SuperQuat N-acyl-5,5-dimethyloxazolidin-2-ones for the asymmetric synthesis of α-alkyl and β-alkyl aldehydes

Abstract

The proclivity of alpha-branched N-2'-benzyl-3'-phenylpropionyl derivatives of (S)-4-benzyl-5,5-dimethyl-, (S)-4-phenyl-5,5-dimethyl-, (S)-4-isopropyl-5,5-dimethyl-, (S)-4-benzyl- and (S)-4-benzyl-5,5-diphenyl-oxazolidin-2-ones to generate directly 2-benzyl-3-phenylpropionaldehyde upon hydride reduction with DIBAL is investigated. The (S)-4-benzyl-5,5-dimethyl-derivative proved optimal for inhibition of endocyclic nucleophilic attack, giving 2-benzyl-3-phenylpropionaldehyde in good yield upon reduction. Application of this methodology for the asymmetric synthesis of chiral aldehydes via diastereoselective enolate alkylation of a range of (S)-N-acyl-4-benzyl-5,5-dimethyloxazolidin-2-ones to afford and array of alpha-substituted-N-acyl-5,5-dimethyloxazolidin- 2-ones (85-94% de) and subsequent reduction with DIBAL afforded directly non-racemic alpha-substituted aldehydes without loss of stereochemical integrity (87-94% ee). The extension of this protocol for the asymmetric synthesis of beta-substituted aldehydes is demonstrated, via the diastereoselective conjugate addition of a range of organocuprates to (S)-N-acyl-4-phenyl-5,5-dimethyloxazolidin-2-ones which proceeds with high diastereoselectivity (generally > 95% de). Reduction of the conjugate addition products with DIBAL gives non-racemic beta-substituted aldehydes in high yields and in high ee (generally > 95% ee). This methodology is exemplified by the asymmetric synthesis of (R)-3-isopropenylhept-6-enal, which has previously been used in the synthesis of (3Z,6R)-3-methyl-6-isopropenyl-3,9-decadien-1-yl acetate, a component of the sex pheromones of the California red scale.

Gold- and Copper-Catalyzed [4+2] Benzannulations between Enynal or Enynone Units and 2π-Systems

“…The diastereomeric ratio, 96% dr, was determined by GCMS, and it was increased up to 99% by recrystallization of 60 from EtOH. The cleavage of chiral auxiliary of 60 by reduction with DIBAL afforded the alkynyl aldehyde 61 in 96% yield, 52 Then, we examined the preparation of the target molecules 56 and 57 from the diyne segment 63 and the naphthalene part of 58 as depicted in Scheme 19. The bromonaphthoquinone 64 was prepared from 1,5-dihydronaphthalene in four steps in 74% yield by the known procedure.…”

“…The diastereomeric ratio, 96% dr, was determined by GCMS, and it was increased up to 99% by recrystallization of 60 from EtOH. The cleavage of chiral auxiliary of 60 by reduction with DIBAL afforded the alkynyl aldehyde 61 in 96% yield, 52 which was converted into the 1,6-heptadiyne derivative 62 in 71% yield using the Corey-Fuchs method. Treatment of 62 with BuLi, followed by addition of Bu Then, we examined the preparation of the target molecules 56 and 57 from the diyne segment 63 and the naphthalene part of 58 as depicted in Scheme 19.…”

SuperQuat chiral auxiliaries: design, synthesis, and utility

“…We demonstrated that the conjugate additions of organocopper reagents to an α,β-unsaturated Nacyl L-Phg-SuperQuat derivatives 88 proceed with very high diastereoselectively to give the corresponding β-functionalised products. 6,7,33 In contrast to the use of derivatives of L-Phg-SuperQuat 25, use of L-Val-SuperQuat 23 or L-Phe-SuperQuat 24 in this reaction manifold results in significantly poorer levels of diastereoselectivity. 6 A similar trend is noted using the analogous N-acyl Evans auxiliaries 34 although the reasons for this disparity are unclear.…”

Direct asymmetric syntheses of chiral aldehydes and ketones via N-acyl chiral auxiliary derivatives including chiral Weinreb amide equivalents

“…121- 125 A limited number of literature reports describe the successful direct conversion of N-acyl oxazolidin-2-ones derived from the Evans auxiliary 70 to the corresponding aldehydes, [126][127][128][129][130][131][132][133][134] although in general this transformation suffers from competing endocyclic cleavage. 135 Accordingly, a two step approach involving either reduction to the corresponding alcohol followed by chemoselective oxidation 136 or transamidation of the N-acyl oxazolidin-2-ones to the corresponding Weinreb amide followed by reduction with DIBAL-H or LiAlH 4 are employed to obtain the desired enantiopure aldehydes. As a solution to this problem, we developed the analogous series of 4-substituted-5,5-dimethyl oxazolidin-2-ones ''SuperQuats'' 71.…”