Palladium-catalyzed oligocyclizations of 2-bromoalk-1-ene-(n+1),(m+n+1)- diynes - Influence of tether lengths and substituents on the outcome of the reaction (Part I)

FULL PAPER

DOI: 10.1002/ejoc.200800826

Palladium-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-(n+1),(m+n+1)-

diynes – Influence of Tether Lengths and Substituents on the Outcome of the

Reaction (Part I)

Wajdi M. Tokan,^[a][‡]Frank E. Meyer,^[a]Stefan Schweizer,^[a]Philip J. Parsons,^[b]and

Armin de Meijere*^[a]

Keywords: Cascade cyclizations / Palladium catalysis / Carbopalladiations / Carbooligocycles / Cyclopropanes

The outcomes and the mechanistic pathways of the palla-

dium-catalyzed Heck-type cascade oligocyclizations of vari-

ous 2-bromoalkenediynes were explored with respect to the

lengths of the tethers between the multiple bonds and the

nature of the substituent at the acetylenic terminus. Just like

substrates containing two three-atom tethers, 2-bromotridec-

1-ene-6,13-diynes 10a,b with one three- and one four-atom

tether undergo two consecutive intramolecular 5- and 6-exo-

dig carbopalladations with subsequent 6π-electrocyclization

methoxycarbonyl group as in 22, 29. Thus, the bisannelated

benzene derivatives 36 and 37 are formed from 22 and 29 in

79 and 18% yield, respectively, whereas 16, 27 and 31 with

their methoxycarbonyl substituents at the acetylenic end

yield tetracyclic systems 38, 39 and 40, consisting of a central

five-membered and two annelated six-membered as well as

an additional annelated three-membered ring, predomi-

nantly (54, 19 and 18% yield, respectively). The cascade re-

action leading to the latter products must involve a 5-exo-

and β-hydride elimination to form tricycles 35a,b with a cen- trig carbopalladation rather than 6π-electrocyclization as the

tral benzene ring in 67 and 61% yield, respectively, indepen-

dent of the fact that 10a contains an electron donor and 10b

an electron acceptor at the acetylene terminus. However,

when 2-bromotetradec-1-ene-7,13-diynes 22, 29 on one side

and 16, 27, 31 on the other are subjected to Heck reaction

conditions, tricycles with a central benzene ring are formed

only, when the substituent at the acetylene terminus is not a

third step. Apparently, the nature and the substitution

pattern of the tether in the substrates 16, 22, 31 linking the

vinyl bromide moiety with the internal acetylene affect the

yield of the tetracyclic product.

Germany, 2008)

complex skeletons. The development of such cascades to

access oligocyclic structures from open-chain precursors

has also been under thorough investigation in our^[4]as well

as other groups^[5]during the last two decades.

In utilizing different types of palladium-catalyzed pro-

cesses (Heck reactions,^[6]cycloisomerizations^[7]) to effect

such oligocyclizations, many investigations were concerned

Introduction

The formation of new carbon–carbon bonds is one of

the primary goals in synthetic organic chemistry. With the

advent of modern synthetic methodologies, such bonds can

be constructed with high chemo-, regio-, and stereoselectivi-

ties. In this regard, organometallic chemistry has provided

a myriad of valuable methods which can be considered a

field by their own. Thus, the variety of modern metal-cata-

lyzed cross-coupling reactions^[1]have significantly facili-

tated the efficient assembly of many complex organic

frameworks as present in natural and non-natural biolo-

gically active compounds. Further advances can be

achieved by making more than one carbon–carbon bond in

a one-pot reaction or at least in a single operation.^[2]Such

domino processes or cascade reactions^[3]are providing ef-

ficient and economical methods for the construction of

[a] Institut für Organische und Biomolekulare Chemie der Georg-

August-Universität Göttingen,

Tammannstrasse 2, 37077 Göttingen, Germany

E-mail: ArmindeMeijere@chemie.uni-goettingen.de

[b] Department of Chemistry, University of Sussex,

Brighton, UK

[‡] Current address: Al-Balqa’ Applied University

Al-Salt, Jordan

Scheme 1. Intramolecular palladium-catalyzed oligocyclization cas-

cades of bromo-enediynes and triynes.

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Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

with the outcomes of these cascades and exploring the lithium in THF at –78 °C and ensuing treatment with di-

mechanistic pathways leading to the observed products.

However, the factors which determine these pathways and

hence control the outcome selectivity of these cascades have

not been determined. Therefore, we have set out to investi-

gate the effect of the tether lengths and nature of the ter-

minal substituents in 2-bromoalk-1-ene-(n+1),(m+n+1)-di-

ynes on determining the mechanistic pathways of their olig-

ocyclizations (Scheme 1).^[8]

ethyl ketone or methyl chloroformate to furnish the desired

substrates 10a and 10b with 2-bromotridec-1-ene-6,12-diyne

skeletons in 28 and 60% yield, respectively.

The synthesis of an analogous oligocyclization substrate

16, in which the unsaturated moieties are linked by two

four-atom tethers started with 1,7-octadiyne (11), prepared

according to a literature procedure by twofold substitution

of 1,4-diiodobutane with sodium acetylide.^[11]Monodepro-

tonation of 11 with one equivalent of n-butyllithium and

addition of the resulting acetylide to ethylene oxide acti-

vated by boron trifluoride diethyl etherate afforded deca-

3,4-diyn-1-ol (12) in 55% yield (Scheme 3). Clearly, the

moderate yield of this reaction must be attributed to the

presence of two terminal acetylene units in 11. Further-

more, the reaction was quenched with water at –78 °C to

avoid subsequent side reactions, and this probably was not

completely efficient. The alcohol 12 was converted into the

corresponding mesylate 13 which was used to alkylate so-

dium dimethyl malonate enolate to give 14 (72%).^[12]The

sodium enolate of the latter was then allylated with 2,3-

dibromopropene in dimethoxyethane (DME) at 70 °C to

provide 15 in very poor yield. The yield could be raised to

75% by adding a small fraction (10–15% by volume) of

dimethylformamide (DMF) to the DME. The final step, the

attachment of the methoxycarbonyl group to the alkyne ter-

minus of 15, was achieved by deprotonation with lithium

diisopropylamide (LDA) at –78 °C and subsequent reaction

with methyl chloroformate to give the desired 2-bromo-

tetradec-1-ene-7,13-diyne derivative 16 (45% yield).

Results and Discussion

Preparation of the Oligocyclization Substrates

The synthesis of the two 2-bromotridec-1-ene-6,12-di-

ynes 10a,b with three- and four-atom tethers, respectively,

between the C,C-multiple bonds started with the previously

described diethyl malonate derivative 5^[9]containing a 2-

bromohept-1-en-6-yne unit. The latter was deprotonated at

the acetylene terminus with n-butyllithium, and the re-

sulting lithium acetylide was treated with 6-(trimethylsilyl)-

hex-5-ynal (6), prepared according to a method reported by

Stetter et al.^[10]to afford the propargyl alcohol derivative

7 in 56% yield (Scheme 2). The hydroxy group in 7 was

methylated by deprotonation with n-butyllithium and sub-

sequent treatment with methyl iodide to give 8, the terminal

acetylene of which was desilylated with silver nitrate in

aqueous ethanol to yield 9 (99%). The terminal acetylene

in 9 was then functionalized by deprotonation with n-butyl-

Scheme 2. Synthesis of 2-bromotridec-1-ene-6,12-diyne derivatives containing a three- and a four-atom tether between the C,C-multiple

bonds; A: 1) nBuLi, –78 °C, THF, 2) aldehyde 6, –78Ǟ0 °C; B: 1) nBuLi, –78 °C, THF, 2) MeI, DMSO, 25 °C, 2 h; C: 1) AgNO₃, EtOH/

H₂O, 2) KCN, 25 °C, 4 h; D: nBuLi, –78 °C, THF, ClCO₂Me; E: nBuLi, –78 °C, THF, Et₂CO. E = CO₂Et.

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An analogous 2-bromotetradec-1-ene-7,13-diyne 22 with

a tert-butyldimethylsilyl group at the alkyne terminus was

prepared by deprotonating 2-(3Ј-butynyloxy)tetrahydro-2H-

pyran (17) with n-butyllithium and treating the resulting

lithium acetylide with 6-bromo-1-(tert-butyldimethylsilyl)-

hexyne (18) to afford 2-(10Ј-(tert-butyldimethylsilyl)deca-

3Ј,9Ј-diynyloxy)tetrahydro-2H-pyran (19) in 46% yield. Ac-

cording to a reported procedure,^[13]treating 19 at –20 °C

with triphenylphosphane and bromine in dichloromethane

directly converted the tetrahydropyranyloxy group of 19

into a bromine substituent and afforded 10-bromo-1-(tert-

Scheme 3. Synthesis of a methoxycarbonyl-terminated 2-bromo-

tetradec-1-ene-7,13-diyne with two four-atom tethers between the

multiple bonds: A: 1) nBuLi, –78 °C, THF, 2) BF₃·Et₂O, ethylene

oxide, –78 °C, 2 h; B: Et₃N, MsCl, CH₂Cl₂–15Ǟ0 °C, 12 h; C:

NaH, dimethyl malonate, KI, THF/DMF, 18 h, 70 °C; D: NaH,

2,3-dibromopropene, DME/DMF, 20 h, 70 °C; E: LDA, ClCO₂Me,

THF, –78 °C, 1 h, room temp., 2 h. E = CO₂Me.

Scheme 5. Syntheses of 2-bromotetradec-1-ene-7,13-diynes 23, 25

without a malonate moiety in the tether linking the vinyl bromide

to the internal acetylene fragment; A: nBuLi, THF, 17, HMPA,

–78 °CǞr.t.; B: Sn, HBr (48%), Et₂O/H₂O (5:2), 2,3-dibromopro-

pene, room temp.; C: imidazole, tBuMe₂SiCl, DMF, 55 °C, 24 h;

D: LDA, ClCO₂Me, THF, –78 °C, 1 h, room temp., 2 h. E:

PdCl₂(PPh₃)₂(0.5 mol-%), CuI (1 mol-%), PPh₃(2 mol-%), Et₃N,

iodobenzene, 40 °C, 14 h; F: Sn, HBr (48%), Et₂O/H₂O (5:2), 2,3-

dibromopropene, room temp., 5 d; G: imidazole, tBuMe₂SiCl,

DMF, 55 °C, 24 h.

Scheme 4. Synthesis of a tert-butyldimethylsilyl-terminated 2-bro-

motetradec-1-ene-7,13-diyne. A: 1) nBuLi, THF, –78 °C, 30 min, 2)

HMPA, 18, room temp., 5 h; B: PPh₃, Br₂, CH₂Cl₂, 30 min, –15 °C,

room temp., 20 h; C: NaH, dimethyl malonate, DMF, 36 h, D:

NaH, 2,3-dibromopropene, DME, 4 h, 70 °C. E = CO₂Me.

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Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

butyldimethylsilyl)-deca-3,9-diyne (20) in 80% yield. The

produced bromodiyne (20) was used to alkylate sodium di-

methyl malonate enolate to produce 21 in 77% yield. The

sodium enolate of 21 was allylated with 2,3-dibromopro-

pene to furnish the desired precursor 22 in 52% yield

(Scheme 4).

Three more oligocyclization substrates with two four-

atom tethers between the multiple bonds, but without a ma-

lonate moiety in the tether linking the vinyl bromide to the

internal acetylene fragment, were prepared. One of these

syntheses started with the alkylation of the monolithiated

1,7-octadiyne with the dioxolane-protected 3-iodopropanal

23^[14]to give 24 in 46% yield (Scheme 5). The acetal-pro-

tected aldehyde 24 was then directly coupled to 2,3-dibro-

mopropene employing tin powder^[15]to give the alcohol 25

in 52% yield, and the hydroxy group in 25 was protected as

the tert-butyldimethylsilyl ether 26 (89% yield). Finally, a

methoxycarbonyl group was installed at the terminal alkyne

Scheme 7. Palladium-catalyzed tricyclization of a dodeca-1,6,11-

triyne and a 2-bromododec-1-ene-6,11-diyne containing two three-

atom tethers according to Negishi et al.^[16]A: Pd(PPh₃)₄(3 mol-

%), HOAc (5 mol-%), MeCN, reflux, 12 h; B: Pd(PPh₃)₄(3 mol-%),

employing the same method as for 16 to give the analogous Et₃N (2 equiv.), MeCN, reflux, 12 h. E = CO₂Et.

substrate 27 (40% yield).

Sonogashira coupling of the terminal acetylene of 24

Thus, when the 2-bromotridec-1-ene-6,12-diynes 10a,b in

with iodobenzene provided the phenyl-substituted diyne 28

with the protected aldehyde terminus, from which the 2-

bromo-14-phenyltetradec-1-ene-7,13-diyne 29 was obtained

in 57% yield by tin-mediated coupling with 2,3-dibro-

mopropene and protecting the resulting hydroxy group as a

tert-butyldimethylsilyl ether (Scheme 5).

acetonitrile were treated with palladium acetate (5 mol-%)

in the presence of triphenylphosphane (20 mol-%) and po-

tassium carbonate (2 equiv.) at 120 °C for 2–3 h, the bisan-

nellated benzene derivatives 35a,b were obtained in 67 and

61% yield, respectively (Scheme 8).

Allylation of the deca-3,9-diyn-1-ol (12) with 2,3-dibro-

mopropene gave the oxygen-linked bromodiyne 30 to which

a methoxycarbonyl group could be attached at the alkyne

terminus to provide 31 (Scheme 6).

Scheme 8. Palladium-catalyzed tricyclization of 2-bromotridec-1-

ene-6,12-diynes containing one three- and one four-atom tether. A:

Pd(OAc)₂(5 mol-%), PPh₃(20 mol-%), K₂CO₃(2 equiv.), MeCN,

120 °C. E = CO₂Et.

Scheme 6. Synthesis of a 2-bromotetradec-1-ene-7,13-diyne with an

oxygen in the tether between the vinyl bromide and the internal

alkyne moiety; A: NaH, 2,3-dibromopropene, THF, 60 °C; B:

LDA, ClCO₂Me, THF, –78 °C, 1 h, room temp., 2 h.

The formation of the aromatic compounds was easily de-

tected by the appearance of a singlet signal in the range

7.30–7.70 ppm and the disappearance of the signals of the

1

vinylic protons in the H NMR spectra. This was further

confirmed by the disappearance of the acetylenic carbon

signals and the appearance of six new signals each in the

Palladium-Catalyzed Oligocyclizations

In an earlier study, Negishi et al.^[16]disclosed palladium- region of aromatic carbon signals in the ¹³C NMR spectra.

catalyzed intramolecular cascade reactions of a triyne like

Apparently, the outcome of these tricyclizations is not

32 and a bromo-enediyne like 33 in which the three multiple affected by the nature of the substituent at the acetylenic

bond fragments were linked by two three-atom tethers, giv- terminus, be it an electron-donating group as in 10a or an

ing rise to tricyclic skeletons, like 34, with two five-mem- electron-withdrawing group as in 10b.

bered rings annelated to a central six-membered aromatic

On the other hand, open-chain enediynes containing two

ring (Scheme 7). The same type of bisannelated benzene de- four-atom tethers which, by the same reaction mode, would

rivatives were formed, when 2-bromotridec-1-ene-6,12-di- lead to tricyclic systems consisting of six-membered rings

ynes and 2-bromotridec-7,12-diynes, i.e. 2-bromoalkene- only, turned out to be highly sensitive to the nature of the

diynes with one three- and one four-atom tether between substituent at the acetylene terminus. Thus, when the

the multiple bonds, were subjected to typical Heck reaction acetylene terminus in such an enediyne was substituted with

conditions [e.g. Pd(OAc)₂, Ph₃P, K₂CO₃, MeCN].^[8a]

a tert-butyldimethylsilyl or a phenyl group as in 22 and 29,

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respectively, treatment with typical Heck precatalyst sys-

tems produced octahydrophenanthrene derivatives 36 and

37 with a central benzene ring in 79 and 18% yield, respec-

tively (Scheme 9).

