Palladium alkyne-coupling reactions

Recent developments in palladium-catalyzed coupling reactions have arisen in the pyrimidine field as well. The Sonogashira coupling of bromopyrimidine 85 with alkynes 86 produced pyrimidines 87, important intermediates reported by Hart and co-workers in their approach to the cylindrospermopsin substructure . 

A separate, quite thorough study of terminal alkyne hydrosilylation with platinum arrived at a similar set of conditions.39 This work utilized a one-pot hydrosilylation with the preformed platinum(O) complex (>Bu3P)Pt[(CH2=CH)Me2Si]20 ([(CH2=CH)Me2Si]20 = DVDS) and subsequent palladium-catalyzed coupling reaction to demonstrate that the platinum catalyst is compatible with cross-coupling conditions, providing a convenient hydrocarbation of terminal alkynes (Table 2). 

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. 

Chloro-3-hydroxypyridine is a readily available starting point for the synthesis of furo[2,3- ]pyridines via iodina-tion followed by a palladium cross-coupling reaction with alkynes to afford alkynylpyridines, 107. Cyclization of compound 107 leads to furo[2,3- ]pyridine products <1998JME1357, 1998JOC7851 Similarly, reaction of 5-bromo-... 

These two fragments arc joined with a palladium-catalyzed alkyne coupling reaction. 

Depending on the alkyne, both six- and five-membered rings may be obtained npon reaction of B-carbomethoxy-alkenyl-ammo carbenes (Scheme 46). Dihydropyridme and indole carbene complexes participate in benzannnlation reactions (Scheme 47). Alkynes containing boronic esters may be used, affording boronic ester-fimctionalized quinones that can be used in palladium-catalyzed coupling reactions (Scheme 48). ... 

A variation of this aryl-alkyne coupling reaction reacted methylthioalkynes (R—C=C—SMe) with arylboronic acids and a palladium catalyst to give the aryl alkyne (R—C=C—Ar). 1-TrialkyIsilylalkynes (R3Si—C=C—R ) were coupled... 

Despite the multitude of functional groups present and the insolubility of the nucleosides in inert solvents, palladium-catalyzed coupling reactions have been used in their synthesis. Thus, the coupling of terminal alkynes with iodinated uracyl nucleosides proceeds in high yield in the presence of a Pd°-Cu catalyst in warm triethylamine, and several of the products obtained by this route have shown useful antiviral activity (Scheme... 

In a similar manner, cyclopropane-containing benzvalene can be used as the alkene component in intermolecular Pauson-Khand reactions.Several examples of intermolecular Pauson-Khand cyclizations of methylenecyclopropanes and alkynes are reported to give bicyclic car-bocycles. Ethynylcyclopropyl-substituted chromium carbonyl complexes have also been used in palladium-catalyzed coupling reactions. 

We have completed the first total synthesis of (-)-ichthyothereol (46) and its acetate 47 by the palladium-catalyzed coupling reaction between the ( )-iodoolefin 63 and the triyne derivative 66. The iodoolefin 63 was prepared from commercially available diethyl L-tartrate through the Co2(CO)8-mediated endo cyclization of the optically active c/.v-epoxy-alkyne derivative 60 in a highly stereoselective manner. 

Joint catalysis by tin(IV) chloride and zinc chloride induces coupling of the acetal 114 with the alkyne 115 to give the propargyl ether 116. Allyl halides condense with terminal alkynes in DMF in the presence of copper(I) iodide, potassium carbonate and tetrabutylammonium chloride under phase-transfer conditions to afford eneynes, e.g. equation 19. Palladium-catalysed coupling reactions of 1-bromoallenes with terminal acetylenes have been reported for the first time thus acetylene and the allenes 117 (R R = Me or Et) in triethylamine in the presence of tetrakis(triphenylphosphine)palladium and... 

