Cross-coupling reactions terminal alkyne synthesis

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

The addition of diboron compounds to alkynes is an excellent method for the synthesis of c -diboryl alkenes (Scheme 2-11) [34], The reaction is catalyzed by Pt(PPh3)4 at 80 and works well not only with terminal but also with internal alkynes. The addition of the Si-B [35] or Sn-B [36] bonds to alkynes gives mixed-metal alkenylboron reagents which have potential ability for use in the stepwise double cross-coupling reaction at both metallated carbons. 

The molecular turnstile was synthesized by regioselective and sequential palladium-catalyzed cross-coupling reactions between aryl halides and terminal alkynes [32]. The successful strategy incorporates the spindle in the first step of the synthesis and the last step is a macrocyclization. Three molecular systems (12-14) with different spindles have been prepared. The compounds, particularly 12 and 13, show low solubility, perhaps due to their relative planarity. 

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). 

Hintermann and his group prepared Soai aldehydes, 2-(alkynyl)-l,3-pyrimidine-5-carbaldehydes, in the absence of base, via a Liebeskind—Srogl cross-coupling reaction of terminal alkynes with 2-mercapto-l,3-pyrimi-dine-5-carbaldehyde (55) (Scheme 37) (140L1282). Optimal conditions for this synthesis were determined to be stirring of 1 equivalent of mer-captoaldehyde 55 with 1.5-2.0 equivalents of the terminal alkyne in a microwave reactor in the presence of 2.0 equivalents of copper(I)... 

Synthesis of Carotenoids and Retinoids. The Pd-catalyzed cross-coupling reactions of 1 with alkenylmetals containing Al, Zn, and Zr have been shown to be high-yielding and selective. The reaction of 1 with /3,/3-disubstituted alkenylalanes under the conditions of double metal catalysis with Pd and Zn is satisfactory, and the >99% stereospecificity level can be maintained in most cases. Thus, this reaction used in conjunction with the Zr-catalyzed carboalumination of terminal alkynes forms the foundation of a highly stereoselective and... 

Recently it has been observed that NCBs have been used as a support for heterogeneous catalyst due to its hollow core, mesoporous and ball-like structure. Park et al. [70] developed Pd(OAC)2 catalyst supported on NCBs and applied it for the synthesis of 2-substituted benzofuran from u-iodo phenol and various substituted terminal alkynes using Sonogashira cross-coupling reaction under copper and ligand-free condition. 

The reaction of certain palladium-heteroatom complexes to alkenes and alkynes is a versatile tool for the synthesis of alkanes and alkene having heteroatoms attached. In particular, the various B-B, B-Si, and B-Sn compounds can be used for palladium-catalyzed borylation of alkenes and alkynes (Scheme 5-2). Borostannylation takes place at ambient temperature, whereas silylboration " only proceeds at a temperature above 80 °C due to the slow oxidative addition of a B-Si bond to a palladium(O) catalyst. Both reactions selectively provide cz j-products via addition of silicone or tin to the internal carbon and boron. The reactions are compatible with various functional groups for both terminal and internal alkynes. Cross-coupling reaction of boranes with organic halides selectively occurs at the terminal C-B bonds to provide regiodefined and stereodefined alkenylboron, alkenylsilicon, and alkenyltin compounds. 

In the direct synthesis of aryl terminal alkynes via Pd-catalyzed cross-coupling of aryl halides with ethynylmetals, formation of diarylethynes is one of the potential side reactions. Indeed, the Kumada coupling of 2-iodo-5-methylthiophene (29) with ethynylmagnesium chloride gave the desired 2-ethynyl-5-methylthiophene (30) in only 35% yield, along with 24% of bis(5-methyl-2-thienyl)ethyne (31) [29], The high propensity for H-Mg exchange reaction to occur was blamed for the diarylethyne formation. 

---