Ring with heteroatom nucleophiles

Ring-opening with heteroatomic nucleophiles is certainly among the most thoroughly studied behavior of epoxides, and this reaction continues to be a versatile workhorse of synthetic utility. This is exemplified in the recent literature by the examples of the p-cyclodextrin-catalyzed aminolysis of simple epoxides by aniline derivatives (i.e., 53 - 54) <00SL339> and the synthesis of oxa-azacrown ethers through the treatment of Ws-epoxides 55 with diamines 56. Yields in the latter synthesis are sensitive to the size of the macrocycle and substitution on the bis-epoxide <00TL1019>. 

Nucleophilic ring opening of epoxides with heteroatom nucleophiles is another valuable method for the synthesis of many heteroatom-modified carbohydrate derivatives. The cyclic nature of epoxides renders the competing elimination process stereoelectronically unfavorable. Analogous to the above-discussed Sn2 nucleophilic mechanism, nucleophiles can open epoxide rings, and give rise to Walden inversion at the attacked carbon, furnishing a-hydroxy derivatives as illustrated in O Scheme 10. 

Ring-Opening Unsymmetrical Oxa- and Aza-bicyclic Alkenes with Heteroatom Nucleophiles 427 Y = halide or excess ligand... 

Table 10.1 Ring opening unsymmetrical oxabicyclical alkenes with heteroatom nucleophiles using an achiral Rh -catalyst.

Ring-Opening of Vinyl Epoxides with Heteroatom Nucleophiles... 

In contrast with aliphatic nucleophilic substitution, nucleophilic displacement reactions on aromatic rings are relatively slow and require activation at the point of attack by electron-withdrawing substituents or heteroatoms, in the case of heteroaromatic systems. With non-activated aromatic systems, the reaction generally involves an elimination-addition mechanism. The addition of phase-transfer catalysts generally enhances the rate of these reactions. 

Vinylketene complexes, generated by treatment of heteroatom-substituted carbene complexes with alkynes, can react intramolecularly with different nucleophiles to yield cyclic compounds (Figure 2.30, Table 2.20). Four- to ten-membered rings have... 

Nucleophilic Attack on Ring Atoms Adjacent to Heteroatom or Conjugated with Heteroatom... 

A very large number of these systems with ring junction heteroatoms exists, and this number is constantly increasing. Only illustrative examples of the preparation of such systems can be given here. The synthetic methods for the formation of this type of heterocycle can be usefully classified as follows (i) various cyclocondensations between the corresponding heterocyclic derivatives and bifunctional units, (ii) intramolecular cyclizations of electrophilic, nucleophilic or (still rare) radical type, (iii) cycloadditions, (iv) intramolecular oxidative coupling, (v) intramolecular insertions, (vi) cyclization of open-chained predecessors, (vii) various reactions (quite often unusual) which are specific for each type of system. Examples given below illustrate all these cases. 

With tetrahexylammonium as the cation of choice and 5 as ligand, the established conditions for the alkylation with carbon nucleophiles has been successfully applied to asymmetric introduction of heteroatoms such as nitrogen, oxygen, and sulfur (Eq. 8E.7), As shown in Table 8E.8, excellent enantioselectivities are observed independent of the counterion of the heteroatom nucleophiles and the ring size. 

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