Intramolecular selectivity atom addition

The same group was able to perform a similar cycloaddition reaction but with complete reversal of the regioselectivity (Scheme 11.45) [126]. They revealed that the O vs. N selectivity is dependent on the presence or absence of a weak hydrogen-bond donor in the catalyst (OH group), which apparentiy coordinates the oxygen atom of nitrosobenzene to facilitate the formation of iV-nitroso aldol products. Nucleophilic attack of the preformed enamine is postulated to occur from the Re face as described in Scheme 11.45. For steric reasons the subsequent intramolecular 0-Michael addition just occurs when R are CH3 groups. 

Table V. Intermolecular and Intramolecular Selectivity in f Atom Addition to Olefins in Excess SFg (6).

Substitution, addition, and group transfer reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some important synthetic applications, since they permit functionalization of carbon atoms relatively remote from the initial reaction site. ° The preference for a six-membered cyclic transition state in the hydrogen abstraction step imparts position selectivity to the process ... 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

A one-pot synthesis of 3,3-disubstituted indolines was achieved by taking advantage of a sequential carbopalladation of allene, nucleophile attack, intramolecular insertion of an olefm and termination with NaBPh4 (Scheme 16.6) [10]. First, a Pd(0) species reacts with iodothiophene selectively to afford ArPdl, probably because the oxidative addition step is facilitated by coordination with the adjacent sulfur atom. Second, the ArPdl adds to allene, giving a Jt-allylpalladium complex, which is captured by a 2-iodoaniline derivative to afford an isolable allylic compound. Under more severe conditions, the oxidative addition of iodide to Pd(0) followed by the insertion of an internal olefm takes place to give an alkylpalladium complex, which is transmetallated with NaBPh4 to release the product. 

The unproven, but reasonable, assumption implicit to SAR-directed conformational studies, both experimental and theoretical, is that one of the stable intramolecular conformers is the "active conformation, A difficulty to applying conformational data in quantitative drug design is selection of conformational features for QSAR development. Moreover, molecular shape properties are preferable features to have available in design studies. Conformation is a component of shape. The properties of the atoms, most notably their "sizes," comprise an additional set of factors needed to specify molecular shape. 

In conclusion, we have found that the intramolecular dynamics in the benzene molecule at low excess energy is not strongly influenced by the additional three vibrational degrees of freedom of the benzene-Ar complex. The coupling of the excited intramolecular modes to the low-frequency inter-molecular modes is weak. The observed 40% decrease of the lifetime of the 61 state does not depend on the individual excited rotation and points to an external heavy-atom effect as the source of the lifetime shortening observed for the same selectively excited rovibronic state. 

Reactivity in the elimination reaction is probably largely determined by the nature of the substituents (in addition to hydrogen) attached to the y-carbon atom. If the reaction is stepwise, one would expect faster reaction with either 2-hexanone or methoxyacetone than with 2-pentanone, because the biradical intermediates would be more stable in the former two cases. Such a conclusion follows from the similarity shown by various ketone triplets in intermolecular reactions333 to the known selectivity of attack by /-butoxy radicals in both inter-353 and intramolecular reactions.354... 

The transformation of 6-bromo-l-hexene (38) into methylcyclopentane by the action of tributyltin hydride (Scheme 7) typifies the richness of the C—C bond forming chemistry in question. A knowledge of the critical rate constants (kc, ku and Br in Scheme 7) allow, through control of substrate concentration, necessary selectivity criteria to be met. Specifically the 5-hexenyl radical (39) must undergo intramolecular addition to form the cyclopentylmethyl radical (40), 40 must abstract a hydrogen atom from tributyltin hydride and the tributylstannyl radical must abstract the halogen in 38 to form 39. These processes must proceed faster than any competing side reaction. 

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