Substituents regioselectivity

The intermediate enol silyl ether permits further regioselective substitutions such as bromination followed by dehydrobromination (Eq. 81)49> and alkylation (Eqs. 82 93) and 83 103)). Thus, in addition to activating the rearrangement, the oxygen substituent regioselectivity creates an enol silyl ether, a powerful enolate synthon. 

We can illustrate the synthesis of allylic alcohols from allylic sulfoxides with this synthesis of the natural product nuciferal. We mentioned this route on p. 1257 because it makes use of a heterocyclic allyl sulfide to introduce an alkyl substituent regioselectively. The allyl sulfide is oxidized to the sulfoxide, which is converted to the rearranged allylic alcohol with diethylamine as the thiophile. Nuciferal is obtained by oxidizing the allylic alcohol to an aldehyde with manganese dioxide. 

A variety of a-substituted ketones (a-halo, -hydroxy, -methoxy and -amino) have been converted into alkenes by reductive elimination. Obviously, this approach, depends not only on the feasibility of a-functionalization but also on the ability to introduce the a-substituent regioselectively. a-Halo ketones, which are readily prepared from the starting ketone," have been subjected to reductive elimination conditions to afford the desired alkenic products. For example, in the preparation of ( )-eriolanin (Scheme 5)," the protected dihydroxy keto ester is treated sequentially with LDA and Br to afford the a-bromo... 

Equation 7 illustrates the regioselective aza-annulation of an unsymmetrical ketone with a 0-substituted acrylate derivative.1 Although the P-phenyl substituent served to retard the aza-annulation process, reaction of 28 with 29 proceeded due to double activation of the acrylate reagent by both the amide and cyano substituents. Regioselective formation of 30 was the result of steric... 

Siegel and coworkers originally introduced the key step, i.e.. Method A, on the basis of reductive benzylic coupling chemistiy pioneered by Prakash and Olah [33] (Scheme 3). The synthetic approach started with 7,10-diethyl-l,6-dimethyl-fluoranthene (11), which was prepared according to Scheme 2 [32]. Bromination of 11 efficiently generated tetrabromide 12. Under titanium-mediated conditions, 12 was converted to tetrahydrocorannulene 14, oxidation of which furnished the desired 2,5-dimethylcorannulene (13). In addition to providing access to corannulene, this synthesis showed that solution phase methods could introduce substituents regioselectively, as in 13,15, and 16, which was not possible by means of pyrolysis methods [34]. 

The prefix regio- refers to the actual pattern of substituents. Regioselectivity means that the reaction is selective with regard to the physical positioning of the atoms involved. 

Regioselectivity in FGIs is dominated by the pattern of substituents and by steric effects in the substrate as well as by the choice of appropriate reagents. 

The stereospedfic and regioselective hydrobromination of alkynes with chlorobis(T -cyclopentadienyl)hydrozirconium and NBS produces ( )-vinylic bromides in good yields. The bromine atom usually adds regioselectively to the carbon atom that bears the smaller substituent and stereoselectively trans to the larger substituent (D.W. Hart, 1975 M. Nakatsuka,... 

Furthermore, the regioselective hydrogenolysis can be extended to internal allylic systems. In this case, clean differentiation of a tertiary carbon from a secondary carbon in an allylic system is a problem. The regioselectivity in the hydrogenolysis of unsymmetrically substituted internal allylic compounds depends on the nature and size of the substituents. The less substituted alkene 596 was obtained from 595 as the main product, but the selectivity was only... 

The regioselectivity of the reaction appears to be determined by a balance of electronic and steric factors. For acrylate and propiolate esters, the carb-oxylate group is found preferentially at C3 of the carbazole product[6-8]. Interestingly, a 4-methyl substituent seems to reinforce the preference for the EW group to appear at C3 (compare Entries 4 and 5 in Table 16.2). For disubstituted acetylenic dicnophiles, there is a preference for the EW group to be at C2 of the carbazole ring[6]. This is reinforced by additional steric bulk in the other substituent[6,9]. 

In general alkyl substituents increase the reactivity of a double bond toward elec trophilic addition Alkyl groups are electron releasing and the more electron rich a dou ble bond the better it can share its tt electrons with an electrophile Along with the observed regioselectivity of addition this supports the idea that carbocation formation rather than carbocation capture is rate determining... 

Section 11 16 Addition reactions to alkenylbenzenes occur at the double bond of the alkenyl substituent and the regioselectivity of electrophilic addition is governed by carbocation formation at the benzylic carbon See Table 11 2... 

Just as there is a marked difference m how methyl and tnfluoromethyl substituents affect the rate of electrophilic aromatic substitution so too there is a marked difference m how they affect its regioselectivity... 

The regioselectivity of substitution like the rate is strongly affected by the sub stituent In the following several sections we will examine the relationship between the structure of the substituent and its effect on rate and regioselectivity of electrophilic aro matic substitution... 

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

Sections How substituents control rate and regioselectivity m electrophilic aro 12 10-12 14 matic substitution results from their effect on carbocation stability An electron releasing substituent stabilizes the cyclohexadienyl cation inter mediates corresponding to ortho and para attack more than meta... 

Diazo compounds react with alkenes to afford A -pyrazolines, which in turn izomerize to A -pyrazolines if there is a hydrogen atom a to the N=N bond (Scheme 54). In those cases where two possible ways of isomerization exist, the more acidic hydrogen migrates preferentially. The alkene configuration is conserved on the A -pyrazoline (stereospecificity) but the regioselectivity depends on the substituents of both the alkene and the diazo compound. 

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