Synthesis and self-assembling properties of polymerizable organogelators

Article abstract of DOI:10.1002/1521-3765(20020415)8:8<1856::AID-CHEM1856>3.0.CO;2-R

In this paper we report the development of a family of polymerizable urea derivatives that are gelators for organic solvents. The design involves amino-acid-based urea derivatives containing methacrylate functional groups. Several of the bis-ureas show ex

Full text of DOI:10.1002/1521-3765(20020415)8:8<1856::AID-CHEM1856>3.0.CO;2-R

FULL PAPER
Total Synthesis of the Turrianes and Evaluation
of Their DNA-Cleaving Properties
Alois F¸rstner,* Frank Stelzer, Antonio Rumbo, and Helga Krause[a]
Abstract: The first total synthesis of
three naturally occurring cyclophane
derivatives belonging to the turriane
family of natural products is described.
Their sterically hindered biaryl entity is
formed by reaction of the Grignard
reagent derived from aryl bromide 10
with the oxazoline derivative 18, and the
macrocyclic tether of the targets is
efficiently forged by ring closing meta-
thesis. While conventional RCMcata-
lyzed by the ruthenium-carbene com-
plexes 33 or 34 invariably leads to the
formation of mixtures of both stereo-
isomers with the undesirable (E)-alkene
prevailing, ring closing alkyne metathe-
sis (RCAM) followed by Lindlar reduc-
tion of the resulting cycloalkynes 37 and
38 opens a convenient and stereoselec-
tive entry into this class of compounds.
RCAMcan either be accomplished by
using the tungsten alkylidyne complex
latter method is significantly accelerated
when carried out under microwave
heating. Furthermore, the judicious
choice of the protecting groups for the
phenolic -OH functions turned out to be
crucial. PMB-ethers were found to be
compatible with the diverse reaction
conditions en route to 3 5; their cleav-
age, however, had to be carried out
under carefully optimized conditions to
ꢀ
[(tBuO)3W CCMe3] or by means of a
catalyst formed in situ from [Mo(CO)6]
and para-trifluoromethylphenol. The
À
minimize competing O C PMB migra-
tion. Turrianes 3 5 are shown to be
potent DNA cleaving agents under ox-
idative conditions when administered in
the presence of copper ions.
Keywords: alkynes ¥ DNA ¥ meta-
thesis ¥ molybdenum ¥ natural prod-
ucts
we became aware of two additional types of naturally
occurring resorcinols which seem to be close relatives of 2.
Introduction
À
Many plants, particularly those belonging to the Proteaceae,
Anacardiaceae, Gingkoaceae and Graminae families, are rich
sources of 5-alkylresorcinol derivatives and related non-
isoprenoid lipids.[1] Compounds of this type exhibit a variety
of biological activities, including inhibitory effects on a
number of enzymes and cytotoxicity against various tumor
cell lines.[2] Therefore, it is particularly noteworthy that
compounds as simple as 1 and its bola-formed analogue 2
isolated from the west Australian shrub Hakea trifurcata were
recently shown to cleave DNA very efficiently under oxida-
tive conditions. Studies by Hecht et al. shed light into their
mechanism of action and have revealed a distinct correlation
between the length of the aliphatic tether with the biological
response to these antineoplastic agents.[3, 4]
Thus, formal oxidative C C coupling of the phenol rings of 2
as indicated in Scheme 1 leads to a cyclophane structure
which is common to all members of the turriane family of
natural products (3 5) isolated from the stem wood of the
Australian tree Grevillea striata R. Br. (called ™turraie∫ by the
Aboriginees).[6] Similarly, oxidative C O coupling entails the
À
formation of the macrocyclic biaryl ether skeleton of robustol
6, a secondary metabolite isolated from the leaves of Grevillea
robusta A. Cunn.[7] Although the permethyl ether of 3 and 6
have previously been prepared,[8, 9] the natural products
themselves have so far resisted total syntheses, not least
because of prohibitively low yields during attempted forma-
tion of their core structures and because of problems in
finding suitable protecting group patterns that allow the
ultimate liberation of the very electron rich and hence rather
sensitive biphenyl entities.[6]
No information is available on either the biological function
of or the physiological response to the turrianes and robustol.
In the light of the studies mentioned above,[3] however, one
may speculate that these compounds share similar DNA-
cleaving properties with the ™parent∫ bola-resorcinol deriv-
ative 2. The chemical challenges posed by these macrocycles
and the hope to study some of their properties if samples can
be made available prompted us to venture into the total
Previous work from this laboratory has led to the develop-
ment of an efficient and flexible methodology for the syn-
thesis of such compounds,[5] thus enabling more detailed
studies of their structure/activity profile. During this program
[a] Prof. A. F¸rstner, Dipl.-Chem. F. Stelzer, Dr. A. Rumbo, H. Krause
Max-Planck-Institut f¸r Kohlenforschung
Kaiser-Wilhelm-Platz 1
45470 M¸lheim/Ruhr (Germany)
Fax : (‡49)208-3 06 29 94
E-mail: fuerstner@mpi-muelheim.mpg.de
1856
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Chem. Eur. J. 2002, 8, No. 8

1856 1871
the 4- rather than the 2-position;[10] as the same likely applies
to 2, an isomeric product would ensue.
Therefore the purely ™chemical∫ analysis spelled out in
Scheme 2 for cyclophane 4 seemed to be more rewarding and
was preferred over the biomimetic approach. Our excellent
Scheme 2. Retrosynthetic analysis of turriane 4.
experiences with metathesis strongly recommended this
transformation as a means to form the macrocyclic ring.[11]
Thereby, alkyne metathesis followed by Lindlar reduction
may be preferable over the more conventional alkene meta-
thesis en route to 4 and 5 containing a (Z)-configured double
bond.[12] We were well aware, however, that the 2,2',6,6'-
tetrasubstituted biaryl entity of the required metathesis
substrate A constitutes a formidable challenge. Transition
metal catalyzed cross coupling reactions allowing the forma-
tion of biphenyl linkages are known to be quite sensitive to
steric hindrance and have hardly been successful when
applied to such encumbered motifs.[13, 14] The previous syn-
thesis of the per-O-methyl ether of 3,[8] however, nicely
illustrates that Meyers oxazoline chemistry[15] represents a
viable alternative although it has to be adapted for our
purposes such that it allows to attach two different lateral
chains to the individual arene rings in A.
Scheme 1. Proposed biosynthetic pathway for the formation of the
turrianes 3 5 and robustol 6.
synthesis of these targets. Summarized below is our meta-
thesis approach to the turriane family together with an interim
report on the effects of these compounds on supercoiled
DNA.
A major concern in the planning (and the execution, see
below) of the turriane synthesis is the choice of the protecting
groups R for the phenolic -OH functions. The presence of
double bonds in two of the final targets precludes hydro-
genolytically labile ones, while the electron rich arenes are
incompatible with groups that are cleaved off under oxidative
conditions. Moreover, one has to keep in mind that the
original publication reporting the isolation of the turrianes
explicitly mentions the pronounced sensitivity of these com-
pounds to basic media.[6] Furthermore, the protecting groups
R must be orthogonal to the residual methyl ether, should not
increase the steric hindrance at the biphenyl linkage any
further, and have to be stable towards organometallic
reagents if the oxazoline route is chosen for the construction
Results and Discussion
Retrosynthetic analysis: Despite the tantalizing possibility of
converting the now readily available bola-resorcinol 2[5] and
unsaturated congeners thereof into 3 5 via a biomimetic
route (Scheme 1), this option was dismissed for the following
reasons: Previous attempts to reduce the desired oxidative
C C coupling to practice were extremely low yielding and the
expected product could never be isolated in pure form.[6]
Although it might be possible to improve on that prior art,
À
À
we actually suppose that a non-enzymatic oxidative C C
coupling of 2 leads to an unwanted isomer. There is strong
evidence in the literature that the normal reactivity mode of
for example orcinol under oxidative conditions involves only
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A. F¸rstner et al.
FULL PAPER
of the biphenyl unit. Taken together, these stringent criteria
severely limit the possible choices. p-Methoxybenzyl (PMB)
or methoxymethyl (MOM) ethers seemed to be suitable
candidates, although we were somewhat apprehensive that
the acidic conditions for their cleavage in the final stages
might be far from ideal.[16]
for -Br exchange on treatment with CuCN in refluxing
DMF.[22] After conversion of the -OH group of 15 into a
PMB-ether, the nitrile in 16 is saponified to afford the
corresponding carboxylic acid. Not unexpectedly, this trans-
formation is rather slow but very high yielding. Subsequent
exposure to amino alcohol 17 in the presence of an excess of
PPh3, CCl4, and (iPr)2NEt in pyridine/MeCN delivers oxazo-
line 18 required for the crucial biaryl formation. This
sequence of reactions gives an excellent overall yield and
can be carried out on a multigram scale without difficulties.
We were pleased to find that the coupling of bromide 10
with oxazoline 18 to the desired product 19 proceeds in 84%
yield if a 2:1 mixture of these compounds is refluxed in the
presence of an excess of Mg activated by 1,2-dibromoethane
(Scheme 5, Table 1, entry 1). Surprisingly though, this chem-
Preparation of the biphenyl core: After model studies had
soon revealed substantial problems upon attempted forma-
tion of the ortho-tetrasubstituted biphenyl unit B by transition
metal catalyzed cross coupling,[17] recourse was taken to the
oxazoline chemistry referred to above as it has previously
been successfully employed in a number of syntheses of
sterically hindered biaryls.[8, 15, 18]
Commercially available 4-bromo-3,5-dihydroxybenzoic
acid (7) serves as a convenient and cheap starting material
(Scheme 3), which is reduced with LiBH4 after esterification
Scheme 5. [a] Mg, 1,2-dibromoethane, THF, reflux, 2 d, see Table 1.
Table 1. Effect of the protecting groups on the outcome of the biaryl
formation depicted in Scheme 5.
Scheme 3. [a] i) SOCl2,
MeOH,
08C;
ii) reflux,
2 h,
96%.
[b] pMeOC6H4CH2Cl, K2CO3, Bu4NI cat., DMF, 808C, 12 h, 84%.
[c] LiBH4, MeOH, THF, reflux, 3 h, 98%. [d] tBuPh2SiCl (TBDPS-Cl),
imidazole, DMF, RT, 12 h, 82%.
Entry
R1
R2
R3
Yield [%]
1
2
3
4
5
PMB
PMB
PMB
MOM
MOM
PMB
PMB
MOM
PMB
MOM
TBDPS
TBS
TBS
TBS
TBS
84
80
61
8
and PMB protection. The resulting benzylic alcohol 9 is
transformed into tert-butyldiphenylsilyl (TBDPS) ether 10
because this group promises excellent stability upon con-
version of 10 into the corresponding Grignard reagent in the
coupling step.[16]
0
istry turned out to be very responsive to the chosen protecting
group pattern. Replacement of only one PMB-ether by a
MOM group renders the coupling process significantly less
productive (entry 3). Even more deleterious is the use of
MOM groups in the Grignard reagent derived from 10
(entry 4), and the attempted coupling of substrates bearing
only MOM-groups failed to afford any of the expected biaryl
(entry 5). Hence, these results exclude one of the protecting
groups initially considered as possible candidate for the
turriane total synthesis.
Vanilline 11 as the source for the second building block
(Scheme 4) is regioselectively brominated at the 5-position to
give compound 12.[19] Subsequent O-methylation[20] followed
by Baeyer Villiger oxidation of the resulting product 13
readily provides phenol 14[21] which undergoes smooth -CN
Preparation of the metathesis precursors: Further elaboration
of 19 into a set of substrates suitable for macrocyclization
starts with N-alkylation of the oxazoline group with methyl
triflate, reduction of the resulting salt with NaBH4 followed
by acid-catalyzed hydrolysis to afford aldehyde 20
(Scheme 6).[23] Reduction of the latter provides the corre-
sponding alcohol 21. It is noteworthy that all attempts to
convert oxazoline 19 directly into 21 according to a literature
protocol[24] met with failure.
Scheme 4. [a] Br2, MeOH, 08C (2.5 h), then RT (1 h), 95%. [b] MeI,
K2CO3, DMF, RT, 24 h, 97%. [c] i) 3-Chloroperbenzoic acid, CH2Cl2,
reflux, 16 h; ii) aq. HCl, aq. MeOH, RT, 30 min, 70%. [d] CuCN, DMF,
reflux, 12 h, 89%. [e] pMeOC6H4CH2Cl, K2CO3, Bu4NI cat., DMF, 808C,
12 h, 82%. [f] LiOH, MeOH/H2O, reflux, 3 d, 98%. [g] Aminoalcohol 17,
PPh3, CCl4, (iPr)2NEt, pyridine, MeCN, 808C, 16 h, 80%.
The severe steric crowding at the biaryl junction was
experienced in our attempts to perform substitution reactions
at the benzylic position of the corresponding iodide 22a,
bromide 22b, or mesylate 22c. Due to the orthogonal
arrangement of the phenyl units, the benzylic site is held
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Turrianes
1856 1871
Table 2. Preparation of the metathesis substrates as shown in Schemes 6
and 7.
under the A-ring and hence hardly accessible for external
nucleophiles (cf. Scheme 6). Although various organometallic
reagents were tried, all attempts to attach the lateral chain in
such a way were unsuccessful. The only carbon nucleophile
that could be introduced was cyanide to give 23 which is,
however, of little furtherance to the total synthesis.
X-(CH2)n-
Series 24 [%] 25 [%] 26 [%] 27 [%] 28 [%]
a
82
79
94
78
97
82
99
95
73
77
b
Therefore we focused our attention on the elaboration of
aldehyde 20. Its treatment with different alkyl Grignard
reagents affords the corresponding alcohols 24a d in good to
excellent yields (Scheme 6, Table 2). These compounds are
c
87
66
94
90
83
76
99
96
76
81
d
Scheme 7. [a] nBu4NF ¥ 3H2O, THF, RT, 2 h, see Table 2. [b] i) Methane-
sulfonic anhydride, Et3N, CH2Cl2, 08C, 30 min; ii) LiBr, THF, 608C, 2 h, see
Scheme 6. [a] i) F3CSO3Me, CH2Cl2, À10 ! 08C, 2 h; ii) NaBH4, MeOH/
THF 4:1, 08C ! RT, 3 h; iii) oxalic acid, THF/H2O (4:1), 12 h, 61 70%.
[b] See text. [c] X-(CH2)nMgBr, THF, 08C, 1 h, see Table 2. [d] PhOC(S)Cl,
pyridine, CH2Cl2, À208C (1 h), then RT (12 h), see Table 2. [e] nBu3SnH,
AIBN, toluene, 758C, 12 h, see Table 2. R ˆ PMB.
ˆ
Table 2. [c] For 29: H2C CH(CH2)8MgBr, Li2CuCl4 cat., THF, À208C, 1 h,
ˆ
65%; for 30: H2C CH(CH2)6MgBr, Li2CuCl4 cat., THF, À208C, 1 h, 66%;
ꢀ
for 31: H3CC C(CH2)8MgBr, Li2CuCl4 cat., THF, À208C, 1 h, 80%; for 32:
ꢀ
H3CC C(CH2)6MgBr, Li2CuCl4 cat., THF, À208C, 1 h, 73 %. R ˆ PMB.
converted into the thiocarbonates 25a d which readily
reduce to the corresponding products 26a d on exposure to
nBu3SnH/AIBN in toluene at 758C (Table 2). In no case does
the intermediate benzyl radical interfere with the alkene or
alkyne moieties in its vicinity.
The attachment of the lateral chain to the other arene
moiety turned out to be more facile. Fluoride mediated
cleavage of the O-TBDPS ether in 26a d followed by
conversion of the resulting alcohols 27a d into the corre-
sponding bromides 28a d proceeds well if carried out under
the conditions shown in Scheme 7 and Table 2.[25] Since this
benzylic position is sterically much more accessible, the
nucleophilic displacement of the bromides by Grignard
reagents in the presence of catalytic amounts of Li2CuCl4 in
THF at À208C delivers the desired products in high yields.
Dienes 29 and 30 as well as diynes 31 and 32 thus obtained
serve as substrates for the envisaged metathetic ring closure.
Macrocyclization by ring closing olefin metathesis: Despite
some early scepticism about the suitability of ring closing
metathesis (RCM) of dienes for the formation of macro-
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A. F¸rstner et al.
FULL PAPER
cycles,[26] this reaction turned out to be a powerful, flexible,
and convenient entry into carbo- and heterocyclic rings of any
ring size ꢁ5.[11, 27] Many previous applications from our
laboratory have encouraged us to pursue RCMen route to
turriane as well.[28] As expected, dienes 29 and 30 smoothly
cyclize to the corresponding 20-membered rings 35 and 36,
respectively, when exposed to catalytic amounts of the
classical Grubbs catalyst 33[29] in refluxing CH2Cl2 (Scheme 8,
conventional RCMis useful only for the synthesis of the
turriane 3 having a saturated tether. Obviously, this method is
inadequate for the preparation of turrianes 4 and 5 containing
a (Z)-alkene, in particular since it is most difficult to separate
the geometrical isomers of 35 and 36 even by preparative
HPLC.
The ring closing alkyne metathesis (RCAM)/Lindlar reduc-
tion manifold: This difficulty can be circumvented by taking
recourse to ring closing alkyne metathesis (RCAM) as
previously outlined by our laboratory.[12, 33] The cycloalkynes
initially formed serve as relays for the stereoselective
formation of alkenes by a subsequent semi-reduction process
(e.g. Lindlar hydrogenation). As this concept has already been
40]
successfully applied to a number of total syntheses,[34
deserves consideration in the present context as well.
it
Three different types of alkyne metathesis catalysts are
known to date. These comprise:
i) the mechanistically well understood tungsten alkylidyne
[41]
ꢀ
complex [(tBuO)3W CCMe3],
ii) the very powerful molybdenum amido complex
[{(tBu)(Ar)N}3Mo] activated with CH2Cl2,[42, 43] and
iii) an ™instant protocol∫ in which a structurally unknown
catalyst is generated in situ from [Mo(CO)6] and phenol
additives.[44]
Scheme 8. Formation of the cyclophane core of the turrianes by RCM.
The latter system is very user-friendly but requires rather
harsh conditions (ꢁ1308C in chlorobenzene).[45, 46] We rea-
soned, however, that it might be applicable in the present case
as the turrianes should be thermally robust enough to
withstand high temperatures.
Table 3). The use of the phenylindenylidene analogue 34,[30, 31]
which was recently introduced as a particularly well accessible
alternative to 33, gave similar results.
