeOH/THF (1:1), reflux, 12 h (63%); (h) 3.0
equiv of TESCl, 6.0 equiv of imidazole, DMAP catalyst, CH2Cl2, 0-
25 ºC, 15 h (62%); (i) 3.0 equiv of allyl bromide, 3.0 equiv of KH,
Bu4NI catalyst, THF, 0ºC, 12 h (88%); (j) 2.5 equiv of Bu4NF, THF,
25 ºC 8 h (93%).
Scheme 3
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
885
As shown in Scheme 4, compound 49 (K-M fragment) an attractive alternative to intermolecular carbon-carbon
was synthesized from the readily available lactone 41 via bond-forming processes which may require elaborate pro-
the enol triflate 42 and side-chain addition following Mu- tection/deprotection protocols.
rai technology15 to give the vinyl ether 43, which was fur-
ther hydrated to the monocyclic trans-syn-trans oxepanyl
derivative 44. Conversion of 44 to 49 was achieved using
allylstannane/aldehyde cyclization. In line with our ex-
1H NMR spectra were recorded on Bruker spectrometers Avance
DPX 300 (300 MHz) or Avance DRX 500 (500 MHz). Chemical
shifts are reported in parts per million from TMS with the solvent
pectations, diene 50 cleanly cyclized to 51 on reaction
with the ruthenium catalyst 1 in CH2Cl2 at 25 ºC (98%).
The fact that neither the acetal function nor any other ox-
ygen atom of the substrate interferes with RCM illustrates
the excellent compatibility and selectivity of the Grubbs
catalyst. The practical aspects of this reaction in the con-
text of a convergent synthetic scheme to trans-fused ox-
epanyl polyethers will be described in due course.
resonance as the internal standard. Data are reported as follows:
chemical shift multiplicity (s = singlet, d = doublet, t = triplet,
q = quartet, br = broad, m = multiplet), integration, coupling con-
stants (Hz) and assignment. 13C NMR spectra were recorded on
Bruker spectrometers Avance DPX 300 (75 MHz) or Avance DRX
500 (125 MHz) with complete proton decoupling. Chemical shifts
are reported in parts per million from TMS with the solvent as the
internal reference. IR spectra were recorded on a Bruker Vector 22
spectrophotometer. High resolution mass spectra were provided by
the Universities of Seville and Cordoba Mass Spectrometry Facili-
ties and were performed on Kratos MS 80 RFA, Finnigan MAT 95
or Micromass AutoSpecQ spectrometers. Microanalyses were per-
formed on Leco CHNS-932 or Fisons EA1108 CHNS-0. Melting
points were determined on a Buchi 241 apparatus and are uncorrect-
ed. Optical rotations were measured on a Perkin Elmer 341 polarim-
eter, using the sodium D line at 25º C. TLC was reformed using
silica gel 60 F254 precoated plates with a fluorescent indicator, Vi-
sualization was accomplished with one or more of the following:
UV light (254 nm), 10% ethanolic phosphomolybdic acid or H2O/
H2SO4/AcOH (1:4:20) solution and heat as a developing agent.
Flash column chromatography was carried out with E. Merck silica
gel (60, particle size 0.015-0.040 mm) using appropriate mixtures
of EtOAc and hexanes as eluents. All chromatographic separations
were monitored by TLC analyses.
O
OH
H
H
H
OH
OH
a
OTf
H
O
O
HO
COOMe
COOMe
O
O
OH
H
39, R=Me
40, R=H
c
38
37
b
OTBS
I(CH2
H
O
H
O
H
O
O
O
O
O
d
)
3OTBS
O
O
e
O
H
H
H
43
42
41
f
R
H
H
H
O
O
O
O
OR1
i
SnBu3
O
O
OR2
O
H
H
H
H
47, R=H, OH
44, R1=TBS, R2=H
j
g
h
48, R=O
45, R1=TBS, R2=CH2CH=CH 2
46, R1=H, R2=CH2CH=CH 2
Bis(tricyclohexylphosphine)benzylidineruthenium(IV) dichloride
(1) was purchased from Strem Chemicals, stored in a dry-box and
used under argon atmosphere with standard Schlenk techniques. All
other reagents were purchased from Aldrich and used without fur-
ther purification unless otherwise stated. All reactions were con-
ducted in flame-dried glassware under an inert atmosphere of dry
argon. THF, Et2O and benzene were distilled from sodium metal/
benzophenone ketyl. CH2Cl2, MeCN, DMSO and Et3N were dried
over CaH2 and distilled.
k
H
H
H
H
H
H
O
O
O
l
O
RO
O
O
O
O
O
H
H
H
H
H
H
49, R=H
50, R=CH2CH=CH 2
51
g
Reagents and conditions: (a) H2, Pd(C), EtOAc, 25 ºC, 6 h, (98%);
(b) THF aq NaOH, 25 ºC, 2 h (90%); (c) 2.0 equiv of 2,4,6-
Cl3C6H2COCl, 1.5 equiv Et3N, 2.0 equiv of DMAP, 5 Å molecular
sieves, CH2Cl2, 25 ºC, 12 h (85%); (d) 1.3 equiv of LiHMS soln 1.0
M in THF, 1.5 equiv of HMPA, -78 ºC, 2 h, then add 1.5 equiv of
PhNTf2, -78 to 0º C, 1 h, 0-25ºC, 1 h (55%); (e) 6.0 equiv of
I(CH2)3OTBS, 10.0 equiv of t-BuLi (1.7 M in pentane), -120 ºC, 30
min, then add 5.0 equiv Cu(2-Th)(CN)Li, 5.0 equiv of HMPA, 1.0
equiv of vinyl triflate 42, 0ºC, 2 h (70%); (f) 5.0 equiv of BH3•THF,
THF, -30 ºC, 12 h, then excess of NaOH (15.0 equiv), excess of H2O2
(35 equiv), 0 ºC, 25 min (79%); (g) 1.3 equiv of NaH, 10.0 equiv of
allyl bromide, Bu4NI catalyst, THF, 0-25 ºC, 6 h (90%); for 49
(93%); (h) 1.5 equiv of Bu4NF, THF, 25 ºC, 2 h (99%); (i) 2.2 equiv
of sec-BuLi, 1.1 equiv of Bu3SnCl, THF, -78º C, 20 min (76%); (j)
3.0 equiv of SO3•Py, 15.0 equiv of DMSO, 5 equiv Et3N, CH2Cl2, 0ºC,
2 h (81%); (k) 2.0 equiv of BF3•OEt2, CH2Cl2, -78∞C, 5 min (93%);
(l) 0.2 mmol of diene, 10 mol% of 1 0.006 M, CH2Cl2, 25ºC, 2 h
(98%)
Alkoxyallyldimethylsilanes; General Procedure
The alcohol (1.0 mmol) was dissolved in anhyd CH2Cl2 (10 mL)
and cooled with stirring to 0º C under N2. Allylchlorodimethylsilane
(0.33 mL, 2.2 mmol) was then added neat via syringe followed by
Et3N (0.42 mL, 3.0 mmol) and a catalytic amount of DMAP. The
reaction mixture was allowed to warm to r.t. and stirred for 3-5 h.
The mixture was then partitioned between CH2Cl2 and H2O. The
combined organic phases were dried (MgSO4), filtered and concen-
trated in vacuo to afford a crude oil which was further purified by
flash chromatography (silica gel, hexanes/EtOAc, 20:1).
(2R,3S)-Allyldimethyl-(2-vinyltetrahydropyran-3-yloxy)si-
lane(4)
Following the above described protocol, 3 (128.2 mg, 1.0 mmol)
was converted to 4 (203.5 mg, 0.9 mmol, 90%) to yield a colourless
oil; [a]D 25+25.4 (c = 0.18, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.88 (ddd, 1 H, J = 5.7, 10.7, 17.3
Hz, H-1’’), 5.74 (dddd, 1 H, J = 8.0, 8.0, 10.1, 17.0 Hz, H-2’), 5.29
(ddd, 1 H, J = 1.7, 1.7, 17.3 Hz, H-2’’), 5.16 (ddd, 1 H, J = 1.6, 10.7
Hz, H-2’’), 4.86 (dd, 1 H, J = 1.9, 17.0 Hz, H-3’), 4.83 (dd, 1 H,
J = 2.0, 10.1 Hz, H-3’), 3.91 (ddd, 1 H, J = 4.0, 4.2, 14.4 Hz, H-6),
3.48 (dddd, 1 H, J = 1.3, 1.3, 5.7, 8.8 Hz, H-2), 3.35 (br dd, 1 H,
J = 3.6, 11.2, 14.4 Hz, H-6), 3.30 (ddd, 1 H, J = 4.6, 8.8, 10.5 Hz,
H-3), 1.98 (dddd, 1 H, J = 1.6, 3.7, 8.3, 12.9 Hz, H-4), 1.71-1.60
Scheme 4
In conclusion, we have shown that the tandem ring-clos-
ing metathesis/allyltin-aldehyde cyclization is an eco-
nomical intramolecular strategy for the synthesis of
complex trans-fused oxepanyl polyethers. In particular,
the consecutive application of these two reactions offers
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

886
I. Brouard et al.
SPECIAL TOPIC
HRMS: m/z calcd for C10H20O2Si 200.1233, found 200.1234.
(m, 2 H, 2 H-5), 1.57 (br dd, 2 H, J = 8.0, 8.0 Hz, 2 H-1’), 1.55-1.45
(m, 1 H, H-4), 0.08 [s, 6 H, (CH3)2Si].
13C NMR (125 MHz, CDCl3): d = 136.7 (CH, C1’’), 134.0 (CH, C2’),
116.6 (CH2, C2’’), 113.8 (CH2, C3’), 82.9 (CH, C2), 71.4 (CH, C3),
67.5 (CH2, C6), 33.6 (CH2, C4), 25.5 (CH2, C5), 25.1 (CH2, C1’),
-1.7 [CH3, (CH3)2Si].
IR (KBr): n = 3022, 1728, 1245 cm-1.
(2R, 3S)-2-(3-Hydroxypropyl)tetrahydropyran-3-ol (7)
A stirred solution of 6 (1.60 g, 8.03 mmol) in THF/MeOH (70 mL)
was treated with KF (2.33 g, 40.1 mmol), KHCO3 (1.55 g,
15.5 mmol) and 30% H2O2 (8.28 mL, 128.3 mmol), and refluxed for
12 h. The mixture was cooled, diluted with EtOAc (60 mL), washed
with brine (3 × 60 mL), dried (MgSO4) and the solvent evaporated.
Flash chromatography (silica, hexanes/EtOAc, 3:1) gave the diol 7
HRMS: m/z calcd for C12H22O2Si 226.1389, found 226.1389.
IR (film): n 3010, 1461, 1458 cm-1.
