Formation of Six-Membered Cycles

Formation of six-membered cycles is the second most common case of heterocyclic Mizoroki-Heck reactions, with, as for the formation of five-membered rings, exo-cyclization reactions being largely favoured compared to c d( -cyclization reactions. As already noted for the five-membered cycles, there are more examples of iV-heterocyclic formation than of oxygen-containing heterocycles. 

A greater selectivity at faster rate along with greater reproducibility compared to classical Mizoroki-Heck conditions were observed in favour of the endo-cyclic product 138. 

An intramolecular microwave-assisted Mizoroki-Heck reaction has been described by Smalley and Mills [111] for the preparation of quinol-2-one derivatives. When amide 144 was subjected to standard Mizoroki-Heck conditions under microwave irradiation. 

Guillou et al. [112] used the same type of 6-cxo-cyclization in the total synthesis of ( )-galanthamine, a natural product that we have already come across in the section on 5-eX(9-cyclizations. 

As for 5-endo- versus 5-exo-cyclization, the 6- xo-cyclization is largely favoured compared to the 6-endo mode. There are, nevertheless, some examples of specific 6-e (i(9-cyclizations nsing, as expected, snbstractures previously mentioned to undergo 5-exo-cyclizations [126-128]. They remain an exception, however, and are generally accompanied by other ring sizes. 

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Formation of six-membered cycles is also possible and best achieved using a copper catalyst (Equation (46)). 

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