Synthesis and stereochemical resolution of functional [5]pericyclynes

Tetrahedron 60 (2004) 10077–10098

Synthesis and stereochemical resolution of

functional [5]pericyclynes

`

Luc Maurette, Christine Tedeschi, Emmanuelle Sermot, Michele Soleilhavoup, Fatima Hussain,

*

Bruno Donnadieu and Remi Chauvin

Laboratoire de Chimie de Coordination, 205 Route de Narbonne 31077 Cedex 4, Toulouse, France

Received 27 April 2004; revised 25 June 2004; accepted 14 July 2004

Available online 15 September 2004

Abstract—Three different kinds of ring carbo-mers of [5]cyclitol ethers were targeted as challenging examples of functional

[5]pericyclynes. Three tertiary pentaaryl-carbo-[5]cyclitol methyl ethers were synthesized through a [11C4] ring-closing double addition

of triphenyl- and tri-p-anisyl-undecatetrayn-diides to dibenzoylacetylene. These compounds, obtained as oily mixtures of stereoisomers, are

stable and can behave as acetylenic ligands of one or two Co₂(CO)₆units. NMR analysis reveals that the broad diasteroisomeric dispersity of

a triether, is consistently reduced in the symmetrized pentaether. Three bis-secondary triaryl-carbo-[5]cyclitol methyl ethers with adjacent

CH(OR) vertices were synthesized through a similar [11C4] ring-closing process, where the same tetrayn-diides add to both the

carbaldehyde ends of the (h²–OCH–C^C–CHO)Co₂(CO)₆complex. Despite the possibility of tautomeric isomerization, the occurrence of

two adjacent bis-propargylic carbinol vertices does not diminish the stability of the [5]pericyclyne framework. Finally, two bis-secondary

carbo-[5]cyclitol methyl ethers with non-adjacent CH(OH) vertices were synthesized through an alternative [10C5] ring-closing process.

The bis-secondary carbo-[5]cyclitols are regarded as isohypsic equivalents of the challenging [C,C]₅carbo-cyclopentadienyl cation. A

diphenyl-hexaoxy-[5]pericyclyne with two non-adjacent secondary carbinol vertices was also prepared through a [10C5] ring-closing

strategy: this molecule is an isohypsic equivalent of the previously calculated zwitterionic carbo-cyclopentadienone, which could be

observed as a DCI/NH₃-MS fragment after treatment with SnCl₂/HCl. Analytical HPLC showed that the C₁₁triphenyl-undecatetrayne

precursor of the [11C4] strategy was obtained as a statistical 1:2:1 mixture of the three possible diastereoisomers. Semi-preparative HPLC

allowed for the resolution of this mixture. The pure major diastereoisomer was employed to prepare a partly resolved sample of

pentamethoxy-pentaphenyl-[5]pericyclyne. Analytical HPLC showed that the latter corresponds to the statistical distribution of the expected

three residual diastereoisomers. Semi-preparative HPLC ﬁnally afforded samples of diastereoisomerically pure pentamethoxy-

[5]pericyclyne as crystalline solids.

1. Introduction

in terms of aromaticity. In a more subtle manner, ring

carbo-mers of saturated cycloalkanes were theoretically

compared in terms of homo-aromaticity.⁶These ‘carbo-

cycloalkanes’ are actually [N]pericyclynes, a generic term

coined by Scott et al. in 1983 as they reported the synthesis

of the ﬁrst representative, decamethyl[5]pericyclyne

(Scheme 1).⁷An octamethyl analogue was later reported.⁸

The fascinating structure and stability of these rigid p-

electron-rich 15-membered rings then attracted a consider-

able theoretical interest.^9,2,4,6Nevertheless, an open ques-

tion is whether the stability of [5]pericyclynes is compatible

with functionalities at the sp³vertices. Hexaoxy-[6]pericy-

clynes,^10aand expanded peroxy-pericyclynes (made with

butadiyne edges and ketal vertices) have been described.^10b

To the best of our knowledge however, beside mentions of

few peralkyl-monohydroxy-[5]periclynes,¹¹no functional

simple [5]pericyclyne was hitherto described in the

literature. We focus here on the synthesis of pentaoxy-

[5]pericyclynes, which can be alternatively regarded as

‘carbo-[5]cyclitol’ derivatives (Scheme 1). Beyond the

In the general ﬁeld of carbon-rich molecules,¹we have been

interested for some time in a carbon ‘enrichment’ process

which could preserve some memory of its poorer parent

molecule. Meeting the ﬁeld of polyacetylenic chemistry,²it

consists in the linear insertion of two sp carbon atoms into

each bond of the parent Lewis skeleton. It is readily checked

from basic VSEPR and mesomerism that the resulting

‘carbo-mer’ structure preserves essential features of the

parent model (connectivity, shape, symmetry, p-resonance,

CIP conﬁgurations of stereogenic centers), while it has

experienced a three-fold size expansion.³Focusing on

cyclic hydrocarbons, carbo-mers of unsaturated rings such

as annulenes⁴and radialenes,⁵were theoretically compared

Keywords: Carbo-mers; Pericyclynes; Cyclization reactions; Acetylenedi-

carbaldehyde; Diastereoisomeric resolution.

* Corresponding author. Tel.: C335-61-33-31-13; fax: C335-61-55-30-

03; e-mail: chauvin@lcc-toulouse.fr

doi:10.1016/j.tet.2004.07.052

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Scheme 1. Scott’s [5]pericyclyne,⁷[5]cyclitol ethers and ring carbo-mer thereof.

Scheme 2. Targeted functional [5]pericyclynes (RsH).

academic aestetical concern, one may ﬁgure out appli-

cations such as, for example, rigid crown ether-like

properties or possible aromatization to the challenging

ring carbo-mers of cyclopentadienyl cations.⁴

and [11C4C11C4] processes, respectively.¹³Just

changing the C₄dielectrophile, the present strategy is

based on a ring-closing double addition to the dibenzoyl-

acetylene 1 (Scheme 3).

The envisioned pathways to tertiary and bis-secondary

carbo-[5]cyclitol ethers (Scheme 2) are based on sequential

alkynyl-propargyl coupling reactions.¹²The results are

described in Sections 1 and 2. Since the stereogenic carbons

of the carbo-[5]cyclitols stand in remote (g) positions, their

relative conﬁguration is likely poorly controlled. A third

section is therefore devoted to the diastereomeric resolution

of carbo-[5]cyclitol ethers using HPLC techniques.

Some procedures will be inspired from those utilized by

Ueda, Kuwatani et al. for the synthesis of homologous

‘carbo-[6]cyclitol’ derivatives.^10aThe synthesis of the

known triphenylundecatetrayne 2a was extended to the

trianisyl analogue 2b.¹³In analogy with 3a, the starting

diyne 3b was thus prepared through the three-step sequence

depicted in Scheme 4. Acylation of bistrimethylsilyl-

acetylene with p-anisoyl chloride afforded the anisyl-

ethynylketone 4b. Reaction of 4b with magnesium acetylide

lead to the diethynyl-anisyl carbinol 5b, the X-ray crystal

structure of which was determined (see Section 2.2.2 and

Fig. 3). The ether 3b was ﬁnally obtained by methylation of

the monolithium salt of 5b.

2. Results and discussion

2.1. Tertiary carbo-[5]cyclitol ethers

Two equivalents of the lithium salt of 3b reacted with

anisoyl chloride to give 6b in 52% yield (instead of 77% in

the phenyl series 6a from 3a).¹³Methylation of the lithium

alkoxide of 6b with MeI/DMSO,^10afollowed by desilylation

with K₂CO₃/MeOH,¹⁴afforded the undecatetrayne 2b. The

The selected strategy is straightforwardly inspired from the

previously attempted [11C4] ring-closing double substi-

tution of 1,4-ditosyloxy-but-2-yne (TsOCH₂C^CCH₂-

OTs). This strategy actually afforded a cyclic isomer and

a cyclic dimer of the desired [5]pericyclyne through [11C4]

Scheme 3. Retrosynthetic analysis to tertiary carbo-[5]cyclitol ethers.

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

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Scheme 4. Synthesis of the 1,4-pentadiynes precursors of the C₁₁tetraynes 2a and 2b.

Figure 1. ¹H (250 MHz) and ¹³C NMR (100 MHz, 62 MHz) spectra in CDCl₃of the less symmetric triether 7a as compared with those of the more symmetric

pentaether 11a.

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L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

Scheme 5. Synthesis of tertiary carbo-[5]cyclitol derivatives (7) and isolated side-products (8–10).

tetraynes 2a and 2b were obtained as statistical mixtures of

stereoisomers (see Section 2.3 for the HPLC analysis of 2a).

The stereoisomers of these open-chain polyynes are nearly

intensities occur at 3.05 and 3.15 ppm. Assuming that the

primary factor determining the chemical shifts of these

hydroxyls is their relative cis or trans orientation with

respect to the mean ring plane, this observation suggests that

the ring closing process is deﬁnitely non-stereoselective.¹⁶

It must be stressed that the ¹³C chemical shifts are much less

sensitive to diastereotopicity than are the ¹H chemical shifts:

the formers solely undergo the inﬂuence of the proximate

(topological) chemical environement (Fig. 1).

1

degenerate in their H and ¹³C NMR spectra (see Section

2.3, Fig. 6). This is due partly to the remote g positions of

the stereogenic centers, but mainly to an averaging free

rotation process. Indeed the NMR degeneracy clears up in

the next locked cyclic derivatives 7 (see discussion below,

and Fig. 1). The latters were indeed obtained upon double-

attack of the dilithium salts of 2a and 2b to dibenzoyl-

acetylene 1, prepared from the trans-1,2-dibenzoylethylene

according to the Schuster’s procedure.¹⁵Beside some

unreacted tetraynes 2 and several acyclic products 8, 9, 10

(isolated in the phenyl series a), pentaphenyl[5]pericyclyne

7a and diphenyl-trianisyl-[5]pericyclyne 7b were formed

rather selectively, in 37 and 31% yield, respectively. These

novel functional pentaoxy-[5]perictyclynes are stable and

could be characterized by MS, IR, ¹H and ¹³C NMR

spectroscopy (Scheme 5).

For the pentaphenyl derivative 7a, methylation of the two

hydroxyl groups results in an increased symmetry (all the

ﬁve vertices become identical in nature: CPh(OMe), and

would allow to reduce the theoretical number of diaster-

eoisomers from ten to four (Scheme 6).

Starting from a mixture of the three stereoisomers of

undecatetraynes 2a–2b, the obtained [5]pericyclynes with

two adjacent CPh(OH) vertices and three CAr(OMe)

vertices are theoretically obtained as mixtures of 10

diastereoisomers (six of them being chiral). Considering

the possible symmetry-equivalence of pairs of MeO groups,

26 different OCH₃signals are a priori expected in the NMR

spectrum of 7a (resp. 7b). Consistently, a large number of

signals (ca. 16) are indeed observed in the range 3.3–

3.7 ppm. The possibility of overlap precludes an exact count

of the stereoisomers of 7a (Fig. 1). Nevertheless, two well-

separated broad D₂O-exchangeable OH signals of equal

Scheme 6. Symmetrization of a carbo-[5]cyclitol triether to the

corresponding pentaether.

The NMR spectra of the pentamethoxy-pentaphenyl-

[5]pericyclyne 11a are indeed signiﬁcantly simpliﬁed

(Fig. 1). Only eight well-resolved ¹H NMR signals are

now observed in the OCH₃region, out of 10 expected in the

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

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Scheme 7. Cobalt complexes of pentaoxy[5]pericyclynes. The depicted regiochemistry of the complexation may not be unique, but it corresponds to

experimental data on decamethyl-[5]pericyclyne.⁸For 12 and 12⁰, the preferred complexation on the ‘butyndiol edge’ is suggested by DFT calculations on a

model butyndiol complex revealing chelating hydrogen bonds involving the carbonyl ligands of the Co₂(CO)₆moiety.¹⁷

statistical distribution. All the possible diastereoisomers are

thus signiﬁcantly present in the product (two signals are

likely degenerate with other(s) under the most intense

signal(s): Fig. 1). As stressed above, the ¹³C chemical shifts

are much less sensitive to diastereotopicity and all carbons

of given chemical type resonate as single frequencies in all

the stereoisomers (only sp-carbon atoms, at the midpoint

between two stereogenic vertices, remain very slightly non-

degenerate: Fig. 1). No stereochemical correlation was thus

possible. A ﬁrst attempt at separation of the diastereo-

isomers by HPLC remained unsuccessful, thus requiring a

stepwise resolution method (see Section 2.3).

2.2. Bis-secondary carbo-[5]cyclitol ethers

[5]Pericyclynes with several secondary carbinol vertices are

speciﬁcally interesting for several reasons: (i) they are not

exempliﬁed in the literature,¹⁸and possibly tautomerically

instable;¹⁹(ii) if stable, they are more versatile than their all-

tertiary counterparts for further functionalization (by full

reduction to CH₂or full oxidation to C]O); and (iii) they

are redox (isohypsic) equivalents of the challenging carbo-

cyclopentadienyl ring cation.^4a,b,6The synthesis of [5]peri-

cyclynes with two secondary carbinol vertices at either

adjacent or non-adjacent positions (Scheme 2) has been

envisioned through two cyclization strategies, [11C4] and

[10C5].

Scott et al. showed that peralkylpericyclynes act as ligands

for one or two Co₂(CO)₆units, and that use of a large excess

Co₂(CO)₈does not lead to further complexation.⁸This

behaviour was tested for functional versions. Reaction of

the carbo-[5]cyclitol ethers 7a, 7b or 11a with a single

equivalent of Co₂(CO)₈lead to two red complexes which

could be separated by chromatography (Scheme 7).

According IR, MS (APCIO0/CH₃CN, MALDI) and

elemental analyses, the less polar products 12a, 12b, 13a

(isolated in 50–60% yield) contain a single Co₂(CO)₆unit.

The most polar products 12a⁰, 13a⁰(20–30% yield) contain

two Co₂(CO)₆units. The proposed structures in Scheme 7

are based on Scott’s results on decamethyl-[5]pericyclyne,

showing that the two Co₂(CO)₆units of the bis-complex are

bound to non-adjacent triple bonds. For 12a, 12a⁰and 12b,

the proposed hapticity of the triple bonds lying between the

CPh(OH) vertices is supported by standard steric

arguments, and by DFT calculations (B3PW91/6-31G**/

LANL2DZ(Co)) on a model Co₂(CO)₆complex of 2R,5R-

diphenyl-hexa-3-yn-2,5-diol displaying two stabilizing

2.2.1. Bis-secondary carbo-[5]cyclitol ethers with adja-

cent CH(OH) vertices: a [11C4] strategy. The preceeding

route to pentaaryl-carbo-[5]cyclitol ethers (Section 2.1)

suggests the replacement of dibenzoylacethylene 1 for

acetylenedicarbaldehyde (CHO–C^C–CHO). Extensive

studies by Gorgues et al. have shown that this highly

functional C₄molecule is however quite instable,²⁰and

cannot be used as such for synthetic purpose. Nonetheless, it

can be stabilized as a ligand in the cobalt(0) complex 14.

