Ring opening reactions of electrophilic cyclopropanes

Dieter, R. Karl; Pounds, Scot

doi:10.1021/jo00137a032

Cited by 51 publications

(25 citation statements)

References 6 publications

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“…Generally speaking, the reactivity of monosubstituted cyclopropanes is much less developed than for donor–acceptor cyclopropanes. Existing ring-opening reactions include oxidative addition into C–C bonds with transition metals, 6 – 8 oxidative 1,3-difunctionalization, 9 frustrated Lewis pairs, 10 , 11 or addition of strong nucleophiles 12 – 14 and mineral acids. 15 One-pot iodination/alkylation procedures are also known.…”

Section: Introductionmentioning

confidence: 99%

Ring-opening hydroarylation of monosubstituted cyclopropanes enabled by hexafluoroisopropanol

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Ring-opening hydroarylation of monosubstituted cyclopropanes enabled by hexafluoroisopropanol

et al. 2018

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“…Finally, the ring‐opening could also take place by direct attack of the alcohol on the cyclopropyl ring (Scheme , left pathway). However, such a direct attack is primarily observed with electrophilic cyclopropanes, and the cyclopropyl substituents in our starting material may just not be electrophilic enough.…”

Section: Discussionmentioning

confidence: 99%

Ferrocenium Cations as Catalysts for the Etherification of Cyclopropyl‐Substituted Propargylic Alcohols: Ene‐yne Formation and Mechanistic Insights

et al. 2019

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Commercial ferrocenium hexafluorophosphate ([FeCp 2 ]PF 6 ) and ferrocenium boronic acid hexafluoroantimonate ([FcB(OH) 2 ]SbF 6 ) were found to be efficient catalysts for the etherification of terminal, tertiary, cyclopropyl-substituted propargylic alcohols through nucleophilic substitution with primary and secondary alcohols. The alcohol nucleophiles and the propargylic alcohols were employed in a nearly equimolar amount and no further additives were required. After 2 h reaction time at 40°C in CH 2 Cl 2 and 3 to 5 mol-% catalyst load, aromatic, cyclopropyl-substituted propargylic alcohols gave rearranged, conjugated ene-yne products as single isomers in 35 to 73 % isolated yields. Cyclopropyl-substituted propargylic alcohols [a] 7349 Accordingly, we decided to synthesize cyclopropyl-substituted propargylic alcohol substrates (4 in Scheme 1c) to investigate whether the reaction proceeds through a radical mechanism. Cyclopropyl-substituted radicals 6 (Scheme 1c) may ringopen to form alkenes, but carbocation 5 may also have this tendency (vide infra). As exemplified in Scheme 1c, ene-ynes 7 can form through rearrangement if a cyclopropyl-substituted propargylic alcohol 4 is employed. [35] The employment of cyclopropyl-substituted propargylic alcohols in reactions with alcohols to give conjugated, achiral enynes has been reported previously only four times, utilizing Yb(OTf ) 3 , [36a] triflic acid (TfOH), [36b] HAuCl 4[36c] and ruthenium complexes [36d] as catalysts. In these reports, the nucleophile was either the solvent [36b,36c] or employed in large excess. [36a,36d] Herein, we report ferrocenium-catalyzed substitution reactions with these substrates and isolated both ene-yne products and cyclopropylsubstituted products, depending on the substituent R in 4. Experimental evidence points toward an ionic mechanism through carbocation 5 (Scheme 1c). [37] Eur.Scheme 2. Formation of the cyclopropyl-substituted intermediate 21 and ring-opening.

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“…Cognizant of the fact that this enamine reacts readily with electrophilic chlorine sources,17 we envisaged that this strategy would provide an unprecedented method for the enantioselective synthesis of 1,3‐dichlorides; a formal addition of Cl 2 across a cyclopropane bond 18. Initially, we investigated the chlorination of the cyclopropane carbaldehyde19 derived from cyclopentene (Table 1); the chlorination products of this material can be readily analyzed by GC on a chiral stationary phase. To facilitate analysis by 1 H NMR spectroscopy, CDCl 3 was chosen as a screening solvent.…”

Section: Methodsmentioning

confidence: 99%

Cyclopropyl Iminium Activation: Reactivity Umpolung in Enantioselective Organocatalytic Reaction Design

2011

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The intrinsic donor-acceptor reactivity pattern of conjugated, unsaturated carbonyl compounds predictably alternates along the carbon chain (Scheme 1). Consequently, electrophiles are predisposed to react at the a (d 2 ) and g (d 4 ) donor positions, whereas nucleophiles add to the b (a 3 ) and d (a 5 ) acceptor positions. Direct inversion of this inherent selectivity is known as reactivity umpolung, [1] and often provides a platform for the development of novel transformations. While various activation modes that allow for a (a 2 /d 2 ), b (a 3 ), g (d 4 ), and e (d 6 ) functionalization have been reported through secondary amine organocatalysis, [2] umpolung strategies remain elusive outwith the confines of SOMO activation [2b] and processes mediated by N-heterocyclic carbenes (NHCs). [3,4] Because pyrrolidine-and imidazolidinone-based organocatalysts require carbonyl substrates to generate the transient intermediates that are central for catalysis, the substrate scope is limited to aldehydes and ketones with varying degrees of unsaturation. With a view to extending the substrate scope of secondary-amine-catalyzed processes, and providing an entry point into the design of homologous variants of addition reactions to a,b-unsaturated iminium ions, we began exploring the reactivity of cyclopropane carbaldehydes.Cyclopropane behaviour has striking parallels with that of olefins.[5] In addition to their ability to interact with adjacent p systems, cyclopropanes function as effective donors when activated by adjacent low-lying empty orbitals: this can be rationalized by considering the Walsh orbitals. [6,7] Striking manifestations of the electron-donating aptitude of cyclopropanes include: 1) the unusual thermodynamic stability of the cyclopropylcarbinyl cation, [8] and 2) the bond-length asymmetry of cyclopropanecarbonitirile (Dd (distalÀvicinal) = 0.033 ) as a consequence of hyperconjugation. [9,10] Of particular pertinence to this study is the latter observation. It was envisaged that the well described conjugation between a cyclopropane moiety and polar multiple bonds might form the basis of an activation strategy involving cyclopropyl iminium salts. Indeed, Wang and co-workers have described that the nucleophilic addition of benzenethiols to cyclopropanecarbaldehydes can be catalyzed by proline.[11] The similarities in bonding between this species and that of conventional a,b-unsaturated iminium ions, together with the expected interaction of the cyclopropyl moiety with the conjugated iminium functionality, motivated us to investigate the reactivity of cyclopropane carbaldehydes [12] upon unification with secondary amines (Scheme 2). Formally, nucleophilic addition to the transient cyclopropyl iminium species would constitute a formal umpolung of the g-position of a dienamine;[2c] d 4 !a 4 (Scheme 1). Moreover, by intercepting the transient enamine with an electrophile, this strategy would give an unprecedented method for the organocatalytic formation of 1,3-difunctionalized products in a single operation (Sche...

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Ring opening reactions of electrophilic cyclopropanes

Cited by 51 publications

References 6 publications

Ring-opening hydroarylation of monosubstituted cyclopropanes enabled by hexafluoroisopropanol

Ring-opening hydroarylation of monosubstituted cyclopropanes enabled by hexafluoroisopropanol

Ferrocenium Cations as Catalysts for the Etherification of Cyclopropyl‐Substituted Propargylic Alcohols: Ene‐yne Formation and Mechanistic Insights

Cyclopropyl Iminium Activation: Reactivity Umpolung in Enantioselective Organocatalytic Reaction Design

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