Cyclopropylcarbinyl-to-homoallyl carbocation equilibria influence the stereospecificity in the nucleophilic substitution of cyclopropylcarbinols DOI Creative Commons
Sean P. Larmore, Pier Alexandre Champagne

Published: Jan. 27, 2023

The synthesis of quaternary homoallylic halides and trichloroacetates from cyclopropylcarbinols, as reported by Marek in 2020 (J. Am. Chem. Soc. 2020, 142, 5543-5548), is one the few examples stereospecific nucleophilic substitution involving chiral bridged carbocations. However, for phenyl-substituted substrates stereoselectivity reaction poor a mixture diastereomers obtained. In order to understand nature intermediates involved this transformation explain loss selectivity certain substrates, we have performed Density Functional Theory investigation mechanism at DLPNO-CCSD(T)/Def2TZVPP level theory. Our results indicate that cyclopropylcarbinyl cations are stable reaction, while bicyclobutonium structures high-energy transition such not involved, regardless pattern on substrate. Instead, multiple rearrangement pathways been located, including rotations around their π-bonds ring openings cations. Importantly, relative energies these activation barriers reach them correlated substituents. While direct attack cation kinetically favored most systems, rearrangements become competitive with leading through rearranged carbocation intermediates. As such, it appears reactions depend ability access structures, which guaranteed.

Language: Английский

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
Cu(I)-Catalyzed Highly Diastereo- and Enantioselective Constructions of Boron/Carbon Vicinal Stereogenic Centers via Insertion Reaction DOI
Guan Zhang,

Xinping Cai,

Junyi Jia

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(14), P. 9502 - 9508

Published: July 3, 2023

The diastereoselective synthesis of boron and carbon vicinal stereogenic centers is a great challenge in current synthetic chemistry due to the paucity efficient strategies. Herein, Cu-catalyzed diastereo- enantioselective B–H bond insertion reaction ene-yne-ketones as furyl-carbene precursors has been developed using chiral bis(oxazolines) (BOX) ligand, thus furnishing series densely functionalized products (42 examples) bearing both high enantioselectivity diastereoselectivity (up 99% ee > 20:1 dr) with good yields 98%).

Language: Английский

Citations

23
Catalyst and Medium Control over Rebound Pathways in Manganese-Catalyzed Methylenic C–H Bond Oxidation DOI Creative Commons
Marco Galeotti, Massimo Bietti, Miguel Costas

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8904 - 8914

Published: March 20, 2024

The C(sp3)–H bond oxygenation of a variety cyclopropane containing hydrocarbons with hydrogen peroxide catalyzed by manganese complexes aminopyridine tetradentate ligands was carried out. Oxidations were performed in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 2,2,2-trifluoroethanol (TFE) using different catalysts carboxylic acid co-ligands, where steric electronic properties systematically modified. Functionalization selectively occurs at the most activated C–H bonds that are α- to cyclopropane, providing access carboxylate or 2,2,2-trifluoroethanolate transfer products, no competition, favorable cases, from generally dominant hydroxylation reaction. formation mixtures unrearranged rearranged esters (oxidation HFIP presence acid) ethers TFE) full control over diastereoselectivity observed, confirming involvement delocalized cationic intermediates these transformations. Despite such complex mechanistic scenario, fine-tuning catalyst sterics electronics leveraging on relative contribution pathways reaction mechanism, product chemoselectivity could be achieved. Taken together, results reported herein provide powerful catalytic tools rationally manipulate ligand oxidations hydrocarbons, delivering novel products good yields and, some outstanding selectivities, expanding available toolbox for development synthetically useful functionalization procedures.

Language: Английский

Citations

7
Expedient synthesis of spiro[3.3]heptan-1-ones via strain-relocating semipinacol rearrangements DOI Creative Commons
Myunggi Jung, Joanna E. Muir, Vincent N. G. Lindsay

et al.

Tetrahedron, Journal Year: 2023, Volume and Issue: 134, P. 133296 - 133296

Published: Feb. 2, 2023

Language: Английский

Citations

17
Borylated Cyclopropanes as Spring-Loaded Entities: Access to Vicinal Tertiary and Quaternary Carbon Stereocenters in Acyclic Systems DOI Creative Commons
André U. Augustin,

Sergio Di Silvio,

Ilan Marek

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(36), P. 16298 - 16302

Published: Aug. 30, 2022

Herein, we present the formation of acyclic frameworks bearing two consecutive stereocenters either tertiary or quaternary nature starting from easily accessible cyclopropenes. This holistic approach involves a regio- and diastereoselective hydro- carboborylation substituted cyclopropenyl esters. Formation boronate complexes latter via addition nucleophiles subsequent stereospecific 1,2-migration with carbon–carbon bond cleavage delivered title compounds.