The results displayed in Scheme 9 and Table 4 show that
this is indeed the case. While the tungsten alkylidyne complex
ꢀ
[(tBuO)3W CCMe3] converts diynes 31 and 32 into the
The data compiled in Table 3, however, also illustrate one
of the present limitations of RCM. While cycloalkenes 35 and
36 are formed in acceptable chemical yields, the stereo-
chemical outcome of the reaction remains beyond control. In
line with most examples reported in the literature,[11] the (E)-
isomer also predominates in the present cases. It is, however,
instructive to see how a change of the site of ring closure
within the target has a quite significant impact on the
stereochemical course (compare entries 1/3 and 2/4). Al-
though this result is certainly not unexpected, our present
understanding of the reaction does not allow us to predict
these changes with reasonable accuracy.[32]
Apart from these more heuristic aspects, the prevalence of
the (E)-isomer in compounds 35 and 36 makes clear that
Scheme 9. Formation of the cyclophane core of the turrianes by ring
closing alkyne metathesis (RCAM).
Table 3. Formation of the cyclophane core by RCM. All reactions have
been carried out in refluxing CH2Cl2 using 5 mol% of the catalyst.
desired cycloalkynes 37 and 38 in reasonable yields (meth-
od A), the use of [Mo(CO)6] activated with 4-trifluorome-
thylphenol in chlorobenzene at 1358C (method B) provides
even better results. The fact that the application of microwave
technology (method C)[47] instead of conventional heating
allows to reduce the reaction time from 4 6 hours to five
Entry
Substrate
Catalyst
Product
Yield [%]
E:Z
1
2
3
4
29
29
30
30
33
34
33
34
35
35
36
36
78
76
73
84
1.2:1
1:1.1
5.8:1
6.9:1
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Turrianes
1856 1871
Table 4. Formation of the cyclophane core by RCAMusing 10 mol% of
the catalyst.
Entry Substr. Catalyst
Con-
ditions[a]
t
Prod. Yield
[%]
ꢀ
1
2
3
4
5
6
31
31
31
32
32
32
[(tBuO)3W CCMe3]
[Mo(CO)6], F3CC6H4OH
[Mo(CO)6], F3CC6H4OH
A
B
C
A
B
C
16 h 37
4 h 37
5 min 37
16 h 38
64
83
69
61
76
71
ꢀ
[(tBuO)3W CCMe3]
[Mo(CO)6], F3CC6H4OH
[Mo(CO)6], F3CC6H4OH
6 h
38
5 min 38
[a] A: toluene, 808C; B: chlorobenzene, 1358C; C: chlorobenzene, 1508C,
microwave heating.
minutes constitutes a particularly appealing facet of this
chemistry. We are presently studying the generality of this
finding.
Completion of the total syntheses: Turriane 3 having a
saturated tether was the first target reached (Scheme 10).
Hydrogenation (1 atm) of the RCMproduct mixture ( E,Z)-36
over palladium on charcoal saturates the ring and leads to the
concurrent cleavage of the O-PMB ethers, thus providing the
desired product in 87% isolated yield.
Scheme 11. [a] H2 (1 atm), Lindlar catalyst, quinoline cat., EtOAc, 6 h,
96%. [b] BF3 ¥ Et2O, EtSH, À208C ! RT, 16 h, 50%. [c] H2 (1 atm),
Lindlar catalyst, quinoline cat., EtOAc/MeOH, 2 h, 96%. [d] BF3 ¥ Et2O,
EtSH, À208C ! RT, 16 h, 54 %.
molten, neat trimethoxybenzene at 708C, the HPLC of the
crude mixture indicates that the desired turrianes 4 and 5 are
formed as the major products which are isolated in 39 and
46% yield. Somewhat better results are obtained with an
excess of BF3 ¥ Et2O (20 equiv) in neat EtSH as the reaction
medium.[51] In this case, preparative HPLC allowed the
isolation of the desired products 4 and 5 in 50 and 54% yield,
respectively. The spectroscopic data of the analytically pure
samples thus obtained are in excellent agreement with the
proposed structures.
Scheme 10. [a] H2 (1 atm), Pd/C, EtOAc/EtOH/H2O, 24 h, 87%.
To complete the syntheses of the other members of this
series, the cycloalkynes 37 and 38 were subjected to Lindlar
hydrogenation delivering (Z)-alkenes (Z)-35 and (Z)-36 in
virtually quantitative yield and excellent stereochemical
integrity (Scheme 11). With these materials in hand, the stage
was set for the final deprotection step which turned out to be
significantly more delicate than anticipated.
The turrianes as effective DNA-cleaving agents: As discussed
in the Introduction, the turrianes might be biogenetically
related to the bola-form resorcinol derivative 2 which is
known to mediate the cleavage of DNA in the presence of
CuII under oxidative conditions.[3] Therefore a study was
called for to see if products 3 5 exert similar functions.
It is well established in the literature that phenols are
regioselectively oxygenated by O2 in the presence of copper-
amine complexes as catalysts.[52] The resulting catechols are
further oxidized to ortho-quinones and derivatives thereof.
During this autooxidation process, H2O2 is produced which is
concomitantly cleaved by the copper catalyst to form
As discussed in the introductory section, PMB-ethers
seemed to match all stringent criteria imposed on the choice
of the protecting groups. Importantly, they can be cleaved
under a variety of conditions, some of which are described to
be particularly mild.[16, 48] Unfortunately, however, all of these
methods invariably led to the formation of very complex
reaction mixtures. Although traces of the desired products
could be detected by LC/MS and NMR, a plethora of
compounds had formed which still contained up to three
PMB-groups in addition to free -OH functions. Obviously, the
electron rich phenol rings are subject to extensive C-alkylation
under the chosen reaction conditions. Hence, a competitive
scavenger for the intermediate para-methoxybenzyl cations
had to be administered to avoid this undesirable intramolec-
ular Friedel Crafts pathway. Attempts to do so by adding a
large excess of NaBH3CN[49] were equally unsuccessful as
those employing admixed EtSH, MeSC6H4OMe, anisole or
trimethoxybenzene (10 equiv each).[50] Only if the cleavage is
performed with SnCl2 (1 equiv) and TMSCl (10 equiv) in
.
diffusible oxygen radicals (most likely HO ) that constitute
severe DNA-damaging agents.[52, 3]
It has also been mentioned earlier that the catalytic action
of copper in this overall process is remarkably specific, as this
metal cation cannot be replaced by other ones known to effect
the decomposition of H2O2.[52] In line with this notion, the
agarose gel depicted in Figure 1 shows that turriane 3 in the
presence of n-butylamine is able to relax purified double-
stranded plasmid DNA (form I) of the bacteriophage FX174
only in the presence of Cu(OAc)2 (lane 11), whereas all other
transition metal salts assayed turned out to be more or less
inactive (some weak activity is detected for MnII, cf. lane 6).
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A. F¸rstner et al.
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Figure 3. Result of an agarose gel electrophoresis showing the extent of
DNA cleavage produced by turrianes 3 5 in the presence of n-butylamine
and Cu(OAc)2 after 1.5 h incubation time at 378C. Lane 1: DNA marker
(500 base pairs); lane 2: DNA alone; lane 3: linear DNA formed from
scDNA by using the restriction endonuclease XhoI; lane 4: DNA ‡ 3 ‡
CuII ‡ nBuNH2; lane 5: DNA ‡ 4 ‡ CuII ‡ nBuNH2; lane 6: DNA ‡ 5 ‡
CuII ‡ nBuNH2.
Figure 1. Result of an agarose gel electrophoresis showing the extent of
DNA cleavage produced by turriane 3 in the presence of n-butylamine and
various metal salts as indicated after 1.5 h incubation time at 378C. Lane 1:
DNA marker (500 base pairs); lane 2: DNA only; lane 3: linear DNA
formed from scDNA by using the restriction endonuclease XhoI; lane 4:
DNA ‡ 3 ‡ nBuNH2; lane 5: DNA ‡ 3 ‡ nBuNH2 ‡ CrIII; lane 6: DNA ‡
3 ‡ nBuNH2 ‡ MnII; lane 7: DNA ‡ 3 ‡ nBuNH2 ‡ FeIII; lane 8: DNA ‡
3 ‡ nBuNH2 ‡ FeII; lane 9: DNA ‡ 3 ‡ nBuNH2 ‡ CoII; lane 10: DNA ‡
3 ‡ nBuNH2 ‡ NiII; lane 11: DNA ‡ 3 ‡ nBuNH2 ‡ CuII; lane 12: DNA ‡
3 ‡ nBuNH2 ‡ ZnII.
Conclusion
The first total synthesis of three members of the turriane
family of natural products has been achieved. Key steps are
the oxazoline-based formation of the sterically hindered
2,2',6,6'-tetrasubstituted biphenyl axis as well as ring closing
metathesis reactions to form the cyclophane rings. Thereby,
conventional olefin metathesis mediated by the ruthenium
carbene complexes 33 or 34, though chemically very produc-
tive, invariably affords mixtures of the diastereomeric cyclo-
alkenes with the undesired (E)-isomer prevailing. In contrast,
alkyne metathesis followed by Lindlar reduction opens a
stereoselective entry into the (Z)-configured macrocycles 4
and 5. This notion has potentially broader ramifications in
synthesis as it suggests that this transformation constitutes a
valuable tool for advanced organic synthesis. The reaction can
be catalyzed either by the alkylidyne complex [(tBuO)3-
The influence of CuII was then investigated in more detail.
The agarose gel depicted in Figure 2 makes clear that neither
Cu(OAc)2‡n-butylamine alone (lane 4), nor turriane 3 itself
(lane 5), nor 3‡Cu(OAc)2 in the absence of base (lane 6) were
able to cleave supercoiled DNA (scDNA) to any noticeable
extent after 90 min incubation time. In contrast, a combina-
tion of 3, Cu(OAc)2 and n-butylamine was very effective.
ꢀ
W CCMe3] or by [Mo(CO)6] in the presence or 4-trifluoro-
methylphenol. The latter method benefits tremendously from
microwave heating. Finally, it has been shown that the
turrianes 3 5 are effective DNA cleaving agents when
administered in the presence of CuII. If seen in the context
of previous studies, this finding suggests that many structur-
ally different phenol derivatives might exert a similar
physiological function.
Figure 2. Result of an agarose gel electrophoresis showing the extent of
DNA cleavage produced by turriane 3 in the presence of n-butylamine and
Cu(OAc)2 with increasing incubation time at 378C. Lane 1: DNA marker
(500 base pairs); lane 2: DNA alone; lane 3: linear DNA formed from
scDNA by using the restriction endonuclease XhoI; lane 4: DNA ‡ CuII ‡
nBuNH2; lane 5: DNA ‡ 3 ‡ nBuNH2; lane 6: DNA ‡ 3 ‡ CuII; lanes 7
11: DNA ‡ 3 ‡ nBuNH2 ‡ CuII after the following incubation times: 10 min
(7), 30 min (8), 60 min (9), 90 min (10), 120 min (11).
Even after 10 min incubation time considerable single strand
cleavage has taken place as can be seen from the gain in
intensity of band II corresponding to the nicked form of the
DNA (lane 7). After 90 min, the supercoiled plasmid DNA
(band I) has almost completely disappeared and only the
nicked (band II), concatemere (band III) and even the linear
form of DNA (band IV) are detectable (lane 10).
Figure 3 proves that all three turrianes available by our
preparative studies behave similarly, with double strand
cleavage being slightly more pronounced in case of the
unsaturated compounds 4 and 5 (lanes 5 and 6). These data
nicely corroborate those reported by Hecht et al. for simple
5-alkylresorcinol derivatives such as 1 or 2.[3] More generally
speaking, they suggest that the ability to damage DNA might
be a rather generic property of electron rich phenols occurring
in nature. Ongoing investigations in this laboratory are meant
to study this hypothesis in more detail.[53]
Experimental Section
General: All reactions were carried out under Ar. The solvents used were
purified by distillation over the drying agents indicated and were trans-
ferred under Ar: THF, Et2O (Mg/anthracene), CH2Cl2 (P4O10), MeCN,
Et3N, pyridine, DMF (CaH2), MeOH (Mg), hexane, toluene (Na/K).
Microwave heating was carried out in sealed vessels using a Smith Creator
reactor (Personal Chemistry, Konstanz, Germany). Flash chromatography:
Merck silica gel 60 (230 400 mesh). NMR: Spectra were recorded on a
DPX 300, AV 400 or DMX 600 spectrometer (Bruker) in the solvents
indicated; chemical shifts (d) are given in ppm relative to TMS, coupling
constants (J) in Hz. IR: Nicolet FT-7199 spectrometer, wavenumbers in
cmÀ1. MS (EI): Finnigan MAT 8200 (70 eV), HRMS: Finnigan MAT 95.
Melting points: B¸chi melting point apparatus (uncorrected). Elemental
analyses: Kolbe, M¸lheim/Ruhr. All commercially available compounds
(Lancaster, Fluka, Aldrich) were used as received.
4-Bromo-3,5-bis-(4-methoxybenzyloxy)-benzoic methyl ester (8): SOCl2
(63.83 g, 39 mL, 0.536 mol) was added dropwise over a period of 1 h to a
solution of 4-bromo-3,5-dihydroxy-benzoic acid (7; 25 g, 0.107 mol) in
methanol (500 mL) at 08C. After the resulting mixture had been refluxed
1862
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0947-6539/02/0808-1862 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 8

Turrianes
1856 1871
for 2 h, the solvent and excess SOCl2 were distilled off, the remaining solid
was triturated with hexanes/diethyl ether (1:1) and was dried in vacuo
affording 4-bromo-3,5-dihydroxy-benzoic acid methyl ester as a colorless
solid (25.4 g, 96%). 1H NMR (300.1 MHz, [D6]acetone): d ˆ 7.15 (s, 2H),
3.82 (s, 3H); 13C NMR (75.5 MHz, [D6]acetone): d ˆ 166.6, 156.1, 131.1,
108.6, 104.3, 52.4; IR: n ˆ 3427, 3342, 3095, 3067, 3037, 2962, 2899, 1704,
1601, 1528, 1424, 1374, 1274, 1251, 1122, 156, 1036, 994, 911, 861, 765, 708,
(160 mL) was slowly introduced over a period of 30 min causing the
precipitation of a colorless solid. The suspension was stirred for 15 min at
ambient temperature and the precipitate was filtered off. Washing with
water and pentane followed by drying in vacuo at 608C afforded aryl
bromide 12 as a colorless solid (72.1 g, 95%). 1H NMR (300.1 MHz,
[D6]acetone): d ˆ 9.81 (s, 1H), 9.43 9.17 (brs), 7.69 (d, J ˆ 1.5 Hz, 1H), 7.43
(d, J ˆ 1.8 Hz, 1H), 3.96 (s, 3H); 13C NMR (75.5 MHz, [D6]acetone): d ˆ
190.3, 150.6, 149.4, 130.8, 129.6, 110.0, 109.3, 56.8; IR: n ˆ 3298, 3103, 3072,
3008, 2974, 2942, 2849, 2774, 1675, 1590, 1502, 1464, 1424, 1406, 1354, 1291,
1159, 1046, 971, 855, 830, 794, 680, 585, 537, 519 cmÀ1; MS (EI): m/z (%):
‡
‡
628, 595, 559 cmÀ1; MS (EI): m/z (%): 249 (6) [M‡3] , 248 (64) [M‡2] ,
‡
‡
247 (7) [M‡1] , 246 (66) [M] , 218 (10), 217 (98), 216 (11), 215 (100), 190
(9), 189 (24), 188 (12), 187 (22), 108 (17), 107 (12), 80 (6), 79 (20), 69 (11), 62
(7), 53 (11), 52 (8), 51 (25), 50 (13), 39 (6), 38 (6); HR-MS (EI) (C8H7BrO4):
calcd 245.9528; found 245.9529.
‡
233 (9), 232 (98), 231 (76), 230 (100) [M] , 229 (68), 217 (5), 215 (5), 203 (5),
201 (6), 189 (14), 187 (15), 161 (10), 159 (11), 136 (8), 135 (10), 131 (5), 108
(5), 107 (11), 94 (9), 91 (6), 80 (5), 79 (28), 78 (5), 77 (7), 66 (5), 65 (9), 63
(14), 62 (14), 61 (7), 53 (19), 52 (10), 51 (39), 50 (23), 49 (5), 39 (5), 29 (9);
HR-MS (EI) (C8H7BrO3): calcd 229.9579; found 229.9577.
K2CO3 (42.3 g, 306 mmol), nBu4NI (7.537 g, 20.4 mmol) and 4-methoxy-
benzyl chloride (47.93 g, 306 mmol) were added to a solution of 4-bromo-
3,5-dihydroxy-benzoic methyl ester (25.2 g, 102 mmol) in DMF (400 mL),
and the resulting mixture was stirred at 808C for 12 h. The reaction was
quenched with brine, the aqueous layer was extracted with tert-butyl
methyl ether, the combined organic layers were washed with brine and
dried over Na2SO4, and the solvent was evaporated. Crystallization of the
residue from pentane/tert-butyl methyl ether (1:1) delivered compound 8 as
colorless crystals. Evaporation of the mother liquor followed by flash
chromatography of the residue (hexanes/ethyl acetate 4:1 ! 3:1) afforded a
second crop of the title compound as a colorless solid (combined yield:
41.8 g, 84%). M.p. 100 1018C; 1H NMR (300.1 MHz, CDCl3): d ˆ 7.40
(AA'XX', 4H), 7.30 (s, 2H), 6.90 (AA'XX', 4H), 5.11 (s, 4H), 3.89 (s, 3H),
3.79 (s, 6H); 13C NMR (75.5 MHz, CDCl3): d ˆ 166.3, 159.4, 156.2, 129.9,
128.8, 128.2, 113.9, 108.4, 107.3, 70.9, 55.2, 52.4; IR: n ˆ 3082, 3015, 2997,
2946, 2899, 2836, 1713, 1613, 1584, 1514, 1469, 1436, 1418, 1371, 1331, 1305,
1249, 1227, 1179, 1105, 1030, 992, 923, 876, 857, 823, 806, 779, 765, 743, 651,
5-Bromo-3,4-dimethoxy-benzaldehyde (13): Methyl iodide (52.35 g,
0.369 mol) was added over a period of 1 h to a suspension of aryl bromide
12 (71 g, 0.307 mol) and K2CO3 (63.72 g, 0.461 mol) in DMF (700 mL) and
stirring was continued for 24 h. Quenching of the mixture with brine,
extraction of the aqueous phase with tert-butyl methyl ether, washing of the
combined organic layers with brine followed by drying (Na2SO4) and
evaporation of the solvent afforded compound 13 as a colorless solid
(73.05 g, 97%). 1H NMR (300.1 MHz, CDCl3): d ˆ 9.79 (s, 1H), 7.59 (d, J ˆ
1.8 Hz, 1H), 7.33 (d, J ˆ 1.8 Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H); 13C NM R
(75.5 MHz, CDCl3): d ˆ 189.7, 154.0, 151.7, 132.9, 128.5, 117.8, 110.1, 60.7,
56.1; IR: n ˆ 3072, 3051, 3006, 2978, 2945, 2860, 2745, 1693, 1588, 1566, 1487,
1471, 1451, 1420, 1393, 1380, 1313, 1281, 1240, 1212, 1189, 1144, 1133, 1048,
991, 856, 838, 817, 787, 751, 699, 666, 585, 566, 516 cmÀ1; MS (EI): m/z (%):
‡
247 (10), 246 (98), 245 (25), 244 (100) [M] , 243 (15), 231 (25), 229 (26), 175
‡
631, 566, 528, 507 cmÀ1; MS (EI): m/z (%): 486 (<1) [M] , 455 (<1), 285
(12), 173 (12), 158 (5), 157 (5), 135 (8), 122 (7), 107 (6), 94 (40), 93 (6), 79
(12), 77 (11), 76 (6), 75 (8), 74 (5), 66 (6), 65 (10), 63 (10), 62 (9), 53 (7), 51
(18), 50 (15), 29 (5); HR-MS (EI) (C9H9BrO3): calcd 243.9735; found
243.9737.