Surprisingly, all of the 2-bromotetradec-1-ene-7,13-di-

ynes 16, 27, 31 with electron-withdrawing methoxycarbonyl

groups at the acetylene terminus, upon treatment with a

palladium precatalyst mixture (10 mol-% of PdOAc₂,

25 mol-% of PPh₃, and 3 equiv. of K₂CO₃) in acetonitrile

at 60 °C (for 16 and 27), and 110 °C (for 31), respectively,

gave the tetracyclic systems, 38, 39 and 40, respectively, each

containing a cyclopropyl moiety (Scheme 10). Apparently,

these cascade cyclizations proceed along routes that are dif-

ferent from those for all of the other bromo-enediynes pre-

sented above.

The tetracyclic structures of these products were assigned

1

on the basis of their H and ¹³C NMR spectra and ad-

ditional 2D-NMR experiments. The disappearance of the

signals of the acetylenic carbons and the appearance of four

new signals of olefinic carbons in each of the ¹³C NMR

spectra indicated the formation of two new double bonds.

DEPT (135°) and APT measurements indicated that one of

them is tetrasubstituted, while the other is trisubstituted.

1

The H NMR spectra each show a signal in the olefinic

region (δ = 5.90–6.10 ppm) which corresponds to an ole-

finic proton. They also show the appearance of two unique

doublets in the regions (δ = 1.03–1.08 and 1.90–2.02 ppm,

²J = 2.9–3.15 Hz) which correspond to the exo- and endo-

Scheme 10. Palladium-catalyzed cascade cyclizations of 2-bromo-

tetradec-1-ene-7,13-diynes containing two four-atom tethers and

protons of a ring-annelated cyclopropyl methylene group. terminal electron-withdrawing groups. A: Pd(OAc)₂(10 mol-%),

1

According to 2D-NMR correlation, especially H-¹³C mul-

PPh₃(25 mol-%), K₂CO₃(3 equiv.), MeCN, 60 °C; B: Pd(OAc)₂

(10 mol-%), PPh₃(25 mol-%), K₂CO₃(3 equiv.), MeCN, 110 °C. E

tiple bond correlation (HMBC) spectra, the positions of the

= CO₂Me.

diene and the cyclopropyl moieties could be assigned. The

large NOE enhancement between the exo-proton of the cy-

clopropyl moiety and the equatorial α-proton in the pyran

ring of 40 (Figure 1) provided further evidence for the pres-

ence and the position of the cyclopropyl moiety.

Figure 1. NOE enhancements in the NOE-NMR spectrum of the

tetracyclic diene 40.

It is noteworthy that the type of substitution on the

tether linking the vinyl bromide moiety and the internal

acetylene would mainly affect the yield.

Discussion

Scheme 9. Palladium-catalyzed tricyclizations of 2-bromotetradec-

The differently proceeding cascade oligocyclizations of

1-ene-7,11-diynes containing two four-atom tethers. A: Pd(OAc)₂

the various 2-bromoalk-1-ene-(n+1),(m+n+1)-diynes can be

(10 mol-%), PPh₃(25 mol-%), K₂CO₃(3 equiv.), MeCN, 20 h,

rationalized on the basis of previous observations

(Scheme 11).

60 °C; B: Pd(OAc)₂(10 mol-%), PPh₃(25 mol-%), HO₂CNa

(1.5 equiv.), DMF, 10 h, 80 °C. E = CO₂Me.

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Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

the two exomethylene groups in intermediate 44 are not in

the same plane. Coplanar or nearly coplanar 1,3,5-hexatri-

enes prefer to undergo 6π-electrocyclization, as is observed

for intermediates 44 (n = m = 5) comprising two five-mem-

bered rings (Figure 2, A).

Figure 2. Optimized geometries of the hexa-1,3,5-trienylpalladium

intermediate 44 varying with the sizes of the two incorporated

rings.

Accordingly, the formation of the tricycle 34 from 33 and

32 most probably arises by 6π-electrocyclization of the in-

termediate of type 44 (n = m = 5) and subsequent β-hydride

elimination from the intermediate 45. Direct formation of

45 by an intramolecular [4+2] cycloaddition in 43 (route A

in Scheme 11) is less likely, because the terminal triple bond

in 32 and 33 is not particularly activated for such a cycload-

dition, yet it cannot be excluded. These results are also in

agreement with the findings of Trost et al.^[17]In their study,

they found that the palladium-catalyzed cycloisomerization

of enediyne substrates comprising two three-atom tethers

can occur by 6π-electrocyclization and by intramolecular

Diels–Alder reaction.

A similar case arises when the intermediate 44 comprises

one five- and one six-membered ring (n = 5, m = 6). In this

case the geometry of the five-membered ring will dominate

the resulting conformation of the intermediate 44, which

will not allow the square-planar σ-palladium complex to

Scheme 11. Possible pathways for cascade oligocyclizations of 2-

bromoalk-1-ene-(n+1),(m+n+1)-diynes 42, n = 5 or 6, m = 5 or 6.

In any event, the reaction does start with an oxidative coordinate to the opposite exomethylene group precluding

addition of the vinyl bromide moiety to the catalytically the possibility for the intermediate 44 to undergo yet an-

active, in situ formed palladium(0) species, and this is suc- other carbopalladation step (Figure 2, B).

ceeded by an intramolecular n-exo-dig carbopalladation

This is further supported by the fact that the outcomes

typical for an intramolecular Heck reaction to form the first of the oligocyclization cascades of the substrates compris-

ring. This might be followed by an intramlecular [4+2] cy- ing one three- and one four-atom tether, such as 10, are

cloaddition to yield the cyclohexadienylpalladium species insensitive to the nature of the substituent at the terminal

45, (route A) or by another m-exo-dig carbopalladation to acetylene. Thus, only a single type of product, namely the

form the 1,3,5-hexatrienylpalladium intermediate 44. A tricyclic aromatic system 35, was observed (Scheme 8). This

third ring may result from either of three processes. Both a apparently leaves 6π-electrocyclization as the only allowed

6π-electrocyclization (route B) or a 6-endo-trig carbopallad- option for the intermediate 44 (n = 5, m = 6). In addition,

ation (route C) would also lead to 45, while a 5-exo-trig intramolecular [4+2] cycloaddition (route A, Scheme 11),

carbopalladation to produce the neopentyl-type σ-alkylpal- cannot be considered an option for the oligocyclization cas-

ladium species 46 (route D) apparently becomes a favored cades of these substrates. This is due to the length of the

option, when the preferred conformation of the square- tether linking the diene to the dienophile.

planar hexa-1,3,5-trienyl-σ-palladium intermediate 44 puts

On the other hand, when the intermediate 44 comprises

the palladium in a suitable position to coordinate the exo- two six-membered rings (n = m = 6), it will have enough

methylene group (see Figure 2). This situation arises when flexibility to adopt a conformation which makes the two

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planes of the two exomethylene not coplanar to each other

The variety of the outcomes of the oligocyclization of

(Figure 2, C). This will put the square-planar σ-palladium these substrates is attributed to the substituent nature at the

complex in an appropriate position to coordinate the oppo- terminal acetylene. Scheme 12 illustrates the electronic ef-

site exomethylene group (Figure 2). Therefore, carbopallad- fect of these substituents.

ation will become a more favored pathway for this interme-

diate than 6π-electrocyclization.

Thus, after the intermediate 44 has undergone a 5-exo-

trig carbopalladation, the generated neopentyl-type system

The formation of the tetracyclic systems such as 38, 39 49 will experience a 3-exo-trig carbopalladation to furnish

and 40 supports this explanation. It also indicates that the 51. Depending on the nature of the R group, 51 can un-

intermediate 44 (n = m = 6) undergoes this carbopallad- dergo cyclopropyl to homoallyl rearrangement in two ways.

ation step in a 5-exo-trig (route D, Scheme 11) and not in The first version occurs when R is an electron-withdrawing

a 6-endo-trig (route C, Scheme 11) fashion. Furthermore, it group. In this way, 51 will experience cyclopropyl to homo-

shows that the oligocyclization cascades for the substrates allyl rearrangement by breaking the cyclopropyl bond

containing two four-atom tethers cannot occur by an intra- which is not substituted with the R group to produce 50.

molecular [4+2] cycloaddition (route A, Scheme 11) or 6π- Subsequently, 50 will undergo a 3-exo-trig carbopalladation

electrocyclization (route B, Scheme 11). After undergoing a and β-hydride elimination to furnish the kinetically stable

5-exo-trig carbopalladation step, the cascade continues by tetracyclic system 54. The second version occurs, when R is

a series of 3-exo-trig carbopalladations and rearrangements an electron-donating group. In this case, 51 will experience

before it terminates by β-hydride elimination.

cyclopropyl to homoallyl rearrangement by breaking the

Scheme 12. The effect of the substituent on the acetylene terminus on the route and outcome of the cascade oligocyclization of 2-

bromotetradec-1-ene-7,13-diynes via 1,3,5-hexatrienylpalladium intermediate 44.

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Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

Microanalysis: Mikroanalytisches Laboratorium des Instituts für

Organische und Biomolekulare Chemie der Georg-August-Uni-

versität Göttingen. Column chromatography: Merck Kieselgel 60

(0.063–0.200 mm). Thick-layer chromatography; Merck Kieselgel

PF₂₅₄containing CaSO₄. Thin-layer chromatography: Macherey–

Nagel Alugram G/UV₂₅₄0.25 mm silica gel with fluorescent indi-

cator. Developer: molybdenumphosphoric acid solution (10% in

ethanol). All operations were performed under a nitrogen or an

argon atmosphere. Solvents were purified and dried according to

conventional methods. The following abbreviations are used: DME

= 1,2-dimethoxyethane, HMPA = hexamethylphosphortriamide,

DMF = dimethylformamide, PE = light petroleum, boiling range

40–50 °C.

cyclopropyl bond which is substituted with the R group to

produce 53. The latter will undergo β-hydride elimination

to produce the thermodynamically more stable bisanellated

benzene system 55.

Conclusions

Palladium-catalyzed cascade oligocyclizations of 2-bro-

moalkenediynes are valuable and economical methods to

access complex organic skeletons. To be able to anticipate

the outcome of such cascades requires an understanding of

the factors which affect the reaction modes of these cas-

cades. It is obvious from this study that the lengths of the General Procedure for Palladium-Catalyzed Oligocyclizations of 2-

Bromoalk-1-ene-(n + 1),(m + n + 1)-diynes Initiated by a Heck-Type

Reaction (GP)

tethers between the multiple bonds and the nature of the

substituents at the terminal acetylene exert a significant ef-

fect on the outcomes and the yields of such oligocyclization

cascades. 2-Bromotetradec-1-ene-7,13-diynes behave like 2-

bromododec-1-ene-6,11-diynes and 2-bromotridec-6,12-di-

ynes only, if they do not carry a methoxycarbonyl substitu-

Method A: Palladium acetate (0.1 equiv.) is added at 60 °C to a

degassed mixture, placed in a Pyrex^®bottle with a screw cap, of

triphenylphosphane (0.25 equiv.), potassium carbonate (2.5 equiv.),

and the respective 2-bromoalk-1-enediyne (1 equiv.) in acetonitrile.

ent at their acetylenic terminus. With such an electron-with- After stirring at 60 °C for 1 to 12 h, the reaction mixture is cooled

to room temperature, filtered through a layer each of Celite^®and

of charcoal, then concentrated. The residue is purified by either

drawing group, the systems undergo tetracyclizations in-

volving a 5-exo-trig carbopalladation rather than 6π-elec-

column chromatography or thick-layer chromatography (TLC)

trocyclization as the third step, which would be succeeded

using 20ϫ20 cm plates coated with silica gel 60 PF₂₅₄containing

by a β-hydride elimination. It is not surprising that a gem-

2.5% CaSO₄.

bis(methoxycarbonyl) substitution as in 16 favors the first

cyclization step by its Thorpe–Ingold effect,^[18]and thus

Method B: Palladium acetate (0.1 equiv.) is added at 80 °C to a

leads to a higher yield of the tetracyclic product.

degassed mixture, placed in a Pyrex^®bottle with a screw cap, of

triphenylphosphane (0.25 equiv.), sodium formate (1.2 equiv.), and

the respective 2-bromoalk-1-enediyene precursor (1 equiv.) in

DMF. After stirring at 80 °C from 1 to 12 h, the reaction mixture

is poured into water (30 mL) and extracted with diethyl ether

(3ϫ20 mL). The combined ether layers are dried (MgSO₄), concen-

trated and the residue is purified by either column chromatography

or thick-layer chromatography (TLC) using 20ϫ20 cm plates

coated with silica gel 60 PF₂₅₄containing 2.5% CaSO₄.

Experimental Section

General Remarks: ¹H NMR spectra were recorded with Bruker AM

250 (250 MHz), Varian INOVA-500 (500 MHz) and Varian IN-

OVA-600 (600 MHz) instruments at ambient temperature in CDCl₃

or C₆D₆with tetramethylsilane (δ = 0.00 ppm) as an internal stan-

dard. The line positions or centers of multiplets are given in ppm

(δ) and the coupling constants (J) are reported as absolute values

in Hertz [Hz]. Abbreviations for the signal multiplicities: s (singlet),

br. s (broad singlet), d (doublet), t (triplet), q (quartet), dd (doublet

of doublets), ddd (doublet of doublets of doublets), dt (doublet of

triplets), tt (triplet of triplets), dq (doublet of quartets), tq (triplet

Diethyl 2-Bromo-8-hydroxy-13-(trimethylsilyl)-1-tridecene-6,12-di-

yne-4,4-dicarboxylate (7): To a solution of dimethyl 2-(2-bromoal-

lyl)-2-(2-propynyl)malonate^[9](5) (3 g, 9.5 mmol) in THF (20 mL)

was added dropwise, at –78 °C, n-butyllithium (4.41 mL,

10.5 mmol, 2.4  in hexane). After stirring at this temperature for

30 min, 6-(trimethylsilyl)hex-5-ynal (6) (1.59 g, 9.4 mmol) was

of quartets),

m (multiplet). Additional abbreviations: J_ax-ax

(J_axial-axial), J_ax-eq(J_{axial-equatorial}), J_eq-eq(J_{equatorial-equatorial}). ¹³C added dropwise, and the reaction mixture was warmed to 0 °C.

