Rationalizing the diverse reactivity of [1.1.1]propellane through σ–π-delocalization

Sterling, Alistair J.; Dürr, Alexander B.; Smith, Russell C.; Anderson, Edward A.; Duarte, Fernanda

doi:10.1039/d0sc01386b

Cited by 47 publications

(53 citation statements)

References 77 publications

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“…A consequence of this unusual bonding situation is the high reactivity of [1.1.1]propellane ( 1 ) towards radicals and anions, including polar organometallics. This unique reactivity behaviour gives access to bicyclopentane (BCP)‐radicals ( 2 ) and ‐organometallics ( 3 , Scheme 1), [1e, 3] which can be further functionalized. The resulting functionalized BCPs are promising bioisosteres for aryl, [4] alkynyl [5] and tert ‐butyl [6] groups in medicinal chemistry.…”

Section: Introductionmentioning

confidence: 99%

Highly Regioselective Addition of Allylic Zinc Halides and Various Zinc Enolates to [1.1.1]Propellane

et al. 2020

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We report ar ange of highly regioselective openings of [1.1.1]propellane with various allylic zinc halides,aswell as zinc enolates of ketones,e sters and nitriles.T he resulting zincated bicyclopentanes (BCPs) were trapped with arange of electrophiles including acyl chlorides,sulfonothioates,hydroxylamino benzoates,t osyl cyanide as well as aryl and allyl halides,generating highly functionalized BCP-derivatives.The unusually high regioselectivity of these reactions has been rationalized using DFT calculations.Abioisostere of the synthetic opioid pethidine was prepared in 95 %y ield in one step using this method.

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Section: Introductionmentioning

confidence: 99%

Highly Regioselective Addition of Allylic Zinc Halides and Various Zinc Enolates to [1.1.1]Propellane

et al. 2020

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“…[11] We first examined the photo-induced degradation of I À BCP À I to [1.1.1]propellane and I 2 . However, the retro-reaction to regenerate I À BCP À I is rapid and barrierless, [12] and in fact, this reaction has been used to titrate [1.1.1]propellane. [13] We considered that a possible solution to this problem would be removal of I 2 from the reaction system by the use of a suitable reducing agent that can rapidly convert I 2 into I À while leaving [1.1.1]propellane intact.…”

Section: Zuschriftenmentioning

confidence: 99%

α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

et al. 2021

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The bicyclo[1.1.1]pentane (BCP) scaffold is useful in medicinal chemistry, and many protocols are available for synthesizing BCP derivatives from [1.1.1]propellane. Here, we report (1) the α‐cyclodextrin (α‐CD) encapsulation of BCP derivatives, affording a stable, readily storable material from which BCPs can be easily and quantitatively recovered and (2) new and simple protocols for deiodination reaction of 1,3‐diiodo BCP to afford [1.1.1]propellane in protic/aprotic/polar/non‐polar solvents. The combination of these methodologies enables simple, on‐demand preparation of [1.1.1]propellane in various solvents under mild conditions from α‐CD capsules containing 1,3‐diiodo BCP.

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“…In keeping with couplings carried out using less sterically‐hindered aryl Grignard reagents with amine additives, we therefore favour a reaction pathway involving single electron transfer from an Fe I species such as 4 to the iodo‐BCP (Scheme ), generating a bicyclopentyl radical 5 . Reaction of this species with the LArFe(II) complex/ArMgBr liberates the cross‐coupled product and results in catalyst turnover; however, the precise mechanism by which C−C bond formation occurs (e.g.…”

Section: Figurementioning

confidence: 99%

Synthesis of All‐Carbon Disubstituted Bicyclo[1.1.1]pentanes by Iron‐Catalyzed Kumada Cross‐Coupling

et al. 2020

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1,3‐Disubstituted bicyclo[1.1.1]pentanes (BCPs) are important motifs in drug design as surrogates for p‐substituted arenes and alkynes. Access to all‐carbon disubstituted BCPs via cross‐coupling has to date been limited to use of the BCP as the organometallic component, which restricts scope due to the harsh conditions typically required for the synthesis of metallated BCPs. Here we report a general method to access 1,3‐C‐disubstituted BCPs from 1‐iodo‐bicyclo[1.1.1]pentanes (iodo‐BCPs) by direct iron‐catalyzed cross‐coupling with aryl and heteroaryl Grignard reagents. This chemistry represents the first general use of iodo‐BCPs as electrophiles in cross‐coupling, and the first Kumada coupling of tertiary iodides. Benefiting from short reaction times, mild conditions, and broad scope of the coupling partners, it enables the synthesis of a wide range of 1,3‐C‐disubstituted BCPs including various drug analogues.

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Rationalizing the diverse reactivity of [1.1.1]propellane through σ–π-delocalization

Abstract: A unified framework that explains the reactivity of [1.1.1]propellane through electron delocalization.

Cited by 47 publications

References 77 publications

Highly Regioselective Addition of Allylic Zinc Halides and Various Zinc Enolates to [1.1.1]Propellane

Highly Regioselective Addition of Allylic Zinc Halides and Various Zinc Enolates to [1.1.1]Propellane

α‐Cyclodextrin Encapsulation of Bicyclo[1.1.1]pentane Derivatives: A Storable Feedstock for Preparation of [1.1.1]Propellane

Synthesis of All‐Carbon Disubstituted Bicyclo[1.1.1]pentanes by Iron‐Catalyzed Kumada Cross‐Coupling

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