X-ray diffraction analyses of single crystals of 14 showed

that the propargylic aldehyde functions do not interact with

the cobalt centers.²¹This structural feature is consistent with

our recent studies showing that the dialdehyde ligand

preserves its theoretical 1,4-electrophilicity, not only

towards neutral nucleophiles (silylenol ethers and tri-

methoxybenzene in Nicholas-type reactions),²²but also

towards anionic nucleophiles.²³Despite the presence of six

‘electrophilic’ carbonyl ligands, alkyl, aryl, ethynyl lithium

and Grignard reactants add to both aldehydic functions in a

17

˚

O–H/(CO) hydrogen bond-like distances (2.34 A).

Scheme 8. [11C4] retrosynthesis of bis-secondary pentaoxy[5]pericyclynes based on the use of Gorgue’s complex 14.

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L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

Scheme 9. Synthesis of bis-secondary pentaoxy[5]pericyclynes via cobaltcarbonyl complexes.

(25% yield, Scheme 9). The same sequence from the

trianisyl-tetrayne 2b afforded the analogous complex 15b

(6% yield. Scheme 9). Rather surprisingly, whereas 2 equiv.

of various monoacetylides (RC^C–Li) were shown to

afford the corresponding acyclic triyndiol complexes in

rather low yields (9–16%) as compared with alkyl and aryl

nucleophiles,²³the yield in the cyclic product 15a is here

relatively high. The tandem cyclic feature of the process is

therefore highly beneﬁcial. Nevertheless, none of the

classical MS methods, including atmospheric pressure

chemical ionization (APCI), gave relevant fragmentation

peaks. Their structure was conﬁrmed in the next step.

Indeed, oxidative decomplexation of the corresponding

samples of 15a–b afforded the bis-secondary carbo-

[5]cyclitols 16a ([MNH₄]^CZ558) and 16b ([M]^CZ630;

[MH–MeOH]^CZ599: stabilized a-p-anisyl carbocationic

fragment). The procedure previously employed for

O-methylation of tertiary diethynyl-aryl carbinols (depro-

tonation with n-BuLi, then MeI/DMSO) turned out to be

unsuccessful for secondary diethynyl carbinols (from diol

16a) in the phenyl series. In one attempt in the anisyl series

(from diol 16b), however, it afforded a crude compound

whose NMR and MS spectra were consistent with the bis-

secondary pentamethoxy-[5]pericyclyne structure 17b

([MH–MeOH]^CZ627).

Scheme 10. Formal isohypsic equivalence of bis-secondary pentaoxy[5]-

pericyclynes with carbo-cyclopentadienyl cations.

Scheme 11. [10C5] retrosynthesis of bis-secondary pentaoxy-

[5]pericyclynes.

chemo- and regio-selective manner. Moreover, the double

additions take place with some stereoselectivity (meso:dl

ratio up to 80:20). We therefore envisioned to apply the

reaction in a ring-closing version from tetraynes 2a and 2b

(Scheme 8).

These stable molecules constitute the ﬁrst examples of

redox (isohypsic) equivalents of carbo-cyclopentadienyl

cations (Scheme 10).^4a,b,6The corresponding fragments

could however not be detected in their mass spectrum. In an

attempt at triggering aromatization through double 1,4-

elimination of methanol, a yellow solution of 17b (CDCl₃,

K60 8C) treated with triﬂic acid turned immediately to

violet with concomitant formation of a black precipitate. No

signal could be detected by ¹H NMR analysis of the highly

diluted supernatent, but the water-sensitive violet color

remained persistent over 12 h at room-temperature. Despite

the expected stabilizing effect of three anisyl substituents,

Double deprotonation of the triphenyl-tetrayne 2a with

n-BuLi in THF followed by addition of the acetylene-

dicarbaldehyde complex 14 and protonation, afforded a

mixture of compounds. Chromatography allowed to isolate

1

a single-spot red complex, whose H, ¹³C NMR and IR

analyses are consistent with the expected structure 15a

Scheme 12. Preparation of the octatriyne precursors of the C₁₀dialdehydes envisioned in the [10C5] strategy (Scheme 11).

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10083

Scheme 13. Double formylations of triynes 20,²⁵affording the key C₁₀dialdehydes for the envisioned [10C5] strategy (Scheme 11).

compound 17b is deﬁnitely more prone to polymerization

than to dissociative aromatization. Speculatively, 1,4-

elimination from 17 is indeed not regio-directed: if it

ﬁrst took place on the bis-secondary edge, the

resulting trisubstituted butatriene edge (^C–

(H)C]C]C]C(OMe)–C^) in a not-yet-aromatic penta-

gonal ring would be likely quite instable. The design of an

optimized precursor structure was therefore suggested as a

prerequisite for any further attempt at quantitative formation

of the carbo-cyclopentadienyl ring cation.

While 20c was isolated as an orange oil, its anisyl couterpart

20d is an orange powder. A single crystal of 20d was

obtained as an orange powder, revealing a meso conﬁgur-

ation in a perfect C₂conformation (Fig. 2). The crystal

structure can be compared with the structure of the 1,4-

diyne precursor 5b. In meso-20d, the measured bond angle

at the C3 sp carbon atom and the corresponding triple bond

distance are C2–C3–C4(H)Z166.5(6)8 and C3–C4Z

˚

1,139(6) A, respectively. These values appear as rather

‘abnormal’ with respect to the classical structural features of

alkynes and to the ‘normal’ values measured from the X-ray

crystal structure of the dialkynylcarbinol 5b (true racemate,

2.2.2. Bis-secondary carbo-[5]cyclitol ethers with non-

adjacent CH(OH) vertices: a [10C5] strategy. The

second kind of bis-secondary carbo-[5]cyclitols (Scheme 2)

was targeted through the alternative [10C5] strategy

disclosed in Scheme 11.

˚

Fig. 3: C1–C2–C3(H)Z177.66(14)8; C2–C3Z1,184(2) A).

Beyond possible experimental error, the apparent bond

shortening can be due to an artifact of the X-ray

measurement, as previously discussed for tetraethynyl-

methane on the basis of a ‘p electron compression’ effect.²⁴

The C₁₀trisacetylenic dialdehyde precursors 18a, 18b were

prepared in three steps from the 1,4-diynes 3a, 3b

(Schemes 12 and 13). Addition of the corresponding lithium

acetylides to trimethylsilylpropynal afforded the corre-

sponding triynes 19a and 19b as mixtures of meso and dl

The carbaldehyde groups were then introduced by double

formylation according to the Journet and Cai’s procedure.²⁵

The hydrolysis step is crucial for a successful production of

1

isomers in an undetermined ratio (the H NMR signals are

not split signiﬁcantly). After methylation of the hydroxyl

group, both the terminal alkynes were readily deprotected

with K₂CO₃/MeOH, affording 20c and 20d in 84 and 67%

yield, respectively.

Figure 3. ORTEP view of 5b with 50% probability displacement ellipsoids

˚

Figure 2. ORTEP view of 20d with 50% probability displacement

˚

for non-hydrogen atoms. Bond distances (A): C(1)–C(2)Z1.475(2); C(1)–

ellipsoids for non-hydrogen atoms. Bond distances (A): C(2)–C(3)Z

C(4)Z1.4832(19); O(1)–C(1)Z1.4437(15); C(2)–C(3)Z1.184(2); Si(1)–

C(5)Z1.8499(17). Bond angles (8): C(3)–C(2)–C(1)Z177.66(14); C(5)–

C(4)–C(1)Z177.02(15); C(2)–C(1)–C(4)Z108.78(11); C(4)–C(5)–

Si(1)Z172.16(12).

1.473(6); C(3)–C(4)Z1.139(6); C(1)–C(2)Z1.494(6); C(2)–O(1)Z

1.450(5); C(1)–C(1)#1Z1.187(8). Bond angles (8): C(1)#1–C(1)–C(2)Z

177.6(5); C(3)–C(2)–C(1)Z107.6(4); C(4)–C(3)–C(2)Z166.5(6).

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the anisyl analogue 18b. The crude dialdehyde 18b obtained

by the ﬁrst method (Scheme 13) was thus used as such in the

cyclization step (see below).

The C₅1,4-diyne moieties 24a, 24b were obtained by

quantitative desilylation of the diynes 3a, 3b in basic

medium (Scheme 15). The [10C5] ring closing step is

based on a double nucleophilic attack of the dilithium salts

of 24a, 24b to the C₁₀dialdehyde moieties 18a, 18b. In the

phenyl series, the carbo-[5]cyclitol ether 25a was isolated in

15% yield. Attempt at templating the triyne electrophiles

with AgBF₄did not increase the yield. In the anisyl series,

two major products were obtained from the crude mixture

18bC21b (Scheme 13). The carbo-[5]cyclitol ether 25b

and the acyclic product 26b could ﬁnally be separated in 19

and 10% yield, respectively.

Scheme 14. Alternative synthesis of the key C₁₀dialdehyde 18a for the

envisioned [10C5] strategy (Scheme 11).

The DCI/NH₃mass spectrum of the carbo-[5]cyclitol ether

25a exhibits a base peak at m/eZ558 ([MNH₄]^C) and a

major peak at m/eZ509 ([MH–MeOH]^C) (Fig. 4). Two

secondary peaks at m/eZ526 and 494 correspond to the

‘carbo-cyclopentene’ ([MCNH₄–MeOH]^C) and ‘carbo-

cyclopentadiene’ ([MK2MeOHCNH₄]^C) parent ions

respectively. The corresponding carbo-cyclopentadienyl

fragments (([MHK3MeOH]^Cor ([MCNH₄K3MeOH]^C)

were not observed. The DCI/NH₃mass spectrum of the

anisyl carbo-[5]cyclitol ether 25b exhibits similar features,

with a main base peak at m/eZ599, corresponding to

[MHKMeOH]^C(stabilized a-p-anisyl carbocation, as in the

case of 7b discussed in Section 2.1).

18a–18b: it consists in the addition of the alkaline solution

into a 1:1 mixture of diethylether and KH₂PO₄aqueous

buffer (alternatively, NaHPO₄CKCl, can be used. The use

of other acids triggered back reaction and untransformed

triyne 20 was recovered). Monoaldehydes 21a, 21b were

formed as side-products in ca. 20% yield according to NMR

analysis of the crude materials.

Attempts at puriﬁcation by chromatography resulted in

partial decomposition, affording pure 18a in 32% yield only.

The anisyl derivative 18b could not be successfully puriﬁed.

To make up this problem, an alternative route was addressed

from commercially available propiolaldehyde diethylacetal

and dibenzoylacetylene 1 (Scheme 14).

As an alternative C₅1,4-diyne fragment, the pentadiyn-3-

one ketal 27 possesses a non-asymmetric bis-propargylic

carbon center. It was used by Bunz et al. for the synthesis of

functional expanded pericyclynes.^10bWithin the framework

of the present [10C5] strategy, the resulting [5]pericyclyne

should be topologically more symmetrical, with a reduced

number of diastereoisomers (ﬁve instead of eight in the

previous case). The known C₅precursor 27 was prepared by

addition of 2 equiv. of trimethylsilylacetylide to ethyl

formate, followed by oxidation of alcohol 28, and ketaliza-

tion of ketone 29 with 2,2-dimethyl-1,3-propandiol under

speciﬁc conditions of dilution in toluene (instead of benzene

in the previously described procedure).^10bQuantitative

Addition of two equivalents of lithium 3,3-diethoxy-

propynide to diketone 1 in THF and subsequent hydrolysis

afforded diol 22a. After methylation of the hydroxyl groups,

hydrolysis of the acetal functions by conventional acidic

treatments (formic acid or PTSA) remained unsuccessful.

Compound 23a could, however, be deprotected in an

‘oxidizing’ neutral medium using DDQ in the dark.²⁶

Dialdehyde 18a was ﬁnally obtained in three steps and 61%

yield. At this stage, the lack of a rapid procedure for the

preparation of the dianisyl analogue of diketone 1,

prevented the use of this strategy (Scheme 14) to obtain

Scheme 15. Ultimate steps of the [10C5] strategy, affording pentaoxy-[5]pericyclynes with non adajacent CH(OH) vertices.

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10085

Figure 4. MS (DCI/NH₃) spectra of bis-secondary pentaoxy-[5]pericyclynes 25a and 25b showing the preferred fragmentations through one or two methanol

eliminations from the protonated or ammoniated species. The third methanol elimination which could produce the corresponding dihydroxy-triphenyl-carbo-

cyclopentadienyl cations was not observed.

Scheme 16. Four-step synthesis of the 2,2-dimethyl-1,3-propanediol ketal of diethynyl ketone,^10ban alternative C₅moiety for the [10C5] strategy.

desilylation of 30 afforded 27 in 27% overall yield

(Scheme 16).

The dilithium salt of 27 was then allowed to react with

dialdehyde 18a, affording the novel [5]pericyclyne 31 as a

pale yellow powder in 18% yield (Scheme 17). All attempts

at deprotection of the ketal vertex of 31 remained

unsuccessful. Inspection of the literature reveals that no

effective deprotection of such hindered ketals of dialkynyl-

ketones has been hitherto reported. In particular, deprotec-

tion of Bunz decaoxy-expanded [5]pericyclyne was not

reported.^10bMoreover, it seems that 30 is the sole known

ketal derivative of the ketone 29, and consistently, our

Scheme 17. [10C5] ring closing process affording a bis-secondary

hexaoxy[5]pericyclyne.

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L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

Scheme 18. Possible aromaticity-stabilized structure of the observed fragment at m/zZ402 in the DCI/NH₃mass spectrum of the hexaoxy-[5]pericyclyne after

acidic treatment.

carbo-cyclopentadienyl resonance form (Scheme 18). The

geometry of the carbo-cyclopentadienone model molecule

(C₁₅H₄O) was optimized at the B3PW91:6-31G** level,²⁷

and it was shown that this model is aromatic in both the

˚

structural sense (planarity, C/O distance of 1.44 A

corresponding to a^CC–O^Ksingle bond description) and

the magnetic sense (NICSZK8.1 ppm,).²⁸This aromaticity

might account for the observed MS fragmentation of ketal

31.

2.3. Diastereoisomeric resolution of carbo-[5]cyclitol

pentaether 11a

As previously stressed (Section 2.1), all the compounds

containing more than two dialkynylcarbinol units were

obtained as mixtures of diastereoisomers. All attempts at

separating them by TLC and column chromatography

failed. Focusing on the most symmetric pentaoxy-[5]peri-

cyclyne target 11a (with four diastereoisomers only:

Scheme 6), we therefore turned to HPLC techniques.

Since 11a is obtained from tetrayne 2a and dibenzoyl-

acetylene 1, and since the three stereogenic sp³carbon atoms

of 2a are retained in 11a, a preliminary diastereoselective

separation of 2a was attempted. In theory, 2a possesses three

diastereisomers A, B and C, anticipated to form in the

statistical distribution A:B:CZ1:2:1 (Scheme 19).

Scheme 19. Stereoisomers A, B, C of the tetrayne 2a and their statistical

ratio.