NMR spectra were recorded with Bruker AM 250 (62.5 MHz),

Varian INOVA-500 (125.7 MHz) and Varian INOVA-600

(150.8 MHz) instruments at ambient temperature in CDCl₃, with δ

(CDCl₃) = 77.0 ppm as an internal standard. When signals could

not be assigned unambiguously, the potentially corresponding

atoms concerned are marked with an asterisk (*). The multiplicities

of ¹³C NMR signals were determined with the help of either DEPT

(Distortionless Enhancement by Polarization Transfer) or APT

(Attached Proton Test) measurements and are designated as fol-

Water (20 mL) was added to the mixture, and the aqueous layer

was extracted with diethyl ether (3ϫ20 mL). The combined or-

ganic layers were washed with brine, dried (MgSO₄) and concen-

trated. The residue was purified by column chromatography (90 g

of flash silica gel, column 2ϫ35 cm, PE/Et₂O, 1:1) to afford 2.7 g

(60%) of 7 as a colorless oil, R (PE/Et O, 1:1) = 0.30. IR (film): ν

˜

f

2

= 3450 (OH), 2950, 2180 (CϵC), 1720 (C=O), 1630 (C=C), 1430,

1290, 1250, 1195, 920, 845, 760 cm^–1. ¹H NMR (250 MHz, CDCl₃):

δ = 0.08 [s, 9 H, Si(CH₃)₃], 1.24 (t, ³J = 7.1 Hz, 6 H, CH₂CH₃),

3

lows: CH₃, CH = (+) (DEPT and APT), CH₂= (–), (DEPT and 1.58–1.77 (m, 4 H, 9- and 10-H), 2.23 (t, J = 6.4 Hz, 3 H, 11-H

5

APT), quaternary C = (–) (APT), (C_quat) (DEPT). Infrared spectra

were recorded with a Bruker FT-IR spectrometer IFS 66. Mass

spectra were recorded with Finnigan MAT CH 7 and MAT 731

spectrometers using electron impact ionization at 70 eV or direct

chemical ionization with NH₃as reactant gas. High-resolution

mass spectra (HRMS) were recorded with a Finnigan MAT 311

or an INCOS 50 with Varian 34000 (GC-MS) instrument using

preselected ion peak matching at R ≈ 10000 to be within Ϯ2 ppm.

and OH), 2.91 (d, J = 1.9 Hz, 2 H, 5-H), 3.23 (s, 2 H, 3-H), 4.18

3

(m, 4 H, OCH₂CH₃), 4.32 (t, J = 6.3 Hz, 1 H, 8-H), 5.58 (br. s, 1

H, 1-H), 5.78 (br. s, 1 H, 1-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): δ = 0.O1 [+, Si(CH₃)₃], 13.9 (+, CH₂CH₃), 19.5 (–, C-11),

22.4 (–, C-5), 24.2 (–, C-10), 36.9 (–, C-9), 42.7 (–), 56.2 (C_quat, C-

4), 61.9 (+, C-8), 61.9 (–, OCH₂CH₃), 79.7 (C_quat, C-7), 84.9 (C_quat

,

C-13), 106.7 (C_quat, C-12), 122.5 (–, C-1), 126.4 (C_quat, C-2), 169.0

(C_quat, 2 COOEt) ppm.

Eur. J. Org. Chem. 2008, 6152–6167

www.eurjoc.org

6159

A. de Meijere et al.

FULL PAPER

Diethyl 2-Bromo-8-methoxy-13-(trimethylsilyl)-1-tridecene-6,12-di-

yne-4,4-dicarboxylate (8): To a solution of 7 (4.57 g, 9.5 mmol) in

THF (40 mL), kept at –78 °C, was added dropwise n-butyllithium

(4.41 mL, 10.5 mmol, 2.4  in hexane). After warming to 0 °C, a

solution of methyl iodide (2.8 g, 19.9 mmol) in anhydrous DMSO

(20 mL) was added, and stirring was continued at ambient tem-

added to water (50 mL), and the mixture was extracted with diethyl

ether (3ϫ50 mL). The combined organic layers were washed with

brine, dried (MgSO₄) and concentrated. The residue was purified

by column chromatography (40 g of flash silica gel, column

2.5ϫ20 cm, PE/Et₂O, 8:1) to afford 0.36 g (28%) of 10a as a color-

less oil, R (PE/Et O, 2:1) = 0.19. IR (film): ν = 3450 (OH), 2930,

˜

f

2

perature for 2 h. Water (20 mL) was added to the reaction mixture, 2230 (CϵC), 1740 (C=O), 1625 (C=C), 1430, 1370, 1290, 1250,

and the aqueous layer was extracted with diethyl ether (3ϫ20 mL).

The combined organic layers were washed with brine, dried

(MgSO₄) and concentrated. The residue was purified by column

chromatography (50 g of flash silica gel, column 2.5ϫ35 cm, PE/

1190, 1100, 1070, 960, 905, 870, 740 cm^–1. ¹H NMR (250 MHz,

CDCl₃): δ = 1.06 (t, ³J = 7.0 Hz, 6 H, CH₂CH₃), 1.13 (t, ³J =

7.1 Hz, 6 H, OCH₂CH₃), 1.47–1.53 (m, 6 H, CH₂CH₃and 10-H),

3

1.53–1.68 (m, 2 H, 9-H), 2.09 (t, J = 6.7 Hz, 2 H, 11-H), 2.40 (s,

5

Et₂O, 8:1) to afford 4.19 g (89%) of 8 as colorless oil, R_f(PE/Et₂O, 1 H, OH), 2.82 (d, J = 1.7 Hz, 2 H, 5-H), 3.13 (s, 2 H, 3-H), 3.20

1:1) = 0.58. IR (film): ν = 2950, 2190 (CϵC), 1745 (C=O), 1630 (s, 3 H, OCH₃), 3.80 (t, ³J = 6.3 Hz, 1 H, 8-H), 4.08 (m, 4 H,

˜

(C=C), 1435, 1390, 1195, 850, 770, 705, 650 cm^–1. ¹H NMR

OCH₂CH₃), 5.47 (d, J = 1.5 Hz, 1 H, 1-H), 5.65 (br. s, 1 H, 1-H)

ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 8.3 (+, CH₂CH₃),

13.6 (+, OCH₂CH₃), 18.0 (–, C-11), 22.2 (–, C-5), 24.2 (–, C-10),

2

(250 MHz, CDCl₃): δ = 0.09 [s, 9 H, Si(CH₃)₃], 1.22 (t, ³J = 7.2 Hz,

3

6 H, CH₂CH₃), 1.55–1.81 (m, 4 H, 9,10-H), 2.19 (t, J = 7.0 Hz, 2

2

H, 11-H), 2.92 (d, J = 1.8 Hz, 2 H, 5-H), 3.23 (s, 2 H, 3-H), 3.29

34.3 (–, C-9), 34.5 (–), 42.5 (–, C-3), 55.8 (+, OCH₃), 55.8 (C_quat

C-4), 61.6 (–, OCH₂CH₃), 70.4 (+, C-8), 71.6 (C_quat, C-6), 80.4

4 H, OCH₂CH₃), 5.56 (br. s, 1 H, 1-H) ppm. ¹³C NMR (62.9 MHz, (C_quat, C-7), 82.3 (C_quat, C-13), 83.5 (C_quat, C-12), 122.0 (–, C-1),

,

5

3

(s, 3 H, OCH₃), 3.88 (tt, J = 1.8, J = 6.4 Hz, 1 H, 8-H), 4.8 (m,

CDCl₃, DEPT): δ = 0.01 [+, Si(CH₃)₃], 13.9 (+, CH₂CH₃), 19.5

126.3 (C_quat, C-2), 168.7 (C_quat, 2 COOEt) ppm. MS (EI, 70 eV):

(–, C-11), 22.4 (–, C-5), 24.2 (–, C-10),34.7 (–, C-9), 42.8 (–, C-3), m/z (%) = 485/483 (6/4) [M⁺– CH₂CH₃], 453/451 (4/3), 331 (4),

56.1 (C_quat, C-4), 56.1 (+, OCH₃), 61.8 (–, OCH₂CH₃), 70.7 (+, C- 241 (6), 130 (10), 109 (4), 91 (14), 71 (11), 57 (100), 44 (23).

8), 71.9 (C_quat, C-6), 80.6 (C_quat, C-7), 82.5 (C_quat, C-13), 106.7

1-Methyl 10,10-Diethyl 12-Bromo-6-methoxy-12-tridecene-1,7-di-

yne-1,10,10-tricarboxylate (10b): solution of lithiated

(C_quat, C-12), 122.3 (–, C-1), 126.6 (C_quat, C-2), 168.9 (C_quat, 2 CO-

OEt) ppm.

A

9

(4.7 mmol) was prepared as described for the preparation of 10a.

To this solution was added at –78 °C a solution of methyl chloro-

formate (3.76 mL, 46.8 mmol) in THF (70 mL), and stirring was

continued at ambient temperature for 2 h. After work-up as for

10a, the resulting residue was purified by column chromatography

Diethyl 2-Bromo-8-methoxy-1-tridecene-6,12-diyne-4,4-dicarboxyl-

ate (9): A solution of 8 (1.45 g, 2.9 mmol) in ethanol (3 mL) was

added slowly to a solution of silver nitrate (658 mg,3.9 mmol) in

ethanol (5 mL) and water (1.6 mL), upon which a precipitate

formed immediately. After stirring at ambient temperature for (55 g of flash silica gel, column 2.5ϫ35 cm, PE/Et₂O, 8:1) to afford

15 min, a solution of potassium cyanide (1.24 g, 19 mmol) in water

(2.7 mL) was added, upon which most of the precipitate dissolved

1.36 g (60%) of 10b as a colorless oil, R_f(PE/Et₂O, 2:1) = 0.25. IR

(film): ν = 2900, 2250 (CϵC), 1730 (C=O), 1635 (C=C), 1440,

˜

again. After stirring for 4 h at ambient temperature, water (50 mL) 1375, 1025, 955, 915, 855, 765 cm^–1. ¹H NMR (250 MHz, CDCl₃):

3

was added, and the reaction mixture was extracted with diethyl

ether (3ϫ50 mL). The combined organic layers were washed with

brine, dried (MgSO₄) and concentrated. The residue was purified

by column chromatography (50 g of flash silica gel, column

2.5ϫ20 cm, PE/Et₂O, 12:1) to afford 1.21 g (98%) of 9 as a color-

δ = 1.19 (t, J = 7.1 Hz, 6 H, CH₂CH₃), 1.64–1.68 (m, 4 H, 4- and

3

5

5-H), 2.29 (t, J = 6.3 Hz, 2 H, 3-H), 2.89 (d, J = 1.6 Hz, 2 H, 9-

H), 3.20 (s, 2 H, 11-H), 3.26 (s, 3 H, OCH₃), 3.66 (s, 3 H, CO-

OCH₃), 3.85 (br. s, 1 H, 6-H), 4.13 (m, 4 H, OCH₂CH₃), 5.53 (d,

²J = 1.5 Hz, 1 H, 13-H), 5.70 (br. s, 1 H, 13-H) ppm. ¹³C NMR

less oil, R (PE/Et O, 2:1) = 0.37. IR (film): ν = 3300 (CϵCH), (62.9 MHz, CDCl₃, DEPT): δ = 13.7 (+, CH₂CH₃), 18.2 (–, C-3),

˜

f

2

2950, 2130 (CϵC), 1740 (C=O), 1640 (C=C), 1450, 1375, 1200, 22.3 (–, C-9), 23.2 (–, C-4), 34.5 (–, C-5), 42.7 (–, C-11), 52.2 (+,

1

3

910, 855, 640 cm^–1. H NMR (250 MHz, CDCl₃): δ = 1.27 (t, J =

COOCH₃), 56.0 (+, OCH₃), 56.0 (C_quat, C-10), 61.7 (–, OCH₂CH₃),

7.1 Hz, 6 H, CH₂CH₃), 1.65 (m, 2 H), 1.73–1.83 (m, 2 H), 1.94 (t,

70.4 (+, C-6), 73.1 (C_quat, C-8), 80.9 (C_quat, C-1), 82.1 (C_quat, C-7),

88.8 (C_quat, C-2), 122.1 (–, C-13), 126.4 (C_quat, C-12), 154 (C_quat,

4

3

⁴J = 2.6 Hz, 1 H, 13-H), 2.21 (dt, J = 2.6, J = 6.6 Hz, 2 H, 11-

5

H), 2.98 (d, J = 1.3 Hz, 2 H, 5-H), 3.29 (s, 2 H, 3-H), 3.34 (s, 3

COOMe), 168.8 (C_quat, 2 COOEt) ppm. MS (EI, 70 eV): m/z (%)

H, OCH₃), 3.93 (t, ³J = 6.3 Hz, 1 H, 8-H), 4.19 (m, 4 H,

= 455 (2), 404 (17) [M⁺– Br], 299 (14), 295 (16), 286 (12), 280 (10),

2

OCH₂CH₃), 5.61 (d, J = 1.5 Hz, 1 H, 1-H), 5.79 (br. s, 1 H, 1-H) 271 (16), 169 (22), 167 (24), 165 (20), 161 (24), 147 (20), 137 (22),

ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ

=

13.9 (+,

115 (27), 111 (24), 105 (32), 91 (58), 85 (35), 79 (59), 71 (61), 59

CH₂CH₃), 18.1 (–, C-11), 22.5 (–, C-5), 24.2 (–, C-10), 34.7 (–, C- (49), 45 (64), 43 (100).

9), 42.8 (–, C-3), 56.2 (C_quat, C-4), 56.2 (+, OCH₃), 61.9 (–,

3,9-Decadiyn-1-ol (12): n-Butyllithium (17.6 mL, 27.4 mmol, 1.56 

OCH₂CH₃), 68.5 (+, C-13), 71.9 (C_quat, C-6), 80.8 (C_quat, C-12),

82.5 (C_quat, C-13), 122.4 (–, C-1), 126.6 (C_quat, C-2), 169.1 (C_quat

in hexane) at –78 °C was added dropwise to a solution of 1,7-oc-

tadiyne (3 g, 28.3 mmol) in THF (175 mL). After stirring for

30 min, boron trifluoride diethyl etherate (BF₃·Et₂O) (3.5 mL,

27.8 mmol) was added to the resulting colorless suspension. The

reaction mixture was stirred for an additional 15 min before adding

ethylene oxide (14.11 mL, 283 mmol). After stirring the mixture for

,

2 COOEt) ppm. MS (EI, 70 eV): m/z (%) = 347 (64) [M⁺– Br],

242 (20), 241 (58), 213 (26), 197 (21), 169 (67), 168 (38), 134 (38),

117 (56), 115 (36), 91 (85), 77 (46), 65 (47), 55 (53), 43 (86), 41

(100).

