Catalytic enantioselective stereoablative reactions: an unexploited approach to enantioselective catalysis

Approaches to the preparation of enantioenriched materials via catalytic methods that destroy stereogenic elements of a molecule are discussed. Although these processes often decrease overall molecular complexity, there are several notable advantages including material recycling, enantiodivergence and convergence, and increased substrate scope. Examples are accompanied by discussion of the critical design elements required for the success of these methods.     

Catalytic enantioselective desymmetrization of meso-N-acylaziridines with TMSCN

A catalytic enantioselective desymmetrization of meso-N-p-nitrobenzoylaziridines with TMSCN was developed using a chiral gadolinium catalyst generated from Gd(OiPr)3 and d-glucose-derived ligand 1. In this reaction, the addition of a catalytic amount of trifluoroacetic acid (TFA) improved enantioselectivity. High enantioselectivity was obtained from a range of meso-aziridines at 0-60 degrees C. The product could be easily transformed into beta-amino acids. Thus, the developed catalytic enantioselective desymmetrization reaction allowed for efficient catalytic synthesis of chiral cyclic beta-amino acids. The incorporation of TFA into the catalyst complex was observed using ESI-MS. Generation of this new complex might be the origin of the improved enantioselectivity.     

Catalytic enantioselective desymmetrization of meso-glutaric anhydrides using a stable Ni2-Schiff base catalyst

We describe the desymmetrization of meso-glutaric anhydrides to chiral hemiesters using a bench-stable homodinuclear Ni(2)-(Schiff base) complex as the catalyst in good to excellent yield (up to 99%) and enantioselectivity (up to 94%). Using the opposite enantiomer of the catalyst, we obtained the same yield and enantioselectivity with the opposite configuration, thereby gaining access to both hemiester enantiomers.     

Guanidine-catalyzed enantioselective desymmetrization of meso-aziridines

An amino-indanol derived chiral guanidine was developed as an efficient Br?nsted base catalyst for the desymmetrization of meso-aziridines with both thiols and carbamodithioic acids as nucleophiles, which provided 1,2-difunctionalized ring-opened products in high yields and enantioselectivities.     

Scaffolding catalysts: highly enantioselective desymmetrization reactions

Ex-changing places: a highly enantioselective desymmetrization of 1,2-diols has been developed in which the catalyst utilizes reversible covalent bonding to the substrate to achieve both high selectivity and rate acceleration (see scheme, PMP=pentalmethylpiperidine, TBS=tert-butyldimethylsilyl). Induced intramolecularity is responsible for the enhanced rate, thus allowing the reaction to be performed at room temperature.     

A review of enantioselective dual transition metal/photoredox catalysis

Transition metal catalysis is one of the most important tools to construct carbon-carbon and carbon-heteroatom bonds in modern organic synthesis. Visible-light photoredox catalysis has recently drawn considerable attention of the scientific community owing to its unique activation modes and significance for the green synthesis. The merger of photoredox catalysis with transition metal catalysts, termed metallaphotoredox catalysis, has become a popular strategy for expanding the synthetic utility of visiblelight photocatalysis. This strategy has led to the discovery of novel asymmetric transformations, which are unfeasible or not easily accessible by a single catalytic system. This contemporary area of organic chemistry holds promise for the development of economical and environmentally friendly methods for the asymmetric synthesis of chiral compounds. In this review, the advances in the enantioselective metallaphotoredox catalysis(EMPC) are summarized.     

Cooperative dual catalysis: application to the highly enantioselective conjugate cyanation of unsaturated imides

Cooperative heterobimetallic catalysis was used as a design principle to achieve a highly reactive system for the enantioselective conjugate addition of cyanide to alpha,beta-unsaturated imides. A dual-catalyst pathway involving chiral (salen)Al complex 1b and chiral (pybox)Er complex 4b provides measurable improvements in rates and enantioselectivities relative to single-catalyst systems. Mechanistic studies point to a cooperative bimetallic mechanism involving activation of the imide by the Al complex and activation of cyanide by the Er complex.     

Palladium-catalyzed enantioselective desymmetrization of silacyclobutanes: construction of silacycles possessing a tetraorganosilicon stereocenter

A palladium-catalyzed desymmetrization of alkyne-tethered silacyclobutanes to give silacycles possessing a tetraorganosilicon stereocenter has been developed, and high chemo- and enantioselectivities have been achieved by the use of a newly synthesized chiral phosphoramidite ligand.     

Synthesis of cyclopropene alpha-amino acids via enantioselective desymmetrization

[reaction: see text] The preparation of cyclopropene alpha-amino acids via the enantioselective desymmetrization of cyclopropene bis-carboxylic acid derivatives is described. The amino acids are stable to harsh reaction conditions, and a derivative has been incorporated into a tripeptide using conventional methods for peptide synthesis.     

Catalytic asymmetric desymmetrization of meso-diamide derivatives through enantioselective N-allylation with a chiral pi-allyl Pd catalyst: improvement and reversal of the enantioselectivity

In the presence of the Trost ligands-Pd catalysts, N-monoallylation of bis(2,4,6-triisopropylbenzne)sulfonylamides derived from meso-1,2-diamines proceeds with good to excellent enantioselectivity (85-96% ee) to give asymmetric desymmetrization products. Under the same conditions, in the reaction with meso-bistolunesulfonylamide derivatives, reversal of the enantioselectivity is observed.     

