Pseudohalides nucleophilic reactions

Reactions of a variety of weaker nucleophiles such as halide and pseudohalide ions and [Pt(PPh3)2(CNCH3)2] have been studied (747) and, as might be expected, ligand replacement is usually observed [Eq. (11)]. 

In these reactions the polarisation effect of the metal can activate an alkyl group towards nucleophilic attack. The incoming nucleophile is most commonly a halide or pseudohalide, and iodide or thiocyanate are particularly active in these processes. Numerous examples of such reactions are known, which are accelerated by co-ordination of the metal to oxygen. An example is shown in Fig. 4-46 in which the metal stabilises a phos-phonate leaving group. 

An alternative approach to 9-substituted acridinium salts and thence the corresponding acridines involves the conversion of 9-acridones into the 9-trifluoromethanesulphonyloxy acridinium salts (17), which react readily with halides, pseudohalides such as azide and isothiocyanate, and sulphur nucleophiles (B. Singer and G. Maas, Z. Naturforsch., 1984, 39b, 1399). The free base restilts on reaction with diisopropyletlylamine. 9,9 -Bisacridine ethers are also available by this methodology. 

The scope of this reaction is limited to electron-rich arenes and heteroarenes such as thiophenes, pyrroles, furans, indoles, and alkoxybenzenes as nucleophilic partners, corresponding to a Mayr ir-nucleophilicily parameter N>-1 [75-78], Electron-neutral to electron-deficient iodo(hetero)arenes are suitable electrophilic partners. Aryl halides or pseudohalides that are less reactive towards oxidative addition (Br, Cl, OTf) are not sufficiently reactive partners in this reaction. The reactivity of sterically hindered and/or ortho substituted iodoarenes has not been demonstrated. However biaryls bearing one ortho substituent of relatively small steric demand (e.g., from methoxybenzene or /V-mcthylindole) have been prepared. 

Nucleophilic anions, i.e. halides, pseudohalides, alkoxides, phenoxides, and thio-phenoxides, are particularly suitable for these reactions. Even anions of lower reactivity in nucleophilic displacements, i.e. carboxylates, nitrates, nitrites and hydroperoxides, find practical application under PTC conditions. Reactions are rigorously Sf,2 in mechanism primary substrates are thus most suitable, since secondary substrates afford elimination products in high yields, especially when reacted at high temperatures, and tertiary substrates only give rise to elimination. This behaviour is consistent with the low polarity of the organic phase, preventing unimolecular mechanisms and favouring elimination over substitution when the reaction center is not a primary carbon atom. 

Oxidative additions of alkyl halides and pseudohalides can occur by an S 2 mechanism in which the metal acts as a nucleophile (Equation 7.1). The first step of this reaction is analogous to the alkylation of an amine. The data in support of an S 2 mechanism for... 

Palladium-catalyzed lactonization with CO insertion is a useful method that has been developed over the years to become an important tool in organic synthesis. The most straightforward approach consists of an oxidative addition of Pd(0) to a vinyl/aryl halide or a pseudohalide (e.g., triflate) followed by insertion of carbon monoxide and subsequent intramolecular attack of the oxygen nucleophile onto the carbonyl, with regeneration of the Pd(0) catalyst. An appropriate base is necessary to trap the acid released during the reaction (Scheme 1). 

Preparations of all these organic materials involve the constmction of new carbon-carbon bonds and have prompted the development of many catalytic cross-coupling reactions. One of the most reliable synthetic methods to form carbon-carbon bonds is transition metal-catalyzed cross-coupling between organo-metallic nucleophiles and electrophilic organic halides or pseudohalides, respectively (Scheme 2a). The mechanisms of common cross-coupling reactions such as the Suzuki, Negishi, or Stille catalysis can be described by a catalytic cycle, differ in detail, but all include three main steps in the order oxidative addition, transmetallation, and reductive elimination (Scheme 1). 

An associative or mechanism involving attack by the anions at the tungsten center was considered unlikely, and a concerted process involving initial attack at a carbonyl carbon was proposed (Scheme 13). The alternative initial addition of X to a carbonyl ligand followed by loss of COX and rapid pick up of X" was eliminated by the failure to trap the five-coordinate [W(CO)5]. On the basis of these and earlier studies it seems probable that most reactions of anionic nucleophiles (N3, halides, pseudohalides) with [M(CO)6] (M = Cr, Mo, or W) complexes involve interaction at a carbonyl carbon. 

The carbonylative palladium-catalyzed reactions discussed in this section proceed by oxidative addition of palladium (0) to the carbon-X bond of aryl/vinyl/acyl halides and pseudohalides followed by carbon monoxide insertion, giving rise to an acylpalla-dium intermediate. The acylpalladium intermediate can in turn react with various tethered nucleophiles (a), be involved in activation/hetero or carbopalladation steps with unsaturated carbon-carbon bonds (b), or participate in cascade reactions (c) (Scheme 13.1). 

The palladium-catalyzed cross coupling reactions can be divided into two general types depending on the nucleophilic coupling partner. Both types of the reactions employ an organohalide or pseudohalide as the electrophilic coupling partner. The accepted general mechanisms are depicted in Scheme 3.11 [47]. 

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