Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones

Javier Francos, Silvia Zaragoza-Calero, Charles T. O'Hara

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with nBu 2Mg, improved enantioselective deprotonation of 4-tert- butylcyclohexanone (with respect to the monometallic lithium amide) at 20°C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0°C were those in which (Me3SiCH2)2Mg (er pro-S 74:26) and (Me3SiCH2)2Mn (er pro-S 72:28) were added, hence the lithium magnesiate "LiMg(2)(CH2SiMe 3)2" was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of "LiMg(2)(CH2SiMe 3)2" appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for "LiMg(2)(CH2SiMe3)2". By adding LiCl to "LiMg(2)(CH2SiMe3)2" the er at 0°C improved to 81:19. At -78°C good yields and an er of 93:7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones. 

LanguageEnglish
Pages1408-1412
Number of pages5
JournalDalton Transactions
Volume43
Issue number3
Early online date1 Nov 2013
DOIs
Publication statusPublished - 21 Jan 2014

Fingerprint

Deprotonation
Ketones
Lithium
Amides
Amines
Salts
Nuclear magnetic resonance

Keywords

  • lithium magnesiate
  • enantioselective deprotonation
  • enantioselectivity
  • amides
  • butylcyclohexanone
  • prochiral ketones
  • organic solvents

Cite this

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title = "Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones",
abstract = "A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with nBu 2Mg, improved enantioselective deprotonation of 4-tert- butylcyclohexanone (with respect to the monometallic lithium amide) at 20°C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0°C were those in which (Me3SiCH2)2Mg (er pro-S 74:26) and (Me3SiCH2)2Mn (er pro-S 72:28) were added, hence the lithium magnesiate {"}LiMg(2)(CH2SiMe 3)2{"} was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of {"}LiMg(2)(CH2SiMe 3)2{"} appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for {"}LiMg(2)(CH2SiMe3)2{"}. By adding LiCl to {"}LiMg(2)(CH2SiMe3)2{"} the er at 0°C improved to 81:19. At -78°C good yields and an er of 93:7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones. ",
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Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones. / Francos, Javier; Zaragoza-Calero, Silvia; O'Hara, Charles T.

In: Dalton Transactions, Vol. 43, No. 3, 21.01.2014, p. 1408-1412.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones

AU - Francos, Javier

AU - Zaragoza-Calero, Silvia

AU - O'Hara, Charles T.

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N2 - A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with nBu 2Mg, improved enantioselective deprotonation of 4-tert- butylcyclohexanone (with respect to the monometallic lithium amide) at 20°C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0°C were those in which (Me3SiCH2)2Mg (er pro-S 74:26) and (Me3SiCH2)2Mn (er pro-S 72:28) were added, hence the lithium magnesiate "LiMg(2)(CH2SiMe 3)2" was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of "LiMg(2)(CH2SiMe 3)2" appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for "LiMg(2)(CH2SiMe3)2". By adding LiCl to "LiMg(2)(CH2SiMe3)2" the er at 0°C improved to 81:19. At -78°C good yields and an er of 93:7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones. 

AB - A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with nBu 2Mg, improved enantioselective deprotonation of 4-tert- butylcyclohexanone (with respect to the monometallic lithium amide) at 20°C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0°C were those in which (Me3SiCH2)2Mg (er pro-S 74:26) and (Me3SiCH2)2Mn (er pro-S 72:28) were added, hence the lithium magnesiate "LiMg(2)(CH2SiMe 3)2" was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of "LiMg(2)(CH2SiMe 3)2" appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for "LiMg(2)(CH2SiMe3)2". By adding LiCl to "LiMg(2)(CH2SiMe3)2" the er at 0°C improved to 81:19. At -78°C good yields and an er of 93:7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones. 

KW - lithium magnesiate

KW - enantioselective deprotonation

KW - enantioselectivity

KW - amides

KW - butylcyclohexanone

KW - prochiral ketones

KW - organic solvents

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