The remarkable effect of titanium tetraisopropoxide in diastereoselective reaction of carbaldehydes with chiral benzenesulfonamide lithium complexes.

Chiral titanium complexes for enantioselective addition of nucleophiles to carbonyl groups

“…91, with 62-82% de. 88 The diastereoselectivity of the lithiated species is much lower, if the transmetalation to titanium is omitted.…”

ortho-Metalation of Enantiopure Aromatic Sulfoxides and Stereocontrolled Addition to Imines

“…Some stereogenic ortho -directing groups have been studied: oxazolines, masked aldehydes, − amides, − sulfonamides, and also sulfoxides. − The prochiral electrophiles used were aldehydes or ketones (leading to chiral alcohols), and the best asymmetric induction (excluding sulfoxides) was observed by Matsui 12,13 with amides (de = 80%). In the course of our studies on the synthesis and metalation of diazine and benzodiazine sulfoxides, ,, we observed that the addition of the metalated species to aldehydes took place in some cases with a remarkable asymmetric induction.…”

Asymmetric Ortholithiation of Amides by Conformationally Mediated Chiral Memory: An Enantioselective Route to Naphtho- and Benzofuranones

“…Ortholithiation is a powerful method for the regioselective functionalisation of an aromatic ring, 1 but attempts to use it to introduce ortho-substituents enantioselectively by, for example, using chiral metallation directing groups, have generally failed. 2 Chiral versions of several classes of metallation directing groups 3 -including amides, 4 oxazolines, 5 hydrazides, 6 sulfonamides, 7 and sulfoxides 8 -have all been examined, but only the last two have been able to show good, though substrate-dependent, levels of diastereoselectivity on addition to prochiral electrophiles. We have reported that an aromatic tertiary amide group, which may possess a stereogenic Ar-CO axis, 9 is capable of directing the diastereoselective formation of a new hydroxyl-bearing centre via ortholithiation and reaction with an aldehyde.…”

“…13 Lithiation of the tertiary amides 1 with s-BuLi in THF 14 gave ortholithiated amides 2 which reacted with (1R, 2S, 5R, SS)-(-)-menthyl toluenesulfinate 3 15 (Scheme 1) to yield sulfoxides 4. 7 Two alternative protocols were employed: initially the sulfinate was added to the lithiated amide ('Method A'). Products of high ee were obtained with this method when the amide was relatively hindered (4a,b,d were all formed in > 95% ee).…”