Diethyl

2-Bromo-14-ethyl-14-hydroxy-8-methoxy-1-hexadecene- 2 h, the reaction was quenched at –78 °C by adding a saturated

6,12-diyne-4,4-dicarboxylate (10a): To a solution of 9 (1.08 g,

2.5 mmol) in THF (20 mL), kept at –78 °C, was added dropwise n-

butyllithium (1.1 mL, 2.6 mmol, 2.4  in hexane) and stirring was

continued for 30 min. After adding diethyl ketone (259 mg,

3.0 mmol), the reaction mixture was warmed to ambient tempera-

ture. After stirring for an additional 2 h, the reaction mixture was

aqueous solution of ammonium chloride (120 mL), and the mix-

ture was extracted with diethyl ether (4ϫ100 mL). The combined

ether fractions were dried (MgSO₄), concentrated, and the residue

was purified by column chromatography (60 g of silica gel, column

2.5ϫ50 cm, and pentane/Et₂O, 2:1) to afford 2.5 g (60%) of 12 as

a colorless liquid. R (pentane/Et O, 1:1) = 0.6. IR (film): ν = 3303,

˜

f

2

6160

www.eurjoc.org

Eur. J. Org. Chem. 2008, 6152–6167

Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

1

2950, 2863, 2116, 1431, 1330, 1272, 1186, 1038, 849, 621 cm^–1. H

23.79 mmol, 60% oil suspension) in 1,2-dimethoxyethane(DME)

NMR (250 MHz, CDCl₃): δ = 1.60 (m, 4 H, 6,7-H), 1.80 (br. s, 1 (90 mL). To the resulting mixture were added 2,3-dibromopropene

4

H, OH), 1.94 (t, J = 2.65 Hz, 1 H, 10-H), 2.15–2.23 (m, 4 H, 5,8-

(7.13 g, 35.68 mmol) and DMF (10 mL). After heating under reflux

at 70 °C for 20 h, the reaction mixture was cooled to ambient tem-

perature, water (120 mL) was added, and the mixture extracted

H), 2.41 (m, 2 H, 2-H), 3.66 (t, J = 6.0 Hz, 2 H, 1-H) ppm. ¹³C

NMR (62.9 MHz, CDCl₃, DEPT): δ = 17.88 (–, C-5), 18.23 (–, C-

3

8), 23.11 (–, C-2), 27.30 (–, C-6*), 27.48 (–, C-7*), 61.31 (–, C-1), with diethyl ether (5ϫ50 mL). The combined organic phases were

68.45 (–, C-10), 76.74 (C_quat, C-3), 81.97 (C_quat, C-4), 84.14 (C_quatdried (MgSO₄), concentrated, and the residue was purified by col-

,

C-9) ppm. MS (DCI, NH₃): m/z (%) = 185 (93) [M + N₂H₇⁺], 168 umn chromatography (200 g of silica gel, column 2.5ϫ120 cm,

(100) [M + NH₄⁺]. C₁₀H₁₄O (150.1): calcd. C 79.96, H 9.39; found

C 79.71, H 9.14.

pentane/dichloromethane, 5:4) to afford 7.8 g (85%) of 15 as a col-

orless oil. R (pentane/dichloromethane, 5:4) = 0.72. IR (film): ν =

˜

f

3311, 2928, 2845, 2116, 1740, 1624, 1464, 1378, 1273, 1200, 1153,

1

898, 741 cm^–1. H NMR (250 MHz, CDCl₃): δ = 1.59 (m, 4 H, 6Ј,

3,9-Decadiynyl Methanesulfonate (13): Methanesulfonyl chloride

(4.2 mL, 54 mmol) was added at –10 °C to a mixture of 3,9-deca-

diyn-1-ol (12)(5.4 g, 36 mmol), triethylamine (Et₃N) (10 mL,

72 mmol) and dichloromethane (120 mL). After stirring at –10 °C

for 12 h, the reaction mixture was poured into water (120 mL), the

two layers were separated, and the aqueous layer was extracted

with dichloromethane (3ϫ30 mL). The combined organic phases

were dried (MgSO₄), concentrated, and the residue was purified by

column chromatography (120 g of silica gel, column 2.5ϫ80 cm,

pentane/Et₂O, 2:1) to afford 7.0 g (85%) of 13 as a yellowish liquid.

7Ј-H), 1.94 (t, ⁴J = 1.96 Hz, 1 H, 10Ј-H), 2.08–2.26 (m, 8 H,

1Ј,2Ј,5Ј,8Ј-H), 3.16 (s, 2 H, 1ЈЈ-H), 3.73 (s, 6 H, COOCH₃), 5.59 (d,

²J = 1.78 Hz, 1 H, 3ЈЈ-H), 5.67 (d, J = 1.67 Hz, 1 H, 3ЈЈ-H) ppm.

2

¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 14.26 (–, C-2Ј), 17.94

(–, C-5Ј), 18.26 (–, C-8Ј), 27.48 (–, C-6Ј*), 27.79 (–, C-7Ј*), 31.15

(–, C-1Ј), 43.19 (–, C-1ЈЈ), 52.74 (+, COOCH₃), 56.45 (C_quat, C-2),

68.40 (C_quat, C-10Ј), 78.65 (C_quat, C-3Ј), 80.41 (C_quat, C-4Ј), 84.20

(C_quat, C-9Ј), 122.08 (–, C-3ЈЈ), 126.83 (C_quat, C-2ЈЈ), 170.54 (C_quat

,

2 COOCH₃) ppm. MS (DCI, NH₃): m/z (%) = 784 (45) [2 M +

NH₄⁺], 400/402 (100/98) [M – H + NH₄⁺], 383/385 (9/9) [M⁺+ H],

303 (8) [M⁺– Br]. C₁₈H₂₃BrO₄(383.2): calcd. C 56.41, H 6.05;

found C 56.70, H 5.82.

R (pentane/Et O, 1:1) = 0.6. IR (film): ν = 3289, 3026, 2940, 2856,

˜

f

2

2115, 1734, 1356, 1175, 964, 904, 801, 649 cm^–1. ¹H NMR

(250 MHz, CDCl₃): δ = 1.54–1.67 (m, 4 H, 6,7-H), 1.94 (t, ⁴J =

2.7 Hz, 1 H, 10-H), 2.13–2.23 (m, 4 H, 5,8-H), 2.6 (m, 2 H, 2-H),

Trimethyl

13-Bromo-13-tetradecene-1,7-diyne-1,11,11-tricarb-

3

3.03 (s, 3 H, CH₃SO₃), 4.25 (t, J = 6.78 Hz, 2 H, 1-H) ppm. ¹³C

oxylate (16): A solution of LDA (14.8 mmol) in THF (25 mL) [pre-

pared by dropwise addition, at –78 °C, of diisopropylamine (1.5 g,

14.8 mmol) to a solution of n-butyllithium (10 mL, 15.6 mmol,

1.56  in hexane) in THF (25 mL) and stirring for 30 min] was

added dropwise, at –78 °C, to a solution of dimethyl 2-(2ЈЈ-bro-

moallyl)-2-(3Ј,9Ј-decadiynyl)malonate (15) (5.4 g, 14.2 mmol) in

THF (25 mL). After stirring for 30 min, HMPA (2.48 mL,

13.7 mmol) and methyl chloroformate (10.8 mL, 142 mmol) were

added, stirring was continued at –78 °C for 1 h, and at room tem-

perature for 2 h. The reaction was then quenched by addition of a

saturated solution of ammonium chloride (50 mL), and the mixture

was extracted with diethyl ether (3ϫ50 mL). The combined or-

ganic layers were dried (MgSO₄) and concentrated. The residue was

purified by column chromatography (100 g of silica gel, column

2.5ϫ80 cm, employing a polarity gradient starting with 8:1 pen-

tane/Et₂O until the starting materials were removed; then with 6:1

pentane/Et₂O and finally with 4:1 pentane/Et₂O to elute the prod-

uct) to afford 2.8 g (44%) of 16 as a colorless oil. R_f(pentane/Et₂O,

NMR (62.9 MHz, CDCl₃, DEPT): δ = 17.90 (–, C-2), 18.12 (–, C-

5), 20.00 (–, C-8), 27.41 (–, C-6*), 27.58 (–, C-7*), 37.61 (+,

CH₃SO₃), 67.85 (–, C-1), 68.51 (C_quat, C-10), 74.50 (C_quat, C-3),

82.43 (C_quat, C-4), 84.07 (C_quat, C-9) ppm. MS (DCI, NH₃): m/z

(%) = 474 (64) [2 M + NH₄⁺], 246.1 (100) [M + NH₄⁺]. C₁₁H₁₆O₃S

(228.1): calcd. C 57.87, H 7.06; found C 57.97, H 6.91.

Dimethyl 2-(3Ј,9Ј-Decadiynyl)malonate (14): Dimethyl malonate

(8.1 g, 61 mmol) was added dropwise at 50 °C to a suspension of

sodium hydride (2.45 g, 61 mmol, 60% oil suspension) in DMF

(200 mL). The resulting clear solution was transferred into a mix-

ture of 3,9-decadiynyl methanesulfonate (13) (7.0 g, 30 mmol), po-

tassium iodide (5.1 g, 30 mmol) and THF (200 mL). The resulting

mixture was heated under reflux at 70 °C for 18 h. The reaction

mixture was then treated with a saturated aqueous solution of am-

monium chloride (200 mL), and the aqueous layer was extracted

with diethyl ether (3ϫ100 mL). The combined organic phases were

dried (MgSO₄), concentrated, and the residue was purified by azeo-

tropic Kugelrohr distillation (at 170 °C, 0.1 mm) after adding 3

drops of dimethoxymethane to produce 6.7 g (83%) of 14 as a col-

orless oil. An analytical sample was further purified by column

chromatography (silica gel, 5:1 pentane/Et₂O). R_f(pentane/Et₂O,

4:1) = 0.36. IR (film): ν = 3002, 2953, 2865, 2236, 1736, 1708,

˜

1

1625, 1433, 1274, 1179, 1152, 1080, 902, 753, 591 cm^–1. H NMR

(250 MHz, CDCl₃): δ = 1.53–1.72 (m, 4 H, 4,5-H), 2.01–2.24 (m,

3

6 H, 6,9,10-H), 2.34 (t, J = 6.80 Hz, 2 H, 3-H), 3.15 (s, 2 H, 12-

2

H), 3.72 (s, 3 H, COOCH₃), 3.74 (s, 3 H, COOCH₃), 5.58 (d, J =

5:1) = 0.16. IR (film): ν = 3304, 3004, 2955, 2865, 2843, 2116, 1762,

˜

2

1.78 Hz, 1 H, 14-H), 5.66 (d, J = 1.62 Hz, 1 H, 14-H) ppm. ¹³C

1728, 1433, 1360, 1250, 1150, 1050, 632 cm^–1. ¹H NMR (250 MHz,

NMR (62.9 MHz, CDCl₃, DEPT): δ = 14.24 (–, C-9), 18.20 (–, C-

6), 18.21 (–, C-3), 26.50 (–, C-5), 27.75 (–, C-4), 31.12 (–, C-10),

43.19 (–, C-12), 52.57 (+, COOCH₃), 52.74 (+, COOCH₃), 56.43

(C_quat, C-11), 73.02 (C_quat, C-1), 78.93 (C_quat, C-8), 80.03 (C_quat, C-

7), 89.30 (C_quat, C-2), 122.09 (–, C-14), 126.79 (C_quat, C-13), 154.18

(C_quat, COOCH₃), 170.52 (C_quat, 2 COOCH₃) ppm. MS (DCI,

NH₃): m/z (%) = 460/458 (100/96) [M – H + NH₄⁺], 340 (4), 208

(4). C₂₀H₂₅BrO₆(441.3): calcd. C 54.43, H 5.71; found C 54.43, H

5.41.

4

CDCl₃): δ = 1.61 (m, 4 H, 6Ј,7Ј-H), 1.94 (t, J = 2.7, 1 H, 10Ј-H),

3

2.08 (q, J = 6.4, 2 H, 1Ј-H), 2.15–2.23 (m, 6 H, 2Ј,5Ј,8Ј-H), 3.61

(t, ³J = 7.2 Hz, 1 H, 2-H), 3.74 (s, 3 H, COOCH₃) ppm. ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): δ = 16.72 (–, C-2Ј), 17.94 (–, C-5Ј),

18.20 (–, C-8Ј), 27.44 (–, C-1Ј), 27.83 (–, C-6Ј*), 28.02 (–, C-7Ј*),

50.27 (+, C-2), 52.58 (+, COOCH₃), 68.39 (+, C-10Ј), 78.19 (C_quat

,

C-3Ј), 81.26 (C_quat, C-4Ј), 83.30 (C_quat, C-9Ј), 169.59 (C_quat, 2 CO-

OCH₃) ppm. MS (DCI, NH₃): m/z (%) = 282 (100) [M + NH₄⁺],

236 (2), 206 (4), 167 (8), 150 (8). C₁₅H₂₀O₄(264.3): calcd. C 68.16,

H 7.63; found C 68.15, H 7.43.

2-[10Ј-(tert-Butyldimethylsilyl)deca-3Ј,9Ј-diynyloxy]tetrahydro-2H-

pyran (19): To a solution of 2-(but-3-ynyloxy)tetrahydro-2H-pyran

(17) (9.04 g, 58.6 mmol) in THF (120 mL) was added dropwise at

–78 °C a solution of n-butyllithium (41.0 mL, 64.0 mmol, 1.5  in

hexane). After stirring at –78 °C for 30 min, 6-bromo-1-(tert-butyl-

Dimethyl 2-(2ЈЈ-Bromoallyl)-2-(3Ј,9Ј-decadiynyl)malonate (15): Di-

methyl 2-(3Ј,9Ј-decadiynyl)malonate (14) (6.4 g, 23.79 mmol) was

added dropwise at 50 °C to a suspension of sodium hydride (0.95 g,

Eur. J. Org. Chem. 2008, 6152–6167

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6161

A. de Meijere et al.

FULL PAPER

dimethylsilyl)hexyne (18) (17.62 g, 64.0 mmol) and HMPA

(11.5 mL, 64.0 mmol) were added to the resulting solution. The

reaction mixture was warmed to room temperature, and stirring

was continued for 5 h. The mixture was then diluted with 50 mL

of water, the two layers were separated, and the aqueous layer was

extracted with diethyl ether (3ϫ20 mL). The combined organic

layers were dried (MgSO₄), concentrated, and the residue was puri-

fied by column chromatography (500 g of silica gel, column

8ϫ60 cm, PE/Et₂O, 10:1) to afford 9.40 g (46%) of 19 as a color-

Si(CH₃)₂], 16.45 [C(CH₃)₃], 16.68 (C-2Ј), 18.13 (C-5Ј), 19.30 (C-8Ј),

26.00 [3 C(CH₃)₃], 27.61 (C-1Ј*), 27.85 (C-6Ј*), 27.99 (C-7Ј*), 50.22

(C-2), 52.52 (2 OCH₃), 78.05 (C-3Ј*), 81.29 (C-4Ј*), 82.60 (C-10Ј*),

107.52 (C-9Ј*), 169.54 (2 C=O) ppm. MS (EI, 70 eV): m/z (%) =

347 (5) [M⁺– OCH₃], 322 (23), 321 (100) [M⁺– C₄H₉], 261 (9),

173 (11), 89 (37), 73 (11), 59 (9). MS (DCI, NH₃): m/z (%) = 774

(62) [2 M + NH₄⁺], 396 (100) [M + NH₄⁺]. C₂₁H₃₄O₄Si (378.6).

Dimethyl 2-Bromo-14-(tert-butyldimethylsilyl)tetradec-1-ene-7,13-

diyne-4,4-dicarboxylate (22): Following the same procedure as for

the preparation of 15, to a suspension of sodium hydride (312 mg,

13 mmol, 60 % oil suspension) in DME (24 mL) were added at

50 °C successively dimethyl 2-[10-(tert-butyldimethylsilyl)deca-3,9-

diynyl]malonate (21) (4.45 g, 12.0 mmol) and 2,3-dibromopropene

(2.60 g, 13 mmol). After work-up, the residue was purified by col-

umn chromatography (80 g of silica gel, column 2.5ϫ40 cm, pen-

tane/Et₂O, 20:1) to produce 4.56 g (52%) of 22 as a colorless oil.

less liquid. R (PE/Et O, 10:1) = 0.29. IR (film): ν = 2927, 2856,

˜

f

2

2173, 1471, 1250, 1123, 1071, 1036, 839, 776, 681 cm^–1. H NMR

(250 MHz, CDCl₃): δ = 0.06 [s, 6 H, Si(CH₃)₂], 0.91 [s, 9 H, C(CH₃)

₃], 1.20–1.35 (m, 2 H, 6Ј-H), 1.50–1.70 (m, 6 H, 3,4,5-H), 2.16 (m,

1

3

5

2 H, 8Ј-H), 2.23 (m, 2 H, 5Ј-H), 2.44 (tt, J = 7.2, J = 2.4 Hz, 2

H, 2Ј-H), 3.52 (m, 2 H, 6-H), 3.80 (m, 2 H, 1Ј-H), 4.63 (m, 1 H,

2-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃): δ = –4.57 [Si(CH₃)₂],

–4.49 [Si(CH₃)₂], 16.48 [C(CH₃)₃], 18.20 (C-2Ј), 19.35 (C-4*), 19.39

(C-8Ј*), 20.16 (C-5Ј), 25.41 (C-5), 26.00 [C(CH₃)₃], 27.65 (C-6Ј**),

27.89 (C-7Ј**), 30.53 (C-3), 62.11 (C-6), 66.14 (C-1Ј), 77.00 (C-

3Ј), 80.69 (C-4Ј), 82.58 (C-10Ј), 98.55 (C-2), 107.67 (C-9Ј) ppm.

