Article
Chemistry, Multidisciplinary
Dong Guk Nam, Su Yong Shim, Hye-Min Jeong, Do Hyun Ryu
Summary: The highly enantioselective Darzens-type epoxidation of diazoesters with glyoxal derivatives was achieved using a chiral boron-Lewis acid catalyst and a chiral oxazaborolidinium ion catalyst, leading to the asymmetric synthesis of trisubstituted alpha,beta-epoxy esters with high yield (up to 99%) and excellent enantio- and diastereoselectivity (up to >99% ee and >20:1 dr, respectively). The synthetic potential of the method was demonstrated by the conversion of the products to various compounds such as epoxy gamma-butyrolactone, tertiary beta-hydroxy ketone, and epoxy diester.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Niklas Radhoff, Constantin G. G. Daniliuc, Armido Studer
Summary: The design, synthesis, and application of benzene bioisosteres have been a subject of great interest in the past two decades. Recently, bicyclo[2.1.1]hexanes have been established as highly attractive bioisosteres for ortho- and meta-substituted benzenes. In this study, we present a mild, scalable, and transition-metal-free method for constructing highly substituted bicyclo[2.1.1]hexan-2-ones through Lewis acid-catalyzed (3+2)-cycloaddition of bicyclo[1.1.0]-butane ketones with disubstituted ketenes. The reaction exhibits high functional group tolerance, as evidenced by the successful synthesis of various 3-alkyl-3-aryl and 3,3-bisalkyl bicyclo[2.1.1]hexan-2-ones (26 examples, up to 89% yield). Additionally, postfunctionalization of the exocyclic ketone moiety is demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Andrea Serafino, Giovanni Maestri
Summary: The synthetic relevance of bicyclo[2.2.2]octadienes is demonstrated by their successful application in various chemical domains, and there is an ongoing interest in the concise assembly of these bridged bicycles. This article presents seminal strategies for crafting these compounds, as well as more recent applications utilizing visible light. A general intramolecular method for the para-cycloaddition of an allenamide arm onto simple aryl rings is highlighted in this context.
Article
Chemistry, Applied
Shuichi Nakamura, Natsuki Matsumoto, Masato Kibe, Kazuki Abe, Tsunayoshi Takehara, Takeyuki Suzuki
Summary: This study reports the enantiodivergent reaction of ketimines derived from alpha-ketoesters with malononitriles using a single chiral source, resulting in the synthesis of various optically active compounds from the obtained malononitrile-derived alpha-amino acids. A proposed reaction mechanism explains the observed enantiodivergency in high yields with high enantioselectivities.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Johannes Grosskopf, Manuel Plaza, Roger Jan Kutta, Patrick Nuernberger, Thorsten Bach
Summary: 2,5-Diketopiperazines are cyclic dipeptides with a wide range of applications, and their enantioselective preparation can be achieved through photochemical deracemization, allowing for stereochemical editing at a single position while maintaining other stereogenic centers unaffected. The chiral benzophenone catalyst in combination with irradiation at lambda=366 nm enables the establishment of configuration at the stereogenic carbon atom C6 at will.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Martin T. Peschel, Piotr Kabacinski, Daniel P. Schwinger, Erling Thyrhaug, Giulio Cerullo, Thorsten Bach, Juergen Hauer, Regina de Vivie-Riedle
Summary: Lewis acids have been recognized as catalysts for enantioselective photochemical transformations, but mechanistic studies on these systems are rare. This work overcomes the challenges by using sub-30-fs transient absorption in the UV and accurate theoretical treatment. Investigations on the 2-cyclohexenone and boron trifluoride complex reveal that the Lewis acid remains attached to the substrate in the triplet state, leading to high enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Applied
Kazuki Ogura, Tsunayoshi Takehara, Takeyuki Suzuki, Shuichi Nakamuraa
Summary: A novel enantioselective vinylogous Mannich reaction was developed for the synthesis of acyclic delta-amino-alpha,beta-unsaturated carbonyl compounds, achieving excellent yields and enantioselectivities using a specific catalyst. This study provides an efficient route for the synthesis of compounds in this specific category.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Organic
Kai Matsui, Kohei Toh, Manabu Hatano, Kazuaki Ishihara
Summary: A multiselective Diels-Alder reaction involving alpha-arylacroleins and cyclopentadiene has been developed using BBr3-assisted chiral BINOL-derived phosphoric acid catalysts. The chiral cavity of the in situ-formed acid-base cooperative catalysts plays a key role in controlling the exo- and enantioselectivity, particularly by suppressing the competitive hetero Diels-Alder reaction effectively.