Their separation was achieved by HPLC, with a direct phase

column of Prontosil type. After several trials, a 70:30

pentane:dichloromethane mixture was determined as an

optimal eluting system. The analytical HPLC chromato-

gram displays three peaks with baseline separation for

retention times of 40.8, 43.7 and 49.4 min, integrating for

25, 50 and 25%, respectively (Fig. 5). The three peaks

correspond to identical UV spectra, as expected for closely

related diastereoisomers A, B, C. This conﬁrmed the

statistical ratio, and allowed for the assignment of the

major intermediate signal (at R_tZ43.7 min) to the structure

B (Scheme 19).

Figure 5. HPLC separation of the stereoisomers A, B, C (Scheme 19).

personal attempts at preparing the less hindered 1,3-

propylene ketal or the acyclic diethylketal of 29 failed.

The three diastereoisomers were then sequentially separated

twice by semi-preparative HPLC. The three stereochemi-

cally pure products are oils, the NMR spectra of which were

recorded separately (Fig. 6). It is predicted that the isomer B

should exhibit three non-equivalent methoxy NMR signals,

while both A and C should exhibit two different signals

only. These features were conﬁrmed, in accordance with the

Aromatisation of the carbo-[5]cyclitol derivative 31 with

the classical reactant SnCl₂/HCl^10aafforded a complex

mixture of products. However, DCI-MS analysis of the

mixture exhibited a secondary peak at m/zZ402 (19%).

This value is consistent with the parent carbo-cyclopenta-

dienone-ammonium structure or with its zwitterionic oxyl-

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10087

Figure 6. NMR spectra (CDCl₃, 250 MHz) of separated diastereoisomers of tetrayne 2a. a) Stereoisomer A or C. b) Stereoisomer B. c) Stereoisomer C or A,

different from the stereoisomer corresponding to spectrum a).

Scheme 20. Statistical stereoisomeric distribution of the pentamethoxy-[5]pericyclyne 11a resulting from a [11C4] ring closing process involving the pure

isomer B of tetrayne 2a. For clarity, the phenyl substituents are not depicted.

HPLC assignment. In particular, only the compound of the

major HPLC peak displays three OCH₃NMR signals of

equal intensities, thus conﬁrming structure B (Fig. 6(b)).

Nonetheless, neither the HPLC integration nor the multi-

plicities of the NMR signals allow for an assignment of

structures A and B to their respective HPLC retention time

1

and H NMR spectrum.

Having pure diastereoisomers of 2a in hand, the double

addition to dibenzoylacetylene 1 was carried out from the

Figure 7. HPLC separation of the three isomers of pericyclyne 11a in

statistical distribution (Scheme 19).

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L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

Figure 8. ¹H NMR spectra (CDCl₃, 250 MHz) of two minor isomers of pentamethoxy-pentaphenyl -[5]pericyclynes (R_tZ16.56 and 20.26 min in Fig. 7). RZ

Me. The exact assignment.

dilithium salt of the major diastereoisomer B (Scheme 20);

the cyclization process creates two additional stereogenic

carbon atoms. After methylation in situ of the intermediate

OLi groups of the partly resolved salt of 7a, the expected

number of stereoisomers of the product 11a is reduced to

three. Their corresponding statistical ratio would be 1:2:1

(Scheme 20).

three peaks were obtained with baseline separation, and

their relative UV-integration conﬁrmed the statistical

distribution (Fig. 7).

Semi-preparative HPLC separation of the mixture was

carried out under optimized conditions (see Section 4). Two

out of three diastereoisomers were ﬁnally isolated as pure

white crystalline compounds. Their respective NMR spectra

conﬁrmed their stereochemical purity, and were consistent

Analytical HPLC resolution was successfully attempted:

Figure 9. MM2-optimized geometries of two stereoisomer of 11a.⁴.

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10089

with the theoretical number (3) and relative intensities

(1:2:2) of non-equivalent OCH₃signals for the proposed

structures (Fig. 8). These compounds are the ﬁrst examples

of disymmetrically and stereoselectively substituted

functional [5]pericyclynes.

120-5-SI column (250 mm!8 mm i.d., particle size: 5 mm,

Bischoff). All IR and NMR spectra were recorded in CDCl₃

solutions. IR absorption frequencies n are in cm^K1. NMR

chemical shifts d are in ppm, with positive values to high

frequency relative to the tetramethylsilane reference;

coupling constants J are in Hz. Since most compounds are

isolated as oily mixtures of diastereoisomers, characteristic

assignments are given to trace the analytical consistency

within the quite homogeneous series of compounds studied

(diethynyl carbinol series and phenyl- and p-anisyl-

derivatives thereof).

3. Conclusion

Functional [5]pericyclynes with either tertiary or secondary

carbinol vertices are deﬁnitely stable compounds. The

stereochemical complexity arising from the stereogenicity

of the sp³vertices (with respect to the symmetrical

decamethyl- and pentacyclopropylidene-derivatives)²⁹has

been studied by NMR and resolved by HPLC techniques.

Monocrystals of stereochemically pure samples were not

suitable for an X-ray structure determination, but insights

may be gained on the basis of MM modeling (Fig. 9). The

phenyl and methoxy substituents do not alter the features

calculated at higher (DFT) level for unsubstituted models

(slight ring distortion from planarity, absence of homo-

aromaticity as revealed by the lengths of ‘ﬁxed’ single and

triple bonds).⁶Although effective dissociation of isohypsic

equivalents of the carbo-cyclopentadienyl cation remains to

be achieved, preliminary MS data on 31 are encouraging.

Much work however has still to be done, especially in terms

of scale-up of the stereoisomeric resolution. Alternatively,

direct stereoselective synthesis under the inﬂuence of chiral

auxiliaries or catalysts deserves to be envisioned.

4.1.1. 3-Trimethylsilyl-1-(4-methoxyphenyl) prop-2-yn-

1-one (4b). Aluminum chloride (9.00 g, 67 mmol) was

added to a solution of bistrimethylsilylacetylene (13.1 mL,

67 mmol) and anisoyl chloride (11.50 g, 67 mmol) in DCM

(160 mL) at 0 8C. After stirring for 3 h at r.t., the mixture

was cooled to 0 8C, hydrolyzed with ice (50 g) and extracted

in dichloromethane. The organic layer was washed with

saturated aqueous NaHCO₃and water, then dried over

MgSO₄. The solvent was removed under reduced pressure

to give crude ketone 4b as an orange oil (15.66 g, 100%),

displaying satisfactory analytical data. R_fz0.45 (heptane/

1

EtOAc 9:1). H NMR: dZ0.24 (s, 9H; Si(CH₃)₃), 3.79 (s,

3H; OCH₃), 6.87 (d, 2H; m-CH), 8.03 (d, 2H; o-CH). ¹³C

1

NMR: dZK0.69 (q, J_CHZ120 Hz; Si(CH₃)₃), 55.51 (q,

¹J_CHZ145 Hz; OCH₃), 99.38 (s; C^CSi), 100.96 (s; ^C–

1

Si), 113.79 (d, J_CH₁Z158 Hz; m-CH), 129.66 (s; ipso-C–

C]O), 131.92 (d, J_CHZ159 Hz; o-CH), 164.48 (s; p-C–

OMe), 176.22 (s; C]O). IR: nZ2978, 2875 (C–H), 2155

(C^CSi), 1634 (C]O), 1598, 1509 (aromatic C–C), 1257

(C–Si), 1166, 1110, 1040–1026 (C–O).

4. Experimental

4.1. General

4.1.2. 1-Trimethylsilyl-3-(4-methoxyphenyl)penta-1,4-

diyn-3-ol (5b). A saturated solution of acetylene in THF

(350 mL) at 0 8C was treated with EtMgBr (81.0 mL,

243 mmol) for 1 h at 0 8C. Anisylketone 4b (15.66 g,

67 mmol) was added, and the stirring was continued

overnight (17 h) at r.t. The reaction mixture was hydrolyzed

with a saturated aqueous NH₄Cl, and extracted with

diethylether. The organic layer was washed with water,

dried over MgSO₄, and concentrated under reduced

pressure. Puriﬁcation through column chromatography on

silicagel (heptane/EtOAc 8:2) afforded diyne 5b as a brown

oil (10.72 g, 61%). R_fz0.20 (heptane/EtOAc 85:15). MS

(DCI/NH₃): m/zZ258 ([M]^C), 241 ([MKOH]^C), 161

([MKC^CSiMe₃)]^C). ¹H NMR: dZ0.20 (s, 9H;

Si(CH₃)₃), 2.74 (s, 1H; ^C–H), 3.24 (s, 1H; OH), 3.78 (s,

3H; OCH₃), 6.91 (d, 2H; m-CH), 8.09 (d, 2H; o-CH). ¹³C

All reagents were used as commercially available from

Acros Organics, Avocado, Aldrich, Lancaster, Strem. THF

and diethylether were dried and distilled on sodium/benzo-

phenone, pentane and dichloromethane on P₂O₅. Com-

mercial solutions of EtMgBr are 3 M in diethylether.

Commercial solutions of n-BuLi are 1.6 or 2.5 M in hexane,

and their effective concentration were checked by titration

with 2,2,2⁰-trimethylpropionanilide.³⁰Previously described

procedures were used for the preparation of 1,¹⁵4a, 5a and

3a,^10a6a, 6c and 2a,¹³14,^21,23, 28, 29, 30 and 27.^10bAll

reactions were carried out under nitrogen or argon

atmosphere, using Schlenk and vacuum line techniques.

Column chromatographies were carried out with SDS

˚

silicagel (60 A C.C 70–200 mm). Thin Layer Chromato-

1

NMR: dZK0.48 (q, J_CHZ121 Hz; Si(CH₃)₃), 55.26 (q,

graphy plates were purchased from SDS (60F254, 0.25 mm)

and revealed by treatment with an ethanolic solution of

phosphomolybdic acid (20%). The following analytical

instruments were used. IR: 0.1 mm CaF₂cell, Perkin-Elmer

¹J_CHZ144 Hz; OCH₃), 64.51 (s, OC(OH)An), 73.03 (d,

2

¹J_CHZ154 Hz; ^C–H), 83.75 (d, J_CHZ49 Hz; C^CH),

89.92 (s; C^CSiMe₃), 104.01 (s; ^C–SiMe₃), 113.61 (d,

1

¹J_CHZ170 Hz; m-CH), 127.62 (d, J_CHZ153 Hz; o-CH),

1

GX FT-IR. H and ¹³C NMR: Brucker AC 200, WM 250,

133.32 (s; ipso-C–C), 159.66 (s; p-C–OMe). IR: nZ3576

(O–H), 3305 (^CH), 2963 (C–H), 2840 (OC–H), 2176

(C^CSi), 2101 (^CH), 1608, 1510 (aromatic C–C), 1252

(C–Si), 1173, 1091, 1035 (C–O).

DPX 300 or AMX 400. X-Ray diffraction: IPds STOE. Mass

spectrometry: Quadrupolar Nermag R10-10H. Elemental

analyses: Perkin-Elmer 2400 CHN (ﬂash combustion and

detection by catharometry). Analytical and semi-prepara-

tive HPLC chains: Waters quaternary chains (600 Con-

troller), coupled with UV detectors and driven with a

Millenium software (version 4.00). HPLC columns: ana-

lytical Prontosil 120-3-SI column 150 mm!4.0 mm i.d.,

particle size: 3 mm, Bischoff); semi-preparative Prontosil

4.1.3. 1-Trimethylsilyl-3-(4-methoxyphenyl)-3-methoxy-

penta-1,4-diyne (3b). A solution of alcohol 5b (10.72 g,

42 mmol) in THF (180 mL) was treated with n-butyllithium

(18.80 mL, 42 mmol) at K78 8C. After stirring for 0.5 h,

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L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

methyl iodide (20.4 mL, 328 mmol) was added dropwise.

The temperature was allowed to warm up to K25 8C, and

DMSO (2.9 mL, 42 mmol) was added. After stirring for 1 h

at K25 8C, then 2 h at r.t., the reaction mixture was treated

with saturated aqueous NH₄Cl and extracted with diethy-

lether. The organic layer was washed with brine, dried over

MgSO₄, and concentrated under reduced pressure to give

ether 3b as an orange powder (8.16 g, 73%). R_fz0.34

(heptane/EtOAc 85:15). MS (DCI/NH₃): m/zZ272

pressure to give ether 6d as a brown oil (7.22 g, 83%). The

crude product displays satisfactory analyses and was used as

such in the next step. R_fz0.23 (heptane/EtOAc 9:1). MS

1

(DCI/NH₃): m/zZ693 ([MH]^C), 661 ([MKOCH₃]^C). H

NMR: dZ0.21–0.22 (s, 18H; Si(CH₃)₃), 3.45–3.54 (s, 9H;

Csp³OCH₃), 3.79–3.80 (m, 9H; C₆H₄OCH₃), 6.83–6.88 (m;

6H; m-CH), 7.63–7.69 (m, 6H; o-CH). ¹³C{¹H}NMR:

dZK0.43 (Si(CH₃)₃), 53.06 (Csp³–OCH₃), 55.13 (C₆H₄–

OCH₃), 71.47 (OC(OMe)An), 83.82 and 84.53 (C^C),

91.86 (C^CSiMe₃), 101.45 (^C–SiMe₃), 113.08 (m-CH),

127.70 (o-CH), 131.81 (ipso-C–C), 159.83 (p-C–OMe). IR:

nZ2960, 2935 (C–H), 2840 (OC–H), 2170 (C^CSi), 1609,

1509 (aromatic C–C), 1252 (C–Si), 1174, 1061 (C–O).

1

([M]^C)Z241 ([MKOCH₃]^C). H NMR: dZ0.22 (s, 9H;

Si(CH₃)₃), 2.73 (s, 1H; ^C–H), 3.46 (s, 3H; Csp³–OCH₃),

3.81 (s, 3H; CH₃O–C₆H₄), 6.87 (d, 2H; m-CH), 7.68 (d, 2H;

o-CH). ¹³C NMR: dZK0.43 (q, ¹J_CHZ121 Hz; Si(CH₃)₃),

1

55.15 (q, J_CHZ144 Hz; OCH₃), 55.66 (q, J_CHZ143 Hz;

1

OCH₃), 71.81 (s, OC(OMe)An), 73.03 (d, J_CHZ254 Hz;

4.1.6. 3,6,9-Trimethoxy-3,6,9-tris(4-methoxyphenyl)-

undeca-1,4,7,10-tetrayne (2b). Tetrayne 6d (7.22 g,

10 mmol) and K₂CO₃(7.20 g, 52 mmol) were dissolved in

methanol (25 mL) at 0 8C. After stirring for 1 h at r.t., the

reaction mixture was ﬁltered, concentrated and diluted with

diethylether (100 mL). The organic layer was washed with

water (2!50 mL) and brine (10 mL), dried over MgSO₄

and concentrated to dryness under reduced pressure to give

crude tetrayne 2b as a brown oil (5.45 g, 99%). R_fz0.18

(heptane/EtOAc 8:2). MS (DCI/NH₃): m/zZ566 ([MC

2

^C–H), 81.27 (d, J_CHZ49 Hz; C^CH), 91.71 (s;

1

–C^CSiMe₃), 101.37 (s; ^C–SiMe₃), 113.41 (d, J_CH

Z

1

154 Hz; m-CH), 127.81 (d, J_CHZ160 Hz; o-CH), 131.79

(s; ipso-C–C–OMe), 159.75 (s; p-C–OMe). IR: nZ3305

(^CH), 2961 (C–H), 2839 (OC–H), 2170 (C^CSi), 2117

(^CH), 1609, 1509 (aromatic C–C), 1252 (C–Si), 1174,

1089, 1060 (C–O).

