Synthesis of optically active pheromones

Biocatalytic asymmetric hydrogen transfer.

2-Chloro-1,3-dimethylimidazolinium chloride (DMC) (3) can act as a powerful dehydrating agent, replacing DCC (1) under nearly neutral conditions. Its application to acylation and dehydration is described.

2-Chloro-1,3-dimethylimidazolinium Chloride. 1. A Powerful Dehydrating Equivalent to DCC

A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the α-oxygen provide enantiomerically enriched α,β-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of α-methoxyacetic acid provide enantiomerically enriched α,β-dihydroxy esters with high anti-diastereoselecitvity.

Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes.

A novel synthesis of (+)-brefeldin A (1) has been accomplished on the basis of triple chirality transfer methodology, intramolecular ester enolate alkylation, and both intra- and intermolecular nitrile oxide cycloaddition strategies.

Asymmetric total synthesis of (+)-brefeldin A from (S)-lactate by triple chirality transfer process and nitrile oxide cycloaddition.

Diastereoselective synthesis of erythro- and threo-2-hydroxy-3-methyl-4-pentenoic acids by the ester enolate claisen rearrangement of 2-butenyl 2-hydroxyacetate

Stereoselective synthesis of (+)-blastmycinone

The ester enolate Claisen rearrangement of (R)-1-methyl-(E)-2-butenyl hydroxyacetate provides complete asymmetric transfer along with 98% erythroselectivity to give (2R,3S)-2-hydroxy-3-methyl-(E)-4-hexenoic acid. Its synthetic utility is demonstrated by the stereocontrolled synthesis of optically active pheromones.

Chirality transfer in the ester enolate claisen rearrangement of (R)-1-methyl-(E)-2-butenyl hydroxyacetate and its application to the stereocontrolled pheromone synthesis.

N,N,N′,N′-Tetramethylchloroformamidinium chloride reacted smoothly with a variety of carboxylic and phosphoric acids in the presence of a tertiary amine to give the corresponding acid anhydrides in high yields.

One-pot Synthesis of Acid Anhydrides from Acids Using N,N,N′,N′-Tetramethylchloroformamidinium Chloride under Mild Conditions

The ester enolate Claisen rearrangement of (E)- or (Z)-2-butenyl 3-hydroxybutanoate was found to give predominantly each one of four isomers of 3-methyl-4-methoxycarbonyl-5-hydroxy-1-hexene by the selection of the reaction conditions via the enolate dianions or silyl ketene acetals.

Kazuhisa Tajima

Papers

Diastereoselective synthesis of erythro- and threo-2-hydroxy-3-methyl-4-pentenoic acids by the ester enolate claisen rearrangement of 2-butenyl 2-hydroxyacetate

Stereoselective synthesis of (+)-blastmycinone

Chirality transfer in the ester enolate claisen rearrangement of (R)-1-methyl-(E)-2-butenyl hydroxyacetate and its application to the stereocontrolled pheromone synthesis.

One-pot Synthesis of Acid Anhydrides from Acids Using N,N,N′,N′-Tetramethylchloroformamidinium Chloride under Mild Conditions

Ester enolate Claisen rearrangement of 2-butenyl 3-hydroxybutanoate.