Asymmetric aldol additions: use of titanium tetrachloride and (-)-sparteine for the soft enolization of N-acyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones.
Asymmetric aldol additions using chlorotitanium enolates of N-acyloxazolidinone, oxazolidinethione, and thiazolidinethione propionates proceed with high diastereoselectivity for the Evans or non-Evans syn product depending on the nature and amount of the base used. With 1 equiv of titanium tetrachloride and 2 equiv of (-)-sparteine as the base or 1 equiv of (-)-sparteine and 1 equiv of N-methyl-2-pyrrolidinone, selectivities of 97:3 to > 99:1 were obtained for the Evans syn aldol products using N-propionyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones. The non-Evans syn aldol adducts are available with the oxazolidinethione and thiazolidinethiones by altering the Lewis acid/amine base ratios. The change in facial selectivity in the aldol additions is proposed to be a result of switching of mechanistic pathways between chelated and nonchelated transition states. The auxiliaries can be reductively removed or cleaved by nucleophilic acyl substitution. Iterative aldol sequences with high diastereoselectivity can also be accomplished.
Crimmins
M T
MT
Venable and Kenan Laboratories of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA. crimmins@email.unc.edu
King
B W
BW
Tabet
E A
EA
Chaudhary
K
K
D009682:Magnetic Resonance Spectroscopy; D023303:Oxazolidinones / Q000737:chemistry*; D013034:Sparteine / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013844:Thiazoles / Q000737:chemistry*; D014025:Titanium / Q000737:chemistry*
D023303:Oxazolidinones; D013844:Thiazoles; D013034:Sparteine; C025096:titanium tetrachloride; D014025:Titanium