Alkynes, activation

This study supports rate-determining H-OH bond breaking, which constrasts with previous reports that identified vinylidene isomerization as the key step in catalytic alkyne activation. The results indicate an enzyme-like mechanism is operative involving cooperative substrate activation by a metal center and proximal hydrogen bond donor/acceptors. In the future we will apply these principles to the activation of additional species. 

This reaction impressively demonstrates that even alkyne activation, to date an exclusive domain of late transition metals such as Pd or Pt, can be performed by the cheap and nontoxic Lewis acid Bi(OTf)3 [90]. 

Indenyl ethers were synthesized via intramolecular carboalkoxylation of alkynes. In this process, a benzylic ether group played a nucleophile role to capture a vinyl gold intermediate obtained by alkyne activation. The first catalytic system tested by Toste and Dube in this study was a mixture of [AuClPPh3] and AgBF4. However, the moderate yield prompted them to research the use of more electrophilic gold(I) complexes such as [AuP(p-CF3-C6H4)3]BF4, which increased the yield of cydized products by 70% [107]. 

Following the proposals of Rooney et al. [85—87], it has generally been assumed that, as with monoolefins, the adsorbed state of an alkyne active in hydrogenation is a 7r-complex formed by the interaction of the 7r-orbitals of the acetylenic bond with two metal atoms. The 7r-complexed alkyne may be represented as structure L. 

Hydrofluorination of alkynes.1 The reagent adds to alkynes activated by CN, COOCH3, COR, or CHO groups to form fluoroalkenes. 

The platinum-catalysed intramolecular domino annulation reaction of o-alkynylben-zaldehydes has been described as a versatile approach to naphthalenes with annulated carbocycles or heterocycles of various sizes (Scheme 32).94 A plausible mechanism for the platinum(II)-catalysed annulation reaction shows that the double annulation process most probably proceeds through the benzopyrylium cation (117), which results from the nucleophilic attack of the carbonyl oxygen at the alkyne, activated by the Lewis-acidic platinum salt. A subsequent intramolecular Huisgen-type 3 + 2-cycloaddition of the second alkyne is assumed to generate intermediate (118). Rearrangement to (119) and the formal 4 + 2-cycloaddition product (118) leads to the aromatized final (116), liberating the active catalyst. In the case of FeCl3 as the Lewis acid, we assume that intermediate (118) is oxidatively transformed to (121). 

The reaction of enyne with either an Au(I) or Au(III) catalytic promoter gave a 6-oxabicyclo[3.2.1]octane (Scheme 98).141 The use of Au(PPh3)Cl in combination with AgC104 is equally effective. The possible involvement of the conjugate Brpnsted acid in the alkyne activation of the alcohol was excluded since treatment with HC1 in the absence of AuC13 gave exclusively tetrahydrofuran. 

Scheme 5.17 Sonogashira coupling with electron-withdrawing halide compounds as a peculiar mode of alkyne activation and entry to coupling-Michael addition sequences.

The concept of alkyne activation by Sonogashira coupling was successfully extended to the in situ generation of alkynones that are highly reactive and versatile synthetic equivalents of 1,3-dicarbonyl compounds. Interestingly, ynones can be readily synthesized in a catalytic fashion by Sonogashira coupling of an acyl chlor-... 

Padwa et al.67 have used 3-oxo-lV-propargylamides and esters to build furopyrro-lidinones and furodihydrofuranones via a silver alkyne activation (Schemes 5.16 and 5.17). 

Recently, cyclopropane derivatives were produced by a ruthenium-catalyzed cyclopropanation of alkenes using propargylic carboxylates as precursors of vinylcarbenoids [51] (Eq. 38). The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of the carboxylate to an internal carbon of alkyne activated by the ruthenium complex. Then, a [2+1] cycloaddition between alkenes and carbenoid species affords vinylcyclo-propanes. 

The Sonogashira coupling can be considered a special case of catalytic alkyne activation. Interestingly, it is also possible to conduct alkyne activation under oxidative conditions in the presence of Pd catalysts without oxidative dimerization. Here, Costa and coworkers [139] have developed a Pd-catalyzed sequential carboxylation-alkoxycarbonylation of acetylenic amines in the presence of oxygen to give mixtures of Z- and -configurcd 2-oxo-oxazolidin-5-ylidene]-acetic acid methyl ester 193 and 194 in good to excellent yields (Scheme 75). 

Several enzymes that halogenate organic substrates are well known and these enzymes have been studied extensively, especially those involving alkenes, alkynes, active methylene compounds, electron-rich heterocycles (pyrroles, indoles), and phenols [1,103-105]. Both chloroperoxidase and bromoperoxidase are widespread in the... 

Palladium-Copper Catalyzed Alkyne Activation as an Entry... 

Scheme 2 Alkyne activation by Sonogashira coupling of an electron-poor halide as an entry to coupling-Michael addition sequences...

A couple of years ago we have disclosed a new mode of alkyne activation towards isomerization as a detouring outcome of the Sonogashira coupling. As a result of coupling electron deficient (hetero)aryl halides (or a,p-unsaturated p-halo carbonyl compounds) 11 and aryl propargyl alcohols 12 a new access to 1,3-di (hetero)aryl propenones 13, i.e., chalcones, was established (Scheme 9) [77, 78]. The scope for electron deficient (hetero)aromatic halides 11 is fairly broad and even organometallic complexes like 13c can be synthesized by this sequence. 

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