Chelate-controlled additions of titanium and lithium enolates to chiral beta-formyl esters - Diastereofacial and simple diastereoselectivity

The aldol-type additions of metal enolates 2-Met derived from pinacolone to the chiral beta-formyl carboxylate la were optimized. The highest trans:cis ratio (86:14) of the products 3 was obtained when the trichlorotitanium enolate 2-TiCl3 was combined with 1a precomplexed with one equivalent of TiCl4. The lithium enolate 2-Li is rather unselective. The simple diastereoselectivity of prochiral enolates 4-Met was first examined with achiral beta-formyl carboxylates 1b and 1c. Appropriate reagents made products with high anti or with high syn selectivity available when the unbranched aldehyde 1b was the electrophile. In contrast, the sterically more hindered aldehyde 1c provided syn products with all enolates 4-Met employed. Finally, chiral aldehyde la was combined with prochiral enolates 4-Met. Conditions could be found which furnished either the trans/anti or the trans/syn product 7 with good selectivity. The results are discussed and compared with reactions of related metal enolates with aldehydes capable of chelate formation.