A R T I C L E S
Shi et al.
years.5,23,39 The Glaser reaction, first reported in 1869, involves
Cu salts as reagents or catalysts and oxidatively homocouples
two terminal alkynes to construct symmetric diynes.15,24,31,33,40-43
Cadiot-Chodkiewicz coupling, developed over four decades
ago, utilizes a 1-haloalkyne as the electrophile and a termi-
nal alkyne as the nucleophile to construct unsymmetrical
diynes.28,29,32,44-48 Though powerful in many cases, Cadiot-
Chodkiewicz coupling often suffers from poor selectivity and
results in a considerable amount of homocoupled byproducts,
especially when the electronic properties of the substituents
attached to the haloalkynes and the terminal alkynes are
similar.8,23,39,49 To inhibit the homocoupling of the haloalkynes,
excessive terminal alkynes are usually required.23 Also, the
Cadiot-Chodkiewicz coupling system is usually complicated,
requiring specific amines as the solvent and reductive reagents
such as hydroxylamine hydrochloride to keep the Cu salts in a
low oxidation state.23,28,32,48 In addition, few mechanistic studies
have been conducted on the process of triple-triple bond
formation of the above two reactions.8,39,50,51
Scheme 1. Palladium-Catalyzed Syntheses of Conjugated Diynes
rearrangement (FBW rearrangement) to furnish unsymmetrical
diynes and polyynes (Scheme 1).4,56-58 Nye,36 Wityak,59 and
Alami49 et al. introduced Pd into the C(sp)-C(sp) cross-coupling
reactions for the synthesis of unsymmetrical diynes and
improved the yield and selectivity in some cases.
However, Pd-catalyzed C(sp)-C(sp) cross-coupling reactions
are not well established yet. The major problem is still the
competitive formation of the two homocoupled products.39
A
speculated mechanism of the Pd-catalyzed C(sp)-C(sp) cou-
pling is outlined in Scheme 2. After oxidative addition of the
1-haloalkyne to the Pd catalyst and transmetalation with the
alknylmetal reagent generated from the terminal alkyne, key
intermediate I was gained. I could undergo direct reductive
elimination to furnish the desired unsymmetrical diynes (path
A) or further transmetalate with the alknylmetal reagents in the
reaction system and release homocoupled side products (paths
B and C). Accordingly, one reasonable way to improve the
selectivity for path A is to facilitate the reductive elimination
of intermediate I.
During the past three decades, several Pd-catalyzed conjugate
diyne formation methods have been reported. Negishi et al.
developed an efficient tandem protocol by combining Pd-
catalyzed coupling of terminal alkynes and ICHdCHCl with
subsequent base-induced elimination to afford the conjugate
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