25
Olefin Metathesis; General Procedure
(771.2 mg, 4.82 mmol, 60%) as a colourless oil; [a]D +34.3
The amount of catalyst necessary in each case was weighed and dis-
solved in anhyd CH2Cl2 in a flame-dried vessel. A solution of the
corresponding diene in CH2Cl2 was then added dropwise via a can-
nula to the above solution under an atmosphere of dry argon (final
concentration of diene was 0.005 M). When the addition was over,
the vessel was sealed and the reaction mixture was stirred at r.t.
Progress of reaction was monitored by TLC and NMR. When the re-
action was complete or when no further progress was observed, the
solvent was removed in vacuo and the residue was purified by flash
chromatography (silica gel, hexanes/EtOAc, 4:1) affording the ex-
pected unsaturated heterocycle.
(c = 0.72, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.86 (ddd, 1 H, J = 2.0, 4.1, 11.3
Hz, H-6), 3.61 (dddd, 2 H, J = 5.2, 5.2, 10.8, 13.8 Hz, 2H-3’), 3.33-
3.26 (m, 2 H, H-3, H-6), 3.00 (ddd, 1 H, J = 2.0, 8.7, 8.7 Hz, H-2),
2.06 (dddd, 1 H, J = 2.0, 4.0, 4.0, 12.4 Hz, H-4), 1.98 (dddd, 1 H,
J = 2.0, 7.3, 7.3, 14.5 Hz, H-1’), 1.72-1.62 (m, 4 H, 2 H-5, 2 H-2’),
1.48 (ddd, 1 H, J = 7.0, 8.4, 14.5 Hz, H-1’), 1.38 (ddd, 1 H, J = 8.5,
8.5, 11.0 Hz, H-2’).
13C NMR (125 MHz, CDCl3): d = 82.4 (CH, C2), 69.9 (CH, C3),
67.6 (CH2, C6), 62.6 (CH2, C3’), 32.8 (CH2, C4), 28.7 (CH2, C1’),
28.5 (CH2, C2’), 25.6 (CH2, C5).
(4aR,9aS)-6,6-Dimethyl-3,4,4a,6,7,9a-hexahydro-2H-1,5-dioxa-
6-silabenzocycloheptene (5)
Following the above described protocol, 4 (200 mg, 0.88 mmol)
was converted to 5 (166 mg, 0.84 mmol, 95%), colourless oil;
[a]D25+27.7 (c = 1.75, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.78 (dddd, 1 H, J = 2.0, 7.0, 8.0,
11.4 Hz, H-8), 5.41 (ddd, 1 H, J = 2.0, 4.4, 11.4 Hz, H-9), 3.87 (ddd,
1 H, J = 2.2, 2.2, 14.4 Hz, H-2), 3.84 (ddd, 1 H, J = 2.0, 4.4, 10.4
Hz, H-9a), 3.61 (ddd, 1 H, J = 4.9, 4.9, 10.4 Hz, H-4a), 3.29 (ddd,
1 H, J = 5.7, 11.2, 14.4 Hz, H-2), 2.04 (dddd, 1H, J = 3.2, 3.2, 4.9,
13.6 Hz, H-4), 1.65-1.58 (m, 3 H, 2 H-3, H-7), 1.48-1.41 (m, 2 H,
H-4, H-7), 0.11 (s, 3 H, CH3Si), 0.09 (s, 3 H, CH3Si).
13C NMR (125 MHz, CDCl3): d = 131.1 (CH, C9), 126.5 (CH, C8),
80.8 (CH, C9a), 71.2 (CH, C4a), 67.4 (CH2, C2), 33.7 (CH2, C4), 25.4
(CH2, C3), 18.5 (CH2, C7), -0.2 (CH3, CH3Si), -2.2 (CH3, CH3Si).
HRMS: m/z C8H16O3 161.1178 (M + H)+, found 161.1182.
IR (film): n = 3622, 3413, 1728 cm-1.
Protection of Primary Alcohols as TBDMS Ethers; General
Procedure
To a stirred solution of the corresponding diol (2.2 mmol) in anhyd
CH2Cl2 (12 mL) were added imidazole (425 mg, 6.25 mmol),
TBDMSCl (413 mg, 2.75 mmol) and a catalytic amount of DMAP
at 0 ºC. The mixture was stirred until TLC showed no remaining
starting material (10-15 h) and then quenched by the addition of aq
satd NH4Cl solution (10 mL). The two layers were separated and the
organic layer washed with brine and dried (MgSO4). Solvent was
removed under reduced pressure and the remaining oil was purified
by flash chromatography (silica gel, hexanes/EtOAc, 4:1).
(2R,3S)-2-[(3’-tert-Butyldimethylsilanyloxy)propyl]tetrahydro-
pyran-3-ol (8)
Following the above described protocol, 7 (835 mg, 5.22 mmol)
was converted to 8 (1.15 g, 4.18 mmol, 80%); colourless oil;
[a]D25+22.8 (c = 1.78, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.86 (dddd, 1 H, J = 2.5, 2.5, 4.2,
11.4 Hz, H-6), 3.62 (ddd, 2 H, J = 2.0, 6.4, 6.4 Hz, 2 H-3’), 3.34-
3.26 (m, 2 H, H-3, H-6), 2.99 (ddd, 1 H, J = 3.1, 8.5, 8.5 Hz, H-2),
2.06 (dddd, 1 H, J = 2.0, 3.7, 4.0, 12.1 Hz, H-4), 1.86 (dddd, 1 H,
J = 3.2, 6.0, 12.7, 14.9 Hz, H-1’), 1.74 (br ddd, 1 H, J = 5.2, 6.5,
13.2 Hz, H-2’) 1.69-1.62 (m, 2 H, 2 H-5), 1.57 (dddd, 1 H, J = 6.2,
6.2, 9.4, 13.2 Hz, H-2’), 1.46 (br dd, 1 H, J = 5.3, 9.3 Hz, H-1’),
1.37 (br dd, 1 H, J = 10.4, 12.4 Hz, H-4), 0.86 [s, 9 H, (CH3)3CSi],
0.02 [s, 6 H, (CH3)2Si].
HRMS: m/z calcd for C10H18O2Si 198.1076, found 198.1077.
IR (film): n = 3040, 1601, 1084 cm-1.
(4aR,9aS)-6,6-Dimethyloctahydro-1,5-dioxa-6-silabenzocyclo-
heptene (6)
A solution of 5 (160 mg, 0.81 mmol) in EtOAc (15 mL), containing
15 mg of PtO2 was stirred under hydrogen pressure at 25 º C. After
30 min, GC-analysis indicated complete transformation of the start-
ing material into a single product. The mixture was filtered, the sol-
vent evaporated under pressure and the residue was purified by
flash chromatography (silica, hexanes/EtOAc, 10:1) to give 6
(149.1 mg, 0.74 mmol, 92%) as a colourless foam; [a]D25+28.2
(c = 1.12, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.80 (ddd, 1 H, J = 3.9, 3.9, 11.2
Hz, H-2), 3.31 (ddd, 1 H, J = 4.9, 8.8, 10.5 Hz, H-4a), 3.24 (ddd,
1 H, J = 5.9, 8.8, 11.2 Hz, H-2), 3.00 (ddd, 1 H, J = 3.8, 8.8, 8.9 Hz,
H-9a), 2.05 (dddd, 1 H, J = 3.8, 7.8, 12.7, 13.8 Hz, H-9), 1.98
(dddd, 1 H, J = 2.0, 3.4, 3.4, 13.1 Hz, H-4), 1.84 (ddddd, 1 H,
J = 1.6, 3.2, 7.4, 7.4, 14.4 Hz, H-8), 1.62-1.57 (m, 2 H, 2 H-3), 1.48
(br dd, 1 H, J = 12.8, 14.4 Hz, H-8), 1.41 (br ddd, 1 H, J = 2.1, 10.5,
13.1 Hz, H-4), 1.28 (dddd, 1 H, J = 1.8, 3.8, 13.7, 13.8 Hz, H-9),
0.76 (dddd, 1 H, J = 2.0, 2.0, 7.4, 15.2 Hz, H-7), 0.57 (ddd, 1 H,
J = 3.1, 12.8, 15.2 Hz, H-7), 0.09 (s, 3 H, CH3Si), 0.01 (s, 3 H,
CH3Si).
13C NMR (125 MHz, CDCl3): d = 82.2 (CH, C2), 70.5 (CH, C3),
67.5(CH2, C6), 63.4 (CH2, C3’), 32.7 (CH2, C4), 28.4 (CH2, C1’), 28.4
(CH2, C2’), 26.0 [CH3, (CH3)3CSi], 25.7 (CH2, C5), 18.2 (Cq), -5.2
[CH3, (CH3)2Si].
HRMS: m/z calcd for C14H30O3Si 275.2043 (M + H)+, found
275.2043.
IR (film): n = 3400, 2863, 1600, 1085 cm-1.
(2’R,3’S)-3-[3’-(3’’-Tributylstannylpropenyloxy)tetrahydropy-
ran-2’-yl]-propan-1-ol (11)
sec-BuLi (2.82 mL, 36.6 mmol, 1.3 M in cyclohexene) was added
under argon at -78 ºC to a solution of 10 (1.83 g, 9.15 mmol) in an-
hyd THF (30 mL). To the resulting solution was added Bu3SnCl
13C NMR (125 MHz, CDCl3): d = 82.9 (CH, C9a), 72.5 (CH, C4a),
67.3 (CH2, C2), 38.6 (CH2, C9), 33.7 (CH2, C4), 25.6 (CH2, C3), 19.0
(CH2, C8), 17.3 (CH2, C7), 0.8 (CH3, CH3Si), 0.9 (CH3, CH3Si).
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
887
(5.92 mL, 21.96 mmol) at -78 ºC over 10 min. The mixture was
maintained at -78 ºC for 15 min, aq NH4Cl solution (100 mL) was
then added and the resulting aqueous suspension was saturated with
NaCl and extracted with Et2O (3 × 50 mL). The combined organic
extracts were dried (MgSO4) and concentrated and the residue was
purified by flash column chromatography (silica gel, hexanes/
EtOAc, 5:3) to yield 11 (2.24 g, 4.56 mmol, 50%); colourless oil:
[a]D25+17.6 (c = 0.59, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.77 (d, 1 H, J = 6.0 Hz, H-1’’),
4.50 (ddd, 1 H, J = 6.0, 9.1, 9.1 Hz, H-2’’), 3.90 (dddd, 1 H, J = 1.9,
1.9, 3.7, 11.2 Hz, H-6’), 3.61 (ddd, 2 H, J = 5.3, 10.8, 11.1 Hz, 2 H-
1), 3.33 (ddd, 1 H, J = 3.6, 11.2, 11.2 Hz, H-6’), 3.24 (ddd, 1 H,
J = 4.5, 10.6, 10.6 Hz, H-3’), 3.17 (ddd, 1 H, J = 2.3, 8.8, 8.8 Hz, H-
2’), 2.15 (ddd, 1 H, J = 4.5, 4.5, 12.5 Hz, H-4’), 2.00 (dddd, 1 H,
J = 2.3, 7.1, 7.1, 14.2 Hz, H-3), 1.74-1.64 (m, 4 H, 2 H-2, 2 H-5’),
1.60 (dd, 2 H, J = 9.1, 9.1 Hz, 2 H-3’’), 1.50-1.38 (m, 8 H, H-3, H-
4’, 3 × CH2), 1.31-1.21 (m, 6 H, 3 × CH2), 0.89-0.85 (m, 9 H,
3 × CH3), 0.82-0.81 (m, 6 H, 3 × CH2).
hexanes/EtOAc, 2:1) afforded cyclized compounds in yields vary-
ing from 88% to 98%.
