Chiral C2-Symmetric CuII Complexes as Catalysts for Enantioselective Hetero-Diels–Alder Reactions

Air-stable and recyclable , the Cu^II–(bis)oxazoline complex 1 efficiently catalyzes diastereo- and enantioselective hetero-Diels–Alder reactions between β,γ-unsaturated α-keto acid derivatives 2 and vinyl ethers for the synthesis of substituted dihydropyrans 3 [Eq. (1)]. Results of the crystal structure analysis of 1 in combination with calculations on model compounds indicate the formation of a reactive intermediate through replacement of the two H₂O ligands with a chelating substrate. X=OEt, N(OMe)Me; R=alkyl, aryl, alkoxy, thiobenzyl.     

Catalytic,Enantioselective Synthesis of α-Aminonitriles with a Novel Zirconium Catalyst

Strecker reactions of aldimines with Bu₃SnCN in the presence of the novel chiral zirconium binuclear catalyst 1 provide α-aminonitriles in good yields and with high enantioselectivities. The reaction can be applied to a wide range of substrates. Since both enantiomers of the chiral sources are readily avaibable, both enantiomers of the α-aminonitriles are easily prepared according to this method. L=N-methylimidazole.     

The First Enantioselective Aza-Diels–Alder Reactions of Imino Dienophiles on Use of a Chiral Zirconium Catalyst

Chiral dihydropyridone derivatives 3 are obtained in high yields and with good enantioselectivities by the title reaction of aldimines such as 1 with Danishefsky's diene 2 . 6,6′-Dibromo-1,1′-binaphthol complexes with Group 4 metals serve as catalysts; zirconium proved to be especially effective.     

Catalytic Enantioselective Aza Diels–Alder Reactions of Imino Dienophiles

1 mol% of catalyst is sufficient : The hetero Diels–Alder reaction of α-imino esters 1 with activated conjugated dienes 2 (R=H, Me) needs only 1 mol% of a 2,2′-bis(diarylphosphanyl)-1,1′-binaphthyl (BINAP) copper(I ) complex as the catalyst to generate the adducts 3 in good yields and with enantioselectivities up to 96%. The reaction can also be carried out on gram scale! Tos=H₃CC₆H₄SO₂; TMS=Me₃Si.     

A Surprising Solid-Phase Effect: Development of a Recyclable “Traceless” Linker System for Reactions on Solid Support

Triazenes as “traceless” linkers for solid-phase synthesis have been utilized for the attachment of arenes to a solid support and yield the corresponding products after various organometallic reactions (Heck reaction and asymmetric dihydroxylation, see the reaction scheme) and cycloadditions (Diels–Alder reaction). The triazene linker is distinguished by its accessibility, thermal robustness, and capability to undergo regeneration.     

Acylzirconocene Chloride as an “Unmasked” Acyl Anion: Enantioselective 1,2-Addition to α,β-Unsaturated Ketone Derivatives

The chiral monodentate phosphane ligand ( R )-MOP facilitated the first enantioselective nucleophilic 1,2-addition of an “unmasked” acyl anion to a carbonyl group in the Pd^II-catalyzed reaction of α,β-unsaturated ketones with acylzirconocene chlorides [Eq. (1), 66 % ee, 88 % yield; (R)-MOP=(R)-2-(diphenylphosphanyl)-2′-methoxy-1,1′-binaphthyl].     

Acylzirconocene Chloride as an “Unmasked” Acyl Anion

Under mild conditions the acyl group of acylzirconocene chloride 1 formed from an alkene or alkyne and [(C₅H₅)₂ZrHCl] reacts as an “unmasked” acyl anion. The Lewis acid mediated reactions with aldehydes that yield α-ketol products in high yields demonstrate the versatility of this reagent for C–C coupling.     

A Mechanochemically Triggered “Click” Catalyst

“Click” chemistry represents one of the most powerful approaches for linking molecules in chemistry and materials science. Triggering this reaction by mechanical force would enable site‐ and stress‐specific “click” reactions—a hitherto unreported observation. We introduce the design and realization of a homogeneous Cu catalyst able to activate through mechanical force when attached to suitable polymer chains, acting as a lever to transmit the force to the central catalytic system. Activation of the subsequent copper‐catalyzed “click” reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of a polymeric material, using a fluorogenic dye to detect the activation of the catalyst. Based on an N‐heterocyclic copper(I) carbene with attached polymeric chains of different flexibility, the force is transmitted to the central catalyst, thereby activating a CuAAC in solution and in the solid state.     