Another palladium-catalyzed coupling reaction performed successfully on soluble polymers is the Sonogashira coupling. In a more recent report it was reported that PEG 4000 acts simultaneously as polymeric support, solvent, and phase transfer catalyst (PTC) in both steps, coupling and hydrolysis [72]. Poly(ethylene glycol) (PEG)-bound 4-iodobenzoic acid was readily reacted with several terminal alkynes under rapid microwave conditions (Scheme 16.50). Cleavage of the coupling products from the PEG support was achieved efficiently by simple saponification with brief microwave irradiation in an open beaker in a domestic microwave oven. 

Several versions of palladium-catalyzed coupling reactions have been used to convert o-nitroaryl halides to o-nitrophenylacetaldehydes or o-nitrobenzyl ketones. Coupling with trimethylsilylethyne gives aryl alkynes which can be converted to o-nitrophenylacetaldehyde enol ethers by sodium ethoxide (Scheme 21) <86CPB2362>. 

Palladium-catalyzed coupling reactions of alkenyl/aryl halides or triflates with alkenes, alkynes, or organometaUic reagents are readily used during the synthesis of pharmaceuticals because of the high yield and great selectivity that can be achieved under mild reaction conditions in these processes [108]. At the same time, there are only a few examples for the same reaction carried out in carbon monoxide atmosphere. 

Sakai N, Annaka K, Konakahara T (2004) Palladium-catalyzed coupling reaction of terminal alkynes with aryl iodides in the presence of indium tribromide and its application to a one-pot synthesis of 2-phenylindole. Org Lett 6 1527-1530. doi 10.1021/ol036499u Sakai N, Annaka K, Eujita A, Sato A, Konakahara T (2008) InBr 3-promoted divergent approach to polysubstituted indoles and quinolines from 2-ethynylanilines switch from an intramolecular cyclization to an intermolecular dimerization by a type of terminal substituent group. J Org Chem 73 4160-4165. doi 10.1021/jo800464u... 

The alkyne-alkyne coupling reaction is mostly promoted with copper-catalysts (Glaser coupling and variants). However, there are examples known for palladium-... 

Palladium And/Or Copper-Mediated Cross-Coupling Reactions Between 1-Alkynes And Vinyl, Aryl, 1-Alkynyl, 1,2-Propadienyl, Propargyl And Allylic Halides Or Related Compounds. A Review, Rossi. R. Carpita, A. Beilina, F. Org. Prep. Proceed. Int., 1995, 27, 129... 

Over the last decade, the chemistry of the carbon-carbon triple bond has experienced a vigorous resurgence [1]. Whereas construction of alkyne-con-taining systems had previously been a laborious process, the advent of new synthetic methodology based on organotransition metal complexes has revolutionized the field [2]. Specifically, palladium-catalyzed cross-coupling reactions between alkyne sp-carbon atoms and sp -carbon atoms of arenes and alkenes have allowed for rapid assembly of relatively complex structures [3]. In particular, the preparation of alkyne-rich macrocycles, the subject of this report, has benefited enormously from these recent advances. For the purpose of this review, we Emit the discussion to cychc systems which contain benzene and acetylene moieties only, henceforth referred to as phenylacetylene and phenyldiacetylene macrocycles (PAMs and PDMs, respectively). Not only have a wide... 

Recently, Pal et al. found that (.S )-prolinol could facilitate the coupling reaction of terminal alkynes with 3-iodoflavone under palladium-copper catalysis in aqueous DMF to give 3-alkynyl substituted flavones of potential biological interest (Eq. 4.17). The coupling of iodobenzene with terminal alkynes at room temperature in water without any cosolvent was completed within 30 minutes, affording the desired product in good yield.36... 

A palladium catalyst with a less electron-rich ligand, 2,2-dipyridyl-methylamine-based palladium complexes (4.2), is effective for coupling of aryl iodides or bromides with terminal alkynes in the presence of pyrrolidine and tetrabutylammonium acetate (TBAB) at 100°C in water.37 However, the reactions were shown to be faster in NMP solvent than in water under the reaction conditions. Palladium-phosphinous acid (POPd) was also reported as an effective catalyst for the Sonogashira cross-coupling reaction of aryl alkynes with aryl iodides, bromides, or chlorides in water (Eq. 4.18).38... 

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