Intramolecular cycloalkylation

Stereochemical positioning of a functional group, relative to a separate enamine moiety in the same molecule, can be done in such a manner that a simple intramolecular alkylation or acylation will cause cyclization. Such intramolecular cycloalkylations with alkyl halides have been reported 107,108). Inftamolecular cycloacylations of enamines with esters 109, 110,110a) and with nitriles 110a,l 11,111a) have also been observed. 

Intramolecular nucleophilic reaction of sp2-geminated organodimetal species gives cycloalkyl metal derivative, which can be converted into the corresponding alkenyl iodide. The iodide can be used for further transition-metal-catalyzed cross-coupling reaction (equations 61 and 62)86. 

Aliphatic ketones (R = alkyl) usually undergo preferential a-cleavage on excitation nevertheless, cyclobutanol formation via intramolecular H-abstraction and cyclization is favoured (a) by an a-fluoro substituent, (b) by the rigidity of the group R (e.g. for R = cycloalkyl or bicycloalkyl), or by irradiation in either (c) inclusion complexes or (d) the crystal itself (solid state irradiation). 

Cycloalkylation (7, 148).2 Cycloalkylation of 2 with (Z)-l was used as one step in a total synthesis of (+ )-sesbanine (6), a constituent of Seshania drummondii seeds with antileukemic activity. The hydroxyl group was introduced into the cyclopentene ring of 4 by iodolactonization followed by reduction to give 5. Final steps included aminolysis of the lactone ring, intramolecular addition of the amide anion to the CN group, and hydrolysis to give 6. 

Christoph, G. Hoppe, D. Asymmetric synthesis of 2-alkenyl-l-cyclopentanols via Sn-Li exchange and intramolecular cycloalkylation. 

The direct functionalization of arenes by primary alcohol sulfonate esters has also been reported.44 5mol% AUCI3/AgOTf was again used as catalyst and high yields (up to 92%) of products obtained in some cases. Higher yields (e.g. 97, 93%) were obtained in intramolecular cycloalkylation reactions of a similar type. 

The rearrangement of [13] bears a close resemblance to the transannular reactions observed in medium sized rings that have been reviewed by Prelog and Traynham (1963) and Cope et al. (1966). Recently Sorensen and coworkers have studied medium sized cycloalkyl cations under stable ion conditions in non-nucleophilic media and demonstrated that their structures are ji.-hydrido-bridged. The bonding situation in these ions contrasts sharply with that in the ions described above and rather corresponds to that of transition states (or intermediates) for intramolecular hydride transfer in these ions. 

Cycloalkyl esters for the side-chain protection of aspartic acid in SPPS have been developed to increase resistance to aspartimide formation. Based on mechanistic studies of this side reaction, these protection groups should fulfill the following criteria provide steric hindrance to intramolecular aminolytic attack of the ester by the amide nitrogen in acidic and basic media, provide increased stability toward repetitive TFA treatments but quantitative cleavage by HE, as well as stabilization of the carbenium ion produced by cleavage of the protecting group to prevent recapture by the peptide. The secondary cycloalkyl esters are more acid stable and more sterically hindered if compared to the primary benzyl esters. In Scheme 7, different cycloalkyl esters are shown. 

Multiple intramolecular ring closures of aryl-substituted unsaturated long chain alcohols, acids, acid chlorides and ethers in the presence of Friedel-Crafts catalysts have been extensively employed to synthesize polynuclear hydroaromatic hydrocarbons and polycyclic ketones. This is illustrated by two examples shown in equations (112) and (113). The application of stereospecific cycloalkylations in approaching the synthesis of complex organic molecules has been reviewed by Barclay. ... 

The solution (dichloromethane) spectra of polymers X, XI, and IX can be seen in Fig. 1. Surprisingly, the absorption spectrum of the l.c. p-methoxycinnamate polymer, IX, showed a 10 nm red shift relative to the two non-l.c.-cinnamate polymers, X and XI. We suggest that, in the thermodynamically most stable conformation the p-methoxycinnamate moiety was intramolecularly perturbed by the phenyl ester group. The ester, phenyl p-methoxycinnamate also shows this perturbation, but the alkyl and cycloalkyl esters do not. CPK (Corey-Pauling-Koltun) molecular models sow that the phenyl ester group could assume an orientation that was almost coplanar with the cinnamate moiety which could easily give rise to a 10 nm red shift (see Fig. 2). 

The functionality of the obtained telechelic polyisobutylenes is affected mainly by the intramolecular cycloalkylation of the initiator. 

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