Asymmetric Lewis Acid Catalysis Research Articles

Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis

The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability of an asymmetric polar cycloaddition of bicyclo[1.1.0]butane using a chiral Lewis acid catalyst and a bidentate chelating bicyclo[1.1.0]butane substrate, as exemplified by the current enantioselective formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with nitrones. In addition to the diverse bicyclo[1.1.0]butanes incorporating an acyl imidazole group or an acyl pyrazole moiety, a wide array of nitrones are compatible with this Lewis acid catalysis, successfully assembling two congested quaternary carbon centers and a chiral aza-trisubstituted carbon center in the pharmaceutically important hetero-bicyclo[3.1.1]heptane product with up to 99% yield and >99% ee.

Enantioselective nickel-catalyzed anodic oxidative dienylation and allylation reactions

Precision control of stereochemistry in radical reactions remains a formidable challenge due to the prevalence of incidental racemic background reactions resulting from undirected substrate oxidation in the absence of chiral induction. In this study, we devised an thoughtful approach—electricity-driven asymmetric Lewis acid catalysis—to circumvent this impediment. This methodology facilitates both asymmetric dienylation and allylation reactions, resulting in the formation of all-carbon quaternary stereocenters and demonstrating significant potential in the modular synthesis of functional and chiral benzoxazole-oxazoline (Boox) ligands. Notably, the involvement of chiral Lewis acids in both the electrochemical activation and stereoselectivity-defining radical stages offers innovative departures for designing single electron transfer-based reactions, significantly underscoring the relevance of this approach as a multifaceted and universally applicable strategy for various fields of study, including electrosynthesis, organic chemistry, and drug discovery.

Recent Development of Bis-Cyclometalated Chiral-at-Iridium and Rhodium Complexes for Asymmetric Catalysis.

The field of asymmetric catalysis has been developing to access synthetically efficacious chiral molecules from the last century. Although there are many sustainable ways to produce nonracemic molecules, simplified and unique methodologies are always appreciated. In the recent developments of asymmetric catalysis, chiral-at-metal Lewis acid catalysis has been recognized as an attractive strategy. The catalysts coordinatively activate a substrate while serving the sole source of chirality by virtue of its helical environment. These configurationally stable complexes were utilized in a large number of asymmetric transformations, ranging from asymmetric Lewis acid catalysis to photoredox and electrocatalysis. Here we provide a comprehensive review of the current advancements in asymmetric catalysis utilizing iridium and rhodium-based chiral-at-metal complexes as catalysts. First, the asymmetric transformations via LUMO and HOMO activation assisted by a chiral Lewis acid catalyst are reviewed. In the second part, visible-light-induced asymmetric catalysis is summarized. The asymmetric transformation via the electricity-driven method is discussed in the final section.

Azotides as Modular Peptide-Based Ligands for Asymmetric Lewis Acid Catalysis.

Synthesis of azotides and evaluation of these as ligands for enantioselective Lewis acid catalysis is reported. The ligands were readily prepared from the chiral pool of amino acids and perform well in the cobalt(II)-catalyzed formation of asymmetric hetero Diels-Alder adducts. A rational for the observed enantioselectivity and conversion rate supported by computational calculations is provided.

Electricity-driven asymmetric Lewis acid catalysis

Catalytic asymmetric electrosynthesis combines the unique features of an electrochemical addition or removal of electrons with the catalytic asymmetric synthesis of enantioenriched molecules. However, identifying suitable catalysts that are compatible with electrochemical conditions and provide a high stereocontrol is a formidable challenge. Here we introduce a versatile electricity-driven chiral Lewis acid catalysis for the oxidative cross-coupling of 2-acyl imidazoles with silyl enol ethers. Powered by an electric current, this work provides a sustainable avenue to synthetically useful non-racemic 1,4-dicarbonyls, which include products that bear all-carbon quaternary stereocentres. A chiral-at-metal rhodium catalyst activates a substrate towards anodic oxidation by raising the highest occupied molecular orbital on enolate formation, which enables mild redox conditions, high chemo- and enantioselectivities (up to >99% enantiomeric excess) and a broad substrate scope. This work demonstrates the potential of combining asymmetric Lewis acid catalysis with electrochemistry and we anticipate that it will spur the further development of catalytic asymmetric electrosynthesis. The use of electrochemistry in asymmetric catalysis can prove challenging, not least due to the difficulty of achieving chemo- and stereoselectivity in combination with very reactive electrochemically generated intermediates. Here, catalytic asymmetric electrosynthesis is reported for the synthesis of 1,4-dicarbonyl compounds with high enantiomeric excess, including compounds with all-carbon quaternary stereocentres. The chiral-at-metal catalyst activates the substrate towards anodic oxidation in addition to controlling the enantioselectivity of the process.

