The exceptional chelating ability of dimethylaluminum chloride and methylaluminum dichloride. The merged stereochemical impact of alpha- and beta-stereocenters in chelate-controlled carbonyl addition reactions with enolsilane and hydride nucleophiles.

A systematic investigation of the stereoselectivity in Lewis acid-promoted (Mukaiyama) aldol reactions of achiral unsubstituted enolsilanes and chiral beta-hydroxy aldehydes proceeding under conditions favoring chelation control is presented. Good stereocontrol can be realized for enolsilane aldol reactions of beta-alkoxy and beta-silyloxy aldehydes bearing only an alpha- or a beta-stereogenic center. Examination of the chelated intermediates for alpha,beta-disubstituted aldehydes concludes that the syn aldehyde diastereomer possesses the arrangement of stereocenters wherein the alpha- and beta-substituents impart a reinforcing facial bias upon the aldehyde carbonyl. Aldol reactions of syn aldehydes were thus observed to proceed with uniformly excellent diastereofacial selectivity. Aldol reactions of the corresponding anti aldehydes containing opposing stereocontrol elements at the alpha- and beta-positions exhibit variable and unpredictable selectivity.

An asymmetric aminohydroxylation approach to the azepine core of (-)-balanol.

[reaction: see text]An efficient formal synthesis of the potent protein kinase C inhibitor (-)-balanol that relies on a modified asymmetric aminohydroxylation of the alpha,beta-unsaturated aryl ester (1) is reported. The aryl ester functionality and the dihydroquinyl alkaloid ligand system (DHQ)2-AQN are used to control the regio- and enantioselectivity of the process.

Reversal of regioselection in the sharpless asymmetric aminohydroxylation of aryl ester substrates.

[formula: see text] The asymmetric synthesis of beta-hydroxy-alpha-amino acids is reported which relies on the use of alpha,beta-unsaturated aryl ester substrates and the dihydroquinyl alkaloid ligand system (DHQ)2-AQN to control the regio- and enantioselectivity of the asymmetric aminohydroxylation (AA) process. alpha,beta-Unsaturated ester substrates of type 1 have a significant effect on the substrate-ligand recognition event which results in a reversal of regioselectivity in the AA reaction.

Total synthesis of (+)-lactacystin.

A double stereodifferentiating crotylation between aldehyde 1 and silane (S)-2 to afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn >30:1) in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a metabolite isolated from Streptomyces sp. OM-6519 that exhibits significant neurotrophic activity. An additional important step in the synthesis is a catalytic asymmetric aminohydroxylation used as the key step in the synthesis of the (2R,3S)-hydroxyleucine synthon.