(2), 122 (15), 121 (100), 91 (3), 78 (5), 77 (5); HR-MS (CI, isobutane)
(C24H23BrO6‡H): calcd 487.0756; found 487.0755; elemental analysis calcd
(%) for C24H23BrO6 (487.35): C 59.15, H 4.76; found C 59.13, H 4.68.
[4-Bromo-3,5-bis-(4-methoxybenzyloxy)-phenyl]-methanol (9): LiBH4
(8.09 g, 371.4 mmol) was added to a solution of compound 8 (36.2 g,
74.29 mmol) in THF (400 mL). MeOH (15 mL, 371.4 mmol) was then
added dropwise to the solution over a period of 30 min at 08C and the
resulting mixture was refluxed for 3 h. Addition of water at 08C, extraction
of the aqueous phase with tert-butyl methyl ether, drying of the combined
organic layers (Na2SO4) and evaporation of the solvent delivered alcohol 9
as a colorless solid (33.5 g, 98%). M.p. 130 1318C; 1H NMR (300.1 MHz,
[D6]acetone): d ˆ 7.44 (AA'XX', 4H), 6.94 (AA'XX', 4H), 6.83 (s, 2H), 5.10
(s, 4H), 4.60 (d, J ˆ 5.4 Hz, 2H), 4.33 (t, J ˆ 5.7 Hz, 1H), 3.78 (s, 6H);
13C NMR (75.5 MHz, [D6]acetone): d ˆ 160.4, 157.1, 144.5, 129.8, 114.6,
105.4, 100.5, 71.2, 64.4, 55.5; IR: n ˆ 3500, 3067, 3039, 2937, 2880, 2842, 1611,
1588, 1516, 1458, 1431, 1378, 1322, 1302, 1249, 1195, 1178, 1097, 1031, 1015,
999, 974, 920, 855, 835, 821, 776, 719, 695, 656, 606, 589, 508 cmÀ1; MS (EI):
5-Bromo-3,4-dimethoxyphenol (14): A solution of compound 13 (40 g,
0.163 mol) and 3-chloroperbenzoic acid (70% w/w, 60.35 g, 0.245 mol) in
CH2Cl2 (600 mL) was refluxed for 16 h. The reaction mixture was carefully
added to vigorously stirred aq. sat. NaHCO3 (1 L) and stirring was
continued for an additional 30 min. The aqueous layer was extracted with
CH2Cl2 and the combined organic phases were successively washed with aq.
sat. NaHCO3, aq. sat. Na2S2O5 (test for peroxides must be negative after
this step) and brine. The organic phase was then dried (Na2SO4) and the
solvent was evaporated. The residue was dissolved in MeOH (300 mL),
conc. HCl/water (1:1, 300 mL) was added and the mixture was stirred for
30 min. The MeOH was then evaporated, the residue was extracted with
tert-butyl methyl ether, the combined organic layers were washed with
brine, dried (Na2SO4) and evaporated to afford phenol 14 as a colorless
solid which was analytically pure and could be used in the next step without
further purification (26.71 g, 70%). 1H NMR (300.1 MHz, [D6]acetone):
d ˆ 8.42 (brs, 1H), 6.59 (d, J ˆ 2.7 Hz, 1H), 6.50 (d, J ˆ 2.7 Hz, 1H), 3.80 (s,
3H), 3.68 (s, 3H); 13C NMR (75.5 MHz, [D6]acetone): d ˆ 155.2, 155.2,
140.5, 117.6, 110.9, 101.3, 60.5, 56.2; IR: n ˆ 3297, 3083, 2993, 2946, 2836,
1610, 1581, 1500, 1477, 1452, 1430, 1345, 1319, 1261, 1228, 1204, 1183, 1145,
1046, 994, 976, 856, 837, 821, 772, 728, 684, 632, 554 cmÀ1; MS (EI): m/z (%):
‡
m/z (%): 458 (<1) [M] , 257 (<1), 122 (11), 121 (100), 91 (3), 78 (4), 77 (4),
51 (1); elemental analysis calcd (%) for C23H23BrO5 (459.34): C 60.14, H
5.05; found C 60.09, H 5.14.
[4-Bromo-3,5-bis-(4-methoxybenzyloxy)-benzyloxy]-tert-butyldiphenylsi-
lane (10): Imidazole (1.885 g, 27.69 mmol) and tBuPh2SiCl (7.612 g,
27.69 mmol) were added to a solution of alcohol 9 (10.6 g, 23.08 mmol) in
DMF (150 mL) and the resulting mixture was stirred for 12 h. A standard
extractive work-up followed by recrystallization of the residue from diethyl
ether/pentane (1:1) delivered compound 10 as a colorless solid (13.2 g,
82%). M.p. 71 738C; 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.71 7.68 (m,
4H), 7.50 7.38 (m, 10H), 6.92 (AA'XX', 4H), 6.68 (s, 2H), 5.04 (s, 4H),
4.74 (s, 2H), 3.81 (s, 6H), 1.13 (s, 9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ
159.9, 156.5, 142.2, 135.9, 133.7, 130.2, 129.3, 129.0, 128.1, 114.2, 104.5, 100.5,
71.0, 65.7, 55.6, 27.0, 19.5; IR: n ˆ 3072, 3045, 2998, 2955, 2928, 2892, 2855,
1613, 1590, 1514, 1462, 1432, 1388, 1377, 1363, 1328, 1302, 1262, 1247, 1212,
1173, 1114, 1094, 1035, 1008, 976, 940, 925, 825, 808, 744, 703, 689, 654, 637,
‡
235 (8), 234 (92), 233 (9), 232 (93) [M] , 220 (8), 219 (98), 218 (10), 217
(100), 191 (45), 189 (46), 176 (11), 174 (12), 138 (7), 137 (6), 135 (5), 133 (8),
110 (44), 109 (9), 108 (10), 95 (15), 93 (7), 81 (5), 79 (8), 69 (30), 66 (6), 65
(15), 63 (6), 59 (8), 53 (27), 51 (17), 50 (11), 39 (19), 38 (8), 29 (5); HR-MS
(EI) (C8H9BrO3): calcd 231.9735; found 231.9735.
5-Hydroxy-2,3-dimethoxybenzonitrile (15): CuCN (10.39 g, 116 mmol) was
added to a solution of phenol 14 (20.8 g, 89.23 mmol) in DMF (400 mL) and
the resulting mixture was refluxed for 12 h. The reaction was quenched by
addition of brine, the aqueous layer was extracted with tert-butyl methyl
ether, the combined organic phases were washed with brine, dried
(Na2SO4), and evaporated to give nitrile 15 as a pale yellow solid which
was analytically pure and could be used in the next step without further
purification (14.23 g, 89%). 1H NMR (300.1 MHz, [D6]acetone): d ˆ 8.85
8.65 (brs, 1H), 6.79 (d, J ˆ 2.8 Hz, 1H), 6.57 (d, J ˆ 2.9 Hz, 1H), 3.85 (s,
3H), 3.83 (s, 3H); 13C NMR (75.5 MHz, [D6]acetone): d ˆ 155.0, 154.7,
145.6, 116.6, 109.3, 107.6, 106.9, 61.7, 56.3; IR: n ˆ 3347, 3095, 3011, 2982,
2953, 2839, 2241, 1612, 1599, 1502, 1476, 1431, 1360, 1337, 1274, 1243, 1209,
1194, 1163, 1080, 998, 928, 859, 825, 776, 737, 681, 627, 608, 567 cmÀ1; M S
‡
‡
618, 573, 505 cmÀ1; MS (EI): m/z (%): 698 (<1) [M‡2] , 696 (<1) [M] ,
641 (2), 639 (2), 241 (<1), 199 (<1), 122 (12), 121 (100), 91 (1), 77 (1);
elemental analysis calcd (%) for C39H41BrO5Si (697.74): C 67.13, H 5.92;
found C 66.94, H 5.84.
5-Bromo-4-hydroxy-3-methoxybenzaldehyde (12): Bromine (57.75 g,
0.361 mol) was added over a period of 2.5 h to a solution of vanilline 11
(50 g, 0.329 mol) in MeOH (400 mL) at 08C and the resulting mixture was
stirred at ambient temperature for 1 h. After cooling to 08C, water
Chem. Eur. J. 2002, 8, No. 8
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1863 $ 20.00+.50/0
1863

A. F¸rstner et al.
FULL PAPER
‡
(EI): m/z (%): 180 (8), 179 (97) [M] , 165 (9), 164 (100), 136 (26), 118 (5),
109 (9), 108 (16), 93 (8), 81 (5), 80 (8), 79 (7), 76 (6), 69 (14), 66 (15), 65 (6),
64 (6), 63 (6), 53 (14), 52 (7), 51 (7), 50 (6), 42 (8), 39 (13); HR-MS (EI)
(C9H9NO3): calcd 179.0582; found 179.0582.
2-[4'-(tert-Butyldiphenylsilanyloxymethyl)-6-methoxy-4,2',6'-tris-(4-methoxy-
benzyloxy)-biphenyl-2-yl]-4,4-dimethyl-4,5-dihydro-oxazole (19; R1 ˆ
R2 ˆ PMB, R3 ˆ TBDPS):
A solution of 1,2-dibromoethane (1.265 g,
6.731 mmol) in THF (10 mL) was added over a period of 20 min to a
refluxing suspension of Mg powder (654 mg, 26.93 mmol) and aryl bromide
10 (9.393 g, 13.46 mmol) in THF (120 mL) and reflux was continued for
another 3 h. Excess magnesium was filtered off, a solution of oxazoline 18
(2.5 g, 6.731 mmol) in THF (40 mL) was added and the resulting mixture
was refluxed for 48 h. The reaction was quenched with aq. sat. NH4Cl, the
aqueous layer was extracted with tert-butyl methyl ether, the combined
organic phases were washed with brine, dried (Na2SO4), the solvent was
evaporated, and the residue was purified by flash chromatography on silica
(hexanes/ethyl acetate 10:1 ! 4:1 ! 2:1) to afford biaryl 19 as a colorless
foam (5.414 g, 84%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.74 (m, 4H),
7.51 7.39 (m, 8H), 7.18 (AA'XX', 4H), 7.12 (d, J ˆ 2.4 Hz, 1H), 6.96
(AA'XX', 2H), 6.82 (AA'XX', 4H), 6.72 (d, J ˆ 2.4 Hz, 1H), 6.67 (s, 2H),
5.07 (s, 2H), 4.90 (m, 4H), 4.79 (s, 2H), 3.83 (s, 3H), 3.77 (s, 6H), 3.75 (s,
2H), 3.71 (s, 3H), 1.15 (s, 6H), 1.13 (s, 9H); 13C NMR (75.5 MHz, CD2Cl2):
d ˆ 162.9, 160.0, 159.5, 159.2, 158.9, 157.8, 142.1, 136.0, 134.0, 131.7, 130.1,
129.9, 129.4, 128.7, 128.1, 117.4, 114.9, 114.3, 114.0, 106.2, 104.0, 101.7, 79.3,
70.5, 70.4, 67.6, 66.2, 56.1, 55.6, 55.5, 28.2, 27.0, 19.6; IR: n ˆ 3070, 3046,
2959, 2931, 2894, 2857, 2835, 1653, 1612, 1601, 1585, 1515, 1462, 1428, 1359,
1333, 1303, 1249, 1174, 1141, 1106, 1032, 999, 975, 937, 822, 742, 704, 610,
2,3-Dimethoxy-5-(4-methoxybenzyloxy)-benzonitrile (16): K2CO3 (12.22 g,
88.39 mmol), nBu4NI (2.177 g, 5.893 mmol) and 4-methoxybenzyl chloride
(11.07 g, 70.71 mmol) were added to a solution of nitrile 15 (10.56 g,
58.93 mmol) in DMF (300 mL) and the resulting suspension was stirred at
808C for 12 h. Addition of brine was followed by extraction of the aqueous
phase with tert-butyl methyl ether. The combined organic layers were
washed with brine, dried over Na2SO4, evaporated, and the residue was
triturated with pentane/tert-butyl methyl ether (1:1). The precipitate was
filtered off and dried in vacuo to give compound 16 as a colorless solid
(14.51 g, 82%). M.p. 88 898C; 1H NMR (300.1 MHz, CDCl3): d ˆ 7.31
(AA'XX', 2H), 6.90 (AA'XX', 2H), 6.72 (d, J ˆ 2.8 Hz, 1H), 6.61 (d, J ˆ
2.7 Hz, 1H), 4.09 (s, 2H), 3.91 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H); 13C NM R
(75.5 MHz, CDCl3): d ˆ 159.7, 155.2, 153.5, 146.3, 129.3, 127.9, 116.2, 114.1,
106.9, 106.7, 106.4, 70.5, 61.8, 55.9, 55.2; IR: n ˆ 3090, 3060, 3008, 2978, 2938,
2874, 2839, 2232, 1613, 1597, 1587, 1518, 1493, 1469, 1450, 1424, 1382, 1351,
1304, 1283, 1254, 1235, 1194, 1176, 1156, 1116, 1077, 1025, 993, 934, 873, 864,
827, 816, 785, 771, 743, 635, 617, 543, 526 cmÀ1; MS (EI): m/z (%): 299 (2)
‡
[M] , 178 (1), 122 (12), 121 (100), 91 (3), 78 (7), 77 (6), 53 (2), 52 (2), 51 (2);
HR-MS (CI, isobutane) (C17H17NO4‡H): calcd 300.1236; found 300.1235;
elemental analysis calcd (%) for C17H17NO4 (299.33): C 68.22, H 5.72, N
4.68; found C 68.20, H 5.66, N 4.66.
‡
504 cmÀ1; MS (EI): m/z (%): 958 (2), 957 (2) [M] , 838 (3), 837 (8), 836 (11),
821 (3), 820 (4), 297 (2), 256 (2), 122 (9), 121 (100); elemental analysis calcd
(%) for C59H63NO9Si (958.24): C 73.95, H 6.63, N 1.46; found C 73.78, H
6.63, N 1.44.
2-[2,3-Dimethoxy-5-(4-methoxybenzyloxy)-phenyl]-4,4-dimethyl-4,5-dihy-
dro-oxazole (18): LiOH (3.21 g, 134.1 mmol) was added to a suspension of
compound 16 (8.03 g, 26.83 mmol) in MeOH (200 mL) and water (50 mL)
and the resulting mixture was refluxed for 72 h. The MeOH was evaporated
and more water (150 mL) was added. Aq. HCl was then introduced at 08C
to adjust the pH of the aqueous layer to ꢂ3.5. Extraction of the aqueous
layer with ethyl acetate, drying of the combined organic phases (Na2SO4)
and evaporation of the solvent delivered 2,3-dimethoxy-5-(4-methoxyben-
zyloxy)-benzoic acid as a colorless solid which had the following analytical
and spectroscopic properties (8.37 g, 98%). M.p. 104 1058C; 1H NM R
(300.1 MHz, [D6]acetone): d ˆ 12.30 10.20 (brs, 1H), 7.40 (AA'XX', 2H),
6.98 (d, J ˆ 3.0 Hz, 1H), 6.94 (AA'XX', 2H), 6.88 (d, J ˆ 3.0 Hz, 1H), 5.03
(s, 2H), 3.88 (s, 3H), 3.87 (s, 3H), 3.79 (s, 3H); 13C NMR (75.5 MHz,
[D6]acetone): d ˆ 166.5, 160.5, 156.1, 154.1, 143.6, 130.3, 129.8, 125.7, 114.6,
106.6, 106.0, 70.1, 61.9, 56.5, 55.5; IR: n ˆ 3436, 3084, 3056, 3008, 2971, 2935,
2879, 2837, 2618, 1693, 1602, 1585, 1517, 1488, 1460, 1446, 1427, 1412, 1378,
1343, 1305, 1280, 1253, 1207, 1184, 1146, 1112, 1061, 1034, 1020, 960, 931,
907, 858, 847, 823, 799, 782, 767, 725, 679, 630, 606, 532 cmÀ1; MS (EI): m/z
4'-(tert-Butyldiphenylsilanyloxymethyl)-6-methoxy-4,2',6'-tris-(4-methoxy-
benzyloxy)-biphenyl-2-carbaldehyde (20; R ˆ PMB): A solution of methyl
triflate (351 mg, 2.139 mmol) in CH2Cl2 (5 mL) was added dropwise over
15 min to a solution of compound 19 (1.025 g, 1.07 mmol) in CH2Cl2
(40 mL) at À108C and the resulting solution was stirred for 2 h while the
temperature was slowly raised to 08C. MeOH/THF (4:1, 15 mL) was
introduced at 08C followed by the careful addition of NaBH4 (202 mg,
5.349 mmol). After stirring for 3 h at ambient temperature the reaction was
quenched with aq. sat. NH4Cl, the aqueous layer was extracted with
CH2Cl2, dried (Na2SO4), and the solvent was evaporated. Oxalic acid
(193 mg, 2.139 mmol) was added to a solution of the residue in THF/H2O
(4:1, 50 mL) and the mixture was stirred for 12 h. Addition of aq. sat.
