Intramolecular reaction displacement

Figure 3.11 shows the relative reactivity as a function of ring size for two other intramolecular displacement reactions, namely, conversion of ethers from ca-bromoalkyl monoethers of 1,2-dihydroxyben-zene. 

The Baeyer-Villiger oxidation of cyclohexanone to form e-caprolactone (78) using peroxybenzoic acid, as indicated in equation (40), may be considered as a further type of intramolecular displacement reaction of value in seven-membered ring synthesis (49JA2571). 

A plausible rationale for the above Mg2+ ion catalysis may be electrostatic facilitation of nucleophilic attack to form a pentacovalent intermediate as depicted in the structures of Figure 12. This rationale already has been proposed by Steffens et al. for the metal ion catalysis in the intramolecular displacement reaction of phenolate ion by car-boxylate (17). 

The electrochemical reduction of R2SiCl2 in the presence of 2,3-dimethylbutadiene proceeds smoothly to give the sila-cyclopentene derivatives [Eq. (53)] [193]. Probably the initial reduction of R2SiCl2 produces an silyl anion, which adds to the 1,3-diene. The intramolecular displacement reaction of the resulting allylic carbanion with the chlorosi-lane moiety gives the cyclized product. 

Deprotonadon of thioanisole and addition of a carbonyl compound affords an isolable hydroxy sulfide which can then be alkylated (Scheme 7). Treatment with base generates the same betaine that would have been formed using the sulfur ylide approach, and effects the intramolecular displacement reaction. The addition of methylthiomethyllithium to 2-cyclohexenone exclusively provides the 1,2-addition prod-uct the dianions derived from phenylmethanethiol or allylthiol react in a similar manner. In one case a 6-keto steroidal substrate was found to undergo smooth methylenation using this procedure. 

Intramolecular displacement reaction of allylic acetate with amines has been applied to the synthesis of certain alkaloid skeletons such as desethylibogamine and ibogamine (183) as shown in Scheme 54 74. The reaction involves allylic rearrange-... 

These react ions can be readily correlated by the assumption of a prc-Jiminary intramolecular displacement reaction effected by the nitrogen or sulfur atom to form a cyclic onium salt. The complete sequence may be outlined as follows ... 

Oxirane formation by intramolecular displacement reactions of halohydrins (2-halo-1-ols) is a general and useful reaction, as discussed in Chapter 1.03.4.2. A unique example of an intramolecular substitution is observed during f-butyllithium addition to (156) the reaction involves 1,2-attack of the resulting alkoxide ion in (157) with concomitant 1,2-alkyl shift to give the protoadamantane derivative (158), reminiscent of a fragmentation reaction (Scheme 29) <91JOC1700>. 

In the substrates shown in Table 1, the LG is attached to a primary carbon atom. The intramolecular displacement reaction is also possible when the LG is present at a secondary or tertiary carbon atom, see Table 2. Of particular note is entry 7 in Table 2 where a triflyl group serves as LG. 

Similar base-catalyzed ring contractions of methyl 3,4-epoxycyclohexanecarboxylate have failed such attempts resulted in intermolecular attack of the epoxide ring rather than in the expected intramolecular displacement reaction. 

Inter- and intramolecular displacement reactions at phosphorus which proceed by way of intermediate phosphoranes incorporated in a small-ring system may be generalized by Eq. (11), in which the convention of assigning indices 1 and 2 to the ring termini is employed. Since a small-ring system is incapable of spanning the a positions, diastereomer 12/12 and its six connect-... 

Intramolecular Displacement Reactions Proceeding Through Cyclic Intermediates... 

Guanidine and substituted guanidino groups can take part in intramolecular displacement reactions to give three- or five-membered rings. Thus, the reaction of refluxing ethanohc benzylamine with the substituted cyanamide (226) yielded the 2-iminoimidazolidine (228) the intermediate guanidine (227) is obviously the precursor of (228). 

The lithiated intermediates could then rearrange to products via ion pairs or concerted intramolecular displacement reactions. Perhaps the major objection to invoking ylid or lithiated ylid intermediates is that more products should have been detected than were actually observed. 

Formation of oxacycles via intramolecular radical addition reactions of oxygen-centered radicals under oxidative and reductive conditions is known [116] (see also Chapter 5.2, Volume 2). However, cyclic ether formation via intramolecular displacement reaction of iodohydrins obtained by hydrogen abstraction of oxy radicals has been more widely used, as exemplified in the reports by Suarez [117]. The usefulness of this reaction was amply demonstrated by Paquette in the synthesis of (-t-)-epoxydiclymene (179) [118] (Scheme 61), in which the strained trans-... 

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