(4aS,6R,7S,9aR)-6-Vinyloctahydro-1,5-dioxabenzocyclohep-
ten- 7-ol (13)
Following the above described protocol, 12 (130 mg, 0.27 mmol)
was converted to 13 (51.7 mg, 0.26 mmol, 98%); colourless foam;
[a]D25+42.7 (c = 1.13, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.87 (ddd, 1H, J = 6.0, 10.5, 17.2
Hz, H-1’), 5.30 (ddd, 1 H, J = 1.6, 1.6, 17.2 Hz, H-2’), 5.16 (ddd, 1
H, J = 1.5, 1.5, 10.5 Hz, H-2’), 3.85 (dddd, 1 H, J = 1.8, 1.8, 4.0,
11.3 Hz, H-2), 3.77 (dddd, 1 H, J = 1.4, 1.4, 6.0, 8.0 Hz, H-6), 3.71
(ddd, 1 H, J = 3.8, 3.8, 8.0 Hz, H-7), 3.30 (br dd, 1 H, J = 11.3, 15.1
Hz, H-2), 3.21 (ddd, 1 H, J = 4.3, 9.1, 11.1 Hz, H-4a), 3.00 (dddd,
1 H, J = 5.5, 7.5, 9.1, 13.1 Hz, H-9a), 2.06 (dddd, 1 H, J = 1.6, 3.6,
7.8, 12.6 Hz, H-4), 1.94-1.88 (m, 2 H, 2 H-8), 1.87-1.82 (m, 2 H,
2 H-9), 1.68-1.62 (m, 2 H, 2 H-3), 1.49-1.40 (m, 1 H, H-4).
13C NMR (125 MHz, CDCl3): d = 137.7 (CH, C1’), 115.9 (CH2, C2’),
86.4 (CH, C6), 83.1 (CH, C9a), 82.1 (CH, C4a), 73.6 (CH, C7), 67.8
(CH2, C2), 31.4 (CH2, C4), 29.7 (CH2, C8), 27.5 (CH2, C9), 25.9
(CH2, C3).
13C NMR (125 MHz, CDCl3): d = 140.1(CH, C1’’), 106.2 (CH, C2’’),
81.0 (CH, C2’), 79.2 (CH, C3’), 67.7 (CH, C6’), 63.0 (CH, C1), 30.3
(CH2, C4’), 29.2 (CH2, C3), 29.2 (CH2, C2), 29.2 (CH2), 27.3 (CH2),
25.4 (CH2, C5’), 13.7 (CH3), 9.3 (CH2), 5.9 (CH2, C3’’).
HRMS: m/z calcd for C23H46O3120 Sn 490.2469, found 490.2466.
IR (film): n = 3623, 2360, 1648, 1463 cm-1.
HRMS: m/z calcd for C11H18O3 198.1256, found 198.1253.
IR (KBr): n = 3695, 3010, 1601, 1235 cm-1.
(4aS,6R,7S,9aR)-Allyldimethyl-(6-vinyloctahydro-1,5-dioxa-
benzocyclohepten-7-yloxy)silane (15)
Following the above described protocol (see general procedure for
the preparation of alkoxyallyldimethyl silanes) 14 (198.1 mg, 1.0
mmol) was converted to 15 (272.3 mg, 0.92 mmol, 92%); colourless
oil; [a]D25+18.3 (c = 1.42, CHCl3).
(2’R,3’S)-3-[3’-(3’’-Tributylstannylpropenyloxy)tetrahydropy-
ran- 2-yl]propionaldehyde (12)
A mixture of alcohol 11 (161.5 mg, 0.33 mmol) and Et3N (0.46 mL,
3.30 mmol) in CH2Cl2/DMSO (3.5 mL, 1:1) was treated at 0 ºC with
SO3•pyridine (260 mg, 1.65 mmol). After stirring at 0 ºC for 2 h, the
mixture was diluted with Et2O (25 mL), washed with brine (20 mL)
and dried (MgSO4). Filtration, concentration and flash chromatog-
raphy (silica gel, hexanes/EtOAc, 9:1) gave the aldehyde 12 (141.8
mg, 0.29 mmol, 88%) as a colourless foam; [a]D25+32.5 (c = 1.13,
CHCl3).
1H NMR (500 MHz, CDCl3): d = 9.72 (s, 1 H, H-1), 5.76 (br d, 1 H,
J = 6.1 Hz, H-1’’), 4.50 (ddd, 1 H, J = 6.1, 9.1, 9.1 Hz, H-2’’), 3.84
(ddd, 1 H, J = 2.2, 2.2, 11.5 Hz, H-6’), 3.26 (ddd, 1 H, J = 3.2, 11.2,
11.5 Hz, H-6’), 3.21 (ddd, 1 H, J = 4.5, 10.6, 10.6 Hz, H-3’), 3.12
(ddd, 1 H, J = 2.8, 8.9, 8.9 Hz, H-2’), 2.53 (br ddd, 1 H, J = 2.0, 7.4,
14.7 Hz, H-2), 2.45 (br ddd, 1 H, J = 1.7, 8.0, 14.7 Hz, H-2), 2.19
(ddd, 1 H, J = 3.0, 7.0, 14.5 Hz, H-3), 2.14 (ddd, 1 H, J = 4.7, 8.0,
12.6 Hz, H-4’), 1.73 (ddd, 1 H, J = 7.3, 14.5, 14.5 Hz, H-3), 1.70-
1.63 (m, 2 H, 2 H-5’), 1.61 (br dd, 2 H, J = 9.0, 11.4 Hz, 2 H-3’’),
1.49-1.44 (m, 6 H, CH2), 1.39 (ddd, 1 H, J = 9.0, 10.5, 12.6 Hz, H-
4’), 1.30-1.23 (m, 6 H, 3 × CH2), 0.88-0.83 (m, 9 H, 3 × CH3),
0.81-0.78 (m, 6 H, 3 × CH2).
1H NMR (500 MHz, CDCl3): d = 5.80 (ddd, 1 H, J = 5.5, 10.6, 17.1
Hz, H-1’’), 5.73 (dddd, 1 H, J = 8.3, 8.3, 10.2, 16.6 Hz, H-2’) 5.25
(ddd, 1 H, J = 1.8, 1.8, 17.1 Hz, H-2’’), 5.08 (ddd, 1 H, J = 1.7, 1.7,
10.6 Hz, H-2’’), 4.86 (dd, 1 H, J = 1.5, 16.6 Hz, H-3’), 4.84 (dd, 1
H, J = 1.0, 10.2 Hz, H-3’), 3.87-3.83 (m, 2 H, H-2, H-6), 3.78 (ddd,
1 H, J = 4.2, 4.2, 8.7 Hz, H-7), 3.29 (ddd, 1 H, J = 6.4, 11.0, 14.7
Hz, H-2), 3.24 (ddd, 1 H, J = 4.5, 9.6, 11.2 Hz, H-4a), 2.96 (ddd, 1
H, J = 4.1, 9.6, 9.6 Hz, H-9a), 2.05 (dddd, 1 H, J = 4.4, 4.4, 12.6
Hz, H-4), 1.87 (dddd, 1 H, J = 5.8, 9.6, 10.5, 14.2 Hz, H-9), 1.77-
1.72 (m, 3 H, 2 H-8, H-9), 1.66-1.60 (m, 2 H, 2 H-3), 1.58 (dd, 2
H, J = 8.3, 8.3 Hz, 2 H-3), 1.41 (br ddd, 1 H, J = 10.0, 11.2, 12.6
Hz, H-4), 0.08 [s, 6 H, (CH3)2Si].
13C NMR (125 MHz, CDCl3): d = 137.7 (CH, C1’’), 133.9 (CH, C2’),
114.9 (CH2, C2’’), 113.8 (CH2, C3’), 86.3 (CH, C6), 82.8 (CH, C9a),
80.5 (CH, C4a), 74.8 (CH, C7), 67.7 (CH2, C2), 31.5 (CH2, C4), 28.8
(CH2, C8), 26.9 (CH2, C3), 25.8 (CH2, C3), 25.0 (CH2, C1’), -1.8
[CH3, (CH3)2Si].
HRMS: m/z calcd for C16H28O3Si 296.1808, found 296.1807.
IR (film): n = 3695, 3018, 1620, 1601, 1235 cm-1.
13C NMR (125 MHz, CDCl3): d = 202.6 (CH, C1), 140.0 (CH, C1’’),
106.4 (CH, C2’’), 79.9 (CH, C2’), 79.2 (CH, C3’), 67.6 (CH2, C6’),
40.1 (CH2, C2), 30.3 (CH2, C4’), 29.1 (CH2), 27.3 (CH2), 25.4 (CH2,
C5’), 25.1 (CH2, C3), 13.7 (CH3), 9.3 (CH2), 5.9 (CH2, C3’’).
(4aR,5aS,9aR,11aS)-6,7,8,9a,10,11,11a-Octahydro-4aH-1,5,9-
trioxadibenzo[a,d]cyclohepten-2-one (16)
Acryloyl ester 14 (142.1 mg, 0.56 mmol) was converted following
the above described protocol for olefin metathesis into 16
(105.1 mg, 0.46 mmol, 82%); colourless foam; [a]D25+17.6
(c = 0.21, CHCl3).
HRMS: m/z calcd for C23H44O3120 Sn 488.2312, found 488.2320.
IR (KBr): n = 2953, 1739, 1472 cm-1.
