Modification of the Fritsch-Buttenberg-Wiechell rearrangement: A facile route to unsymmetrical butadiynes

Article abstract of DOI:10.1016/S0040-4039(01)01901-3

A modification of the Fritsch-Buttenberg-Wiechell rearrangement has been used to form unsymmetrically substituted 1,3-butadiynes from 1,1-dibromo-olefin precursors. The reaction proceeds via lithium-halogen exchange, followed by migration of the aryl or alkynyl moiety to provide the butadiyne framework. The facile formation of the dibromo-olefins in three steps from commercially available aryl aldehydes or carboxylic acid chlorides makes this procedure an attractive alternative to traditional methods for butadiyne synthesis.

Full text of DOI:10.1016/S0040-4039(01)01901-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 8575–8578
Modification of the Fritsch–Buttenberg–Wiechell rearrangement:
a facile route to unsymmetrical butadiynes
Erin T. Chernick, Sara Eisler and Rik R. Tykwinski*
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Received 14 August 2001; accepted 9 October 2001
Abstract—A modification of the Fritsch–Buttenberg–Wiechell rearrangement has been used to form unsymmetrically substituted
1,3-butadiynes from 1,1-dibromo-olefin precursors. The reaction proceeds via lithium–halogen exchange, followed by migration of
the aryl or alkynyl moiety to provide the butadiyne framework. The facile formation of the dibromo-olefins in three steps from
commercially available aryl aldehydes or carboxylic acid chlorides makes this procedure an attractive alternative to traditional
methods for butadiyne synthesis. © 2001 Elsevier Science Ltd. All rights reserved.
The rigid and conjugated nature of the 1,3-butadiyne
moiety makes it a useful building block that has been
employed in the formation of new photonic materials,1
oligomers and polymers,2 macrocycles,3 as well as
supramolecular scaffolds.4 In addition, this functional
group has a rich history as a precursor for single crystal
polydiacetylene formation via topochemical polymeri-
zation.5
formation of aromatic 1,3-butadiynes. Using
PdCl2(PPh3)2 or Pd(PPh3)4, these reactions generally
work quite well with aryl iodides and with electron-
deficient aryl bromides. With unactivated aryl bro-
mides, however, rigorous conditions are often
necessary.
Br
Li
Br
Br
Ar
R
Ar
Ar
The synthesis of symmetrically substituted butadiynes is
relatively straightforward using Hay6 or Eglinton/
Galbraith7 conditions, which proceed via oxidative
homocoupling of terminal acetylenes with Cu(I)/Cu(II)
catalysis.8 Hay or Eglinton/Galbraith conditions are
not suitable, however, for the synthesis of unsymmetri-
cal substituted butadiynes, as mixtures of products are
usually encountered. The cross-coupling of terminal
acetylenes with alkynyl bromides or iodides, the
Cadiot–Chodkiewicz9 coupling, often provides a useful
method for accessing unsymmetrical diynes. The pre-
dominant limitation of this and related methods,10 how-
ever, is that they all require the prior synthesis of a
terminal alkyne as one coupling partner and an alkynyl
halide as the other.
R
R
1
2
3
The Fritsch–Buttenberg–Wiechell (FBW) rearrange-
ment is a well precedented technique for the formation
of alkynes.12,13 We recently reported a modification of
this method and demonstrated that it is suitable for the
formation of a variety of polyynes via alkyne migration
in carbene/carbenoid intermediates.14,15 The high
propensity for alkyne and/or aryl migration suggested
that dibromo-olefins such as 1 would serve well as
precursors to diynes 3. This reaction would involve a
sequence of lithium halogen exchange to give the car-
bene/carbenoid intermediate 2 followed by rearrange-
ment to 3. We now report the successful synthesis of a
range of unsymmetrical 1,3-butadiynes16 via this
method. In contrast to other methods of butadiyne
formation that rely on arylyne or aryl halide precur-
sors, the method described herein utilizes aryl aldehydes
or aryl carbonyl chlorides as starting materials. As a
result, this route is particularly useful for the formation
of electron-rich aryl diynes that are unactivated toward
palladium catalyzed alkynylations.
