The Exceptional Chelating Ability of Dimethylaluminum Chloride and Methylaluminum Dichloride. The Merged Stereochemical Impact of α- and β-Stereocenters in Chelate-Controlled Carbonyl Addition Reactions with Enolsilane and Hydride Nucleophiles

Abstract

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.

Highly Stereoselective Total Synthesis of (+)‐9‐epi‐Dictyostatin and (–)‐12,13‐Bis‐epi‐dictyostatin

“…[26] When aluminum Lewis acids (Me 2 AlCl or MeAlCl 2 ) are used, exceptional chelation control reinforces the 1,3-anti stereochemical outcome (model C, axial attack). [27] In the case of α-OTBS substituted aldehydes, addition reactions of (Z)-disubstituted vinylzinc reagents, in the presence of added RZnX (1.5 equiv. ), have been shown to proceed via a Cramchelation mechanism.…”

A Theoretical Study of the Stereoselectivities of the Diels–Alder Addition of Cyclopentadiene to Ethyl‐(S)‐lactyl Acrylate Catalyzed by Aluminium Chloride

“…[33] The interesting conclusion drawn from the above discussion is that if chelated complexes are not formed with ligands of low energetic demands, they should also not be formed with ligands that demand high energy for conformational change. If this is true, then the mechanisms proposed by Evans et al and extensively used thereafter [12,[51][52][53] may need a different analysis and, perhaps, a few adjustments. We aim to contribute, in the near future, further work in this field.…”

Total Synthesis of Carolacton, a Highly Potent Biofilm Inhibitor

“…After oxidation, aldehyde 20 was subjected to different aldol protocols. [17] Efforts to prepare the desired anti-Felkin aldol product (3R)-21 by exploiting 1,2-, 1,3-substrate control [18] using different Lewis acids preferentially delivered the undesired diastereomer (3S)-21 (Table 1, [a] Reactions were conducted with 2 equiv of ketene silyl acetal; Lewis acids were added 30 s prior to addition of ketene silyl acetal for chelation.…”