1H NMR (500 MHz, CDCl3): d = 6.81 (dd, 1 H, J = 1.4, 10.0 Hz, H-
3), 5.89 (dd, 1 H, J = 2.3, 10.0 Hz, H-4), 4.26 (ddd, 1 H, J = 2.0, 2.0,
10.7 Hz, H-4a), 4.22 (ddd, 1 H, J = 6.4, 6.4, 10.7 Hz, H-11a), 3.86
(dddd, 1 H, J = 2.0, 2.0, 4.3, 12.2 Hz, H-8), 3.27 (ddd, 1 H, J = 4.7,
7.4, 12.2 Hz, H-8), 3.24 (ddd, 1 H, J = 4.4, 4.4, 9.0 Hz, H-5a), 3.07
(ddd, 1 H, J = 4.8, 7.3, 9.0 Hz, H-9a), 2.18 (dddd, 1 H, J = 5.0, 6.4,
11.0, 18.0 Hz, H-11), 2.14-2.10 (m, 1 H, H-6), 2.10 (dddd, 1 H,
J = 4.0, 6.4, 7.8, 18.0 Hz, H-11), 2.02 (dddd, 1 H, J = 4.0, 4.8, 11.0,
16.0 Hz, H-10), 1.91 (dddd, 1 H, J = 5.0, 7.3, 7.8, 16.0 Hz, H-10),
Allylstannane-Aldehyde Cyclization; General Procedure
To a solution of allylstannane (1.0 mmol) in anhyd CH2Cl2 (30 mL)
was added dropwise BF3•OEt2 (20.0 mL of 0.1 M in CH2Cl2,
2.0 mmol) over a period of 15-20 min at -78 ºC. After 10-20 min
at -78 ºC the mixture was slowly warmed to -10 ºC over 5 min pe-
riod and then poured onto a stirred mixture of CH2Cl2 (30 mL) and
aq satd NaHCO3 solution (100 mL). After separation, the organic
portion was washed with H2O (2 × 50 mL) and dried (MgSO4). Fil-
tration, concentration and flash column chromatography (silica gel,
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

888
I. Brouard et al.
SPECIAL TOPIC
1.70-1.64 (m, 2 H, 2 H-7), 1.44 (dddd, 1 H, J = 7.5, 11.0, 12.3, 17.0
(ddd, 1 H, J = 4.3, 9.1, 13.4 Hz, H-4a), 2.95 (ddd, 1 H, J = 4.2, 8.9,
8.9 Hz, H-9a), 2.05 (dddd, 1 H, J = 1.5, 3.7, 3.9, 12.5 Hz, H-4),
1.85-1.74 (m, 5 H, 2 H-8, 2 H-9, H-1’), 1.71 (ddd, 1 H, J = 6.0, 7.8,
13.7 Hz, H-2’), 1.66-1.58 (m, 3 H, 2 H-3, H-2’), 1.48 (dddd, 1 H,
J = 6.0, 7.8, 9.5, 13.8 Hz, H-1’), 1.40 (br ddd, 1 H, J = 1.2, 6.6,
11.2, 13.4 Hz, H-4).
13C NMR (125 MHz, CDCl3): d = 86.1 (CH, C6), 83.1 (CH, C9a),
82.9 (CH, C4a), 74.6 (CH, C7), 67.8 (CH2, C2), 62.4 (CH2, C3’), 31.4
(CH2, C1’), 31.1 (CH2, C4), 30.4 (CH2, C8), 29.1 (CH2, C2’), 27.1
(CH2, C9), 25.8 (CH2, C3).
Hz, H-6).
13C NMR (125 MHz, CDCl3): d = 163.5 (Cq, C2), 150.1 (CH, C3),
119.9 (CH, C4), 81.7 (CH, C5a), 81.6 (CH, C9a), 81.4 (CH, C11a),
75.7 (CH, C4a), 67.8 (CH2, C8), 31.1 (CH2, C6), 29.6 (CH2, C10), 28.4
(CH2, C11), 25.8 (CH2, C7).
HRMS: m/z calcd for C12H16O4 224.1048, found 224.1047.
IR (KBr): n = 2928, 2855, 1732, 1463, 1380 cm-1.
(4aS,5aR,10aS,12aR)-9,9-Dimethyl-3,4,4a,5a,8,9,10a,11,12,12a-
decahydro-2H-1,5,10-trioxa-9-silabenzo[b]heptalene (17)
Following the general protocol described above for olefin metathe-
sis, 15 (270 mg, 0.91 mmol) was converted to 17 (226.8 mg,
0.85 mmol, 93%); colourless oil; [a]D25+34.1 (c = 1.18, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.65 (dddd, 1 H, J = 1.7, 5.4, 8.7,
11.0 Hz, H-6), 5.59 (ddd, 1 H, J = 2.8, 5.1, 11.0 Hz, H-7), 4.12 (ddd,
1 H, J = 5.8, 7.5, 8.7 Hz, H-5a), 3.92 (ddd, 1 H, J = 2.4, 4.2, 8.0 Hz,
H-10a), 3.85 (dddd, 1 H, J = 1.8, 1.8, 4.0, 11.3 Hz, H-2), 3.29 (ddd,
1 H, J = 8.2, 8.2, 11.3 Hz, H-2), 3.12 (ddd, 1 H, J = 4.1, 9.3, 11.2
Hz, H-4a), 2.91 (ddd, 1 H, J = 3.3, 9.3, 9.3 Hz, H-12a), 2.04 (dddd,
1 H, J = 1.6, 3.6, 7.5, 12.4 Hz, H-4), 1.93-1.83 (m, 1 H, H-12),
1.82-1.74 (m, 3 H, 2 H-11, H-12), 1.74-1.66 (m, 1 H, H-8), 1.67-
1.60 (m, 2 H, 2 H-3), 1.44 (dddd, 1 H, J = 11.2, 11.2, 12.4 Hz, H-
4), 1.30-1.24 (m, 1 H, H-8), 0.09 (s, 3 H, CH3Si), 0.06 (s, 3 H,
CH3Si).
HRMS: m/z calcd for C12H22O4 230.1518, found 230.1519.
IR (film): n = 3622, 3413, 3011, 2360 cm-1.
(4aS,6R,7S,9aR)-6-(tert-Butyldimethylsilanyloxypropyl)octahy-
dro-1,5-dioxabenzocyclohepten-7-ol (20)
Following the same procedure used to convert 7 to 8, diol 19 (318
mg, 1.38 mmol) was converted to 20 (389.3 mg, 1.13 mmol, 82%),
colourless foam; [a]D25+26.2 (c = 1.42, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.83 (dddd, 1 H, J = 2.0, 2.0, 4.0,
11.4 Hz, H-2), 3.68 (br s, 1 H, H-7), 3.60 (ddd, 2 H, J = 3.5, 6.3,
16.2 Hz, 2 H-3´), 3.31-3.22 (m, 2 H, H-2, H-6), 3.04 (ddd, 1 H,
J = 4.3, 9.1, 11.1 Hz, H-4a), 2.93 (ddd, 1 H, J = 4.0, 9.0, 9.0 Hz, H-
9a), 2.03 (ddd, 1 H, J = 1.5, 3.7, 4.0, 12.5 Hz, H-4), 1.88-1.75 (m,
4 H, 2 H-8, 2 H-9), 1.75-1.66 (m, 2 H, H-1’, H-2’), 1.66-1.60 (m,
2 H, 2 H-3), 1.60-1.55 (m, 1 H, H-2’), 1.49-1.35 (m, 2 H, H-4, H-
1’), 0.86 [s, 9 H, CH3)3CSi], 0.02 [6 H, (CH3)2Si].
13C NMR (125 MHz, CDCl3): d = 86.3 (CH, C6), 83.3 (CH, C9a),
83.0 (CH, C4a), 74.8 (CH, C7), 67.8 (CH2, C2), 62.3 (CH2, C3’), 31.7
(CH2, C1’), 31.3 (CH2, C4), 30.4 (CH2, C8), 29.4 (CH2, C2’), 27.2
(CH2, C9), 26.0 [CH3, (CH3)3CSi], 25.9 (CH2, C3), 18.5 [C,
(CH3)3CSi], 5.3 [CH3, (CH3)2Si].
13C NMR (125 MHz, CDCl3): d = 134.4 (CH, C7), 124.0 (CH, C6),
84.4 (CH, C5a), 84.5 (CH, C4a), 84.2 (CH, C12a), 76.2 (CH, C10a),
67.9 (CH2, C2), 31.8 (CH2, C11), 31.6 (CH2, C4), 27.4 (CH2, C12),
26.1 (CH2, C3), 18.9 (CH2, C8), -0.5 (CH3, CH3Si), -0.2 (CH3,
CH3Si).
HRMS: m/z calcd for C14H24O3Si 268.1494, found 268.1495.
IR (film): n = 3691, 3019, 1602, 1265 cm-1.
HRMS: m/z calcd for C18H36O4Si 344.2382, found 344.2387.
IR (KBr): n = 3400, 3010, 1600, 1218 cm-1.
(4aS,5aR,10aS,12aR)-9,9-Dimethyldodecahydro-2H-1,5,10-tri-
oxa-9-silabenzo[b]heptalene (18)
Following the same procedure used to convert 5 to 6, compound 17
(225 mg, 0.84 mmol) was converted to 18 (217.8 mg, 0.81 mmol,
96%); colourless oil; [a]D25+36.2 (c = 1.43, CHCl3).
(1’’Z)-(4’aS,6’R,7’S,9’aR)-3-[7-(3-Tributylestannylpropenyl-
oxy)octahydro-1,5-dioxabenzocyclohepten-6-yl]propan-1-ol
(23)
Following the same procedure to convert 10 to 11, compound 22
(120 mg, 0.44 mmol) was converted to 23 (144 mg, 0.26 mmol,
58%) as a colourless foam; [a]D +31.4 (c = 0.93, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.84 (dddd, 1 H, J = 2.0, 2.0, 4.0,
11.4 Hz, H-2), 3.73 (ddd, 1 H, J = 3.7, 7.7, 11.1 Hz, H-5a), 3.28
(ddd, 1 H, J = 3.7, 8.0, 11.4 Hz, H-2), 3.22 (ddd, 1 H, J = 3.5, 7.7,
11.0 Hz, H-10a), 3.18 (ddd, 1 H, J = 4.1, 9.3, 11.2 Hz, H-4a), 2.89
(ddd, 1 H, J = 3.9, 9.3, 9.3 Hz, H-12a), 2.06 (ddd, 1 H, J = 2.9, 6.3,
9.9 Hz, H-11), 2.00 (dddd, 1 H, J = 1.6, 3.9, 7.8, 12.4 Hz, H-4),
1.90-1.73 (m, 5 H, 2 H-6, H-7, 2 H-12), 1.66-1.61 (m, 2 H, 2H-3),
1.51 (dddd, 1 H, J = 2.3, 4.4, 11.9, 11.9 Hz, H-7), 1.49-1.38 (m, 2
H, H-4, H-11), 0.69 (ddd, 1 H, J = 2.7, 8.0, 15.3 Hz, H-8), 0.62
(ddd, 1 H, J = 2.8, 12.2, 15.3 Hz, H-8), 0.08 (s, 3 H, CH3Si), 0.05
(s, 3 H, CH3Si).
13C NMR (125 MHz, CDCl3): d = 88.0 (CH, C10a), 84.7 (CH, C4a),
84.0 (CH, C12a), 76.2 (CH, C5a), 67.9 (CH2, C2), 38.9 (CH2, C11),
31.8 (CH2, C4), 31.8 (CH2, C12), 27.5 (CH2, C6), 26.1 (CH2, C7),
19.7 (CH2, C7), 15.7 (CH2, C8), 1.0 (CH3, CH3Si), -1.4 (CH3,
CH3Si).
