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The first highly enantioselective intramolecular N−H bond insertion was realized by using copper catalysts modified with chiral spirobisoxazoline ligands, which provides a novel strategy for the synthesis of chiral 2-carboxytetrahydroquinolines. This reaction features fast reaction rate, high yield, high enantioselectivity, and mild reaction conditions.

A protocol for nickel-catalyzed hydrocarboxylation of alkynes with formic acid was developed. The protocol allowed for highly efficient synthesis of acrylic acid with a TON of up to 7700.

A new strategy for the enantioselective construction of chiral 2,3-cis-dimethyldihydrobenzofurans has been developed by a ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryloxybutanone via dynamic kinetic resolution (DKR), combined with a palladium-catalyzed intramolecular reductive Heck cyclization. Starting from optically active 2,3-cis-dimethyldihydrobenzofuran, the natural products (+)/(−)-PI-220 and (+)-3-epi-furaquinocin C were synthesized in high yields.

An iridium complex with a newly prepared chiral spiro amino-phosphine ligand efficiently catalyzed the hydrogenation of both β-aryl-β-methyl-nitroalkenes and β-alkyl-β-methyl-nitroalkenes to the corresponding saturated nitroalkanes, which represents the first report of a chiral catalyst that exhibits high enantioselectivity for the challenging hydrogenation of β,β-dialkyl-nitroalkenes.

The first nickel-catalyzed intermolecular hydroacylation reaction of alkenes with simple aldehydes has been developed. This reaction offers a new approach to the selective preparation of branched ketones in high yields (up to 99%) and branched selectivities (up to 99:1). Experimental data provide evidence for reversible formation of acyl–nickel–alkyl intermediate, and DFT calculations show that the aldehyde C–H bond transfer to a coordinated alkene without oxidative addition is involved. The origin of the reactivity and regioselectivity of this reaction was also investigated computationally, which are consistent with experimental observations.

This method provides access to Boc-protected β,γ-unsaturated α-amino acid esters with excellent yields and enantioselectivities.

The SBIP-catalyzed reaction of benzofuranone alkene (I) with allenes (II) affords γ-addition [3 + 2] cycloadducts (III) with high enantioselectivity, whilst the reaction with allenes (IV) gives rise to α-addition [3 + 2] cycloadducts (V).

The chiral tridentate spiro P-N-S ligands (SpiroSAP) were developed, and their iridium complexes were prepared. Introduction of a 1,3-dithiane moiety into the ligand resulted in a highly efficient chiral iridium catalyst for asymmetric hydrogenation of β-alkyl-β-ketoesters, producing chiral β-alkyl-β-hydroxyesters with excellent enantioselectivities (95-99.9% ee) and turnover numbers of up to 355,000.

A substituent adjacent to the pyridine N atom is crucial to block the coordination ability of the pyridine moiety, an effect which is evidently overturned by the proximate second N atom in substrate (Vb).

This review describes recent advances in the development of chiral metal catalysts for the asymmetric hydrogenation of ketones to give chiral alcohols, important building blocks for biologically active substances such as pharmaceuticals and natural products. Chiral ruthenium–diphosphine/diamine complexes have received intensive study and many efficient chiral ruthenium catalysts bearing chiral diphosphine and diamine ligands have been developed over the past few decades. In addition, chiral ruthenium, iridium, osmium, iron, copper, and palladium complexes with various chiral ligands have also emerged as highly efficient chiral metal catalysts for the asymmetric hydrogenation of ketones. A wide range of ketones are hydrogenated using these chiral metal catalysts to give chiral alcohols with excellent enantioselectivity with high turnover numbers (TONs) and turnover frequencies (TOFs). 1 Introduction 2 Chiral Ruthenium Catalysts 3 Chiral Iridium Catalysts 4 Other Chiral Metal Catalysts 5 Conclusion and Outlook

An iron-catalyzed asymmetric intramolecular cyclopropanation was realized in high yields and excellent enantioselectivity (up to 97 % ee) by using the iron complexes of chiral spiro-bisoxazoline ligands as catalysts. The superiority of iron catalysts exhibited in this reaction demonstrated the potential abilities of this sustainable metal in asymmetric carbenoid transformation reactions.

The catalytic hydrogenation of α-keto acids employing an Ir/SpiroPAP (IRC) catalyst proceeds under mild conditions with potential application on large scale synthesis.

Reaction is successfully applied in the synthesis of drugs (R)-clorprenaline (VII) (β2-agonist) and (R)-phenylephrine (VIII) (α-adrenergic receptor agonist).

The title compounds (II) are obtained by asymmetric hydrogenation of α-oxymethylcinnamic acids using chiral spiro phosphine-oxazoline/iridium complexes as catalysts.

A new type of readily available, air-stable ruthenium complex of tetradentate bipyridine ligands has been developed. These complexes displayed exceptional efficiency for the hydrogenation of aromatic and aliphatic carboxylic esters and lactones at as low as 10 ppm catalyst loading under very mild conditions.

This is the first asymmetric N—H insertion of α-diazoketones giving α-aminoketones in good yields and with high enantioselectivities.

The carboxy-directed hydrogenation prohibits the isomerization of the terminal olefins, and realizes the chemoselective hydrogenation of various dienes.

A palladium-catalyzed asymmetric O-H insertion reaction was developed. Palladium complexes with chiral spiro bisoxazoline ligands promoted the insertion of α-aryl-α-diazoacetates into the O-H bond of phenols with high yield and excellent enantioselectivity under mild reaction conditions. This palladium-catalyzed asymmetric O-H insertion reaction provided an efficient and highly enantioselective method for the preparation of synthetically useful optically active α-aryl-α-aryloxyacetates.

