Stereochemistry electrophilic aromatic substitution

The bromination of phenyl n-pentyl ether is more para-selective in anionic micelles than it is in water. This contrasts with the lower para-selectivity of nitration of bromobenzene in the cationic micelles formed by dissolving lauric acid in 95% H2S04. It is not clear whether these effects are due to substrate orientation or to micelle-induced changes in the selectivity parameter for electrophilic aromatic substitution. The rates of solvolysis of alkyl p-trimethyl-ammoniumbenzenesulphonate trifluoromethanesulphonates (42) are strongly inhibited by anionic micelles of sodium lauryl sulphate or sodium dodecanoate. In water, homomicelles of (42) or sodium dodecanoate micelles, undergo inversion of stereochemistry, but in sodium lauryl sulphate 22% retention of... 

High anti-diastereoselectivity is observed for several aromatic imines for ortho-substituted aromatic imines the two newly formed stereocenters are created with almost absolute stereocontrol. Aliphatic imines can also be used as substrates and the reaction is readily performed on the gram scale with as little as 0.25 mol% catalyst loading. Furthermore, the Mannich adducts are readily transformed to protected a-hydroxy-/8-amino acids in high yield. The absolute stereochemistry of the Mannich adducts revealed that Et2Zn-linked complex 3 affords Mannich and aldol adducts with the same absolute configuration (2 R). However, the diastereoselectiv-ity of the amino alcohol derivatives is anti, which is opposite to the syn-l,2-diol aldol products. Hence, the electrophiles approach the re face of the zinc enolate in the Mannich reactions and the si face in the aldol reactions. The anti selectivity is... 

Knolker et al. have developed a one-pot diastereoselective spiroannela-tion by electrophilic substitution of an aromatic system with an iron-complexed cation, which led to the construction of the A, B, C, and D rings of the prianosins and discorhabdins. This novel diastereoselective spiroannulation involved the reaction between the tricarbonyliron-complexed cation 520, which was prepared in six steps (2/9), and an arylam-ine, the 6-aminoindoline (521), to construct A, B, C, and D rings (512) (Scheme 61) (220). The stereochemistry of the product was determined by X-ray crystallographic analysis the stereodirecting effect of Fe(CO)3 was indicated to be anti to the aryl ring (2/9). 

This reaction presumably proceeds by electrophilic substitution at C3 and dehydration of the resulting carbinol, followed by cycloaddition. The reaction also involves the decarboxylation of an indole-2-acetic acid, which is known to be facile. Similarly, reaction of indole, a carbonyl compound and 7V-phenylmaleimide generates tetrahydrocarbazoles of structure (68). The yields vary from 15-20% for simple aldehydes to 70% and above for cyclic ketones <93JHC8l>. The stereochemistry, which is predominantly all-cw, arises as the result of an endo addition followed by protonation from the less hindered side of the molecule in the step resulting in aromatization (Scheme 145). 

Apparently, the electronic nature of the substituents and their position on the aromatic ring in the aUsynes had no effect on the stereochemistry and efficiency of this process. The carbometallated intermediates were also successfully converted with variously substituted allyl bromide or propargyl bromide electrophiles leading... 

The point has been made that successful drug candidates contain a large number of sp carbons with respect to sp carbons, a characteristics that is not easily introduced in practice, especially when stereochemistry is considered. However, Kutateladze pointed out that in this sense photochemistry is situated in a favorite position, since catalytic sp -sp carbon coupling and electrophilic substitution are well-developed methods that allow building of polysubstituted aromatic molecules, which in turn... 

Satisfactory syntheses are achieved, especially for tertiary centers, when one component is rather sterically hindered (Figure 9.48). In the first example, the reaction is exclusively Sn2 rather than Sj.j2, for steric reasons, and goes with clean inversion of stereochemistry. In the second reaction, the nitrogen is not a particularly good nucleophile, because of the interaction of the lone pair with the x-electrons of the aromatic rings we need to make it more nucleophilic by deprotonation with sodium hydride. A second substitution would also be sterically disfavored. Alternatively, the synthesis works well when the electrophile bears another electron-withdrawing group such as carboxylate, which renders the first-formed product less, rather than more, electrophilic than the... 

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