4.1.4. 1,11-Bis(trimethylsilyl)-3,9-dimethoxy-3,6,9-

tris(4-methoxyphenyl)undeca-1,4,7,10-tetrayn-6-ol (6b).

A solution of diyne 3b (12.64 g, 46 mmol) in THF

(100 mL) was treated with n-butyllithium (19.73 mL,

46 mmol) at K78 8C. After stirring for 10 min, anisoyl

chloride (3.96 g, 23 mmol) was added and the reaction

mixture was stirred for 3 h at r.t. The mixture was

hydrolyzed with saturated NH₄Cl and extracted with

diethylether. The organic layer was washed with saturated

aqueous NH₄Cl and brine, dried over MgSO₄, and

concentrated under reduced pressure. Puriﬁcation through

column chromatography (heptane/EtOAc 9:1) afforded

tetrayne 6b as a brown oil (8.18 g, 52%). R_fz0.21

(heptane/EtOAc 85:15). MS (DCI/NH₃): m/zZ679

([MH]^C), 661 ([MKOH]^C), 647 ([MKOCH₃]^C). ¹H

NMR: dZ0.19–0.21 (m, 18H; Si(CH₃)₃), 3.12 (s, 1H;

OH), 3.41–3.46 (m, 6H; Csp³OCH₃), 3.71–3.81 (m, 9H;

C₆H₄OCH₃), 6.83–6.91 (m, 6H; m-CH), 7.62–7.73 (m, 6H;

o-CH). ¹³C NMR: dZK0.02 (q, ¹J_CHZ120 Hz; Si(CH₃)₃),

1

NH₄]^C), 548 ([MH]^C), 517 ([MKOCH₃)]^C). H NMR:

dZ2.76 (s, 2H; ^C–H), 3.49–3.53 (m, 9H; Csp³–OCH₃),

3.79–3.81 (m, 9H; C₆H₄OCH₃), 6.84–6.92 (m, 6H; m-CH),

1

7.65–7.70 (m, 6H; o-CH). ¹³C NMR: dZ53.75 (q, J_CH

Z

152 Hz; Csp³–OCH₃), 54.53 (q, J_CHZ144 Hz; C₆H₄–

1

OCH₃), 71.65 (s; ^C–H), 72.41 (s; OC(OMe)An), 74.95

1

(s, C^CH), 84.01 and 84.33 (s; C^C), 113.57 (d, J_CH

Z

1

155 Hz; m-CH), 127.82 (d, J_CHZ154 Hz; o-CH), 131.62

(s; ipso-C–C), 159.93 (s; p-C–OMe). IR: nZ3305 (^CH),

3003, 2957, 2936 (C–H), 2839, 2826 (OC–H), 2117

(^CH), 1609, 1508 (aromatic C–C), 1258, 1177, 1060

(C–O).

4.1.7. 1,4,13-Trimethoxy-1,4,7,10,13-pentaphenylcyclo-

pentadeca-2,5,8,11,14-pentayn-7,10-diol (7a) and side-

products. A solution of tetrayne 2a (300 mg, 0.65 mmol) in

THF (10 mL) was treated with n-butyllithium (0.59 mL,

1.31 mmol) for 10 min between K78 8C and K15 8C while

the color turned to deep green. After cooling back to

K78 8C, a solution of dibenzoylacetylene 1 (153 mg,

65 mmol) in THF (12 mL) was added dropwise. The

temperature was allowed to warm up to r.t. over a 45 min

period, and stirring was continued for a further 1.5 h. The

mixture was diluted with diethylether (50 mL), treated with

saturated aqueous NH₄Cl (30 mL). The organic layer was

separated, washed with aqueous NH₄Cl (30 mL) and brine

(20 mL), dried over MgSO₄, and concentrated under

reduced pressure. The dark brown crude oil (370 mg) was

chromatographed over silicagel (heptane/acetone 8:2) to

afford [5]pericyclyne 7a as an orange oil (166 mg, 37%).

R_fZ0.20 (heptane/acetone 8:2). MS (DCI/NH₃): m/zZ710

([MCNH₄]^C), 661 ([MKCH₃O]^C). ¹H NMR: dZ3.09 and

3.18 (2s, 2H; OH), 3.40–3.69 (m, 9H; OCH₃), 7.32–7.47 (m,

15H; m-, p-CH), 7.68–7.90 (m, 10H; o-CH). ¹³C{¹H} NMR:

dZ53.96–54.10 (OCH₃), 65.68 (OC(OH)Ph), 72.58 (O

C(OMe)Ph), 81.80–82.30 and 83.77–84.48 and 86.05–86.31

(C^C), 126.26–127.00 (m-, p-CH), 128.87–129.67 (o-CH),

139.50–139.78 (ipso-C–C–OMe), 140.82–140.95 (ipso-C–

C–OH). IR: nZ3683, 3558, 3291 (O–H), 3062–2896

1

52.92 (q, J_CHZ144 Hz; Csp³–OCH₃), 55.29 (q, J_CH

Z

144 Hz; C₆H₄–OCH₃), 67.94 (s; OC(OH)An), 74.48 (s;

OC(OMe)An), 83.02 and 86.18 (s; C^C), 92.08 (s;

1

C^CSiMe₃), 101.50 (s; ^C–SiMe₃), 113.65 (d, J_CH

Z

1

155 Hz, m-CH), 127.20 (d, J_CHZ154 Hz, o-CH), 132.00

(broad s; ipso-C–O), 159.96 (s; p-C–OMe). IR: nZ3570

(O–H), 2961 (C–H), 2840 (OC–H), 2171 (C^CSi), 1609,

1510 (aromatic C–C), 1252 (C–Si), 1174, 1061, 1035

(C–O).

4.1.5. 1,11-Bis(trimethylsilyl)-3,6,9-dimethoxy-3,6,9-

tris(4-methoxyphenyl)undeca-1,4,7,10-tetrayne (6d). A

solution of alcohol 6b (8.18 g, 12 mmol) in THF (200 mL)

was treated with n-butyllithium (7.6 mL, 12 mmol) at

K78 8C for 10 min. Iodomethane (6.0 mL, 96 mmol) was

added and the temperature was allowed to warm up to

K25 8C. DMSO (0.86 mL, 12 mmol) was added, and

stirring was continued for 1 h at K20 8C, then for 3 h at

r.t. After treatment with saturated aqueous NH₄Cl and

extraction with ether, the organic layer was washed with

brine, dried over MgSO₄, and concentrated under reduced

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10091

(C–H), 2822 (OC–H), 1604, 1490 (aromatic C–C), 1451 (C–

H), 1224, 1178, 1069 (C–O). The main characteristics of

three side-products (8a–10a, 10–25%) are listed below.

solution of [5]pericyclyndiol 7a (80 mg, 0.12 mmol) in THF

(3 mL) at K78 8C. After stirring for 15 min, methyl iodide

was added (115 mL, 1.85 mmol), and the temperature was

allowed to warm up to K25 8C. DMSO (20 mL; 0.23 mmol)

was added and stirring was continued at K25 8C for 1 h,

then at r.t. for a further 1 h. The reaction mixture was

quenched with saturated aqueous NH₄Cl solution, and

extracted with diethylether. The organic layer was washed

with aqueous NH₄Cl and brine, dried with magnesium

sulfate and the solvent was removed under reduced pressure.

Puriﬁcation by column chromatography (heptane/acetone

7:3) gave 11a as a yellow oil (80 mg, 92%). R_fz0.26

(heptane/acetone 7:3). MS (DCI/NH₃): m/zZ738 ([MC

NH₄]^C), 689 ([MKCH₃O]^C). MS (APCI/CH₃CN): m/zZ

730 ([MKCH₃OCCH₃CN]^C). ¹H NMR: dZ3.37–3.69 (8s,

15H; OCH₃), 7.33–7.45 (m, 15H; m-, p-CH), 7.74–7.90 (m,

10H; o-CH). ¹³C{¹H} NMR: dZ53.73 (OCH₃), 72.35

(OC(OMe)Ph), 83.42–83.86 (C^C), 126.57 (m-, p-CH),

128.32–129.16 (o-CH), 139.53 (ipso-C–C–OMe). IR: nZ

3067–2902 (C–H), 2827 (OC–H), 1601, 1490, 1451

(aromatic C–C), 1230, 1178, 1154, 1071 (C–O). Notice:

the cylization step (4.8) and methylation steps can also be

performed subsequently in one pot.

4.1.8. 4-Hydroxy-7,10,17-trimethoxy-1,4,7,10,13-penta-

phenylpentadeca-2,5,8,11,14-pentayn-1-one

(8a).

R_fz0.26 (heptane/acetone 8:2). MS (DCI/NH₃): m/zZ710

1

([MCNH₄]^C). H NMR: dZ2.76 (s, 1H; ^C–H), 3.50–

3.55 (m, 9H; OCH₃), 7.32–7.46 (m, 12H; Csp³-phenyl m-,

p-CH), 7.52–7.58 (m, 3H; benzoyl m-, p-CH), 7.72–7.82 (m,

8H; Csp³-phenyl o-CH), 8.05–8.10 (m, 2H; benzoyl o-CH).

¹³C{¹H} NMR: dZ53.62 (OCH₃), 65.56 (OC(OH)Ph),

71.97 (OC(OMe)Ph), 75.52 (^C–H), 80.64 (C^CH),

81.21–91.87 (C^C), 125.78–136.33 (aromatic CH), 139.36

(ipso-C–C–OCH₃), 139.89 (ipso-C–C–OH), 177.37 (CZ

O). IR: nZ3571 (O–H), 3305 (^C–H), 1649 (C]O).

4.1.9. 3,6,9,18,21,24-Hexamethoxy-3,6,9,12,15,18,21,24-

octaphenylhexacosa-1,4,7,10,13,16,19,22,25, 28-nonayn-

12,15-diol (9a). R_fz0.15 (heptane/acetone 8:3). MS (DCI/

NH₃): m/zZ1168 ([MCNH₄]^C). ¹H NMR: dZ2.75 (s, 2H;

^C–H), 3.09 (m, 2H; OH) 3.46–3.51 (m, 18H; OCH₃),

7.31–7.34 (m, 18H; m-, p-CH), 7.71–7.73 (m, 12H; o-CH).

¹³C{¹H} NMR: dZ53.33 and 53.48 (OCH₃), 65.17

(OC(OH)Ph), 71.92 (OC(OMe)Ph), 75.45 (^C–H), 80.52

(C^CH), 82.55–86.34 (C^C), 125.84–129.01 (aromatic

CH), 139.44 (ipso-C–C–OMe), 140.76 (ipso-C–C–OH). IR:

nZ3571 (O–H), 3305 (^C–H).

4.1.13. Dicobalthexacarbonyl-1,4,13-trimethoxy-1,4,7,

10,13-pentaphenylcyclopentadeca-2,5,8, 11,14-pentayn-

7,10-diol (12a), and side-product. Dicobaltoctacarbonyle

(126 mg, 0.37 mmol) was added into a solution of

[5]pericyclyndiol 7a (256 mg, 0.37 mmol) in diethylether

(25 mL) at 0 8C. The color turned red, and the reaction was

monitored by TLC. After stirring for 30 min, the solution

was concentrated and the oily residue was chromatographed

over silicagel (heptane/acetone 8:2). The dinuclear complex

12a was obtained as a red-orange oil (231 mg, 64%).

R_fz0.33 (heptane/acetone 7:3). MS (APCIO0/CH₃CN):

m/zZ716 ([MKCo₂(CO)₆–OHCCH₃CN]^C), 702 ([MK

Co₂(CO)₆–CH₃OCCH₃CN]^C). MS (MALDI/dithranol–

NaI): m/zZ1001 ([MCNa]^C), 715 ([MCNa–

Co₂(CO)₆]^C). Elemental analysis % (calcd): CZ65.96

(66.27), HZ4.22 (3.71), CoZ10.07 (12.04). ¹H NMR:

dZ3.27–3.72 (m, 9H; OCH₃), 7.19–7.42 (m, 15H; m-,

p-CH), 7.52–7.80 (m, 10H; o-CH). ¹³C{¹H} NMR: dZ

52.11–52.92 (OCH₃), 72.02 (OC(OMe)Ph), 85.26–86.03

(C^C), 100.72–101.55 ((C^C)(Co₂(CO)₆)), 125.56–

129.16 (aromatic CH), 139.54 (ipso-C–C–OMe), 141.78

(ipso-C–C–OH), 198.75 (Co₂(C^O)₆). IR: nZ3689, 3536

(O–H), 2097, 2063 and 2037 (CoC^O).

4.1.10. 4,16-Dihydroxy-7,10,13-trimethoxy-1,4,7,10,13,

16,19-heptaphenylnonadeca-2,5,8,11,14,17-hexayn-1,19-

dione (10a). R_fz0.15 (heptane/acetone 8:2). MS (DCI/

NH₃): m/zZ944 ([MCNH₄]^C). ¹H NMR: dZ3.49–3.52

(m, 9H; OCH₃), 3.90 (m, 2H; OH), 7.25–7.44 (m, 15H;

Csp³-phenyl m-, p-CH), 7.54–7.60 (m, 6H; benzoyl m-,

p-CH), 7.70–7.80 (m, 10H; Csp³–phenyl o-C₆H₅), 8.04–

8.10 (m, 4H; benzoyl o-CH). ¹³C{¹H} NMR: dZ53.62

(OCH₃), 64.94 (OC(OH)Ph), 72.02 (OC(OMe)Ph), 81.64–

85.79 and 92.02 (C^C), 125.89–136.33 (aromatic CH),

139.12 (ipso-C–C–OMe), 139.78 (ipso-C–C–OH), 177.52

(C]O).

4.1.11. 1,4,13-Trimethoxy-1,4,13-tris(4-methoxyphenyl)-

7,10-diphenyl-cyclopentadeca-2,5,8,11, 14-pentayn-7,10-

diol (7b). The above Section 4.1.9 for the preparation of 7a

was applied to tetrayne 2b (412 mg, 0.75 mmol) and

dibenzoylacetylene 1 (176 mg, 0.75 mmol) to afford

trianisyl-[5]pericyclyne 7b as an orange oil (180 mg,

31%). R_fz0.20 (heptane/EtOAc 7:3). MS (DCI/NH₃):

m/zZ800 ([MCNH₄]^C), 768 ([MKMeOHCNH₄]^C), 751

The less polar tetranuclear complex 12a⁰was also isolated

as a red oil from the chromatography column (79 mg, 17%):

bis(dicobalthexacarbonyl)-1,4,13-trimethoxy-1,4,7,10,13-

penta-phenylcyclo-pentadeca-2,5,8,11,14-pentayn-7,10-

diol (12a⁰) R_fz0.48 (heptane/acetone 7:3). MS (MALDI/

dithranol–NaI): m/zZ715 ([MCNa–2Co₂(CO)₆]^C).

