Ketone-olefin coupling intermolecular

Matsuda et al. have studied the hydroxyl group directed intermolecular ketone-olefin coupling reactions, induced by Sml2, between a-hydroxy ketones and a,P-unsaturated esters or nitriles (Scheme 30). It was noted that reactions... 

The halogenated derivatives of six membered heterocycles, like their carbacyclic analogues, usually participate readily in coupling reactions that involve the incorporation of an olefin or carbon monoxide. The insertion of carbon monoxide commonly leads to the formation of either a carboxylic acid derivative or a ketone, depending on the nature of the other reactants present. Intermolecular and intramolecular variants of the insertion route are equally popular, and are frequently utilized in the functionalization of heterocycles or the formation of annelated ring systems. 

Under conditions of high dilution to prevent intermolecular reactions, two allylic halide groups in the same molecule can be coupled to give a cyclic product. Macrocyclic lactones have been made in this way. Coupling occurs only at the primary centres. Note that the nickel reagents do not attack ester groups. Neither do they react with acid chlorides, ethers, nitriles, olefins or alkyl, aryl or vinyl chlorides (in contrast to bromides or iodides). Aldehydes and cyclic ketones are attacked, however, above 40°C affording homoallylic alcohols. 

Initial work in the early 1970s by Stetter and co-workers established the scope of the intermolecular reaction. Aromatic and heteroaromatic aldehydes are smoothly coupled to a,(3-unsaturated ketones, esters and nitriles under sodium cyanide or thiazolylidine catalysis (entries 1-5, 3a-d). In contrast, the coupling of aliphatic aldehydes and activated olefins (entry 6, 3e) is successful only under thiazolylidine catalysis. ... 

There is only one example in the literature where an enyne RCM coupled to an intermolecular CM in a sequence process has been applied in the synthesis of a natural product. The synthesis of (-i-)-8-epi-xanthatin, isolated from the leaves extracts from Xanthium canadense, was proposed by Martin et al. through an enyne RCM-CM cascade combining ring closing of 8 with a CM with 9 [13]. The special challenge for this transformation consists in the use of an electron-poor olefin for the final metathesis reaction. The use of [Ruj-III (20mol%), the catalyst of choice for this type of transformations [14], and an excess (10 equiv.) of the methyl vinyl ketone 9 resulted in the formation of the desired product in 83% yield (Scheme 11.3). 

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