Asymmetric Amplification Coupling Enantioselective Autocatalysis and Asymmetric Induction for Alkylation of Azaaryl Aldehydes

Romagnoli, Carlo; Sieng, Bora; Amedjkouh, Mohamed

doi:10.1002/ejoc.201500508

Cited by 20 publications

(10 citation statements)

References 41 publications

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“…This explains also the excellent selectivities of the 2‐(adamantylacetylene‐1‐yl)‐ and 2‐(trimethylsilylacetylene‐1‐yl)‐substituted pyrimidyl alcohols [10c, 37] . Furthermore these mixing experiments are in good agreement with the experiments by Amedjkouh using pyrimidine alcohol 1 as chiral additive in the Soai reaction of pyridyl‐3‐carbaldehydes [12d, 48] …”

Section: Resultssupporting

confidence: 83%

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

Trapp

Lamour

Maier

et al. 2020

Chemistry A European J

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Chemical reactions that lead to as pontaneous symmetry breaking or amplification of the enantiomeric excess are of fundamental interesti ne xplaining the formation of ah omochiral world.Ano utstanding example is Soai's asymmetric autocatalysis, in which small enantiomerice xcesses of the added product alcohol are amplified in the reaction of diisopropylzinc and pyrimidine-5-carbaldehydes. The exact mechanism is still in dispute due to complex reaction equilibria and elusive intermediates. In situ high-resolution mass spectrometric measurements, detailed kinetic analyses and doping with in situ reacting reaction mixtures show the transient formationo fh emiacetal complexes, whichc an establish an autocatalytic cycle.W ep ropose a mechanism that explainst he autocatalytic amplification involving these hemiacetal complexes.C omprehensivek inetic experiments and modelling of the hemiacetal formation and the Soai reactiona llow the precise predictiono ft he reaction progress, the enantiomeric excessa sw ell as the enantiomeric excess dependentt ime shift in the induction period. Experimental structurald ata give insights into the privileged properties of the pyrimidyl units and the formationof diastereomeric structures leading to an efficient amplification of even minimalenantiomeric excesses, respectively.

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Section: Resultssupporting

confidence: 83%

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

Trapp

Lamour

Maier

et al. 2020

Chemistry A European J

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“…al ., 2015) to show chiral erosion. 42 We have been unable to reproduce the observation reported by Amedjkouh et al Instead, we have observed amplifying autocatalysis for both substrates – diisopropylzinc alkylation of 5-(t-butylethynyl)pyridine-3-carbaldehyde also demonstrates amplifying autocatalysis (See Supplementary Figure 2 ).…”

Section: Resultscontrasting

confidence: 65%

Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies

et al. 2020

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The Soai reaction has profoundly impacted chemists’ perspective of chiral symmetry breaking, absolute asymmetric synthesis and its role in the origin of biological homochirality. Herein, we describe the unprecedented observation of asymmetry amplifying autocatalysis in the alkylation of 5-(trimethylsilylethynyl)pyridine-3-carbaldehyde using diisopropylzinc. Kinetic studies with a surrogate substrate and spectroscopic analysis of a series of zinc-alkoxides that incorporate specific structural mutations reveal a ‘pyridine-assisted cube escape’. The new tetrameric cluster functions as a catalyst that activates the substrate through a two point binding mode and poises a coordinated diisopropylzinc moiety for alkyl group transfer. Transition-state models leading to both the homochiral and heterochiral products were validated by density functional theory calculations. Moreover, experimental and computational analysis of the heterochiral complex provides a definitive explanation for the non-linear behavior of this system. Our deconstruction of the Soai system reveals the structural logic for autocatalyst evolution, function and substrate compatibility – a central mechanistic aspect of this iconic transformation.

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“…However, in 2006, Wang et al developed a one-pot alkynylation-isomerizationalkynylation sequence for coupling aldehydes and alkynes without a transition-metal catalyst for the synthesis of 1-en-4-yn-3ols. [37][38][39] During our investigations, an interesting rearrangement was observed with electron-deficient alkynes under the same reaction conditions, which gave rise to heteroaromatic enone. However, the reaction was limited to substituted phenyl acetylenes.…”

Section: Introductionmentioning

confidence: 64%

“…[35,36] We have recently reported on the use of the Soai's autocatalyst in the asymmetric alkynylation of azaaryl aldehydes with various zinc acetylinides. [37][38][39] During our investigations, an interesting rearrangement was observed with electron-deficient alkynes under the same reaction conditions, which gave rise to heteroaromatic enone. Such isomerization occurred spontaneously in situ without the addition of any base or transition metal.…”

Section: Introductionmentioning

confidence: 64%

One‐Pot Alkynylation of Azaaryl Aldehydes and Spontaneous Base‐Free Rearrangement into Enone Esters: an Autoinductive Mechanism

et al. 2018

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A direct synthesis of γ‐oxo‐α,β‐unsaturated esters has been developed. When heteroaromatic aldehydes are reacted with deprotonated ethyl propiolate, in the presence of Me2Zn or BuLi, the newly formed propargylic alcohol rearranged spontaneously to give the corresponding unsaturated keto ester. Isotope labeling, allenol intermediate trapping and crossover experiments provided insight into the reactive sequence and suggest an autocatalytic mechanism.

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Asymmetric Amplification Coupling Enantioselective Autocatalysis and Asymmetric Induction for Alkylation of Azaaryl Aldehydes

Cited by 20 publications

References 41 publications

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

In Situ Mass Spectrometric and Kinetic Investigations of Soai's Asymmetric Autocatalysis

Demystifying the asymmetry-amplifying, autocatalytic behaviour of the Soai reaction through structural, mechanistic and computational studies

One‐Pot Alkynylation of Azaaryl Aldehydes and Spontaneous Base‐Free Rearrangement into Enone Esters: an Autoinductive Mechanism

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