Carbonyl Orientation Determines Regio- and Enantioselectivity in 1,2-/1,4-Reduction of an NAD Model Compound

Abstract

An optically active, axially chiral NAD model compound(1) with a quinoline ring system was reduced by the chiral NADH model compound (4), affording a mixture of 1,2- and 1,4-dihydroquinolines. The carbonyl orientation governs the molecular arrangement in the transition state of the reaction and determines the regio- and enantioselectivity of the product.

Consideration of molecular arrangements in regio- and enantioselective reduction of an NAD model compound controlled by carbonyl oxygen orientation

“…22,23,25,31 In this article, we analyze the role of the carbonyl oxygen orientation in determining the regio-and stereoselectivity of the reduction of non-annulated NAD model compound, 3-piperidinylcarbonyl-1,2,4-trimethylquinolinium ion (1), which has axial chirality with respect to the C 3 (quinolinium)-C(carbonyl) bond. As reported in our previous communication, 32 when (aS)-1 was reduced by a chiral NADH model compound, (4R,9R)-2,4dimethyl-3-(N-a-methylbenzylcarbamoyl)-1-propyl-1,4-dihydropyridine ((4R)-Me 2 PNPH ((4R)-4), Chart 1), the main product was 1,4-dihydroquinoline (4R)-2, which is the compound where the hydride was introduced at the C4 position from the carbonyl oxygen face direction. The axial chirality was lost upon reduction, thus, axial chirality was converted to central chirality in this system.…”

“…Preliminary results from this reaction have been reported earlier with the exception of the enantioselectivity in 3. 32 In this paper, we re-examined the whole set of the reactions and completed the evaluation of the selectivity as shown in Table 1.…”

Grignard Reactions in Pyridinium and Phosphonium Ionic Liquids

“…[33] Indeed, NADH mimicks containing a dihydropyridine core have been used by Mikata and co-workers in asymmetric reductions. [34] In order to test this hypothesis, IL 10a was dried overnight (28 h) under high vacuum (0.5-1 Torr) at 60°C, freshly prepared MgMeI (1.0 m in Et 2 O) was added dropwise to the IL and was allowed to react for 50 min at ambient temperature. The diethyl ether was removed under house vacuum for ca.…”

Hydride Reduction of NAD(P)+ Model Compounds with a Ru(II)–Hydrido Complex

“…Many asymmetric reduction systems of various carbonyl compounds using chiral NAD­(P)­H model compounds with a methyl group at the C-4 position as a reductant have been reported . For example, the NAD­(P) + model compounds shown in eqs and 3 could transfer the hydride to the substrates in high optical yields. …”