Steering Asymmetric Lewis Acid Catalysis Exclusively with Octahedral Metal-Centered Chirality.

Catalysts for asymmetric synthesis must be chiral. Metal-based asymmetric catalysts are typically constructed by assembling chiral ligands around a central metal. In this Account, a new class of effective chiral Lewis acid catalysts is introduced in which the octahedral metal center constitutes the exclusive source of chirality. Specifically, the here discussed class of catalysts are composed of configurationally stable, chiral-at-metal Λ-configured (left-handed propeller) or Δ-configured (right-handed propeller) iridium(III) or rhodium(III) complexes containing two bidentate cyclometalating 5-tert-butyl-2-phenylbenzoxazole (dubbed IrO and RhO) or 5-tert-butyl-2-phenylbenzothiazole (dubbed IrS and RhS) ligands in addition to two exchange-labile acetonitriles. They are synthetically accessible in an enantiomerically pure fashion through a convenient auxiliary-mediated synthesis. Such catalysts are of interest due to their intrinsic structural simplicity (only achiral ligands) and the prospect of an especially effective asymmetric induction due to the intimate contact between the chiral metal center and the metal-coordinated substrates or reagents. With respect to chiral Lewis acid catalysis, the bis-cyclometalated iridium and rhodium complexes provide excellent catalytic activities and asymmetric inductions for a variety of reactions including Michael additions, Friedel-Crafts reactions, cycloadditions, α-aminations, α-fluorinations, Mannich reactions, and a cross-dehydrogenative coupling. Mechanistically, substrates such as 2-acyl imidazoles are usually activated by two-point binding. Exceptions exist as for example for an efficient iridium-catalyzed enantioselective transfer hydrogenation of arylketones with ammonium formate, which putatively proceeds through an iridium-hydride intermediate. The bis-cyclometalated iridium complexes catalyze visible-light-induced asymmetric reactions by intertwining asymmetric catalysis and photoredox catalysis in a unique fashion. This has been applied to the visible-light-induced α-alkylation of 2-acyl imidazoles (and in some instances 2-acylpyridines) with acceptor-substituted benzyl, phenacyl, trifluoromethyl, perfluoroalkyl, and trichloromethyl groups, in addition to photoinduced oxidative α-aminoalkylations and a photoinduced stereocontrolled radical-radical coupling, each employing a single iridium complex. In all photoinduced reaction schemes, the iridium complex serves as a chiral Lewis acid catalyst and at the same time as precursor of in situ assembled photoactive species. The nature of these photoactive intermediates then determines their photochemical properties and thereby the course of the asymmetric photoredox reactions. The bis-cyclometalated rhodium complexes are also very useful for asymmetric photoredox catalysis. Less efficient photochemical properties are compensated with a more rapid ligand exchange kinetics, which permits higher turnover frequencies of the catalytic cycle. This has been applied to a visible-light-induced enantioselective radical α-amination of 2-acyl imidazoles. In this reaction, an intermediate rhodium enolate is supposed to function as a photoactivatable smart initiator to initiate and reinitiate an efficient radical chain process. If a more efficient photoactivation is required, a rhodium-based Lewis acid can be complemented with a photoredox cocatalyst, and this has been applied to efficient catalytic asymmetric alkyl radical additions to acceptor-substituted alkenes. We believe that this class of chiral-only-at-metal Lewis acid catalysts will be of significant value in the field of asymmetric synthesis, in particular in combination with visible-light-induced redox chemistry, which has already resulted in novel strategies for asymmetric synthesis of chiral molecules. Hopefully, this work will also pave the way for the development of other asymmetric catalysts featuring exclusively octahedral centrochirality.

Asymmetric Lewis acid organocatalysis of the Diels-Alder reaction by a silylated C-H acid.

Silylium ion equivalents have shown promise as Lewis acid catalysts for a range of important C-C bond-forming reactions. Here we describe chiral C-H acids that upon in situ silylation, generate silylium-carbanion pairs, which are extremely active Lewis acid catalysts for enantioselective Diels-Alder reactions of cinnamates with cyclopentadiene. Enantiomeric ratios of up to 97:3 and diastereomeric ratios of more than 20:1 are observed across a diverse set of substitution patterns with 1 mole percent (mol %) of C-H acid catalyst and 10 mol % of a silylating reagent. The results show promise for broad applications of such C-H acid-derived silylium ion equivalents in asymmetric Lewis acid catalysis.