Article
Chemistry, Organic
Prasoon Raj Singh, Pratibha Kalaramna, Shamsad Ali, Avijit Goswami
Summary: A simple protocol has been developed to access thio-/selenopyrrolines through a (3+2)-cycloaddition reaction using SnCl4 as a Lewis acid catalyst. Good chemoselectivity was observed when DACs were treated, indicating that thiocyanate is more reactive than nitrile moiety in such reactions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Rodger Rausch, Ana-Maria Krause, Ivo Krummenacher, Holger Braunschweig, Frank Wuerthner
Summary: A synthetic procedure was developed to introduce nitronyl nitroxide radical moieties into electron-poor chromophores, resulting in stable open shell compounds with preserved absorption spectral signatures. This method allowed for the prediction of optical properties while maintaining intrinsic characteristics of the electron deficient chromophores.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jin Tanaka, Yuki Nagashima, Antonio Junio Araujo Dias, Ken Tanaka
Summary: A novel photoinduced in situ reduction reaction of half-sandwich metal [Rh(III)] complexes to low-valent anionic metal [Rh(II)] ate complexes has been reported, enabling room temperature ortho-C-H borylation of arenes. This strategy was facilitated by using a functionalized cyclopentadienyl (Cp-A3) Rh(III) catalyst developed by the researchers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Martin Berger, Davide Carboni, Paolo Melchiorre
Summary: The study presents the first catalytic enantioselective conjugate addition of allyl groups to alpha, beta-unsaturated aldehydes, utilizing the visible-light-excitation of chiral iminium ions to activate allyl silanes toward the formation of allylic radicals. This radical mechanism overcomes issues seen in traditional conjugate allylation processes and selectively installs prenyl fragments at the beta-carbon of enals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Caifang Han, Wei Meng, Xiangqing Feng, Haifeng Du
Summary: Asymmetric intramolecular hydroalkoxylation is an important method for accessing optically active cyclic ethers. The cyclization of 2-vinylbenzyl alcohols can be catalyzed by B(C6F5)3 with low catalyst loading, resulting in high yields. A novel chiral boro-phosphate was developed to achieve high enantioselective hydroalkoxylation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Wataru Matsuoka, Hideto Ito, David Sarlah, Kenichiro Itami
Summary: Nanographenes and polycyclic aromatic hydrocarbons are important compounds with numerous applications, yet challenging to access. The authors present a diversity-oriented, growth-from-template synthesis of nanographenes enabled by iterative annulative pi -extension reactions from small PAH starting materials.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Zhong-Tao Jiang, Zhengzhao Chen, Yaxin Zeng, Jiang-Ling Shi, Ying Xia
Summary: In this study, an effective method for the synthesis of chiral gem-difluorinated cyclopropanes containing an all-carbon quaternary stereocenter was reported using rhodium-catalyzed stereoablative kinetic resolution. The method showed high enantioselectivity and the resulting compounds demonstrated promising applications in various postfunctionalization reactions.
Article
Chemistry, Organic
Noah Jeremias, Martin T. Peschel, Constantin Jaschke, Regina de Vivie-Riedle, Thorsten Bach
Summary: In this study, it was found that cyclopent-2-enones can undergo a photochemical rearrangement to form ketenes when substituted in the 5,5-position, accompanied by the formation of cyclopropane. By trapping the ketene intermediates with primary amines, efficient synthesis of 2,2-disubstituted cyclopropaneacetic amides was achieved.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Audrey Gilbert, Thorsten Bach
Summary: Photochemical cascade (domino) reactions can construct complex molecular architectures through consecutive reactions with high diastereoselectivity.
Article
Chemistry, Multidisciplinary
Roger Jan Kutta, Johannes Grosskopf, Nils van Staalduinen, Antonia Seitz, Philipp Pracht, Stefan Breitenlechner, Christoph Bannwarth, Patrick Nuernberger, Thorsten Bach
Summary: In the presence of a chiral benzophenone catalyst, a racemic mixture of a chiral imidazolidine-2,4-dione can be converted into the same compound with high enantiomeric excess through photochemical deracemization. Mechanistic experiments revealed that the catalyst binds the two enantiomers through hydrogen bonding and facilitates hydrogen atom transfer to the photoexcited benzophenone. Quantum chemical calculations showed that the back hydrogen atom transfer occurs to the oxygen atom of the hydantoin radical. The results provide insights into a synthetically useful photochemical deracemization reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Johannes Hofer, Franziska Pecho, Thorsten Bach
Summary: Under visible light irradiation, cyclic 2-alk-4enyl-substituted 1,3-diketones undergo an intramolecular endo-addition onto the double bond, resulting in spirocyclic products with yields ranging from 62 to 92%. The reaction can be promoted by both an organic photocatalyst (thioxanthone, 20 mol%) and an organometallic Ir-based photocatalyst (5 mol%). The addition of triisopropylthiophenol is necessary to obtain high yields.
Article
Chemistry, Multidisciplinary
Johannes Grosskopf, Alexandra A. Heidecker, Thorsten Bach
Summary: Racemic 3-substituted oxindoles can be converted into enantiomerically pure or enriched material through photochemical deracemization process. Light energy compensates for the loss of entropy and enables predictable editing of the stereogenic center. The obtained oxindoles are valuable intermediates for further transformations with complete retention at the stereogenic center.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Editorial Material
Chemistry, Organic
Anat Milo, Takashi Ooi, Thorsten Bach
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Niklas Rauscher, Christian Jandl, Thorsten Bach
Summary: A recent photochemical cascade reaction has been developed to access diastereomeric pentacyclic products that possess the carbon skeleton of prezizane natural products. The minor diastereoisomer, with a 2 beta-Me configuration, was transformed into (+)-prezizaan-15-ol through 12 reaction steps. Similarly, the major diastereoisomer, with a 2 alpha-Me configuration, yielded (+)-jinkohol II in an analogous route and was further oxidized at C13 to yield (+)-jinkoholic acid. Total synthesis of these natural products helped clarify their configurations.
