Palladium catalysed acylation

Palladium catalysed acylation of organozincs preparation of S-nonyn-2-one45... 

Zinc derivatives seem to be more amenable, for example l-benzyloxy-l,2,3-triazol-5-ylzinc iodide (prepared via direct lithiation) couples well, bnt the corresponding stannane is less stable and can only be nsed for palladium-catalysed acylations. ... 

Metal exchange of 5-lithio-l-benzyloxy-l,2,3-triazole with zinc iodide gives a relatively stable zinc derivative which can be used in palladium-catalysed couplings. The corresponding tin compound is less stable and can be used only for palladium-catalysed acylations. ... 

Trimethylstannylfuran can be utilised in palladium-catalysed acylation and arylation." ... 

Palladium-catalysed acylation of tri-O-acetyl-D-glucal is known to give (ISO) as major product and now, by x-ray analysis of its deacetylated derivative, the minor product has been shown to be also the a-linked (151) and not 0- as initially indicated (Can. J. 

Bumagin, N.A. Nikitin, K.V. Beletskaya, I.P. (1990) Palladium catalysed acylation of amines effected by aryl iodides and carbon monooxide, Dokl Akad. Nauk SSSR, 320, 887-90. 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

Palladium-mediated addition of silyl stannane reagents to alkynyl ethers has been employed for the synthesis of aliphatic acyl silanes in very good yields via the intermediate a-alkoxy-/J-stannyl vinyl silanes (enol ethers of acyl silanes)82. In a second palladium-catalysed step, the vinyl stannane moiety could be coupled to suitable halides before hydrolysis to the acyl silanes with trifluoroacetic acid (Scheme 11). 

Reductive cleavage of the carbon-silicon bond of acyl silanes, including a-alkoxy and t/./i-dialkoxy derivatives, to give aldehydes may be accomplished by palladium-catalysed hydrogenolysis at ambient temperature and pressure212. 

Another catalytic methodology that is widely used for C-C bond formation is the Heck and related coupling reactions [86, 87]. The Heck reaction [88] involves the palladium-catalysed arylation of olefinic double bonds (Fig. 1.31) and provides an alternative to Friedel-Crafts alkylations or acylations for attaching carbon fragments to aromatic rings. The reaction has broad scope and is currently being widely applied in the pharmaceutical and fine chemical industries. For example, Albemarle has developed a new process for the synthesis of the anti-in-... 

Palladium-catalysed carbonylation of halides, with carbon monoxide, can be used to prepare esters, amides and ketones by trapping the intermediate acylpalladium halide with alcohols,amines and organometal-lics, respectively. Boronic acids are probably the best organometallics for the preparation of ketones, but conditions must be adjusted to give the best selectivity between the acylation reaction and simple Suzuki coupling of the boronic acid with the starting halide. ... 

Iodination of 4-amino-3-nitrobenzoic acid 9a with iodine monochloride followed by esterification gives iodide 9b. Acylation of 9b with hot acetic anhydride provides amide 9c. Palladium catalyses coupling of amide 9c with Z-vinylstanne [45], generate cis olefin 9d. Treatment of 9d with osmium tetraoxide followed by acetylation with acetic anhydride in pyridine gives triol 9e. 

The synthesis of isosophoramine (26) employs as crucial stages the partial hydrogenation of iV-alkyl salts of ) -acyl (or cyano) pyridines, and acid-catalysed cyclization of the resulting l-alkyl-3-acyl (or cyano)-2-piperideines. Alkylation of nicotinonitrile with 6-bromohexan-2-one ethylene ketal afforded the salt (27), which on palladium-catalysed hydrogenation yielded the piperideine (28). Anhydrous acid-catalysed (TsOH) cyclization of (28) gave the three quinolizidine stereoisomers (29)—(31), which were separated and analysed by n.m.r. spectroscopy and equilibration studies in acid (TsOH-CgH ) and alkaline (KOBu -Bu OH)... 

Allenyl ketones presynthesised, or generated in situ by acylation of silyl-allenes, or by palladium(0)-catalysed isomerisation of conjugated or non-conjugated alkynyl ketones, can be cyclised to furans. The ring closure has been effected with silver or palladium catalysis acylation of silylallenes leads to the furan directly. In the presence of water, palladium(II)-catalysed closure of / ,7-alkynyl ketones is believed to proceed via the enol, not the allene. l,2,3-Trienyl-4-ols have also been shown to cyclise to give furans. ... 

Bromo- and -iodoindoles, and the similarly reactive 2- and 3-triflates, " undergo palladium-catalysed couplings as normal aryl halides. Since 2- and 3-haloindoles are unstable it is expedient to employ their A -acyl derivatives. Halogen and triflate on the benzene ring of indoles take part unexceptionally in coupling reactions. 

The acylation of arenes with alcohols has been shown to be possible using a palladium chloride catalyst in the presence of f-butylhydroperoxide. In 2-arylpyridines, substitution is directed to the ortho-position and, after initial paUadation, the formation of intermediate (59) is likely before reductive elimination yields the acylated product. The regioselective acetoxylation of indoles, at the 3-position, has been achieved using the palladium-catalysed reaction with phenyliodonium acetate. 3-Acyl indoles may also be prepared using acetyl chlorides with zirconium tetrachloride as a Lewis acid catalyst. 

Alkynols 4.105 may be cyclized to a-methylene lactones 4.106 using palladium-catalysed carbonylation (Scheme 4.42)." The reaction is proposed to proceed via formation of an acyl palladium species 4.107, which undergoes intramolecular alkyne insertion. Protonolysis of the carbon-palladium bond of the vinyl complex 4.108 yields the product. 

The ortfro-acylation of IV-benzyltriflamides with benzylic and aliphatic alcohols has been reported using palladiiun catalysis with t-butyl hydroperoxide (TBHP) as an oxidant. The reaction is likely to involve formation of acyl radicals from the alcohols and their reaction with a cyclopalladated intermediate to produce (149). Reductive elimination yields the acylated product. A similar pathway is probable in the palladium-catalysed ortfro-acylation of 2-arylbenzothiazoles to give derivatives (150). There has been an investigation involving both kinetic and DFT studies of the factors affecting the reactivity of aminoesters in cyclopalladation reactions carbonylation may yield products such as (151). 

In the palladium-catalysed carbonylation of aryl bromides to yield benzaldehyde derivatives, IV-formylsaccharin is used as the source of the acyl function. A double carbonylation has been observed in the reaction of aryl halides with carbon monoxide and terminal alkenes which yields 4-arylfuranones such as (152). The proposed mechanism involves oxidative addition of the aryl halide to palladium and insertion of the carbon monoxide to give an acyl palladium species. This is followed by coordination and insertion of the alkene. A second carbon monoxide insertion is faster than -hydride elimination and, after intramolecular attack, leads to the product. The palladium-catalysed reaction of aryl iodides with simple ketones such as acetone in the presence of carbon monoxide has been shown to yield 1,3-diketones such as... 

There have also been reports of palladium-catalysed decarboxylative acylations with a-oxocarboxylic acids. The ortho-acylation of phenylacetamide with phenylglyoxilic acid is likely to involve decarboxylation of a cyclopalladated complex, (157), to... 

The palladium-catalysed regioselective 3 + 2-cycloaddition of vinylic oxiranes with imines produces the corresponding 1,3-oxazolidines in good to excellent yields. The thermal hetero 1,3-dipolar cycloaddition of trimethylenemethane with IV-sulfonyl- and A-acyl-imines produce o -methylene-y-pyrrolidone acetals which can be hydrolysed to y-amino acids. ... 

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