A novel approach for the synthesis of Crizotinib (1) is described. In addition, new efficient procedures have been developed for the preparation of (S)-1-(2,6-dichloro-3-fluorophenyl)ethanol (2) and tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (4), the key intermediates required for the synthesis of Crizotinib.

The method is extended to the preparation of (VI), the key intermediate for the synthesis of (+)-chelidonine (VII).

The title methodology allows the preparation of chiral α-substituted carboxylic acids in excellent yields and enantioselectivities.

This method yields the title compounds in high yields and with excellent enantioselectivities under mild reaction conditions and with low catalyst loadings.

The synthetic value of this protocol is demonstrated by an efficient preparation of nipecotic acid (VI).

A copper-catalyzed asymmetric allylic oxidation of acyclic olefins has been developed. By using the complexes of copper and chiral spiro bisoxazoline ligands as catalysts, the oxidation of various acyclic olefins was accomplished with excellent regioselectivity (>20:1 in most cases) and up to 67% ee under mild reaction conditions, which represents one of the best results for the enantioselective allylic oxidation of acyclic olefins.

The cyclization of various diazo ester substrates in the presence of the optimal ligands (Sa)-INH and (Sa)-IOP is advantageous with regards to high yields, excellent enantioselectivity, and wide substrate scope.

A selective oxidation of benzylic C(sp3)–H bonds to C(sp3)–O bonds catalyzed by copper complexes of quinoline–imine ligands was developed with peresters as oxidants under mild reaction conditions, which converted benzylic methylenes directly into benzylic alcohols and esters by means of direct C–H bond functionalization.

The carboxy group in the substrates is crucial for this reaction as it acts as an anchor for the Ir-catalysts.

The spiro pyridine-aminophosphine catalyst ligands (I) are successfully applied in the title reaction to afford the alcohol products with excellent enantioselectivity.

The reaction is carried out in the presence of phosphine PHL-1 and phosphite PHL-2 to produce both enantiomers of the desired amines, building blocks of natural products, form either (E)- or (Z)-substrates.

By using iridium catalyst based on chiral spiro phosphine–oxazoline ligands, the hydrogenation of α-arylcinnamic acids was accomplished under ambient pressure and low catalyst loading (as low as 0.01 mol %), providing useful 2,3-diarylpropionic acids in high yields with excellent enantioselectivities (up to 99% ee). A catalytic enantioselective synthesis of (S)-equol with the present hydrogenation reaction as a key step was accomplished starting from commercially available starting materials in six steps with 48.4% overall yield.

The synthetic value of the present protocol is demonstrated by preparation of herbicide (X).

Ruthenium-catalyzed highly selective codimerization of N-acetyl α-arylenamines with ethyl acrylates is reported. This codimerization reaction provides a new efficient method for the synthesis of α,β-unsaturated γ-amino esters with a quaternary center.

An efficient chiral iridium catalyst that bears a tridentate spiro P—N—N ligand catalyzes the asymmetric hydrogenation of ketones with excellent enantioselectivities and extremely high turnover numbers.

Conjugate hydrovinylation takes place if the enamine substrate has a vinyl group at the α-position [cf.

By using a sterically hindered chiral monodentate spiro phosphite ligand, aromatic or aliphatic aldehydes undergo the title reaction with allylic alcohols as well as allylic donors.

The asymmetric O—H insertion of α-diazo phosphonates with alcohols in the presence of a catalyst, generated in situ from a Cu(I) precursor, a chiral spiro bisoxazoline ligand and a sodium borate, provides good yields of α-alkoxy phosphonates with high enantioselectivities.

Transition metal-catalyzed enantioselective hydrogenation of enamides and enamines is one of the most important methods for the preparation of optically active amines. This review describes the recent developments of highly efficient catalytic asymmetric hydrogenation of enamides, and enamines. It specifically focuses on the substrates because hydrogenation of enamides and enamines is highly dependent on the substrates although the chiral metal catalysts play a significant role.

The title iridium complexes allow the asymmetric hydrogenation of ketones with up to 97% e.e.

A copper-catalyzed asymmetric intramolecular O-H insertion of ω-hydroxy-α-diazoesters has been accomplished by using chiral spiro bisoxazoline ligands. This highly enantioselective intramolecular O-H insertion reaction provides an efficient approach to a variety of synthetically important chiral 2-carboxy cyclic ethers with different ring sizes as well as substitution patterns.

Chiral spiro monophosphoramidites are synthesized and applied as ligands in the iridium-catalyzed asymmetric hydrogenation of enamines (I), (III), and (V) to offer the corresponding chiral tertiary amines with moderate to high enantioselectivities.

Cyclopenta-fused benzopyran and naphthalene derivatives are prepared using a spirobiindane-based chiral phosphine as catalyst.

The direct use of highly stable and easily available allylic alcohols instead of allylic metal reagents facilitates the preparation of chiral homoallylic amines.

Good to excellent yields are obtained if imines resulting from aromatic aldehydes are used.

Summary Dirhodium(II) tetrakis[methyl 1-(3-phenylpropanoyl)imidazolidin-2-one-4(S)-carboxylate], Rh 2 (4S-MPPIM) 4 , provides significant enhancement in enantiocontrol for intramolecular cyclopropanation reactions of allylic diazoacetates and optimal enantiocontrol/diastereocontrol for intramolecular C-H insertion reactions of secondary alkyl diazoacetates.