Asymmetric iodolactamization induced by chiral oxazolidine auxiliary

Asymmetric iodolactamization reactions of unsaturated amides with oxazolidines as the chiral auxiliaries were investigated. With (4S)-4-((2R)-2-butyl)-2,2-dimethyloxazolidine as the auxiliary and LiH as the base, a number of unsaturated amides underwent iodolactamization smoothly to afford the corresponding gamma- and delta-lactams in 30-98% yield with de values up to 97%.     

Asymmetric synthesis of chiral bisoxazolines and their use as ligands in metal catalysis

Novel C₂- and C₁-symmetric chiral bisoxazolines with a cyclic backbone have been synthesized in an asymmetric manner starting from meso anhydrides. All synthetic steps are easy to perform and lead to the desired products in good overall yields. Preliminary investigations revealed the applicability of these new compounds as ligands in transfer hydrogenations and various metal-catalyzed enantioselective C–C-bond forming reactions such as cyclopropanations and Diels–Alder reactions.     

Asymmetric catalysis by chiral hydrogen-bond donors

Hydrogen bonding is responsible for the structure of much of the world around us. The unusual and complex properties of bulk water, the ability of proteins to fold into stable three-dimensional structures, the fidelity of DNA base pairing, and the binding of ligands to receptors are among the manifestations of this ubiquitous noncovalent interaction. In addition to its primacy as a structural determinant, hydrogen bonding plays a crucial functional role in catalysis. Hydrogen bonding to an electrophile serves to decrease the electron density of this species, activating it toward nucleophilic attack. This principle is employed frequently by Nature's catalysts, enzymes, for the acceleration of a wide range of chemical processes. Recently, organic chemists have begun to appreciate the tremendous potential offered by hydrogen bonding as a mechanism for electrophile activation in small-molecule, synthetic catalyst systems. In particular, chiral hydrogen-bond donors have emerged as a broadly applicable class of catalysts for enantioselective synthesis. This review documents these advances, emphasizing the structural and mechanistic features that contribute to high enantioselectivity in hydrogen-bond-mediated catalytic processes.     

Enantioselective alkynylation of aromatic aldehydes catalyzed by new chiral oxazolidine ligands

New chiral oxazolidines were conveniently synthesized from natural amino acids in three simple steps with good yields. The use of chiral oxazolidine ligands for the enantioselective alkynylation of aldehydes provides a simple, practical and inexpensive method to generate chiral propargyl alcohols with 85-99% ee.     

Enantioselective catalysis with tropos ligands in chiral ionic liquids

Enantioselective homogeneous rhodium-catalysed hydrogenation using tropoisomeric biphenylphosphine ligands was accomplished in readily available chiral ionic liquids and the catalytic system could be reused after extraction with scCO(2).     

Asymmetric hydrogenation of enamides with catalysts containing chiral thiourea ligands

The asymmetric reduction of enamides with molecular hydrogen and catalytic amounts of rhodium, iridium or ruthenium complexes containing chiral N,S-ligands is reported. Various enantiomerically pure mono- and dithioureas were examined. The C₂-symmetry of the dithiourea ligands seems essential to the enantioselectivity achieved. Ee values of up to 70% were observed.     

Asymmetric nitrile-hydration with bifunctional ruthenium catalysts bearing chiral N-sulfonyldiamine ligands

The asymmetric hydration of α-benzyl-α-methylmalononitrile was examined by using chiral bifunctional catalysts. Enantiomer discrimination of the prochiral dinitrile in the presence of water was demonstrated with a well-defined bifunctional amido-Ru complex having N-sulfonyldiamine ligands, and providing the corresponding amidato(amine) complexes diastereoselectively. Under the catalytic conditions, the (R)-cyanoamide was successfully obtained without further hydrolysis to carboxylic acids.     

Asymmetric transfer hydrogenation: chiral ligands and applications

Hydrogen transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity and high selectivity. In this tutorial review the most significant advances recently achieved in the stereoselective reduction of unsaturated organic compounds catalyzed by homogeneous transition metal complexes are critically reviewed. A sharp growth of the synthetic applications of this technique in the synthesis of fine chemicals is predictable as the use of transition metal catalyzed reactions will become more familiar to synthetic chemists.     

Asymmetric catalysis by chiral titanium perchlorate for carbonyl-ene cyclization

The chiral binaphthol-derived titanium perchlorate (or triflate) is shown to serve efficiently as an asymmetric catalyst for the ene cyclization of type {3,4_exo,exo} and {2,4_exo′,exo} involving -alkoxy aldehyde as an internal enophile to afford the 6- and 7- membered cyclic ethers in high enantiomeric purity.     

Asymmetric catalysis using self-assembled chiral bidentate P,P-ligands

A strategy is described for modular catalyst development based upon metal-directed self-assembly of bifunctional subunits around a structural metal to form a heteroleptic complex in which a second set of ligating groups are now suitably disposed to bind a second metal to form a catalytic site. A library of chiral diphosphites was prepared via metal-directed self-assembly and used in a simple asymmetric allylic amination, giving enantiomeric excesses as high as 97%.     

