Cyclofunctionalization heteroatom

The above definition excludes a number of types of heteroatom cyclofunctionalization reactions from discussion in this chapter. Examples include neighboring group participation in which the cyclic structure is only a transient intermediate cyclization reactions where the C—C tr-bond is internally activated... 

While the regiochemistry of simple electrophilic additions to double bonds is controlled by a combination of electronic (Maikovnikov rule), stereoelectronic (trans diaxial addition to cyclohexenes) and steric factors,9 the intramolecular nature of electrophilic heteroatom cyclizations introduces additional conformational, stereoelectronic and entropic factors. The combination of these factors in cyclofunctionalization reactions results in a general preference for exo cyclization over endo cyclization (Scheme 4).310 However, endo closure may predominate in cases where electronic or ring strain factors strongly favor that mode of cyclization. The observed regiochemistry may differ under conditions of kinetic control from that observed under conditions of thermodynamic control. 

The stereochemistry and regiochemistry of cyclofunctionalization reactions in the following sections are discussed in terms of the above mechanistic concepts. Emphasis is placed on the relationship between the products and the heteroatom-substituted substrates thus, examples of electrophilic heterocycli-zation involving two sequential additions to nonconjugated dienes are not discussed. These reactions have been covered in a recent review. ... 

Cyclofunctionalization reactions involving oxygen nucleophiles have been studied more extensively than reactions involving any other heteroatom. Examples of functional groups used as oxygen nucleophiles are shown in Figure 1. 

Alkyl ethers can act as nucleophiles in cyclofunctionalization reactions,17 and recently acetal oxygens have been shown to be excellent nucleophiles for participation in heteroatom cyclizations (Scheme 9). This reaction has been used as a nonhydrolytic procedure for unraveling complex acetals (conversion of 9 to 10),180 for specific liberation of an anomeric center (conversion of 11 to 12),181a for preparation of glycosyl bromides18115 and for saccharide coupling (reaction of 13 and 14 to give 15).182... 

As can be observed in Scheme 70, these transformations have parallels with well-established selenium processes.195 Contrary to the cyclofunctionalization using selenium reagents, the tellurium version does not tolerate the presence of amines to capture the HC1 formed during the process, since amines react with organotellurium trichlorides.5,196 In this way, although several cyclizations can be successfully performed using tellurium electrophiles, the selenium methodology continues to be the method of choice for this purpose in view of the milder cyclofunctionalization conditions and the easier removal of the heteroatom at the end of the process. 

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