Evidence that Additions of Grignard Reagents to Aliphatic Aldehydes Do Not Involve Single-Electron-Transfer Processes

Otte, Douglas A. L.; Woerpel, K. A.

doi:10.1021/acs.orglett.5b01893

Cited by 24 publications

(27 citation statements)

References 58 publications

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“…45). This large electron-transfer energy is consistent with Woerpel’s observations that Grignard reagents do not react with electrophiles (for example, aldehydes) through one-electron transfer 46 . The ~30 kcal mol −1 strain energy of the oxaziridine ring and the relatively weak N–O bond could suggest homolytic cleavage of the N–O bond.…”

supporting

confidence: 89%

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

et al. 2016

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Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C–C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (–NH2) and hydroxyl (–OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N–H and N–alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts/ligands/additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.

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supporting

confidence: 89%

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

et al. 2016

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“…60,113,114 Experiments with cyclopropanecarboxaldehydes provide evidence that additions of allylmagnesium halides to alkyl aldehydes do not proceed via a single-electron-transfer mechanism (Scheme 12). 50 Additions by the single-electron transfer pathway should form ring-opened products because, if a ketyl intermediate were formed, the rate of ringopening (k ≈ 10 11 •s -1 ) should be similar to the rate of recombination of radical pairs. Additions of allylmagnesium halides to aldehyde 59, however, provided only the addition products regardless of the specific reaction conditions, indicating that the addition proceeded through a concerted mechanism.…”

Section: Single-electron Transfer Mechanismsmentioning

confidence: 99%

“…Although these investigations have been informative, [46][47][48] aromatic substrates are predisposed to react through singleelectron-transfer pathways, 49 which may not be representative of alkyl aldehydes and ketones. 50 Few studies have examined the mechanisms of these reactions as it affects the stereoselectivity of reactions with chiral substrates. 51,52 This review will summarize the current understanding of the reactions of allylmagnesium halides with carbonyl compounds, focusing on aspects most relevant to synthetic chemists: reactivity, structure, and mechanism.…”

Section: Introductionmentioning

confidence: 99%

Reactions of Allylmagnesium Halides with Carbonyl Compounds: Reactivity, Structure, and Mechanism

et al. 2017

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The additions of allylmagnesium reagents to carbonyl compounds are important methods in synthetic organic chemistry, but the mechanisms of these reactions are likely to be distinct from mechanisms followed by other organomagnesium reagents. Additions to alkyl aldehydes and ketones are likely to be concerted, proceeding through six-membered-ring transition states. These highly reactive reagents appear to react at rates that approach the diffusion limit, so chemoselectivity is generally low. Furthermore, reactions of allylmagnesium halides with carbonyl compounds are unlikely to follow stereochemical models that require differentiation between competing transition states. This Short Review discusses the current state of understanding of these reactions, including the structure of the reagent and unique aspects of the reactivity of allylmagnesium reagents.1 Introduction2 Reactions with Carbonyl Compounds2.1 Reactivity of Allylmagnesium Halides2.2 Selectivity of Addition3 Structure of Allylmagnesium Reagents3.1 Schlenk Equilibrium and Aggregation3.2 Spectroscopic Studies3.3 X-ray Crystallographic Studies3.4 Computational Studies of Structure4 Reaction Mechanism4.1 Substrate-Dependent Mechanisms4.2 Concerted Mechanisms4.3 Single-Electron Transfer Mechanisms4.4 Open, SE2′-Like Transition State4.5 Computational Studies of Mechanism5 Conclusion

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“…The reactivity-selectivity relationships exhibited by allylmagnesium halides are difficult to reconcile with one reaction mechanism. Single-electron transfer may occur in reactions with aromatic carbonyl compounds, forming species such as A . ,, By contrast, single-electron pathways are unlikely to be involved in additions to aliphatic carbonyl compounds . Experimental results have been used to support an open, S E 2′-like transition state ( B ), although computational studies suggest that a closed six-membered ring transition state, such as C , is favored .…”

mentioning

confidence: 52%

“…10,52,53 By contrast, single-electron pathways are unlikely to be involved in additions to aliphatic carbonyl compounds. 54 Experimental results have been used to support an open, S E 2′like transition state (B), 44 although computational studies suggest that a closed six-membered ring transition state, such as C, is favored. 55 Regardless of the mechanism, which could depend upon the electrophile, addition must be particularly rapid to be consistent with the reactivity-selectivity relationships reported here.…”

Section: Scheme 3 Competition Experiments Between Sterically Differen...mentioning

confidence: 99%

Allylmagnesium Halides Do Not React Chemoselectively Because Reaction Rates Approach the Diffusion Limit

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Woerpel

2017

J. Org. Chem.

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Competition experiments demonstrate that additions of allylmagnesium halides to carbonyl compounds, unlike additions of other organomagnesium reagents, occur at rates approaching the diffusion rate limit. Whereas alkylmagnesium and alkyllithium reagents could differentiate between electronically or sterically different carbonyl compounds, allylmagnesium reagents reacted with most carbonyl compounds at similar rates. Even additions to esters occurred at rates competitive with additions to aldehydes. Only in the case of particularly sterically hindered substrates, such as those bearing tertiary alkyl groups, were additions slower.

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Evidence that Additions of Grignard Reagents to Aliphatic Aldehydes Do Not Involve Single-Electron-Transfer Processes

Cited by 24 publications

References 58 publications

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

Reactions of Allylmagnesium Halides with Carbonyl Compounds: Reactivity, Structure, and Mechanism

Allylmagnesium Halides Do Not React Chemoselectively Because Reaction Rates Approach the Diffusion Limit

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