Metal-Catalyzed Cyclopropanation and Cycloaddition

Reaction 7.4.2.4 is another example of Suzuki-Miyaura coupling in pharmaceutical synthesis. The product 3-amino-2-phenylpyridine is present in nonpeptidic NKl receptor antagonists. The first step is a one-pot reaction where protection of the amino group with PhCHO and the coupling reaction are carried out simultaneously. In the second step simple hydrolysis deprotects the amino group and gives the desired product. 

Structures of three other valuable products 7.61-7.63 are shown later. Total syntheses of all the three include palladium-catalyzed crosscoupling reaction as one of the steps. The synthesis of 7.61, which is used in electronic industries as an adhesive, involves the Heck-Mizoroki reaction, while that of 7.62 and 7.63 includes Negishi and Suzuki-Miyaura reactions, respectively. 

In both metal-catalyzed cyclopropanation and cycloaddition reactions, new C-C bonds are formed. Thus from the point of view of synthetic organic chemistry, they are of substantial importance. 

The fact that activated zinc is a catalyst for reaction 7.5.1 has been known for more than 50 years. However, in recent times certain rhodium and copper complexes have been shown to be particularly efficient as precatalysts for this reaction. It may be noted that when R and R are not hydrogen and not identical, reaction 7.5.1 gives a mixture of four stereoisomers. 

By using chiral precatalysts, in many cyclopropanation reactions, significant diastereo- and enantioselectivity have been achieved. Structures of a few typical precatalysts are shown by 7.64-7.66. 

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