C₂₁H₃₆O₂Si (348.6).

R (pentane/Et O, 10:1) = 0.25. IR (film): ν = 3951, 2857, 2172

˜

f

2

(CϵC), 1738 (C=O), 1625, 1435, 1248, 1199, 838, 775, 680 cm^–1.

¹H NMR (250 MHz, C₆D₆): δ = 0.19 [s, 6 H, Si(CH₃)₂], 1.08 [s, 9

H, C(CH₃)₃], 1.45 (m, 4 H, 10, 11-H), 2.02 (m, 4 H, 5-H, CH₂),

2.23 (m, 2 H, CH₂), 2.52 (m, 2 H, CH₂), 3.27 (m, 2 H, 3-H), 3.33

2

(s, 6 H, OCH₃), 5.28 (m, 1 H, 1-H), 5.31 (d, J = 1.70 Hz, 1 H, 1-

10-Bromo-1-(tert-butyldimethylsilyl)deca-1,7-diyne (20): To a solu-

tion of triphenylphosphane (15.76 g, 60 mmol) in dichloromethane

(150 mL) was added bromine (9.60 g, 60 mmol) dropwise at –20 °C.

After stirring at –20 °C for 30 min, 2-[10Ј-(tert-butyldimethylsilyl)-

deca-3Ј,9Ј-diynyloxy]tetrahydro-2H-pyran (19) (9.40 g, 27 mmol)

was added to the colorless suspension of the triphenylphenylphos-

phane-bromine complex, and stirring was continued at room tem-

perature for 20 h. The reaction mixture was then diluted with water

(100 mL), the two layers were separated, and the aqueous layer was

extracted with dichloromethane (100 mL). The organic layer was

dried (MgSO₄), concentrated, and the resulting residue was puri-

fied by column chromatography (120 g of silica gel, column

5ϫ35 cm, pentane) to afford 7.07 g (80%) of 20 as a colorless li-

H) ppm. ¹³C NMR (62.9 MHz, C₆D₆): δ = –4.18 [2 Si(CH₃)₂], 14.79

(C-6), 16.75 [C(CH₃)₃], 18.51 (C-9), 19.57 (C-12), 26.33 [3

C(CH₃)₃], 27.79 (C-10*), 28.23 (C-11*), 31.86 (C-5), 43.60 (C-3),

52.24 (2 OCH₃), 56.76 (C-4), 79.09 (C-7**), 80.79 (C-8**), 82.84

(C-13), 108.11 (C-14), 122.06 (C-1), 127.43 (C-2), 170.40 (2 C=O)

ppm. MS (DCI, NH₃): m/z = 517/516/515/514 (26/100/26/92) [M +

NH₄⁺]. C₂₄H₃₇BrO₄Si (497.6): calcd. C 57.93, H 7.49; found C

57.50, H 7.41.

2-(3Ј,9Ј-Decadiynyl)-1,3-dioxolane (24): n-Butyllithium (12.5 mL,

18.7 mmol, 1.5  in hexane) was added dropwise at –78 °C to a

solution of 1,7-octadiyne (2.0 g, 18.8 mmol) in THF (40 mL). The

mixture was stirred for 30 min and to the resulting colorless suspen-

sion was added sequentially HMPA (3.3 mL, 18.8 mmol) and 2-

(1,3-dioxolan-2-yl)ethyl iodide (23) (4.5 g, 19.7 mmol). Stirring was

continued at –78 °C for 2 h and at room temperature for 14 h. The

reaction mixture was diluted with 150 mL of water, the two layers

were separated, and the aqueous layer was extracted with diethyl

ether (5 ϫ 50 mL). The combined organic phases were dried

(MgSO₄), concentrated, and the residue was purified by column

chromatography (70 g of silica gel, column 2.5ϫ50 cm, pentane/

Et₂O, 40:1) to afford 1.8 g (46%) of 24 as a colorless liquid. R_f

1

quid. R_f(PE/Et₂O, 20:1) = 0.50. H NMR (250 MHz, CDCl₃): δ =

0.05 [s, 6 H, Si(CH₃)₂], 0.90 [s, 9 H, C(CH₃)₃], 1.55 (m, 4 H, 4,5-

3

5

H), 2.1–2.3 (m, 4 H, 3,6-H), 2.68 (tt, J = 7.4, J = 2.4 Hz, 2 H, 9-

H), 3.39 (t, J = 7.4 Hz, 2 H, 10-H) ppm. ¹³C NMR (62.9 MHz,

3

CDCl₃): δ = –4.47 [2 Si(CH₃)₂], 16.50 [C(CH₃)₃], 18.15 [C-3,6],

23.30 (C-9), 26.05 [3 C(CH₃)₃], 27.63 (C-4*), 27.70 (C-5*), 30.32

(C-10), 77.21 (C-8), 82.06 (C-1), 82.71 (C-7), 107.51 (C-9) ppm.

MS (DCI, NH₃): m/z (%) = 347/346/345/344 (20/100/21/95) [M +

NH₄⁺]. C₁₆H₂₇BrSi (327.4).

(pentane/Et O, 40:1) ν = 0.16. IR (film): ν = 3287, 2944, 2863,

˜

2

Dimethyl 2-[10Ј-(tert-Butyldimethylsilyl)deca-3Ј,9Ј-diynyl]malonate

(21): Dimethyl malonate (3.17 g, 24 mmol) was added dropwise at

room temperature to a suspension of sodium hydride (0.63 g,

26 mmol, 60% oil suspension) in DMF (75 mL). The resulting clear

solution was transferred into a solution of 10-bromo-1-(tert-butyl-

dimethylsilyl)deca-1,7-diyne (20) (6.38 g, 19.5 mmol) in DMF

(35 mL). After stirring for 36 h, the reaction mixture was treated

with a saturated aqueous solution of ammonium chloride

(100 mL), the two layers were separated, and the aqueous layer was

extracted with diethyl ether (3ϫ50 mL). The combined organic

phases were dried (MgSO₄), concentrated, and the residue was

purified by column chromatography (100 g of silica gel, column

2.5ϫ50 cm, PE/Et₂O, 10:1) to afford 3.87 g (52%) of 21 as a color-

2712, 2657, 2116, 1434, 1412, 1330, 1147, 1127, 1072, 1045, 943,

1

898, 626 cm^–1. H NMR (250 MHz, CDCl₃): δ = 1.55–1.68 (m, 4

3

4

H, 6Ј,7Ј-H), 1.82 (dt, J = 4.8, J = 7.4, 2 H, 1Ј-H), 1.93 (t, J =

3

2.6 Hz, 1 H, 10Ј-H), 3.81–3.91 (m, 4 H, O-CH₂CH₂-O), 4.95 (t, J

= 4.8 Hz, 1 H, 2-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT):

δ = 13.68 (–, C-2Ј), 17.92 (–, C-5Ј*), 18.20 (–, C-8Ј*), 27.46 (–, C-

6Ј**), 27.88 (–, C-7Ј**), 33.30 (–, C-1Ј), 64.88 (–, O-CH₂CH₂-O),

68.34 (+, C-10Ј), 79.30 (C_quat, C-3Ј), 79.84 (C_quat, C-5Ј), 84.21

(C_quat, C-9Ј), 103.31 (+, C-2). MS (DCI, NH₃): m/z (%) = 430 (11)

[2 M + NH₄⁺], 224 (100) [M + NH₄⁺], 207 (6) [M + H⁺]. C₁₃H₁₈O₂

(206.1): calcd. C 75.69, H 8.75; found C 75.61, H 8.60.

2-Bromo-4-(tert-butyldimethylsilyloxy)tetradec-1-ene-7,13-diyne

(26): To a suspension of tin powder (2 g, 17.2 mmol) in diethyl ether

(16.6 mL) and water (6.5 mL) was added successively at room tem-

less oil. R (PE/Et O, 10:1) = 0.19. IR (film): ν = 2951, 2855, 2172,

˜

f

2

1737, 1635, 1250, 1155, 839, 776, 681 cm^–1. ¹H NMR (250 MHz,

CDCl₃): δ = 0.05 [s, 6 H, Si(CH₃)₂], 0.90 [s, 9 H, C(CH₃)₃], 1.55 perature, 2,3-dibromopropene (3.3 g, 16.6 mmol), 48% HBr (40

(m, 4 H, 6Ј, 7Ј-H), 2.05 (dt, ³J = 7.0, ³J = 7.0 Hz, 2 H, 1Ј-H), 2.10– drops) and 2-(3,9-decadiynyl)-1,3-dioxolane (24) (2.5 g,

3

2.28 (m, 6 H, 2Ј,5Ј,8Ј-H), 3.58 (t, J = 6.9 Hz, 1 H, 2-H), 3.72 (s, 12.2 mmol). The mixture was vigorously stirred at room tempera-

6 H, OCH₃) ppm. ¹³C NMR (62.9 MHz, CDCl₃): δ = –4.51 [2

ture for 5 d, then diluted with water (200 mL) and diethyl ether

6162

www.eurjoc.org

Eur. J. Org. Chem. 2008, 6152–6167

Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

(200 mL), and the aqueous layer was extracted thoroughly with

diethyl ether (12ϫ100 mL). The combined ether fractions were

dried (MgSO₄) and concentrated. The produced alcohol was imme-

diately purified by column chromatography (70 g of silica gel, col-

umn 2.5ϫ50 cm, employing a polarity gradient starting with 10:1

pentane/Et₂O to remove the starting material, then with 20:3 pen-

tane/Et₂O) to afford 1.8 g (52%) of 25 as a colorless oil. R_f(pen-

Si(CH₃)₂], 0.87 [s, 9 H, C(CH₃)₃], 1.52–1.73 (m, 6 H, 5, 6,11-H),

2.15–2.23 (m, 4 H, 7, 10-H), 2.35 (t, J = 6.8 Hz, 2 H, 4-H), 2.47–

3

2.57 (m, 2 H, 13-H), 3.75 (s, 3 H, COOCH₃), 4.06 (m, 1 H, 12-H),

2

5.43 (d, ²J = 1.5 Hz, 1 H, 15-H), 5.60 (d, J = 1.13 Hz, 1 H, 15-H)

ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = –4.62 [+,

Si(CH₃)₂], –4.40 [+, Si(CH₃)₂], 14.69 (–, C-10), 18.01 [C_quat

,

C(CH₃)₃], 18.15 (–, C-7), 18.23 (–, C-4), 25.82 [+, 3 C(CH₃)₃], 26.54

(–, C-6), 27.92 (–, C-5), 35.73 (–, C-11), 49.32 (–, C-13), 52.55 (+,

COOCH₃), 68.82 (+, C-12), 77.19 (C_quat, C-2), 79.61 (C_quat, C-9),

80.24 (C_quat, C-8), 89.35 (C_quat, C-3), 119.16 (–, C-15), 130.79

(C_quat, C-14), 154 (C_quat, COOCH₃) ppm. MS (DCI, NH₃): m/z

tane/Et O, 10:3) = 0.20. IR (film): ν = 3500, 3305, 2948, 2862, 2173,

˜

2

2116, 1719, 1631, 1432, 1330, 1120, 1070, 893, 842, 634 cm^–1. ¹H

NMR (250 MHz, CDCl₃): δ = 1.59–1.69 (m, 4 H, 10,11-H), 1.94

4

(t, J = 2.5 Hz, 1 H, 14-H), 2.07 (br. s, 1 H, OH), 2.15–2.24 (m, 4

3

H, 9, 12-H), 2.27–2.37 (m, 2 H, 6-H), 2.55 (d, J = 6.30 Hz, 2 H, (%) = 472/474 (90/100) [M + NH₄⁺], 457 (18) [M + H⁺], 394 (18)

2

3-H), 4.09 (m, 1 H, 4-H), 5.53 (d, J = 1.5 Hz, 1 H, 1-H), 5.69 (d,

²J = 0.87 Hz, 1 H, 1-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): δ = 15.33 (–, C-6), 17.94 (–, C-9), 18.21 (–, C-12), 27.49

(–, C-10*), 27.87 (–, C-11*), 35.11 (–, C-5), 49.12 (–, C-3), 68.31

(+, C-4), 68.41 (C_quat, C-14), 79.56 (C_quat, C-7), 80.67 (C_quat, C-8),

84.19 (C_quat, C-13), 119.60 (–, C-1), 130.44 (C_quat, C-2) ppm. MS

(DCI, NH₃): m/z (%) = 584 (6) [2 M + NH₄⁺], 301 (100) [M +

NH₄⁺].

[M – Br + NH₄⁺].