Article
Chemistry, Organic
Johanna Proessdorf, Christian Jandl, Thomas Pickl, Thorsten Bach
Summary: Naturally occurring sesquiterpenes with a protoilludane skeleton are frequently oxygenated at carbon atoms C4 and C8. Boronic acid pinacol esters (BPin) can serve as precursors for hydroxy groups at these positions and synthetic methods have been developed for their preparation. Introduction of a boronate at position C4 was achieved through Cu-catalyzed hydroboration of a photochemically generated cyclobutene precursor, while introduction of BPin at carbon atom C8 was accomplished through a photochemical transformation starting with an alkenyl boronate. Subsequent reactions showed the oxidative transformation of boronates into the respective alcohols.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Physical
Malte Leverenz, Hendrik Brockmann, Andreas Dreuw, Thorsten Bach, Golo Storch
Summary: A strong enantiodivergence was observed in the oxadi-x-methane rearrangement of 2,4cyclohexadienones, ranging from +92% ee to -45% ee. The stereochemical outcome is determined solely by the oxazaborolidine substituents. The change in enantioselectivity is linked to a change in substrate binding, and TDDFT studies in the S1 excited state provided further mechanistic insights.
Article
Chemistry, Multidisciplinary
Johannes Grosskopf, Manuel Plaza, Roger Jan Kutta, Patrick Nuernberger, Thorsten Bach
Summary: 2,5-Diketopiperazines are cyclic dipeptides with a wide range of applications, and their enantioselective preparation can be achieved through photochemical deracemization, allowing for stereochemical editing at a single position while maintaining other stereogenic centers unaffected. The chiral benzophenone catalyst in combination with irradiation at lambda=366 nm enables the establishment of configuration at the stereogenic carbon atom C6 at will.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lilla Koser, Thorsten Bach
Summary: The first total synthesis of (-)-5-deoxyenterocin has been accomplished, starting from pentane-1,3,5-triol with a linear sequence of 16 steps and an overall yield of 0.2%. Key steps of the synthesis include aldol reactions, hydroxylation reactions, and an intramolecular aldol reaction. Despite attempts, a functionalization reaction at position C5 was unsuccessful.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Daniel P. Schwinger, Thomas Pickl, Thorsten Bach
Summary: Cyclohept-1-ene-1-carbaldehyde undergoes photoinduced E & RARR; Z isomerization at & lambda; =350 nm. The ring strain facilitates various reactions, including Diels-Alder cycloadditions, [3 + 2] cycloadditions, and enereactions. The products obtained are trans-fusedat the cycloheptane core and yield up to 82%. Single crystal X-ray analyses confirm the structure and relative configuration. In the presence of BF3 and 2,3-dimethylbuta-1,3-diene, cyclohept-1-ene-1-carbaldehyde undergoes a stereoselective rearrangement to form a tricyclic ketone (87%).
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Morgane de Robichon, Thilo Kratz, Frederike Beyer, Julian Zuber, Christian Merten, Thorsten Bach
Summary: Substituted bicyclo[1.1.0]butanes add enantioselectively to 2(1H)-quinolones upon irradiation, leading to the formation of products with a chiral bicyclo[2.1.1]hexane skeleton. A two-point hydrogen bond between the quinolone and the template is responsible for stereocontrol in the photocycloaddition reaction. The chiral template can be recovered and reused, and sensitization is a suitable tool for performing the reaction with visible light.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Johannes Grosskopf, Thorsten Bach
Summary: Upon irradiation with a suitable chiral catalyst, racemic compounds can be converted into enantiopure compounds through a process called photochemical deracemization. This review comprehensively covers the research and current developments in this field, discussing the reactions and mechanistic details underlying the presented reaction. Photochemical deracemization offers a unique opportunity to directly obtain enantiopure compounds from racemates, and short-lived intermediates play a key role in determining the enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Freya M. M. Harvey, Alexandra H. H. Heidecker, Christian Merten, Thorsten Bach
Summary: Allenes with different substituents at their terminal carbon atom exhibit axial chirality and can be obtained in enantiopure form through a photochemical deracemization protocol. This study investigates the conditions under which allenoic acid derivatives undergo a Diels-Alder reaction with 1,3-cyclopentadienes and the resulting products. Cyclic derivatives (lactams, lactones) exhibited an exo-selective reaction catalyzed by the Lewis acid Eu(fod)(3), while acyclic derivatives mainly produced endo-products (with EtAlCl2 as the preferred Lewis acid). The exocyclic double bond exhibited excellent diastereoselectivity and achieved near-perfect chirality transfer. The method was successfully applied to the synthesis of sesquiterpenes beta-santalol (1) and 10(E)-beta-santalic acid (13).
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