1H NMR (500 MHz, CDCl3): d = 5.66 (d, 1 H, J = 6.0 Hz, H-1’’),
5.53 (ddd, 1 H, J = 6.0, 9.1, 9.1 Hz, H-2’’), 3.84 (dddd, 1 H, J = 2.0,
2.0, 4.0, 11.4 Hz, H-2´), 3.63-3.59 (m, 2 H, 2 H-1), 3.58 (ddd, 1 H,
J = 3.5, 3.5, 5.8 Hz, H-7’), 3.46 (ddd, 1 H, J = 2.8, 5.7, 9.2 Hz, H-
6’), 3.28 (ddd, 1 H, J = 3.8, 8.8, 11.4 Hz, H-2’), 3.14 (ddd, 1 H,
J = 4.4, 9.1, 11.2 Hz, H-4’a), 2.94 (ddd, 1 H, J = 4.5, 10.0, 10.0 Hz,
H-9’a), 2.06 (dddd, 1 H, J = 1.3, 3.6, 8.0, 12.5 Hz, H-4’), 1.96 (dd,
1 H, J = 5.2, 5.2 Hz, H-2), 1.92 (br dd, 1 H, J = 4.0, 7.5 Hz, H-8’),
1.86-1.78 (m, 1 H, H-9’), 1.76-1.55 (m, 8 H, 2 H-3, 2 H-3’, H-8’,
H-9’), 1.53-1.40 (m, 8 H, H-3, H-4’, 6 ¥ CH2), 1.35-1.25 (m, 6 H,
3 × CH2), 0.93-0.80 (m, 15 H, 3 × CH2, 3 × CH3).
13C NMR (125 MHz, CDCl3): d = 139.9 (CH, C1’’), 107.2 (CH,
C2’’), 84.3 (CH, C6’), 84.2 (CH, C7’), 82.8 (CH, C9’a), 82.2 (CH,
C4’a), 67.6 (CH2, C2’), 62.7 (CH2, C1), 31.8 (CH2, C3), 31.2 (CH2,
C4’), 29.6 (CH2, C2), 29.2 (CH2), 27.4 (CH2), 27.2 (CH2, C9’), 26.2
(CH2, C8’), 25.8 (CH2, C3’), 13.7 (CH3), 9.4 (CH2), 6.2 (CH2, C3’’).
HRMS: m/z calcd for C14H26O3Si 270.1651, found 270.1648.
IR (film): n = 3622, 3413, 2360, 1728, 1601 cm-1.
HRMS: m/z calcd for C27H5O4120Sn 560.2887, found 560.2897.
IR (KBr): n = 3623, 3013, 1648, 1463 cm-1.
(4aS,6R,7S,9aR)-6-(3’-Hydroxypropyl)octahydro-1,5-dioxa-
benzacyclohepten-7-ol (19)
Following the same procedure used to convert 6 to 7, compound 18
(216 mg, 0.80 mmol) was converted to 19 (121.5 mg, 0.53 mmol,
66%); colourless oil; [a]D20 +24.6 (c = 1.18, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.85 (dddd, 1 H, J = 2.0, 2.0, 3.9,
11.4 Hz, H-2), 3.71 (ddd, 1 H, J = 3.4, 3.4, 6.5 Hz, H-7), 3.64 (dd,
2 H, J = 6.2, 6.2 Hz, 2H-3´), 3.31-3.24 (m, 2 H, H-2, H-6), 3.10
(1’’Z)-(4’aS,6’R,7’S,9’aR)-3-[7’-(3-Tributylstannylpropenyl-
oxy)octahydro-1’,5’-dioxabenzocyclohepten-6’-yl]propionalde-
hyde (24)
Following the same procedure to convert 11 to 12, compound 23
(142 mg, 0.25 mmol) was converted to 24 (129 mg, 0.23 mmol,
91%); colourless foam; [a]D25 +32.8 (c = 1.18, CHCl3).
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
889
1H NMR (500 MHz, CDCl3): d = 9.72 (dd, 1 H, J = 1.4, 2.5 Hz, H-
1), 5.66 (d, 1 H, J = 6.0 Hz, H-1’’), 4.54 (ddd, 1 H, J = 6.0, 9.1, 9.1
Hz, H-2’´), 3.84 (dddd, 1 H, J = 1.9, 1.9, 4.0, 11.3 Hz, H-2’), 3.58
(ddd, 1 H, J = 3.6, 3.6, 5.9 Hz, H-7’), 3.43 (ddd, 1 H, J = 3.3, 6.0,
9.8 Hz, H-6’), 3.27 (ddd, 1 H, J = 6.0, 9.0, 11.3 Hz, H-2’), 3.07
(ddd, 1 H, J = 4.4, 9.1, 11.1 Hz, H-4’a), 2.91 (ddd, 1 H, J = 4.4, 9.9,
9.9 Hz, H-9’a), 2.52 (dddd, 1 H, J = 2.5, 7.3, 7.3, 17.1 Hz, H-2),
2.45 (dddd, 1 H, J = 1.5, 6.8, 6.8, 17.1 Hz, H-2), 2.00 (br dd, 1 H,
J = 7.5, 12.6 Hz, H-4’), 1.95-1.92 (m, 2 H, H-3, H-8’), 1.85-1.74
(m, 3 H, 2 H-9’, H-3), 1.73-1.68 (m, 1 H, H-8’), 1.66-1.59 (m, 4
H, 2 H-3’, 2 H-3’’), 1.52-1.44 (m, 6 H, 3 × CH2), 1.43-1.31 (m, 1
H, H-4’), 1.29-1.24 (m, 6 H, 3 × CH2), 0.88-0.81 (m, 15 H,
3 × CH2, 3 × CH3).
octahydro-1,6,9,14,17-pentaoxa-2,13-disiladiheptalen[2,3-
b,2,3,-f]oxepine (32)
1H NMR (500 MHz, CDCl3): d = 5.66 (dddd, 2 H, J = 2.0, 6.0, 8.3,
11.1 Hz, H-4, H-11), 5.53 (ddd, 2 H, J = 2.5, 5.1, 11.1 Hz, H-5, H-
10), 4.04 (ddd, 2 H, J = 2.0, 5.1, 8.7 Hz, H-5a, H-9a), 3.81 (ddd, 2
H, J = 4.3, 8.7, 8.7 Hz, H-14a, H-19a), 3.32 (ddd, 2 H, J = 3.6, 8.7,
8.7 Hz, H-16a, H-17a), 3.28 (ddd, 2 H, J = 4.3, 8.7, 8.7 Hz, H-6a,
H-8a), 2.06 (dddd, 2 H, J = 4.0, 4.0, 8.7, 17.4 Hz, H-16, H-18), 1.89
(br ddd, 2 H, J = 4.0, 8.0, 14.0 Hz, H-7, H-8), 1.84 (dddd, 2 H,
J = 4.3, 4.5, 7.0, 14.0 Hz, H-7, H-8), 1.82-1.74 (m, 6 H, 2 H-15, 2
H-19, H-16, H-18), 1.67 (ddd, 2 H, J = 2.5, 6.0, 15.0 Hz, H-3, H-
12), 1.30 (dd, 2 H, J = 8.3, 15.0 Hz, H-3, H-12), 0.89 (s, 6 H,
CH3Si), 0.81 (s, 6 H, CH3Si).
13C NMR (125 MHz, CDCl3): d = 202.5 (CH, C1), 139.9 (CH, C1’’),
107.5 (CH, C2’’), 84.2 (CH, C7’), 83.5 (CH, C6’), 82.9 (CH, C9’a),
82.6 (CH, C4’a), 67.7 (CH2, C2’), 41.1 (CH2, C2), 31.0 (CH2, C4’),
29.2 (CH2), 29.1 (CH2), 28.1 (CH2, C3), 27.4 (CH2), 27.3 (CH2, C9’),
26.4 (CH2, C8), 25.7 (CH2, C3’), 13.7 (CH3), 9.4 (CH2), 6.2 (CH3).
13C NMR (125 MHz, CDCl3): d = 134.1 (CH C5, C10), 124.4 (CH,
C4, C11), 86.3 (CH, C16a, C17a), 84.7 (CH, C6a, C8a), 84.6 (CH, C5a
C9a), 76.2 (CH, C14a, C19a), 31.1 (CH2, C16, C18), 28.5 (CH2, C7, C8),
18.8 (CH2, C3, C12), -0.4 (CH3, CH3Si), -3.0 (CH3, CH3Si).
HRMS: m/z calcd for C24H40O5Si2 464.2414, found 464.2415.
IR (film): n = 3690, 3014, 1609, 1260 cm-1.
IR (KBr): n = 3012, 1720, 1648, 1462 cm-1.
(4aS,5aR,8S,9R,10aS,12aR)-9-Vinyldodecahydro-1,5,10-trioxa-
benzo[b]heptalen-8-ol (25)
Following the above described general method for aldehyde-allyl-
stannane cyclization, compound 24 (116 mg, 0.21 mmol) was con-
verted to 25 (48.3 mg, 0.18 mmol, 87%); colourless oil; [a]D25+37.4
(c = 0.85, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.85 (ddd, 1 H, J = 6.3, 10.5, 17.3
Hz, H-1’), 5.29 (ddd, 1 H, J = 1.5, 1.5, 17.3 Hz, H-2’), 5.17 (ddd, 1
H, J = 1.5, 1.5, 10.5 Hz, H-2’), 3.83 (dddd, 1 H, J = 2.0, 2.0, 3.8,
11.3 Hz, H-2), 3.70 (ddd, 1 H, J = 1.1, 1.1, 6.1 Hz, H-9), 3.58-3.49
(m, 2 H, H-5a, H-8), 3.46 (br dd, 1 H, J = 5.0, 8.7 Hz, H-10a), 3.25
(br ddd, 1 H, J = 4.4, 8.0, 14.9 Hz, H-2), 3.09 (ddd, 1 H, J = 4.2, 9.0,
11.0 Hz, H-4a), 2.95 (ddd, 1 H, J = 4.0, 9.0, 9.0 Hz, H-12a), 2.08-
1.97 (m, 2 H, H-4, H-6), 1.90-1.77 (m, 7 H, H-6, 2 H-7, 2 H-11, 2
H-12), 1.65-1.55 (m, 2 H, 2 H-3), 1.43-1.36 (m, 1 H, H-4).
