Intermolecular addition reactions regioselectivity

Aoyama and co-workers have also investigated the intramolecular photoamination reactions of several tertiary (aminoal-kyl)styrenes. Irradiation of the (dibcnzylaminoalkyl)styrenes 28 and 29 results, respectively, in the formation of the pyrrolidine 30 and the piperidine 31 as mixtures of diastereomeric adducts. Irradiation of the (aminoalkyl)styrene 32 provides the bicyclic adduct 33 in good yield. Unlike the highly regioselective intramolecular addition of 22 and intermolecular addition reaction of stiibene with W,AI-dimethylisopropylamine (Scheme 3), the intramolecular reaction of the A/-methyl-Af-isopropylamine 34 yields a mixture of adducts 35 and 36 which result from N-methyl and Al-isopropyl hydrogen abstraction, respectively. 

Aryldiazoacetates constitute an effective class of donor/acceptor diazo compounds in the realm of intermolecular carbenoid transformations [79], Because of their electronic profile, they were expected to display increased chemoselectivity for the desired C-H insertion event, while suppressing unwanted side reactions such as carbene dimerization. Additionally, the regioselectivity was expected to be enhanced in more complex systems due to the attenuated reactivity of the carbenoid. 

The gold-catalysed cascade intermolecular addition-intramolecular carbocyclization reaction of dialkynylbenzenes has been reported to occur with regioselective addition of... 

In general, the PET decarboxylation of carboxylic acids exhibits low product selectivity, due to the subsequent radical coupling in solution however, the PET reaction between potassium propionate and the methyl ester of N-methyltrimellitic acid imide is highly regioselective to the para-addition product. This contrasts with other intramolecular and intermolecular PET reactions of quinolinic acid imides, which do not show a high degree of regioselectivity (Scheme S)." ... 

It is much more difficult to control the pair-selectivity and regioselectivity of the intermolecular cyclic carbozirconation. The fundamentally dynamic and reversible nature of most of the microsteps in these reactions is primarily responsible for the often capricious nature of these reactions. Nevertheless, considerable progress has been made recently. In particular, the use of (ethylene)zirconocene in place of (l-butene)zirconocene has been shown to provide convenient and selective procedures, as shown in Scheme 39 13,13c,212,226,227 q [lcsc procedures, however, are still not fully satisfactory, especially in terms of regioselectivity, and additional developmental works are desirable. 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

Recent advances in the rhodium-catalyzed [4-1-2] reactions have led to the development of the first highly regioselective intermolecular cyclization, providing access to new classes of carbocycles with both activated and unactivated substrates. The chemo- and stereoselective carbocyclizations of tethered diene-allene derivatives afford new classes of 5,6- and 6,6-bicyclic systems. Additionally, examination of a wide range of factors that influence both diastereo- and enantioselectivity has provided a significant advance in the understanding of catalyst requirements across these systems. 

Intermolecular cyclotrimerization of alkynes using Wilkinson s catalyst has also afforded substituted carbazole derivatives. This reaction was extended to an intramolecular version by offering the possibility for a six-membered ring annotation that cannot be achieved easily in the corresponding intermolecular version. Intramolecular cyclotrimerization is completely regioselective due to an additional tether. 

Pericas and Jeong demonstrated independently that sulfur-tethered substrates, when subjected to the PKR conditions, afforded the desired bicyclic products. The sulfur tether is removed cleanly by Pummerer reaction after oxidation of sulfur to sulfoxide or 1,4-addition of bisalkyl cuprate followed by hydrogenolysis of sulfide with Raney nickel. It is worth mentioning that the regioselectivity regarding the acetylene part is opposite to that of the intermolecular version (Equation (30)). 

The choice of mercury salt for this reaction appears to be less critical than intermolecular variants and many salts (X = Cl, OAc, NO3, SO4, CIO4, CF3CO2) have been successfully utilized. The electrophilicity of the salt can effect the regio- and stereo-chemistry of addition.434-438 The regioselectivity is also determined by the substitution pattern of the unsaturated alcohol. For cycloalkenes, steric factors, ring strain, and other reaction variables become important (equation 264). High regio- and stereo-selectivity are often encountered in these intramolecular processes. 

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