Cross with terminal acetylene

C. Cross-Coupling of Halogenopyrazoles with Terminal Acetylenes and Their Copper(I) Salts (Tables X to XV)... 

Similarly, the limitations and peculiarities of the cross-coupling of pyrazolyl-halides with terminal acetylenes have been fully and systematically studied by Russian chemists (86TH1 97TH1). 

In spite of the common conception that Ni catalysts are useless in the Sonogashira reaction, NiCl2(PPh3) has been disclosed as being able to catalyze the cross-coupling of aryl iodides with terminal acetylenes in aqueous dioxane, in the presence of Cul.147... 

Substituted propargylic carbonates react with terminal acetylenes in the presence of a catalytic amount of Pd(PPh3)4 and Cul to produce Sonogashira-type cross-coupling products (Eq. 9.114) [84]. Presumably, the reaction proceeds through an allenylpalladium complex. Addition of a salt, such as KBr, increased the yield of the coupling product. Only tetrasubstituted allenes could be obtained by this procedure. 

Methyl 2,3-alkadienoates undergoes cross-coupling reactions with terminal acetylenes to give enynes in a highly regioselective manner (Scheme 16.94) [100],... 

Scheme 2. Mechanism of the Sonogashira reaction for Pd/ Cu-catalyzed cross-coupling of sp2-C halides with terminal acetylenes.

A particularly interesting application of this protocol, in conjunction with the direct cross-coupling with terminal acetylenes is shown in Scheme 5-2. Here, the first coupling occurs between the alkynyltin reagent 50 and the cyclized palladium intermediate 49 and is followed by the second direct coupling with the terminal acetylene 52 at the vinyl bromide moiety to yield unsymmetrical cyclic dienediyne 53 [32]. 

The cross-coupling reaction of (2)- and ( )-vinyl bromides with terminal acetylenes is stereospecific. For example, (Z)-methyl 3-bromoacrylate 127 reacts with 1-hexyne in the presence of a Pd catalyst to form the (Z)-enyne as the only product [Eq. (42)] [63]. 

JEl-vinyl bromide, cross-coupling reaction with terminal acetylenes 220... 

This protocol and the Pd-Cu-catalyzed direct cross-coupling with terminal acetylenes (Section 5.3.5) directly complement each other. The following examples, which cannot be applied to the latter, give normal coupling products only by Stille method [Eqs. 17-20] [28-31]. This method is especially useful for the cross-coupling reactions of organometallic complexes with cyclopentadienyl ligand that are sensitive to amines [Eq. 19] [30]. 

These ease of preparation of vinyl and aryl triflates and the availability of the starting materials have expanded their use as a coupling partner with a terminal acetylene. Facile Pd-Cu coupling of vinyl triflates with terminal acetylenes was reported by Cacchi [51]. The cross-coupling of enol triflate 88 with phenylacetylene proceeds easily under normal conditions [Eq. (33)] [52]. For the double cross-coupling of aromatic 1,2-ditriflates with TMSA, the addition of Bu4NI accelerates enediyne formation [Eq. (34)] [53]. 

The Sonogashira reaction is of considerable value in heterocyclic synthesis. Heteroaryl halides like bromooxazoles are viable substrates for the Pd-catalyzed cross-coupling reactions with terminal acetylene in the presence of Pd/Cu catalyst. In 1987, Yamanaka s group described the Pd-catalyzed reactions of halothiazoles with terminal acetylenes [50]. Submission of 4-bromo- (72) and 5-bromo-4-methyloxazoles (73) to the Sonogashira reaction conditions with phenylacetylene led to the expected acetylenes (74 and 75). 

The (o-aminoaryl)acetylenes 27 are easily accessible by Pd-mediated SONOGASHIRA cross coupling reactions of (o-halogeno)aniline derivatives 26 (X preferably I) with terminal acetylenes. Alternatively, 27 is prepared by Sonogashira coupling of 26 with TMS-acetylene (to give 29), desilylation of 29 and base-induced alkylation at the free acetylene terminus (29 29a -> 27). 

Cross-coupling of aryl and vinyl halides with terminal acetylenes (the Sonogashira reaction) is among the fundamental methods of Pd-catalyzed C-C bond forming reactions. Cu-Pd co-catalysis is considered a standard requirement for this method. 

B. METAL-CATALYZED CROSS-COUPLING REACTIONS BETWEEN ARYL OR VINYL HALIDES WITH TERMINAL ACETYLENES... 

B.i. Pd-Catalyzed Cross-Coupling Reactions Between Aryl or Vinyl Halides with Terminal Acetylenes... 

B.iii. Pd/Cu-Catalyzed Cross-Coupliiig Reactions of Organic Halides or Triflates with Terminal Acetylenes... 

In general, enediynes are prepared by a Pd/Cu-mediated cross-coupling reaction of vinyl dihalides or analogs with terminal acetylenes under standard conditions in good to excellent yields. In the synthesis of endiyne 63, acceptable monosubstitution of a vinyl dihalide 62 can be achieved by using a large excess of the dihalides over the alkyne (Scheme 24). 

Reliable and practical procedures for the synthesis of arylacetylenes by Pd-catalyzed cross-coupling of aryl bromides with terminal acetylenes have been developed, which... 

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