Grubbs reaction Intermolecular

Another intramolecular ene-yne metathesis followed by an intermolecular metathesis with an alkene to give a butadiene which is intercepted by a Diels-Alder reaction was used for the synthesis of condensed tricyclic compounds, as described by Lee and coworkers [266]. However, as mentioned above, the dienophile had to be added after the domino metathesis reaction was completed otherwise, the main product was the cycloadduct from the primarily formed diene. Keeping this in mind, the three-component one-pot reaction of ene-yne 6/3-94, alkene 6/3-95 and N-phenylmaleimide 6/3-96 in the presence of the Grubbs II catalyst 6/3-15 gave the tricyclic products 6/3-97 in high yield (Scheme 6/3.28). 

In 2001, Grubbs and co-workers reported the first intermolecular CM reactions for the preparation of unsaturated phosphonates. " Using the highly active NHC catalyst 5, the CM reactions of both allyl and vinyl phosphonates were... 

Enyne systems are also capable of impressive multiple RRM transformations. For the first such example see Ref. [119]. The reaction of a ruthenium alkyli-dene with an alkyne produces a new vinyl alkylidene, which can participate in further intramolecular or intermolecular metathesis reactions to form fused ring systems. This has led Grubbs to designate alkynes in such systems as relays . In a noteworthy example, Zuercher et al. [ 120] constructed the four fused rings of the steroid backbone 68 in one efficient step using tandem enyne re-... 

The intermolecular Mitsunobu alkylation can be followed by a number of other reactions to make larger cyclic structures. The example below shows a phenol alkylation to make a chiral precursor for the synthesis of repintonan (BAY-3702), a high affinity 5-HTia receptor agonist in clinical trials as an ischemic stroke treatment.After the initial Mitsunobu reaction, the alkylated intermediate 99 is converted into the chromene 100 according to a protocol initially developed by Grubbs and Chang. 

An efficient approach to a new family of highly functionalised phosphorus analogues of a-trifluoromethyl-substituted phenylalanine (492) and its homologues via Ru-catalysed intermolecular ene-yne metathesis has been developed. Thus, cross-metathesis of a-allynyl-a-trifluoromethyl-ot-aminophosphonates (489) with alkenes (490) catalysed by a second-generation Grubbs carbene complex (493) afforded corresponding aminophosphonates (491) with 1,3-diene backbone. Finally, one-pot Diels-Alder reaction-aromatisation step gave desired products (492) (Scheme 146). ... 

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