Substituent electronic effects in chiral ligands for asymmetric catalysis

The majority of reports of ligand modification for catalysis have followed from systematic variation of the spatial demands of the catalyst. The focus of this review is to highlight selected major contributions to the area of substituent controlled electronic-tuning of some well known chiral ligands and the subsequent effect of these changes during asymmetric catalysis. The ligand types discussed include the salens, phosphites and phosphoramidites, ferrocene-containing ligands, oxazolines and axially chiral ligands. For each ligand type we attempt analyse the effect of systematic variation of electronics and note whether any improvements in catalyst activity and selectivity are obtained.     

Recent applications of chiral ferrocene ligands in asymmetric catalysis

Despite the impressive progress achieved in asymmetric catalysis during the last decade, an increasing number of new catalysts, ligands, and applications are reported every year to satisfy the need to embrace a wider range of reactions and to improve the efficiency of existing processes. Because of their availability, unique stereochemical aspects, and wide variety of coordination modes and possibilities for the fine-tuning of the steric and electronic properties, ferrocene-based ligands constitute one of the most versatile ligand architectures in the current scenario of asymmetric catalysis. Over the last few years ferrocene catalysts have been successfully applied in an amazing variety of enantioselective processes. This Review documents these recent advances, with special emphasis on the most innovative asymmetric processes and the development of novel, efficient types of ferrocene ligands.     

Asymmetric Pauson-Khand reaction with chiral, electron-deficient mono- and bis-phosphine ligands

The intermolecular Pauson-Khand reaction between norbornene and dicobalt carbonyl complexes of phenylacetylene substituted with chiral phosphorus ligands has been investigated. High yields (?98%) and enantiomeric excesses of up to 56% have been observed.     

Asymmetric hydrogenation of simple ketones with planar chiral ruthenocenyl phosphinooxazoline ligands

Ruthenocenyl phosphinooxazoline ligands have been shown to be highly efficient catalysts in the asymmetric hydrogenation. Both simple aromatic and heteroaromatic ketones were examined and excellent conversions and enantioselectivities were achieved.     

Diastereo- and enantioselective synthesis of oxazine and oxazolidine derivatives with a chiral quaternary carbon center under multifunctional catalysis

An easy one-pot, multistep cascade reaction which could afford a series of substituted benzo[d]pyrido[2,1-b]oxazolidine and [1,3]oxazine derivatives in a highly enantio- (up to 98% ee) and diastereoselective (4:1 to >20:1 dr) manner with generally good to excellent yields (up to 99%) has been developed. This well designed strategy could be applied to a wide scope of substrates under mild conditions with simple operations.     

Asymmetric auto-inductive aldol reaction by self-assembly of chiral ligands

The Ti(IV)/(R)-BINOL catalyzed aldol condensation of trimethylsilyloxydiene, deriving from 2,2,6-trimethyl-4H-[1,3]-dioxin-4-one, is shown to proceed through an auto-inductive process with amplification of enantiomeric excess (e.e.).     

Synthesis of chiral titanium-containing phosphinoamide ligands for enantioselective heterobimetallic catalysis

The synthesis of six chiral titanium-containing phosphinoamide ligands is discussed. These ligands assemble chiral heterobimetallic Pd–Ti complexes, enable enantioselective intramolecular allylic aminations with hindered amine nucleophiles and achieve selectivity up to 53% ee. Mechanistic studies demonstrate the reversibility of the enantio-determining C–N bond forming step, which leads to a gradual increase in the % ee of the reaction over time. These results represent a rare example of enantioselective heterobimetallic catalysis and suggest that these new ligands could find broad application in enantioselective transition metal catalysis.     

BINEPINES: chiral binaphthalene-core monophosphepine ligands for multipurpose asymmetric catalysis

The atropisomeric structure of 4,5-dihydro-3H-dinaphtho[2,1-c;1',2'-e]phosphepine is the common axially chiral scaffold of a library of monophosphine ligands nicknamed BINEPINES that have shown a quite remarkable stereoselection efficiency in a broad variety of enantioselective reactions involving the formation of new C-H or C-C or C-X bonds. In this critical review the properties and scope of this type of chiral ligands are illustrated (70 references).     

Asymmetric catalysis with peptides

Over the past decade several peptides have been developed as effective asymmetric catalysts for a range of synthetically useful reactions. Many have properties that are difficult to achieve with other catalysts. The article highlights features that render peptidic organocatalysts unique and attractive for future applications. Challenges such as the design of peptidic catalysts are discussed.     

Asymmetric synthesis of chiral Roche ester and its derivatives via Rh-catalyzed enantioselective hydrogenation with chiral phosphine-phosphoramidite ligands

Methyl 3-hydroxy-2-methylpropionate, known as the Roche ester, was prepared with high enantioselectivity (up to 96.7% ee) via the Rh-catalyzed asymmetric hydrogenation of methyl 2-hydroxymethylacrylate with a chiral 1,2,3,4-tetrahydro-1-naphthylamine-derived phosphine-phosphoramidite ligand (THNAPhos 5a) even at a low catalyst loading (0.1 mol %). An investigation on the substrate scope revealed that the ester group present in the substrate has a significant effect on the enantioselectivity, and the substrate with the bulkier ester group tended to give lower enantioselectivity.