Formation by intramolecular

Ring formation by intramolecular acylation is exemplified by the isatin syntheses shown in Schemes 37c and 37d (75AHC(18)l). 

Double ring-closure comprising two-bond formation by intramolecular heterocyclrzation of (9-10) atoms open structures consisting of five carbons and four nitrogens (C5N4) (Scheme 32). 

Vinyl radical formation by intramolecular addition of a carbon-centered radical to an alkyne... 

Ring formation by intramolecular reaction between an allylsilane and an aldehyde or ketone is well precedented54, 55. 

Some examples of alkylation reactions involving relatively acidic carbon acids are shown in Scheme 1.3. Entries 1 to 4 are typical examples using sodium ethoxide as the base. Entry 5 is similar, but employs sodium hydride as the base. The synthesis of diethyl cyclobutanedicarboxylate in Entry 6 illustrates ring formation by intramolecular alkylation reactions. Additional examples of intramolecular alkylation are considered in Section 1.2.5. Note also the stereoselectivity in Entry 7, where the existing branched substituent leads to a trans orientation of the methyl group. 

Several examples have been reported for furanone formation by intramolecular C-H insertion of electrophilic carbene complexes [1006,1148] (Table 4.7). Yields can, however, be low with some substrates, possibly as a result of several potential side-reactions. Oxonium ylide formation and hydride abstraction, in particular, [1090,1149-1152] (see Section 4.2.9) seem to compete efficiently with the formation of some types of furanones. 

Scheme 3.18. Ring-formation by intramolecular trapping of the vinylcuprates resulting from silylcupration of alkynes with magnesium silylcuprates [75a] or lithium silylcuprates (mCPBA = m-chloroperbenzoic acid) [75bj.

Ring-chain equilibria involving cyclic tautomer formation by intramolecular reversible amidrazone NH-group addition to the C=0 bond were observed (85KGS849 86ZOR500) in solutions of the products formed in the reactions of pentane-2,4-dione and its 3-methyl derivatives with benzamidrazinium iodides. The ring-chain equilibrium was detected only in solutions of iodides or picrates. The free bases exist as the open-chain tautomers, like the hydrazones or enhydrazines. In contrast with the acyl-... 

One of the earliest reports of C-C bond formation by intramolecular C —H insertion was, in fact, the observation32 that on exposure to lithium diethylamide, ra-9-oxabicyclo[6.1.0]nonane... 

In the last ten years C—C bond formation by intramolecular C—II insertion has evolved from a laboratory curiosity to an effective tool for molecular construction. Procedures for C —C bond formation with control of relative and. in some cases, absolute configuration are now available. The greatest growth has been in the development of rhodium-catalyzed diazocarbonyl insertion reactions. The development of effective cnantioselective catalysts for this process will make it an even more valuable method for ring construction. 

Diketopiperazine formation by intramolecular nucleophilic cleavage proceeds particularly smoothly if a linker prone to facile nucleophilic cleavage is used. In most of... 

Ring formation by intramolecular condensation of oximes has specific geometrical requirements. The oximes 22 formed from the pentafluorodeoxybenzoins cyclize to 1,2-benzisoxazoles 23 at 140-1 50c C indimethylformamide when the hydroxy group is syn to the pentafluorophcnyl... 

The product of Michael addition of an enolate to an a,p-unsaturated carbonyl compound will normally be a 1,5-dicarbonyl compound. The two reactive carbonyl groups separated from one another by three carbon atoms present the opportunity for ring formation by intramolecular aldol condensation. If one of the carbonyls acts as an electrophile while the other forms a nucleophilic enolate, this cyclization gives a six-membered ring. 

In these C-H insertion reactions, the similarity with cyclopropane formation by intramolecular cycloadditions to alkenes is clear, and the mechanisms mirror one another quite closely. As with the cyclopropanation reactions, the path of the reaction differs according to whether the carbene is a singlet or triplet. Singlet carbenes can insert in a concerted manner, with the orbitals overlapping constructively provided the carbene approaches side-on. 

Density functional theory calculations using the hybrid functional B3LYP have been performed to study tetrazole formation by intramolecular [2+3] dipolar cycloaddition of organic azides and nitriles <03JOC9076>. 

Scheme 11.59 Dihydropyran formation by intramolecular reaction of propargylic carbonate with alcohol.

Carbon-carbon bond formation by intramolecular cyclization of conjugated iminium ions is also possible, as illustrated by the transformation of amine oxide (36) to (37), a key intermediate in the synthesis of the pyridocarbazole alkaloid ellipticine (38 Scheme 7). ... 

Lactone formation, by intramolecular condensation of a-acetoxy-ketones in strongly basic media, has been examined systematically. Lithium di-isopropylamide in ether is effective as the base conditions must be chosen according to the reactant. Scheme 8 illustrates successful reactions, which afforded either the /3-hydroxy-y-lactone or the butenolide, depending upon the ease of adoption of the conformation necessary for elimination of water. The method appears to be limited to tertiary a-acetoxy-ketones. 

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>. 

Our synthesis started from hydroxy ketone B (Figure 5.31), which was obtained by asymmetric reduction of prochiral diketone A with fermenting baker s yeast.38 The key step in the present synthesis was the ring formation by intramolecular alkylation of C to give D. To obtain C, the enfifo-hydroxy group of B was first epimerized via retro-aldol/aldol by treatment with p-toluenesulfonic acid in carbon tetrachloride. The tricyclic intermediate D was converted to (+)-pinthunamide (146), mp 187-189°C, [a]D215 = +60 (EtOH), which was identical with the natural product. Its absolute configuration was thus determined as depicted in 146.39... 

For pyrimidine nucleosides, the ease of anhydro-ring formation by intramolecular displacement is in the order 2,2 > 2,3 > 2,5. An-hydrocytidine derivatives are formed more readily than the corresponding anhydrouridines, and N4-acylation further enhances the nucleophilicity of the cytosine residue.419 N-Acyl-2,2 -anhydro-1 -/3-D-arabinofiiranosylcytosines are also more susceptible to hydrolysis at pH 7 than either 2,2 -anhydrouridine or 2,2 -anhydrocytidine. The product isolated after p-toluenesulfonylation of a mixture containing N-acetyl-3 -5 -di-0-acetylcytidine (146) was N-acetyl-l-(3,5-di-0-acetyl-/3-D-arabinofuranosyl)cytosine (149). The 2 -O-p-tolylsulfonyl intermediate (147) presumably cyclizes, to give the 2,2 -anhydride (148), which is rapidly hydrolyzed419 to 149. 

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