NaHCO3, extraction with tert-butyl methyl ether, drying of the combined
organic layers (Na2SO4), evaporation of the solvent and flash chromatog-
raphy of the residue on silica (hexanes/ethyl acetate 4:1) afforded aldehyde
20 as a colorless foam (670 mg, 70%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ
9.67 (s, 1H), 7.74 7.71 (m, 4H), 7.51 7.39 (m, 8H), 7.18 (d, J ˆ 2.5 Hz, 1H),
7.08 (AA'XX', 4H), 6.95 (AA'XX', 2H), 6.86 (d, J ˆ 2.4 Hz, 1H), 6.81
(AA'XX', 4H), 6.74 (s, 2H), 5.08 (s, 2H), 4.91 (s, 4H), 4.81 (s, 2H), 3.83 (s,
3H), 3.77 (s, 6H), 3.75 (s, 3H), 1.14 (s, 9H); 13C NMR (75.5 MHz, CD2Cl2):
d ˆ 193.0, 160.1, 159.8, 159.6, 159.3, 158.0, 143.7, 136.2, 136.0, 133.8, 130.2,
129.9, 129.5, 129.1, 128.8, 128.2, 122.0, 114.3, 114.1, 110.4, 105.4, 103.7, 101.5,
70.4, 66.0, 56.3, 55.6, 55.5, 27.1, 19.6; IR: n ˆ 3070, 3045, 2998, 2955, 2932,
2856, 2836, 1689, 1612, 1602, 1586, 1515, 1463, 1429, 1374, 1334, 1303, 1282,
1250, 1175, 1151, 1104, 1034, 997, 936, 823, 742, 704, 657, 613, 505 cmÀ1; M S
‡
(%): 319 (1), 318 (5) [M] , 197 (<1), 137 (2), 122 (13), 121 (100), 91 (3), 78
(5), 77 (5), 53 (2), 52 (1), 51 (2), 39 (2); HR-MS (CI, isobutane)
(C17H18O6‡H): calcd 319.1182; found 319.1185; elemental analysis calcd
(%) for C17H18O6 (318.33): C 64.14, H 5.70; found C 64.20, H 5.62.
A solution of PPh3 (8.24 g, 31.42 mmol) in pyridine/MeCN (1:1, 50 mL) was
added over a period of 30 min to a mixture of 2,3-dimethoxy-5-(4-
methoxybenzyloxy)-benzoic acid (2.0 g, 6.283 mmol), 2-amino-2-methyl-
propan-1-ol 17 (560 mg, 6.283 mmol), (iPr)2NEt (4.06 g, 31.42 mmol) and
CCl4 (4.833 g, 31.42 mmol) in pyridine/MeCN (1:1, 50 mL) at 08C. The
resulting mixture was stirred at 808C for 16 h, all volatiles were evaporated
in vacuo at 608C, and the residue was dissolved in ethyl acetate. Water was
added, the aqueous layer was extracted with ethyl acetate, the combined
organic phases were washed with aq. sat. CuSO4, dried (Na2SO4), and the
solvent was evaporated. The residue was purified by flash chromatography
on silica (hexanes/ethyl acetate 4:1 ! 2:1) to deliver oxazoline 18 as a pale
yellow solid (1.86 g, 80%). M.p. 89 908C; 1H NMR (300.1 MHz, CD2Cl2):
d ˆ 7.36 (AA'XX', 2H), 6.92 (AA'XX', 2H), 6.87 (d, J ˆ 2.9 Hz, 1H), 6.66
(d, J ˆ 2.9 Hz, 1H), 4.96 (s, 2H), 4.08 (s, 2H), 3.82 (s, 3H), 3.81 (s, 3H), 3.75
(s, 3H), 1.36 (s, 6H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 161.0, 160.0, 155.2,
154.5, 143.3, 129.7, 129.3, 123.6, 114.2, 105.8, 104.1, 79.3, 70.6, 67.9, 61.6, 56.3,
55.6, 28.4; IR: n ˆ 3070, 2965, 2935, 2894, 2836, 1646, 1612, 1588, 1515, 1490,
1465, 1426, 1363, 1337, 1302, 1249, 1192, 1172, 1138, 1112, 1029, 976, 935,
900, 824, 786, 749, 712, 627, 602, 571, 525 cmÀ1; MS (EI): m/z (%): 372 (5),
‡
(EI): m/z (%): 889 (3), 888 (4) [M] , 767 (1), 241 (1), 199 (2), 122 (13), 121
(100), 77 (1); elemental analysis calcd (%) for C55H56O9Si (889.13): C 74.30,
H 6.35; found C 74.18, H 6.32.
1-[4'-(tert-Butyldiphenylsilanyloxymethyl)-6-methoxy-4,2',6'-tris-(4-methoxy-
benzyloxy)-biphenyl-2-yl]-pent-4-en-1-ol (24a; R ˆ PMB, n ˆ 2, X ˆ
ˆ
CH CH2): A solution of 3-butenylmagnesium bromide (0.5m in THF,
2.7 mL, 1.35 mmol) was added dropwise to a solution of aldehyde 20
(400 mg, 0.45 mmol) in THF (20 mL) at 08C and the resulting mixture was
stirred for 1 h at that temperature. A standard extractive work-up followed
by flash chromatography on silica (hexanes/ethyl acetate 4:1) provided
alcohol 24a as a colorless syrup (350 mg, 82%). 1H NMR (300.1 MHz,
CD2Cl2): d ˆ 7.73 7.70 (m, 4H), 7.49 7.38 (m, 8H), 7.10 (AA'XX', 2H),
7.07 (AA'XX', 2H), 6.94 (AA'XX', 2H), 6.80 (m, 5H), 6.72 (s), 6.69 (s, 2H),
6.55 (d, J ˆ 2.3 Hz, 1H), 5.60 (ddt, J ˆ 16.9, 10.2, 6.5 Hz, 1H), 5.04 (s, 2H),
4.91 4.78 (m, 6H), 4.77 (s, 2H), 4.40 (t, J ˆ 6.5 Hz, 1H), 3.82 (m, 3H), 3.76
(brs, 6H), 3.70 (brs, 3H), 2.03 (m, 1H), 1.88 (m, 2H), 1.65 (m, 2H), 1.54 (s,
9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 160.0, 160.0, 159.7, 159.5, 158.6,
158.2, 157.1, 146.1, 142.7, 139.0, 136.0, 133.8, 130.1, 129.9, 129.8, 129.7, 129.4,
129.1, 128.5, 128.1, 115.2, 114.3, 114.3, 114.2, 114.1, 113.9, 104.6, 104.1, 102.6,
‡
371 (20) [M] , 356 (2), 340 (5), 122 (13), 121 (100), 91 (2), 78 (3), 77 (3);
HR-MS (EI) (C21H25NO5): calcd 371.1733; found 371.1732; elemental
analysis calcd (%) for C21H25NO5 (371.43): C 67.91, H 6.78, N 3.77; found C
68.04, H 6.72, N 3.70.
1864
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1864 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 8

Turrianes
1856 1871
98.7, 71.1, 70.9, 70.2, 70.0, 66.0, 56.0, 55.6, 55.5, 36.4, 30.4, 27.0, 19.5; IR: n ˆ
3452, 3070, 2998, 2955, 2928, 2854, 1639, 1612, 1604, 1585, 1514, 1462, 1428,
1418, 1373, 1323, 1303, 1249, 1175, 1150, 1101, 1032, 999, 911, 822, 777, 742,
successively added to a solution of alcohol 24a (135 mg, 0.143 mmol) in
CH2Cl2 (15 mL) at À208C. The resulting solution was stirred for 1 h at
À208C and for 12 h at ambient temperature. All volatiles were evaporated
and the residue was purified by flash chromatography on silica (hexanes/
ethyl acetate 6:1 ! 4:1) to deliver thiocarbonate 25a as a colorless foam
(145 mg, 94%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.72 7.68 (m, 4H),
7.48 7.21 (m, 11H), 7.12 (AA'XX', 2H), 7.07 (AA'XX', 2H), 6.95
(AA'XX', 2H), 6.83 6.78 (m, 7H), 6.70 (m), 6.65 (m, 2H), 6.64 (d, J ˆ
2.4 Hz, 1H), 6.15 (m, 1H), 5.62 (ddt, J ˆ 17.0, 10.4, 6.2 Hz, 1H), 5.05 (s,
2H), 4.96 4.84 (m, 6H), 4.78 (s, 2H), 3.82 (s, 3H), 3.77 (s, 3H), 3.76 3.74
(m, 6H), 1.92 (m, 4H), 1.10 (s, 9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ
194.3, 160.0, 159.9, 159.5, 159.3, 158.8, 158.1, 157.3, 153.8, 143.1, 140.5, 138.1,
136.0, 133.9, 130.1, 129.9, 129.8, 129.7, 129.5, 128.7, 128.6, 128.1, 128.0, 126.6,
122.3, 116.0, 114.8, 114.3, 114.1, 114.0, 112.5, 103.6, 103.5, 103.3, 99.4, 84.4,
70.2, 70.0, 69.6, 66.1, 56.2, 55.6, 55.5, 35.0, 29.4, 27.0, 19.5; IR: n ˆ 3070, 2998,
2954, 2930, 2856, 2835, 1639, 1605, 1586, 1514, 1490, 1461, 1429, 1365, 1322,
1301, 1249, 1193, 1152, 1105, 1034, 1000, 914, 822, 770, 742, 703, 690, 613,
‡
702, 607 cmÀ1; MS (EI): m/z (%): 945 (<1), 944 (<1) [M] , 824 (2), 823 (3),
808 (2), 807 (3), 806 (4), 752 (2), 751 (3), 688 (2), 687 (4), 629 (2), 122 (14),
121 (100); elemental analysis calcd (%) for C59H64O9Si (945.24): C 74.97, H
6.82; found C 74.86, H 6.78.
1-[4'-(tert-Butyldiphenylsilanyloxymethyl)-6-methoxy-4,2',6'-tris-(4-meth-
oxybenzyloxy)-biphenyl-2-yl]-hept-6-en-1-ol (24b; R ˆ PMB, n ˆ 4, X ˆ
ˆ
CH CH2): Prepared as described above from aldehyde 20 (500 mg,
0.562 mmol) and 5-hexenylmagnesium bromide (0.4m in THF, 4.22 mL,
1.687 mmol). Colorless syrup (430 mg, 79%). 1H NMR (300.1 MHz,
CD2Cl2): d ˆ 7.71 (m, 4H), 7.50 7.38 (m, 8H), 7.09 (m, 4H), 6.94 (AA'XX',
2H), 6.80 (m, 5H), 6.72 (s), 6.69 (s, 2H), 6.56 (d, J ˆ 2.2 Hz, 1H), 5.71 (ddt,
J ˆ 17.0, 10.3, 6.7 Hz, 1H), 5.05 (s, 2H), 4.95 4.83 (m, 6H), 4.77 (s, 2H),
4.37 (t, J ˆ 6.6 Hz, 1H), 3.82 (s, 3H), 3.76 (s, 6H), 3.70 (s, 3H), 2.11 1.97
(m, 1H), 1.87 (m, 2H), 1.67 1.48 (m, 2H), 1.23 1.10 (m, 4H), 1.12 (s, 9H);
13C NMR (75.5 MHz, CD2Cl2): d ˆ 160.0, 160.0, 159.7, 159.5, 158.5, 158.2,
157.1, 146.3, 142.6, 139.5, 136.0, 133.8, 130.1, 129.9, 129.8, 129.7, 129.4, 129.1,
128.4, 129.1, 115.3, 114.3, 114.2, 114.1, 114.1, 104.6, 104.2, 102.6, 98.6, 71.5,
70.9, 70.1, 70.0, 66.0, 56.0, 55.6, 55.5, 36.9, 34.0, 29.1, 27.1, 25.7, 19.6; IR: n ˆ
3447, 3070, 2998, 2931, 2856, 2835, 1639, 1604, 1585, 1514, 1461, 1428, 1372,
1323, 1303, 1249, 1175, 1150, 1112, 1035, 999, 911, 822, 742, 703, 611,
‡
505 cmÀ1; MS (EI): m/z (%): 1046 (<1) [M À H2S] , 926 (2), 807 (2), 806
(5), 805 (4), 752 (2), 751 (4), 750 (5), 749 (8), 686 (2), 685 (2), 670 (2), 642
(2), 641 (3), 631 (2), 630 (2), 629 (4), 550 (2), 199 (8), 135 (2), 122 (9), 121
(100); elemental analysis calcd (%) for C66H68O10SSi (1081.41): C 73.30, H
6.33; found C 73.41, H 6.30.
Thiocarbonic acid O-{1-[4'-(tert-butyldiphenylsilanyloxymethyl)-6-meth-
oxy-4,2',6'-tris-(4-methoxybenzyloxy)-biphenyl-2-yl]-hept-6-enyl}ester O-
‡
504 cmÀ1; MS (EI): m/z (%): 972 (<1) [M] , 850 (<1), 834 (1), 833 (2), 779
(<1), 715 (1), 657 (<1), 122 (9), 121 (100); elemental analysis calcd (%) for
C61H68O9Si (973.29): C 75.28, H 7.04; found C 75.22, H 7.09.
ˆ
phenyl ester (25b; R ˆ PMB, n ˆ 4, X ˆ CH CH2): Prepared as described
above from alcohol 24b (380 mg, 0.39 mmol) and phenyl chlorothionofor-
mate (135 mg, 0.781 mmol). Colorless foam (339 mg, 78%). 1H NM R
(300.1 MHz, CD2Cl2): d ˆ 7.71 7.68 (m, 4H), 7.47 7.20 (m, 11H), 7.11
(AA'XX', 2H), 7.07 (AA'XX', 2H), 6.94 (AA'XX', 2H), 6.82 6.77 (m,
7H), 6.69 (brs), 6.66 (m, 2H), 6.63 (d, J ˆ 2.3 Hz, 1H), 6.13 (™t∫, J ˆ 6.4 Hz,
1H), 5.70 (ddt, J ˆ 17.0, 10.2, 6.6 Hz, 1H), 5.04 (brs, 2H), 4.97 4.84 (m,
6H), 4.77 (brs, 2H), 3.82 (m, 3H), 3.77 (s), 3.76 (s), 3.74 (s), 3.73 (s, 9H),
1.85 (m, 4H), 1.22 1.14 (m, 4H), 1.10 (s, 9H); 13C NMR (75.5 MHz,
CD2Cl2): d ˆ 194.3, 160.0, 159.9, 159.5, 159.3, 158.7, 158.1, 157.3, 153.8, 143.1,
140.7, 139.3, 136.0, 133.9, 130.1, 129.9, 129.6, 129.5, 128.7, 128.4, 128.1, 128.1,
126.6, 122.3, 116.0, 114.3, 114.1, 114.0, 112.6, 103.6, 103.5, 103.4, 99.4, 84.8,
70.2, 70.0, 69.6, 66.1, 56.1, 55.6, 55.5, 35.5, 33.9, 29.0, 27.0, 24.6, 19.5; IR: n ˆ
3070, 2998, 2931, 2856, 2835, 1639, 1605, 1585, 1514, 1490, 1461, 1429, 1364,
1322, 1302, 1286, 1249, 1193, 1152, 1106, 1034, 998, 938, 912, 823, 769, 742,
1-[4'-(tert-Butyldiphenylsilanyloxymethyl)-6-methoxy-4,2',6'-tris-(4-meth-
oxybenzyloxy)-biphenyl-2-yl]-hex-4-yn-1-ol (24c; R ˆ PMB, n ˆ 2, X ˆ
ꢀ
C CCH3): Prepared as described above from aldehyde 20 (185 mg,
0.208 mmol) and 3-pentynylmagnesium bromide (0.4m in THF, 1.56 mL,
0.624 mmol). Colorless syrup (174 mg, 87%). 1H NMR (300.1 MHz,
CD2Cl2): d ˆ 7.73 7.70 (m, 4H), 7.50 7.39 (m, 8H), 7.14 (AA'XX', 2H),
7.10 (AA'XX', 2H), 6.94 (AA'XX', 2H), 6.84 6.78 (m, 5H), 6.73 (s), 6.72
(s, 2H), 6.56 (d, J ˆ 2.3 Hz, 1H), 5.04 (s, 2H), 4.95 4.86 (m, 4H), 4.78 (s,
2H), 4.53 (m, 1H), 3.83 (s, 3H), 3.77 (s), 3.77 (s, 6H), 3.71 (s, 3H), 2.09 (m,
1H), 2.08 1.97 (m, 2H), 1.82 1.65 (m, 2H), 1.60 (t, J ˆ 2.5 Hz, 3H), 1.12 (s,
9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 160.0, 160.0, 159.7, 159.5, 158.6,
158.4, 157.1, 145.8, 142.6, 136.0, 133.8, 130.2, 129.9, 129.8, 129.6, 129.5, 129.0,
128.7, 128.1, 115.2, 114.3, 114.2, 114.1, 113.8, 104.3, 103.9, 102.6, 98.7, 78.9,
75.8, 70.8, 70.6, 70.2, 70.1, 65.9, 56.0, 55.6, 55.5, 36.7, 27.0, 19.5, 15.7, 3.5; IR:
n ˆ 3511, 3070, 3047, 2998, 2955, 2932, 2856, 2836, 1604, 1585, 1515, 1462,
1429, 1378, 1323, 1303, 1251, 1175, 1150, 1111, 1035, 1000, 954, 940, 824, 742,
704, 690, 611 cmÀ1; MS (EI): m/z (%): 1074 (<1) [M À H2S] , 955 (2), 954
‡
(2), 835 (3), 834 (5), 833 (5), 777 (2), 714 (2), 713 (3), 657 (2), 199 (3), 135
(2), 122 (11), 121 (100); elemental analysis calcd (%) for C68H72O10SSi
(1109.47): C 73.62, H 6.54; found C 73.49, H 6.46.
‡
706, 613, 505 cmÀ1; MS (EI): m/z (%): 956 (<1) [M] , 818 (1), 763 (<1), 700
(1), 699 (2), 443 (<1), 241 (1), 199 (1), 122 (14), 121 (100), 91 (<1), 77 (1);
elemental analysis calcd (%) for C60H64O9Si (957.25): C 75.28, H 6.74;
found C 75.15, H 6.79.
