Chiral Bidentate Lithium Amides Research Articles

ChemInform Abstract: Stereoselective Reactions. Part 34. Enantioselective Deprotonation of Prochiral 4‐Substituted Cyclohexanones Using Chiral Bidentate Lithium Amides Having a Bulky Group Instead of a Phenyl Group on the Chiral Carbon.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Stereoselective reactions. XXXIV. Enantioselective deprotonation of prochiral 4-substituted cyclohexanones using chiral bidentate lithium amides having a bulky group instead of a phenyl group on the chiral carbon.

Using chiral bidentate lithium amides having a bulky group instead of a phenyl group on the chiral carbon, enantioselective deprotonation of prochiral 4-substituted cyclohexanones in the presence of excess trimethylsilyl chloride was examined in THF in the absence and in the presence of HMPA. It is shown that enantioselectivity of the reactions decreases as the substituent on the chiral carbon of the chiral lithium amides and the substituent at the 4-position of cyclohexanones become reasonably bulky. An eight-membered cyclic transition state model is proposed for this deprotonation reaction.

Stereoselective reactions. XXXIIII. Design and synthesis of chiral bidentate amines having a bulky group on the chiral carbon.

Based on the solution structures of chiral bidentate lithium amides ((R)-3a,b) having a phenyl group on the chiral carbon, chiral bidentate amines ((R)-5a,b-8a,b and (S)-9a,b) having a bulkier group instead of a phenyl group on the chiral carbon were designed and synthesized.

ChemInform Abstract: Enantioselective α‐Alkylation of Phenylacetic Acid Using a Chiral Bidentate Lithium Amide as a Chiral Auxiliary.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Stereoselective Reactions. Part 28. Effects of the Alkyl Group at the Amide Nitrogen of Chiral Bidentate Lithium Amides on Enantioselective Deprotonation Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Stereoselective reactions. 29. Lithium-hydrogen interchange between achiral tridentate lithium amides and chiral bidentate amines. An approach to catalytic enantioselective deprotonation

1H-NMR spectral studies have shown that lithium-hydrogen interchange between a chiral bidentate amine ( (R)- 3b ) and an achiral tridentate lithium amide ( 5a) occurs rapidly in THF, favoring the exclusive formation of a chiral bidentate lithium amide ( (R)- 2b ) at equilibrium. This finding was applied to catalytic asymmetric deprotonation of prochiral 4-substituted cyclohexanones ( 1) using 0.3 equivalent of (R)- 3b in the presence of 2.4 equivalents of 5a in THF in the presence of DABCO and HMPA.

Stereoselective reactions. 28. Effects of the alkyl group at the amide nitrogen of chiral bidentate lithium amides on enantioselective deprotonation reaction

Enantioselective deprotonation of 4-substituted cyclohexanones ( 1a∼d ) by chiral bidentate lithium amides ( (R)- 2a∼j ) having an alkyl- or a fluoroalkyl substituent at the amide nitrogen was examined. (R)- 2i having a 2,2,2-trifluoroethyl group at the amide nitrogen was found to be an excellent chiral base for the present deprotonation reaction. Structures of (R)- 2i in solution and solid state are discussed.

Stereoselective reactions. 26. Solution structures of chiral bidentate lithium amide in relation to the solvent-dependent enantioselectivities in deprotonation reaction

Abstract 6 Li- and 15 N-NMR spectroscopic analyses of a labeled chiral bidentate lithium amide ( [ 6 Li , 15 N 2 ]-(R)- 1 ) have shown that it exists as a chelated monomer ( 5 ) in THF and in DME, as a chelated dimer ( 6 ) in toluene and in ether, while as a chelated monomer ( 5 ) in any of these solvents in the presence of 2 equivalents of HMPA. Solvent-dependent enantioselectivities in deprotonation of 4- tert -butylcyclohexanone ( 2 ) by (R)- 1 appear to be correlated to these solution structures.

Asymmetric synthesis using chiral bases

Studies have been made to design chiral bidentate lithium amides and chiral tetradentate amines, and to explore the use of these chiral bases for enantioselective formation and reactions of lithium enolates. Chiral bidentate lithium amides having a chiral amide nitrogen made by virtue of chelation were successfully applied to the enantioselective deprotonation reaction of prochiral cyclic ketones, the kinetic resolution of racemic cyclohexanone derivatives by deprotonation, and the regioselective deprotonation of optically active 3-keto steroids. Structures of some of these chiral bidentate lithium amides in the solid state and in solution were elucidated by X-ray and NMR spectroscopic analyses. By the use of chiral tetradentate amines, enantioselective reactions of lithium enolates with electrophiles, such as alkylation, protonation, and Michael addition, proceeded successfully. Examples of catalytic enantioselective deprotonation, alkylation, and protonation by the present strategy are also presented and discussed.

Stereochemistry of enantioselective deprotonation of 4-substituted cyclohexanones by chiral bidentate lithium amides

Enantioselective deprotonation of 4-substituted cyclohexanones ( 1) in the presence of excess trimethylsilyl chloride was examined using chiral bidentate lithium amides ((R)- 3∼(R)- 7) in THF. The solution structures of (R)- 3a in THF in the presence and in the absence of lithium chloride were studied by NMR. It is concluded that the eight-membered cyclic transition state ( 10) offers reasonable explanation of the stereochemical course of the present reaction using (R)- 3a.

Enantioselective .ALPHA.-Alkylation of Phenylacetic Acid Using a Chiral Bidentate Lithium Amide as a Chiral Auxiliary.

Enantioselective alkylation at the α-position of phenylacetic acid (1) can be realized in up to 68% ee by treating the dilithiated 1 with alkyl halides in the presence of a chiral bidentate lithium amide ((R)-3).

An approach to catalytic asymmetric deprotonation of 4-substituted cyclohexanones

Lithium-hydrogen interchange between a chiral bidentate amine ((R)- 4b ) and an achiral tridentate lithium amide ( 8) occurs rapidly in situ, favoring the exclusive formation of a chiral bidentate lithium amide ((R)- 5b ) . Based on this finding, catalytic asymmetric deprotonation of 4-substituted cyclohexanones ( 1a∼d) was realized by using less than a stoichiometric amount of (R)- 4b as a chiral auxiliary.

Crystallographic and lithium-6 and nitrogen-15 NMR studies of a chiral bidentate lithium amide. An effect of aggregation states on an enantioselective deprotonation reaction

Crystallographic and lithium-6 and nitrogen-15 NMR studies of a chiral bidentate lithium amide. An effect of aggregation states on an enantioselective deprotonation reaction