Thrilling Strain! Donor–Acceptor‐Substituted Cyclobutanes for the Synthesis of (Hetero)Cyclic Compounds

Reißig, Hans‐Ulrich; Zimmer, Reinhold

doi:10.1002/anie.201501135

Cited by 64 publications

(24 citation statements)

References 29 publications

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“…1 They are also precursors to functional materials via ring-opening polymerization (ROP) 2 and key synthetic intermediates en route to complex molecules by cycloaddition reactions. 3 Prototypical three and four-membered carbon rings I and II (Scheme 1, top) are highly strained, but nevertheless resist nucleophilic, electrophilic, or dipolar ring opening due to the high barrier for heterolytic fission for non-polar C-C bonds (ca. 1300 kJ mol -1 in ethane).…”

Section: Introductionmentioning

confidence: 99%

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Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

et al. 2017

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Heterolytic cleavage of homoatomic bonds is a challenge, as it requires separation of opposite charges. Even highly strained homoatomic rings (e.g., cyclopropane and cyclobutane) are kinetically stable and do not react with nucleophiles or electrophiles. In contrast, cycloalkanes bearing electron-donating/withdrawing substituents on adjacent carbons have polarized C-C bonds and undergo numerous heterolytic ring-opening and expansion reactions. Here we show that upon electrophile activation phosphorus homocycles exhibit analogous reactivity, which is modulated by the amount of ring strain and extent of bond polarization. Neutral rings (BuP), 1, or (BuP), 2, show no reactivity toward nitriles, but the cyclo-phosphinophosphonium derivative [(BuP)Me], [3Me], undergoes addition to nitriles giving five-membered PCN heterocycles. Because of its lower ring strain, the analogous four-membered ring, [(BuP)Me], [4Me], is thermodynamically stable with respect to cycloaddition with nitriles, despite similar P-P bond polarization. We also report the first example of isonitrile insertion into cyclophosphines, which is facile for polarized derivatives [3Me] and [4Me], but does not proceed for neutral 1 or 2, despite the calculated exothermicity of the process. Finally, we assessed the reactions of [4R] R = H, Cl, F toward 4-dimethylaminopyridine (dmap), which suggest that the site of nucleophilic attack varies with the extent of P-P bond polarization. These results deconvolute the influence of ring strain and bond polarization on the chemistry of inorganic homocycles and unlock new synthetic possibilities.

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Section: Introductionmentioning

confidence: 99%

“…nitriles, 5 , 6 , 7 , 8 nitrosyls, 9 , 10 ketones, 11 aldehydes 12 ), permitting the rapid assembly of complex four-, five-, and six-membered heterocycles. 3,13 In these reactions, donor-acceptor functionalized strained cycloalkanes behave as masked dipoles whose reactivity is analogous to that of canonical dipoles like the azide anion.…”

Section: Introductionmentioning

confidence: 99%

Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

et al. 2017

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“…Chemical stability. Indeed, because the donor-acceptor cyclobutanes sometimes undergo ring-fragmentation, 28 we next checked a chemical stability of difluorobicyclo[1.1.1]pentaines, being strained cyclobutanes. Luckily, treatment of acid 17 and amine 27 with aq.…”

Section: Synthesis Of Building Blocksmentioning

confidence: 99%

Difluoro-Substituted bicyclo[1.1.1]pentanes as Novel Motifs for Medicinal Chemistry: Design, Synthesis and Characterization

Bychek¹,

Hutskalova²,

Bas³

et al. 2019

Preprint

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“… 2 − 7 Moreover, cyclobutanes are also interesting synthetic intermediates as they show a particular reactivity due to the high ring strain. 8 − 11 …”

Section: Introductionmentioning

confidence: 99%

Reactivity of (Z)-4-Aryliden-5(4H)-thiazolones: [2 + 2]-Photocycloaddition, Ring-Opening Reactions, and Influence of the Lewis Acid BF₃

et al. 2021

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The irradiation of ( Z )-2-phenyl-4-aryliden-5(4 H )-thiazolones 2 with blue light (465 nm) in CH 2 Cl 2 solution promotes [2 + 2]-photocycloaddition of the exocyclic C=C bonds and the formation of the dispirocyclobutanes 3 . This reaction takes place with high stereoselectivity, given that the ε-isomer (1,3 head-to-tail syn coupling) is formed in more than 90% yield in most of the cases. However, irradiation of 5(4 H )-thiazolones 2 with blue light (456 nm) in dry MeOH in the presence of BF 3 ·OEt 2 leads to the monospirocyclobutanes 4 with full stereoselectivity, also affording the ε-isomer. A ring-opening reaction of only one of the thiazolone rings appears to have taken place in 4 upon methanolysis, leading to the corresponding ester and thioamide groups. The treatment of free 4-aryliden-5(4 H )-thiazolones 2 with a base in alcohol (NaOR/ROH) also produces a ring-opening reaction of the heterocycle by methanolysis, although, under these reaction conditions, further intramolecular S-attack at the exocyclic C(H)=C bond and cyclization is observed, forming the dihydrothiazoles 5 or 6 as mixtures of cis ( RS / SR )- and trans ( RR / SS )-isomers with high diastereomeric excess. trans -( RR/SS )-Dihydrothiazoles 6 can be isolated as pure diastereoisomers by column chromatography. Surprisingly, dihydrothiazoles 5 can also be obtained by the treatment of 4-aryliden-5(4 H )-thiazolones 2 with BF 3 ·OEt 2 in methanol in the absence of a base.

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Thrilling Strain! Donor–Acceptor‐Substituted Cyclobutanes for the Synthesis of (Hetero)Cyclic Compounds

Abstract: The analogy goes further: Following the often-studied donor-acceptor-substituted cyclopropanes, the corresponding cyclobutane derivatives were employed for the ring-strain-driven stereoselective syntheses of carbo- and heterocycles.

Cited by 64 publications

References 29 publications

Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

Difluoro-Substituted bicyclo[1.1.1]pentanes as Novel Motifs for Medicinal Chemistry: Design, Synthesis and Characterization

Reactivity of (Z)-4-Aryliden-5(4H)-thiazolones: [2 + 2]-Photocycloaddition, Ring-Opening Reactions, and Influence of the Lewis Acid BF₃

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Thrilling Strain! Donor–Acceptor‐Substituted Cyclobutanes for the Synthesis of (Hetero)Cyclic Compounds

Abstract: The analogy goes further: Following the often-studied donor-acceptor-substituted cyclopropanes, the corresponding cyclobutane derivatives were employed for the ring-strain-driven stereoselective syntheses of carbo- and heterocycles.

Cited by 64 publications

References 29 publications

Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

Difluoro-Substituted bicyclo[1.1.1]pentanes as Novel Motifs for Medicinal Chemistry: Design, Synthesis and Characterization

Reactivity of (Z)-4-Aryliden-5(4H)-thiazolones: [2 + 2]-Photocycloaddition, Ring-Opening Reactions, and Influence of the Lewis Acid BF3

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Reactivity of (Z)-4-Aryliden-5(4H)-thiazolones: [2 + 2]-Photocycloaddition, Ring-Opening Reactions, and Influence of the Lewis Acid BF₃