Thiocarbonic acid O-{1-[4'-(tert-butyldiphenylsilanyloxymethyl)-6-meth-
oxy-4,2',6'-tris-(4-methoxybenzyloxy)-biphenyl-2-yl]-hex-4-ynyl}ester O-phen-
ꢀ
yl ester (25c; R ˆ PMB, n ˆ 2, X ˆ C CCH3): Prepared as described above
from alcohol 24c (670 mg, 0.7 mmol) and phenyl chlorothionoformate
(242 mg, 194 mL, 1.4 mmol). Colorless foam (717 mg, 94%). 1H NM R
(300.1 MHz, CD2Cl2): d ˆ 7.73 7.69 (m, 4H), 7.49 7.22 (m, 11H), 7.18
(AA'XX', 2H), 7.07 (AA'XX', 2H), 6.96 (AA'XX', 2H), 6.86 6.80 (m,
6H), 6.78 (d, J ˆ 2.3 Hz, 1H), 6.72 (s, 1H), 6.65 (s, 1H), 6.64 (d, J ˆ 2.3 Hz,
1H), 6.20 (t, J ˆ 5.6 Hz, 1H), 5.05 (s, 2H), 4.95 (s, 2H), 4.92 4.83 (m, 2H),
4.79 (s, 2H), 3.83 (s), 3.82 (s, 3H), 3.78 (s), 3.77 (s, 3H), 3.75 (s, 3H), 3.73 (s),
3.72 (brs, 3H), 2.09 2.02 (m, 4H), 1.67 (m, 3H), 1.11 (s, 9H); 13C NM R
(75.5 MHz, CD2Cl2): d ˆ 194.1, 160.0, 159.9, 159.6, 159.3, 158.9, 158.2, 157.4,
153.8, 143.0, 140.1, 136.0, 133.8, 133.8, 130.1, 129.9, 129.8, 129.6, 129.5, 128.9,
128.8, 128.1, 128.0, 126.6, 122.3, 116.1, 114.3, 114.1, 114.0, 112.3, 103.6, 103.4,
103.1, 99.6, 83.7, 78.2, 76.2, 70.3, 70.1, 69.6, 66.0, 56.2, 55.6, 55.5, 35.4, 27.0,
19.5, 15.2, 3.6; IR: n ˆ 3069, 3044, 2998, 2955, 2931, 2856, 2835, 1605, 1585,
1514, 1490, 1461, 1429, 1365, 1322, 1302, 1275, 1249, 1192, 1151, 1104, 1032,
1-[4'-(tert-Butyldiphenylsilanyloxymethyl)-6-methoxy-4,2',6'-tris-(4-meth-
oxybenzyloxy)-biphenyl-2-yl]-oct-6-yn-1-ol (24d; R ˆ PMB, n ˆ 4, X ˆ
ꢀ
C CCH3): Prepared as described above from aldehyde 20 (1.5 g,
1.687 mmol) and 5-heptynylmagnesium bromide (0.3m in THF, 11.2 mL,
3.374 mmol). Colorless syrup (1.105 g, 66%): Rf 0.41 (hexanes/ethyl acetate
2:1); 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.76 7.73 (m, 4H), 7.53 7.41 (m,
8H), 7.13 (m, 4H), 6.97 (AA'XX', 2H), 6.86 6.82 (m, 5H), 6.76 (s), 6.74 (s,
2H), 6.56 (d, J ˆ 2.3 Hz, 1H), 5.08 (s, 2H), 4.96 (s, 2H), 4.92 (s), 4.90 (s,
2H), 4.82 (s, 2H), 4.41 (t, J ˆ 6.7 Hz; 1H), 3.84 (s, 3H), 3.79 (s), 3.78 (s, 6H),
3.74 (s, 3H), 2.13 (m, 1H), 1.98 1.92 (m, 2H), 1.72 (t, J ˆ 2.5 Hz; 3H),
1.67 1.55 (m, 2H), 1.35 1.25 (m, 4H), 1.15 (s, 9H); 13C NMR (75.5 MHz,
CD2Cl2): d ˆ 160.0, 160.0, 159.8, 159.5, 158.6, 158.3, 157.1, 146.2, 142.7, 136.0,
133.8, 130.2, 129.9, 129.8, 129.7, 129.4, 129.1, 128.4, 128.2, 115.3, 114.3, 114.2,
114.1, 114.0, 104.6, 104.2, 102.6, 98.7, 79.5, 75.5, 71.5, 70.9, 70.1, 70.0, 66.0,
56.0, 55.6, 55.5, 36.6, 29.3, 27.1, 25.5, 19.6, 18.8, 3.5; IR: n ˆ 3475, 3133, 3070,
3048, 2998, 2932, 2856, 2835, 1604, 1585, 1514, 1461, 1428, 1372, 1323, 1303,
1249, 1174, 1149, 1104, 1033, 999, 822, 742, 703, 612, 504 cmÀ1; MS (EI): m/z
‡
999, 821, 770, 742, 703, 690, 612, 503 cmÀ1; MS (ESI-pos): 1131 [M‡K] ,
‡
‡
‡
1115 [M‡Na] , 1099 [M‡Li] , 961 [M À C6H5OH À COS‡Na] , 939 [M À
‡
C6H5OH À COS‡H] ; elemental analysis calcd (%) for C67H68O10SSi
‡
(1093.42): C 73.60, H 6.27; found C 73.49, H 6.18.
(%): 984 (<1) [M] , 846 (2), 845 (3), 727 (1), 200 (1), 199 (4), 136 (1), 135
(2), 122 (12), 121 (100), 91 (2), 79 (2), 78 (2), 77 (3), 40 (4); MS (ESI-pos):
Thiocarbonic acid O-{1-[4'-(tert-butyldiphenylsilanyloxymethyl)-6-meth-
oxy-4,2',6'-tris-(4-methoxybenzyloxy)-biphenyl-2-yl]-oct-6-ynyl}ester O-
‡
‡
1023 [M‡K] , 1007 [M‡Na] ; elemental analysis calcd (%) for C62H68O9Si
(985.30): C 75.58, H 6.96; found C 75.65, H 7.08.
ꢀ
phenyl ester (25d; R ˆ PMB, n ˆ 4, X ˆ C CCH3): Prepared as described
Thiocarbonic acid O-{1-[4'-(tert-butyldiphenylsilanyloxy-methyl)-6-meth-
oxy-4,2',6'-tris-(4-methoxybenzyloxy)-biphenyl-2-yl]-pent-4-enyl}ester O-
above from alcohol 24d (1.0 g, 1.015 mmol) and phenyl chlorothionofor-
mate (350 mg, 281 mL, 2.03 mmol). Colorless foam (1.03 g, 90%). 1H NM R
(300.1 MHz, CD2Cl2): d ˆ 7.74 7.70 (m, 4H), 7.49 7.22 (m, 11H), 7.15
(AA'XX', 2H), 7.10 (AA'XX', 2H), 6.97 (AA'XX', 2H), 6.87 6.80 (m,
ˆ
phenyl ester (25a; R ˆ PMB, n ˆ 2, X ˆ CH CH2): Phenyl chlorothiono-
formate (49.3 mg, 0.286 mmol) and pyridine (33.9 mg, 0.428 mmol) were
Chem. Eur. J. 2002, 8, No. 8
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1865 $ 20.00+.50/0
1865

A. F¸rstner et al.
FULL PAPER
7H), 6.72 6.66 (m, 3H), 6.15 (t, J ˆ 6.5 Hz, 1H), 5.07 (s, 2H), 4.97 (s, 2H),
4.93 4.91 (m, 2H), 4.80 (s, 2H), 3.84 (m, 3H), 3.79 (s), 3.78 (s, 3H), 3.76 (s,
6H), 1.97 1.83 (m, 4H), 1.72 (t, J ˆ 2.5 Hz, 3H), 1.33 1.18 (m, 4H), 1.14
(s), 1.12 (s, 9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 194.3, 160.0, 159.9,
159.5, 159.3, 158.8, 158.1, 157.3, 153.8, 143.1, 140.6, 136.0, 133.9, 133.9, 130.1,
129.9, 129.7, 129.5, 128.7, 128.5, 128.2, 128.1, 126.6, 122.4, 116.1, 114.3, 114.1,
114.0, 112.6, 103.7, 103.5, 103.3, 99.4, 84.7, 79.3, 75.6, 70.2, 69.9, 69.7, 66.1,
56.1, 55.6, 55.6, 35.2, 29.1, 27.1, 24.4, 19.6, 18.8, 3.5; IR: n ˆ 3039, 3070, 2998,
2932, 2856, 2835, 1605, 1585, 1514, 1490, 1461, 1429, 1419, 1364, 1322, 1303,
1288, 1249, 1193, 1152, 1105, 1034, 999, 939, 822, 770, 742, 704, 691, 613,
Prepared as described above from thiocarbonate 25d (995 mg,
0.887 mmol). Colorless oil (650 mg, 76%). 1H NMR (300.1 MHz, CD2Cl2):
d ˆ 7.74 7.70 (m, 4H), 7.50 7.39 (m, 8H), 7.13 (AA'XX', 4H), 6.95
(AA'XX', 2H), 6.82 (AA'XX', 4H), 6.69 (s, 2H), 6.56 (d, J ˆ 2.3 Hz, 1H),
6.50 (d, J ˆ 2.3 Hz, 1H), 5.03 (s, 2H), 4.92 (s, 4H), 4.78 (s, 2H), 3.83 (s, 3H),
3.77 (s, 6H), 3.71 (s, 3H), 2.34 (™t∫, J ˆ 7.7 Hz, 2H), 1.96 (m, 2H), 1.71 (t,
J ˆ 2.6 Hz, 3H), 1.45 1.18 (m, 6H), 1.12 (s, 9H); 13C NMR (75.5 MHz,
CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.7, 157.8, 144.4, 142.2, 136.0, 133.9, 130.1,
130.0, 129.8, 128.6, 128.1, 116.2, 114.7, 114.2, 114.1, 106.4, 104.0, 96.9, 79.6,
75.4, 70.2, 70.1, 66.1, 55.9, 55.6, 55.5, 34.0, 30.1, 29.3, 29.0, 27.1, 19.6, 18.8, 3.5;
IR: n ˆ 3070, 3046, 2998, 2931, 2835, 1612, 1602, 1580, 1514, 1462, 1428,
1418, 1371, 1323, 1302, 1249, 1174, 1150, 1102, 1035, 999, 938, 822, 742, 703,
‡
‡
504 cmÀ1; MS (ESI-pos): 1143 [M‡Na] , 989 [M À C6H5OH À COS‡Na] ,
‡
967 [M À C6H5OH‡COS‡H] ; elemental analysis calcd (%) for
‡
C69H72O10SSi (1121.48): C 73.90, H 6.47; found C 74.06, H 6.40.
612, 505 cmÀ1; MS (EI): m/z (%): 969 (<1), 968 (1) [M] , 849 (3), 848 (7),
847 (10), 122 (9), 121 (100); elemental analysis calcd (%) for C62H68O8Si
(969.30): C 76.83, H 7.07; found C 76.72, H 7.11.
tert-Butyl-[2'-methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-6'-pent-4-enyl-bi-
ˆ
phenyl-4-ylmethoxy]-diphenylsilane (26a; R ˆ PMB, n ˆ 2, X ˆ CH CH2):
nBu3SnH (172 mg, 0.592 mmol) and AIBN (9.7 mg, 0.059 mmol) were
added to a solution of thiocarbonate 25a (320 mg, 0.296 mmol) in toluene
(30 mL) and the resulting mixture was stirred at 758C for 12 h. Evaporation
of the solvent followed by flash chromatography of the residue on silica
(hexanes (ca. 1 L), then hexanes/ethyl acetate 10:1 ! 6:1) afforded
compound 26a as a colorless oil (268 mg, 97%). 1H NMR (300.1 MHz,
CD2Cl2): d ˆ 7.72 (m, 4H), 7.49 7.39 (m, 8H), 7.12 (AA'XX', 4H), 6.94
(AA'XX', 2H), 6.81 (AA'XX', 4H), 6.69 (s, 2H), 6.56 (m, 1H), 6.50 (m,
1H), 5.65 (ddt, J ˆ 16.9, 10.2, 6.6 Hz, 1H), 5.02 (s, 2H), 4.95 4.84 (m, 6H),
4.78 (s, 2H), 3.82 (m, 3H), 3.77 (m, 6H), 3.71 (m, 3H), 2.36 (t, J ˆ 7.8 Hz,
2H), 1.90 (m, 2H), 1.52 (m, 2H), 1.12 (s, 9H); 13C NMR (75.5 MHz,
CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.8, 157.8, 144.2, 142.2, 139.3, 136.0,
133.9, 130.1, 130.0, 129.8, 128.7, 128.7, 128.1, 116.2, 114.6, 114.3, 114.3, 114.1,
106.5, 104.0, 97.0, 70.2, 70.1, 66.1, 55.9, 55.6, 55.5, 33.8, 33.7, 29.8, 27.1, 19.6;
IR: n ˆ 3070, 3047, 2998, 2954, 2932, 2857, 2835, 1638, 1612, 1602, 1584,
1514, 1462, 1429, 1418, 1373, 1324, 1303, 1249, 1174, 1150, 1111, 1035, 1000,
954, 912, 823, 741, 704, 612, 505 cmÀ1; MS (EI): m/z (%): 929 (1), 928 (1)
[2'-Methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-6'-pent-4-enyl-biphenyl-4-
ˆ
yl]-methanol (27a; R ˆ PMB, n ˆ 2, X ˆ CH CH2): TBAF ¥ 3H2O
(22.9 mg, 0.073 mmol) was added to a solution of compound 26a (45 mg,
0.048 mmol) in THF (5 mL) and the mixture was stirred for 2 h. The solvent
was evaporated and the residue was purified by flash chromatography on
silica (hexanes/ethyl acetate 1:1) affording alcohol 27a as a colorless oil
(33 mg, 99%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.41 (AA'XX', 2H), 7.13
(AA'XX', 4H), 6.94 (AA'XX', 2H), 6.82 (AA'XX', 4H), 6.71 (s, 2H), 6.55
(d, J ˆ 2.3 Hz, 1H), 6.48 (d, J ˆ 2.3 Hz, 1H), 5.64 (ddt, J ˆ 17.0, 10.4, 6.6 Hz,
1H), 5.02 (s, 2H), 4.94 (s, 4H), 4.90 4.82 (m, 2H), 4.66 (brs, 2H), 3.82 (s,
3H), 3.77 (s, 6H), 3.67 (s, 3H), 2.34 (t, J ˆ 7.8 Hz, 2H), 1.92 1.84 (m, 3H),
1.48 (m, 2H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.5, 158.7,
158.0, 144.1, 142.4, 139.3, 129.9, 129.8, 128.8, 128.8, 116.0, 115.3, 114.3, 114.2,
114.0, 106.5, 104.7, 97.0, 70.3, 70.1, 65.7, 55.9, 55.6, 55.6, 33.8, 33.7, 29.8; IR:
n ˆ 3427, 3072, 3037, 2997, 2933, 2865, 2835, 1638, 1612, 1602, 1580, 1515,
1461, 1430, 1418, 1376, 1322, 1303, 1249, 1175, 1150, 1103, 1033, 1000, 913,
‡
822, 774, 705, 626, 514 cmÀ1; MS (EI): m/z (%): 691 (2), 690 (4) [M] , 571
‡
[M] , 810 (1), 809 (4), 808 (9), 807 (12), 241 (2), 199 (1), 135 (2), 123 (1), 122
(22), 121 (100), 91 (1), 77 (1); elemental analysis calcd (%) for C59H64O8Si
(929.24): C 76.26, H 7.03; found C 76.30, H 7.03.
(2), 570 (6), 569 (9), 450 (1), 449 (2), 241 (1), 156 (1), 122 (15), 121 (100), 91
(1), 78 (1), 77 (2); HR-MS (ESI-pos) (C43H46O8‡Na): calcd 713.3090; found
713.3084; elemental analysis calcd (%) for C43H46O8 (690.83): C 74.76, H
6.71; found C 74.80, H 6.65.
tert-Butyl-[6'-hept-6-enyl-2'-methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-bi-
ˆ
phenyl-4-ylmethoxy]-diphenylsilane (26b; R ˆ PMB, n ˆ 4, X ˆ CH CH2):
[6'-Hept-6-enyl-2'-methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-biphenyl-4-
Prepared as described above from thiocarbonate 25b (325 mg,
0.293 mmol). Colorless oil (230 mg, 82%). 1H NMR (300.1 MHz, CD2Cl2):
d ˆ 7.72 (m, 4H), 7.50 7.39 (m, 8H), 7.13 (AA'XX', 4H), 6.96 (AA'XX',
2H), 6.81 (AA'XX', 4H), 6.69 (s, 2H), 6.57 (d, J ˆ 2.3 Hz, 1H), 6.50 (d, J ˆ
2.3 Hz, 1H), 5.75 (ddt, J ˆ 17.0, 10.2, 6.6 Hz, 1H), 5.03 (s, 2H), 4.96 4.86
(m, 2H), 4.92 (s, 4H), 4.78 (s, 2H), 3.83 (s, 3H), 3.77 (s, 6H), 3.71 (s, 3H),
2.34 (t, J ˆ 7.8 Hz, 2H), 1.91 (m, 2H), 1.42 (m, 2H), 1.30 1.11 (m, 4H), 1.12
(s, 9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.7, 157.8,
144.5, 142.2, 139.6, 136.0, 133.9, 130.1, 129.8, 128.6, 128.1, 116.2, 114.7, 114.2,
114.1, 106.4, 104.0, 96.9, 70.2, 70.1, 66.1, 55.9, 55.6, 55.5, 34.1, 34.0, 30.4, 29.3,
29.1, 27.1, 19.6; IR: n ˆ 3070, 2998, 2931, 2856, 1639, 1612, 1602, 1580, 1514,
1462, 1429, 1418, 1373, 1323, 1303, 1249, 1174, 1150, 1111, 1035, 999, 939,
ˆ
yl]-methanol (27b; R ˆ PMB, n ˆ 4, X ˆ CH CH2): Prepared as described
above from compound 26b (210 mg, 0.219 mmol). Colorless oil (150 mg,
95%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.41 (AA'XX', 2H), 7.14
(AA'XX', 4H), 6.94 (AA'XX', 2H), 6.83 (AA'XX', 4H), 6.70 (s, 2H),
6.55 (d, J ˆ 2.3 Hz, 1H), 6.48 (d, J ˆ 2.3 Hz, 1H), 5.73 (ddt, J ˆ 17.0, 10.2,
6.7 Hz, 1H), 5.02 (s, 2H), 4.95 (s, 4H), 4.95 4.85 (m, 2H), 4.66 (brs, 2H),
3.82 (™s∫, 3H), 3.77 (™s∫, 6H), 3.67 (™s∫, 3H), 2.32 (t, J ˆ 7.8 Hz, 2H), 1.87
(m, 3H), 1.40 (m, 2H), 1.25 1.12 (m, 4H); 13C NMR (75.5 MHz, CD2Cl2):
d ˆ 159.9, 159.5, 159.5, 158.7, 158.0, 144.5, 142.4, 139.7, 130.0, 129.8, 128.7,
116.0, 115.4, 114.2, 114.1, 114.0, 106.4, 104.8, 96.9, 70.3, 70.1, 65.7, 55.9, 55.6,
55.6, 34.1, 33.9, 30.3, 29.2, 29.0; IR: n ˆ 3427, 3071, 2997, 2931, 2855, 2836,
1639, 1612, 1602, 1580, 1514, 1461, 1430, 1418, 1377, 1322, 1303, 1248, 1174,
1150, 1102, 1034, 1000, 966, 909, 823, 705, 626, 512 cmÀ1; MS (EI): m/z (%):
‡
910, 822, 742, 704, 613, 505 cmÀ1; MS (EI): m/z (%): 957 (2), 956 (3) [M] ,
837 (5), 836 (12), 835 (15), 241 (2), 122 (15), 121 (100); elemental analysis
calcd (%) for C61H68O8Si (957.29): C 76.54, H 7.16; found C 76.64, H 7.10.
