Regiocontrolling factors

The regioselective synthesis can be carried out in the limits of only electrochemical synthesis. In these transformations, the nature of metal complex-former (material of the anode) and of donor atom X (N, O) are the main regiocontrolling factors forming, for instance (4.38), the coordination sphere of the chelates 864 and 865 [119] ... 

High regiocontrol is based on the predominant contribution of electronic factors. Since the nitrone carbon and the a-carbon of the acceptor are the sterically more hindered termini in each reagent, the formation of the electronically controlled regioisomer (e.g., the 4-acylisoxazolidines) should be much less favored. 

Steric factors, in some cases, are the key to the regiocontrol in intermolecular cyclopropanation reactions. The inertness of trisubstituted double bonds to palladium catalysed cyclopropanation may explain the extremely regoselective cyclopropanation observed with FK 506 (equation 10)20. 

An additional issue of regiocontrol arises in asymmetric induction when the n-allyl complex possesses a primary terminus. Although steric factors favor the formation of the achiral linear product, alkylations with reactive nucleophiles often benefit from electronic effects leading to the branched product [ 147,148]. Of particular interest is the reaction of the crotyl system because... 

At this point, consideration was next accorded to proper introduction of the pair of substituents as in 34. As expected, the regiocontrolled introduction of a methyl group proved not to be problematic, and lithium diisopropylamide came to be favored as the base. The p isomer 29 predominted by a factor of 5 1 over the a isomer for the usual steric reasons (Scheme 5). To reach silyl enol ether 31, it was most efficient and practical to react the 29/30 mixture with chlorotrimethylsilane under thermodynamic conditions. This step proved to be critical, as it allowed for implementation of the Lewis acid-catalyzed acetylation of 31 under conditions where the benzyloxy substituent was inert. Equally convenient was the option to transform the modest levels of enol acetate produced competitively back to starting ketone by saponification with methanolic potassium hydroxide. 

Donor/acceptor-substituted carbenoids are usually much more chemoselective than the more established carbenoids functionalized solely with acceptor groups [lc]. The development of these donor/acceptor-substituted carbenoids has enabled enantioselective intermolecular C-H insertions to become a very practical process. These carbenoids have a strong preference for functionalizing C-H bonds where positive charge build-up at C in the transition state is favored but these electronic effects are counter-balanced by steric factors. Benzylic and allylic sites and C-H bonds adjacent to oxygen and nitrogen functionality are favored but these sites can also be sterically protected if desired. By appropriate consideration of the regiocontrolling elements, effective intermolecular C-H insertions at methyl, methylene, and methine sites have been achieved. 

In addition to enantiocontrol, the problem of regiocontrol arises in these reactions. There are various factors that influence the regioselectivity of allylic substitutions [3,4,13, 36, 37, 38, 39]. Electronic effects exerted by the catalyst and the allylic substituents, steric interactions between the nucleophile, the allyl system and the catalyst, and the relative stabilities of the Ti-olefin complexes formed after nucleophilic addition, can all play a role. The relative importance of these factors varies with the catalyst, the substrate, the nucleophile, the solvent and other reaction parameters and is difficult to predict. 

Thus, there are two likely factors responsible for regiocontrol strain-induced selective activation of one of the allyUc termini and sterically controlled rotation of the allyl ligand during nucleophiUc attack. This mechanistic model is also consistent with results obtained with other types of C2-symmetric N,N- and P,P-ligands [66,82,83]. 

Beyond the chemoselectivity, the regioselectivity of the alkyne incorporation is another important criterion for the synthetic value of the benzannulation. The regiocontrol mainly arises from steric factors which favour a coupling of the alkyne carbon bearing the less bulky alkyne substituent with the carbene... 

Low meta substitution allows favorable regiocontrol in the subsequent preparation of dinitrotoluenes. In general, the nitric add-trifluoro-methanesulfonic acid system shows less meta substitution than other nitrating systems at comparable temperatures (Table IV). The major factor, however, effecting low meia nitration is the use of extremely low temperatures. Solubility of the formed nitronium salt at low temperature in halomethane solutions is limited and unusual ortho/para ratios ma> be also a consequence of the heterogeneous nature of the reaction mixtures. 

Regiocontrol for the Robinson annotation is an important factor that can infiuence a synthetic route because there are two a-carbons to the keto group to be considered. Consequently, techniques for regiocontrol have been developed. Under either the basic or acidic standard annulation conditions deprotonation occurs under thermodynamic control at the higher substituted carbon and hence forms an angular substitution at the fused side of the end-product. An exception to this is steric hindrance where alkylation occurs at the least substituted a-carbon, as shown in the synthesis of 9. ... 

Without doubt, it is possible to characterize the developments made in the area of pyridinium salt photochemistry as slow and far between. More recent investigations of this chemistry have begun to uncover its synthetic significance. However, a number of questions pertaining to the mechanism of the photocyclization process, the factors governing the rates of ring isomerization, and the regiocontrol of nucleophilic addition to the unsymmetricaUy substituted cation intermediates still need to be answered before the full potential of this unique excited-state process can be elaborated. 

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