ChemInform Abstract: Asymmetric Lewis Acid Catalysis Directed by Octahedral Rhodium Centrochirality.

AbstractThe catalytic activities of the rhodium‐based asymmetric catalysts Δ‐ and Λ‐RBO are compared to the activities of the corresponding iridium catalysts.

Asymmetric Lewis acid catalysis directed by octahedral rhodium centrochirality.

A rhodium-based asymmetric catalyst is introduced which derives its optical activity from octahedral centrochirality. Besides providing the exclusive source of chirality, the rhodium center serves as a Lewis acid by activating 2-acyl imidazoles through two point binding and enabling a very effective asymmetric induction mediated by the propeller-like C2-symmetrical ligand sphere. Applications to asymmetric Michael additions (electrophile activation) as well as asymmetric α-aminations (nucleophile activation) are disclosed, for which the rhodium catalyst is found to be overall superior to its iridium congener. Due to its straightforward proline-mediated synthesis, high catalytic activity (catalyst loadings down to 0.1 mol%), and tolerance towards moisture and air, this novel class of chiral-at-rhodium catalysts will likely to become of widespread use as chiral Lewis acid catalysts for a large variety of asymmetric transformations.

'Click'-BINOLs: A New Class of Tunable Ligands for Asymmetric Catalysis

A new class of easily tunable 1,2,3-triazole-BINOL ligands, 'click'-BINOLs, have been synthesized from readily available alkynes and several azido-BINOL derivatives using the powerful Huisgen [3+2] cycloaddition 'click' approach. The activity of these ligands in asymmetric Lewis acid catalysis has been explored for the first time in the diethylzinc addition to aldehydes. The <i>C</i> ₂-symmetric ligand <b>1d</b> showed an interesting catalytic behavior, which suggests the non-innocent participation of the triazole units. Thus, good enantioselectivities (up to 86% ee) were obtained by both the right selection of the substitution pattern at the triazole ring and the fine tuning of the reaction conditions.

Corrigendum to “Highly enantioselective Michael-cyclization cascade promoted by synergistic asymmetric aminocatalysis and Lewis acid catalysis” [Tetrahedron Lett. 51 (2010) 1742–1744

Corrigendum to ‘‘Highly enantioselective Michael-cyclization cascade promoted by synergistic asymmetric aminocatalysis and Lewis acid catalysis” [Tetrahedron Lett. 51 (2010) 1742–1744] Chenguang Yu , Yinan Zhang , Shilei Zhang , Jing He *, Wei Wang a,* Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA b State Key Laboratory of Chemical Resources Engineering, Beijing University of Chemical Technology, Beijing 100029, China

Asymmetric Lewis Acid Catalysis in Water: α‐Amino Acids as Effective Ligands in Aqueous Biphasic Catalytic Michael Additions

AbstractThis article explores the potential of native α‐amino acids as chiral ligands in aqueous asymmetric Lewis acid catalysis, employing the C–C bond forming Michael addition as a model reaction. Some insights are provided regarding the details of Yb(OTf)3/α‐amino acid‐catalyzed Michael additions in water through new kinetic data as well as studies on how both yield and selectivity are influenced by variations in metal/ligand ratio, pH, temperature, and structure of the α‐amino acid. Through this investigation it was found that reaction conditions that require only 5 mol‐% of the Lewis acid, provides enantiomeric excesses of up to 79 % and is applicable to a wider range of donors and acceptors than previously demonstrated. Importantly, it was also demonstrated that the α‐amino acid complexed ytterbium catalyst might have potential for large‐scale applications as it displays not only large ligand accelerations, but also good solubility and stability in water. It can be recycled multiple times without appreciable loss of activity. The result is a promising example of a water‐compatible chiral Lewis acid.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)

Chiral triaryl phosphite-based palladacycles and platinacycles: synthesis and application to asymmetric Lewis acid catalysis

