Glaser-type Couplings

In 1869, Glaser found that copper(i) phenylacetylide prepared from phenylacetylene and a copper salt gave the acetylene dimer by air oxidation 

Selective crosscoupling of two different terminal allqmes is difficult in the usual Glaser coupling reaction. For these unsymmetrical conjugated diynes. 

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Despite the high turnover rates of Glaser-type couplings, their applicability to the synthesis of macro-molecular structures is limited by two points ... 

Formation of macrocyclic di- and oligoacetylenes in acceptable yields is rendered more difficult, because of the poor selectivity of Glaser-type couplings. 

To prepare cyclic tetraynes consisting of 1,4-donor-substituted butadiyne units one can use the Glaser type coupling of terminal dithiadiynes 28(3) or 28(4) (Scheme 7.8). This method produces the 18- and 20-membered rings 29(3) and 29(4), respectively, but no trimerization products were found [40]. 

Scheme 7.8. Glaser type coupling of dithiadiynes to yield tetrathiacyclotetraynes 29(3) and 29(4). (a) CuCI, NH3, MeOH, O2, r.t.

The availability of 3(2)-6(2) from a Glaser-type coupling of 1,5-hexadiyne (1(2)) was used by Sondheimer and Wolovsky [26] to generate the fully conjugated cyclic... 

The recent work of Diederich/ Haley,Roger,de Meijere and Scott,Fallis, Bunz, and several others has established Glaser-type couplings as the preeminent synthetic route to a multitude of complex cyclic polyacetylenes. A limited selection of these molecules is illustrated here, 69-76. Hdger has pointed out that copper salts may act as a template in the intermolecular dimerization of functionalized bisacetylenes. The trimer corresponding to 74 is isolated in 9%. Annulene 76 is unusually stable, being sterically protected by the bulky trimethylsilyl groups. ... 

The final major application of Glaser-Type coupling of terminal dialkynes is the synthesis of polymeric acetylenes.Following the seminal work of Hay ° and others,polymeric coupling of terminal bis-acetylenes has led to a myriad of polymeric acetylenes. Some pioneering examples are 85 (polymerization of w-diethynylbenzene), ° 86 (polymerization of 1,8-nonadiyne), a-carbyne (polyyne) (87) (polymerization of dicopper... 

Whereas Glaser-type oxidative coupling opens efficient synthetic pathways toward symmetrical diynes, its performance in heterocoupling is poor. The latter may be accomplished by Cadiot-Chodkiewicz coupling of terminal alkynes with 1-haloalkynes (usually 1-bromoalkynes). The reaction is conducted in the presence of an amine and catalytic amounts of a copper(I) salt. Because, in contrast with the Glaser-type reactions described above, it follows a nonoxidative reaction mechanism, oxygen is not necessary - but needs often not to be excluded (Scheme 4) [9]. 

It must be emphasized that current mechanistic understanding of copper-mediated oxidative acetylenic couplings is unsatisfactory. Several studies have shown the strong dependency of the mechanism on the experimental setup, suggesting highly complex coherences and interactions. Nevertheless, the mechanistic idea of Bohlmann et al. described above still provides the most accepted picture for Glaser-type oxidative acetylenic homocouplings. 

The main driving forces behind the development of new tertiary phosphine palladium complexes for C(sp )—C(sp) couplings have been (i) a reduction or elimination of side reactions, such as Glaser-type homocouplings (ii) the development of environmentally friendly reaction protocols, such as copper-free reactions in benign solvents (iii) the improvement of catalyst stabihty and activity [higher turnover number (TON) and turnover frequency (TOP)] and (iv) a cost reduction by using less-expensive aryl bromides, or even aryl chlorides under mild reaction conditions, for example, at ambient temperature. 

The homo-coupling of terminal alkynes is a frequent side reaction in Sonogashira and Heck-type alkynylation reaction. However, this reaction can be optimized to obtain Glaser-type products in good yields. The power of this reaction has been demonstrated in the synthesis of a wheel-like structure by Hoger and colleagues (Experimental Procedure below). ... 

As demonstrated by Hartmann and Hahn (1962), energy-matched conditions can be created with the help of rf irradiation that generates matched effective fields (see Section IV). Although Hartmann and Hahn focused on applications in the solid state in their seminal paper, they also reported the first heteronuclear polarization-transfer experiments in the liquid state that were based on matched rf fields. A detailed analysis of heteronuclear Hartmann-Hahn transfer between scalar coupled spins was given by Muller and Ernst (1979) and by Chingas et al. (1981). Homonuclear Hartmann-Hahn transfer in liquids was first demonstrated by Braunschweiler and Ernst (1983). However, Hartmann-Hahn-type polarization-transfer experiments only found widespread application when robust multiple-pulse sequences for homonuclear and heteronuclear Hartmann-Hahn experiments became available (Bax and Davis, 1985b Shaka et al., 1988 Glaser and Drobny, 1990 Brown and Sanctuary, 1991 Ernst et al., 1991 Kadkhodaei et al., 1991) also see Sections X and XI). 

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