N-Acyl-5,5-dimethyloxazolidin-2-ones as latent aldehyde equivalents

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

“…141 The improved alkylation diastereoselectivity of the SuperQuat derived enolate 92 was reasoned to be due to the gem-dimethyl group at C(5) serving to direct the stereodirecting group [i.e., the C(4)-isopropyl group] closer to the site of reaction at C(2 0 ). The generality of this superior diastereoselectivity has been demonstrated with applications in stereoselective enolate alkylations, 25,142,143 aldol reactions, [144][145][146][147] conjugate addition reactions, 114,140,148 kinetic resolutions, 141 Diels-Alder cycloadditions, 141 radical cyclisations, 149 epoxidations, 150,151 cyclopropanation reactions 152,153 and Pd-catalysed asymmetric acetalisation reactions (Scheme 14). 141 The direct conversion of N-acyl SuperQuats to the corresponding enantiopure aldehydes requires treatment with DIBAL-H at low temperature (typically À78 1C).…”

“…We have developed the use of achiral N-acyl-5,5-dimethyloxazolidin-2-ones as alternative Weinreb amide equivalents which possess similar reductive cleavage properties to Weinreb amides, but allow enolate formation and functionalisation, resulting in efficient access to a-substituted aldehydes and ketones. 25 Chiral auxiliary approaches to a-substituted aldehydes and ketones…”

“…As a solution to this problem, we developed the analogous series of 4-substituted-5,5-dimethyl oxazolidin-2-ones ''SuperQuats'' 71. 25,114,135,137,138 SuperQuat auxiliaries 71 are easily prepared on a multi-gram scale (B100 g batches of the auxiliary are produced routinely within our laboratory) 139 in 4 steps starting from the corresponding a-amino acid methyl esters. This synthesis involves N-Boc protection and addition of excess MeMgI, followed by treatment with KO t Bu to promote cyclisation.…”

Utilization of Cyclic Amides as Masked Aldehyde Equivalents in Reductive Amination Reactions

“…However, if a partial reduction product of an amide, for instance, an aminol or other masked aldehyde equivalent, could be readily further functionalized in a coupling reaction, such a protocol would be synthetically attractive, effectively rendering the amide group a useful synthon for further manipulations. Indeed, lactams have been reported to be utilized as starting materials to build molecular complexity . Substituted N -Boc pyrrolidinones (functionally imides) have been treated with a variety of reducing agents (generally DIBAL-H, LAH, or LiEt 3 BH) to afford isolable aminol intermediates, which have been used effectively in a variety of subsequent transformations (Scheme , top). , …”

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

“…14 Previous investigations from this laboratory have shown that DIBAL reduction of achiral N-acyl-5,5-dimethyloxazolidinones generate stable, tetrahedral carbinol species which may be fragmented upon treatment with base to the aldehyde, or in a tandem protocol with a lithiated phosphonate reagent to the α,β-unsaturated ester. 15 This, combined with the ability of homochiral SuperQuat auxiliaries to control the stereoselectivity of alkylation reactions of attached enolate fragments, 16 and conjugate addition reactions to attached enones, 17 suggested a direct stereoselective synthesis of homochiral α-substituted and β-substituted aldehydes. The realisation of this strategy is described herein, part of which has been communicated previously.…”