Rhodium(III)‐Catalyzed Enantiotopic C−H Activation Enables Access to P‐Chiral Cyclic Phosphinamides

Compounds with stereogenic phosphorus atoms are frequently used as ligands for transition‐metal as well as organocatalysts. A direct catalytic enantioselective method for the synthesis of P ‐chiral compounds from easily accessible diaryl phosphinamides is presented. The use of rhodium(III) complexes equipped with a suitable atropochiral cyclopentadienyl ligand is shown to enable an enantiodetermining C−H activation step. Upon trapping with alkynes, a broad variety of cyclic phosphinamides with a stereogenic phosphorus(V) atom are formed in high yields and enantioselectivities. Moreover, these can be reduced enantiospecifically to P ‐chiral phosphorus(III) compounds.     

Stereogenic‐Only‐at‐Metal Asymmetric Catalysts

Chirality is an essential feature of asymmetric catalysts. This review summarizes asymmetric catalysts that derive their chirality exclusively from stereogenic metal centers. Reported chiral‐at‐metal catalysts can be divided into two classes, namely, inert metal complexes, in which the metal fulfills a purely structural role, so catalysis is mediated entirely through the ligand sphere, and reactive metal complexes. The latter are particularly appealing because structural simplicity (only achiral ligands) is combined with the prospect of particularly effective asymmetric induction (direct contact of the substrate with the chiral metal center). Challenges and solutions for the design of such reactive stereogenic‐only‐at‐metal asymmetric catalysts are discussed.     

Configurational control in stereochemically pure ligands and metal complexes for asymmetric catalysis

Enantioselective synthesis relies on suitable chiral mediators, which, in many cases, owe their stereochemical information to chiral ligands coordinated to metals. Like nature, which uses (diastereomerically pure) enzymes with several stereogenic centers to catalyze biological processes, chemists, for their purposes, tend more and more to turn their attention towards ligands and metal complexes with more than one stereogenic center or element of chirality. Selected issues of the resulting diastereomeric interactions as well as the advantages that result from the use of such complexes in catalysis are presented and discussed here.     

Predetermined chirality at metal centers of various coordination geometries: a chiral cleft ligand for tetrahedral (T-4), square-planar (SP-4), trigonal-bipyramidal (TB-5), square-pyramidal (SPY-5), and octahedral (OC-6) complexes

Two tetradentate bispinene-bipyridine type ligands, each with six stereogenic carbon centers, were synthesized from (-)-alpha-pinene. Their ability to predetermine chiral configurations at metal centers was studied. The two diastereoisomers, L1 and L2, differ in their absolute configuration at the bridgehead position. These ligands form metal complexes with Ag(I), Pd(II), Zn(II), Cu(II), and Cd(II), with coordination numbers four, five, and six and with complete control of chirality at the metal centers. Using L1 rather than L2 leads to complexes of inverted absolute configuration at the metal centers. These diastereomeric coordination species can be obtained either as separate compounds or, in some cases, as solids containing them in a 1:1 ratio. Ligands L1 and L2 thus show that the pinene-bipyridines are versatile molecules for the formation of metal complexes with predetermined chirality. In all cases, absolute configurations were determined in the solid state by X-ray diffraction methods and in solution by CD spectroscopy. The sign of exciton couplets from the pi-pi* transitions always agrees with the expectations for a given local configuration at the metal center. The five-coordinate, inherently chiral species of Zn(II) and Cu(II) described in this article are the first examples of trigonal-bipyramidal metal complexes with predetermined absolute configuration containing topologically linear ligands.     

Accessing N‐Stereogenicity through a Double Aza‐Michael Reaction: Mechanistic Insights

Further development of the chemistry and applications of chiral compounds that possess configurationally stable stereogenic nitrogen atoms is hampered by the lack of efficient strategies to access such compounds in an enantiomerically pure form. Esters of propiolic acid and chiral alcohols were evaluated as cheap and readily available Michael acceptors in a diastereoselective synthesis of N‐stereogenic compounds by means of a double aza‐Michael conjugate addition. Diastereomeric ratios of up to 74:26 and high yields were achieved with (?)‐menthyl propiolate as a substrate. Furthermore, a detailed mechanistic investigation was undertaken to shed some light on the course of this domino transformation. Kinetic studies revealed that the protic‐solvent additive acts as a Brønsted acid and activates the ester toward the initial attack of the tetrahydrodiazocine partner. Conversely, acidic conditions proved unfavorable during the final cyclization step that provides the product.     

Stereodivergent‐at‐Metal Synthesis of [60]Fullerene Hybrids

Chiral fullerene–metal hybrids with complete control over the four stereogenic centers, including the absolute configuration of the metal atom, have been synthesized for the first time. The stereochemistry of the four chiral centers formed during [60]fullerene functionalization is the result of both the chiral catalysts employed and the diastereoselective addition of the metal complexes used (iridium, rhodium, or ruthenium). DFT calculations underpin the observed configurational stability at the metal center, which does not undergo an epimerization process.     