Elemental analysis % (calcd): CZ57.79 (56.98), HZ3.00

1

([MKMeO]^C). H NMR: dZ3.30–3.62 (m, 9H; OCH₃),

3.69–3.86 (m, 9H; C₆H₄OCH₃), 6.78–6.92 (m, 6H; p-anisyl

m-CH), 7.30–7.40 (m, 6H; phenyl m-, p-CH), 7.51–7.84 (m,

10H; o-CH). ¹³C{¹H} NMR: dZ53.44 (Csp³–OCH₃), 55.45

(C₆H₄OCH₃), 65.22 (OC(OH)Ph), 71.76 (OC(OMe)An),

81.63–85.85 (C^C), 113.87 (p-anisyl m-CH), 125.94–

129.07 (phenyl CH), 128.63 (p-anisyl o-CH), 131.45 (anisyl

ipso-C–C–OMe), 140.67 (phenyl ipso-C–C–OH), 160.15

(p-anisyl p-C–OMe).

1

(2.87). H NMR: dZ3.29–3.57 (m, 9H; OCH₃), 7.21–7.44

(m, 15H; m-, p-CH), 7.59–7.80 (m, 10H; o-CH). IR: nZ

3689, 3409 (O–H), 2095, 2064, 2035 (Co₂(C^O)₆).

4.1.14. Dicobalthexacarbonyl-1,4,13-trimethoxy-1,4,13-

tris(4-methoxyphenyl)-7,10-diphenyl-cyclopentadeca-

2,5,8,11,14-pentayn-7,10-diol (12b). The above Section

4.1.13 for the preparation of 12a was applied to

4.1.12. 1,4,7,10,13-Pentamethoxy-1,4,7,10,13-penta-

phenylcyclopentadeca-2,5,8,11,14-pentayne (11a).

n-Butyllithium (105 mL, 0.23 mmol) was syringed into a

10092

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

pericyclyndiol 7b (180 mg, 0.23 mmol) and dicobalt–

octacarbonyle (80 mg, 0.23 mmol) to afford the dinuclear

complex 12b as a red oil (180 mg, 57%). R_fz0.24 (heptane/

EtOAc 7:3). ¹H NMR: dZ3.21–3.57 (m, 9H; OCH₃), 3.61–

3.86 (m, 9H; C₆H₄–OCH₃), 6.64–6.97 (m, 6H; m-CH),

7.31–7.50 (m, 6H; phenyl m-, p-CH), 7.53–7.81 (m, 10H;

o-CH). ¹³C{¹H} NMR: dZ53.43 (Csp³–OCH₃), 55.44

(C₆H₄–OCH₃), 64.55 (OC(OH)Ph), 71.83 (OC(OMe)An),

84.32–89.35 (C^C), 103.06 (C^C(Co₂(CO)₆)), 113.87

(p-anisyl m-CH), 125.53–129.45 (aromatic CH), 128.17

(p-anisyl o-CH), 133.67 (ipso-C–C–OMe), 143.83 (ipso-

C–C–OH), 160.12 (p-C–OMe), 198.29 (C^O). IR: nZ

3536 (O–H), 2097, 2062, 2036 (Co₂(C^O)₆).

9H; OCH₃), 5.76–5.79 (m, 2H; OCH(OH)), 7.36–7,44 (m,

9H; m-, p-CH), 7.69–7.77 (m, 6H; o-CH). ¹³C{¹H} NMR:

dZ53.35–53.51 (OCH₃), 63.50 and 63.94 (OCH(OH)),

(OC(OMe)Ph), 83.34–85.68 (C^C), 92.21–93.13

((C^C)(Co₂(CO)₆)), 126.50–129.09 (aromatic CH),

138.93 (ipso-C–C–OMe), 198.39–198.63 (C^O). IR: nZ

3583 (O–H), 3066–2900 (C–H), 2827 (OC–H), 2100, 2066,

2038 (Co₂(C^O)₆), 1600–1577, 1490 (aromatic C–C),

1450 (C–H), 1228, 1178, 1069 (C–O).

4.1.17. Dicobalthexacarbonyle-1,4,13-trimethoxy-1,4,13-

tris(4⁰-methoxyphenyl)cyclopentadeca- 2,5,8,11,14-pen-

tayn-7,10-diol (15b). The above Section 4.1.16 for the

preparation of 15a was applied to tetrayne 2b (197 mg,

0,36 mmol), n-butyllithium (0.29 mL, 0.72 mmol) and

complex 14 (130 mg, 0.36 mmol) to afford complex 15b

as a red-orange oil (22 mg, 6%). R_fz0.25 (heptane/EtOAc

7:3). ¹H NMR: dZ3.29–3.50 (m, 9H; OCH₃), 3.80–3.81 (m,

9H; C₆H₄–OCH₃), 5.74 and 5.78 (2s, 2H; CH(OH)), 6.80–

6.92 (m, 6H; anisyl m-CH), 7.57–7.70 (m, 6H; anisyl o-CH).

¹³C{¹H} NMR: dZ53.32 (Csp³–OCH₃), 55.34 (C₆H₄–

OCH₃), 63.96 (CH(OH)), 71.67 (OC(OMe)An), 84.02 and

84.34 (C^C), 92.65 ((C^C)Co₂(CO)₆), 113.63 (anisyl

m-CH), 127.85 (anisyl o-CH), 131.66 (ipso-C–C–OMe),

160.13 (anisyl p-C–OMe), 198.52 (Co₂(C^O)₆). IR: nZ

3689, 3587, 3537 (O–H), 2097, 2062, 2036 (Co₂(C^O)₆).

4.1.15.

Dicobalthexacarbonyle-1,4,7,10,13-penta-

methoxy-1,4,7,10,13-pentaphenylcyclopenta-deca-2,5,

8,11,14-pentayne (13a). The above Section 4.1.13 for the

preparation of 12a was applied to pericyclyne 11a (80 mg;

0.11 mmol) and dicobaltoctacarbonyle (38 mg; 0.11 mmol)

to afford the dinuclear complex 13a as a reddish oil (56 mg,

54%). R_fz0.38 (heptane/acetone 7:3). MS (APCI/CH₃CN):

m/zZ730 ([MKCo₂(CO)₆–CH₃OCCH₃CN]^C), 689 ([MK

Co₂(CO)₆–CH₃O]^C). ¹H NMR: dZ3.11–3.81 (m, 15H;

OCH₃), 6.89–7.20, 7.35–7.45 and 7.54–7.94 (m, 25H;

aromatic CH). ¹³C{¹H} NMR: dZ52.51–53.94 (OCH₃),

85.23–87.05 (C^C), 100.77–101.57 (C^C(Co₂CO)₆)),

125.63–129.15 (aromatic CH), 139.57 (ipso-C–C–OMe),

141.75 (ipso-C–C–OMe in b position from Co), 198.73–

199.33 (C^O). IR: nZ3065–2900 (C–H), 2827 (OC–H),

2094, 2060, 2034 (Co₂(C^O)₆). 1600, 1490 (aromatic

C–C), 1450 (C–H), 1230, 1177, 1151, 1068 (C–O).

4.1.18. 1,4,13-Trimethoxy-1,4,13-triphenylcyclopenta-

deca-2,5,8,11,14-pentayn-7,10-diol (16a). Cerium

ammonium nitrate (146 mg, 0.27 mmol) was added to a

solution of complex 15a (110 mg, 0.14 mmol) in acetone

(6 mL) at 0 8C. After 15 min, the reaction mixture was

warmed to r.t. and stirring was continued for 1.5 h. The IR

spectrum reveals the complete disappearance of carbonyl

stretching vibrations. The reaction mixture was treated with

water and diluted with diethylether. The organic layer was

separated, washed with water (2!10 mL), dried over

MgSO₄, and concentrated under reduced pressure. The

residue was chromatographed over silicagel (heptane/

acetone 8:2) to give free [5]pericyclyndiol 16a as a brown

oil (50 mg, 70%). R_fz0.22 (heptane/acetone 7:3). MS

(DCI/NH₃): m/zZ558 ([MCNH₄]^C), 526 ([MKMeOHC

NH₄]^C), 509 ([MHKMeOH]^C), 494 ([MK2MeOHC

The less polar tetranuclear complex 13a⁰was also isolated

as a red oil from the chromatography column (38 mg, 27%):

bis(dicobalthexacarbonyl)-1,4,7,10,13-pentamethoxy-1,4,

7,10,13-penta-phenylcyclopentadeca-2,5,8,11,14-pentayne

1

(13a⁰) R_fz0.50 (heptane/acetone 7:3). H NMR: dZ3.29–

3.57 (m, 9H; OCH₃), 7.21–7.44 (m, 15H; m-, p-CH), 7.59–

7.80 (m, 10H; o-CH). ¹³C{¹H} NMR: dZ52.52–53.95

(OCH₃),

85.26–87.04

(C^C),

100.72–101.55

(C^C(Co₂(CO)₆)), 125.64–129.14 (aromatic CH), 139.54

(ipso-C–C–OMe), 141.73 (ipso-C–C–OMe in b position

from Co), 198.75–199.32 (C^O). IR: nZ2095, 2064, 2035

(Co₂(C^O)₆).

1

NH₄]^C). H NMR: dZ3.35–3.62 (m, 9H; OCH₃), 5.14–

5.21 (m, 2H; OCH(OH)), 7.21–7.39 (m, 9H; m-, p-CH),

7.60–7.79 (m, 6H; o-CH). ¹³C{¹H} NMR: dZ52.89 and

53.04 (OCH₃), 63.22 and 63.36 (OCH(OH)), 71.97

(OC(OMe)Ph), 83.32–85.75 (C^C), 126.53–129.15

(aromatic CH), 138.97 (ipso-C–C–OMe).

4.1.16. Dicobalthexacarbonyle-1,4,13-trimethoxy-1,4,13-

triphenylcyclopentadeca-2,5,8,11,14-pentayn-7,10-diol

(15a). n-Butyllithium (1.00 mL, 2.18 mmol) was added

dropwise into a solution of tetrayne 2a (500 mg, 1.09 mmol)

in THF (30 mL) at K78 8C. The temperature was allowed to

warm up to K15 8C while the color turned to green. After

cooling back to K78 8C, a solution of complex 14 (401 mg,

1.09 mmol) in THF (25 mL) was added dropwise. The

temperature was allowed to warm up to K30 8C and then

quenched with saturated aqueous NH₄Cl (30 mL), and

diluted with diethylether (50 mL). The organic layer was

separated, then washed with saturated aqueous NH₄Cl (2!

20 mL) and brine (10 mL), dried over MgSO₄, and

concentrated under reduced pressure. The deep red residue

(580 mg) was puriﬁed by column chromatography over

silicagel (heptane/acetone 7:3). Complex 15a was isolated

as a deep red oil (226 mg, 25%). R_fz0.36 (heptane/acetone

4.1.19. 1,4,13-Trimethoxy-1,4,13-tri(4-methoxyphenyl)-

cyclopentadeca-2,5,8,11,14-pentayn-7,10-diol (16b). The

above Section 4.1.18 for the preparation of 16a was applied

to complex 15b (22 mg; 0,03 mmol), ceric ammonium

nitrate (33 mg, 0,06 mmol) to afford free [5]pericyclyndiol

16b as an orange oil (16 mg, 100%). R_fz0.31 (heptane/

EtOAc 5:5). MS (DCI/NH₃): m/zZ630 ([M]^C), 599 ([MK

1

CH₃O]^C). H NMR: dZ2.82 (m, 2H; OH), 3.37–3.60 (s,

9H; OCH₃), 3.80–3.82 (s, 9H, C₆H₄–CH₃O), 5.15–5.21 (m,

2H; CH(OH)), 6.87–6.90 (m, 6H; m-CH), 7.59–7.68 (m, 6H;

o-CH). ¹³C{¹H} NMR: dZ53.32 (OCH₃), 55.44 (C₆H₄–

OCH₃), 65.76 (CH(OH)), 71.55 (OC(OMe)An), 83.03 and

83.56 (C^C), 113.82 (m-CH), 128.45 (o-CH), 131.12

1

7:3). H NMR: dZ3.21–3.27 (m, 2H; OH), 3.32–3.69 (m,

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10093

1

2

(ipso-C–C–OMe), 160.15 (p-C–OMe). IR: nZ3686 (O–H),

2923 (C–H), 2843 (OC–H), 1605, 1509 (aromatic C–C),

1457 (C–H), 1250, 1170, 1060, 1034 (C–O).

C^C–SiMe₃), 113.55 (dd, J_CHZ160 Hz, J_CHZ5 Hz;

1 2

m-CH), 127.39 (dd, J_CHZ160 Hz, J_CHZ5 Hz; o-CH),

133.66 (s; ipso-C–C–OH), 159.39 (s; p-C–OMe).

4.1.20. 1,4,7,10,13-Pentamethoxy-1,4,13-tri(4-methoxy-

phenyl)cyclopentadeca-2,5,8,11,14-pentayne (17b).

n-Butyllithium (20 mL, 0.05 mmol) was syringed dropwise

into a solution of [5]pericyclyndiol 16b (16 mg, 0.03 mmol)

in THF (3 mL) at K78 8C. After stirring for 10 min, methyl

iodide (27 mL; 0.40 mmol) was added, and the temperature

was allowed to warm up to K25 8C. DMSO (4 mL;

0.05 mmol) was introduced and the reaction mixture was

stirred for 1 h at K25 8C, and then for a further 2 h at r.t.

The reaction mixture was diluted with diethylether (20 mL)

and treated with saturated aqueous NH₄Cl (20 mL). The

organic layer was separated, washed with saturated aqueous

NH₄Cl (2!10 mL) and brine (10 mL), dried over MgSO₄,

and concentrated under reduced pressure. Crude penta-

methoxy[5]pericyclyne 17b (13 mg, 67%) exhibited con-

sistent spectroscopic data. R_fz0.40 (heptane/EtOAc 5:5).

4.1.23. 1,8-Bis(trimethylsilyl)-3,6-dimethoxy-3,6-di-

phenylocta-1,4,7-triyne (20a). n-Butyllithium (2.20 mL,

5.50 mmol) was added dropwise into a solution of alcohol

19a (1.18 g, 2.75 mmol) in THF (20 mL) at K78 8C. After

stirring for 10 min, methyl iodide was added (2.74 mL,

44 mmol), and the temperature was allowed to warm up to

K25 8C before addition of DMSO (0.40 mL, 5.50 mmol).

