Ti-mediated addition of diethylzinc to benzaldehyde. The effect of chiral additives

Sulfonamide Ligands from Chiral Aziridines − Application to the Titanium-Mediated Addition of Diethylzinc to Benzaldehyde

“…The reason for the increase in enantioselectivity over time is unclear, but it has been previously observed that the addition of for example chiral alcohols affects the stereoselectivity of the reaction. [57] That steric bulk in the side chain did not improve the stereoselectivity was further demonstrated by use of ligand 6 (69% ee, Entry 7), which bears two phenyl groups at the benzylic position, and ligand 7 (63% ee, Entry 10), which contains an anthracene group at the same position. The reaction catalysed by ligand 6 proved to be as fast as those catalysed by 3 and 4, and full conversion was achieved after 15 min.…”

“…We have previously demonstrated that the enantioselectivity as well as the reactivity vary considerably with the reaction conditions. [57] The amount of Ti(OiPr) 4 employed in the process was found to be particularly crucial. In the present study, the conditions found to result in highest enantioselectivity of the product for ligand 2 were employed, although optimal conditions probably have to be determined for each particular ligand.…”

“…of (S)-2-isopropyl-N-(trifluoromethylsulfonyl)aziridine (1a) has previously been shown to yield bis(sulfonamide) 2, [43] which serves as a versatile ligand in the titanium-mediated addition of diethylzinc to benzaldehyde, [43,57] as well as in the aluminium-catalysed ketene aldehyde cycloadditions. [26,27] The synthetic approach used for the preparation of 2 allows for wide structural variations of the product, as both aziridines with different substituents and a variety of primary amines can be used in the process.…”

Indolizidine and quinolizidine alkaloids

“…124 It also induced only modest enantioselectivity during the reaction of lithiated α-(arylthio)benzyl precursors with electrophiles (ee 12-16%), 125 and in the α-methylation of isochromane (ee 5%). 140,141 Several miscellaneous examples of enantioselective reactions mediated by (Ϫ)-sparteine merit brief mention. 128 Other examples of asymmetric deprotonations induced by (Ϫ)-sparteine in combination with organolithium bases include the following: deprotonation and electrophilic trapping of tert-butyl(phenyl)phosphine-borane 129 and aryldimethylphosphine-borane complexes (ee 75-99%); 130 asymmetric lithiation and substitution of various arenetricarbonylchromium() complexes to form planar chiral products (ee up to 92%); 131 and the deprotonation and silylation of terminal epoxides.…”

“…137 (Ϫ)-Sparteine-assisted addition reactions to polarised double bonds include the reaction of organolithium reagents with 3,4-dihydroisoquinolines in toluene (ee up to 47%) as a prelude to the synthesis of isoquinoline alkaloids; 139 and the addition of organozinc reagents to aldehydes in the presence of various chiral ligands. 140,141 Several miscellaneous examples of enantioselective reactions mediated by (Ϫ)-sparteine merit brief mention. The alkaloid has been used in combination with titanium tetrachloride for 'soft' enolisation in syn-and anti-aldol condensations of N-acyloxazolidin-2-ones, oxazolidine-2-thiones and thazolidine-2-thiones with aldehydes.…”