Regioselectivity in alkylation

This difference of regioselectivity in alkylation of CHT is explained by the difference of the electrophile which reacts with the first active intermediate formed from CHT. Thus, the first active intermediate formed by one-electron transfer to CHT is an anion radical species (A) in both the electrochemical and the Li-metal reduction. 

Dianions allow unusual regioselectivity In alkylations of methyl acetoacetate... 

Similarly, the enamine salt 15 is obtained by lithiation of 14 (equation 5). In both cases the lower steric hindrance leads to higher stability of the enaminic system33 where the double bond is formed on the less substituted carbon. The Af-metalated enamines 11 and 15 are enolate analogs and their contribution to the respective tautomer mixture of the lithium salts of azomethine derivatives will be discussed below. Normant and coworkers34 also reported complete regioselectivity in alkylations of ketimines that are derived from methyl ketones. The base for this lithiation is an active dialkylamide—the product of reaction of metallic lithium with dialkylamine in benzene/HMPA. Under these conditions ( hyperbasic media ), the imine compound of methyl ketones 14 loses a proton from the methyl group and the lithium salt 15 reacts with various electrophiles or is oxidized with iodine to yield, after hydrolysis, 16 and 17, respectively (equation 5). 

Jung and coworkers reported an exclusive regioselectivity in alkylation reactions of the dianionic oxime ketone. They showed that a primary or secondary oxime undergoes lithiation when reacting with two equivalents of /-BuLi for 15 min at 0 °C only when it has a syn geometry. Oxime dianion with an anti configuration is formed after a long time, and in a very low yield (equation 35). 

The formylation reaction can be used to prepare ( )-a,p-unsaturated aldehydes from vinylsilanes by ipso substitution (eq 41). Regioselectivity in alkylation reactions may depend on the Lewis catalyst. In a fluorene, regioselective 1,8-chloromethylation results with TiCU (eq 42). TiCU aetivates... 

The problems associated with predicting regioselectivity in quinone Diels-Alder chemistry have been studied, and a mechanistic model based on frontier molecular orbital theory proposed (85). In certain cases of poor regioselectivity, eg, 2-methoxy-5-methyl-l,4-ben2oquinone with alkyl-substituted dienes, the use of Lewis acid catalysts is effective (86). 

The regiochcmistry for stoichiometric alkylation with butyl(cyano)copper magnesium bromide is the same as that for the copper cyanide catalyzed reaction. The regiochemistry with dibutyl-copper magnesium bromide is also very similar to that of the copper(I) bromide catalyzed reaction. Lithium cuprates do not exhibit y regioselectivity in this biased system. 

Scheme 2.27 Proposed mechanism to account for the observed regioselectivity in the allylic alkylations catalysed by Fe-NHC complexes. Other co-hgands on Fe are omitted for clarity...

It is well documented that hydrosilylation of alkyl-substituted terminal olefins catalyzed by transition metal complexes proceeds with high regioselectivity in giving linear hydrosilylation products which do not possess a stereogenic carbon center.2 It follows that the asymmetric synthesis by use of the hydrosilylation of alkyl-substituted... 

Whereas zirconium-catalyzed alkylalumination of alkynes is at present limited to some simple alkyl groups, it has been found that carbozirconation with Cp2Zr(R)Cl considerably expands the scope of the alkylmetalation of alkynes. The reactions are initiated by catalytic amounts of additives (typically Ph3C[B(C6F5)4]), which probably serve to generate cationic zirconocene species. Regioselectivity in favor of attack at the more highly substituted carbon is observed [70,71] (Scheme 8.35). 

The regioselectivity in palladium-catalyzed alkylations has been attributed to the dynamic behavior of trihapto pentadienyl metal complexes60. For example, competing electronic and steric effects influence product formation in dienyl epoxides, but in palladium-catalyzed reactions steric factors were often found to be more important. Thus, alkylation of dienyl epoxide 76 with bulky nucleophiles such as bis(benzenesulfonyl)me-thane in the presence of (Ph3P)4Pd occurred exclusively at the terminal carbon of the dienyl system producing allyl alcohol 77 (equation 39). However, the steric factors could be overcome by electronic effects when one of the terminal vinylic protons was replaced with an electron-withdrawing group. Thus, alkylation of dienyl epoxide 78 affords homoal-lylic alcohol 79 as the major product (equation 40). 

Alkylation of the 2-(l,2-dihydropyrid-2-yl)indane-l,3-diones (3) (Scheme 5.18) by traditional methods, using sodium hydride in apolar or dipolar solvents, leads to a mixture of the C2- and A-alkylated derivatives in moderate to low yield (Scheme 5.18). In contrast, two-phase alkylation results in almost complete regioselective N-alkylation in high yield [64],... 

Allylic substitutions with nonstabilized C-nucleophiles are an important domain of organocopper chemistry [51]. However, on close inspection of the literature, it becomes apparent that regioselectivity in favor of the branched allylic alkylation products is only obtained with alkyl copper compounds, while aryl copper compounds mainly give the linear alkylation products. This observation was an incentive for Alexakis et al. [52] to probe the reactions of aryl zinc hahdes in the Ir-catalyzed allylic substitution (Scheme 9.18). 

In the synthesis through the highly regioselective a-alkylation of a pyridinium... 

---