Language: Английский

Citations

21
Stereoselective Construction of Tertiary Homoallyl Alcohols and Ethers by Nucleophilic Substitution at Quaternary Carbon Stereocenters DOI Creative Commons
Chen Xu,

Kaushalendra Patel,

Ilan Marek

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(3)

Published: Nov. 22, 2022

An efficient method for the stereoselective construction of tertiary C-O bonds via a stereoinvertive nucleophilic substitution at quaternary carbon stereocenter cyclopropyl carbinol derivatives using water, alcohols and phenols as nucleophiles has been developed. This reaction proceeds under mild conditions tolerates several functional groups, providing new access to formation highly congested homoallyl ethers.

Language: Английский

Citations

21
Cyclopropylcarbinyl cation chemistry in synthetic method development and natural product synthesis: cyclopropane formation and skeletal rearrangement DOI
Jiaxin Xie, Guangbin Dong

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(9), P. 2346 - 2358

Published: Jan. 1, 2023

In this Review, the underrecognized utilities of cyclopropylcarbinyl cation chemistry are summarized in cyclopropane synthesis and skeletal rearrangements, their applications natural product total highlighted.

Language: Английский

Citations

12
Stereospecific nucleophilic substitution at quaternary carbon stereocenters of cyclopropyl carbinols DOI Creative Commons
Chen Xu,

Kaushalendra Patel,

Ilan Marek

et al.

Chem, Journal Year: 2023, Volume and Issue: 9(2), P. 266 - 279

Published: Jan. 26, 2023

Language: Английский

Citations

11
Cyclopropylcarbinyl-to-Homoallyl Carbocation Equilibria Influence the Stereospecificity in the Nucleophilic Substitution of Cyclopropylcarbinols DOI
Sean P. Larmore, Pier Alexandre Champagne

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(11), P. 6947 - 6954

Published: May 4, 2023

The synthesis of quaternary homoallylic halides and trichloroacetates from cyclopropylcarbinols, as reported by Marek (J. Am. Chem. Soc.2020, 142, 5543-5548), is one the few examples stereospecific nucleophilic substitution involving chiral bridged carbocations. However, for phenyl-substituted substrates, poor specificity observed mixtures diastereomers are obtained. To understand nature intermediates involved explain loss certain we have performed a computational investigation reaction mechanism using ωB97X-D optimizations DLPNO-CCSD(T) energy refinements. Our results indicate that cyclopropylcarbinyl cations stable in this reaction, while bicyclobutonium structures high-energy transition not involved. Instead, multiple rearrangement pathways were located, including ring openings to cations. activation barriers required reach such correlated substituents; direct attack on kinetically favored most systems, rearrangements become competitive with leading through rearranged carbocation intermediates. As such, reactions depend energies access their corresponding structures, which selectivity guaranteed.

Language: Английский

Citations

11
Asymmetric Synthesis of Chiral 2-Cyclohexenones with Quaternary Stereocenters via Ene-Reductase Catalyzed Desymmetrization of 2,5-Cyclohexadienones DOI Creative Commons

Michael Frieß,

Amit Singh Sahrawat,

Bianca Kerschbaumer

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 7256 - 7266

Published: April 24, 2024

Stereoselective synthesis of quaternary stereocenters represents a significant challenge in organic chemistry. Herein, we describe the use ene-reductases OPR3 and YqjM for efficient asymmetric chiral 4,4-disubstituted 2-cyclohexenones via desymmetrizing hydrogenation prochiral 2,5-cyclohexadienones. This transformation breaks symmetry cyclohexadienone substrates, generating valuable with high enantioselectivities (ee, up to >99%). The mechanistic causes observed were investigated both experimentally (stopped-flow kinetics) as well theoretically (quantum mechanics/molecular mechanics calculations). synthetic potential resulting enones was demonstrated several diversification reactions which stereochemical integrity stereocenter could be preserved.

Language: Английский

Citations

4