10-(1Ј,3Ј-Dioxolan-2Ј-yl)-1-phenyl-1,7-decacdiyne (28): 2-(3Ј,9Ј-De-

cadiynyl)-1,3-dioxolane (24) (1.5 g, 7.28 mmol) was added to a mix-

ture of dichlorobis(triphenylphosphane)palladium (30 mg,

0.042 mmol) [PdCl₂(PPh₃)₂], cuprous iodide (20 mg, 0.1 mmol)

(CuI), triphenylphosphane (40 mg, 0.15 mmol), iodobenzene (1.5 g,

7.30 mmol) and triethylamine (50 mL)(Et₃N). The reaction mixture

was stirred at 40 °C for 14 h, during which a substantial amount

tert-Butyldimethylsilyl chloride (1.2 g, 8 mmol) was added at 55 °C of a colorless solid was formed. The reaction was then quenched

to a solution of freshly prepared 2-bromotetradec-1-ene-7,13-diyn-

4-ol (25) (1.6 g, 5.67 mmol) and imidazole (1.3 g, 19.84 mmol) in

DMF (20 mL). After stirring at 55 °C for 12 h, the reaction mixture

was poured into water (100 mL) and the aqueous mixture was ex-

tracted with diethyl ether (3ϫ50 mL). The combined ether layers

were dried with MgSO₄, and concentrated. The residue was puri-

fied by column chromatography (50 g of silica gel, column

2.5ϫ35 cm, pentane/Et₂O, 80:1) to afford 2 g (89%) of 26 as a

by addition of a saturated solution of ammonium chloride to the

mixture, and the whole mixture was extracted with diethyl ether

(5ϫ50 mL). The combined ether layers were concentrated, and the

residue was purified by column chromatography (70 g of silica gel,

column 2.5ϫ40 cm, pentane/Et₂O, 20:1) to afford 1.3 g (63%) of

28 as a colorless liquid. IR (film): ν = 3056, 2942, 2861, 2837, 2230,

˜

1951, 1877, 1598, 1490, 1441, 1330, 1146, 1128, 1072, 1046, 943,

896, 758, 693, 525 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 1.61–

3

colorless oil. R (pentane/Et O, 80:1) = 0.71. IR (film): ν = 3311,

1.73 (m, 4 H, 4,5-H), 1.84 (dt, J = 4.8, J = 7.4 Hz, 2 H, 10-H),

2.17–2.33 (m, 4 H, 3,6-H), 2.42 (t, ³J = 6.7 Hz, 2 H, 9-H), 3.88–

3.96 (m, 4 H, O-CH₂CH₂-O), 4.95 (t, ³J = 4.7 Hz, 1 H, 2Ј-H),

7.24–7.41 (m, 5 H, phenyl-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃,

˜

f

2

2959, 2928, 2857, 1631, 1469, 1432, 1255, 1101, 1077, 1005, 836,

776, 628 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 0.087 [s, 6 H,

Si(CH₃)₂], 0.91 [s, 9 H, C(CH₃)₃], 1.52–1.74 (m, 6 H, 5, 10, 11-H),

1.93 (t, ⁴J = 2.6 Hz, 1 H, 14-H), 2.15–2.23 (m, 6 H, 6, 9, 12-H), DEPT): δ = 13.72 (–, C-9), 18.30 (–, C-6), 18.95 (–, C-3), 27.79

2.44–2.62 (m, 2 H, 3-H), 4.08 (m, 1 H, 4-H), 5.43 (d, ²J = 1.47 Hz, (–, C-5*), 28.11 (–, C-4*), 33.32 (–, C-10), 64.89 (–, O-CH₂CH₂-

1 H, 1-H), 5.60 (br. s, 1 H, 1-H) ppm. ¹³C NMR (62.9 MHz, O), 79.29 (C_quat, C-8), 80.00 (C_quat, C-7**), 80.76 (C_quat, C-1**),

CDCl₃, DEPT): δ = 4.62 [+, Si(CH₃)₂], - 4.40 [+, Si(CH₃)₂], 14.71

89.90 (C_quat, C-2), 103.33 (+, C-2Ј), 123.92 (C_quat, phenyl-C),

(–, C-6), 17.96 (–, C-9), 18.01 [C_quat, C(CH₃)₃], 18.22 (–, C-12), 127.48 (+, o-phenyl-C), 128.14 (+, m-phenyl-C), 131.50 (+, p-

25.74 [+, 3 C(CH₃)₃], 27.51 (–, C-10*), 27.95 (–, C-11*), 35.76 (–,

C-5), 49.32 (–, C-3), 68.35 (C_quat, C-14), 68.82 (+, C-4), 79.93

phenyl-C) ppm. MS (DCI, NH₃): m/z (%) = 582 (2) [2 M + NH₄⁺],

300 (100) [M + NH₄⁺], 283 (6) [M + H⁺]. C₁₉H₂₂O₂(282.2): calcd.

(C_quat, C-7), 80.00 (C_quat, C-8), 84.21 (C_quat, C-13), 119.11 (–, C- C 80.82, H 7.85; found C 80.56, H 7.62.

1), 130.82 (C_quat, C-2) ppm. MS (DCI, NH₃): m/z (%) = 416 (100)

[M + NH₄⁺], 399 (2) [M + H⁺], 336 (1) [M – Br + NH₄⁺].

C₂₀H₃₃BrOSi (397.2): calcd. C 60.44, H 8.37; found C 60.27, H

8.11.

1-[13-Bromo-11-(tert-butyldimethylsilyloxy)tetradec-13-ene-1,7-di-

ynyl]benzene (29): To a suspension of tin powder (0.73 g, 6.1 mmol)

in a mixture of diethyl ether (8.7 mL) and water (3.5 mL) was

added successively 2,3-dibromopropene (1.2 g, 6.1 mmol), 48%

HBr (40 drops) and 10-(1Ј,3Ј-dioxolan-2Ј-yl)-1-phenyl-1,7-deca-

Methyl 14-Bromo-12-(tert-butyldimethylsilyloxy)-14-pentadec-14-

ene-2,8-diynoate (27): Following the same procedure as for the diyne (28) (1.1 g, 3.9 mmol). The mixture was vigorously stirred at

preparation of 16, a solution of LDA (4.2 mmol) in THF (10 mL)

[prepared by dropwise addition, at –78 °C, of diisopropylamine

(0.42 g, 4.2 mmol) to a solution of n-butyllithium (2.8 mL,

room temperature for 5 d, then diluted with water (150 mL) and

diethyl ether (150 mL), and the aqueous phase was extracted thor-

oughly with diethyl ether (10ϫ100 mL). The combined ether layers

4.2 mmol, 1.56  in hexane) in THF (10 mL) and stirring for were dried with MgSO₄, and concentrated. The produced alcohol

30 min] was added dropwise, at –78 °C, to a solution of 2-bromo-

4-(tert-butyldimethylsilyloxy)tetradec-1-ene-7,13-diyne (26) (1.5 g,

was immediately purified by column chromatography [50 g of silica

gel, column 2.5ϫ40 cm, eluting with pentane/Et₂O (10:1) until the

3.8 mmol) in THF (10 mL). After stirring for 30 min, HMPA starting material had been removed and then raising the polarity

(0.7 mL, 3.9 mmol) and methyl chloroformate (2.9 mL, 37 mmol) to (20:3) to elute the product] to give 1.0 g (70%) of 2-bromo-14-

were added, stirring was continued at –78 °C for 1 h, then at room

temperature for 2 h. After work-up as described for 16, the re-

sulting residue was purified by column chromatography (60 g of

silica gel, column 2.5ϫ35 cm, pentane/Et₂O, 40:1) to afford 0.7 g

(40%) of 27 as a colorless oil. R_f(pentane/Et₂O, 20:1) = 0.33. IR

phenyltetradec-1-ene-7,13-diyn-4-ol as a colorless oil. R_f(pentane/

Et O, 20:3) = 0.18. IR (film): ν = 3500, 3079, 3056, 2948, 2901,

˜

2

2838, 2228, 1949, 1876, 1631, 1490, 1439, 1331, 1121, 1068, 913,

891, 758, 693 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 1.62–1.72

(m, 6 H, 5, 10, 11-H), 2.08 (s, 1 H, OH), 2.22 (m, 2 H, 12-H), 2.33

2

(film): ν = 2950, 2928, 2843, 2173, 1750, 1250, 1073, 941, 823, (m, 2 H, 9-H), 2.43 (m, 2 H, 6-H), 2.55 (d, J = 6.25 Hz, 2 H, 3-

˜

764 cm^–1

.

¹H NMR (250 MHz, CDCl₃): δ = 0.09 [s, 6 H, H), 4.10 (m, 1 H, 4-H), 5.53 (d, ²J = 1.5 Hz, 1 H, 1-H), 5.69 (d, ²J =

Eur. J. Org. Chem. 2008, 6152–6167

www.eurjoc.org

6163

A. de Meijere et al.

FULL PAPER

0.85 Hz, 1 H, 1-H), 7.24–7.41 (m, 5 H, phenyl-H) ppm. ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): δ = 15.37 (–, C-6), 18.30 (–, C-9), 18.97

(–, C-12), 27.81 (–, C-10*), 28.09 (–, C-11*), 35.09 (–, C-5), 49.11

of LDA (9.1 mmol) in THF (15 mL) [prepared by dropwise ad-

dition, at –78 °C, of diisopropylamine (0.92 g, 9.1 mmol) to a solu-

tion of n-butyllithium (4.5 mL, 9 mmol, 2  in hexane) in THF

(–, C-3), 68.38 (+, C-4), 79.55 (C_quat, C-7), 80.10 (C_quat, C-8**) (15 mL) and stirring for 30 min] was added dropwise at –78 °C to

80.84 (C_quat, C-14**), 89.85 (C_quat, C-13), 119.64 (–, C-1), 123.90 a solution of 2Ј-bromoallyl 3,9-decadiynyl ether (30) (2.3 g,

(C_quat, phenyl-C), 127.50 (+, o-phenyl-C), 128.15 (+, m-phenyl-C),

8.5 mmol) in THF (15 mL). After stirring for 30 min, HMPA

130.42 (C_quat, C-2), 131.51 (+, p-phenyl-C) ppm. MS (DCI, NH₃): (1.5 mL, 8.2 mmol) and methyl chloroformate (6.4 mL, 81.6 mmol)

m/z (%) = 736 (1) [2 M + NH₄⁺], 376/378 (100/98) [M + NH₄⁺], were added and stirring was continued at –78 °C for 1 h, then at

298 (11) [M – Br + NH₄⁺].

room temperature for 2 h. After work-up as described for 16, the

resulting residue was purified by column chromatography (80 g of

silica gel, column 2.5ϫ40 cm, pentane/Et₂O, 10:1) to afford 1.9 g

(68%) of 31 as a colorless oil. R_f(pentane/Et₂O, 20:1) = 0.12. IR

Following the same procedure as applied for the preparation of

26, tert-butyldimethylsilyl chloride (0.5 g, 3.33 mmol) was added at

55 °C to a solution of the freshly prepared 2-bromo-14-phenyltetra-

dec-1-ene-7,13-diyn-4-ol (1 g, 2.77 mmol) and imidazole (0.65 g,

9.8 mmol) in DMF (10 mL). After stirring at 55 °C for 12 h, the

reaction mixture was poured into water (70 mL), and the aqueous

mixture was extracted with diethyl ether (3ϫ40 mL). The com-

bined ether layers were dried with MgSO₄and concentrated. The

residue was purified by column chromatography (50 g of silica gel,

column 2.5ϫ40 cm, pentane/Et₂O, 80:1) to afford 1.1 g (82%) of

(film): ν = 3409, 3305, 2954, 2866, 2235, 1719, 1639, 1434, 1251,

˜

1

1109, 1078, 894, 752, 670 cm^–1. H NMR (250 MHz, CDCl₃): δ =

3

1.56–1.72 (m, 4 H, 5,6-H), 2.15–2.21 (m, 2 H, 7 H), 2.35 (t, J =

6.83 Hz, 2 H, 4-H), 2.41–2.49 (m, 2 H, 10-H), 3.55 (t, ³J = 6.91 Hz,

2

4

11-H), 3.75 (s, 3 H, COOCH₃), 4.12 (dd, J = 2.26, J = 1.05 Hz,

2

4

2 H, 1Ј-H), 5.61 (dd, J = 1.75 Hz, J = 0.95 Hz, 1 H, 3Ј-H), 5.94

(dd, ²J = 2.69 Hz, ⁴J = 1.28 Hz, 1 H, 3Ј-H) ppm. ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): δ = 18.16 (–, C-7*), 18.21 (–, C-4*),

20.09 (–, C-10), 26.52 (–, C-6), 27.76 (–, C-5), 52.52 (+, COOCH₃),

29 as a colorless oil. R (pentane/Et O, 80:1) = 0.63. IR (film): ν =

˜

f

2

3081, 3053, 2957, 2928, 2856, 2232, 1631, 1490, 1434, 1362, 1255,

69.02 (–, C-11), 74.84 (–, C-1Ј), 77.08 (C_quat, C-2**), 77.17 (C_quat

,

1075, 1005, 890, 836, 777, 755, 692 cm^–^{1 1}H NMR (250 MHz,

.

C-9**), 80.58 (C_quat, C-8), 89.28 (C_quat, C-3), 117.37(–, C-3Ј),

129.33 (C_quat, C-2Ј), 159.94 (C_quat, COOCH₃) ppm. MS (DCI,

NH₃): m/z (%) = 344/346 (98/100) [M – H + NH₄⁺].

CDCl₃): δ = 0.095 [s, 6 H, Si(CH₃)₂], 0.88 [s, 9 H, C(CH₃)₃], 1.67–

1.72 (m, 6 H, 4, 5,10-H), 2.22 (m, 4 H, 3,6-H), 2.40–2.47 (m, 2 H,

9-H), 2.51–2.57 (dd, ²J = 6.4, J = 4 Hz, 2 H, 12-H), 4.10 (m, 1 H,

2

11-H), 5.43 (d, J = 1.3 Hz, 1 H, 14-H), 5.61 (d, J = 1.3 Hz, 1 H,

14-H), 7.24–7.41 (m, 5 H, phenyl-H) ppm. ¹³C NMR (62.9 MHz,

CDCl₃, DEPT): δ = –4.60 [+, Si(CH₃)₂], –4.40 [+, Si(CH₃)₂], 14.74

(–, C-9), 18.022 [C_quat, C(CH₃)₃], 18.32 (–, C-6), 18.99 (–, C-3),

25.84 [+, 3 C(CH₃)₃], 27.83 (–, C-5*), 28.18 (–, C-4*), 35.78 (–, C-

Diethyl 8-(1-Ethyl-1-hydroxypropyl)-13-methoxytricyclo[7.4.0. 0^2,6]-

trideca-1(9),2(6),7-triene-4,4-dicarboxylate (35b): According to GP

method A, diethyl 2-bromo-14-ethyl-14-hydroxy-8-methoxyhexa-

dec-1-ene-6,12-diyne-4,4-dicarboxylate (10b) (350 mg, 0.68 mmol)

was added to a mixture of palladium acetate (9 mg, 0.04 mmol,

6 mol-%), triphenylphosphane (36 mg, 0.14 mmol, 20 mol-%) and

potassium carbonate (189 mg, 1.36 mmol, 2 equiv.) in acetonitrile

(10 mL). The mixture was heated at 120 °C for 2 h and the resulting

residue after work-up was purified by column chromatography (8 g

of flash silica gel, column 1ϫ15 cm, PE/Et₂O, 2:1) to give 197 mg

of 35b (67%) as a light brown oil. R_f(PE/Et₂O, 2:1) = 0.42. IR

10), 49.34 (–, C-12), 68.83 (–, C-10), 79.92 (C_quat, C-8), 80.13 (C_quat

,

C-7**), 80.78 (C_quat, C-1**), 89.88 (C_quat, C-2), 119.12 (–, C-14),

123.94 (C_quat, phenyl-C), 127.48 (+, o-phenyl-C), 128.14 (+, m-

phenyl-C), 130.83 (C_quat, C-13), 131.51 (+, p-phenyl-C) ppm. MS

(DCI, NH₃): m/z (%) = 490/492 (88/100) [M + NH₄⁺], 412 (20)

[M – Br + NH₄⁺].

(film): ν = 3550 (OH), 2940, 1720 (C=O), 1450, 1245, 1190, 1095,

˜

2Ј-Bromoallyl 3,9-Decadiynyl Ether (30): 3,9-Decadiyn-1-ol (12)

(3.8 g, 25.25 mmol) was added dropwise at 70 °C to a suspension

of sodium hydride (1.5 g, 38 mmol, 60% oil suspension) in THF

(60 mL). 2,3-Dibromopropene (7.6 g, 38 mmol) was added, and the

resulting mixture was heated at reflux at 70 °C for 12 h. After cool-

ing to ambient temperatue, the reaction mixture was diluted with

a saturated solution of ammonium chloride (80 mL) and extracted

with diethyl ether (4 ϫ40 mL). The combined ether layers were

dried (MgSO₄) and concentrated. The residue was purified by col-

umn chromatography (100 g of silica gel, column 2.5ϫ60 cm, pen-

tane/Et₂O, 20:1) to afford 2.9 g (42%) of 30 as a colorless oil. R_f

910, 875 cm^–1. ¹H NMR (250 MHz, CDCl₃): δ = 0.65 (m, ³J =

7.0 Hz, 6 H, CH₂CH₃), 1.16 (m, ³J = 7.1 Hz, 6 H, OCH₂CH₃),

1.51–2.11 (m, 8 H, 2 CH₂CH₃, 11, 12-H), 2.51–2.61 (m, 1 H, 10-

H), 2.96–3.03 (m, 1 H, 10-H), 3.33 (s, 3 H, OCH₃), 3.43–3.58 (m,

4 H, 3,5-H), 4.05–4.17 (m, 4 H, OCH₂CH₃), 4.23 (br. s, 1 H, 13-H),

7.26 (br. s, 1 H, 7-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ

= 7.9 (+, CH₂CH₃), 8.0 (+, CH₂CH₃), 13.7 (+, OCH₂CH₃), 18.4

(–, C-7), 25.9 (–, C-8*), 28.2 (–, C-6*), 33.1 (–, 2 CH₂CH₃), 39.2 (–,

C-3), 40.4 (–, C-5), 55.5 (+, OCH₃), 60.0 (C_quat, C-4), 61.3 (–,

OCH₂CH₃), 75.0 (+, C-13), 78.6 (C_quat, COH), 122.6 (+, C-7),

132.5 (C_quat, C-2), 134.2 (C_quat, C-9), 136.9 (C_quat, C-1), 139.1

(pentane/Et O, 10:1) = 0.40. IR (film): ν = 3304, 2948, 2907, 2864,

˜

2

(C_quat, C-6), 141.5 (C_quat, C-8), 171.4 (C_quat, C=O), 171.8 (C_quat

,

2116, 1735, 1640, 1434, 1333, 1110, 895, 638 cm^–1

.