Design and Enantioselective Synthesis of Cashmeran Odorants by Using “Enol Catalysis”

Novel Cashmeran odorants were designed by molecular modeling. Their short syntheses involve a novel asymmetric Brønsted acid catalyzed Michael addition of unactivated α‐substituted ketones. This key transformation was realized by utilizing a new type of enol activation catalysis and affords different cyclic ketones bearing α‐quaternary stereocenters in good to excellent yields and with high enantioselectivity. Subsequent McMurry coupling and Saegusa–Ito oxidation furnished the enantiopure target odorants, one enantiomer of which indeed possesses the typical olfactory aspects of Cashmeran.     

ChemInform Abstract: Model Studies of Palladium-Catalyzed Coupling Reactions for the “South- North” Attachment of Avermectins.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.     

Highly Enantioselective Catalytic Hetero-Diels–Alder Reaction with Inverse Electron Demand

Valuable substrates for the synthesis of natural products , compounds 3 (R¹=alkyl, aryl, alkoxy; R², R³=alkyl) are formed from β,γ-unsaturated α-keto esters 1 and vinyl ethers 2 by the title reaction [Eq. (1)]. Copper(II ) bisoxazolines act as catalysts, and in many cases enantiomeric excesses higher than 99.5 % are achieved.     

A Powerful Chiral Phosphoric Acid Catalyst for Enantioselective Mukaiyama–Mannich Reactions

A new BINOL‐derived chiral phosphoric acid bearing 2,4,6‐trimethyl‐3,5‐dinitrophenyl substituents at the 3,3′‐positions was developed. The utility of this chiral phosphoric acid is demonstrated by a highly enantioselective (ee up to >99 %) and diastereoselective (syn/anti up to >99:1) asymmetric Mukaiyama–Mannich reaction of imines with a wide range of ketene silyl acetals. Moreover, this method was successfully applied to the construction of vicinal tertiary and quaternary stereogenic centers with excellent diastereo‐ and enantioselectivity. Significantly, BINOL‐derived N‐triflyl phosphoramide constitutes a complementary catalyst system that allows the title reaction to be applied to more challenging imines without an N‐(2‐hydroxyphenyl) moiety.     

Enantioselective Cascade Michael Addition/Cyclization Reactions of 3‐Nitro‐2H‐Chromenes with 3‐Isothiocyanato Oxindoles: Efficient Synthesis of Functionalized Polycyclic Spirooxindoles

An unprecedented Zn(OTf)₂‐catalyzed asymmetric Michael addition/cyclization cascade of 3‐nitro‐2H‐chromenes with 3‐isothiocyanato oxindoles has been disclosed. This transformation provides an efficient access to various synthetically important polycyclic spirooxindoles in a highly stereoselective manner under mild conditions (72–99 % yields, up to >95:5 d.r. and >99 % ee). The reaction leads to the formation of three consecutive stereocenters, including 1,3‐nonadjacent tetrasubstituted carbon stereocenters, in a single operation. A bifunctional activation model of the chiral Zn(OTf)₂/bis(oxazoline) complex was proposed based on control experiments, wherein the Zn^II moiety serves as a Lewis acid and the N atom of the free NH group acts as a Lewis base by a hydrogen‐bonding interaction.     

Cationic Chiral Pd‐Catalyzed “Acetylenic” Diels–Alder Reaction: Computational Analysis of Reversal in Enantioselectivity

The highly enantioselective Diels–Alder reaction of acetylenic dienophiles is shown to be effectively catalyzed by cationic chiral palladium complexes. Not only the degree but also the sense of enantioselectivity critically depends on the steric demand of ligands. Computational analyses indicate that the steric demand does not affect the endo/exo‐selectivity but the enantioface selectivity of dienes.     

Enzyme Catalysis “Reilluminated”

In a new light : The NADPH:protochlorophyllide (Pchlide) oxidoreductase (POR; see structure, green Pchlide, yellow NADPH) is a good model to investigate catalytical processes in enzymes, as its light activation allows an immediate start of the catalyzed reaction. By irradiation with weak, short laser pulses it is possible to detect conformation changes during the reaction and thus to uncover the elementary steps of the catalytic process.

     

Radical Cyclization/β-Elimination Tandem Reactions: Enantiopure Sulfoxides as Temporary Chiral Auxiliaries

Alkylidene-substituted cyclopentane derivatives are formed in high enantiomeric purity by the reaction shown below. A highly diastereoselective radical cyclization is followed by elimination of a β-sulfinyl radical. Interestingly, the addition of the Lewis acid methylaluminum bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD) totally reverses the stereochemical outcome of the reaction. E=CO₂Me.