‡
719 (2), 718 (3) [M] , 689 (1), 688 (2), 599 (2), 598 (4), 597 (6), 568 (1), 567
(2), 241 (2), 123 (1), 122 (18), 121 (100), 91 (1), 77 (2); elemental analysis
calcd (%) for C45H50O8 (718.89): C 75.18, H 7.01; found C 75.25, H 7.11.
tert-Butyl-[6'-hex-4-ynyl-2'-methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-bi-
ꢀ
phenyl-4-ylmethoxy]-diphenylsilane (26c; R ˆ PMB, n ˆ 2, X ˆ C CCH3):
Prepared as described above from thiocarbonate 25c (621 mg,
0.568 mmol). Colorless oil (444 mg, 83%). 1H NMR (300.1 MHz, CD2Cl2):
d ˆ 7.71 (m, 4H), 7.49 7.38 (m, 8H), 7.12 (AA'XX', 4H), 6.94 (AA'XX',
2H), 6.81 (AA'XX', 4H), 6.68 (s, 2H), 6.56 (d, J ˆ 2.3 Hz, 1H), 6.50 (d, J ˆ
2.3 Hz, 1H), 5.01 (s, 2H), 4.91 (s, 4H), 4.77 (s, 2H), 3.83 (s, 3H), 3.76 (s,
6H), 3.69 (s, 3H), 2.42 (™t∫, J ˆ 7.7 Hz, 2H), 1.94 (m, 2H), 1.67 (t, J ˆ
2.4 Hz, 3H), 1.56 (m, 2H), 1.11 (s, 9H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ
159.9, 159.5, 159.4, 158.8, 157.8, 143.6, 142.2, 136.0, 133.8, 130.1, 130.0, 129.8,
129.8, 128.7, 128.1, 116.3, 114.5, 114.2, 114.1, 106.5, 103.9, 97.1, 79.3, 75.7,
70.2, 70.1, 66.1, 55.9, 55.6, 55.5, 33.3, 30.0, 27.0, 19.5, 18.7, 3.5; IR: n ˆ 3070,
3045, 2997, 2954, 2932, 2857, 1602, 1580, 1514, 1461, 1428, 1372, 1323, 1303,
1249, 1174, 1150, 1105, 1035, 1000, 940, 824, 742, 704, 611, 506 cmÀ1; M S
[6'-Hex-4-ynyl-2'-methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-biphenyl-4-
ꢀ
yl]-methanol (27c; R ˆ PMB, n ˆ 2, X ˆ C CCH3): Prepared as described
above from compound 26c (78 mg, 0.083 mmol). Colorless oil (54 mg,
99%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.40 (AA'XX', 2H), 7.14
(AA'XX', 4H), 6.93 (AA'XX', 2H), 6.82 (AA'XX', 4H), 6.71 (s, 2H),
6.55 (d, J ˆ 2.3 Hz, 1H), 6.47 (d, J ˆ 2.3 Hz, 1H), 5.00 (s, 2H), 4.94 (s, 4H),
4.66 (d, J ˆ 5.7 Hz, 2H), 3.82 (s, 3H), 3.77 (s, 6H), 3.66 (s, 3H), 2.40 (™t∫,
J ˆ 7.7 Hz, 2H), 1.92 (m, 2H), 1.81 (t, J ˆ 5.9 Hz, 1H), 1.68 (t, J ˆ 2.5 Hz,
3H), 1.54 (m, 2H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.6, 159.5,
158.7, 158.0, 143.5, 142.4, 129.9, 129.8, 129.7, 128.8, 116.1, 115.2, 114.2, 114.0,
106.5, 104.7, 97.1, 79.3, 75.7, 70.3, 70.1, 65.7, 55.9, 55.6, 55.6, 33.3, 30.0, 18.7,
3.5; IR: n ˆ 3439, 3063, 3035, 2997, 2933, 2864, 2835, 1612, 1603, 1584, 1514,
1461, 1431, 1417, 1383, 1323, 1303, 1248, 1174, 1149, 1102, 1032, 999, 821,
‡
(EI): m/z (%): 941 (1), 940 (2) [M] , 820 (2), 819 (2), 818 (3), 699 (<1), 241
773 cmÀ1; MS (EI): m/z (%): 703 (<1), 702 (2) [M] , 582 (1), 581 (2), 461
(<1), 199 (<1), 122 (9), 121 (100), 77 (<1); elemental analysis calcd (%)
for C60H64O8Si (941.25): C 76.56, H 6.85; found C 76.63, H 6.96.
‡
(<1), 122 (9), 121 (100), 91 (1), 77 (<1); HR-MS (ESI-pos)
(C44H46O8‡Na): calcd 725.3090; found 725.3092; elemental analysis calcd
(%) for C44H46O8 (702.84): C 75.19, H 6.60; found C 75.26, H 6.55.
tert-Butyl-[6'-methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-2'-oct-6-ynyl-bi-
ꢀ
phenyl-4-ylmethoxy]-diphenylsilane (26d; R ˆ PMB, n ˆ 4, X ˆ C CCH3):
1866
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1866 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 8

Turrianes
1856 1871
‡
[2'-Methoxy-2,6,4'-tris-(4-methoxybenzyloxy)-6'-oct-6-ynyl-biphenyl-4-yl]-
1034, 999, 818, 772, 704, 655, 634, 505 cmÀ1; MS (ESI-pos): 787 [M‡Na] ;
ꢀ
methanol (27d; R ˆ PMB, n ˆ 4, X ˆ C CCH3): Prepared as described
elemental analysis calcd (%) for C44H45BrO7 (765.74): C 69.02, H 5.92;
found C 69.11, H 5.84.
above from compound 26d (620 mg, 0.64 mmol). Colorless oil (450 mg,
96%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.44 (AA'XX', 2H), 7.18
(AA'XX', 4H), 6.98 (AA'XX', 2H), 6.86 (AA'XX', 4H), 6.75 (s, 2H),
6.60 (d, 1H, J ˆ 2.4 Hz), 6.52 (d, J ˆ 2.4 Hz, 1H), 5.05 (s, 2H), 4.98 (s, 4H),
4.68 (brs, 2H), 3.84 (s, 3H), 3.80 (s, 6H), 3.70 (s, 3H), 2.37 (™t∫, J ˆ 7.8 Hz,
2H), 2.15 (m, 1H), 1.95 (m, 2H), 1.77 (t, J ˆ 2.5 Hz, 3H), 1.48 1.20 (m,
6H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.5, 158.7, 157.9,
144.3, 142.6, 130.0, 129.8, 128.7, 116.0, 115.3, 114.2, 114.0, 106.5, 104.8, 96.9,
79.7, 75.5, 70.3, 70.0, 65.7, 55.9, 55.6, 55.5, 34.0, 30.0, 29.1, 28.9, 18.7, 3.5; IR:
n ˆ 3435, 3071, 2998, 2932, 2857, 2835, 1612, 1602, 1580, 1515, 1461, 1430,
1418, 1376, 1322, 1302, 1248, 1175, 1150, 1101, 1065, 1033, 1000, 972, 822,
4'-Bromomethyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyloxy)-6-oct-6-yn-
yl-biphenyl (28d; R ˆ PMB, n ˆ 4, X ˆ C CCH3): Prepared as described
ꢀ
above from alcohol 27d (438 mg, 0.599 mmol). Colorless oil (385 mg,
81%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.41 (AA'XX', 2H), 7.15
(AA'XX', 4H), 6.95 (AA'XX', 2H), 6.84 (AA'XX', 4H), 6.75 (s, 2H),
6.55 (d, J ˆ 2.3 Hz, 1H), 6.48 (d, J ˆ 2.3 Hz, 1H), 5.02 (s, 2H), 4.95 (s, 4H),
4.53 (s, 2H), 3.83 (s, 3H), 3.78 (s, 6H), 3.69 (s, 3H), 2.31 (™t∫, J ˆ 7.8 Hz,
2H), 1.94 (m, 2H), 1.74 (t, J ˆ 2.5 Hz, 3H), 1.44 1.14 (m, 6H); 13C NM R
(75.5 MHz, CD2Cl2): d ˆ 159.9, 159.6, 158.6, 157.9, 144.3, 138.5, 129.8, 129.7,
129.7, 128.8, 116.8, 115.5, 114.2, 114.1, 107.2, 106.4, 96.9, 79.6, 75.4, 70.4, 70.1,
55.9, 55.6, 55.6, 34.9, 34.0, 30.0, 29.2, 28.9, 18.8, 3.5; IR: n ˆ 3064, 3035, 2999,
2934, 2858, 2836, 1612, 1600, 1578, 1514, 1461, 1431, 1419, 1376, 1324, 1303,
1248, 1175, 1152, 1100, 1034, 1000, 954, 824, 736, 705, 655, 635, 517 cmÀ1; M S
‡
769, 624, 511 cmÀ1; MS (EI): m/z (%): 731 (1), 730 (2) [M] , 610 (2), 609 (5),
314 (<1), 294 (2), 122 (11), 121 (100); HR-MS (CI, isobutane)
(C46H50O8‡H): calcd 731.3584; found 731.3582; elemental analysis calcd
(%) for C46H50O8 (730.90): C 75.59, H 6.90; found C 75.66, H 7.06.
‡
(ESI-pos): 815 [M‡Na] ; elemental analysis calcd (%) for C46H49BrO7
(793.80): C 69.60, H 6.22; found C 69.54, H 6.18.
4'-Bromomethyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyloxy)-6-pent-4-en-
ˆ
yl-biphenyl (28a; R ˆ PMB, n ˆ 2, X ˆ CH CH2): A solution of alcohol
2-Methoxy-4,2',6'-tris-(4-methoxybenzyloxy)-6-pent-4-enyl-4'-undec-10-
enyl-biphenyl (29; R ˆ PMB): A solution of 9-decenylmagnesium bromide
(0.3m in THF, 1.93 mL, 0.578 mmol) was added dropwise to a solution of
bromide 28a (218 mg, 0.289 mmol) and Li2CuCl4 (0.1m in THF, 289 mL,
0.029 mmol) in THF (12 mL) at À208C. The color of the mixture gradually
changed from red to black. After stirring for 1 h at À208C, the reaction was
quenched with aq. sat. NH4Cl, the aqueous layer was extracted with diethyl
ether, the combined organic phases were dried (Na2SO4) and evaporated,
and the residue was purified by flash chromatography on neutral alumina
(hexanes/ethyl acetate 8:1 ! 6:1) to give diene 29 as a colorless oil (152 mg,
65%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.40 (AA'XX', 2H), 7.12
(AA'XX', 4H), 6.93 (AA'XX', 2H), 6.81 (AA'XX', 4H), 6.52 (m, 3H),
6.46 (d, J ˆ 2.2 Hz, 1H), 5.83 (ddt, J ˆ 17.0, 10.2, 6.7 Hz, 1H), 5.59 (ddt, J ˆ
17.0, 10.4, 6.5 Hz, 1H), 5.30 4.80 (m, 4H), 5.00 (s, 2H), 4.90 (s, 4H), 3.82 (s,
3H), 3.77 (s, 6H), 3.67 (s, 3H), 2.60 (t, J ˆ 7.7 Hz, 2H), 2.31 (t, J ˆ 7.8 Hz,
2H), 2.05 (m, 2H), 1.86 (m, 2H), 1.64 (m, 2H), 1.50 1.25 (m, 14H);
13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.8, 157.7, 144.3,
144.1, 139.7, 139.3, 130.2, 129.8, 128.8, 116.3, 114.2, 114.2, 114.0, 113.6, 106.7,
106.5, 97.0, 70.3, 70.0, 55.9, 55.6, 55.6, 36.9, 34.2, 33.8, 33.7, 31.7, 29.9, 29.9,
29.9, 29.8, 29.5, 29.4; IR: n ˆ 3075, 2997, 2925, 2854, 1639, 1612, 1601, 1585,
1576, 1515, 1462, 1439, 1418, 1374, 1321, 1302, 1248, 1192, 1174, 1152, 1104,
27a (20 mg, 0.029 mmol) and triethylamine (4.4 mg, 0.043 mmol) in CH2Cl2
(10 mL) at 08C was treated with methanesulfonic anhydride (7.6 mg,
0.043 mmol). The resulting mixture was stirred at that temperature for
30 min prior to quenching with aqueous saturated NaHCO3. The aqueous
layer was extracted with CH2Cl2, the combined organic phases were dried
(Na2SO4) and the solvent was evaporated. LiBr (25.1 mg, 0.29 mmol) was
added to a solution of the residue in THF (10 mL) and the resulting mixture
was stirred at 608C for 2 h. The precipitate was filtered off, the filtrate was
diluted with water, the aqueous phase was extracted with diethyl ether, the
combined organic layers were dried (Na2SO4), the solvent was evaporated
and the residue was purified by flash chromatography on silica (hexanes/
ethyl acetate 3:1) to deliver bromide 28a as a colorless oil (16 mg, 73%
1
over both steps). H NMR (300.1 MHz, CD2Cl2): d ˆ 7.40 (AA'XX', 2H),
7.13 (AA'XX', 4H), 6.93 (AA'XX', 2H), 6.82 (AA'XX', 4H), 6.74 (s, 2H),
6.53 (d, J ˆ 2.4 Hz, 1H), 6.47 (d, J ˆ 2.3 Hz, 1H), 5.59 (m, 1H), 5.00 (s, 2H),
4.93 (s, 4H), 4.89 4.80 (m, 2H), 4.52 (s, 2H), 3.82 (s, 3H), 3.77 (s, 6H), 3.67
(s, 3H), 2.31 (t, J ˆ 7.8 Hz, 2H), 1.87 (m, 2H), 1.46 (tt, 2H, J ˆ 9.5, 7.5 Hz);
13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.6, 158.7, 157.9, 144.1, 139.2,
138.6, 129.8, 129.7, 129.6, 128.8, 116.7, 115.5, 114.4, 114.2, 114.1, 107.2, 106.5,
97.0, 70.4, 70.1, 55.9, 55.6, 55.6, 34.9, 33.7, 33.6, 29.8; IR: n ˆ 3071, 3034, 2997,
2931, 2864, 2834, 1638, 1613, 1601, 1577, 1514, 1461, 1430, 1418, 1377, 1324,
1303, 1248, 1174, 1151, 1100, 1033, 999, 911, 822, 654, 635, 513 cmÀ1; M S
‡
1036, 1000, 909, 823, 627, 517 cmÀ1; MS (EI): m/z (%): 813 (2), 812 (3) [M] ,
693 (4), 692 (8), 691 (9), 572 (2), 571 (3), 122 (14), 121 (100); elemental
analysis calcd (%) for C53H64O7 (813.09): C 78.29, H 7.93; found C 78.15, H
8.06.
‡
‡
(ESI-pos): 775 [M‡Na] , 753 [M‡H] ; elemental analysis calcd (%) for
C43H45BrO7 (753.73): C 68.52, H 6.02; found C 68.58, H 6.12.
4'-Bromomethyl-6-hept-6-enyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyl-
6-Hept-6-enyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyloxy)-4'-non-8-enyl-
biphenyl (30; R ˆ PMB): Prepared as described above from bromide 28b
(98 mg, 0.125 mmol) and 7-octenylmagnesium bromide (0.3m in THF,
627 mL, 0.251 mmol). Colorless oil (67 mg, 66%). 1H NMR (300.1 MHz,
CD2Cl2): d ˆ 7.42 (AA'XX', 2H), 7.14 (AA'XX', 4H), 6.95 (AA'XX', 2H),
6.83 (AA'XX', 4H), 6.55 (d, J ˆ 2.5 Hz, 1H), 6.54 (s, 2H), 6.48 (d, J ˆ
2.3 Hz, 1H), 5.86 (ddt, J ˆ 17.0, 10.2, 6.6 Hz, 1H), 5.75 (ddt, J ˆ 17.0, 10.2,
6.7 Hz, 1H), 5.07 4.86 (m, 4H), 5.03 (s, 2H), 4.93 (s, 4H), 3.83 (s, 3H), 3.78
(s, 6H), 3.69 (s, 3H), 2.62 (t, J ˆ 7.7 Hz, 2H), 2.32 (t, J ˆ 7.8 Hz, 2H), 2.09
(m, 2H), 1.90 (m, 2H), 1.65 (m, 2H), 1.47 1.10 (m, 14H); 13C NM R
(75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.8, 157.7, 144.6, 144.0, 139.7,
139.7, 130.2, 129.9, 129.8, 128.8, 116.3, 114.2, 114.1, 114.0, 113.7, 106.7, 106.4,
96.9, 70.3, 70.0, 55.9, 55.6, 55.6, 36.9, 34.2, 34.2, 33.9, 31.6, 30.4, 29.8, 29.5,
29.4, 29.3, 29.0; IR: n ˆ 3073, 3035, 2997, 2927, 2854, 1639, 1612, 1601, 1585,
1576, 1514, 1462, 1418, 1374, 1321, 1302, 1248, 1174, 1151, 1103, 1036, 1000,
ˆ
oxy)-biphenyl (28b; R ˆ PMB, n ˆ 4, X ˆ CH CH2): Prepared as described
above from alcohol 27b (140 mg, 0.195 mmol). Colorless oil (117 mg,
77%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.43 (AA'XX', 2H), 7.16
(AA'XX', 4H), 6.96 (AA'XX', 2H), 6.85 (AA'XX', 4H), 6.77 (s, 2H),
6.57 (d, J ˆ 2.3 Hz, 1H), 6.50 (d, J ˆ 2.2 Hz, 1H), 5.76 (ddt, J ˆ 17.0, 10.2,
6.7 Hz, 1H), 5.03 (s, 2H), 4.96 (s, 4H), 4.93 4.87 (m, 2H), 4.54 (s, 2H), 3.83
(s, 3H), 3.79 (s, 6H), 3.70 (s, 3H), 2.33 (t, J ˆ 7.8 Hz, 2H), 1.91 (m, 2H), 1.41
(m, 2H), 1.27 1.14 (m, 4H); 13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9,
159.6, 158.6, 157.9, 144.4, 139.6, 138.5, 129.8, 129.8, 129.7, 128.8, 116.8, 115.5,
114.2, 114.1, 114.1, 107.2, 106.5, 96.9, 70.4, 70.0, 55.9, 55.6, 55.6, 34.9, 34.1,
33.9, 30.4, 29.2, 29.0; IR: n ˆ 3071, 3035, 2998, 2931, 2856, 2836, 1639, 1613,
1576, 1514, 1457, 1419, 1377, 1325, 1303, 1254, 1175, 1151, 1098, 1033, 1000,
955, 912, 825, 773, 757, 706, 675, 655, 635, 594, 517 cmÀ1; MS (ESI-pos): 819
‡
‡
‡
[M‡K] , 803 [M‡Na] , 781 [M‡H] ; elemental analysis calcd (%) for
‡
910, 823, 756, 627, 512 cmÀ1; MS (EI): m/z (%): 813 (2), 812 (4) [M] , 693
C45H49BrO7 (781.78): C 69.14, H 6.32; found C 69.06, H 6.25.
