Chiral Stereogenic Center Research Articles

Cobaltaelektro‐katalysierte C−H‐Aktivierung für zentrale und axiale doppelte Enantioinduktion

AbstractIn den letzten Jahren hat sich die enantioselektive Elektrokatalyse zunehmend als eine effektive Methode für die nachhaltige molekulare Synthese herausgestellt. Trotz unbestreitbarer Fortschritte bleiben Strategien zur Kontrolle über zwei unterschiedliche stereogene Elemente mit hoher Selektivität schwer fassbar. Im Gegensatz dazu beschreiben wir hier elektrochemische Cobalt‐katalysierte C−H‐Aktivierungen, welche die Installation chiraler stereogener Zentren zusammen mit einer chiralen Achse mit hoher Enantio‐ und Diastereoselektivität ermöglichen. Die entwickelte elektrokatalytische Strategie erlaubte C−H/N−H‐Aktivierungen/Anellierungen mit cyclischen und acyclischen Alkenen und gewährte einen direkten Zugang zu vielseitigen sowohl zentralen als auch atropo‐chiralen Dihydroisochinolinonen gepaart mit der wertvollen Wasserstoffbildungsreaktion. Studien zur Atropo‐Stabilität der erhaltenen Verbindungen demonstrierten, dass die äußerst milden Bedingungen, gewährleistet durch den elektrokatalytischen Prozess, entscheidend für die hohen erzielten Stereoselektivitäten waren.

Cobaltaelectro-Catalyzed C-H Activation for Central and Axial Double Enantio-Induction.

In recent years, enantioselective electrocatalysis has surfaced as an increasingly-effective platform for sustainable molecular synthesis. Despite indisputable progress, strategies that allow the control of two distinct stereogenic elements with high selectivity remain elusive. In contrast, we, herein, describe electrochemical cobalt-catalyzed C-H activations that enable the installation of chiral stereogenic centers along with a chiral axis with high levels of enantio- and diastereoselectivities. The developed electrocatalysis strategy allowed for C-H/N-H activations/annulations with cyclic and non-cyclic alkenes providing expedient access to various central as well as atropo-chiral dihydroisoquinolinones paired to the valuable hydrogen evolution reaction. Studies on the atropo-stability of the obtained compounds demonstrated that the exceedingly mild conditions ensured by the electrocatalytic process were key for the achieved high stereoselectivities.

Organocatalytic Synthesis of Chiral Halogenated Compounds.

This account summarizes our recent efforts in the enantioselective organocatalytic synthesis of chiral halogenated compounds. The enantioselective α-halogenation of aldehydes, decarboxylative chlorination of β-keto acids, and enantioselective C-C bond formation at the trifluoromethylated prochiral carbon to yield the corresponding organohalides with chlorinated, fluorinated, or trifluoromethylated chiral stereogenic centers are discussed. We applied common organocatalysts, such as Jørgensen-Hayashi catalyst and cinchona alkaloid-derivatived catalyst, and developed novel chiral amine catalysts for these reactions. This account also discusses stereospecific derivatizations of the resulting chiral halogenated compounds via nucleophilic substitution. Thus, we synthesized many novel chiral compounds that have not been reported, even as racemates.

Asymmetric syntheses of spiro[benzofuro-cyclopenta[1,2-b]indole-indoline] scaffolds via consecutive cyclization.

An efficient method to construct enantioenriched spiro[benzofuro-cyclopenta[1,2-b]indole-indoline] scaffolds via consecutive cyclization is described here. The new scaffolds possess five successive chiral stereogenic centers and two spiroheterocycles. A range of highly enantioenriched scaffolds has been obtained with up to 93% yield, 99% ee and >19 : 1 d.r. catalyzed by Brønsted acid catalysts.

A Bispidine-Based Chiral Amine Catalyst for Asymmetric Mannich Reaction of Ketones with Isatin Ketimines.

A unique chiral amine organocatalyst with a bispidine structure was found to be efficient for the diastereo- and enantioselective Mannich reaction of isatin ketimines with ketones. A series of 3-substituted 3-amino-2-oxindoles bearing vicinal tertiary and quaternary chiral stereogenic centers were obtained in excellent yields with excellent dr and ee values. The gram-scale synthesis and transformation of the product showed the practicability of this methodology. In addition, a possible transition state model was proposed to explain the origin of the stereoselectivity.

Copper-catalyzed asymmetric tandem borylative addition and aldol cyclization

A highly enantioselective asymmetric copper-catalyzed tandem conjugate addition/aldol cyclization of electron-deficient olefins with B2pin2 was developed, which provided a rapid access to indanes bearing three consecutive chiral stereogenic centers.

