Enantioselective Allylation of (2E,4E)‐2,4‐Dimethylhexadienal: Synthesis of (5R,6S)‐(+)‐Pteroenone

Abstract

Allylation, trans- and cis-crotylation of (2E,4E)-2,4-dimethylhexadienal, a representative α,β,γ,δ-unsaturated aldehyde, was carried out under different catalytic and stoichiometric conditions. The reactions catalyzed by organocatalysts TRIP-PA and N,N'-dioxides gave the best results with respect to yields, asymmetric induction, and catalyst load in comparison to other procedures. The developed methodology was applied in the enantioselective synthesis of (5R,6S)-(+)-pteroenone, a defensive metabolite (ichthyodeterrent) of the Antarctic pteropod Clione antarctica.

Heteroaromatic N-Oxides in Asymmetric Catalysis: A Review

“…Additionally, the resulting homoallylic alcohols are considered the cornerstones of organic synthesis. Mostly, they are used in the synthesis of numerous natural products as building blocks but also in the synthesis of drug candidates and other functional molecules [11][12][13][14][15][16][17]. Apart from allylation there were also reported examples of using N-oxides in the catalytic ring-opening of meso-epoxides [18][19][20][21], propargylation [22], allenylation [23], aldol reaction [24,25] and reduction of ketoimines [26,27].…”

“…Inversion of product configuration was observed when dichloromethane was applied. N-oxide catalysts were successfully applied to the synthesis of a few natural products [12][13][14][15][16][17]. For example, duloxetine, which is used in the treatment of major depression, was synthesized involving the allylation of 2-thiophenecarboxaldehyde with (aR,S)-34a as catalyst (see Scheme 7) [12].…”

Synthesis of γ‐Boryl‐Substituted Homoallylic Alcohols with anti Stereochemistry Based on a Double‐Bond Transposition

“…The anti isomer of the homoallylic acetate 7 ka [Eq. 3] is a key intermediate for the synthesis of (±)‐pteroenone, a defensive metabolite of the Antarctic pteropod Clione antarctica . It was easily prepared by the present allylation using the dienal 4 k as the aldehyde.…”

Synthesis of γ‐Boryl‐Substituted Homoallylic Alcohols with anti Stereochemistry Based on a Double‐Bond Transposition

“…The anti isomer of the homoallylic acetate 7ka [Eq. (3)] is ak ey intermediate for the synthesis of (AE)-pteroenone, [20] ad efensive metabolite of the Antarctic pteropod Clione antarctica. It was easily prepared by the present allylation using the dienal 4k as the aldehyde.…”