13C NMR (125 MHz, CDCl3): d = 137.6 (CH, C1’), 116.4 (CH, C2’),
87.1 (CH, C9), 83.8 (CH, C5a), 83.0 (CH, C10a), 82.3 (CH, C12a), 81.9
(CH, C4a), 73.8 (CH, C8), 67.8 (CH2, C2), 31.4 (CH2, C4), 30.3 (CH2,
C11), 29.4 (CH2, C7), 28.8 (CH2, C12), 28.6(CH2, C6), 25.9 (CH2, C3).
meso-(2R,3S,5aR,6aS,9R,10S,11aR,13aS)-3-[3,9-Bisallyloxy-10-
(3-hydroxipropyl)tetradecahydro-1,6,11-trioxacyclohepta-
[b]heptalen-2-yl] propan-1-ol (36)
1H NMR (500 MHz, CDCl3): d = 5.84 (dddd, 2 H, J = 5.5, 5.5, 10.4,
17.2 Hz, 2 H-2’’), 5.22 (dddd, 2 H, J = 1.5, 1.5, 1.5, 17.2 Hz, 2H-
3’’), 5.11 (dddd, 2 H, J = 1.3, 1.3, 1.3, 10.4 Hz, 2H-3’’), 3.97 (dddd,
2 H, J = 1.5, 1.5, 5.5, 12.6 Hz, 2H-1’’), 3.78 (dddd, 2 H, J = 1.4,
1.4, 5.5, 12.6 Hz, 2H-1’’), 3.65-3.55 (m, 4 H, 4 H-1’), 3.44 (ddd, 2
H, J = 3.5, 3.5, 9.6 Hz, H-2, H-10), 3.40 (br ddd, 2 H, J = 3.0, 3.0,
9.0 Hz, H-5a, H-6a), 3.34 (dddd, 2 H, J = 2.0, 2.0, 3.5, 3.5 Hz, H-3,
H-9), 3.23 (br ddd, 2 H, J = 5.0, 7.0, 9.0 Hz, H-11a, H-13a), 1.90-
1.80 (m, 4 H, 2 H-5, 2 H-7), 1.83-1.77 (m, 2 H, H-4, H-8), 1.77-
1.72 (m, 4 H, 2 H-12, 2 H-13), 1.68-1.52 (m, 8 H, H-4, H-8, 4 H-
2’, 2 H-3’), 1.46-1.38 (m, 2 H, 2 H-3’).
13C NMR (125 MHz, CDCl3): d = 134.9 (CH, C2’’), 116.7 (CH2,
C3’’), 85.2 (CH, C11a, C13a), 83.7 (CH, C2, C10), 83.4 (CH, C5a C6a),
82.0 (CH, C3, C9), 69.6 (CH2, C1’’), 62.8 (CH2, C1’), 31.8 (CH2, C3’),
29.5 (CH2, C2’), 29.5 (CH2, C5, C7), 27.9 (CH2, C12, C13), 23.6 (CH2,
C4, C7),
HRMS: m/z calcd for C15H24O4 268.1675, found 268.1678.
IR (film): n = 3070, 1610, 1250 cm-1.
HRMS: m/z calcd for C26H44O7 469.3164 (M+H)+, found 469.3165.
IR (film): n = 3630, 3011, 1640, 1452 cm-1.
meso-(4aS,5aR,7aS,12aS,14aR,15aS,17aR)-
Lactone Derived Enol Triflate 42
4a,5a,6,7,7a,8a,12a,13, 14,14a,15a,16,17,17a-Tetradecahydro-
1,5,8,12,14-pentaoxadibenzo[b:k]cyclohepta[1,2-b’]heptalene-
2,11-dione (31)
A solution of lactone 41 (138 mg, 0.69 mmol) and HMPA (0.18 mL,
1.04 mmol) in THF (5 mL) was treated with lithium bis(trimethyls-
ilyl)amide (0.9 mL of a 1.0 M solution in THF, 0.90 mmol) at
-78ºC. After stirring at -78 ºC for 1 h, N-phenyl-trifluormethane-
sulfonimide (295.8 mg, 1.04 mmol) was added and the mixture was
allowed to warm to 25 ºC. After stirring for 1 h at 25 ºC, the reaction
was quenched with H2O (10 mL containing 1% of Et3N) and ex-
tracted with Et2O (50 mL). The organic layer was dried (MgSO4),
concentrated and subjected to flash chromatography (silica gel, hex-
ane containing 1% of Et3N) to give the enol triflate 42 (234 mg, 7.04
mmol, 55%).
1H NMR (500 MHz, CDCl3): d = 4.73 (br t, J = 3.8 Hz, 1 H, H-7),
4.10-4.06 (m, 2 H, H-4, H-4a), 3.99 (dddd, 1 H, J = 2.0, 3.0, 9.4,
9.4 Hz, H-9a), 3.95-3.91 (m, 1 H, H-4), 2.21 (ddd, 2 H, J = 4.0, 5.0,
7.3 Hz, 2 H-8), 2.05 (ddddd, 1 H, J = 2.0, 2.3, 7.3, 7.3, 14.0 Hz, H-
9), 1.69 (br ddd, 1 H, J = 8.0, 8.0, 14.0 Hz, H-9), 1.39 (s, 3 H, CH3-
2), 1.34 (s, 3 H, CH3-2).
1H NMR (500 MHz, CDCl3): d = 6.78 (dd, 2 H, J = 1.3, 10.0 Hz, H-
3, H-10), 5.89 (dd, 2 H, J = 1.7, 10.0 Hz, H-4, H-9), 4.14 (ddd, 2 H,
J = 2.0, 2.0, 10.8 Hz, H-4a, H-8a), 4.11 (ddd, 2 H, J = 3.8, 10.5,
10.8 Hz, H-12a, H-17a), 3.45 (ddd, 2 H, J = 7.0, 7.0, 8.2 Hz, H-5a,
H-7a), 3.37 (ddd, 2 H, J = 5.4, 8.2, 8.2 Hz, H-14a, H-15a), 2.14
(dddd, 2 H, J = 4.4, 6.7, 10.5, 14.1 Hz, H-13, H-17), 2.09 (dddd, 2
H, J = 5.4, 5.5, 6.7, 14.4 Hz, H-14, H-16), 2.03 (dddd, 2 H, J = 3.8,
5.0, 5.5, 14.1 Hz, H-13, H-17), 1.94 (dddd, 2 H, J = 4.1, 4.3, 7.0,
15.4 Hz, H-6, H-7), 1.92 (dddd, 2 H, J = 4.1, 7.0, 7.2, 15.4 Hz, H-6,
H-7), 1.86 (dddd, 2 H, J = 3.0, 4.4, 8.2, 14.4 Hz, H-14, H-16).
13C NMR (125 MHz, CDCl3): d = 163.3 (Cq, C2, C11), 149.5 (CH,
C3, C10), 119.8 (CH, C4, C9), 85.2 (CH, C14a, C15a), 83.8 (CH, C5a
C7a), 81.1 (CH, C12a, C17a), 77.1 (CH, C4a, C8a), 29.9 (CH2, C14, C16),
29.1 (CH2, C6, C7), 28.1 (CH2, C13, C17).
HRMS: m/z calcd for C20H24O7 376.1522, found 376.1521.
IR (film): n = 2942, 2872, 1731, 1640 cm-1.
13C NMR (125 MHz, CDCl3): d = 149.1 (Cq, C6), 118.5 (q, J = 320
Hz, CF3), 109.9 (Cq, C2), 88.4 (CH, C7), 80.2 (CH, C9a), 75.3 (CH,
C4a), 66.8 (CH2, C4), 26.7 (CH3, CH3-2), 25.0 (CH3, CH3-2), 23.1
(CH2, C9), 18.9 (CH2, C8).
meso-(5aR,6aS,8aR,9aS,14aR,16aS,17aR,19aS)-2,2,13,13-Tet-
ramethyl-2,3,5a,6a,7,8,8a,9a,12,13,14a,15,16,16a,17a,18,19,19a-
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

890
I. Brouard et al.
SPECIAL TOPIC
HRMS: m/z calcd for C11H15F3O6S 332.0541, found 332.0548.
IR (film): n = 1701, 1421, 1094 cm-1.
(4aR,9aS,6S,7R)-[3-(7-Allyloxy-2,2-dimethylhexahydro-1,3,5-
trioxabenzocyclohepten-6-yl)propoxy]-tert-butyldimethylsi-
lane (45)
Compound 44 (405 mg, 1.08 mmol) was converted to 45 (403 mg,
0.97 mmol, 90%) to yield a colourless oil; [a]D25-31.6 (c = 1.43,
CHCl3).
Enol Ether 43
A
solution of 3-(tert-butyldimethylsilyloxy)-1-iodopropane
(2.429 g, 8.10 mmol) in Et2O (33 mL) was treated with t-BuLi (7.94
mL of a 1.7 M solution in pentane, 13.2 mmol) at -120 ºC. After
stirring at -120 ºC for 30 min, the mixture was allowed to warm to
-78 ºC and lithium 2-thienylcyanocuprate (27.0 mL of a 0.25 M so-
lution in THF, 6.75 mmol) was added. After stirring at -30 ºC for
30 min, the mixture was cooled to -78 ºC and treated with HMPA
(33 mL) and a solution of enol triflate 42 (448 mg, 1.35 mmol) in
THF (10.4 mL). The mixture was allowed to warm to 0 ºC over 2 h,
diluted with Et2O (220 mL) and washed with brine (2 × 175 mL).
The organic layer was dried (MgSO4), filtered, concentrated and
subjected to flash chromatography (silica gel, 10-20% Et2O in hex-
anes containing 1% of Et3N) to give the enol ether 43 (337 mg,
0.945 mmol, 70%); colourless oil; [a]D25-30.2 (c = 0.93, CHCl3).
1H NMR (500 MHz, CDCl3): d = 4.46 (br s, 1 H, H-7), 4.07 (dd, 1
H, J = 5.3, 8.0 Hz, H-4), 4.02 (ddd, 1 H, J = 5.3, 5.3, 7.6 Hz, H-4a),
3.93 (dd, 1 H, J = 5.3, 8.0 Hz, H-4), 3.68 (ddd, 1 H, J = 1.2, 7.6, 7.6
Hz, H-9a), 3.57 (t, 2 H, J = 6.5 Hz, 2 H-1’), 2.05-1.96 (m, 5 H, 2
H-8, H-9, 2 H-3’), 1.62 (ddd, 2 H, J = 6.5, 7.0, 14.6 Hz, 2H-2’),
1.56-1.49 (m, 1 H, H-9), 1.34 (s, 3 H, CH3-2), 1.39 (s, 3 H, CH3-2),
0.87 (s, 9 H), 0.02 (s, 6 H).
