Titanocene catalyzed 4-exo cyclizations: mechanism, experiment, catalyst design

Journal of the American Chemical Society
Joachim FriedrichAndreas Gansäuer

Abstract

A method for the preparation of a variety of cyclobutanes via 4-exo cyclization of radicals is presented. Radical generation is carried out by electron transfer from titanocene(III) chlorides to epoxides. The reaction relies on the acceleration of the cyclization through the use of alpha,beta-unsaturated carbonyl compounds as radical traps and the thermodynamic stabilization of the cyclobutylcarbinyl radicals through conjugation. The mechanism of the transformation was investigated by a combined theoretical and experimental study. The computational results provide the crucial energetic and structural features of pertinent intermediates and transition structures. Moreover, the origins of the diastereoselectivity of the 4-exo cyclization are outlined for the first time. Catalysts for those cases where "Cp2TiCl" did not perform in a satisfactory manner have been devised. Through the introduction of tert-butyl or cyclo-hexyl substituted cyclopentadienyl ligands the longevity of the pivotal beta-titanoxy radicals is increased sufficiently enough to enable the slow but often surprisingly diastereoselective formation of the cyclobutylcarbinyl radical. The resulting transformation constitutes the first general approach to cyclobutanes ...Continue Reading

References

Sep 15, 1988·Physical Review A: General Physics·A D Becke
Dec 26, 2001·Chemical Reviews·A Gansäuer, H Bluhm
Feb 1, 1996·Chemical Reviews·Gary A. Molander, Christina R. Harris
Oct 9, 2002·Angewandte Chemie·Dietmar Heidrich
Jun 24, 2004·Journal of the American Chemical Society·Rasmus Juel EnemaerkeKim Daasbjerg
Sep 17, 2004·Chemistry : a European Journal·Andreas GansäuerDaniel Geich-Gimbel
Dec 9, 2004·Journal of the American Chemical Society·Alexandru D Asandei, Isaac W Moran
May 12, 2005·Journal of the American Chemical Society·Joachim FriedrichThorsten Lauterbach
Oct 20, 2005·Journal of the American Chemical Society·José JusticiaDiego J Cárdenas
Nov 17, 2006·Organic Letters·Rosa E EstévezJ Enrique Oltra
Feb 27, 2007·Chemistry : a European Journal·Gerhard HiltKlaus Harms

❮ Previous
Next ❯

Citations

Oct 12, 2013·Inorganic Chemistry·Asli CangönülMaurice van Gastel
Nov 26, 2015·Journal of Chemical Theory and Computation·Tony AnackerJoachim Friedrich
Nov 18, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·A GansäuerR A Flowers Ii
Sep 23, 2014·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Jan Streuff
Oct 30, 2014·Chemistry : a European Journal·Andreas GansäuerRobert A Flowers Ii
Jan 1, 2012·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Bianca RossiCarlo Punta
Oct 23, 2010·Angewandte Chemie·Lei ShiMichael F Greaney
Jan 24, 2012·Chemistry : a European Journal·Andreas GansäuerJoachim Friedrich
Aug 28, 2020·Chemical Society Reviews·Manfred Manßen, Laurel L Schafer
Apr 14, 2011·Chemical Society Reviews·José JusticiaJuan M Cuerva
Oct 27, 2009·Angewandte Chemie·Andreas GansäuerGregor Schnakenburg
Aug 28, 2014·Beilstein Journal of Organic Chemistry·Andreas GansäuerAram Prokop
Sep 26, 2013·Beilstein Journal of Organic Chemistry·Andreas GansäuerStefan Grimme
May 2, 2014·Chemistry, an Asian Journal·Andreas GansäuerFrank Neese
Apr 17, 2019·Nature Reviews. Chemistry·Evan P BeaumierIan A Tonks
Jan 22, 2009·The Journal of Organic Chemistry·María Martín-RodríguezFrancisco A Bermejo
Dec 9, 2009·Organic Letters·Andrew D Kosal, Brandon L Ashfeld
Jan 9, 2014·Journal of the American Chemical Society·Andreas GansäuerRobert A Flowers
Apr 7, 2015·The Journal of Organic Chemistry·A Fernández-MateosR Rubio González
Dec 16, 2010·Journal of the American Chemical Society·Andreas GansäuerLei Shi
Nov 6, 2010·Organic Letters·Hassan Y HarbDavid J Procter
Jul 16, 2014·The Journal of Organic Chemistry·Antonio RosalesJ Enrique Oltra
Apr 29, 2014·Journal of the American Chemical Society·Sara P MorcilloJuan M Cuerva
Nov 5, 2020·The Journal of Organic Chemistry·Antonio Rosales MartínezIgnacio Rodríguez-García

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.