Stirring was continued for 1 h at K25 8C, for a further 1 h at

r.t. Diethylether (25 mL) was added and the organic layer

was washed with saturated aqueous NH₄Cl (2!20 mL) and

brine (20 mL), then dried over MgSO₄, and concentrated

under reduced pressure. Crude diether 20a was obtained as

an orange oil (1.23 g, 97%) displaying satisfactory analyti-

1

cal data. H NMR: dZ0.20–0.24 (s, 18H; Si(CH₃)₃), 3.50

and 3.51 (2s, 6H; OCH₃), 7.34–7.38 (m, 6H; m-, p-CH),

7.74–7.78 (m, 4H; o-CH). ¹³C{¹H} NMR: dZK0.25

(Si(CH₃)₃), 53.25 (OCH₃), 72.17 (OC(OMe)Ph), 84.55

(C–C^C–C), 92.28 (–C^CSiMe₃), 101.53 (^C–SiMe₃),

126.62–128.89 (m; aromatic CH), 139.84 (ipso-C–C–OMe).

IR: nZ3065–2901 (C–H), 2826 (OC–H), 2171 (C^CSi),

1600, 1490 (aromatic C–C), 1450 (C–H), 1251 (C–Si), 1062

(C–O).

1

MS (DCI/NH₃): m/zZ627 ([MKCH₃O]^C). H NMR: dZ

3.32–3.66 (s, 9H; Csp³–OCH₃), 3.81–3.83 (s, 9H; C₆H₄–

OCH₃), 5.19 (m, 2H; CH(OMe)), 6.83–6.98 (m, 6H; m-CH),

7.51–7.73 (m, 6H; o-CH). ¹³C{¹H} NMR: dZ53.3–55.4

(OCH₃), 71.7 (OC–OMe), 113.8 (m-CH), 128.5 (o-CH),

131.1 (ipso-C–C–OMe), 160.2 (p-CKOMe).

4.1.24. 1,8-Bis(trimethylsilyl)-3,6-dimethoxy-3,6-di(4-

methoxyphenyl)octa-1,4,7-triyne (20b). The above Sec-

tion 4.1.23 for the preparation of 19a was applied to alcohol

19b (0.83 g, 1.68 mmol), n-butyllithium (1.69 mL,

3.69 mmol), methyl iodide (1.67 mL, 27 mmol) and

DMSO (0.26 mL, 3.69 mmol). Crude diether 20b was

obtained as an orange oil with a single TLC spot and a

consistent ¹H NMR spectrum (0.87 g, quant.). R_fz0.25

(heptane/EtOAc 7:3). ¹H NMR: dZ0.21 (s, 18H; Si(CH₃)₃),

3.51 and 3.53 (2s, 6H; OCH₃), 3.76 (s, 6H; C₆H₄–OCH₃),

6.84–6.92 (m, 4H; m-CH), 7.65–7.70 (m, 4H; o-CH).

4.1.21. 1,8-Bis(trimethylsilyl)-6-methoxy-3,6-diphenyl-

octa-1,4,7-triyn-3-ol

(19a).

EtMgBr

(0.33 mL,

0.99 mmol) was added dropwise into a solution of diyne

3a (239 mg, 0.99 mmol) in THF (4 mL) at 0 8C. After

stirring for 1 h at 0 8C, benzoylethynylketone 4a (200 mg,

0.99 mmol) was introduced and the reaction mixture was

stirred for 2 h at r.t. The reaction mixture was quenched with

saturated aqueous NH₄Cl (10 mL) and diluted with

dietehylether (20 mL). The organic layer was separated,

washed with saturated aqueous NH₄Cl (2!5 mL) and brine

(10 mL), dried over magnesium sulfate, and concentrated

under reduced pressure. Puriﬁcation by column chromato-

graphy (heptane/acetone 8:2) gave 19a as a brown oil

4.1.25. 3,6-Dimethoxy-3,6-diphenylocta-1,4,7-triyne

(20c). K₂CO₃(1.86 g, 13.45 mmol) was added into a

solution of 20a (1.23 g, 2.70 mmol) in methanol (60 mL).

TLC monitoring indicates that the reaction was completed

after 1.5 h. The reaction mixture was ﬁltered, concentrated

to few milliters under reduced pressure, and diethylether

(60 mL) was added. The organic layer was washed with

saturated aqueous NH₄Cl (2!40 mL) and brine (10 mL),

dried over MgSO₄and concentrated to give crude 20c as a

red-orange oil (0.85 g, quant.). MS (DCI/NH₃): m/zZ332

([MCNH₄]^C), 315 ([MH]^C), 283 ([MKOCH₃]^C). ¹H

NMR: dZ2.77 (s, 2H; ^C–H), 3.54 (s, 6H; OCH₃), 7.35–

7.43 (m, 6H; m-, p-CH), 7.74–7.78 (m, 4H; o-CH). ¹³C

1

(415 mg, 87%). R_fz0.30 (heptane/acetone 8:2). H NMR:

dZ0.22 and 0.24 (2s, 18H; Si(CH₃)₃), 3.02 (s, 1H; OH),

3.50–3.51 (m, 3H; OCH₃), 7.36–7.40 (m, 6H; m-, p-CH),

7.77–7.83 (m, 4H; o-CH). ¹³C NMR: dZK0.21 (q, ¹J_CH

Z

1

120 Hz; Si(CH₃)₃), 53.14 (q, J_CHZ143 Hz; OCH₃), 65.33

(s; OC(OH)Ph), 72.07 (s, OC(OMe)Ph), 82.7 and 86.77 (2

s; C–C^C–C), 90.54 (s, (HO)C–C^C–SiMe₃), 92.32 (s,

(MeO)C–C^C–SiMe₃), 101.39 (s; (MeO)C–C^C–

SiMe₃), 104.05 (s; (HO)C–C^C–SiMe₃), 126.03–129.67

(m; aromatic CH), 139.75 (s; ipso-C–C–OMe), 141.18 (s;

ipso-C–C–OH).

1

NMR: dZ53.74 (q, J_CHZ152 Hz; OCH₃), 71.42 (s;

4.1.22. 1,8-Bis(trimethylsilyl)-6-methoxy-3,6-di(4-meth-

oxyphenyl)octa-1,4,7-triyn-3-ol (19b). The above Section

4.1.21 for the preparation of 19a was applied to diyne 3b

(5.00 g, 183 mmol), EtMgBr (6.70 mL, 183 mmol) and

anisoylethynylketone 4b (4.28 g; 183 mmol) to afford triyne

OC(OMe)Ph), 75.26 (d, ¹J_CHZ254 Hz; ^C–H), 80.52 (d,

²J_CHZ50 Hz; –C^CH), 84.05 (s; C–C^C–C), 126.32–

128.96 (m; aromatic CH), 139.43 (s; ipso-C–C–OMe). IR:

nZ3306 (^C–H), 3065–2901 (C–H), 2827 (OC–H), 2116

(C^CH), 1600, 1490 (aromatic C–C), 1450 (C–H), 1068

(C–O).

1

19b as an orange oil (8.8 mg, 92%). H NMR: dZ0.20 (s,

18H; Si(CH₃)₃), 3.56 (m, 2H; OH), 3.78 (s, 6H; C₆H₄–

3

OCH₃), 6.89 (d, J_HHZ9 Hz, 4H; m-CH), 7.70 (d, J_HH

Z

9 Hz, 4H; o-CH). ¹³C NMR: dZK0.37 (q, J_CHZ12 Hz;

Si(CH₃)₃), 55.19 (q, ¹J_CHZ144 Hz; C₆H₄–OCH₃), 64.66 (s;

C–OH), 84.74 (s, C^C), 89.73 (s; C^CSiMe₃), 104.35 (s;

4.1.26. 3,6-Dimethoxy-3,6-di(4-methoxyphenyl)octa-

1,4,7-triyne (20d). The above Section 4.1.25 for the

preparation of 20c was applied to triyne 20b (0.87 g,

1

10094

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

1

1.68 mmol) and K₂CO₃(2.32 g; 16.80 mmol) to give 20d as

an orange powder. R_fz0.26 (heptane/EtOAc). MpZ

103 8C. MS (DCI/NH₃): m/zZ374 ([M]^C), 343 ([MK

¹J_CHZ171 Hz; CH(OEt)₂), 126.53 (td-like, J_CHZ160 Hz;

1

m or o-CH), 128.32 (td-like, J_CHZ165 Hz; o-or m-CH),

128.96 (dt-like, J_CHZ160 Hz; p-CH), 139.67 (broad s;

ipso-C–C–OMe).

1

OCH₃]^C). H NMR: dZ2.79 (s, 2H; ^C–H), 3.52 (s, 6H;

3

OCH₃), 3.78 (s, 6H; C₆H₄–OCH₃), 6.91 (d, J_HHZ9 Hz,

3

4H; m-CH), 7.69 (d, J_HHZ9 Hz, 4H; o-CH). ¹³C{¹H}

4.1.29. 3,6-Dimethoxy-3,6-diphenylocta-1,4,7-triyn-1,8-

dial (18a) by formylation of bisterminal triyne (20c).

n-Butyllithium (1.00 mL, 2.48 mmol) was added dropwise

into a solution of triyne 20c (391 mg, 1.24 mmol) in THF

(20 mL) at K78 8C. After warming up to K40 8C, the

solution was stirred for 10 min before addition of DMF

(1.00 mL, 25 mmol). The reaction mixture was then placed

at r.t. and stirring was continued for a further 30 min. The

solution was poured into a biphasic mixture of diethylether

(7 mL) and 10% aqueous NaH₂PO₄(7 mL, ca8 equivalents

of H₂PO^K₄) at 0 8C. The organic layer was separated,

washed with water (2x20 mL), dried over MgSO₄, and

concentrated under reduced pressure. Chromatography of

the residue over silicagel (heptane/acetone 8:2) afforded

dialdehyde 18a as an orange oil (146 mg, 32%). R_fz0.16

(heptane/acetone 8:2). MS (DCI/NH₃): m/zZ388 ([MC

NH₄]^C), 356 ([MKMeOHCNH₄]^C), 339 ([MKMeO]^C),

NMR: dZ53.23 (OCH₃), 55.34 (C₆H₄–OCH₃), 71.33

(OC(OMe)An), 75.18 (^C–H), 80.93 (–C^CH), 84.25

(C–C^C–C), 113.75 (m-CH), 127.95 (o-CH), 131.90 (ipso-

C–C–OMe), 160.11 (ipso-C–OMe).

4.1.27. 1,10-Bis(diethoxy)-4,7-diphenyldeca-2,5,8-triyn-

4,7-diol (22a). n-Butyllithium (15.4 mL, 38.5 mmol) was

added into a solution of 3,3-diethoxy-1-propyne (4.94 g,

38.5 mmol) in THF (50 mL) at K78 8C. After 15 min, a

solution of diketone 1 (5.67 mL; 19.3 mmol) in THF

(50 mL) was added dropwise, and the solution was stirred

for a further 30 min at K78 8C. The temperature was

allowed to warm up slowly to r.t. After stirrring for another

30 min, the reaction was quenched by saturated aqueous

NH₄Cl (30 mL) and diluted with diethylether (50 mL). The

organic layer was washed with saturated aqueous NH₄Cl

(2!20 mL) and brine (10 mL), dried over MgSO₄, and

concentrated under reduced pressure. Diol 22a was obtained

as a brown oil (10.97 g, 97%) which was used without

1

324 ([MK2MeOHCNH₄]^C). H NMR: dZ3.56 (s, 6H;

OCH₃), 7.38–7.45 (m, 6H; m-, p-CH), 7.67–7.72 (m, 4H;

o-CH), 9.31 (s, 2H; ^C–CHO). ¹³C NMR: dZ53.92 (q,

¹J_CHZ144 Hz; OCH₃), 71.84 (s; OC(OMe)Ph), 83.88,

84.32 and 90.59 (3s; C–C^C–C), 126.18–129.52 (m;

aromatic CH), 137.77 (s; ipso-C–C–OMe), 175.90 (d,

¹J_CHZ190 Hz; –CHO). IR: nZ3088, 2887 (C–H), 2829

(OC–H), 2740 (aldehydic C–H), 1679 (CH]O), 1599,

1490 (aromatic C–C), 1451 (C–H), 1178–1072 (C–O).

1

further puriﬁcation in the next step. H NMR: dZ1.19 (t,

³J_HHZ7 Hz, 12H; C–CH₃), 3.62 and 3.63 (2m, 2^dorder

pattern, 8H; CH₂Me), 3.83 (s, 2H; OH), 5.32 (s; 2H;

CH(OEt)₂), 7.29–7.40 (m, 6H; m-, p-CH), 7.71–7.77 (m,

1

4H; o-CH). ¹³C{¹H} NMR: dZ15.06 (q, J_CHZ126 Hz;

1

2

C–CH₃), 61.11 (tt-like, J_CHZ143 Hz, J_CHz4 Hz;

O–CH₂Me), 64.68 (s; OC(OH)Ph), 80.49, 84.92 and 85.13

1

(3 s; C–C^C–C), 91.23 (d, J_CHZ168 Hz; CH(OEt)₂),

The monoaldehyde 3,6-dimethoxy-3,6-diphenylocta-1,4,7-

triynal (21a) was also isolated as side-product from the

chromatography (85 mg, 20%). R_fz0.18 (heptane/acetone

8:2). MS (DCI/NH₃): m/zZ360 ([MCNH₄]^C), 343

([MH]^C), 328 ([MKMeOHCNH₄]^C), 311 ([MK

125.82 (broad d, ¹J_CHZ167 Hz; m-or o-CH), 128.45 (broad

1

d, J_CHZ159 Hz; o-or m-CH), 129.76 (d, J_CHZ160 Hz;

2

p-CH), 141.18 (t, J_CHZ7 Hz; ipso-C–C–OH). IR: nZ

3572, 3380 (O–H), 2980, 2932, 2889 (C–H), 1599, 1490

(aromatic C–C), 1450 (C–H), 1328, 1144, 1116, 1051

(C–O).

1

MeO]^C), 296 ([MK2MeOHCNH₄]^C). H NMR: nZ2.85

(s, 1H; ^C–H), 3.57–3.60 (m, 6H; OCH₃), 7.39–7.45 (m,

6H; m-, p-CH), 7.72–7.81 (m, 4H; o-CH), 9.29 (s, 1H; ^C–

CHO). ¹³C{¹H} NMR: dZ53.31 and 53.70 (OCH₃), 71.51

and 71.71 (OC(OMe)Ph), 75.76 (^C–H), 80.07 (C^CH),

81.91, 84.07, 86.11 and 90.59 (C–C^C–C), 126.27–129.53

(m; aromatic CH), 138.05 and 139.11 (ipso-C–C–OMe),

175.90 (–CHO).