A palladium-catalyzed enantioselective alkylative desymmetrization of meso-succinic anhydrides

Monoalkylation of cyclic anhydrides provides an opportunity to couple a carbon-carbon bond-forming event with the control of backbone stereochemistry. We have developed a palladium-JOSIPHOS catalyst system that desymmetrizes meso-succinic anhydrides using organozinc reagents as nucleophiles, and have found that, in many cases, this reaction proceeds at ambient temperature.     

Lipase catalyzed enantioselective desymmetrization of a prochiral pentane-1,3,5-triol derivative

The enantioselective desymmetrization of the prochiral 3-O-silyl protected pentanetriol derivative 3 was carefully investigated. At −10 °C, the bacterial lipase from Burkholderia cepacia immobilized on ceramic particles led to monoacetate (S)-4 in 52% yield and >99.9% ee. At a reaction temperature of −40 °C the yield and enantioselectivity were even higher, but the reaction time was very long. Theoretical simulations of the reaction progress indicated an enantioselectivity of 25:1 at −10 °C and 35:1 at −40 °C. (S)-4 was converted into the enantiomerically pure building block 5-azidopentane-1,3-diol (S)-7 in two steps. The absolute configuration of (S)-7 was determined by exciton-coupled circular dichroism (ECCD) of diester (S)-8.     

Copper phosphoramidite-catalyzed enantioselective desymmetrization of meso-cyclic allylic bisdiethyl phosphates

[reaction: see text] A highly regio-, diastereo-, and enantioselective desymmetrization of five-, six-, and seven-membered meso-cyclic allylic bis-diethyl phosphates (2a, 2b, and 2c, respectively) was obtained with diethylzinc, using catalytic amounts of [Cu(OTf)](2).C(6)H(6) and phosphoramidite ligands 5. Enantiomeric excesses of up to 87, 94, and >98% were obtained for the addition of diethylzinc to cyclopentene, cyclohexene, and cycloheptene bis-diethyl phosphates, respectively.     

Rhodium-catalyzed enantioselective desymmetrization of bicyclic hydrazines with alkynylboronic esters

The first successful asymmetric transfer of rhodium-alkynyl species to symmetrical strained alkenes has been realized starting from bicyclic hydrazines and alkynylboronic esters.     

Catalytic enantioselective tert-aminocyclization by asymmetric binary acid catalysis (ABC): stereospecific 1,5-hydrogen transfer

Selective H transfer by ABC: A new asymmetric binary acid catalyst was developed to promote 1,5-H transfer specifically and stereoselectively in tert-aminocyclization reactions with excellent activity, high enantioselectivity, and broad substrate scope. The H atom (in red) was proven to transfer through a stereospecific suprafacial pathway (see scheme).     

Fluxional additives: a second generation control in enantioselective catalysis

The concept of "fluxional additives", additives that can adopt enantiomeric conformations depending on the chiral information in the ligand, is demonstrated in enantioselective Diels-Alder and nitrone cycloaddition reactions. The additive design is modular, and diverse structures are accessible in three steps. Chiral Lewis acids from main group and transition metals show enhancements in enantioselectivity in the presence of these additives.     

Catalytic enantioselective fluorination of beta-keto esters by phase-transfer catalysis using chiral quaternary ammonium salts

[reaction: see text] The catalytic enantioselective electrophilic fluorination promoted by quaternary ammonium salt from cinchonine as a phase-transfer catalyst is described. Treatment of beta-keto esters with N-fluorobenzenesulfonimide as the fluorine source under mild reaction conditions afforded the corresponding alpha-fluoro beta-keto esters in exellent yields with good to moderate enantiomeric excesses     

Dendrizymes: Expanded ligands for enantioselective catalysis

Dendrizymes are a new class of expanded ligands, designed for enantioselective catalysis with transition metal complexes. These expanded ligands consist of a strongly binding chelate core, which is surrounded by space-filling dendrimer substituents, built-up by branching units and optically active groups. In a complex of such a dendrimer ligand a reaction is supposed to take place in the same way as in the pocket of an enzyme.     

Chiral proton catalysis: a catalytic enantioselective direct aza-Henry reaction

Despite Nature's longstanding ability to use a proton, the most prevalent Lewis acid, to both activate and orient a substrate during an enantioselective reaction, this work represents the first example of this phenomenon outside of a protein. A chiral, nonracemic BisAMidine (BAM) ligand was designed, synthesized, and complexed to the proton of a Br?nsted acid. The resulting coordination compound catalyzed the production of enantioenriched product from the combination of a Schiff base and nitroalkane (the aza-Henry reaction). This particular reaction is also considered a model for many analogous carbon-carbon bond-forming reactions catalyzed by enzymes (e.g., the Mannich reaction). This discovery suggests the use of ionic hydrogen bonds in asymmetric catalysis may not only be more general than previously thought, but also a viable "green" approach to single-enantiomer organic compounds.