Palladium catalyzed cross-coupling reactions of termi-
nal alkynes with aryl halides or triflates, such as the
Sonogashira reaction,11 are an alternative route into the
Keywords: alkylidene carbene; 1,3-butadiyne; dibromo-olefin; alkyne
migration.
* Corresponding author. Tel.: 780 492 5307; fax: 780 492 8231;
e-mail: rik.tykwinski@ualberta.ca
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01901-3

8576
E. T. Chernick et al. / Tetrahedron Letters 42 (2001) 8575–8578
The general synthetic route to trimethylsilyl protected
aryl 1,3-butadiynes is outlined in Scheme 1.17 An excess
of trimethylsilyl acetylene (1.25 equiv.) is lithiated with
n-BuLi (1.2 equiv.) at −78°C in Et2O to give the
acetylide 4. The aryl carboxaldehyde (1 equiv.) is added
at −78°C, and the reaction mixture was slowly warmed
to ca. −10°C until the reaction was judged complete by
TLC. The reaction is cooled again to −78°C and
quenched with aqueous NH4Cl.18 As a result of the
slight excess of acetylide, complete reaction with the
aldehyde can generally be effected, and the resultant
alcohols 5 can be isolated pure and in high yield
following aqueous work-up.
OH
Oxidation of alcohol 5 to ketone 6 with PCC is accom-
plished at rt in CH2Cl2, with reaction times of less than
1 h for most derivatives. Concentration of the reaction
mixture, followed by filtration through a short plug of
silica affords the crude ketones 6a–h, which are of
sufficient purity to be carried on to the dibromo-olefi-
nation step.19 They can, however, be isolated pure by
flash chromatography, as demonstrated for ketones 6b
and 6e. The oxidation of ferrocenyl alcohol 5h was
particularly difficult with PCC, affording only 36%
yield. Using BaMnO4 as the oxidant,20 however, ketone
6h could be obtained in 94% yield. The well-established
dibromo-olefination method using PPh3/CBr4 was
employed to provide derivatives 7.21 For sterically
unhindered ketones, the dibromo-olefins can be formed
at rt in CH2Cl2 in 1–2 h. For ketones 6e and 6h,
however, reactions were sluggish at rt in CH2Cl2, and
they were therefore carried out in benzene at reflux. In
all cases, the dibromo-olefinic product is considerably
less polar than the ketone precursor, as well as any
by-products of the reaction, and can be easily purified
by column chromatography.
O
a
+
Li–C≡CTMS
Ar
Ar
H
TMS
4
5a–h
Br
Ar
Br
O
c
b
Ar
TMS
TMS
6a–h
7a–h
d
Ar
TMS
8a–h
Scheme 1. Reagents and conditions: (a) Et2O, −78°C; (b) PCC,
Celite, mol. sieves (4 A), CH2Cl2, rt; (c) PPh3 (2 equiv.), CBr4,
CH2Cl2 @ rt or C6H6 @ reflux; (d) n-BuLi, −78 to −40°C,
,
hexanes.
Table 1. Synthesis of diynes 8a–h
To date, the conversion of the dibromo-olefins to the
desired diynes 8 has been more successful in hexanes, as
opposed to more polar solvents such as Et2O or THF.22
Thus, diyne formation is effected by the dropwise addi-
tion of n-BuLi to a hexanes solution of 7 cooled to
−78°C. The mixture is subsequently warmed to ca.
−40°C over 0.5 h to ensure complete rearrangement of
the carbenoid intermediate and then quenched at
−78°C. If anhydrous reaction conditions have been
maintained, the diyne is generally the sole product
observed by TLC analysis.23 The diynes can thus be
isolated pure in good to excellent yields by passing the
concentrated reaction mixture through a plug of silica
to remove more polar, baseline material.24
Scheme 2 outlines an alternative pathway to aryl 1,3-
diynes that exploits readily available aryl acid chlorides.
