Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation

Abstract

A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring α-amino- or α-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular carbolithiation reactions, outperforming the benchmark ligand (-)-sparteine. The ligand could be used in a substoichiometric amount (0.25 equiv) without significant loss of enantioselectivity.

Selective Monovalent Galectin‐8 Ligands Based on 3‐Lactoylgalactoside

“…The synthesis of candidate compounds predicted by our in silico studies was accomplished as shown in Scheme 1. Intermediate 11 was obtained starting from α‐ d ‐cyclohexylglycine ( 8 ), via a diazotization−hydrolysis reaction [28] (→ 9 ) and subsequent esterification of the carboxylic group with benzyl bromide (→ 10 ). The hydroxyl group of 10 was transformed into a good leaving group by reacting it with triflic anhydride to give donor 11 .…”

Regio- and stereoselective intermolecular carbolithiation reactions

“…In fact, they have provided promising results in the enantioselective intramolecular carbolithiation, where chiral 1,2-aminoethers derived from pseudoephedrine or ephedrine 75 and, more recently, from naturally occurring a-amino or a-hydroxy acids have been employed. 76 In the latter example, both high enantioselectivity (up to 90% e.e.) and good substrate versatility in the intramolecular cyclization of aryl-allyl lithium derivatives were obtained.…”

“…amounts of the ligand. 76 This result could open the way to the development of novel catalytic procedures, thus signicantly enlarging the synthetic appeal of the reaction. A further, signicant, improvement could be provided by the use in the carbolithiations of functionalized organolithiums, [77][78][79] which would allow the construction of complex molecular systems.…”

IntramolecularAnti‐Carbolithiation of Alkynes: Stereo‐Directing Effect of Lithium‐Coordinating Substituents

“…[16][17][18] A few examples of anti-addition of alkyllithiums onto triple bonds have also been sporadically reported, however factors explaining these unexpected stereoselectivities have not yet been clearly identified. [19][20][21] In the course of our ongoing studies on the formation of carbocycles via intramolecular carbolithiation, [22,23] we took an interest in the 5-exodig cyclization of o-homopropargyl aryllithiums. Such reaction provides an access to functionalized indans, which are useful scaffolds for the development of pharmaceuticals.…”