A Maitland–Japp inspired synthesis of dihydropyran-4-ones and their stereoselective conversion to functionalised tetrahydropyran-4-ones

The Maitland–Japp reaction has been extended to the synthesis of highly functionalised dihydropyran-4-ones. These dihydropyran-4-ones can in turn be converted stereoselectively into tetrahydropyran-4-ones with tertiary and quaternary stereocentres via the one-pot addition of hydride or carbon nucleophiles and trapping with carbon electrophiles. The utility of this method is demonstrated by providing access to the functionalised tetrahydropyran units present in a component of the Civet fragrance and the anticancer polyketide lasonolide A

Freezing properties of alkenyl succinic anhydrides derived from linear isomerised olefins

Alkenyl succinic anhydrides are important specialty chemicals that are used in the paper, oilfield and fuel additives industries. In this paper we investigate the link between the physical properties of alkenyl succinic anhydrides and the identities of their linear alkyl olefin precursors. We describe a straightforward GC analysis of olefin isomer distributions and show that these correlate well with the freezing temperatures of the subsequent alkenyl succinic anhydride products. This allows the identification of olefin isomer profiles that are required to give the desired physical properties in the alkenyl succinic anhydrides; it also provides a method to predict the freezing temperatures of alkenyl succinic anhydrides synthesised from a particular supply of olefin

Synthesis of 2,6-trans- and 3,3,6-Trisubstituted Tetrahydropyran-4-ones from Maitland-Japp Derived 2H-Dihydropyran-4-ones: A Total Synthesis of Diospongin B

6-Substituted-2H-dihydropyran-4-one products of the Maitland-Japp reaction have been converted into tetrahydropyrans containing uncommon substitution patterns. Treatment of 6-substituted-2H-dihydropyran-4-ones with carbon nucleophiles led to the formation of tetrahydropyran rings with the 2,6-trans-stereochemical arrangement. Reaction of the same 6-substituted-2H-dihydropyran-4-ones with l-Selectride led to the formation of 3,6-disubstituted tetrahydropyran rings, while trapping of the intermediate enolate with carbon electrophiles in turn led to the formation 3,3,6-trisubstituted tetrahydropyran rings. The relative stereochemical configuration of the new substituents was controlled by the stereoelectronic preference for pseudo-axial addition of the nucleophile and trapping of the enolate from the opposite face. Application of these methods led to a synthesis of the potent anti-osteoporotic diarylheptanoid natural product diospongin B

Diastereoselective synthesis of functionalized 2-methyltetrahydropyran-4-ones

A simple procedure for the synthesis of functionalized 2-methyl-2,3-dihydropyran-4-ones, based on the Maitland–Japp reaction, and their diastereoselective conversion into functionalized 2-methyltetrahydropyran-4-ones has been developed. This allows access to a structural unit present in a large number of biologically active natural products, and has been successfully applied to the synthesis of the molecule found in Civet cat secretion

Axially chiral enamides : substituent effects, rotation barriers, and implications for their cyclization reactions

The barrier to rotation around the N-alkenyl bond of 38 N-alkenyl-N-alkylacetamide derivatives was measured (ΔG⧧ rotation varied between 20 kcal mol–1) were studied to determine the regiochemistry of cyclization. Those with high barriers (>27 kcal mol–1) did not lead to cyclization, but those with lower values produced highly functionalized γ-lactams via a 5-endo-trig radical–polar crossover process that was terminated by reduction, an unusual cyclopropanation sequence, or trapping with H2O, depending upon the reaction conditions. Because elevated temperatures were necessary for cyclization, this precluded study of the asymmetric transfer in the reaction of individual atropisomers. However, enantiomerically enriched atropsiomeric enamides should be regarded as potential asymmetric building blocks for reactions that can be accomplished at room temperature