6-Lactones optically active chiral base

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). 

Ketene can also be added to trihalosubstituted aldehydes or ketones (12) to form 4-trihalomethyloxetanones. If this addition is performed in the presence of optically active bases such as quinine [130-95-0] chiral lactones are obtained (41,42). 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

Optically active dihydropyranones were synthesized by Smith and co-workers [43] by a highly stereoselective chiral isothiourea-catalyzed intermolecular Michael/lactonization cascade from arylacetic acids and p,7-unsaturated a-ketoesters (Scheme 16.21). This strategy is based on the generation of chiral enolate directly from carboxylic acid activated by the in situ formation of a mixed anhydride and the organocatalyst. 

In addition, silver-catalyzed asymmetric aza-Diels-Alder reactions provide a useful route to optically active nitrogen-heterocyclic compounds such as piperidines or pyrid-azines. Substituted dihydrobenzofurans can also be enantioselectively prepared through silver-promoted allylation of aldehydes. Other types of silver-mediated cyclizations can also be used in the synthesis of tetrahydrofnrans, tetrahydropyrans, 1,2-dioxetanes, 1,2-dioxolanes, medium-sized lactones, dihydroisoqninolines, and so on. Silver salts can also be used as cocatalysts with other transition metals. Unique activity was observed for these silver-based systems in several cases. Conseqnently, the use of silver can enrich several available heterocyclization methods, and fnrther developments in the application of chiral silver complexes will hopefnlly appear in the near future. 

Other routes to optically active CFs-containing molecules are based on the diastereoselective addition of TMSCF3 to chiral substrates, including aldehydes, ketones (eq 12), a-ketoesters or lactones. " ... 

---