The optically pure monophosphites P(OAr)(BINOLate) (7, where Ar = 2,4-di-tert-butylphenyl) have been prepared by treatment of PCl2(OAr) with R- or S-BINOL. Treatment of [PdCl2(NCMe)2] with 7 gave [PdCl2(7)2] (9) or the binuclear orthometallated complex [Pd2Cl2(7-H)2] (8) depending on the reaction conditions. Bridge cleavage reactions of 8 gave [PdCl(7-H)(L)] with L trans to carbon when L = PPh3 or 7 and cis to carbon when L = N-heterocyclic carbene. Treatment of [PtCl2(NCtBu)2] with 7 gave [PtCl2(7)2] (18) which upon further reaction with PtCl2 furnished a mixture of binuclear [Pt2Cl2(7-H)2] (17) and cis-[PtCl(7-H)(7)] (19). The palladium complexes containing cyclometallated 7 were screened for catalysis of 1,4-conjugate addition of phenylboronic acid to cyclohexen-2-one and the allylation of benzaldehyde with allyltributyltin. Conversions were generally high in each case but enantioselectivities were low (15% e.e. at best). The X-ray crystal structures of 8, 17 and [PdCl(7-H)(NHC)] (10a, where NHC = 1,3-(dimesityl)imidazolidin-2-ylidene) have been determined.

Asymmetric Bisboranes as Bidentate Catalysts for Carbonyl Substrates

A new class of C(2) symmetric bisoxazaborolidinone compounds is described which exhibits bidentate binding to carbonyl substrates. Using the Diels-Alder reaction as a model system, the catalytic activity of these bis-Lewis acids is probed. Reaction rates and selectivities are observed that are higher than the corresponding mono-Lewis acids. This novel system offers a potentially powerful new approach to asymmetric Lewis acid catalysis.

Bis(oxazolinyl)phenyl transition metal complexes: synthesis, asymmetric catalysis, and coordination chemistry

Molecular catalysts for organic synthesis should be constructed to be tailored to target reactions and their desirable conditions. In our search for them, we have studied new types of transition metal molecular catalysts dressed with a tridentate N,C,N modular ligand, which consists of a C2-symmetric side-by-side phenyl group with chiral bis(oxazolinyl) substituents. The ligand, 2,6-bis(oxazolinyl)phenyl abbreviated as Phebox, can connect covalently to transition metals by the central carbon atom. Here, we review our recent work on the chemistry of Phebox and its metal complexes, including preparation, structural analysis, asymmetric Lewis acid catalysis, asymmetric hydrosilylation, asymmetric conjugate reduction, asymmetric reductive aldol reaction, and organometallic reactions.

Exploiting C3‐Symmetry in the Dynamic Coordination of a Chiral Trisoxazoline to Copper(II): Improved Enantioselectivity, and Catalyst Stability in Asymmetric Lewis Acid Catalysis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enantiodiscrimination and Enantiocontrol of Neutral and Cationic PtII Complexes Bearing the Tropos Biphep Ligand: Application to Asymmetric Lewis Acid Catalysis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Enantiodiscrimination and Enantiocontrol of Neutral and Cationic PtII Complexes Bearing the Tropos Biphep Ligand: Application to Asymmetric Lewis Acid Catalysis

S oder R, je nach Wunsch: Der enantiomerenreine, konfigurativ stabile Komplex [(biphep)Pt] wirkt als atropos-differenzierender Katalysator bei einer Temperatur von 50 °C und darunter. Beide enantiomeren Formen des Komplexes können erhalten werden, indem man entweder das chirale Diamin (R)-Dabn oder das Diamid (R)-DabnTf verwendet, die bei höheren Temperaturen (>60 °C) konfigurationskontrolliert (R)- bzw. (S)-Biphep-Pt liefern (siehe Schema; Tf=Trifluormethansulfonat).

Enantiodiscrimination and Enantiocontrol of Neutral and Cationic PtII Complexes Bearing the Tropos Biphep Ligand: Application to Asymmetric Lewis Acid Catalysis

The stereochemically stable, enantiopure biphep–Pt complexes can be employed as an atropos asymmetric catalyst at 50 °C or below. Both enantiomeric forms of this complex can be obtained by using either the chiral diamine (R)-dabn or its diamide (R)-dabnTf followed by chirally controlled formation of the single biphep–Pt enantiomer at higher (>60 °C) temperatures (see scheme; Tf=trifluoromethanesulfonate).

Exploiting C3-symmetry in the dynamic coordination of a chiral trisoxazoline to copper(ii): improved enantioselectivity, and catalyst stability in asymmetric lewis acid catalysis

Chiral C3-symmetric trisoxazolines are highly efficient stereodirecting ligands in enantioselective Cu(II) Lewis acid catalysis which is based on the concept of a stereoelectronic hemilability of the divalent copper; in direct comparison with the analogous bisoxazoline systems they are more efficient in the enantioselective alpha-amination as well as the enantioselective Mannich reaction of prochiral beta-ketoesters.