Mechanism of enantioselective protonation of an enolate in the presence of a chiral phenolic additive

Eames, Jason; Weerasooriya, Neluka

doi:10.1002/(sici)1520-636x(1999)11:10<787::aid-chir8>3.0.co;2-0

Cited by 15 publications

(5 citation statements)

References 15 publications

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“…Norephedrine (7), N-methylephedrine (8), and O-methylephedrine (9) gave no asymmetric induction (Table 5, Entries 4, 5, 6 respectively), and pseudoephedrine (10) In our next investigation, asymmetric protonation of lithium enolate 4a was performed under the standard conditions, but D 2 O was used to quench the reaction mixture in order to evaluate the amount of deuterium incorporation at the α-carbon. [34,35] In a preliminary experiment, we checked that the reaction between D 2 O and 4a, at -78°C, led to the deuteriated amide 2a-D in 100 % yield (Table 6, Entry 1, Scheme 1, route "a"). The results summarized in Table 6 show that, under the same conditions of temperature and time, quenching of the reaction mixture with D 2 O led to deuterium levels of 75-80 % with diamine (+)-5 (Entries 2, 3) and 25 % with (-)-ephedrine [(-)-6, Entry 7].…”

Section: Origin Of the Transferred Protonmentioning

confidence: 99%

Efficient Deracemization of Pipecolic Acid Amides through Enantioselective Protonation of Their Lithium Enolates: Insights into the Origin of the Transferred Proton

et al. 2009

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A detailed study of the deracemization of pipecolic acid amides is reported. Enantioselective protonation of the lithium enolates of these amides with use of commercially available ephedrines led to enantiomeric excesses (ee values) higher than 99 %. The success of the reaction was strongly dependent on the following parameters: the base, the reaction temperature, the structure of the chiral source, and the achiral quenching reagent. sBuLi and the bimetallic base "potassium alkoxide/nBuLi" were the only bases to allow complete formation of the enolate in conjunction with high stereocontrol of the protonation. Experiments with (+)-or (-)-ephedrine derivatives as chiral sources and deuteriated

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Section: Origin Of the Transferred Protonmentioning

confidence: 99%

Efficient Deracemization of Pipecolic Acid Amides through Enantioselective Protonation of Their Lithium Enolates: Insights into the Origin of the Transferred Proton

et al. 2009

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“…We have recently attempted to probe this competition between an internal and an external protonation using acetic acid as the proton source. We used the diamine (R,R)-49 46 and phenolate (S)-51 47 scaffold to study the protonation of 2-methyltetralone involving an external quench. The selectivities were modest; 47% e.e.…”

Section: Enantioselective Protonation Of Endocyclic Enolatesmentioning

confidence: 99%

Recent Studies on the Regioselective C-Protonation of Enol Derivatives using Carbonyl-Containing Proton Donors

Eames

Weerasooriya

2001

Journal of Chemical Research

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Both enantio-1 and diastereoselective 2 C-protonation of achiral and chiral enolates is well known. Many of these reports deal with proton transfer under kinetic control, 3 whereas protonation under thermodynamic control has become more popular when diastereoselective control is required. 4 There are only a few cases where the stereochemistrydetermining protonation step is under reagent control, 5 the most notable examples being the use of chelating proton donors (CPDs) such as salicylic esters 1, 6 and β-amino alcohols 2 (Scheme 1). 7 The salient feature of these chelating acids such as 4 is their ability to chelate to the metal cation of an enolate such as 3 and aid protonation directly onto carbon 8 of the corresponding enolate 6 (to give the carbonyl derivative 7), rather than in some cases the preferred protonation on oxygen (to give the enol 5), 9 tautomerisation of which would lead to the thermodynamically preferred carbonyl derivative 7. 10 2 J. CHEM. RESEARCH (S), 2001 * To receive any correspondence.

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“…2.5 for the LDA route (b). vi) While there were clear CH 2 Cl 2 solutions at all times when the reactions were carried out under conditions a and c (Scheme), precipitations 10 ) Since the SiO 2 column on which we put the crude product mixture (TADDOL 1 and non-racemic methyltetralone) is a chiral column, the ratio (R)-2/(S)-2 could possibly differ in different fractions [29]. We have, therefore, made sure that all ketone is eluted from the column, and we have performed the er analysis with the entire ketone sample recovered.…”

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confidence: 99%

“…Protonations with alcohols in which the OH group is not bonded to a stereogenic center have, so far, always led to modest selectivities[10] [41].…”

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confidence: 99%

Highly Enantioselective Protonation of the 3,4-Dihydro-2- methylnaphthalen-1(2H)-one Li-Enolate by TADDOLs

Cuenca¹,

Medio‐Simón²,

Aguilar³

et al. 2000

HCA

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A series of nine TADDOLs ( a,a,a',a'-tetraaryl-1,3-dioxolane-4,5-dimethanols) 1a ± 1i, have been tested as proton sources for the enantioselective protonation of the Li-enolate of 2-methyl-1-tetralone ( 3,4-dihydro-2-methylnaphthalen-1(2H)-one). The enolate was generated directly from the ketone (with LiN(i-Pr) 2 (LDA)/ MeLi) or from the enol acetate (with 2 MeLi) or from the silyl enol ether (with MeLi) in CH 2 Cl 2 or Et 2 O as the solvent (Scheme). The Li-enolate (associated with LiBr/LDA, or LiBr alone) was combined with 1.5 ± 3.0 equiv. of the TADDOL at À 788 by addition of the latter or by inverse addition. 2-Methyl-1-tetralone of (S)-configuration is formed ( 80% yield) with up to 99.5% selectivity if and only if (R,R)-TADDOLs (1d, e, g) with naphthalen-1-yl groups on the diarylmethanol unit are employed (Table). The reactions were carried out on the 0.1-to 1.0-mm scale. The selectivity is subject to non-linear effects (NLE) when an enantiomerically enriched TADDOL 1d is used (Fig. 1). The performance of TADDOLs bearing naphthalen-1-yl groups is discussed in terms of their peculiar structures (Fig. 2).

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Mechanism of enantioselective protonation of an enolate in the presence of a chiral phenolic additive

Cited by 15 publications

References 15 publications

Efficient Deracemization of Pipecolic Acid Amides through Enantioselective Protonation of Their Lithium Enolates: Insights into the Origin of the Transferred Proton

Efficient Deracemization of Pipecolic Acid Amides through Enantioselective Protonation of Their Lithium Enolates: Insights into the Origin of the Transferred Proton

Recent Studies on the Regioselective C-Protonation of Enol Derivatives using Carbonyl-Containing Proton Donors

Highly Enantioselective Protonation of the 3,4-Dihydro-2- methylnaphthalen-1(2H)-one Li-Enolate by TADDOLs

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