Intramolecular processes oxygen nucleophiles

Several types of intramolecular allylic substitution reactions of carbon, nitrogen, and oxygen nucleophiles catalyzed by metalacyclic iridium phosphoramidite complexes have been reported. Intramolecular allylic substitution is much faster than the competing intermolecular process when conducted in the presence of iridium catalysts. Thus, conditions involving high dilution are not required. Intramolecular... 

The second set of examples involves the use of thionium ions as electrophiles in inter- and intramolecular processes to obtain a-substituted sulfides (see 24 25, Scheme 20.7T which is the most common type of Pummerer reaction. Applications of this classical Pummerer rearrangement are exemplified in the synthesis of trans-solamin, the synthesis of indolizidine alkaloids, and the synthesis of the CDE ring of erinacine E. The first exanple fScheme 20.10 uses Pummerer chemistry in the generation of a thionium ion, which reacts in an intermolecular tin-mediated ene reaction the second one fScheme 20.11 uses Pummerer chemistry to introduce a nitrogen-containing heterocycle by intramolecular addition to form the coniceine core and the third example fScheme 20.12 is an intramolecular silicon-induced Pummerer reaction with oxygenated nucleophiles applied to the synthesis of a precursor of erinacine. Details of these Pummerer-based strategies are discussed below. 

Catalytic and stoichiometric additions of oxygen nucleophiles to coordinated dienes are summarized in Equations 11.33 and 11.34. Early studies involved 1,4-additions of two acetoxy or alkoxy groups across a diene. More recently, intermolecular additions of two different nucleophiles have been developed. The stereochemistry for additions across cyclic dienes makes this procedure particularly valuable. Conditions for either cis or trans additions have been developed. Cis addition is typically observed in the presence of added chloride, and trans addition occurs in the absence of chloride. Both intermolecular and intramolecular " 1,4 additions to dienes have been developed, and reactions of nitrogen and carbon nucleophiles have also been reported. More details on these processes are reported in Chapter 16. 

The oxidations of olefins with many oxygen nucleophiles other than water have also been reported. These reactions include the s5mthesis of vinylic and allylic ethers from reactions of olefins with alcohols and phenols, and vinylic and allylic esters from reactions of olefins with carboxylic acids. These reactions have been conducted with both monoenes and 1,3-dienes. Both intermolecular and intramolecular versions of each of these processes have been developed. Some discussion of these reactions was included in Chapter 11 because of their connection to the nucleophilic attack of oxygen nucleophiles on coordinated olefins and dienes. 

Carbanions are some of the most common nucleophiles through which a new C—C bond can be formed. C—C instead of C—O or C—N bond formation can be achieved with oxygen and nitrogen bidentate nucleophiles in intermolecular reactions. However, in the intramolecular processes, C—O and C—N bonds could be formed. Nucleophiles derived from other heteroatoms react to form a new C-hetCToatom bond. 

Nitrogen nucleophiles such as amines, and in intramolecular reactions amides and tosylamides, readily add to alkenes complexed to Pd derived from PdCl2 (RCN)2 with reactivity and regiochemi-cal features paralleling those observed for oxygen nucleophiles. Intramolecular nucleophilic attack by heteroatom nucleophiles also occurs in conjunction with other palladium-catalyzed processes presented in the following sections. 

Overall intramolecular nucleophilic substitutions at the -position of an indole ring by oxygen nucleophiles have been described. In these reactions PhS02 is displaced from nitrogen by an Sn2 process followed by tautomerism an a-acyl substituent is a prerequisite for the process. 

We have already proposed such a plausible biogenetic pathway for three subtypes of vibsane-type diterpenes as vibsanin B (1) could be transformed into vibsanin C (2) by a Cope-type reaction, based on the results of thermal reactions of 1 [13,19]. Additional isolation of these furanovibsanins compel us to elaborate their biosynthetic process after 2 is produced. Thus, our proposed biosynthetic sequences leading to the furanovibsanins from 2 are outlined in Schemes 6 and 7. Biogenetic conversion of compounds 53-56 and 60 from vibsanin C (2) can be rationalized by a cationic process like (a) in Scheme 6 followed by an acetal formation between C-4 and C-7 ketones and intramolecular addition of oxygen nucleophiles. This is based on the fact that this type of tricyclic formation can be readily realized by... 

The use of oximes as nucleophiles can be quite perplexing in view of the fact that nitrogen or oxygen may react. Alkylation of hydroxylamines can therefore be a very complex process which is largely dependent on the steric factors associated with the educts. Reproducible and predictable results are obtained in intramolecular reactions between oximes and electrophilic carbon atoms. Amides, halides, nitriles, and ketones have been used as electrophiles, and various heterocycles such as quinazoline N-oxide, benzodiayepines, and isoxazoles have been obtained in excellent yields under appropriate reaction conditions. 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

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