Design, Synthesis, and Application of Chiral Nonracemic Lithium Amide Bases in Enantioselective Deprotonation of Epoxides

Abstract

The reaction of epoxides with chiral nonracemic lithium amide bases, designed and prepared from (R)-phenylglycine, has been studied in detail. A maximum of 80% ee was obtained for conversion of cyclohexene oxide to (S)-2-cyclohexen-1-ol. Enantioselective deprotonation of a variety of other epoxides was studied. A cyclopentanoid core unit for prostaglandin synthesis was synthesized in 97% ee.

Kinetic and computational studies of the composition and structure of activated complexes in the asymmetric deprotonation of cyclohexene oxide by a norephedrine-derived chiral lithium amide†

“…The development of stereoselective lithium amides for deprotonations has mainly been carried out in a trial-and-error fashion. [8][9][10][11][12][13][14][15][16][17] To be able to rationally develop new and highly selective chiral lithium amides knowledge is needed about the detailed reaction mechanisms and, in particular, the composition and structures of the ratelimiting activated complexes involved. By use of multinuclear NMR studies of isotopically labelled lithium amides the molecular composition of the lithium amide aggregates in the initial state has been determined.…”

Diastereoselective reductive N-alkylation of (R,R)-trans-1,2-diaminocyclohexane with prochiral ketones using the Ti(OiPr)4/NaBH4 system

“…The secondary chiral N-alkyl amines have been used as ligands for asymmetric deprotonation of epoxides. 21 Previously, the 1,2-diaminocyclohexane derivative 4a containing a chiral N-alkyl group was prepared by the opening of an aziridine with (S)-a- in situ reduction, 5.0 mmol of NaBH 4 in 5.0 mL of absolute EtOH was used at rt and stirred for 12 h. b Products were identified using spectroscopic data (IR and 1 H and 13 C NMR). c Yields are of the isolated product and correspond to the three diastereomers.…”

Three‐Membered Heterocycles. Structure and Reactivity

“…Thus, the challenging substrate cyclopentene oxide (560) was cleanly isomerized to the chiral cyclopentenol 561 in 81% yield and with 96% ee -a significant improvement over the 49% ee obtained with higher loadings of the earlier generation catalyst 558 [618]. Diamines derived from (R)-phenylglycine have also given promising results [619]. The chiral amide approach has also been applied to the catalytic kinetic resolution of racemic epoxides.…”