Atom carbon-heteroatom coupling reaction

The 1,3-disposition of the heteroatoms also imparts differential acidities to the ring positions, enabling sequential deprotonation. This rich acid-base chemistry permits selective functionalization of each ring-carbon atom. The synthesis of other organometaUic oxazoles and transition-metal-catalyzed cross-coupling reactions are also described. Applications of new cross-coupling methods for preparing polyoxazoles in the context of the syntheses of natural products are described in Section 1.5. 

The reactions in Scheme 38 with allenes as coupling components proceed regioselec-tively with C—C bond formation at the central carbon and carbon-heteroatom bond formation at the more highly substituted terminal carbon atom t i Reactions of this type have recently been performed enantioselectivelyJ " Remarkably, for the macrocyclization in Scheme 39 the carbon-heteroatom bond formation takes place at the unsubstituted terminal carbon atomJ ... 

The sole method of synthesis that has been developed thus far involves the formation of a diGrignard or dilithio reagent from o,o -dibromobi-benzyl. The dibromo derivative is prepared by the coupling of o-bromobenzylbromide with phenyllithium (215). An alternative route that would utilize ring closure at the bridging carbon atoms (i.e., a site remote from the heteroatom) has not yet been explored. The dibenzazepin and dibenzoxepin derivatives have been prepared by this approach 35). The Grignard reactions are summarized in Eq. (97). 

The coupling of an allyl or acyl moiety onto carbon atoms is achieved by anodic oxidation of a-heteroatom substituted organostannanes or Oj -acetals in the presence of allylsilanes or silyl enol ethers. The reaction probably involves carbocations as intermediates that undergo electrophilic addition to the double bond [245c]. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

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