Sonogashira palladium-catalyzed reactions

R. Roy, S. K. Das, F. Santoyo-Gonzalez, F. Hemandez-Mateo, T. K. Dam, and C. F. Brewer, Synthesis of sugar-rods with phytohemagglutinin cross-linking properties by using the palladium-catalyzed Sonogashira reaction, Chem. Eur. J., 6 (2000) 1757-1762. 

Wang s approach for the synthesis of enyne-allenes focused on ene-allenyl iodide 45 (Scheme 14.12) [24]. Palladium-catalyzed Sonogashira reaction of 45 with terminal alkynes 46 (R= Ph or CH2OH) proceeded smoothly under mild reaction conditions in the presence of the cocatalyst cuprous iodide and n-butylamine. The initially formed enyne-allene 47b with substituent R= CH2OH cyclized spontaneously to the corresponding a-methylstyrene derivative 48. 

The palladium-catalyzed Sonogashira reaction between l-(2-propynyl)-l//-indole 1460 and l-iodo-2-(2-phenylethy-nyl)benzene 1461 was successful in producing 17/-indole 1462 in excellent yield (Scheme 279) <2005JOC6647>. Treatment of indole 1462 with a strong base produced 12-phenyl-7//-indeno[l, 2 4,5]pyrido[l,2- ]indole 1463 in... 

The regioselective coupling reaction of 2,3-dibromobenzo[/ ]furan with several terminal acetylenes was achieved using a palladium-catalyzed Sonogashira reaction, as exemplified in Equation (91) <2003S925>. 

Bohm, V. P. W., Herrmann, W. A. Coordination chemistry and mechanisms of metal-catalyzed C-C coupling reactions, 13 a copper-free procedure for the palladium-catalyzed Sonogashira reaction of aryl bromides with terminal alkynes at room temperature. Eur. J. Org. Chem. 2000,3679-3681. 

Scheme 15.49. Palladium-catalyzed Sonogashira reaction with trimethylsilylacetylene.

In 2006, Lu and co-workers developed a practical and economical one-pot process for the synthesis of 2,3-disubstituted indoles. " This palladium-catalyzed domino indolization procedure allows rapid access to a variety of 2,3-disubstituted indoles regiospecifically under fairly mild conditions (Scheme 2.91). The reaction consisted of a palladium-catalyzed Sonogashira reaction and organopalladium-mediated amidopalladation. 

Another palladium-catalyzed coupling reaction that has been successfully performed on soluble polymers is the Sonogashira coupling. Xia and Wang have presented an approach in which the PEG 4000 utilized simultaneously serves as polymeric support, solvent, and phase-transfer catalyst (PTC) in both the coupling and... 

The bromine atoms in 2,5-dibromo-l,3,4-thiadiazole 54 undergo a palladium-catalyzed Stille reaction with the organostannyl derivative 55 (Equation 7) <1998CEJ2211>. The thiadiazole 54 was co-polymerized with diethynyl benzene 56 (Equation 8) and diethynyl pyrrole in a Sonogashira cross-coupling reaction <2005MM4687>. 

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 . 

Aqueous palladium-catalyzed Sonogashira coupling reactions were also applied for the preparation of polymers (see Chapter 7). 

The palladium catalyzed benzannulation reaction, described by Yamamoto, was successfully extended to the synthesis of condensed pyranone derivatives. The precursor to the cyclization underwent the benzannulation spontaneously under the applied Sonogashira coupling conditions (8.40.) on formation, to give the desired dibenzo />,ri pyranone. The functionalities tolerated in the process include unsaturated bonds and polar functional groups, such as hydroxyl.52... 

Similarly, palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the 3-iodoindoles proceed smoothly in good yields to give 2,3-disubstituted indoles 848, 849, and 850, respectively (Scheme 162) <2006JOC62>. 

Palladium-catalyzed coupling reactions of 2-(5-iodoisoxazol-3-yl)pyridine 274 with a variety of organometallic compounds led to derivatives 275-278 through Sonogashira, Suzuki, Negishi, and Stille reactions, respectively (Scheme 64) <20010L4185>. 

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. 

No additional phosphines or cooper salts were required, and InCfi itself catalyzed this transformation. Additional studies are required in order to carefully evaluate the mechanism of this transformation, which undoubtedly is different from that of the palladium-mediated Sonogashira reactions. Nonetheless, the simplicity and activity of the catalytic system, as well as its generality with respect to the nature of the leaving group, renders this a promising alternative for the synthesis of internal alkynes. 

Scheme 5.1 Palladium-catalyzed Sonogashira coupling reaction...

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