Asymmetric reduction of α-ketoesters with Hantzsch esters (dialkoxycarbonyldihydropyridines)

Abstract

Single and double asymmetric inductions were achieved by the reduction of pyruvates and benzoylformates with 2,6-dimethyl-3,5-dialkoxycarbonyl-1,4-dihydropyridine in the presence of a mono-ionised zinc species ; differentiation is made between enantiotopic faces of the substrate carbonyl by diastereotopic hydrogen, and between diastereotopic faces by equivalent and diastereotopic hydrogen.ASYMMETRIC reduction of carbonyl compounds by the use of dihydropyridine derivatives is of particular interest from the viewpoint of models of the NAD(P)H reaction as well as for their synthetic utility.

NADH Model Reaction: Asymmetric Reduction of Non-activated Carbonyl Compounds with N-Anionized Hantzsch Ester

“…The same was the case in the reductions of 2-octanone (runs 8 and 9). For this substrate, however, the product configuration was reversed from (R) to (8) by changing the solvent and metal species, and the enantiomeric excesses were considerably lower than those obtained for the other aromatic substrates including those in runs 10 and 11 ..This tendency is not excep-tional as viewed from the. asymmetric reduction of prochiral acyclic alkyl ketones with various chiral reducing agents.…”

“…The results were compared with th'ose by using sodium or Preparation of chital 1,4-dihydropyridines. According to the standard condensation reaction 12 ) as applied for the preparation of 1,8) novel chiral 1,4-dihydropyridines (4, 6, and 9) were prepared as follows (Scheme 1).…”

Stereochemistry of 1,3-Eliminative Cyclopropanation

“…The product distributions of optically active diastereomeric cyclopropanes primarily formed from these chiral systems were determined indirectly by deriving the cyclopropanecarboxylates into the correDownloaded by [Northeastern University] at 21:55 01 December 2014 1,3-E1iminative Cyc1opropanation sponding isomeric cyclopropyldiacetates 5 ) with lithium aluminum hydride reduction followed by acetylation, which has been established by the previous studies 3c ) to reflect the original distribution exactly as it resulted from t,he kinetically controlled cyclization. Asymmetric reaction systems and the stereochemical outcome were summarized in Table III.…”

“…Thus designed were the two systems in which the catalyst base sodium hydride was replaced by sodium hydride plus dibenzo-IS-crown-6 (run 9) or I,Sdiaza-bicyclo [5,4,0]undecene-7 (DBU; run 10) under the same conditions as for run 1 with sodium hydride employed and the product distribution was estimated by vpc (Table II). The observed great preponderance (21: 1) of the cis over the trans products obtained by the NaH-catalyzed reaction in pure benzene (run 1) was upset by the addition of crown ether which switched the steric course of the original system (run 1) so as to favor the formation of the trans counterpart in reversed ratio (0.9; run 9).…”

Asymmetric Reduction of Iminium Salt with Chiral Dihydropyridines

“…Amino group of (S)-( -)-I-phenylethylamine(optical purity, 96.1 ' ;Yo, 3.0 g, 24.8 mmole) was cyclized with 1,4-dibromobutane (5.40 g, 25.0 mmole) to give (7) according to the method reported by Abbot. 2 ) Optical rotation of the amine was [aliI -64.29° (c= 10.19, CHCI 3 ).…”