Terminal alkynes palladium-catalyzed coupling

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

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). 

The Merck process group in Rahway has developed two syntheses of rizatriptan (4) utilizing palladium catalyzed indolization reactions (Schemes 19 and 20). Both routes start from the iodoaniline 51, which was prepared by reaction of 47 with iodine monochloride in the presence of CaCOa. " Palladium catalyzed coupling of iodoaniline 51 with bis-triethylsilyl protected butynol in the presence of NaaCOa provided a mixture of indoles 52a and 52b. This mixture was desilylated with aqueous HCl in MeOH to furnish the tryptophol 53 in 75% yield from 51. Protection of the alkyne prevented coupling at the terminal carbon of the alkyne and tnethylsilyl (TES) was found to be optimal because it offered the correct balance between reactivity (rate of coupling) and... 

Bisethynylation of yic-dichloroethylenes.u Enediynes can be prepared by the palladium-catalyzed coupling of terminal alkynes with v/c-dichloroethylenes, particularly with the ds-isomer (equation I). 

Although catalytic amounts of Ag20 have been found to promote the palladium-catalyzed coupling of aryl boronic acids and terminal alkynes, the authors in this case do not attribute the desired reactivity to the formation, and subsequent transmetalla-tion, of a silver acetylide. Rather, it is proposed that the Ag20 activates the alkynylpalladium complex to allow transmetallation from the boronic acid, and that any competing formation of the silver acetylide results in a homocoupling of the alkynes (Scheme 1.55).123... 

Haloheterocycles undergo palladium-catalyzed coupling with terminal alkynes and alkenes, for example, 4-bromo-(Scheme 153) and 5-bromooxazoles give coupled products in fair to good yields. (See also Section 3.4.3.10.2 for other palladium-catalyzed cross coupling examples.)... 

Pirguliyev, N. S., Brel, V. K., Zefirov, N. S., Stang, P. J. Stereoselective synthesis of conjugated alkenynes via palladium-catalyzed coupling of alkenyl iodonium salts with terminal alkynes. Tetrahedron 1999, 55, 12377-12386. 

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... 

Gelman, D. Buchwald, S. Efficient palladium-catalyzed coupling of aryl chlorides and tosylates with terminal alkynes use of a copper cocatalyst inhibits the reaction. Angew. Chem., Int. Ed. 2003, 42, 5993-5996. 

Zhang et al. reported that the palladium-catalyzed coupling/indole cyclization of the terminal alkynes 590 with the resin-bound o-iodoaniline 589 and subsequent treatment with TBAF gave the indole derivatives 591 in high yields and with high purities (Scheme 182).256a The reaction proceeds through... 

Z)-l-Bromoalkenes 144a can be prepared in situ as intermediates for the synthesis of terminal alkynes 145 by elimination in the presence of DBU or for the preparation of (Z)-enines 146 by palladium-catalyzed coupling with alkynes (Scheme 5.40) [84c]. Both reactions were performed with microwave irradiation and gave good to excellent yields. 

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. 

Alkynes are known to undergo the Cassar-Sonogashira reaction, which consists of the palladium-catalyzed coupling of a terminal alkyne with an aryl halide... 

Concurrent with this disclosure, Rossi reports a similar protocol wherein 2-acyl-l-(phenylsulfonyl)-3-iodoindoles 189 undergo room temperature palladium-catalyzed coupling with terminal alkynes to afford the corresponding 3-alkynylindoles 190 <01S2477>. Subsequent treatment with ammonia in methanol leads to formation of the p-carbolines 191 through sequential addition/elimination/cycloamination reactions accompanied by loss of the A -phenylsulfonyl group. 

Application of carbon-carbon cross-coupling/67C-electrocyclization cascade reactions in pyridine synthesis is well known. Larock and coworkers developed a palladium-catalyzed coupling of vinylic imines 279 with terminal alkynes 280 followed by subsequent copper-catalyzed cyclization of 281 to give aryl, vinyl, and alkyl-substituted pyridines 282 in moderate yields. ... 

Thorand, S. and N. Krause. 1998. Improved procedures for the palladium-catalyzed coupling of terminal alkynes with aryl bromides (Sonogashira coupling). J Org Chem 63 8851. 

An alternative approach to multicomponent heterocycle synthesis involves the use of palladium catalysis to construct keto-alkynes for cycloaddition reactions. Muller has demonstrated the power of this approach in the construction of a range of aromatic heterocycles. For example, the palladium-catalyzed coupling of acid chlorides with terminal alkynes provides a method to assemble 36. The trapping of this substrate can provide routes to aromatic heterocycles. As an example, the addition of amidines provides a multicomponent synthesis of pyrimidines (Scheme 6.69) [97]. This same substrate 36 is available via the carhonylative coupling of aryl halides with terminal alkynes, providing a four-component synthesis of pyrimidines (98j. 36 can also be employed in 1,3-dipolar cydoaddition reactions. For example, cydoaddition... 

Palladium-catalyzed coupling of the silyl bromide to the terminal alkyne (10) gives the propargylic allylsilane (11), which is a key intermediate in the synthesis of a 10-membered cyclodiynol analog (12) of the antitumor agent neocarzinostatin (eq 19). ... 

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... 

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

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