Intramolecular competition

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

Butynylthio)[l,2,4]triazin-5-ones 504 participate in competitive intramolecular Diels-Alder and intramolecular coplanar cycloamination processes to provide triazinones 505, and pyridinones 506. In relatively inert aromatic solvent systems, their ratios are markedly dependent on the electronic disposition of the substituent at C-6 of 504 (84H1225 88JOC5093). 

Knowledge of the intramolecular product distribution may allow for the partitioning of k between competitive intramolecular reactions, but one must be certain that noncarbenic routes to the products do not compete with the carbenic pathways. In particular, we must be concerned with the possible intervention of RIES (cf. Section m.C), especially when diazirines or diazoalkanes are the carbene precursors. Again, corrections for RIES can be made to quantitate the carbenic routes see, for example, the discussion of the cyclobutylhalocarbene rearrangements (Section m.C.1). 

In this solvent approximately 70% of the molecules adopt a non-planar conformation. A substantially higher proportion of TINS molecules in solution adopt a non-planar conformation as compared with TIN. This may be due to competitive intramolecular hydrogen bonding by the... 

While for 6,6-dialkyIcyclohexa-2,4-dienones. a-cleavage is much too efficient to allow competitive intramolecular cycloaddition processes, 4-alkenyloxy-6-methyl-2-pyrones, such as 17, form oxatricyclic lactones of type 18 on sensitized irradiation.50 51... 

Less satisfactory results have been frequently encountered in the related asymmetric cycloaddition of a vinyl epoxide to an isocyanate as in Scheme 8E.30 [160]. The modest enantioselectivities of this process are indicative of the competitive intramolecular nucleophilic addition with enantioface exchange. When the oxazolidinone was generated from an achiral substrate, somewhat higher enantioselectiviites were obtained presumably due to superposition of the enantioselection obtained in the ionization step. 

N-Tfa- and iV-Fmoc-a-amino ketones have been synthesized56 by reaction of some N -heterocycles or benzene with chiral AM Tfa- and Fmoc-a-aminoacyl)benzotriazoles [e.g. (49)] in the presence of aluminium trichloride. Full preservation of chirality was reported. Aromatic side-chains in some of the (a-amineacyl)benzotriazole compounds gave a competitive intramolecular cyclization, again with retention of chirality [e.g. (49) to (50)]. A full report57 on the intramolecular acylation of aromatics with Meldrum s acid derivatives catalysed by metal trifluoromethanesulfonates under mild reaction conditions has appeared [e.g. (51) to (52)]. The method tolerates many functional groups and was extended to the synthesis of 1-tetralones, 1-benzosuberones and donepezil (53). 

Z)-Benzyl-3-(2-halophenyl)-3-hydroxy-2-(pyridin-2-yl)acrylates 664 can undergo competitive intramolecular ipso-substitutions to form the intermediates 665 and 666. The irreversible elimination of benzyl chloride from intermediate 666 affords 4-hydroxy-3-(2 -pyridyl)coumarins in high yield (Scheme 158) <2001CC639>. 

In general [for a review, see (92KGS851)], this type of equilibrium actually proceeds via the scheme ring-chain-ring, but with a very small concentration of the intermediate open-chain tautomer at equilibrium, which prevents its detection by the methods used for the investigation of these equilibria. The two cyclic tautomers may be formed either by the competitive intramolecular addition of two different nucleophilic groups XH to one multiple bond, or by the same process, but of one nucleophilic group to the two different polar multiple bonds. 

Investigations of the influence of the structure of the substituent R4 on the state of the equilibrium 78B 78B (R1 = Rs = Ph R2 = Me R3 = H) showed that increase of the steric demands of R4 leads to a strong equilibrium shift toward 78B. Apparently, of the two competitive intramolecular NH group addition pathways, the addition to the sterically less shielded C=N bond predominates (see Table XIII). The equilibrium 78B 78B was reached over several hours. The character of the solvent and temperature change exerted little influence on the equilibrium. 

FIGURE 13. Molecular structure of the chloro(alkyl)stannylene 61a (left) and of chloro(alkyl)plum-bylene 62b (right) in the crystal, both forming asymmetric halogen-bridged dimers due to competitive intramolecular Lewis acid/Lewis base interactions. These are depicted as dashed lines (----) and the longer E—Cl bonds as thin solid lines... 

Shinkai, S., Ishira, M., Ueda, K., and Manabe, O. Photoresponsive crown ethers. Part 14. Photoregulated crown-metal complexation by competitive intramolecular tailfammonium)-biting./. Chem. Soc. Perkin Trans. 2 1985, 511-518. 

Photochemically generated cyclopropylchlorocarbene exhibits competitive intramolecular and intermolecular chemistry. 

Introduction of a methyl group at C-2 resulted in competitive intramolecular [2 + 2] cycloaddition followed by [3,3] sigmatropic rearrangement. 

There is another interesting variation of this reaction that involves intramolecular N—H insertion of a-diazo-carbonyls. When diazoketone 397 was treated with cupric bis(acetylacetonate), for example, a 74% yield of azetidinone (398) was obtained. It was shown that competitive intramolecular C—H insertion by the carbenoid was not a problem, illustrated by the presence of 10 equivalents of styrene in the reaction. The styrene actually seemed to enhance the N—H insertion reaction. 

Indeed, the solution conformation of sucrose is surmized to depend on the nature of the solvent and therefore the disruption of one or both of the intramolecular hydrogen bonds that are present in the crystal structure. For aprotic polar solvents such as DMSO and DMF, the occun ence of two conformations with competitive intramolecular hydrogen bonds was suggested, namely 2-0 HO-l and 2-0 HO-3, the equilibrium being in favour of the former (Fig. 7.4) [7]. 

Further evidence to exclude the triplet radical pathway includes the use of cyclopropyl substrates, which serve as a radical clock. In all cases, the reaction proceeds with no indication of ring fragmentation. The nature of the transition state of the C—H insertion step has been analyzed, via a Hammett study of the intermo-lecular C—H amination with p-substituted benzenes. A negative q value of 0.73 is obtained for the intermolecular reaction with trichloroethylsulfamate [71]. Such data indicate that there is a small, but significant, preference for electron-rich substrates, thus the resonance does contribute to the stabilization of a partial positive charge at the insertion carbon in the transition state. A kinetic isotope value of 1.9 is observed for competitive intramolecular C—H amination with a deuterated substrate (Eq. (5.21)). 

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