¹H NMR

C=O) ppm. MS (EI, 70 eV): m/z (%) = 403 (39) [M⁺– CH₂CH₃],

400 (20), 371 (39), 309 (22), 108 (22), 86 (26), 79 (27), 57 (100).

C₂₅H₃₆O₆(432.2).

4

(250 MHz, CDCl₃): δ = 1.57–1.65 [m, 4 H, 6 (7)-H], 1.94 (t, J =

2.69 Hz, 1 H, 10-H), 2.15–2.23 (m, 4 H, 5,8-H), 2.43–2.49 (m, 2 H,

2-H), 3.56 (t, ³J = 7.00 Hz, 2 H, 1-H), 4.12 (s, 2 H, 1Ј-H), 5.61 (dd,

²J = 1.75, J = 0.64 Hz, 1 H, 3Ј-H), 5.95 (d, J = 1.36 Hz, 1 H, 3Ј-

H) ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 17.93 (–, C-

5*), 18.02 (–, C-8*), 20.10 (–, C-2), 27.47 (–, C-6**), 27.79 (–, C-

4

2

4,4-Diethyl 8-Methyl 13-Methoxytricyclo[7,4.0.0^2,6]trideca-

1(9),2(6),7-triene-4,4,8-tricarboxylate (35a): According to GP

method A, 10,10-diethyl 1-methyl 12-bromo-6-methoxytridec-12-

ene-1,7-diyne-1,10,10-tricarboxylate (10a) (400 mg, 0.82 mmol) was

added to a mixture of palladium acetate (6 mg, 0.026 mmol, 3 mol-

%), triphenylphosphane (26 mg, 0.10 mmol, 12 mol-%) and potas-

sium carbonate (229 mg, 1.64 mmol, 2 equiv.) in acetonitrile

(10 mL). After heating the mixture at 120 °C for 14 h and work-up

as described in GP method A, the resulting residue was purified by

column chromatography (50 g of flash silica gel, column

7**), 68.36 (+, C-10), 69.07 (–, C-1), 74.83 (–, C-1Ј), 76.76 (C_quat

,

C-3), 80.97 (C_quat, C-4), 84.17 (C_quat, C-9), 117.34 (–, C-3Ј), 129.33

(C_quat, C-2Ј) ppm. MS (DCI, NH₃): m/z (%) = 286/288 (100/98) [M

+ NH₄⁺]. C₁₃H₁₇BrO (269.2): calcd. C 58.01, H 6.37; found C

58.32, H 6.25.

Methyl 11-(2Ј-Bromoallyloxy)-2,8-undecadiynoate (31): Following

the same procedure as applied for the preparation of 16, a solution

6164

www.eurjoc.org

Eur. J. Org. Chem. 2008, 6152–6167

Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

3

2.5ϫ20 cm, PE/Et₂O, 4:1) to give 202 mg (61%) of 35a as a color-

1.92 (m, 3 H, 11,14-H), 2.10 (m, 1 H, 14-H), 2.56 (t, J = 10 Hz, 2

less oil. R (PE/Et O, 1:1) = 0.35. IR (film): ν = 2940, 1730 (C=O), H, 4-H), 2.58–2.74 (m, 2 H, 13-H), 2.74–2.88 (m, 3 H, 6,12-H),

˜

f

2

1580 (C=C), 1440, 1375, 1080, 1020, 920, 870, 790 cm^–1. H NMR

2.96 (dd, ²J = 4, ³J = 15 Hz, 1 H, 6-H), 4.08 (m, 1 H, 5-H), 6.84 (s,

1 H, 8-H), 7.25–7.40 (m, 5 H, Ph-H) ppm. ¹³C NMR (150.82 MHz,

1

(250 MHz, CDCl₃): δ = 1.22 (m, 6 H, OCH₂CH₃), 1.50–1.85 (m, 3

H, 11, 12-H), 2.10–2.27 (m, 1 H, 12-H), 2.70–2.90 (m, 1 H, 10-H), CDCl₃, APT): δ = –4.62 [+, Si(CH₃)₂], –4.59 [+, Si(CH₃)₂], 18.30

3.10–3.25 (dt, ³J = 3.9, ²J = 18.1 Hz, 1 H, 10-H), 3.42 (s, 3 H, [–, C(CH₃)₃], 22.90 (–, C-3), 23.15 (–, C-11), 25.87 (–, C-12), 25.95

OCH₃), 3.43–3.62 (m, 4 H, 3,5-H), 3.81 (s, 3 H, COOCH₃), 4.12– [+, 3 C(CH₃)₃], 27.02 (–, C-13), 28.83 (–, C-4), 32.60 (–, C-14),

3

4.25 (m, 4 H, 2 OCH₂CH₃), 4.28 (t, J = 3.6 Hz, 1 H, 13-H), 7.64

39.55 (–, C-6), 68.13 (+, C-5), 126.53 (+, Ph-C), 127.91 (+, Ph-C),

128.12 (+, Ph-C), 128.44 (+, Ph-C), 128.49 (+, Ph-C), 128.52 (+,

(s, 1 H, 7-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = 13.9

(+, OCH₂CH₃), 17.6 (–, C-11), 25.5 (–, C-12), 27.9 (–, C-10), 39.4 Ph-C), 128.73 (+, Ph-C), 129.27 (+, C-8), 132.22 (–, C-1), 132.37

(–, C-3), 40.0 (–, C-5), 51.5 (+, OCH₃), 55.8 (+, COOCH₃), 60.2 (–, C-2), 133.53 (–, C-7), 133.66 (+, Ph-C), 133.78 (+, Ph-C), 135.22

(C_quat, C-4), 61.6 (+, OCH₂CH₃), 74.3 (+, C-13), 125.6 (+, C-7), (–, C-10), 139.95 (–, Ph-C), 142.06 (–, C-9) ppm. MS (DCI, NH₃):

129.0 (C_quat, C-8), 133.3 (C_quat, C-1), 137.5 (C_quat, C-9*), 138.2 m/z (%) = 410 (100) [M + NH₄⁺], 495 (26) [(M – CH₃) + NH₄⁺],

(C_quat, C-6*), 145.3 (C_quat, C-2), 168.1 (C_quat, COOCH₃), 171.1 352 (7) [M + H – C(CH₃)₃+ NH₄⁺], 296 (12) [(M – tBuMe₂Si) +

(C_quat, COOCH₂CH₃), 171.6 (C_quat, COOCH₂CH₃) ppm. MS (EI, NH₄⁺], 279 (16) [M – H – tBuMe₂SiO + NH₄⁺], 263 (27).

70 eV): m/z (%) = 404 (0.2) [M⁺], 388 (1), 373 (4) [M⁺– OCH₃], C₂₆H₃₆OSi (392.6): calcd. C 79.53, H 9.24; found C 79.41, H 9.08.

299 (28), 167 (13), 165 (12), 140 (26), 112 (11), 110 (14), 91 (20),

45 (24), 44 (100). HRMS: calcd. for C₂₂H₂₈O₇404.183506 (correct

mass).

Trimethyl Tetracyclo[8.4.0.0^1,3.0^4,9]tetradeca-4,9-diene-3,6,6-tricarb-

oxylate (38): Following GP method A, palladium acetate (150 mg,

0.66 mmol) was added at 60 °C to a degassed mixture of tri-

Dimethyl 9-[tert-Butyl(dimethyl)silyl]tricyclo[8.4.0.0^2,7]tetradeca-

phenylphosphane (430 mg, 1.64 mmol), of potassium carbonate

1,7,9-triene-5,5-dicarboxylate (36): According to GP method A, di-

(2.72 g, 19.7 mmol), trimethyl 13-bromo-13-tetradecene-1,7-diyne-

methyl 2-bromo-14-(tert-butyldimethylsilyl)-1-tetradecen-7,13-di-

1,11,11-tricarboxylate (16) (2.9 g, 6.59 mmol) and acetonitrile

yne-4,4-dicarboxylate (22) (249 mg, 0.50 mmol) was added to a

(100 mL). After stirring the reaction mixture at 60 °C for 20 h and

mixture of palladium acetate (11 mg, 0.05 mmol, 10 mol-%), tri-

work-up as described in the GP, the residue was purified by column

phenylphosphane (33 mg, 0.13 mmol, 25 mol-%) and potassium

chromatography (60 g of silica gel, column 2 ϫ30 cm, pentane/

carbonate (207 mg, 1.5 mmol, 3 equiv.) in acetonitrile (5 mL). After

Et₂O, 4:1) to afford 1.3 g (54%) of 38 as an orange oil. R_f(pentane/

heating the reaction mixture at 60 °C for 20 h and work-up as de-

Et O, 4:1) = 0.17. IR (film): ν = 2996, 2954, 2855, 1755, 1715, 1433,

˜

2

scribed in the GP, the resulting residue was purified by column

chromatography (20 g of flash silica gel, column 2ϫ35 cm, hexane/

Et₂O, 10:1) to give 163 mg (79%) of 36 as a colorless oil. R_f(PE/

1302, 1226, 1197, 1154, 1076, 1062, 851, 833, 735, 702 cm^–1. ¹H

NMR (250 MHz, CDCl₃): δ = 1.07 (d, ²J = 2.9 Hz, 1 H, 2-H), 1.24

2

3

(m, 1 H, 12-H), 1.46–1.56 (m, 1 H, 12-H), 1.68 (dt, J = 2.8, J =

15 Hz, 1 H, 14-H), 1.8–1.89 (m, 2 H, 11, 14-H), 1.95 (d, ²J =

3.0 Hz, 1 H, 2-H), 2.00–2.37 (m, 4 H, 7,8,13-H), 2.40–2.61 (m, 3

H, 8, 11, 13-H), 3.70 (s, 3 H, COOCH₃), 3.72 (s, 3 H, COOCH₃),

3.75 (s, 3 H, COOCH₃), 6.09 (s, 1 H, 5-H) ppm. ¹³C NMR

(62.9 MHz, CDCl₃, DEPT): δ = 19.15 (–, C-8), 24.82 (–, C-12),

24.93 (–, C-11), 25.36 (–, C-13), 27.98 (–, C-14), 28.70 (–, C-7),

36.65 (C_quat, C-3), 39.29 (–, C-2), 45.88 (C_quat, C-1), 51.80 (+, CO-

OCH₃), 52.68 (+, COOCH₃), 52.82 (+, COOCH₃), 55.28 (C_quat, C-

6), 115.88 (+, C-5), 126.03 (C_quat, C-9), 143.53 (C_quat, C-4), 144.75

(C_quat, C-10), 170.96 (C_quat, COOCH₃), 171.35 (C_quat, COOCH₃),

171.72 (C_quat, COOCH₃) ppm. MS (EI, 70 eV): m/z (%) = 360 (10)

[M⁺], 328 (24) [M⁺– CH₃OH], 301 (30) [M⁺– COOCH₃], 269 (46)

[M⁺– CH₃OH – COOCH₃], 241 (39), 209 (20), 159 (30), 115 (72),

74 (79), 59 (100), 45 (64), 43 (27). C₂₀H₂₄O₆(360.4): calcd. C 66.65,

H 6.43; found C 66.76, H 6.43.

Et O, 10:1) = 0.15. IR (film): ν = 2978, 2868, 1741 (C=O), 1638,

˜

2

1444, 1383, 1351, 1277, 1044, 935, 846 cm^–1. HNMR (250 MHz,

1

CDCl₃): δ = 0.50 [m, 6 H, Si(CH₃)₂], 1.07 [s, 9 H, C(CH₃)₃], 1.95

(m, 4 H, 12, 13-H), 2.53 (t, ³J = 6.6 Hz, 2 H, 4-H), 2.74 (t, ³J =

3

6.0 Hz, 2 H, 11-H), 2.83 (t, J = 6.6 Hz, 2 H, 3-H), 3.00 (t, J =

6.0 Hz, 2 H, 14-H), 3.47 (s, 2 H, 6-H), 3.91 (s, 6 H, OCH₃), 7.08

(s, 1 H, 8-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃, DEPT): δ = –2.61

[+, 2 Si(CH₃)₂], 17.97 [C_quat, C(CH₃)₃], 22.85 (–, C-12*), 23.00 (–,

C-13*), 23.37 (–, C-3), 26.73 (–, C-11), 27.00 [+, 3 C(CH₃)₃], 28.21

(–, C-4), 32.08 (–, C-14), 35.14 (–, C-6), 52.64 (+, 2 OCH₃), 53.10

(C_quat, C-5), 129.07 (C_quat), 133.62 (C_quat), 133.94 (C_quat), 134.31

(C_quat), 134.47 (+, C-8), 141.13 (C_quat), 171.81 (C_quat, 2 C=O) ppm.

MS (DCI, NH₃): m/z (%) = 850 (17) [2 M + NH₄⁺], 434 (100) [M

+ NH₄⁺]. C₂₄H₃₆O₄Si (416.6): calcd. C 69.16, H 8.71; found C

69.51, H 8.97.