1H NMR (500 MHz, CDCl3): d = 5.86 (dddd, 1H, J = 6.0, 6.0, 10.3,
17.2 Hz, H-2’’), 5.22 (d, 1 H, J = 17.2 Hz, H-3’’), 5.12 (d, 1 H,
J = 10.3 Hz, H-3’’), 4.05 (ddd, 1 H, J = 6.0, 11.0, 11.6 Hz, H-1’’),
4.02 (ddd, 1 H, J = 4.0, 9.0, 9.0 Hz, H-4), 3.91-3.83 (m, 3 H, H-4,
H-4a, H-1’’), 3.59 (dd, 2 H, J = 6.5, 10.0 Hz, 2 H-1’), 3.17 (br dd, 1
H, J = 7.5, 8.7 Hz, H-9a), 3.10 (br dd, 1 H, J = 8.1, 9.0 Hz, H-6),
2.93 (ddd, 1 H, J = 5.0, 9.0, 9.5 Hz, H-7), 2.21-2.19 (m, 1 H, H-8),
1.97-1.89 (m, 2 H, H-9, H-3’), 1.67 (ddddd, 1 H, J = 5.8, 6.0, 6.0,
14.0, 14.0 Hz, H-2’), 1.50 (ddddd, 1 H, 5.8, 6.0, 6.0, 14.0, 14.0 Hz,
H-2’), 1.37 (s, 3 H, CH3-2), 1.35 (m, 3 H, H-8, H-9, H-3’), 1.31 (s,
3 H, CH3-2), 0.86 (s, 9 H), 0.02 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 135.1 (CH, C2’’), 116.8 (CH2,
C3’’), 109.3 (Cq, C2), 80.9 (CH, C6), 78.2 (CH, C9a), 78.2 (CH, C4a),
77.5 (CH, C7), 70.1 (CH2, C1’’), 67.4 (CH2, C4), 63.4 (CH2, C1’),
29.0 (CH2, C8), 28.6 (CH2, C2’), 27.8 (CH2, C9), 27.7 (CH2, C3’),
26.7 (CH3, CH3-2), 26.0 (CH3), 25.3 (CH3, CH3-2), 18.4 (Cq), -5.2
(CH3).
HRMS: m/z calcd for C22H42O5Si 414.2802, found 414.2806.
IR (film): n = 3696, 3603, 3004, 2360, 1601 cm-1.
13C NMR (125 MHz, CDCl3): d = 114.1 (Cq, C6), 109.4 (Cq, C2),
95.5 (CH, C7), 77.3 (CH, C4a), 76.0 (CH, C9a), 67.1 (CH2, C4), 62.6
(CH2, C1’), 30.4 (CH2, C3’), 30.2 (CH2, C2’), 26.7 (CH3, CH3-2), 26.0
(CH3), 25.4 (CH3, CH3-2), 24.1 (CH2, C9), 19.6 (CH2, C ), -5.3
(CH3).
(4aR,9aS,6S,7R)-3-(7-Allyloxy-2,2-dimethylhexahydro-1,3,5-
trioxabenzocyclohepten-6-yl)propan-1-ol (46)
Compound 45 (397 mg, 0.96 mmol) was converted to 46 (285 mg,
0.95 mmol, 99%) to yield a colourless oil; [a]D -45.3 (c = 1.27,
CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.86 (dddd, 1 H, J = 6.0,,6.0,,10.4,
17.2 Hz, H-2’’), 5.22 (d, 1 H, J = 17.2 Hz, H-3’’), 5.13 (d, 1 H,
J = 10.4 Hz, H-3’’), 4.05 (ddd, 1 H, J = 6.0, 12.6, 12.6 Hz, H-1’’),
3.99 (br d, 1 H, J = 8.4 Hz, H-4), 3.91-3.82 (m, 3 H, H-4, H-4a, H-
1’’), 3.59 (t, 2 H, J = 6.2 Hz, 2 H-1’), 3.22 (br dd, 1 H, J = 7.2, 8.5
Hz, H-9a), 3.15 (br dd, 1 H, J = 9.0, 9.0 Hz, H-6), 2.98 (ddd, 1 H,
J = 4.5, 9.0, 9.5 Hz, H-7), 2.22-2.20 (m, 1 H, H-8), 2.11 (br s, 1 H,
OH-1’), 1.95 (br ddd, 1 H, J = 8.0, 14.0, 14.0 Hz, H-3’), 1.91 (br d,
1 H, J = 10.0 Hz, H-9), 1.68 (br ddd, 1 H, J = 7.0, 14.0, 14.0 Hz, H-
2’), 1.60 (br ddd, 1 H, J = 6.8, 14.0, 14.0 Hz, H-2’), 1.42 (ddd, 1 H,
J = 7.0, 8.0, 14.0 Hz, H-3’), 1.37 (s, 3 H, CH3-2), 1.33 (s, 3 H, CH3-
2), 1.18 (m, 2 H, H-8, H-9).
8
HRMS: m/z calcd for C19H36O4Si 356.2383, found 356.2387.
IR (film): n = 3008, 2360, 1601, 1257 cm-1.
Alcohol 44
A solution of enol ether 43 (448 mg, 1.26 mmol) in THF (13 mL)
was treated with BH3•THF (6.0 mL of a 1.0 M solution in THF,
6.0 mmol) at -30 ºC and stirred at -30 ºC for 12 h. The resulting
mixture was treated with aq 3 N NaOH solution (5.0 mL) and 30%
H2O2 (3.0 mL) at 0 ºC and stirred for 1 h at 25 ºC. The mixture was
diluted with Et2O (100 mL) and the organic layer was washed with
brine (2 × 50 mL), dried (MgSO4), filtered and concentrated. Flash
chromatography (silica gel, 20-30% Et2O in hexanes) gave the al-
cohol 44 (374 mg, 1.0 mmol, 79%); colourless oil; [a]D25-14.6
(c = 1.18, CHCl3).
1H NMR (500 MHz, CDCl3): d = 4.02 (dd, 1 H, J = 8.7, 10.3 Hz, H-
4), 3.87-3.84 (m, 2 H, H-4, H-4a), 3.60 (ddd, 2 H, J = 2.6, 6.3, 6.3
Hz, 2H-1’), 3.24 (br s, 1 H, H-7), 3.17 (br dd, 1 H, J = 10.0, 10.0 Hz,
H-9a), 3.01 (ddd, 1 H, J = 2.5, 9.0, 9.0 Hz, H-6), 2.08 (br d, 1 H,
J = 9.6 Hz, H-8), 1.93 (br s, 1 H, OH-7), 1.91 (br d, 1 H, J = 11.0
Hz, H-9), 1.88-1.83 (m, 1 H, H-3’), 1.75-1.67 (m, 1 H, H-2’),
1.56-1.48 (m, 1 H, H-2’), 1.43-1.40 (m, 1 H, H-3’), 1.41 (s, 3 H ,
CH3-2), 1.39 (m, 1 H, H-8), 1.34 (m, 1 H, H-9), 1.31 (s, 3 H, CH3-
2), 0.86 (s, 9 H), 0.02 (s, 6 H).
13C NMR (125 MHz, CDCl3): d = 135.1 (CH, C2’’), 117.0 (CH2,
C3’’), 109 (Cq, C2), 80.9 (CH, C6), 78.2 (CH, C9a), 77.8 (CH, C4a),
77.0 (CH, C7), 70.0 (CH2, C1’’), 67.1 (CH2, C4), 62.8 (CH2, C1’),
29.0 (CH2, C2’), 28.7 (CH2, C8), 28.6 (CH2, C3’), 27.4 (CH2, C9),
26.7 (CH3, CH3-2), 25.2 (CH3, CH3-2).
HRMS: m/z calcd for C16H28O5 300.1937, found 300.1935.
IR (film): n = 3624, 3010, 1640, 1451 cm-1.
(4aR,9aS,6S,7R)-3-[2,2-Dimethyl-7-(3-tributylstannanylprop-
enyloxy)hexahydro-1,3,5-trioxabenzocyclohepten-6-yl]propan-
1-ol (47)
13C NMR (125 MHz, CDCl3): d = 109.4 (Cq, C2), 82.1 (CH, C6),
78.2 (CH, C9a), 78.0 (CH, C4a), 70.6 (CH, C7), 67.3 (CH2, C4), 62.3
(CH2, C1’), 32.4 (CH2, C8), 28.6 (CH2, C2’), 28.0 (CH2, C9), 27.9
(CH2, C3’), 26.7 (CH3, CH3-2), 26.0 (CH3), 25.3 (CH3, CH3-2), 18.4
(Cq), -5.5 (CH3).
Following the described procedure for the preparation of 11 from
10, compound 46 (100 mg, 0.33 mmol) was converted to 47
(150 mg, 0.25 mmol, 76%) to yield a colourless oil; [a]D25-36.5
(c = 1.31, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.75 (d, 1 H, J = 6.0 Hz, H-3’’),
4.50 (ddd, 1 H, J = 6.0, 6.0, 9.0 Hz, H-2’’), 4.04 (dd, 1 H, J = 6.1,
7.8 Hz, H-4), 3.89 (ddd, J = 6.0, 6.0, 7.0 Hz, H-4a), 3.86 (dd, 1 H,
J = 6.0, 8.0 Hz, H-4), 3.64-3.56 (m, 2 H, 2 H-1’), 3.28-3.22 (m, 1
H, H-9a), 3.23-3.18 (m, 2 H, H-6, H-7), 2.17 (br ddd, 1 H, J = 3.0,
3.0, 12.0 Hz, H-8), 2.01-1.91 (m, 3 H, H-9, H-2’, H-3’), 1.69 (ddd,
1 H, J = 7.0, 7.0, 13.0 Hz, H-2’), 1.70-1.57 (m, 3 H, H-3’, 2 H-1’’),
HRMS: m/z calcd for C19H38O5Si 374.2489, found 374.2490.
IR film): n = 2991, 2954, 2341, 1382 cm-1.
Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

SPECIAL TOPIC
891
(4aR,5aS,8R,9S,10aR,12aS)-8-Allyloxy-2,2-dimethyl-9-vinyl-
decahydro-1,3,5,10-tetraoxabenzo[b]heptalene (50)
Compound 49 (12.6 mg, 0.042 mmol) was converted to 50 (13.3
mg, 0.039 mmol, 93%) to yield a colourless foam; [a]D25 -26.6
(c = 0.35, CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.91-5.80 (m, 2 H, H-2’, H-1’’),
5.28 (ddd, 1 H, J = 1.7, 1.7, 17.8 Hz, H-2’’), 5.24 (dd, 1 H, J = 1.7,
17.7 Hz, H-3’), 5.15 (dd, 1 H, J = 1.5, 10.4 Hz, H-3´), 5.08 (ddd, 1
H, J = 1.7, 1.7, 10.6 Hz, H-2’’), 4.03-3.96 (m, 3 H, H-4, H-9, H-1’),
3.90-3.82 (m, 3 H, H-4, H-4a, H-1’), 3.47 (br dd, 1 H, J = 4.7, 7.6
Hz, H-8), 3.24-3.18 (m, 2 H, H-10a, H-12a), 3.04 (ddd, 1 H,
J = 5.0, 10.0, 10.0 Hz, H-5a), 2.08 (br dddd, 1 H, J = 4.0, 4.5, 4.5,
12.7 Hz, H-11), 1.94-1.89 (m, 2 H, H-7, H-12), 1.79 (br dddd, 1 H,
J = 10.5, 10.5, 11.8, 12.3 Hz, H-6), 1.76-1.71 (m, 1 H, H-6), 1.62
(dddd, 1 H, J = 2.4, 2.4, 12.7, 13.4 Hz, H-7), 1.46 (dddd, 1 H,
J = 4.0, 12.5, 12.7, 13.4 Hz, H-11), 1.38 (s, 3 H, CH3-2), 1.36-1.33
(m, 1 H, H-12), 1.32 (s, 3 H CH3-2).
