Thermal Stereomutations of Cyclopropanes and Vinylcyclopropanes

Baldwin, John E.

doi:10.1002/9780470682531.pat0035

Cited by 1 publication

(1 citation statement)

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“…Construction of the more stable trans-divinylcyclopropane, followed by isomerization to cis requires high temperature (approximately 200 °C) and occurs under racemization [19][20][21][22] . Such thermally or photochemically induced homolytic scissions towards diradical intermediates 23 can also trigger the cis-to-trans isomerization of alternatively substituted cyclopropanes and, with appropriate metal complexation for specific substrates, also at lower temperature (80 °C) 24 , albeit under loss of enantiopurity towards the racemic, thermodynamic trans-isomer. Isomerization may also occur in a polar mechanism via zwitterionic intermediates, oxidatively 25 , reductively or under Lewis acid catalysis for specific substrates with the analogous challenges on enantiopurity (that is, its loss) 18 , although remarkable strides towards photochemically assisted chiral resolution with a chiral catalyst have been made recently for specifically substituted cyclopropyl ketones 26,27 .…”

Section: Articlementioning

confidence: 99%

Dynamic stereomutation of vinylcyclopropanes with metalloradicals

Mendel,

Karl,

Hamm

et al. 2024

Nature

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The ever increasing demands for greater sustainability and lower energy usage in chemical processes call for fundamentally new approaches and reactivity principles. In this context, the pronounced prevalence of odd-oxidation states in less precious metals bears untapped potential for fundamentally distinct reactivity modes via metalloradical catalysis1–3. Contrary to the well-established reactivity paradigm that organic free radicals, upon addition to a vinylcyclopropane, lead to rapid ring opening under strain release—a transformation that serves widely as a mechanistic probe (radical clock)4 for the intermediacy of radicals5—we herein show that a metal-based radical, that is, a Ni(I) metalloradical, triggers reversible cis/trans isomerization instead of opening. The isomerization proceeds under chiral inversion and, depending on the substitution pattern, occurs at room temperature in less than 5 min, requiring solely the addition of the non-precious catalyst. Our combined computational and experimental mechanistic studies support metalloradical catalysis as origin of this profound reactivity, rationalize the observed stereoinversion and reveal key reactivity features of the process, including its reversibility. These insights enabled the iterative thermodynamic enrichment of enantiopure cis/trans mixtures towards a single diastereomer through multiple Ni(I) catalysis rounds and also extensions to divinylcyclopropanes, which constitute strategic motifs in natural product- and total syntheses6. While the trans-isomer usually requires heating at approximately 200 °C to trigger thermal isomerization under racemization to cis-divinylcyclopropane, which then undergoes facile Cope-type rearrangement, the analogous contra-thermodynamic process is herein shown to proceed under Ni(I) metalloradical catalysis under mild conditions without any loss of stereochemical integrity, enabling a mild and stereochemically pure access to seven-membered rings, fused ring systems and spirocycles.

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