(2), 692 (6), 691 (12), 122 (9), 121 (100); HR-MS (CI, isobutane)
(C53H64O7‡H): calcd 813.4730; found 813.4730; elemental analysis calcd
(%) for C53H64O7 (813.09): C 78.29, H 7.93; found C 78.22, H 7.86.
4'-Bromomethyl-6-hex-4-ynyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyl-
ꢀ
oxy)-biphenyl (28c; R ˆ PMB, n ˆ 2, X ˆ C CCH3): Prepared as described
above from alcohol 27c (330 mg, 0.47 mmol). Colorless oil (274 mg, 76%).
1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.42 (AA'XX', 2H), 7.17 (AA'XX',
4H), 6.96 (AA'XX', 2H), 6.85 (AA'XX', 4H), 6.77 (s, 2H), 6.57 (d, J ˆ
2.3 Hz, 1H), 6.50 (d, J ˆ 2.3 Hz, 1H), 5.03 (s, 2H), 4.96 (s, 4H), 4.54 (s, 2H),
3.83 (s, 3H), 3.79 (s, 6H), 3.69 (s, 3H), 2.43 (™t∫, J ˆ 7.7 Hz, 2H), 1.96 (m,
2H), 1.72 (t, J ˆ 2.5 Hz, 3H), 1.57 (m, 2H); 13C NMR (75.5 MHz, CD2Cl2):
d ˆ 159.9, 159.6, 159.6, 158.7, 158.0, 143.4, 138.5, 129.8, 129.7, 129.6, 128.9,
116.6, 115.6, 114.2, 114.1, 107.1, 106.5, 97.1, 79.3, 75.7, 70.5, 70.1, 55.9, 55.6,
55.6, 34.8, 33.2, 30.0, 18.6, 3.6; IR: n ˆ 3067, 3034, 2999, 2958, 2929, 2864,
2835, 1613, 1577, 1515, 1458, 1419, 1379, 1326, 1304, 1250, 1173, 1153, 1101,
4'-Dodec-10-ynyl-6-hex-4-ynyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyl-
oxy)-biphenyl (31; R ˆ PMB): Prepared as described above from bromide
28c (265 mg, 0.346 mmol) and 9-undecynylmagnesium bromide (0.3m in
THF, 3.46 mL, 1.038 mmol). Colorless oil (232 mg, 80%). 1H NM
R
(300.1 MHz, CD2Cl2): d ˆ 7.41 (AA'XX', 2H), 7.15 (AA'XX', 4H), 6.95
(AA'XX', 2H), 6.84 (AA'XX', 4H), 6.56 (d, 1H), 6.55 (s, 2H), 6.48 (d, J ˆ
2.3 Hz, 1H), 5.02 (s, 2H), 4.93 (s, 4H), 3.83 (s, 3H), 3.78 (s, 6H), 3.68 (s,
3H), 2.62 (t, J ˆ 7.8 Hz, 2H,), 2.41 (t, J ˆ 7.7 Hz, 2H), 2.13 (m, 2H), 1.93 (m,
2H), 1.77 (t, J ˆ 2.6 Hz, 3H), 1.70 (t, J ˆ 2.5 Hz, 3H), 1.70 1.29 (m, 16H);
Chem. Eur. J. 2002, 8, No. 8
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1867 $ 20.00+.50/0
1867

A. F¸rstner et al.
FULL PAPER
13C NMR (75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.8, 157.7, 144.1,
143.6, 130.2, 129.8, 128.8, 116.4, 114.2, 114.0, 113.5, 106.7, 106.5, 97.1, 79.6,
79.4, 75.7, 75.5, 70.3, 70.1, 55.9, 55.6, 55.6, 36.9, 33.3, 31.6, 30.0, 29.9, 29.9,
29.6, 29.6, 29.3, 19.0, 18.7, 3.5, 3.5; IR: n ˆ 3062, 3035, 2994, 2925, 2854, 2835,
1606, 1577, 1515, 1462, 1436, 1420, 1384, 1363, 1344, 1322, 1302, 1248, 1177,
1166, 1148, 1104, 1086, 1061, 1037, 993, 960, 922, 857, 830, 814, 767, 746, 719,
Ring closing olefin metathesis–Preparation of compound (E,Z)-36 (R ˆ
PMB)
Method A: A solution of diene 30 (65 mg, 0.08 mmol) and ruthenium
carbene 33 (3.3 mg, 0.004 mmol, 5 mol%) in CH2Cl2 (20 mL) was refluxed
for 2 h. The solvent was evaporated and the residue was purified by flash
chromatography on silica (hexanes/ethyl acetate 10:1 ! 6:1) to afford
olefin 36 as a pale yellow oil (46 mg, 0.059 mmol, 73%). The product
consisted of a mixture of isomers (E:Z ˆ 5.8:1).
‡
649, 627, 608, 565, 519, 504 cmÀ1; MS (EI): m/z (%): 836 (3) [M] , 835 (4),
717 (2), 716 (6), 715 (11), 566 (1), 122 (9), 121 (100); HR-MS (CI,
isobutane) (C55H64O7‡H): calcd 837.4730; found 837.4724; elemental
analysis calcd (%) for C55H64O7 (837.11): C 78.91, H 7.71; found C 79.08,
H 7.80.
Method B: A solution of diene 30 (80 mg, 0.098 mmol) and ruthenium
indenylidene complex 34 (4.5 mg, 0.0049 mmol, 5 mol%) in CH2Cl2
(40 mL) was refluxed for 3 h. Workup as described above afforded olefin
36 (65 mg, 0.083 mmol, 84%) as mixture of isomers (E:Z ˆ 6.9:1). 1H NM R
(600.2 MHz, CD2Cl2): d [E-isomer] ˆ 7.42 (AA'XX', 2H), 7.15 (AA'XX',
4H), 6.95 (AA'XX', 2H), 6.83 (AA'XX', 4H), 6.57 (d, J ˆ 2.3 Hz, 1H), 6.50
(s, 2H), 6.47 (d, J ˆ 2.3 Hz, 1H), 5.24 (m, 2H), 5.02 (s, 2H), 4.93 (s, 4H),
3.83 (s, 3H), 3.78 (s, 6H), 3.69 (s, 3H), 2.61 (t, J ˆ 6.5 Hz, 2H), 2.22 (m, 2H),
1.96 (m, 2H), 1.91 (m, 2H), 1.59 (m, 2H), 1.39 (m, 2H), 1.35 1.05 (m,
12H); 1H NMR (300.1 MHz, CD2Cl2): d [Z-isomer] ˆ 7.41 (AA'XX', 2H),
7.14 (AA'XX', 4H), 6.94 (AA'XX', 2H), 6.82 (AA'XX', 4H), 6.54 (d, J ˆ
2.3 Hz, 1H), 6.49 (s, 2H), 6.47 (d, J ˆ 2.4 Hz, 1H), 5.37 5.24 (m, 2H), 5.01
(s, 2H), 4.92 (s, 4H), 3.82 (s, 3H), 3.77 (s, 6H), 3.69 (s, 3H), 2.61 (t, J ˆ
6.2 Hz, 2H), 2.24 (m, 2H), 2.05 1.87 (m, 4H), 1.63 1.02 (m, 16H);
13C NMR (150.9 MHz, CD2Cl2): d [E-isomer] ˆ 159.9, 159.5, 159.5, 158.8,
157.5, 144.9, 143.7, 131.5, 130.6, 130.2, 129.9, 129.8, 128.8, 116.3, 114.2, 114.0,
113.8, 107.2, 106.2, 96.9, 70.3, 70.1, 55.9, 55.6, 55.5, 36.6, 34.5, 33.4, 31.8, 31.8,
31.3, 29.8, 29.6, 29.0, 28.5, 28.5, 27.8; 13C NMR (75.5 MHz, CD2Cl2): d [Z-
isomer] ˆ 159.9, 159.5, 159.5, 158.8, 157.5, 144.9, 143.7, 130.5, 130.2, 129.9,
129.9, 129.8, 128.8, 116.3, 114.2, 114.0, 113.7, 107.3, 106.5, 96.9, 70.3, 70.0,
55.9, 55.6, 55.5, 36.8, 35.0, 31.6, 30.9, 30.5, 29.8, 29.7, 29.1, 28.7, 28.6, 27.8,
26.8; IR [E:Z ˆ 5.8:1]: n ˆ 3062, 2997, 2927, 2852, 1612, 1602, 1576, 1514,
1461, 1440, 1418, 1370, 1321, 1302, 1249, 1174, 1151, 1100, 1034, 1000, 967,
822, 753, 626, 511 cmÀ1; [Z-isomer]: n ˆ 3064, 3001, 2926, 2851, 1618, 1600,
1585, 1573, 1515, 1462, 1419, 1375, 1338, 1301, 1249, 1191, 1157, 1113, 1031,
1000, 856, 824, 758, 708, 644, 632, 596, 517 cmÀ1; MS (EI): m/z (%): [E:Z ˆ
4'-Dec-8-ynyl-2-methoxy-4,2',6'-tris-(4-methoxybenzyloxy)-6-oct-6-ynyl-
biphenyl (32; R ˆ PMB): Prepared as described above from bromide 28d
(260 mg, 0.328 mmol) and 7-nonynylmagnesium bromide (0.3m in THF,
3.28 mL, 0.983 mmol). Colorless oil (200 mg, 73%). 1H NMR (300.1 MHz,
CD2Cl2): d ˆ 7.41 (AA'XX', 2H), 7.14 (AA'XX', 4H), 6.94 (AA'XX', 2H),
6.83 (AA'XX', 4H), 6.54 (™d∫, 1H), 6.54 (s, 2H), 6.47 (d, J ˆ 2.3 Hz, 1H),
5.02 (s, 2H), 4.92 (s, 4H), 3.82 (s, 3H), 3.78 (s, 6H), 3.68 (s, 3H), 2.64 (™t∫,
J ˆ 7.7 Hz, 2H), 2.31 (™t∫, J ˆ 7.7 Hz, 2H), 2.13 (m, 2H), 1.93 (m, 2H), 1.77
(t, J ˆ 2.6 Hz, 3H), 1.73 (t, J ˆ 2.5 Hz, 3H), 1.72 1.15 (m, 16H); 13C NM R
(75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.8, 157.7, 144.5, 144.0, 130.2,
129.8, 129.8, 128.8, 116.3, 114.2, 114.0, 113.6, 106.7, 106.4, 96.9, 79.6, 79.6,
75.5, 75.3, 70.3, 70.0, 55.9, 55.6, 55.5, 36.9, 34.0, 31.6, 30.0, 29.7, 29.6, 29.4,
29.2, 29.2, 29.0, 19.0, 18.8, 3.5; IR: n ˆ 3063, 3034, 2998, 2931, 2856, 2837,
1612, 1601, 1585, 1576, 1514, 1462, 1429, 1418, 1372, 1322, 1302, 1249, 1174,
1152, 1103, 1036, 1000, 824, 756, 736, 628, 515 cmÀ1; MS (EI): m/z (%): 837
‡
(3), 836 (4) [M] , 835 (4), 717 (3), 716 (11), 715 (22), 241 (1), 122 (18), 121
(100); HR-MS (CI, isobutane) (C55H64O7‡H): calcd 837.4730; found
837.4727; elemental analysis calcd (%) for C55H64O7 (837.11): C 78.91, H
7.71; found C 79.07, H 7.82.
Ring closing olefin metathesis–Preparation of compound (E,Z)-35 (R ˆ
PMB)
Method A: A solution of diene 29 (65 mg, 0.08 mmol) and ruthenium
carbene 33 (3.3 mg, 0.004 mmol, 5 mol%) in CH2Cl2 (35 mL) was refluxed
for 4 h. The solvent was evaporated and the residue was purified by flash
chromatography on silica (hexanes/ethyl acetate 6:1) to afford olefin 35 as a
colorless oil (49 mg, 78%). The product consisted of a mixture of isomers
(E:Z ˆ 1.2:1).
‡
5.8:1] 785 (3), 784 (5) [M] , 664 (7), 663 (13), 543 (1), 241 (1), 122 (13), 121
‡
(100); m/z (%) [Z-isomer]: 785 (3), 784 (5) [M] , 665 (2), 664 (5), 663 (9),
‡
543 (1), 241 (1), 122 (9), 121 (100); MS (ESI-pos): 785 [M‡H] ; HR-MS
(CI, isobutane) (C51H60O7‡H): calcd 785.4417; found 785.4414; [Z-isomer]
(C51H60O7‡H): calcd 785.4417; found 785.4411; elemental analysis calcd
(%) for C51H60O7 (785.03): C 78.03, H 7.70; found C 78.11, H 7.79.
Method B: A solution of diene 29 (150 mg, 0.184 mmol) and ruthenium
indenylidene complex 34 (8.5 mg, 0.009 mmol, 5 mol%) in CH2Cl2 (60 mL)
was refluxed for 1 h. Workup as described above delivered olefin 35
(110 mg, 76%) as a mixture of isomers (E:Z ˆ 1:1.1). Colorless syrup.
1H NMR (600.2 MHz, CD2Cl2): d [E-isomer] ˆ 7.40 (AA'XX', 2H), 7.14
(AA'XX', 4H), 6.94 (AA'XX', 2H), 6.83 (AA'XX', 4H), 6.54 (d, J ˆ 2.4 Hz,
1H), 6.54 (s, 2H), 6.46 (d, 1H, J ˆ 2.4 Hz), 5.24 (m, 1H), 5.04 (m, 1H), 5.01
(s, 2H), 4.93 (m, 4H), 3.82 (s, 3H), 3.78 (s, 6H), 3.67 (s, 3H), 2.63 (t, J ˆ
6.8 Hz, 2H), 2.34 (m, 2H), 1.87 (m, 4H), 1.66 (m, 2H), 1.55 1.05 (m, 14H);
d [Z-isomer] ˆ 7.40 (AA'XX', 2H), 7.14 (AA'XX', 4H), 6.94 (AA'XX',
2H), 6.82 (AA'XX', 4H), 6.55 (d, J ˆ 2.4 Hz, 1H), 6.53 (s, 2H), 6.46 (d, J ˆ
2.4 Hz, 1H), 5.35 (m, 1H), 5.27 (m, 1H), 5.01 (s, 2H), 4.90 (m, 4H), 3.82 (s,
3H), 3.78 (s, 6H), 3.67 (s, 3H), 2.65 (t, J ˆ 6.2 Hz, 2H), 2.29 (m, 2H), 1.87
(m, 4H), 1.65 (m, 2H), 1.55 1.05 (m, 14H); 13C NMR (150.9 MHz,
CD2Cl2): d [E-isomer] ˆ 159.9, 159.5, 159.4, 158.8, 157.7, 144.6, 144.0, 130.6,
130.4, 130.2, 129.9, 129.8, 128.8, 116.4, 114.2, 114.0, 113.6, 106.9, 106.6, 96.9,
70.3, 70.1, 55.9, 55.6, 55.6, 36.3, 33.7, 32.5, 31.6, 30.7, 30.2, 27.9, 27.7, 27.4, 27.2,
27.1, 26.4; d [Z-isomer] ˆ 159.9, 159.5, 159.5, 158.8, 157.7, 144.7, 143.4, 130.2,
130.2, 130.1, 129.9, 129.8, 128.9, 116.4, 114.2, 114.0, 113.7, 107.2, 106.0, 96.9,
70.4, 70.1, 55.9, 55.6, 55.6, 36.3, 34.2, 31.5, 30.5, 29.1, 28.7, 28.4, 28.2, 28.0,
27.0, 26.9, 26.3; IR [E:Z ˆ 1.2:1]: n ˆ 3068, 3035, 3001, 2926, 2853, 1613,
1603, 1585, 1514, 1460, 1442, 1417, 1383, 1320, 1303, 1248, 1173, 1151, 1100,
1033, 1000, 966, 821 cmÀ1; [Z-isomer]: n ˆ 3064, 2999, 2927, 2854, 1612,
1602, 1585, 1576, 1514, 1460, 1442, 1418, 1371, 1338, 1320, 1302, 1248, 1174,
1151, 1103, 1034, 1000, 822, 755, 719, 629, 514 cmÀ1; MS (EI): m/z (%):
Ring closing alkyne metathesis–Preparation of compound 37 (R ˆ PMB)
Method A:
A
solution of diyne 31 (63 mg, 0.075 mmol) and
ꢀ
[(tBuO)3W CCMe3] (3.6 mg, 0.0075 mmol, 10 mol%) in toluene (40 mL)
was stirred at 808C for 16 h. The solvent was evaporated and the residue
was purified by flash chromatography on silica (hexanes/ethyl acetate
6:1 ! 4:1) to afford alkyne 37 as a colorless solid (38 mg, 64%).
