Aminoferrocene Lithiation by Boron Trifluoride Activation

Metallinos, Costa; Zaifman, Josh; Dodge, Laura

doi:10.1021/ol8013182

Cited by 30 publications

(31 citation statements)

References 49 publications

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“…[13] Methyl tert-butyl ether (MTBE) was the preferred solvent for these experiments because of the higher solubility of zwitterion 11·BF 3 at low temperatures. The use of 1.1 equivalents of n-BuLi resulted in lower product yields for all ligands, while (À)-sparteine-or (S,S)-TMCDA-mediated lithiation with secondary alkyllithiums did not improve selectivity.…”

Section: Methodsmentioning

confidence: 99%

“…[25] Reductive amination of 10 with NaBH 3 CN and paraformaldehyde in acetic acid gave N,N-dimethylaminoferrocene [26] (11) in 91% yield. N-Ferrocenyl pyrrolidine (13) was obtained in 71% overall yield by sequential treatment of 10 with succinic anhydride to give imide 12, which underwent reduction with BH 3 ·THF.…”

Section: Complexed Aminoferrocenesmentioning

confidence: 99%

“…Column chromatography was performed on silica gel 60 (70-230 mesh) or neutral alumina. NMR spectra were obtained on a Bruker Avance 300 or 600 MHz instrument and are referenced to TMS or to the residual proton signal of the deuterated solvent for 1 H spectra, and to the carbon multiplet of the deuterated solvent for 13 C spectra according to published values.…”

Section: Experimental Section Generalmentioning

confidence: 99%

“…Almost concurrently, our group reported that the BF 3 -activated lithiation of dimethylaminoferrocene proceeds readily with 1.1 equivalents of n-BuLi in THF at À40 8C (9) to give a broad range of products in high yields (77-94%) after addition of electrophiles. [13] Unlike anilines, tertiary aminoferrocenes are prochiral and therefore should be amenable to asymmetric deprotonation. [14] The resulting carbanions would be expected to have configurational stability in the same way that (À)-sparteine-mediated lithiation of 5 and 6 generates enantiomerically enriched intermediates.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetric Lithiation of Boron Trifluoride‐Activated Aminoferrocenes: An Experimental and Computational Investigation

et al. 2010

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Tertiary aminoferrocenes complexed to boron trifluoride (BF 3 ) are shown to undergo asymmetric lithiation with alkyllithiums in the presence of bulky chiral 1,2-diaminocyclohexane ligands. This reaction represents the first BF 3 -activated asymmetric lithiation of a prochiral aromatic amine and the first such transformation to be mediated by a chiral di-A C H T U N G T R E N N U N G amine other than (À)-sparteine. The process provides rapid access to a broad range of enantiomerically enriched 2-substituted-1-aminoferrocenes, including derivatives with uncommon substitution patterns that are of interest in catalysis. The enantioselectivity of the process is high enough (87:13 to 91:9 er) to allow for isolation of single enantiomers of several products after simple recrystallization as either the free aminoferrocenes or their ammonium fluoroborate salts. Both antipodes of the planar chiral 2-substituted-1-aminoferrocene products are accessible, as confirmed by single crystal X-ray diffraction analysis of two compounds with opposite relative stereochemistry. Single-point calculation of thirty-two different transition states of the reaction at the M06-2X/6-311 + gA C H T U N G T R E N N U N G (2d,2p) level produced a computational model that correctly predicted both the sense and extent of chiral induction. Three factors appeared to play important roles in determining enantioinduction during lithiation of BF 3 -complexed tertiary aminoferrocenes: (i) the maintenance of a highly organized eight-membered ring transition state; (ii) the existence of a strong Li···F contact which placed the chiral diamine ligand in close proximity to the ferrocene substrate; (iii) the orientation of the sterically demanding N-alkyl groups of the chiral diamine additives, either away or towards, the aminoferrocene and the alkyllithium. The model may serve as a predictive tool for the rational design of new ligands for this and related asymmetric lithiations.

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Section: Methodsmentioning

confidence: 99%

Section: Complexed Aminoferrocenesmentioning

confidence: 99%

Section: Experimental Section Generalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Asymmetric Lithiation of Boron Trifluoride‐Activated Aminoferrocenes: An Experimental and Computational Investigation

et al. 2010

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“…Recently, the BF 3 -complexed dimethylaminoferrocene 122 was found by Metallinos [97] to undergo ortho-lithiation upon treatment with n-BuLi. Exposure of the lithioferrocene to nine different carbon and heteroatom-based electrophiles gave racemic products in 76-94% yield.…”

Section: Enantioselective Directed Ortho-metalation Of Ferrocenes Witmentioning

confidence: 99%

Stereoselective Synthesis of Planar Chiral Ferrocenes

Deng¹,

Snieckus²,

Metallinos³

2009

Chiral Ferrocenes in Asymmetric Catalysis

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Diastereoselective Synthesis of N‐Substituted Planar Chiral Ferrocenes Using a Proline Hydantoin‐Derived Auxiliary

et al. 2012

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An N-substituted ferrocene bearing a proline-derived chiral directing group undergoes diastereoselective lithiation-electrophile quench to give planar chiral products in > 95:5 dr. The starting material is synthesized by imidation of iodoferrocene with l-proline hydantoin, followed by hydrosilylation. Although the auxiliary is stable to lithium bases of the types RLi and R 2 NLi, the ortho-substituted products may be converted to solely planar chiral derivatives with simple reagents thanks to a labile triethylsilyloxy moiety.

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Aminoferrocene Lithiation by Boron Trifluoride Activation

Cited by 30 publications

References 49 publications

Asymmetric Lithiation of Boron Trifluoride‐Activated Aminoferrocenes: An Experimental and Computational Investigation

Asymmetric Lithiation of Boron Trifluoride‐Activated Aminoferrocenes: An Experimental and Computational Investigation

Stereoselective Synthesis of Planar Chiral Ferrocenes

Diastereoselective Synthesis of N‐Substituted Planar Chiral Ferrocenes Using a Proline Hydantoin‐Derived Auxiliary

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