108
I. A. Balo6a et al. / Tetrahedron Letters 44 (2003) 107–109
then suitable for subsequent Sonogashira couplings,
especially as these are carried out in the presence of an
organic amine base and hence the residual a,v-diamine
does not interfere, thereby obviating the need to isolate
the sensitive alka-1,3-diynes. The method is summa-
rized in Scheme 1.
Although most examples of aryl iodides in this present
study are relatively electron poor and hence particularly
well suited to Sonogashira coupling reactions, the
finding that 1-amino-2-iodobenzene (cf. 4) also partici-
pates very efficiently indicates that this ‘one-pot’
method should be widely applicable to a range of both
aryl and heteroaryl halides.
For example, starting with dodeca-5,7-diyne 1b, treat-
ment with three equivalents of lithium 2-aminoethyl-
amide (LAETA) at 16–18°C for 10 min results in
Acknowledgements
complete isomerization, following which,
a small
amount of water is added to release the free alka-1,3-
diyne 3b from the salt 2b. This is followed by the
addition of an aryl iodide, palladium(II) acetate,
triphenylphosphine, triethylamine and copper(I) iodide
in this order, to set up the catalyst system usually
associated with the Sonogashira coupling reaction.1 In
all cases, these final coupling reactions took place under
very mild conditions, either at ambient temperature or
slightly above (35–45°C) during 3–8 h. A routine work-
up and chromatography then delivered the isolated
yields of the representative 1-arylalka-1,3-diynes 4–8.7
We gratefully acknowledge financial support from
INTAS, Grant 97-31999 and RFBR Grant 02-03-
32229.
References
1. (a) Sonogashira, K.; Tohada, Y.; Hagihara, N. Tetra-
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Organomet. Chem. 1975, 93, 253.
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(c) Remizova, L. A.; Krukov, A. V.; Balova, I. A.;
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6. (a) Balova, I. A.; Remizova, L. A.; Favorskaja, I. A. Zh.
Org. Khim. (Engl. Transl.) 1988, 24, 2523; (b) An improved
method for the ‘acetylene zipper’ reaction was used.
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7. Full spectroscopic and analytical data has been obtained
for all compounds reported herein. For example, 2-
(dodeca-1,3-diynyl)aniline (4b): lH (300 MHz, CDCl3):
0.88 (3H, t, J=7 Hz, Me), 1.21–1.42 (10H, 5×CH2), 1.57
(2H, p, J=7 Hz, CH2), 2.37 (2H, t, J=7 Hz, CH2C), 4.47
(2H, s, NH2), 6.67–6.75 (2H, m), 7.12 (1H, t, J=7 Hz,
Ar-H) and 7.28 (1H, t, J=7 Hz, Ar-H); lC (75 MHz,
CDCl3): 14.5 (Me), 20.1 (CH2C), 23.1, 28.7, 29.3 29.5,
29.6, 32.3 (all CH2), 65.4, 72.0, 80.0, 86.4 (all C), 107.1,
114.8, 118.4, 130.6 133.5, and 149.6 (all ArC), m/z 253
(C18H23N=253). Anal. found: C, 85.24; H, 9.12; N, 5.63.
C18H23N requires: C, 85.32; H, 9.15; N, 5.53%.
In our initial experiments, a 10% excess of the aryl
iodide relative to the diyne 3b was used. Under these
conditions, between 4 and 10% of the dehydrodimeriza-
tion product 9b was formed as a by-product. With a
view to reducing this amount, we investigated the effect
of varying the stoichiometry of the diyne and the aryl
iodide and found the best yields of the aryl-1,3-diynes
4–8 were obtained using a molar ratio of 1.2:1 of these
two reactants, that is, slightly less aryl iodide than
formally required to react with all of the diyne. It is
also important that the copper(I) iodide is added last.
Given these two conditions, yields of the tetrayne by-
products 9 were reduced from levels of ca. 10% to
2–4%.8 It is also worth noting that, under the mild
coupling conditions used, no intramolecular cyclization
products were formed during the synthesis of the ortho-
aminoarylalka-1,3-diynes 4 and 7.
8. Typical experimental procedure: LAETA was obtained by
the reaction of Li (53 mg, 7.5 mmol) with absolute EDA
(0.6 ml, 7.5 mmol) in dry THF (1.8 ml) under Ar. After
the addition of benzene (1.8 ml) and hexane (1.8 ml), the