Method B: A solution of diyne 31 (200 mg, 0.239 mmol), Mo(CO)6 (6.3 mg,
0.0239 mmol,
10 mol%)
and
4-trifluoromethylphenol
(38.7 mg,
0.239 mmol) in chlorobenzene (60 mL) was refluxed for 4 h while a gentle
stream of Ar was bubbled through the solution. The solvent was evaporated
and the residue was purified by flash chromatography on neutral alumina
(hexanes/ethyl acetate 10:1 ! 6:1) to deliver alkyne 37 (155 mg, 83%) as a
1
colorless solid. M.p. 136 1398C; H NMR (300.1 MHz, CD2Cl2): d ˆ 7.39
(AA'XX', 2H), 7.15 (AA'XX', 4H), 6.93 (AA'XX', 2H), 6.82 (AA'XX',
4H), 6.55 (m, 2H), 6.49 (d, J ˆ 2.4 Hz, 1H), 6.47 (d, J ˆ 2.3 Hz, 1H), 4.99 (s,
2H), 4.92 (s, 4H), 3.82 (s, 3H), 3.77 (s, 6H), 3.67 (s, 3H), 2.64 (t, J ˆ 6.4 Hz,
2H), 2.42 (m, 2H), 2.08 1.93 (m, 4H), 1.72 1.20 (m, 16H); 13C NM R
(75.5 MHz, CD2Cl2): d ˆ 159.9, 159.5, 159.4, 158.9, 157.7, 143.9, 143.7, 130.2,
129.8, 128.9, 116.5, 114.2, 114.0, 113.5, 107.0, 106.5, 97.0, 80.4, 80.3, 70.4, 70.1,
56.0, 55.6, 55.6, 36.2, 33.8, 30.4, 29.4, 28.2, 28.2, 28.0, 28.0, 27.4, 27.1, 19.1,
18.3; IR: n ˆ 3072, 3035, 2997, 2928, 2853, 1612, 1602, 1576, 1514, 1461, 1440,
1418, 1375, 1321, 1302, 1248, 1174, 1152, 1103, 1034, 1000, 941, 823, 768, 625,
‡
516 cmÀ1; MS (EI): m/z (%): 783 (3), 782 (4) [M] , 663 (2), 662 (6), 661 (9),
541 (2), 122 (9), 121 (100); HR-MS (CI, isobutane) (C51H58O7‡H): calcd
783.4261; found 783.4266; elemental analysis calcd (%) for C51H58O7
(783.02): C 78.23, H 7.47; found C 78.18, H 7.46.
‡
[E:Z ˆ 1.2:1] 785 (2), 784 (3) [M] , 665 (1), 664 (4), 663 (7), 543 (2), 390 (1),
241 (<1), 122 (10), 121 (100), 91 (<1), 77 (<1); m/z (%) [Z-isomer]: 785
‡
(1), 784 (2) [M] , 665 (1), 664 (3), 663 (4), 543 (<1), 421 (< 1), 241 (<1),
‡
122 (9), 121 (100), 91 (<1), 78 (1), 77 (1); MS (ESI-pos): 785 [M‡H] ; HR-
Method C: A SmithProcess vial (10 mL) containing a magnetic stir bar was
charged with diyne 31 (20 mg, 0.024 mmol), 4-trifluoromethylphenol
(3.9 mg, 0.024 mmol), Mo(CO)6 (0.6 mg, 0.002 mol%) and chlorobenzene
(2.5 mL). The vial was sealed and evacuated through a cannula, and the
MS (CI, isobutane) (C51H60O7‡H): calcd 785.4417; found 785.4415;
elemental analysis calcd (%) for C51H60O7 (785.03): C 78.03, H 7.70; found
C 78.09, H 7.75.
1868
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1868 $ 20.00+.50/0
Chem. Eur. J. 2002, 8, No. 8

Turrianes
1856 1871
resulting mixture was heated to 1508C in a microwave oven (SmithCreator
reactor) for 5 min. Work-up as described above provided cycloalkyne 37 as
a colorless solid (13 mg, 69%). The analytical and spectroscopic data are
identical with those compiled above.
107.7, 97.8, 56.2, 35.8, 33.9, 31.7, 30.8, 29.5, 28.7, 28.3, 28.0, 27.8, 27.8, 27.7, 27.4,
27.4, 27.2; IR: n ˆ 3409, 2926, 2854, 1635, 1605, 1584, 1523, 1459, 1435, 1334,
1259, 1157, 1105, 1082, 1033, 1000, 943, 838, 723, 636, 583, 520 cmÀ1; M S
‡
(EI): m/z (%): 428 (5), 427 (29), 426 (100) [M] , 425 (4), 384 (4), 260 (10),
245 (4), 243 (6), 137 (2); HR-MS (EI) (C27H38O4): calcd 426.2770; found
426.2771; elemental analysis calcd (%) for C27H38O4 (426.60): C 76.02, H
8.98; found C 76.15, H 9.06.
Ring closing alkyne metathesis–Preparation of compound 38 (R ˆ PMB)
Method A:
A
solution of diyne 32 (80 mg, 0.096 mmol) and
ꢀ
[(tBuO)3W CCMe3] (4.5 mg, 0.0096 mmol, 10 mol%) in toluene (20 mL)
was stirred at 808C for 16 h. The solvent was evaporated and the residue
was purified by flash chromatography on silica (hexanes/ethyl acetate
10:1 ! 6:1 ! 4:1) to give cycloalkyne 38 as a colorless solid (46 mg, 61%).
Turriane 4
Method A: Olefin (Z)-35 (80 mg, 0.102 mmol) was dissolved in 1,3,5-
trimethoxybenzene (~ 2 g) at 708C. SnCl2 (19.3 mg, 0.102 mmol) and
TMSCl (129 mL, 1.019 mmol) were added and the resulting mixture was
stirred at 708C for 30 min. Addition of water followed by extraction with
ethyl acetate, drying of the combined organic layers (Na2SO4) and
evaporation of the solvent provided a residue which was first subjected
to flash chromatography on silica (hexanes/ethyl acetate 10:1 (750 mL)
!6:1 ! 4:1 ! 2:1) followed by further purification of the product con-
taining fractions by preparative HPLC, thus providing turriane 4 as a
colorless waxy solid (17 mg, 39%).
Method B: A solution of diyne 32 (45 mg, 0.054 mmol), Mo(CO)6 (1.4 mg,
0.0054 mmol, 10 mol%) and 4-trifluoromethylphenol (8.7 mg, 0.054 mmol)
in chlorobenzene (30 mL) was refluxed for 6 h while a gentle stream of Ar
was bubbled through the solution. After evaporation of the solvent, the
residue was purified by flash chromatography on neutral alumina (hexanes/
ethyl acetate 10:1 ! 6:1) to give alkyne 38 (32 mg, 76%) as a colorless
solid. M.p. 131 1348C; 1H NMR (300.1 MHz, CD2Cl2): d ˆ 7.41 (AA'XX',
2H), 7.15 (AA'XX', 4H), 6.94 (AA'XX', 2H), 6.83 (AA'XX', 4H), 6.56 (d,
J ˆ 2.3 Hz, 1H), 6.51 (m, 2H), 6.47 (d, J ˆ 2.3 Hz, 1H), 5.01 (s, 2H), 4.94 (s,
4H), 3.82 (s, 3H), 3.78 (s, 6H), 3.69 (s, 3H), 2.63 (t, J ˆ 6.4 Hz, 2H), 2.25 (m,
2H), 2.16 2.03 (m, 4H), 1.68 1.05 (m, 16H); 13C NMR (75.5 MHz,
CD2Cl2): d ˆ 159.9, 159.5, 158.8, 157.6, 144.8, 143.5, 130.2, 129.8, 129.8, 128.7,
116.3, 114.2, 114.0, 113.7, 107.1, 106.1, 96.9, 80.7, 80.3, 70.2, 70.0, 55.9, 55.6,
55.5, 36.2, 34.3, 31.6, 30.8, 29.8, 29.2, 28.8, 28.6, 28.4, 28.0, 19.3, 18.7; IR: n ˆ
3063, 3036, 3013, 2927, 2852, 1612, 1600, 1585, 1573, 1514, 1461, 1443, 1418,
1375, 1356, 1338, 1301, 1247, 1194, 1173, 1157, 1115, 1074, 1053, 1030, 1000,
954, 927, 855, 838, 824, 774, 759, 730, 710, 665, 646, 632, 604, 517 cmÀ1; M S
Method B: BF3 ¥ OEt2 (118 mL, 0.943 mmol) was added via syringe over
2 min to a solution of olefin (Z)-35 (37 mg, 0.047 mmol) in EtSH (2 mL) at
À208C and the resulting mixture was stirred at ambient temperature for
16 h. The reaction was quenched with aq. sat. NaHCO3, the organic phase
was extracted with ethyl acetate, the combined organic layers were dried
(Na2SO4) and evaporated, and the residue was purified by flash chroma-
tography on silica (hexanes/ethyl acetate 10:1 ! 6:1 ! 4:1 ! 2:1) followed
by further purification of the product containing fractions by preparative
HPLC to afford turriane 4 as a colorless waxy solid (10 mg, 50%). 1H NM R
(400.1 MHz, CD2Cl2): d ˆ 6.50 (d, J ˆ 2.3 Hz, 1H), 6.43 (d, J ˆ 2.3 Hz, 1H),
6.38 (s, 2H), 5.40 5.24 (m, 2H, OH), 4.63 (brs, 2H, OH), 3.71 (s, 3H), 2.60
(t, J ˆ 6.2 Hz, 2H), 2.27 (m, 2H), 1.87 (m, 4H), 1.68 1.58 (m, 2H), 1.50
1.42 (m, 2H), 1.35 1.15 (m, 12H); 13C NMR (100.6 MHz, CD2Cl2): d ˆ
160.3, 158.5, 154.2, 148.0, 144.8, 130.7, 129.5, 109.2, 109.1, 107.9, 97.9, 56.2,
35.7, 33.6, 31.8, 30.4, 29.1, 28.8, 28.5, 28.2, 28.0, 27.1, 27.1, 26.3; IR: n ˆ 3411,
3004, 2927, 2855, 1633, 1604, 1585, 1522, 1457, 1433, 1336, 1259, 1188, 1158,
1105, 1085, 1036, 1001, 841, 818, 721, 700, 637, 521 cmÀ1; MS (EI): m/z (%):
‡
(EI): m/z (%): 783 (2), 782 (3) [M] , 663 (1), 662 (4), 661 (9), 241 (1), 122
(10), 121 (100), 77 (1); HR-MS (CI, isobutane) (C51H58O7‡H): calcd
783.4261; found 783.4259; elemental analysis calcd (%) for C51H58O7
(783.02): C 78.23, H 7.47; found C 78.20, H 7.55.
Method C: A SmithProcess vial (10 mL) containing a magnetic stir bar was
charged with diyne 32 (27 mg, 0.032 mmol), 4-trifluoromethylphenol
(5.2 mg, 0.032 mmol), Mo(CO)6 (0.9 mg, 0.003 mol%) and chlorobenzene
(3 mL). The vial was sealed and evacuated through a cannula, and the
resulting mixture was heated to 1508C in a microwave oven (SmithCreator
reactor) for 5 min. Work-up as described above provides cycloalkyne 38 as
a colorless solid (18 mg, 71%). The analytical and spectroscopic data are
identical with those compiled above.
‡
426 (5), 425 (30), 424 (100) [M] , 423 (5), 273 (3), 272 (4), 271 (3), 261 (3),
260 (18), 259 (3), 257 (6), 245 (5), 244 (3), 243 (9), 241 (5), 229 (3), 227 (4),
213 (3), 163 (3), 137 (3), 81 (3), 69 (3), 67 (3), 55 (6), 41 (4); HR-MS (EI)
(C27H36O4): calcd 424.2614; found 424.2615; elemental analysis calcd (%)
for C27H36O4 (424.58): C 76.38, H 8.55; found C 76.31, H 8.46.
Preparation of (Z)-35 by Lindlar reduction of cycloalkyne 37: Commer-
cially available Lindlar catalyst (20 mg) was added to a solution of alkyne
37 (105 mg, 0.134 mmol) and quinoline (20 mL) in ethyl acetate (15 mL).
The flask was flushed with H2 (two freeze/thaw cycles) and the reaction
mixture was stirred under H2 (1 atm) for 6 h. The mixture was filtered
through a pad of Celite, the Celite was carefully washed with ethyl acetate,
and the combined organic phases were washed with 2n HCl and dried over
Na2SO4. Evaporation of the solvent followed by flash chromatography of
the residue on silica (hexanes/ethyl acetate 10:1 ! 6:1) afforded olefin (Z)-
35 as a colorless oil (101 mg, 0.129 mmol, 96%). The analytical and
spectroscopic data were identical in all respects to those compiled above.
Turriane 5: BF3 ¥ OEt2 (176 mL, 1.401 mmol) was added through a syringe
over 2 min to a solution of olefin (Z)-36 (55 mg, 0.07 mmol) in EtSH
(2 mL) at À208C and the resulting mixture was stirred at ambient
temperature for 16 h. The reaction was quenched with aq. sat. NaHCO3,
the aqueous layer was extracted with ethyl acetate, the combined organic
phases were dried (Na2SO4) and evaporated, and the residue was purified
by flash chromatography on silica (hexanes/ethyl acetate 10:1 ! 6:1 !
4:1 ! 2:1) followed by further purification of the product containing
fractions by preparative HPLC, thus delivering turriane 5 (16 mg, 54%) as
a colorless waxy solid. 1H NMR (400.1 MHz, CD2Cl2): d ˆ 6.48 (d, J ˆ
2.3 Hz, 1H), 6.44 (d, J ˆ 2.3 Hz, 1H), 6.35 (s, 2H), 5.30 (m, 2H), 5.15 (brs,
1H, OH), 4.62 (brs, 2H, OH), 3.73 (s, 3H), 2.57 (t, J ˆ 6.3 Hz, 2H), 2.24 (m,
2H), 1.94 (m, 4H), 1.63 1.10 (m, 16H); 13C NMR (100.6 MHz, CD2Cl2):
d ˆ 160.4, 158.4, 154.1, 148.3, 145.1, 130.3, 130.1, 109.5, 109.0, 108.1, 108.0,
97.8, 56.2, 36.3, 34.5, 31.4, 31.2, 30.3, 29.8, 29.5, 29.2, 28.8, 28.7, 27.7, 26.9; IR:
n ˆ 3495, 3323, 3001, 2926, 2853, 1628, 1615, 1587, 1538, 1485, 1462, 1425,
1364, 1337, 1317, 1270, 1213, 1185, 1152, 1092, 1067, 1025, 1003, 834, 818,
Preparation of (Z)-36 by Lindlar reduction of cycloalkyne 38: Commer-
cially available Lindlar catalyst (40 mg) was added to a solution of alkyne
38 (145 mg, 0.185 mmol) in ethyl acetate/MeOH (10:1, 20 mL) and
quinoline (10 mL). The flask was flushed with H2 (two freeze/thaw cycles)
and the mixture was stirred under H2 (1 atm) for 2 h. Workup as described
above followed by flash chromatography of the crude product on silica
(hexanes/ethyl acetate 10:1 ! 6:1) afforded olefin (Z)-36 as a colorless oil
(141 mg, 0.18 mmol, 97%). The analytical and spectroscopic data were
identical in all respects to those compiled above.
‡
713, 667, 637 cmÀ1; MS (EI): m/z (%): 426 (5), 425 (29), 424 (100) [M] , 423
(4), 272 (3), 260 (11), 257 (4), 245 (5), 243 (8), 241 (4), 227 (3), 137 (3), 67
(3), 55 (5), 41 (4); HR-MS (EI) (C27H36O4): calcd 424.2614; found 424.2612;
elemental analysis calcd (%) for C27H36O4 (424.58): C 76.38, H 8.55; found
C 76.46, H 8.40.
Turriane 3: Pd/C (10% w/w, 40 mg) was added to a solution of olefin 36
(E:Z ˆ 5.8:1; 40 mg, 0.051 mmol) in ethyl acetate/EtOH (1:1, 15 mL,
containing two drops of water). The flask was flushed with H2 (two freeze/
thaw cycles) and the mixture was stirred under H2 (1 atm) for 24 h. The
catalyst was filtered off through a pad of Celite, the filtrate was evaporated
and the residue was purified by flash chromatography on silica (hexanes/
ethyl acetate 10:1 ! 4:1 ! 2:1) to give turriane 3 as a pale yellow oil
(19 mg, 87%). 1H NMR (300.1 MHz, CD2Cl2): d ˆ 6.49 (d, J ˆ 2.3 Hz, 1H),
6.42 (d, J ˆ 2.3 Hz, 1H), 6.37 (s, 2H), 4.64 (brs, <3H, OH), 3.71 (s, 3H),
2.57 (t, J ˆ 6.7 Hz, 2H), 2.27 (m, 2H), 1.67 1.05 (m, 24H); 13C NM R
(75.5 MHz, CD2Cl2): d ˆ 160.3, 158.4, 154.2, 148.3, 145.1, 109.3, 109.0, 107.9,
DNA cleavage assay
Representative procedure: A solution of purified scDNA (2 mL of a stock
solution containg ca. 400 mgmLÀ1) [FX174 RF1 DNA, purchased from
MBI Fermentas GmbH, St. Leon-Rot, Germany; the EDTA contained in
the commercial sample was removed according to the Qiaex II protocol for
desalting and concentrating DNA by using a Qiaex II Gel Extraction Kit]
was incubated at 378C for the time given in the Figure with the respective
turriane derivative (2 mL of a 2mm stock solution), Cu(OAc)2 (2 mL of a
Chem. Eur. J. 2002, 8, No. 8
¹ WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
0947-6539/02/0808-1869 $ 20.00+.50/0
1869

A. F¸rstner et al.
FULL PAPER
1 mm stock solution), n-butylamine (2 mL of a 20 mm stock solution), aq.
NaCl (3 mL of a 0.5mm stock solution) in water (complemented to give a
total volume of 20 mL). The mixture was quenched with loading buffer
(BioRad laboratories) and the DNA resolved by electrophoresis (Power-
pac 300, BioRad) (85 V, 1 h) on a 0.8% agarose gel (containing ethidium
bromide) in Tris/boronic acid buffer (BioRad). The bands detected by UV
were analyzed and processed using the Bio Doc II software (Biometra).
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¬
ƒ
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chloride/LiBr afforded an inseparable mixture of the desired benzyl
bromide and the corresponding benzyl chloride. Hence, the choice of
methanesulfonic anhydride is decisive.
Acknowledgement
Generous financial support by the Deutsche Forschungsgemeinschaft
(Leibniz award to A.F.), the Fonds der Chemischen Industrie (Kekule
¬
stipend to F.S.), and the European Union (Marie-Curie stipend to A.R.) is
gratefully acknowledged. We thank Mrs. C. Wirtz and Dr. R. Mynott for
their help with the interpretation of some of the NMR spectra and for the
unequivalent assignment of the stereochemistry of the RCMproducts.
Moreover, we are indebted to Mr. A. Deege and co-workers for
preparative HPLC separations.
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Received: November 5, 2001 [F3655]
Chem. Eur. J. 2002, 8, No. 8
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0947-6539/02/0808-1871 $ 20.00+.50/0
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