Alkynyl halides, reactions with carbonyls

An entirely different situation is found in alkynyl halides. Here only examples in which the rearrangement is supported by carbonyl groups [106, 164] or electron-withdrawing pentafluorophenyl groups [165] are known. As one example, the selective reaction of the alkynyl bromide next to the carbonyl group, in the presence of a second alkynyl bromide with a propargylic C-O sigma bond, is shown (88 —> 89) [164] (Scheme 1.38). 

In the synthesis of propargylic alcohols, we saw the reaction of an alkynyl nucleophile (either the anion RC=CNa or the Grignard RC CMgBr, both prepared from the alkyne RC CH) with a carbonyl electrophile to give an alcohol product. Such acetylide-type nucleophiles will undergo Sn2 reactions with alkyl halides to give more substituted alkyne products. With this two-step sequence (deprotonation followed by alkylation), acetylene can be converted to a terminal alkyne, and a terminal alkyne can be converted to an internal alkyne. Because acetylide anions are strong bases, the alkyl halide used must be methyl or 1° otherwise, the E2 elimination is favored over the Sn2 substitution mechanism. 

Mono-a-arylation of carbonyl compounds with aryl halides in dioxane has been effected using the [Pd(cinnamyl)Cl]2/DalPhos catalyst system. 1-Methylimidazole exhibits unusually high efficiency as a base catalyst for conversion of ArCOCH3 to tra 5 -ArCOCH=CHNMe2 on reaction with DMF-DMA this has been ascribed to supramolecular domino catalysis. An unusual a-carboxylative y-lactonization of (g) y-alkynyl ketones (50) on reaction with CO2 has been catalysed by AgOBz with a triazabicyclo decene (Scheme 38). ... 

Until recently, a-substitution of carbonyl compounds was largely restricted to those cases where alkyl groups, such as Me, allyl, and benzyl, were introduced via classical enolate alkylation. a-Aiylation of ketones with aryl halides can be effected using K in NH3 [120-123]. However, this reaction does not appear to be satisfactory for selective -alkenylation and a-alkynylation. -Arylation of ketones has also been catalyzed by Ni [124] and Pd [125,126]. The Pd-catalyzed version employed enolstannanes. This reaction has also been applied to a-alkenylation [127]. However, these reactions appear to be of very limited scope. Thus, the Pd-catalyzed procedures appear to be satisfactory mainly for a-substitution of methyl ketones. Furthermore, none of them addresses the critical question of how to control the regiochemistry of c-substitution, i.e., a vs. a. Critically needed from the viewpoint of selective synthesis were... 

Cross-Coupling Reactions. TASF(Et) activates vinyl-, alkynyl-, and allylsilanes in the Pd-mediated cross-coupling with vinyl and aryl iodides and bromides. As illustrated in eqs 8-10, the reaction is stereospecific and chemoselective. This crosscoupling protocol is remarkably tolerant towards a variety of other functional groups such as carbonyl, amino, hydroxy, and nitro. Vinylsilanes can be synthesized from hexamethyldisilane and vinyl iodides in the presence of TASF(Et) (eq 10) via cleavage of a Si-Si bond. Aryl iodides can also be synthesized by this method. TASF is superior to tetra-n-butylanunonium fluoride for these reactions. In the absence of a vinylsilane reagent, one of the methyl groups from the difluorotrimethylsilicate is substituted for the halide (eq 11). ... 

Abstract The use of organoaluminum-based Lewis acids (A1R X3 R = alkyl, alkynyl, X = halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C-X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels-Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions). 

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