Highly Enantioselective Synthesis of 11‐Substituted 10,11‐Dihydrodibenzo[b,f][1,4]thiazepines through a Proline‐Catalyzed Mannich Reaction of Seven‐Membered Cyclic Imines with Ketones

AbstractHighly enantioselective Mannich addition reactions of N,S‐heterocyclic dibenzo[b,f][1,4]thiazepines as seven‐membered cyclic imine substrates with ketones were developed by using proline as an organocatalyst. Substituted dibenzo[b,f][1,4]thiazepines and various unsymmetrical alkyl methyl ketones were used as substrates and optimized reaction conditions offered an efficient method to synthesize optically active 11‐substituted 10,11‐dihydrodibenzo[b,f][1,4]thiazepine derivatives that contained a carbonyl functional group in 91–99 % ee. Furthermore, we found that the reactions could also be performed on a gram scale, whilst maintaining high yields and enantioselectivities. The carbonyl group of the Mannich products also underwent diastereoselective reduction, thus yielding a new hydroxy‐substituted chiral stereogenic center with moderate‐to‐excellent diastereoselectivities, good yields, and without the loss of enantiomeric excess.

ChemInform Abstract: Catalytic Enantioselective Constructions of Trifluoromethylated Chiral Stereogenic Centers via the Conjugate Addition to CF3‐Alkenes: Overview of Current Progress

AbstractReview: 66 refs.

ChemInform Abstract: Pd(II)‐Catalyzed Diastereoselective and Enantioselective Domino Cyclization/Cycloaddition Reactions of Alkenyl Oximes for Polycyclic Heterocycles with Four Chiral Stereogenic Centers.

Abstract Diastereoselective and enantioselective domino cyclization/cycloaddition reactions of alkenyl oximes were established using a Pd(II)–( R )-Tol-SDP complex and triflic acid. The present process gave polycyclic heterocycles with four chiral stereogenic centers in almost quantitative yields and high stereoselectivities (up to 70% ee, exo / endo = 97/3).

Catalytic Enantioselective Constructions of Trifluoromethylated Chiral Stereogenic Centers <i>via</i> the Conjugate Addition to CF<sub>3</sub>-Alkenes: Overview of Current Progress

Catalytic Enantioselective Constructions of Trifluoromethylated Chiral Stereogenic Centers <i>via</i> the Conjugate Addition to CF<sub>3</sub>-Alkenes: Overview of Current Progress

Pd(II)-catalyzed diastereoselective and enantioselective domino cyclization/cycloaddition reactions of alkenyl oximes for polycyclic heterocycles with four chiral stereogenic centers

Diastereoselective and enantioselective domino cyclization/cycloaddition reactions of alkenyl oximes were established using a Pd(II)–(R)-Tol-SDP complex and triflic acid. The present process gave polycyclic heterocycles with four chiral stereogenic centers in almost quantitative yields and high stereoselectivities (up to 70% ee, exo/endo=97/3).

Manganese(III) complexes of novel chiral unsymmetrical BINOL-Salen ligands: Synthesis, characterization, and application in asymmetric epoxidation of olefins

Several chiral unsymmetrical and C 2-symmetric Mn(III)-BINOL-Salen complexes have been designed, synthesized and applied to the asymmetric epoxidation of non-functionalized alkenes. Experimental results show these complexes are effective in the catalytic asymmetric epoxidation of alkenes. The catalyst 4c exhibited better enantioselectivity and reactivity than the catalysts 4b and 4a due to the steric effect of the ligands. To understand the synergistic effect of the two different chiral centers in the catalyst, the catalyst 6a has been investigated. By comparison of the enantioselectivity obtained by using 4c and 6a, respectively, the positive experimental results have proved that the chiral stereogenic centers in the diaminocyclohexane-derived catalysts played an important role in the current enantioselective epoxidation. Besides, the comparison of enantioselectivity displayed by 4c and 7a further demonstrates the significant influence through the cooperation of steric factors and chiral centers in catalyst.

Total Synthesis of Rhazinilam: Axial to Point Chirality Transfer in an Enantiospecific Pd-Catalyzed Transannular Cyclization

A total synthesis of rhazinilam based on a transannular cyclization strategy is described. Using a Heck reaction, the axial chirality of a halogenated 13-membered lactam can be exploited to create the quaternary chiral stereogenic center in the target molecule with high enantiospecificity.