5-(tert-Butyldimethylsilyloxy)-9-phenyltricyclo[8.4.0.0^2,7]tetradeca-

1,7,9-triene (37): Following GP method B, palladium acetate

(9.48 mg, 0.042 mmol) was added at 80 °C to a degassed mixture of

triphenylphosphane (28 mg, 0.10 mmol), sodium formate (34.4 mg,

0.50 mmol), 1-[13Ј-bromo-11Ј-(tert-butyldimethylsilyloxy)-13Ј-

tetradecene-1Ј,7Ј-diynyl]benzene (29) (200 mg, 0.42 mmol) and

DMF (5 mL). After stirring at 80 °C for 5 h, the reaction mixture

was poured into water (30 mL), and the aqueous mixture was ex-

tracted with diethyl ether (3ϫ20 mL). The combined ether layers

were dried (MgSO₄), concentrated, and the residue was purified

by thick-layer chromatography using 20ϫ20 cm plates coated with

silica gel, type 60 PF₂₅₄containing CaSO₄, eluting with pentane/

dichloromethane, 2:1. The third fraction from the top of the plates

afforded 25 mg (15%) of 37 as a yellow oil. R_f(pentane/dichloro-

Methyl 13-(tert-Butyldimethylsilyloxy)tetracyclo[8.4.0.0^1,3.0^4,9]-

tetradeca-4,9-diene-3-carboxylate (39): Following GP method A,

palladium acetate (9.8 mg, 0.050 mmol) was added at 60 °C to a

degassed mixture of triphenylphosphane (29 mg, 0.11 mmol), po-

tassium carbonate (182.6 mg, 1.3 mmol), methyl-14-bromo-12-

(tert-butyldimethylsilyloxy)-14-pentadecene-2,8-diynoate (27)

(200 mg, 0.44 mmol) and acetonitrile (5 mL). After heating the

mixture at 60 °C for 18 h and work-up as described in the GP, the

residue was purified by thick-layer chromatography using

20ϫ20 cm plates coated with silica gel, type 60 PF₂₅₄containing

CaSO₄. The plates were developed twice, first eluting with pentane/

dichloromethane, 2:1, then with pentane/Et₂O, 10:1. The first frac-

tion from the top of the plates afforded 32 mg (19%) of 2:1 of a

mixture of diastereomers of 39 as a colorless oil. R_f(pentane/Et₂O,

methane, 2:1) = 0.55. IR (film): ν = 3057, 2927, 2856, 1462, 1251,

˜

1095, 882, 773 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.12 [s, 6

H, Si(CH₃)₂], 0.94 [s, 9 H, C(CH₃)₃], 1.60–1.72 (m, 2 H, 3-H), 1.76–

5:1) = 0.12. IR (film): ν = 2957, 2854, 2240, 1734, 1437, 1255, 1202,

˜

835, 777, 736 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 0.04 [s, 6 H,

Eur. J. Org. Chem. 2008, 6152–6167

www.eurjoc.org

6165

A. de Meijere et al.

FULL PAPER

Si(CH₃)₂], 0.88 [s, 9 H, C(CH₃)₃], 1.03 (d, J = 3.1 Hz, 1 H, 2-H),

2

Acknowledgments

3

1.40 (m, 1 H, 14-H), 1.54–1.72 (m, 1 H, 7-H), 1.74 (t, J = 4 Hz, 1

H, 8-H), 1.80 (m, 3 H, 10, 14-H), 1.90 (d, ²J = 3.15 Hz, 1 H, 2-H),

2.00 (m, 1 H, 8-H), 2.10 (m, 1 H, 6-H), 2.20–2.34 (m, 3 H, 6, 7,

11-H), 2.50 (d, ³J = 5 Hz, 1 H, 11-H), 3.70 (s, 3 H, COOCH₃), 4.24

This work profited from financial support by the Land Nieder-

sachsen. BASF AG, Bayer AG and Chemetall GmbH generously

provided chemicals. The authors are grateful to Stefan Beus-

shausen, Göttingen, for technical help in the preparation of the

final manuscript.

(br. s, 1 H, 13-H), 5.88 (t, J = 5.5 Hz, 1 H, 5-H) ppm. ¹³C NMR

3

(125.705 MHz, CDCl₃, APT): δ = –4.88 [+, 2 Si(CH₃)₂], 17.99 [–,

C(CH₃)₃], 19.10 (–, C-11), 22.46 (–, C-7), 22.65 (–, C-8), 25.43 (–,

C-6), 25.75 [+, 3 C(CH₃)₃], 31.68 (–, C-14), 34.82 (–, C-12), 35.53

(–, C-3), 38.77 (–, C-2), 43.37 (–, C-1), 51.63 (+, COOCH₃), 66.77

(+, C-13), 120.52 (+, C-5), 128.21 (–, C-9), 139.45 (–, C-10), 142.12

(–, C-4), 171.92 (–, COOCH₃) ppm. MS (DCI, NH₃): m/z (%) =

392 (100) [M + NH₄⁺], 375 (70) [M + H⁺], 260 (8) [M⁺– tBu-

Me₂Si]. C₂₂H₃₄O₃Si (374.6): calcd. C 70.54, H 9.15; found C 70.42,

H 9.03.

[1] For comprehensive reviews see: a) Metal-Catalyzed Cross-

Coupling Reactions, 2^ndCompletely Revised Edition (Eds.: A. de

Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004; b) Hand-

book of Palladium Chemistry for Organic Synthesis (Eds: E. Ne-

gishi, A. de Meijere) Wiley, New York, 2002.

[2] For examples of such metal-catalyzed processes see: a) Ruthe-

nium-catalyzed non-metathesis reactions: B. M. Trost, F. D.

Toste, A. B. Pinkerton, Chem. Rev. 2001, 101, 2067–2096; b)

Ruthenium-catalyzed metathesis reactions: T. M. Trenka,

R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18–29; c) Nickel-cata-

lyzed reactions: S. Ikeda, Acc. Chem. Res. 2000, 33, 511–519;

d) Cobalt-catalyzed reactions: K. C. Nicolaou, E. J. Sorensen

in Classics in Total Synthesis, Wiley-VCH, Weinheim, 1996, pp.

153–166; e) F. Slowinski, C. Aubert, M. Malacria, Eur. J. Org.

Chem. 2001, 3491–3500, and references cited therein.

Methyl 1,4,7,8,9,10-Hexahydro-2H-benzo[f]isochromene-6-carbox-

ylate (41) and Methyl 1,5,5a,7,8,9-Hexahydro-2H-cyclopropa[2,3]in-

deno[2,1-c]pyran-5a-carboxylate (40): Following GP method A, pal-

ladium acetate (34 mg, 0.15 mmol) was added to a mixture of tri-

phenylphosphane (99.8 mg, 0.38 mmol), potassium carbonate

(630 mg, 4.5 mmol), methyl 11-(2Ј-bromoallyloxy)-2,8-undeca-

diynoate (31) (500 mg, 1.5 mmol) and acetonitrile (30 mL). After

stirring the reaction mixture at 106 °C for 18 h and work-up as

described in the GP, the residue was purified by thick-layer

chromatography using 20ϫ20 cm plates coated with silica gel type

60 PF₂₅₄containing CaSO₄. The plates were eluted twice with pen-

tane/dichloromethane, 5:1, and once with pentane/Et₂O, (10:1) to

afford two fractions:

[3] a) L. F. Tietze, U. Beifuss, Angew. Chem. 1993, 105, 137–170;

Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163; b) L. F. Tietze,

Chem. Rev. 1996, 96, 115–136; c) L. F. Tietze, G. Brasche, K.

M. Gericke, Domino Reactions in Organic Synthesis, Wiley-

VCH, Weinheim, 2006.

[4] a) F. E. Meyer, P. J. Parsons, A. de Meijere, J. Org. Chem. 1991,

56, 6487–6488; b) F. E. Meyer, H. Henniges, A. de Meijere, Tet-

rahedron Lett. 1992, 33, 8039–8042; c) F. E. Meyer, J. Branden-

burg, P. J. Parsons, A. de Meijere, J. Chem. Soc., Chem. Com-

mun. 1992, 390–392; d) F. E. Meyer, K. H. Ang, A. G. Steinig,

A. de Meijere, Synlett 1994, 191–193; e) K. H. Ang, S. Bräse,

A. G. Steinig, F. E. Meyer, A. Llebaria, K. Voigt, A. de Mei-

jere, Tetrahedron 1996, 52, 11503–11528; f) S. Schweizer, Z.-Z.

Song, F. E. Meyer, P. J. Parsons, A. de Meijere, Angew. Chem.

1999, 111, 1550–1552; Angew. Chem. Int. Ed. 1999, 38, 1452–

1454; for reviews see: g) A. de Meijere, P. von Zezschwitz, S.

Bräse, Acc. Chem. Res. 2005, 38, 413–422; h) A. de Meijere, P.

von Zezschwitz, H. Nüske, B. Stulgies, J. Organomet. Chem.

2002, 653, 129–140; P. von Zezschwitz, A. de Meijere, Domino-

Heck Pericyclic Reactions in Top. Organomet. Chem. Springer,

Berlin 2006, pp. 49–89.

I: 35 mg (10%) of 41 as a colorless viscous oil. R_f(pentane/Et₂O,

5:1) = 0.23. IR (film): ν = 2938, 1719, 1430, 1292, 1202, 1184, 1155,

˜

1

1017, 925, 778 cm^–1. H NMR (500 MHz, CDCl₃): δ = 1.68–1.77

3

(m, 2 H, 8-H), 1.78–1.84 (m, 2 H, 9-H), 2.57 (t, J = 5.5 Hz, 2 H,

3

10-H), 2.64 (t, J = 5.6 Hz, 2 H, 1-H), 3.01 (t, J = 6 Hz, 2 H, 7-

3

H), 3.82 (s, 3 H, COOCH₃), 4.00 (t, J = 6.1 Hz, 2 H, 2-H), 4.71

(s, 2 H, 4-H), 7.34 (s, 1 H, 5-H) ppm. ¹³C NMR (62.9 MHz, CDCl₃,

DEPT): δ = 22.37 (–, C-9), 22.61 (–, C-8), 26.08 (–, C-1), 26.55

(–, C-10), 28.19 (–, C-7), 51.77 (+, COOCH₃), 65.21 (–, C-2), 67.97

(–, C-4), 123.86 (+, C-5), 127.77 (C_quat), 131.59 (C_quat), 136.00

(C_quat), 136.50 (C_quat), 136.60 (C_quat), 168.42 (C_quat, COOCH₃)

ppm. MS (EI, 70 eV): m/z (%) = 246 (100) [M⁺], 231 (21) [M⁺

–

CH₃], 214 (88) [M⁺– OCH₃], 187 (77) [M⁺– COOCH₃], 159 (36),

157 (19) [M⁺– COOCH₃– H₂C=O], 141 (17), 129 (25), 115 (23),

91 (16). HRMS: Calcd. for C₁₅H₁₈O₃(246.1): 246.1256 (correct

mass).

[5] a) Y. Zhang, E. Negishi, J. Am. Chem. Soc. 1989, 111, 3454–

3456; b) Y. Zhang, G. Wu, G. Agnel, E. Negishi, J. Am. Chem.

Soc. 1990, 112, 8590–8592.

[6] a) A. de Meijere, F. E. Meyer, Angew. Chem. 1994, 106, 2473–

2506; Angew. Chem. Int. Ed. Engl. 1994, 33, 2379–2411; b) S.

Bräse, A. de Meijere, in Metal-Catalyzed Cross-Coupling Reac-

tions (Eds.: A. de Meijere; F. Diederich), Wiley-VCH,

Weinheim, 2004, pp. 217–315; c) J. T. Link, L. Overman, in

Metal-Catalyzed Cross-Coupling Reactions (Eds.: F. Diederich,

P. J. Stang), Wiley-VCH, Weinheim, 1998, pp. 231–269.

[7] a) B. M. Trost, Acc. Chem. Res. 1990, 23, 34–42; b) B. M. Trost,

M. J. Krische, Synlett 1998, 1–16; c) B. M. Trost, Y. Li, J. Am.

Chem. Soc. 1996, 118, 6625–6633; d) B. M. Trost, Angew.

Chem. Int. Ed. Engl. 1995, 34, 259–281; e) B. M. Trost, D. L.

Romero, F. Rise, J. Am. Chem. Soc. 1994, 116, 4268–4278; f)

B. M. Trost, M. Lautens, C. Chan, D. T. MacPherson, J. Am.

Chem. Soc. 1994, 116, 4255–4267; g) L. J. van Boxtel, S. Körbe,

M. Noltemeyer, A. de Meijere, Eur. J. Org. Chem. 2001, 2283–

2292.

II: 80 mg (21%) of 40 as a colorless oil. R_f(pentane/Et₂O, 5:1) =

0.18. IR (film): ν = 2992, 2926, 2857, 2827, 1715, 1436, 1382, 1363,

˜

1298, 1247, 1221, 1199, 1163, 1082, 1050, 971, 855, 731, 666,

1

2

611 cm^–1. H NMR (600 MHz, CDCl₃): δ = 1.08 (d, J = 3.1 Hz,

2

1 H, 5-H), 1.63 (m, 2 H, 8-H), 2.02 (d, J = 3 Hz, 5-H), 2.05–2.15

(m, 2 H, 7,9-H), 2.23 (m, 1 H, 7-H), 2.30 (m, 1 H, 9-H), 2.37 (dt,

³J_ax-ax

=

²J = 10, ³Jax-eq = 5 Hz, 1 H, 2-H), 3.67 (s, 3 H, CO-

2

OCH₃), 3.74 (d, J = 12 Hz, 1 H, 4-H), 3.99 (d, J = 12 Hz, 1 H,

2

3

4-H), 4.10 (ddd, J = 11, J_eq-eq= 5.5, Jeq-ax = 2 Hz, 1 H, 2-H),

6.0 (t, ³J = 4 Hz, 1 H, 6-H) ppm. ¹³C NMR (150.82 MHz, CDCl₃,

DEPT): δ = 22.19 (–, C-8), 22.52 (–, C-9), 25.34 (–, C-7), 26.23

(–, C-1), 35.52 (C_quat, C-5a), 37.30 (–, C-5), 42.87 (C_quat, C-4a),

51.71 (+, COOCH₃), 66.86 (–, C-2), 70.03 (–, C-4), 121.78 (+, C-

6), 130.30 (C_quat, C-9a), 134.77 (C_quat, C-9b), 141.08 (C_quat, C-5b),

171.30 (C_quat, COOCH₃) ppm. MS (EI, 70 eV): m/z (%) = 246 (23)

[M⁺], 215 (6) [M⁺– OCH₃], 187 (100) [M⁺– COOCH₃], 157 (43)

[M⁺– COOCH₃– H₂C=O], 141 (14), 129 (25), 115 (12). HRMS:

Calcd. for C₁₅H₁₈O₃(246.1): 246.1256 (correct mass).

[8] For preliminary results of a fraction of this report see: a) F. E.

Meyer, A. de Meijere, Synlett 1991, 777–778; b) S. Schweizer,

M. Schelper, C. Thies, P. J. Parsons, M. Noltemeyer, A. de Mei-

jere, Synlett 2001, 920–922.

[9] H. Henniges, F. E. Meyer, U. Schick, F. Funke, P. J. Parsons,

A. de Meijere, Tetrahedron 1996, 52, 11545–11578.

6166

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Eur. J. Org. Chem. 2008, 6152–6167

Pd-Catalyzed Oligocyclizations of 2-Bromoalk-1-ene-diynes

[10] H. Stetter, E. Reske, Chem. Ber. 1970, 103, 634–644.

[11] F. D. Gunstone, P. J. Sykes, J. Chem. Soc. 1962, 3055–3058.

[12] S. Girard, P. Deslongchamps, Can. J. Chem. 1992, 70, 1256–

1273.

[13] P. E. Sonnet, Synth. Commun. 1976, 6, 21–26.

[14] G. L. Larson, R. J. Klesse, J. Org. Chem. 1985, 50, 3627.

[15] T. Mandai, J. Nokami, T. Yano, Y. Yoshinaga, J. Otera, J. Org.

Chem. 1984, 49, 172–174.

[16] E. Negishi, L. S. Harring, Z. Owczarczyk, M. M. Mohamud,

M. Mehmet, Tetrahedron Lett. 1992, 33, 3253–3256.

[17] B. M. Trost, Y. Shi, J. Am. Chem. Soc. 1993, 115, 12491–12509.

[18] Review, see: A. Kirby, Adv. Phys. Org. Chem. 1980, 17, 183–

279.

Received: August 27, 2008

Published Online: November 12, 2008

Eur. J. Org. Chem. 2008, 6152–6167

www.eurjoc.org

6167

Article Doi

Palladium-catalyzed oligocyclizations of 2-bromoalk-1-ene-(n+1),(m+n+1)- diynes - Influence of tether lengths and substituents on the outcome of the reaction (Part I)

DOI: 10.1002/ejoc.200800826

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