13C NMR (125 MHz, CDCl3): d = 138.2 (CH, C1’’), 135.3 (CH, C2’),
117.2 (CH2, C3’), 115.0 (CH2, C2’’), 109.7 (Cq, C2), 84.3 (CH, C9),
82.8 (CH, C5a), 81.7 (CH, C8), 80.8 (CH, C10a), 78.5 (CH, C12a), 78.3
(CH, C4a), 70.3 (CH2, C1’), 67.7 (CH2, C4), 31.2 (CH2, C11), 28.1
(CH2, C12), 27.2 (CH2, C6), 27.1 (CH3, CH3-2), 25.7 (CH3, CH3-2),
24.2 (CH2, C7).
1.48-1.40 (m, 8 H, H-8, H-9, 3 × CH2), 1.38 (s, 3 H, CH3-2), 1.31
(s, 3 H, CH3-2), 1.30-1.23 (m, 6 H, 3 × CH2), 0.87-0.79 (m, 15 H,
3 × CH2, 3 × CH3).
13C NMR (125 MHz, CDCl3): d = 140.3 (CH, C3’’), 109.4 (Cq, C2),
106.4 (CH, C2’’), 80.7 (CH, C6), 79.2 (CH, C7), 78.2 (CH, C9a), 77.8
(CH, C4a), 67.1 (CH2, C4), 62.8 (CH2, C1’), 29.8 (CH2, C8), 29.2
(CH2, C2’), 29.1 (CH2), 29.0 (CH2, C3’), 28.5 (CH2), 27.6 (CH2),
27.5 (CH2), 27.4 (CH2), 27.2 (CH2, C9), 26.7 (CH3, CH3-2), 25.2
(CH3, CH3-2), 13.8 (CH3), 10.6 (CH2), 9.4 (CH2), 5.9 (CH2, C2’’).
HRMS: m/z calcd C28H54O5120Sn 590.2994, found 590.2993.
IR (film): n = 3650, 1630 cm-1.
(4aR,9aS,6S,7R)-3-[2,2-Dimethyl-7-(3-tributylstannanylprop-
enyloxy)hexahydro-1,3,5-trioxabenzocyclohepten-6-yl]propi-
onaldehyde (48)
Following the described procedure for the preparation of 12 from
11, compound 47 (113 mg, 0.19 mmol) was converted to 48
(90.5 mg, 0.15 mmol, 81%) to yield a colourless oil; [a]D25-39.2
(c = 0.87, CHCl3).
1H NMR (500 MHz, CDCl3): d = 9.69 (s, 1 H, H-1’), 5.76 (d, 1 H,
J = 6.1 Hz, H-3’’), 4.51 (ddd, 1 H, J = 6.1, 6.1, 9.0 Hz, H-2’’), 4.01
(dd, 1 H, J = 6.1, 8.1 Hz, H-4), 3.82 (ddd, 1 H, J = 5.5, 6.1, 7.0 Hz,
H-4a), 3.79 (dd, 1 H, J = 5.5, 8.1 Hz, H-4), 3.23-3.17 (m, 3 H, H-6,
H-7, H-9a), 2.47 (dddd, 1 H, J = 2.1, 7.0, 7.0, 13.0 Hz, H-2’), 2.44
(ddd, 1 H, J = 7.0, 7.0, 13.0 Hz, H-2’), 2.23-2.15 (m, 2 H, H-8, H-
3’), 1.93 (br d, 1 H, J = 2.6, 12.6 Hz, H-9), 1.73 (dddd, 1 H, J = 8.0,
8.0, 8.0, 13.5 Hz, H-3’), 1.57 (ddd, 2 H, J = 9.0, 9.0, 17.0 Hz, 2 H-
1’’), 1.53-1.40 (m, 7 H, H-8, 3 × CH2), 1.37 (s, 3 H, CH3-2), 1.34
(m, 1 H, H-9), 1.31 (s, 3 H, CH3-2), 1.28-1.22 (m, 6 H, 3 × CH2),
0.87-0.79 (m, 15 H, 3 × CH3, 3 × CH2).
13C NMR (125 MHz, CDCl3): d = 202.5 (Cq, C1’), 140.0 (CH, C3’’),
109.4 (Cq, C2), 106.6 (CH, C2’’), 79.8. (CH, C6), 79.2 (CH, C7), 78.3
(CH, C9a), 77.8 (CH, C4a), 67.3 (CH2, C4), 40.3 (CH2, C2’), 29.7
(CH2), 29.2 (CH2, C8), 29.2 (CH2), 29.1 (CH2), 29.0 (CH2, C9), 27.5
(CH2), 27.4 (CH2), 26.7 (CH3, CH3-2), 25.3 (CH2, C-3’), 25.2 (CH3,
CH3-2), 13.8 (CH3), 9.4 (CH2), 5.9 (CH2,C2’’).
HRMS: m/z calcd for C19H30O5 338.2094, found 338.2093.
IR (KBr): n = 3017, 2933, 1601, 1455 cm-1.
(4aR,5aS,7aR,11aS,12aR,14aS)-2,2-Dimethyl-
4,4a,5a,6,7,7a,9,11a, 12a,13,14,14a-dodecahydro-1,3,5,8,12-
pentaoxa-dibenzo[b,h]heptalene (51)
Following the above described protocol (see general procedure for
RCM), 50 (5.85 mg, 0.018 mmol) was converted to 51 (5.46 mg,
0.018 mmol, 98%) to yield a colourless oil; [a]D25+40.7 (c = 0.26,
CHCl3).
1H NMR (500 MHz, CDCl3): d = 5.77 (ddd, 1 H, J = 1.4, 1.4, 10.4
Hz, H-11), 5.73 (dd, 1 H, J = 1.4, 10.4 Hz, H-10), 4.09 (br d, 1H,
J = 13.0 Hz, H-9), 4.06 (br d, 1 H, J = 13.0 Hz, H-9), 4.01 (dd, 1 H,
J = 5.8, 7.6 Hz, H-4), 3.94 (br d, 1 H, J = 8.3 Hz, H-11a), 3.88 (dd,
1 H, J = 5.7, 8.4 Hz, H-4a), 3.86 (dd, 1 H, J = 5.8, 7.5 Hz, H-4),
3.33 (ddd, 1 H, J = 7.2, 8.4, 8.4Hz H-7a), 3.16-3.20 (m, 2 H, H-
12a, H-14a), 3.10 (ddd, 1 H, J = 4.2, 8.4, 8.4 Hz, H-5a), 2.17-2.09
(m, 2 H, H-7, H-13), 1.97-1.86 (m, 3 H, 2 H-6, H-14), 1.77 (dddd,
1 H, J = 7.0, 7.0, 8.4, 12.5 Hz, H-7), 1.50-1.44 (m, 1 H, H-13),
1.43-1.35 (m, 1 H, H-14), 1.38 (s, 3 H, CH3-2), 1.32 (s, 3 H CH3-2).
13C NMR (125 MHz, CDCl3): d = 128.0 (CH, C10), 127.9 (CH, C11),
109.4 (Cq, C2), 81.4 (CH, C5a), 80.8 (CH, C14a), 78.1 (CH, C12a), 77.9
(CH, C4a), 77.8 (CH, C7a), 75.3 (CH2, C13), 30.3 (CH2, C6), 29.2
(CH2, C7), 27.8 (CH2, C14), 26.7 (CH3, CH3-2), 25.3 (CH3, CH3-2).
HRMS: m/z calcd for C28H52O5 120Sn 588.2837, found 588.2841.
IR (film): n = 3640, 3080, 1620 cm-1.
(4aR,5aS,8R,9S,10aR,12aS)-2,2-Dimethyl-9-vinyldecahydro-
1,3,5,10-tetraoxabenzo[b]heptalen-8-ol (49)
Following the above described protocol (see general procedure for
allylstannane-aldehyde cyclization), 48 (91 mg, 0.15 mmol) was
converted to 49 (42.9 mg, 0.14 mmol, 93%) as a crystalline solid;
[a]D25+53.9 (c = 0.59, CHCl3); mp 128-130 ºC.
1H NMR (500 MHz, CDCl3): d = 5.87 (ddd, 1 H, J = 6.0, 10.5, 17.3
Hz, H-1’), 5.30 (d, 1 H, J = 17.3 Hz, H-2’), 5.17 (d, 1 H, J = 10.5
Hz, H-2´), 4.03 (dd, 1 H, J = 10.8, 10.8 Hz, H-4), 3.88 (m, 2 H, H-
4, H-4a), 3.76 (dd, 1 H, J = 6.0, 7.0 Hz, H-9), 3.71 (m, 1 H, H-8),
3.20 (m, 2 H, H-10a, H-12a), 3.06 (dd, 1 H, J = 8.4, 13.4 Hz, H-5a),
2.10 (ddd, 1 H, J = 4.5, 7.9, 12.3 Hz, H-11), 1.92 (br d, 1 H, J = 14.0
Hz, H-12), 1.84 (m, 3 H, 2 H-6, H-7), 1.61 (m, 2 H, H-7, OH-8),
1.48 (dddd, 1 H, J = 4.2, 12.2, 12.2, 12.3 Hz, H-11), 1.38 (s, 3 H,
CH3-2), 1.38 (m, 1 H, H-12), 1.32 (s, 3 H CH3-2).
HRMS: m/z calcd for C17H26O5 310,1782, found 310.1780.
IR (film): n = 3006, 1602, 1456 cm-1.
Acknowledgement
MEC (Spain, PB97-1123) and the Ramón Areces Foundation are
gratefully acknowledged for funding this work.
13C NMR (125 MHz, CDCl3): d = 137.7 (CH, C1’), 116.0 (CH2, C2’),
109.4 (Cq, C2), 86.4 (CH, C9), 82.8 (CH, C5a), 81.9 (CH, C10a), 78.3
(CH, C12a), 77.9 (CH, C4a), 73.6 (CH, C8), 67.2 (CH2, C4), 30.8
(CH2, C11), 29.7 (CH2, C7), 27.9 (CH2, C12), 26.7 (CH2, C6), 25.9
(CH3, CH3-2), 25.3 (CH3, CH3-2).
References
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HRMS: m/z calcd for C16H26O5 298.1780, found 298.1782.
IR (KBr): n = 3612, 1603, 1455, 1382 cm-1.
(a) Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897.
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Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York

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Article Identifier:
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Synthesis 2000, No. 6, 883–892 ISSN 0039-7881 © Thieme Stuttgart · New York