Friedel–Crafts acylation of acid chlorides 9a–c with
bis(trimethylsilyl)acetylene in the presence of AlCl3
afforded ketones 10a–c in excellent yields.25 Dibromo-
olefination of 10a–c generated 11a–c in 60–91% yields.
Subjecting dibromides to n-BuLi at −78°C according to
the standard protocol affords 4-t-butylphenyl diyne
12a24 in 88% yield, 4-hexylphenyl diyne 12b in 70%
yield, and the trimethoxy aryl diyne 12c in 51% yield.
This method for diyne synthesis is also extendable to
systems other than those with trimethylsilylethynyl sub-
stituents. As shown in Scheme 3, rearrangement of
alkyl substituted dibromo-olefins 13a and 13b affords
1,3-diynes 14a and 14b in high yields.26

E. T. Chernick et al. / Tetrahedron Letters 42 (2001) 8575–8578
8577
2. (a) Carbon-Rich Compounds II, Top. Curr. Chem. 1999,
201; (b) Bunz, U. H. F.; Rubin, Y.; Tobe, Y. Chem. Soc.
Rev. 1999, 107–119; (c) Diederich, F.; Rubin, Y. Angew.
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and Interesting Organic Molecules; Halton, B., Ed.; JAI
Press: New York, 2000; Vol. 8, pp. 1–41; (b) Ho¨ger, S.;
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38, 1940–1943.
O
O
R2
R1
a
R2
R1
Cl
TMS
R2
R2
9a R1 = t-Bu, R2 = H
9b R1 = n-Hex, R2 = H
9c R1 = R2 = OMe
10a 76%
10b 90%
10c 91%
b
Br Br
R2
4. Campbell, K.; McDonald, R.; Branda, N. R.; Tykwinski,
R. R. Org. Lett. 2001, 3, 1045–1048.
5. (a) For polydiacetylenes, see: In Polydiacetylenes; Bloor,
D.; Chance, R. R., Eds.; Martinus Nijhoff: Dordrecht,
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347–357.
6. Hay, A. S. J. Org. Chem. 1962, 27, 3320–3321.
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8. For an excellent review of butadiyne formation under
both homo- and heterocoupling conditions, see: Siemsen,
P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int.
Ed. 2000, 39, 2633–2657.
R2
R1
c
R1
TMS
TMS
R2
R2
12a 88%
12b 70%
12c 51%
11a 60%
11b 79%
11c 91%
Scheme 2. Reagents and conditions: (a) TMSCꢀCTMS, AlCl3,
CH2Cl2, 0 to 25°C; (b) PPh3 (2 equiv.), CBr4, CH2Cl2; (c)
n-BuLi, hexanes, −78 to −40°C.
Br
Ar
Br
9. (a) Chodkiewicz, W.; Cadiot, P. C. R. Hebd. Seances
Acad. Sci. 1955, 241, 1055–1057; (b) Chodkiewicz, W.
Ann. Chim. (Paris) 1957, 2, 819–869.
n-BuLi,
hexanes,
Ar
n-Bu
–78 to –40°C
n-Bu
10. (a) Negishi, E.; Hata, M.; Xu, C. D. Org. Lett. 2000, 2,
3687–3689; (b) Godt, A. J. Org. Chem. 1997, 62, 7471–
7474; (c) Kitamura, T.; Tanaka, T.; Taniguchi, H.; Stang,
P. J. J. Chem. Soc., Perkin Trans. 1 1991, 2892–2893; (d)
Nishihara, Y.; Ikegashira, K.; Mori, A.; Hiyama, T.
Tetrahedron Lett. 1998, 39, 4075–4078; (e) Wityak, J.;
Chan, J. B. Synth. Commun. 1991, 21, 977–979; (f) Ama-
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11. Sonogashira, K. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F.; Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1997; Chapter 5.
