Chiral halogenation

Halogen Transfer Reactions from bis-Amino Halonium Ions to Acceptor Olefins Mechanism and Strategies for Chiral Halogenation... 

One of the most interesting, yet unsolved questions about vanadium bromoperoxi-dase is still the biogenesis of the chiral halogenated marine natural products. With... 

Of similar nature are chiral halogenations using auxiliary groups. Typical examples are the conversion of esters to enantiomerically pure halohydrins (precursors to chiral epoxides) using camphor-10-sulfonic acid derivatives583 and the chiral synthesis of a-amino acid synthons via diastereoselective bromination of TV-acyl oxazolidone derivatives584. 

Asymmetric Lewis acid-catalyzed hetero Diels-Alder reactions of 2-aza-1,3-dienes have been studied for isolated cases. Highly selective thermal cycloadditions have been observed in the reactions of chiral, halogenated 2-aza-1,3-dienes with acyclic diazo compounds conducted at 80°C. ... 

An enantioselective halogenation reaction of silyl enolates mediated by ZrCU with chiral halogen source was reported (Equation 14) [19]. Dichloromalonate ester (43) was employed for the reaction as a halogen source. 

This encouraging precedent led us to develop new asymmetric syntheses of haiothane (27) and desflurane plus the desflurane analogue "Hoechst s ether" (22). The cornerstone of the second-generation syntheses is stereoselective decarboxylation. In both cases, a chiral halogenated acid derivative was prepared which had the carboxyl group attached directly to the chiral center. Rather than use salt formation and repeated crystallization for resolution of the acids, we chose to form secondary amides and use chromatography for separation of the resulting diastereomers. The diastereomerically enriched amides would then he converted to enantiomerically enriched acids to be used as decarboxylation substrates. 

The situation is the same when the two chirality centers are present m a ring There are four stereoisomeric 1 bromo 2 chlorocyclopropanes a pair of enantiomers m which the halogens are trans and a pair m which they are cis The cis compounds are diaste reomers of the trans... 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

Some of the newer compounds may contain both saturated and unsaturated rings, heteroatoms such as oxygen, nitrogen, or sulfur, and halogen substituents. Others, such as synthetic pyrethroids, may have one or more chiral centers, often needing stereospecific methods of synthesis or resolution of isomers (42). Table 4 Hsts examples of some more complex compounds. Stmctures are shown ia Eigure 1 (25). 

Darzens reactions between the chiral imine 52 and a-halo enolates 53 for the preparation of nonracemic aziridine-2-carboxylic esters 54 (Scheme 3.17) were studied by Fujisawa and co-workers [61], It is interesting to note that the lithium enolate afforded (2K,3S)-aziridirie (2i ,3S)-54 as the sole product, whereas the zinc enolate give rise to the isomer (2S,3i )-54. The a-halogen did not seem to affect the stereoselectivity. 

Chiral alcohols have also been used in an asymmetric synthesis of sulphoxides based on halogenation of sulphides. Johnson and coworkers have found319 that the reaction of benzyl p-tolyl sulphide with JV-chlorobenzotriazole (NCBT) followed by addition of (—) menthol and silver tetrafluoroborate afforded diastereoisomeric menthoxysulphonium salts 267 which, upon recrystallization and hydrolysis, gave benzyl p-tolyl sulphoxide with 87% optical purity (equation 145). More recently, Oae and coworkers reported320 that optically active diaryl sulphoxides (e.e. up to 20%) were formed either by hydrolysis or thermolysis of the corresponding diaryl menthoxysulphonium salts prepared in situ from diaryl sulphides using ( —) menthol and t-butyl hypochlorite. 

Alkanes undergo substitution of hydrogen atoms when treated with halogens. Bromination of which of the following compounds could give rise to chiral monosubstituted products ... 

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