Pseudohalides cross-coupling reactions

For the ketone synthesis via the present protocol, acid chlorides are useful precursors, in deed. Nevertheless, carbonylative cross coupling with organic halides is strategically the most simple and direct way to this purpose. The palladium-catalyzed carbonylative cross-coupling reaction with various organic halides has been extensively investigated, because of its merits from synthetic as well as phenomenal point of view. Acid chlorides are not always readily available, and their preparation is not always compatible with many sensitive functionalities. Therefore the development of this type of reaction widens the scope of the ketone synthesis in the present protocol because of the ready availability and storability of organic halides and pseudohalides. 

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). 

Cross-coupling Reactions. Trimethylsilylmethylmagnesium chloride reacts with organic halides (or pseudohalides), especially aryl and alkenyl halides, in the presence of transition metal catalysts. The reactions directly provide allylic or benzylic trimethyl-silanes of significant synthetic use. 

We reasoned that such a decarboxylation step could also be employed in a redox-neutral cross-coupling reaction with carbon electrophiles. On this basis, we drew up a catalytic cycle that starts with an oxidative addition of aryl halides or pseudohalides to a coordinatively unsaturated palladium(O) species f (Scheme 5). The more weakly coordinating the leaving group X, the easier should be its subsequent replacement by a carboxylate. At least for X = OTf, the palladium(ll) carboxylate h should form quantitatively, whereas for X = halide, it should be possible to enforce this step by employing silver or thallium salts as species g. The ensuing thermal decarboxylation of the palladium(ll) intermediate i represents the most critical step. Myers results indicated that certain palladium(ll) carboxylates liberate carbon dioxide on heating. However, it remained unclear whether arylpalladium (II) carboxylate complexes such as i would display a similar reactivity. If this were to be the case, they would form Ar-Pd-Ar intermediates k, which in turn are... 

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]. 

The first step in most palladium-catalysed cross-coupling reactions is the oxidative addition of an organohalide (or pseudohalide) to a coordinatively unsaturated Pd species. While numerous catalytic systems exist for the activation of C(sp )-I and C(sp )-Br bonds, activation of C(sp )-Cl bonds is a greater challenge owing to their increased stability. There is also an issue in that sterically unhindered electron-rich Pd centres undergo oxidative addition most readily, yet electron-poor and sterically-hindered Pd intermediates... 

In particular, sulfonylhydrazones are valuable coupling partners in Pd-catalyzed cross-coupling reactions with aryl halides and pseudohalides giving rise to alkenes. As an example, the reaction of a chloroarene with the tosylhydrazone derived from 4-tert-butylcyclohexanone leads to an aryl substituted cyclohexenone (Experimental Procedure below). " " Moreover, the reaction can be conducted directly from the carbonyl... 

Cross-coupling reactions between amines and aryl halides or pseudohalides have been employed for the preparation of a number of chiral, nonracemic ligands for asymmetric catalysis. For example, early studies by Buchwald illustrated that chiral amino binaphthol derivatives could be generated by Pd-catalyzed Af-arylation of binaphthol-derived triflates (Eq. 74) [417]. A similar strategy was employed by Erase for the synthesis of planar-chiral [2.2]paracyclophane ligands (Eq. 75) [418]. The A -arylation of [2.2]paracyclophane-derived triflates has also been used for the construction of planar-chiral benzimidazoles [419]. The IV-arylation of a substituted pyrrolidine with 4-bromopyridine played a key role in the synthesis of a chiral nucleophilic catalyst related to DMAP [420]. 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

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