4.1.28. 1,10-Bis(diethoxy)-4,7-dimethoxy-4,7-diphenyl-

deca-2,5,8-triyne (23a). n-Butyllithium (4.8 mL,

12.05 mmol) was added into a solution of diol 22a

(2.95 g, 6.0 mmol) in THF (15 mL) at K78 8C. After

30 min, methyl iodide (6.0 mL, 96 mmol) was added

dropwise, and the temperature was allowed to warm up to

K25 8C. DMSO (0.87 mL, 12 mmol) was then added, and

the reaction mixture was stirred for 1 h at K25 8C, and then

for 10 h at r.t. (TLC monitoring). The reaction mixture was

diluted with diethylether (50 mL) and saturated aqueous

NH₄Cl (80 mL). The organic layer was separated, dried over

MgSO₄and concentrated under reduced pressure. Puriﬁ-

cation by column chromatography (heptane/acetone 8:2)

afforded diether 23a (2.14 g, 69%) as a brown oil. MS (DCI/

NH₃): m/zZ536 (100%, [MCNH₄]^C) 487 (38%, [MK

CH₃O]^C). ¹H NMR: dZ1.20 (t, ³J_HHZ7 Hz, 12H; C–CH₃),

3.53 (s, 6H; OCH₃), 3.66 and 3.67 (2qd-like 2^dorder pattern

4.1.30. 3,6-Dimethoxy-3,6-diphenylocta-1,4,7-triyn-1,8-

dial (18a) by deprotection of bisketal (23a). Bisketal

23a (4.859 g, 9.4 mmol)) and DDQ (2.127 g, 9.4 mmol)

were dissolved in a mixture of acetonitrile (243 mL) and

water (27 mL). The mixture was reﬂuxed in the dark for 2 h.

After cooling to r.t., the mixture was diluted with

diethylether and water. The organic layer was separated

washed with water, dried over MgSO₄, and concentrated

under reduced pressure. The brown residue was ﬂash-

chromatographed over silicagel (heptane/EtOAc 8:2).

Dialdehyde 18a was obtained a light orange oil (2.118 g,

61%). The spectroscopic data are identical to those of

samples of 18a prepared by the formylation method (see

Section 4.1.29). Notice: some decomposition occurs on

silicagel, and the yield is actually quite erratic (between 40

and 75%).

2

³J_HHz7 Hz, J_HHz18 Hz, 8H; CH₂Me), 5.35 (s, 2H;

CH(OEt)₂), 7.29–7.40 (m, 6H; m-, p-CH), 7.71–7.77 (m,

4H; o-CH). ¹³C NMR: dZ15.09 (q, ¹J_CHZ128 Hz; C–CH₃),

1

53.44 (q, J_CHZ143 Hz; OCH₃), 61.05 (tq-like, J_CH

Z

2

144 Hz, J_CHz4 Hz; O–CH₂Me), 71.86 (s; OC(OMe)Ph),

82.08, 82.68 et 84.39 (3s; C–C^C–C), 91.31 (broad d,

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10095

4.1.31. 3,6-Dimethoxy-3,6-di(4-methoxyphenyl)octa-

1,4,7-triyn-1,8-dial (18b). The formylation Section 4.1.29

for the preparation of 18a was applied to bisketal 20d

(400 mg, 1.07 mmol), n-butyllithium (0.94 mL, 2.35 mmol)

and DMF (0.50 mL, 6.42 mmol) to give crude dialdehyde

18b in an orange oil containing 17% of side product

assigned to the monoaldehyde structure 21b (spectroscopic

yield of 18b z83%). Attempts at puriﬁcation by chroma-

tography failed, but the main spectrospcopic characteristics

of 18b could be attributed. R_fz0.20 (heptane/EtOAc 8:2).

saturated aqueous NH₄Cl (10 mL). The organic layer was

separated, washed with and saturated aqueous NH₄Cl

(10 mL) and brine (20 mL), dried over magnesium sulfate,

and concentrated to dryness under reduced pressure. The

brown residue (190 mg) was chromatographed over silica-

gel (heptane/acetone 8:2) to give [5]pericyclyndiol 25a as

an orange oil (35 mg, 15%). MS (DCI/NH₃): m/zZ558

([MCNH₄]^C), 526 ([MKMeOHCNH₄]^C), 509 ([MK

MeO]^C), 494 ([MK2MeOHCNH₄]^C). MS (APCI/

CH₃CN): m/zZ568 ([MKMeOCMeCN]^C), 559

1

([MH]^C). H NMR: dZ2.41 (m, 2H; OH), 3.40–3.58 (m,

MS (DCI/NH₃): m/zZ448 ([MCNH₄]^C), 416 ([MK

MeOHCNH₄]^C), 399 ([MKMeO]^C), 384 ([MK

2MeOHCNH₄]^C). ¹H NMR: dZ3.53 (s, 6H; OCH₃),

9H; OCH₃), 5.24–5.34 (m, 2H; OCH(OH)), 7.36–7.39 (m,

9H; m-, p-CH), 7.69–7.90 (m, 6H; o-CH). ¹³C{¹H} NMR:

dZ52.23 and 53.30 (OCH₃), 62.19 (OCH(OH)), 71.72

(OC(OMe)Ph), 80.79–82.63 (C^C), 126.43–128.99

(aromatic CH), 138.77 (ipso-C–C–OMe).

3

3.81 (s, 6H; C₆H₄–OCH₃), 6.92 (d, J_HHZ9 Hz, 4H;

m-CH), 7.64 (d, ³J_HHZ9 Hz, 4H; o-CH), 9.31 (s, 2H; ^C–

1

CHO). ¹³C NMR: dZ53.70 (q, J_CHZ144 Hz; OCH₃),

1

55.39 (q, J_CHZ139 Hz; C₆H₄–OCH₃), 71.53 (s; OC(O-

Me)An), 84.00, 84.33 and 91.11 (3s; C–C^C–C), 114.01

4.1.35. 4,7,13-Trimethoxy-4,7,13-tri(4-methoxyphenyl)-

cyclopentadeca-2,5,8,11,14-pentayn-1,10-diol (25b). The

above Section 4.1.34 for the preparation of 25a was applied

to pentadiyne 24b (168 mg, 0.84 mmol), n-butyllithium

(0.70 mL, 1.68 mmol) and crude dialdehyde 18b of 83%

spectroscopic purity (361 mg, ca0.84 mmol). The peri-

cyclyne 25b was isolated as an orange oil (100 mg, 19%).

R_fz0.12 (heptane/acetone 7:3). MS (DCI/NH₃): m/zZ648

([MCNH₄]^C), 630 ([M]^C), 616 ([MKMeOHCNH₄]^C),

599 ([MKMeO]^C), 584 ([MK2MeOHCNH₄]^C). ¹H

NMR: dZ3.35–3.53 (m, 9H; OCH₃), 3.78–3.87 (s, 9H;

C₆H₄–OCH₃), 5.31 (m, 2H; CH(OH)), 6.83–6.93 (m,

6H; m-CH), 7.57–7.72 (m, 6H; o-CH). ¹³C{¹H} NMR: dZ

53.15, 52.97 and 52.20 (3s; OCH₃), 55.21 (C₆H₄–OCH₃),

64.85 (CH–OH), 71.67 (OC(OMe)An), 83.05–84.57

(C^C), 113.70 (m-CH), 128.17 (o-CH), 138.53 (ipso-C–

C–OMe), 160.07 (p-C–OMe).

1

(d, J_CHZ161 Hz; m-CH), 127.85 (d, J_CHZ158 Hz;

o-CH), 129.99 (s; ipso-C–C–OMe), 160.53 (s; p-C–OMe),

1

176.08 (d, J_CHZ197 Hz; –CHO). IR: nZ3006–2862

(C–H), 2840, 2741 (aldehydic C–H), 2828 (OC–H), 1674

(C]O), 1608, 1463 (aromatic C–C), 1063 (C–O).

4.1.32. 3-Phenyl-3-methoxypenta-1,4-diyne (24a). A sol-

ution of diyne 3a (4.19 g, 16 mmol) in methanol (60 mL)

and water (few drops) was treated at 0 8C with K₂CO₃

(11.29 g, 82 mmol). After stirring for 1 h at r.t., the reaction

mixture was ﬁltered, concentrated to few milliters under

reduced pressure, and diluted with diethylether (100 mL).

The organic phase was washed with saturated aqueous

NH₄Cl (2!50 mL) and brine (10 mL), dried over MgSO₄,

and concentrated under reduced pressure to give diyne 24a

as a spectroscopically pure brown oil (2.78 g, quant.).

1

R_fz0.29 (heptane/acetone 8:2). H NMR: dZ2.78 (s, 2H;

^C–H), 3.54 (s, 3H; OCH₃), 7.37–7.40 (m, 3H; m-, p-CH),

7.75–7.80 (m, 2H; o-CH).

The side-product resulting from the attack of the mono-

aldehyde impurity (21b) was also isolated and partly

characterized: 3,9,12-trimethoxy-3,6,9,12-tetra(4-methoxy-

phenyl)tetradeca-1,4,7, 10,13-pentayn-6-ol (26b) R_fz0.25

1

(heptane/acetone 7:3). H NMR: nZ2.76 (s, 2H; ^C–H),

4.1.33. 3-(4-Methoxyphenyl)-3-methoxypenta-1,4-diyne

(24b). The above Section 4.1.32 for the preparation of 24a

was applied to diyne 3b (3.61 g, 5.22 mmol) and K₂CO₃

(3.60 g, 26 mmol) to give 1,4-pentadiyne 24a as a spectro-

scopically pure brown oil (1.05 g, quant.). R_fz0.29

3.46–3.48 (m, 9H; –OCH₃), 3.78–3.79 (s, 9H, CH₃O–An–),

5.32 (d, 1H; CH(OH)), 6.83–6.90 (m, 6H; m-CH), 7.62–7.68

(m, 6H; o-CH).

1

(heptane/acetone 8:2). H NMR: dZ2.77 (s, 2H; ^C–H),

3.50 (s, 3H; OCH₃), 3.81 (s, 3H; C₆H₄–OCH₃), 6.89 (d, 2H;

4.1.36. 12,15-Dimethoxy-12,15-diphenyl-3,3-dimethyl-

1,5-dioxaspiro[5.14]icosa-7,10,13,16,19-pentayn-9,18-

diol (31). n-Butyllithium (2.26 mL, 5.66 mmol) was added

to a solution of diyne 27^10b(465 mg, 2.83 mmol) in THF

(100 mL) at K78 8C. After stirring for 40 min at K50 8C,

the solution was cooled back to K78 8C and a solution of

dialdehyde 18a (1.049 g, 2.83 mmol) in THF (100 mL) was

added. The reaction mixture was allowed to warm up to r.t.

over a 3 h period, and stirring was continued for 1 h at r.t.

The reaction was quenched with saturated aqueous NH₄Cl

and diluted with diethylether. The organic layer was

separated, washed with aqueous NH₄Cl and brine, dried

over magnesium sulfate, and the solvents were removed

under reduced pressure. Puriﬁcation through column

chromatography (heptane/acetone 8:2) gave [5]pericyclyne

31 as a pale yellow solid (271, mg, 18%). MS (DCI/NH₃)

m/zZ552 (60%; [MNH₄]^C), 503 (31%; [MHKMeOH]^C),

520 (21%; [MNH₄KMeOH]^C), 488 (7%; [MNH₄K

2MeOH]^C). ¹H NMR (250 MHz): dZ0.98 (s, 6H;

m-CH), 7.68 (d, 2H; o-CH). ¹³C NMR: dZ52.87 (q, ¹J_CH

Z

1

143 Hz; C₆H₄–OCH₃), 55.17 (q, J_CHZ144 Hz; Csp³–

1

OCH₃), 71.81 (s; OC(OMe)An), 74.89 (d, J_CHZ263 Hz,

2

^C–H), 80.80 (d, J_CHZ49 Hz; C^CH), 113.46 (dd,

2

1

¹J_CHZ160 Hz, J_CHZ5 Hz; m-CH), 127.61 (dd, J_CH

Z

2

160 Hz, J_CHZ5 Hz; o-CH), 131.89 (s; ipso-C–C(OMe)–),

159.53 (broad s; p-C–OMe).

4.1.34. 4,7,13-Trimethoxy-4,7,13-triphenylcyclopenta-

deca-2,5,8,11,14-pentayn-1,10-diol (25a). n-Butyllithium

(0.32 mL, 0.80 mmol) was added into a solution of diyne

24a (150 mg, 0.40 mmol) in THF (8 mL) at K78 8C. After

stirring for 10 min, a solution of dialdehyde 18a (68 mg;

0.40 mmol) in THF (8 mL) was added dropwise. The

temperature was allowed to warm up to r.t. and stirring was

continued for a further 40 min. The reaction mixture was

diluted with diethylether (20 mL) and hydrolyzed with

10096

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

C(CH₃)₂), 2.44K2.71 (m, 2H; OH), 3.33K3.71 (m, 10H;

OCH₃CCH₂OK), 5.23K5.33 (m, 2H; CHOH); 7.33K7.78

(m, 10H; aromatic CH). ¹³C NMR (62.9 MHz): dZ22.29

(C(CH₃)₂), 29.96 (C(CH₃)₂), 52.15 (OCH(OH)), 53.51

(OCH₃), 71.94 (OC(OMe)Ph), 72.88 (CH₂O), 78.67 (^C–

CO₂), 80.42, 81.11, 82.15 and 83.26 (other –C^), 87.22

(OCO₂), 126.53 and 128.52 (o- and m-CH), 129.15 (p-CH),

139.89 (ipso-C–C–OMe). In another assay, the spectrum

exhibited higher resolution, and most signals were split in two

or three lines byca. 0.05 ppm. IR: nZ3585(O–H), 2961, 2934

and 2872 (C–H), 2827 (OC–H), 1601, 1490, 1450 (aromatic

C–C), 1254, 1203, 1178, 1229, 1145, 1116, 1072, 1009(C–O).

dissolved in dichloromethane (0.5 mL). Samples (20 mL)

were sequentially injected and divided by HPLC (Prontosil

column, pentane:EtOAc 97:3, 4.8 mL/min) in three pools,

respectively enriched in one of the three diastereoisomers

(Scheme 20). Each pool was puriﬁed further under the same

conditions, affording separated diastereoisomers (ca. 1 mg,

1 mg, 2 mg).

4.4. X-ray crystallographic structure determinations

Data were collected on a Stoe Imaging Plate Diffraction

System (IPDS), equipped with an Oxford Cryosystems

Cryostream Cooler Device, and using graphite-mono-

˚

chromated Mo K radiation (lZ0.71073 A). The ﬁnal unit

4.2. Semi-preparative HPLC resolution of tetrayne 2a

cell parameters were obtained by means of a least-squares

reﬁnement of a set of well-measured reﬂections, and crystal

decay was monitored during data collection; no signiﬁcant

ﬂuctuations in intensity were observed. The structures were

solved by Direct Methods using the program SIR92,³¹and

reﬁned by least-squares procedures on F2 with SHELXL-

97.³²All hydrogen atoms were located on a difference

Fourier maps, but introduced and reﬁned by using a riding

model, except for OH hydrogen atoms, which were

isotropically reﬁned. All non-hydrogens atoms were

anisotropically reﬁned.

A diastereoisomeric mixture of tetrayne 2a (152 mg) was

dissolved in dichloromethane (1 mL). Samples (20 mL)

were sequentially injected and divided by HPLC (Prontosil

column, pentane/dichloromethane 65:35, 4.8 mL/min) in

three pools, respectively, enriched in diastereoisomer A, B

and C. Each pool was puriﬁed further under the same

conditions, affording separated diastereoisomers A (30 mg),

B (35 mg) and C (21 mg).

