Stereoinvertive SN1 Through Neighboring Group Participation DOI Creative Commons
Rahul Suresh, Noam Orbach, Ilan Marek

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(31)

Published: May 20, 2024

Abstract Neighboring group participation, the assistance of non‐conjugated electrons to a reaction center, is fundamental phenomenon in chemistry. In framework nucleophilic substitution reactions, neighboring participation known cause rate acceleration, first order kinetics (S N 1), and retention configuration. The latter result double inversion: one when displaces leaving group, second nucleophile substitutes group. This powerful control stereoretention has been widely used organic synthesis for more than century. However, may also lead inversion configuration, which often overlooked. Herein, we review this unique mode stereoinversion, dividing relevant reactions into three classes with aim introduce fresh perspective on different modes stereoinversion via as well factors that stereochemical outcome.

Language: Английский

Taming nonclassical carbocations to control small ring reactivity DOI Creative Commons
Ryan E. McNamee, Nils Frank, Kirsten E. Christensen

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(2)

Published: Jan. 12, 2024

Prediction of the outcome ring opening small organic rings under cationic conditions can be challenging due to intermediacy nonclassical carbocations. For example, solvolysis cyclobutyl or cyclopropylmethyl derivatives generates up four products on nucleophilic capture elimination via cyclopropylcarbinyl and bicyclobutonium ions. Here, we show that such reaction outcomes controlled by subtle changes structure carbocation. Using bicyclo[1.1.0]butanes as cation precursors, regio- stereochemistry is shown depend degree nature substituents intermediates. Reaction are rationalized using computational models, resulting in a flowchart predict product formation from given precursor.

Language: Английский

Citations

11
Stereospecific molecular rearrangement via nucleophilic substitution at quaternary stereocentres in acyclic systems DOI

Kaushalendra Patel,

Ilan Marek

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

Citations

1
Integrating I(I)/I(III) catalysis in reaction cascade design enables the synthesis of gem-difluorinated tetralins from cyclobutanols DOI Creative Commons
Joel Häfliger, Louise Ruyet,

Nico Stübke

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 2, 2023

Partially saturated, fluorine-containing rings are ubiquitous across the drug discovery spectrum. This capitalises upon biological significance of native structure and physicochemical advantages conferred by fluorination. Motivated aryl tetralins in bioactive small molecules, a reaction cascade has been validated to generate novel gem-difluorinated isosteres from 1,3-diaryl cyclobutanols single operation. Under Brønsted acidity catalysis conditions, an acid-catalysed unmasking/fluorination sequence generates homoallylic fluoride situ. species serves as substrate for I(I)/I(III) cycle is processed, via phenonium ion rearrangement, (isolable) 1,3,3-trifluoride. A final C(sp3)-F bond activation event, enabled HFIP, forges difluorinated tetralin scaffold. The highly modular, enabling intermediates be intercepted: this provides expansive platform generation structural diversity.

Language: Английский

Citations

18
Substituent Effects on the Equilibria between Cyclopropylcarbinyl, Bicyclobutonium, Homoallyl, and Cyclobutyl Cations DOI
Sean P. Larmore, Pier Alexandre Champagne

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(11), P. 8146 - 8156

Published: May 16, 2024

The cyclopropylcarbinyl (CPC) and bicyclobutonium (BCB) structures of the C

Language: Английский

Citations

4
Highly Diastereoselective Preparation of Tertiary Alkyl Isonitriles by Stereoinvertive Nucleophilic Substitution at a Nonclassical Carbocation DOI Creative Commons
Chen Xu, Ilan Marek

Organic Letters, Journal Year: 2023, Volume and Issue: 25(13), P. 2285 - 2288

Published: March 28, 2023

A highly efficient SnCl4-catalyzed nucleophilic isocyanation of cyclopropyl ethers has been developed. The reaction proceeds at the quaternary carbon stereocenter cyclopropane with a complete inversion configuration, providing new avenue for construction synthetically challenging tertiary alkyl isonitriles high diastereopurity. diversity incorporated isocyanide group demonstrated by transformation into corresponding amines, amides, and cyclic ketoimines.