12. (a) Fritsch, P. Liebigs Ann. Chem. 1894, 279, 319–323; (b)
Buttenberg, W. P. Liebigs Ann. Chem. 1894, 279, 324–
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13a Ar = 2-thienyl
14a Ar = 2-thienyl 86%
13b Ar = 3-MeO-C6H4
14b Ar = 3-MeO-C6H4 89%
Scheme 3.
In summary, the modified FBW rearrangement
described herein provides a facile route to a range of
aryl diyne systems. This synthetic route offers several
attractive features versus more commonly employed
palladium coupling methods including (1) the wide
range of commercially availability of aryl aldehydes
and carboxylic acid precursors, (2) applicability to elec-
tron-rich aryl groups, (3) generally rapid reaction times
and easy purification/isolation.27
13. For reviews, see: (a) Kirmse, W. Angew. Chem., Int. Ed.
Engl. 1997, 36, 1164–1170; (b) Stang, P. J. Chem. Rev.
1978, 78, 383–405; (c) Hartzler, H. D. In Carbenes; Moss,
R. A.; Jones, Jr., M., Eds.; Wiley and Sons: New York,
1983; Vol. 2, pp. 43–100. See also: (d) Rezaei, H.;
Yamanoi, S.; Chemla, F.; Normant, J. F. Org. Lett. 2000,
2, 419–421; (e) Mourie`s, V.; Waschbu¨sch, R.; Carran, J.;
Savignac, P. Synthesis 1998, 271–274; (f) Sato, H.; Isono,
N.; Miyoshi, I.; Mori, M. Tetrahedron 1996, 52, 8143–
8158; (g) Kawase, T.; Darabi, H. R.; Uchimiya, R.; Oda,
M. Chem. Lett. 1995, 499–500.
Acknowledgements
Financial support for this work has been provided by
the University of Alberta, the Alberta Science,
Research, and Technology Authority, and NSERC. We
also gratefully acknowledge NSERC for a summer
undergraduate research scholarship to Ms. Chernick.
14. Eisler, S.; Tykwinski, R. R. J. Am. Chem. Soc. 2000, 122,
10736–10737.
References
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17. All new compounds have been completely characterized
by 1H and 13C NMR, IR, MS and either HRMS or
combustion analysis. Typical procedure for diyne forma-
tion: To the appropriate dibromo-olefin (0.368 mmol) in
dry hexanes (10 mL) at −78°C was added dropwise over
10 min 1.1 equiv. of n-BuLi (0.16 mL, 2.5 M in hexanes,
0.40 mmol). The mixture was warmed to approximately
−40°C for 30 min, re-cooled to −78°C, and quenched
with a satd aq. solution of NH4Cl. The organic layer was
separated, washed with satd aq. NH4Cl, and dried over
magnesium sulfate. Solvent removal in vacuo and passage
through a short plug of silica gel yielded the desired
diyne.
22. A full investigation of the mechanistic aspects of this
reaction is underway, including solvent effects.
23. Using TLC to monitor these reactions is problematic, as
warming of the sample in the capillary tube used for TLC
application can lead to the inaccurate observation that
the reaction had reached completion.
24. Diynes 8c and 12a have been reported. See: Wan, W. B.;
Haley, M. M. J. Org. Chem. 2001, 66, 3893–3901.
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26. Dibromo-olefins 13a and 13b were prepared from 1-
hexyne and the appropriate aryl carboxaldehyde, in the
same manner as that described in Scheme 1.
27. It is worth noting that in most of the cases outlined in
Table 1 and Scheme 2, the complete sequence of reac-
tions, from the carboxaldehyde (or acid chloride) to the
desired aryl diyne could be completed by a graduate
student in a single day (<12 h).
18. Similar routes have been reported, inter alia: (a) Brown,
R. F. C.; Jackson, W. R.; McCarthy, T. D. Tetrahedron
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19. For synthetic convenience, the CH2Cl2 solutions resulting