4.3. Semi-peparative HPLC resolution of the [5]peri-

cylyne 11a prepared from the isomer B of tetrayne 2a

4.5. Crystallographic and structural parameters for 5b

(Fig. 3)

A diastereoisomeric mixture of the title sample (11 mg) was

Empirical formula

Temperature

C₁₅H₁₈O₂Si; MWZ258.38

180(2) K

Crystal system, space group

Unit cell dimensions

Volume

Z, Calculated density

Absorption coefﬁcient

F(000)

Monoclinic, P21/n

˚

aZ6.449(5) A bZ24.646(5) A cZ9.420(5) A bZ99.650(5)8

3

˚

1476.0(14) A

4, 1.163 mg/cm³

0.151 mm^K1

552

2.34–26.088

Theta range for data collection

Index ranges

7%h%7, K30%k%30, K11%l%11

11012/2831 [R(int)Z0.0328]

97.0%

Full-matrix least-squares on F2

2831/0/171

1.023

R1Z0.0337, wR2Z0.0867

R1Z0.0427, wR2Z0.0913

(0.225 and K0.206) e A^K3

Reﬂections collected/unique

Completeness to 2thetaZ26.08

Reﬁnement method

Data/restraints/parameters

Goodness-of-ﬁt on F2

Final R indices [IO2sigma(I)]

R indices (all data)

Largest diff. peak and hole

Bond lengths [A] and angles [deg] for 5b

Si(1)–C(5)

Si(1)–C(13)

Si(1)–C(14)

C(1)–C(4)

C(1)–C(6)

C(7)–C(8)

C(10)–C(11)

C(5)–Si(1)–C(13)

C(5)–Si(1)–C(14)

C(13)–Si(1)–C(14)

C(5)–Si(1)–C(15)

C(13)–Si(1)–C(15)

C(14)–Si(1)–C(15)

C(1)–O(1)–H(1O)

C(9)–O(2)–C(12)

C(10)–C(9)–C(8)

1.8499(17)

1.8513(18)

1.8521(18)

1.4832(19)

1.5321(17)

1.380(2)

1.3928(19)

109.57(8)

105.93(8)

111.40(10)

107.35(8)

111.53(9)

110.82(9)

107.2(13)

117.81(12)

119.70(13)

Si(1)–C(15)

O(1)–C(1)

O(1)–H(1O)

C(2)–C(3)

C(4)–C(5)

C(8)–C(9)

1.857(2)

1.4437(15)

0.86(2)

1.184(2)

1.203(2)

1.388(2)

O(2)–C(9)

O(2)–C(12)

C(1)–C(2)

C(6)–C(11)

C(6)–C(7)

C(9)–C(10)

1.3641(17)

1.427(2)

1.475(2)

1.380(2)

1.390(2)

1.382(2)

O(1)–C(1)–C(2)

O(1)–C(1)–C(4)

C(2)–C(1)–C(4)

O(1)–C(1)–C(6)

C(2)–C(1)–C(6)

C(4)–C(1)–C(6)

C(3)–C(2)–C(1)

C(5)–C(4)–C(1)

C(9)–C(10)–C(11)

109.93(11)

109.42(11)

108.78(11)

106.00(10)

112.36(11)

110.30(11)

177.66(14)

177.02(15)

119.31(13)

C(4)–C(5)–Si(1)

C(11)–C(6)–C(7)

C(11)–C(6)–C(1)

C(7)–C(6)–C(1)

C(8)–C(7)–C(6)

C(7)–C(8)–C(9)

O(2)–C(9)–C(10)

O(2)–C(9)–C(8)

C(6)–C(11)–C(10)

172.16(12)

118.53(13)

120.86(12)

120.56(12)

120.53(14)

120.45(14)

124.67(13)

115.63(13)

121.47(13)

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

10097

4.6. Crystallographic and structural parameters for 20d

(Fig. 2)

Empirical formula

Temperature

Crystal system, space group

Unit cell dimensions

Volume

Z, Calculated density

Absorption coefﬁcient

F(000)

Crystal size

Theta range for data collection

Index ranges

Reﬂections collected/unique

Completeness to 2thetaZ23.258

Reﬁnement method

Data/restraints/parameters

Goodness-of-ﬁt on F2

Final R indices [IO2sigma(I)]

R indices (all data)

C₁₂H₁₁O₂; MWZ187.21

293(2) K

Triclinic, PK1

˚

aZ6.5680(10) A, bZ8.382(2) A, cZ9.674(2) A aZ105.68(3)8, bZ103.88(3)8, gZ93.24(3)8

3

˚

493.58(17) A

2, 1.260 mg/cm³

0.085 mm^–1

198

0.1!0.1!0.1 mm³

2.27–23.258

K7%h%7, K9%k%9, K10%l%10

3643/1347 [R(int)Z0.0469]

94.4%

Full-matrix least-squares on F2

1347/0/129

1.080

R1Z0.0769, wR2Z0.2114

R1Z0.1063, wR2Z0.2465

K3

˚

(0.317 and K0.247) e A

Largest diff. peak and hole

Bond lengths [A] and angles [deg] for 20d

C(1)–C(1)#1

C(1)–C(2)

C(2)–O(1)

C(2)–C(3)

C(2)–C(6)

C(1)#1–C(1)–C(2)

O(1)–C(2)–C(3)

O(1)–C(2)–C(1)

C(3)–C(2)–C(1)

O(1)–C(2)–C(6)

C(3)–C(2)–C(6)

C(1)–C(2)–C(6)

1.187(8)

1.494(6)

1.450(5)

1.473(6)

1.521(6)

177.6(5)

112.9(3)

111.2(3)

107.6(4)

105.3(3)

108.4(3)

111.5(3)

C(3)–C(4)

C(5)–O(1)

C(6)–C(7)

C(6)–C(11)

C(7)–C(8)

C(4)–C(3)–C(2)

C(7)–C(6)–C(11)

C(7)–C(6)–C(2)

C(11)–C(6)–C(2)

C(8)–C(7)–C(6)

C(7)–C(8)–C(9)

O(2)–C(9)–C(10)

1.139(6)

1.364(5)

1.384(6)

1.400(6)

1.380(6)

166.5(6)

118.1(4)

122.0(4)

119.8(4)

121.5(4)

119.3(4)

116.1(3)

C(8)–C(9)

C(9)–O(2)

C(9)–C(10)

C(10)–C(11)

C(12)–O(2)

O(2)–C(9)–C(8)

C(10)–C(9)–C(8)

C(11)–C(10)–C(9)

C(10)–C(11)–C(6)

C(5)–O(1)–C(2)

C(9)–O(2)–C(12)

1.398(6)

1.371(5)

1.373(6)

1.370(6)

1.423(5)

124.3(4)

119.6(4)

120.7(4)

118.5(4)

117.3(3)

7. Scott, L. T.; DeCicco, G. J.; Hyunn, J. L.; Reinhardt, G. J. Am.

Chem. Soc. 1983, 105, 7760.

Acknowledgements

8. Scott, L. T.; DeCicco, G. J.; Hyunn, J. L.; Reinhardt, G. J. Am.

Chem. Soc. 1985, 107, 6546.

`

The authors wish to thank the Ministere de l’Education

Nationale de la Recherche et de la Technologie for ACI

ﬁnancial support.

9. (a) Houk, K. N.; Scott, L. T.; Rondan, N. G.; Spellmeyer,

D. C.; Reinhardt, G.; Hyun, J. L.; DeCicco, G. J.; Weiss, R.;

Chen, M. H. M.; Bass, L. S.; Clardy, J.; Jorgensen, F. S.;

Eaton, T. A.; Sarkozi, V.; Petit, C. M.; Ng, L.; Jordan, K. D.

J. Am. Chem. Soc. 1985, 107, 6556. (b) Schaad, L. J.; Hess,

B. A.; Scott, L. T. J. Phys. Org. Chem. 1993, 6, 316. (c) Jiao,

H.; Hommes, N. R. J.v. E.; Schleyer, P.v. R.; de Meijere, A.

J. Org. Chem. 1996, 61, 2826.

References and notes

1. (a) de Meijere, A., Ed.; Topics in Current Chemistry; 1998,

196. (b) de Meijere, A., Ed.; Topics in Current Chemistry;

1999, 201.

10. (a) Suzuki, R.; Tsukuda, H.; Watanabe, N.; Kuwatani, Y.;

Ueda, I. Tetrahedron 1998, 54, 2477. (b) Brake, M.;

Enkelmann, V.; Bunz, U. H. F. J. Org. Chem. 1996, 61, 1190.

11. Scott, L. T.; Cooney, M. J. Macrocyclic homoconjugated

polyacetylenes. In Modern Acetylene Chemistry; Stang, P. J.,

Diederich, F., Eds.; VCH: Weinheim, 1995; p 321.

12. Tedeschi, C.; Saccavini, C.; Maurette, L.; Soleilhavoup, M.;

Chauvin, R. J. Organomet. Chem. 2003, 670, 151.

13. Maurette, L.; Godard, C.; Frau, S.; Lepetit, C.; Soleilhavoup,

M.; Chauvin, R. Chem. Eur. J. 2001, 7, 1165.

2. Stang, P. J., Diederich, F., Eds.; Modern Acetylene Chemistry.

VCH: Weinheim, 1995.

3. Chauvin, R. Tetrahedron Lett. 1995, 36, 397.

4. (a) Godard, C.; Lepetit, C.; Chauvin, R. Chem. Commun. 2000,

19, 1833–1834. (b) Lepetit, C.; Godard, C.; Chauvin, R. New

J. Chem. 2001, 25, 572. (c) Ducere, J.-M.; Lepetit, C.; Lacroix,

P. G.; Heully, J.-L.; Chauvin, R. Chem. Mater. 2002, 14, 3332.

5. Lepetit, C.; Nielsen, M. B.; Diederich, F.; Chauvin, R. Chem.

Eur. J. 2003, 5056.

14. Rubin, Y.; Knobler, C. B.; Diederich, F. Angew. Chem., Int.

Ed. Engl. 1991, 30, 698.

6. Lepetit, C.; Silvi, B.; Chauvin, R. J. Phys. Chem. A 2003, 107,

464.

15. Zhang, Z. Z.; Schuster, G. B. J. Am. Chem. Soc. 1989, 111,

7149.

10098

L. Maurette et al. / Tetrahedron 60 (2004) 10077–10098

16. It can, however, not be ruled out that the reaction could be

partly stereospeciﬁc with respect to diastereoisomeric pairs of

the reacting undecatetraynes 2

5181. (b) Meyer, A.; Bigorgne, M. Organometallics 1984, 3,

1112.

22. Soleilhavoup, M.; Maurette, L.; Lamirand, C.; Donnadieu, B.;

McGlinchey, M. J.; Chauvin, R. Eur. J. Org. Chem. 2003, 9,

1652.

17. Lepetit, C.; Maurette, L.; Chauvin, R. unpublished results.

18. Hydroxynonamethyl[5]pericyclyne with a single secondary

carbinol center has been reported: (a) Scott, L. T.; Cooney,

M. J. Macrocyclic homoconjugated polyacetylenes. In Modern

Acetylene Chemistry; Stang, P. J., Diederich, F., Eds.; VCH:

Weinheim, 1995; p 321. (b) Cooney, M. J. PhD Dissertation,

23. Sui-Seng, C.; Soleilhavoup, M.; Maurette, L.; Tedeschi, C.;

Donnadieu, B.; Chauvin, R. Eur. J. Org. Chem. 2003, 9, 1641.

24. (a) Feldman, K. S.; Weinreb, C. K.; Youngs, W. J.; Bradshaw,

J. D. J. Am. Chem. Soc. 1994, 116, 9016. (b) Ma, B.; Sulzbach,

H. M.; Xie; Schaefer, F. H. J. Am. Chem. Soc. 1994, 116, 3529.

25. Journet, M.; Cai, D.; DiMichele, L. M.; Larsen, R. D.

Tetrahedron Lett. 1998, 39, 6427.

´

Universite du Nevada: Reno, 1993.

19. Isolated acyclic dialkynyl carbinols R–C^C–CH(OH)–

C^C–R⁰are however stable. Natural representatives were

even recently discovered in marine sponges: (a) Zdero, C.;

Bohlmann, F.; King, R. M.; Robinson, H. Phytochemistry

1998, 27, 1105. (b) Lim, Y. J.; Kim, J. S.; Im, K. S.; Jung,

J. H.; Lee, C.-O.; Hong, J.; Kim, D.-K. J. Nat. Prod. 1999,

62, 1215. (c) Kim, J. S.; Lim, Y. J.; Im, K. S.; Jung, J. H.; Shim,

C. J.; Lee, C. O.; Hong, J.; Lee, H. J. Nat. Prod. 1999, 62, 554.

(d) Chill, L.; Miroz, A.; Kashman, Y. J. Nat. Prod. 2000, 63, 523.

(e) Lim, Y. J.; Lee, C.-O.; Hong, J.; Kim, D.-K.; Im, K. S.; Jung,

J. H. J. Nat. Prod. 2001, 64, 565.

26. (a) Chauvin, R. Tetrahedron Lett. 1995, 36, 401.

(b) Tanemura, K.; Suzuki, T.; Horaguchi, T. J. Chem. Soc.

Chem. Commun. 1992, 979.

27. Lepetit, C.; Lacroix, P. G.; Peyrou, V.; Saccavini, C.; Chauvin,

R. J. Comput. Meth. Sci. Eng. 2004 in press.

28. Lepetit, C.; Peyrou, V.; Chauvin, R. Phys. Chem. Chem. Phys.

2004, 6, 303.

29. de Meijere, A.; Kozhushkov, S. I. Top. Curr. Chem. 1999, 201,

1.

30. Suffert, J. J. Org. Chem. 1989, 54, 509.

20. (a) Gorgues, A.; Le Coq, A. Chem. Commun. 1979, 767.

(b) Gorgues, A.; Le Coq, A. Tetrahedron Lett. 1979, 50,

4825–4828. (c) Gorgues, A.; Le Coq, A. Tetrahedron Lett.

1979, 50, 4829. (d) Gorgues, A.; Stephan, D.; Belyasmine, A.;

Khanous, A.; Le Coq, A. Tetrahedron 1990, 465, 2817.

21. (a) Meyer, A.; Gorgues, A.; Le Floc’h, Y.; Pineau, Y.;

Guilleviv, J.; Le Marouille, J. Y. Tetrahedron Lett. 1981, 22,

31. Watkin, D. J.; Prout, C. K.; Carruthers, J. R.; Betteridge,

P. W. Crystals Issue10; Chemical Crystallography Labora-

tory: Oxford, UK, 1996. (b) Altomare, A.; Cascarano, G.;

Giacovazzo, G.; Guagliardi, A.; Burla, M. C.; Polidori, G.;

Camalli, M. SIR92 program for automatic solution of crystal

structures by direct methods J. Appl. Cryst. 1994, 27, 435.

32. Carruthers, J. R.; Watkin, D. J. Acta Cryst. 1979, A35, 698.

Article Doi

Synthesis and stereochemical resolution of functional [5]pericyclynes

DOI: 10.1016/j.tet.2004.07.052

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