Language: Английский

Citations

9
Stereoinvertive SN1 Through Neighboring Group Participation DOI Creative Commons
Rahul Suresh, Noam Orbach, Ilan Marek

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(31)

Published: May 20, 2024

Abstract Neighboring group participation, the assistance of non‐conjugated electrons to a reaction center, is fundamental phenomenon in chemistry. In framework nucleophilic substitution reactions, neighboring participation known cause rate acceleration, first order kinetics (S N 1), and retention configuration. The latter result double inversion: one when displaces leaving group, second nucleophile substitutes group. This powerful control stereoretention has been widely used organic synthesis for more than century. However, may also lead inversion configuration, which often overlooked. Herein, we review this unique mode stereoinversion, dividing relevant reactions into three classes with aim introduce fresh perspective on different modes stereoinversion via as well factors that stereochemical outcome.

Language: Английский

Citations

3
Formally Stereoretentive SN1 Reactions of Homoallylic Tertiary Alcohols Via Nonclassical Carbocation DOI Creative Commons

Kaushalendra Patel,

Leonie Wilczek,

Francesco Calogero

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: May 27, 2025

We present a stereoretentive nucleophilic substitution of homoallylic tertiary alcohols via the formation nonclassical cyclopropyl carbinyl (CPC) carbocation intermediate. This strategy enables creation highly congested centers with preserved stereocontrol, addressing typical challenges instability and reactivity in SN1 mechanisms. The stabilization CPC intermediate is crucial for achieving precise regio- stereoselectivity, significantly enhancing utility SN1-type mechanisms complex molecule synthesis.

Language: Английский

Citations

0
Highly Diastereoselective Preparation of Tertiary Alkyl Thiocyanates en Route to Thiols by Stereoinvertive Nucleophilic Substitution at Nonclassical Carbocations DOI

Kaushalendra Patel,

Lior Oginetz,

Ilan Marek

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(47), P. 8474 - 8477

Published: Nov. 20, 2023

An effective InBr3-catalyzed nucleophilic thiocyanation of cyclopropyl alcohols has been developed. The reaction takes place at the quaternary carbon stereocenter carbinol with a complete inversion configuration, offering novel pathway for creation complex tertiary alkyl thiocyanates high diastereopurity. These substitution reactions proceed under mild conditions and tolerate several functional groups. Additionally, were converted to thiols using lithium aluminum hydride.

Language: Английский

Citations

7
Stereoselective Nucleophilic Halogenation at CF3-Substituted Nonclassical Carbocation DOI

Veronika Myronova,

Dominique Cahard, Ilan Marek

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(17), P. 3657 - 3660

Published: April 24, 2024

CF3-substituted cyclopropyl carbinol derivatives undergo regioselective and diastereoselective nucleophilic halogenation at the quaternary carbon center to provide acyclic products as a single diastereomer. The selectivity of substitution is rationalized by formation nonclassical cyclopropylcarbinyl cation intermediate, reacting most-substituted center. Tertiary alkyl chlorides, bromides, fluorides adjacent stereogenic C–CF3-motif are diastereomerically pure can be obtained in few catalytic steps from commercially available alkynes.

Language: Английский

Citations

1
Synthesis and Functionalization of Tertiary Propargylic Boronic Esters by Alkynyllithium-Mediated 1,2-Metalate Rearrangement of Borylated Cyclopropanes DOI Creative Commons
Tereza Pavlíčková, Yannick Stöckl, Ilan Marek

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(48), P. 8901 - 8906

Published: Nov. 29, 2022

Implementing the use of alkynyllithium reagents in a stereospecific 1,2-metalate rearrangement-mediated ring opening polysubstituted cyclopropyl boronic esters provides variety tertiary pinacol boranes bearing adjacent or quaternary carbon stereocenters with high levels diastereomeric purity. The potential this strategy was demonstrated through selection α- and γ-functionalization propargyl esters.

Language: Английский

Citations

4