Rational creation of chiral multinuclear and metallosupramolecular compounds from thiol-containing amino acids

Developments in the rational creation of chiral multinuclear and metallosupramolecular compounds based on linear-type metal complexes with penicillaminate (pen), as well as their functionality as a multidentate chiral metalloligand, is the main subject of this paper. The reactions of a mononuclear Au(I) complex, [Au(d-pen)(2)](3-), in which two d-pen ligands bind to an Au(I) center through thiolato S atoms, with transition metal ions afford a variety of S-bridged heterobimetallic multinuclear complexes, the structures and properties of which are highly dependent on the nature of reacting metal ions. The created multinuclear complexes still act as a metalloligand when they possess free amine and/or carboxylate groups, leading to the formation of heterotrimetallic supramolecular structures by reacting with third metal ions. While the Au-S bonds in [Au(d-pen)(2)](3-) are generally retained in the course of the reactions with metal ions, this is not the case for the Hg-S bonds in the corresponding Hg(II) complex, [Hg(d-pen)(2)](2-). A remarkable chiral behavior of multinuclear complexes composed of [Au(l-cys)(2)](3-) (cys = cysteinate), which is opposite to that composed of [Au(l-pen)(2)](3-), is also presented.     

Direct observation of chiral metal-organic complexes assembled on a Cu100 surface

We report single-molecule level STM observations of chiral complexes generated by the assembly of achiral components at a metal surface. Following co-deposition of iron atoms and 1,3,5-tricarboxylic benzoic acid (trimesic acid, TMA) on Cu(100) in ultrahigh vaccum, TMA molecules react with the metal centers, and metal-ligand interactions stabilize R and S chiral complexes which are clearly distinguished by STM.     

Chiral olefins as steering ligands in asymmetric catalysis

Metal-catalyzed asymmetric processes offer one of the most straightforward ways to introduce stereogenic centers. Hence, the development of novel chiral ligands that can effectively induce asymmetry in reactions is crucial in modern organic synthesis. While many established chiral ligands bind to a metal through heteroatoms, structures that coordinate to metals through carbon atoms have received little attention so far. Here, we highlight the increasing number of such chiral chelating olefin ligands as well as their application in a variety of metal-catalyzed transformations.     

Asymmetric dearomatization of the furan ring promoted by conjugate organolithium addition to (menthyloxy)(3-furyl)carbene complexes of chromium

The sequential low-temperature addition reaction of an organolithium compound and methyl triflate to (menthyloxy)(3-furyl)carbene complexes of chromium and tungsten proceeded with excellent regioselectivity (1,4-addition) and diastereoselectivity (2,3-trans disposition of the nucleophile and electrophile groups) to afford new 2,3-disubstituted (2,3-dihydro-3-furyl)carbene complexes. In addition, a high degree of diastereofacial selectivity was achieved by employing alkenyllithium compounds. After detachment of both the metal fragment and the chiral auxiliary group, trisubstituted 2,3-dihydrofuran derivatives containing a quaternary stereogenic center at the C3 position were obtained. The characterization, including X-ray crystallography, of a novel type of stable four-membered chelate (eta(2)-alkene)tetracarbonylcarbene complex of chromium is also reported.     

Catalytic uses of helicenes displaying phosphorus functions

This review presents an updated state of art of the catalytic uses of chiral phosphorus compounds characterized by a helical scaffold as the key stereogenic element of their structures. These include both helical scaffolds with appended phosphorus functions and helical scaffolds with embedded phosphorus-containing rings (phosphahelicenes). Catalytic applications of helical phosphines in both transition metal catalysis and organocatalysis are presented.     

Darstellung und NMR-spektroskopische Charakterisierung von konfigurationsstabilen Diorganozinn(IV)-Komplexen RPhSnL mit Zinn als chiralem Zentrum

Synthesis and Characterization of Configurationally Stable Diorganotin(IV) Complexes with Tin as a Chiral Centre Contrary to the high optical stability of tetraorganotin compounds most heteroleptic organic tin compounds are configurationally instable. We report the synthesis and the characterization of some new enantiomeric and diastereomeric diorganotin(IV) complexes of stable configuration with tin as a chiral centre. The stabilization of the chiral tin atom was realized by complexation with tridentate diacidic esterhydrazone ligands H₂L, which prevent an interconversion at the stereogenic centre. Multinuclear NMR-studies in solution demonstrate, that the configuration of the chiral tin center is configurationally stable up to 160°C. The molecular structure of the complexes Neophyl-phenyl-tin-2[(2-methyl-mercaptothiocarbonyl)-hydrazono]propionate II b and (2-Methyl-butyl-1-yl)-phenyl-tin-[S-methyl-β-N-(2-salicylmethylidene)thiocarbazat] III g have been determined by single crystal X-ray diffraction analysis.     

Recent Advances in Asymmetric Catalysis Using p-Block Elements

The development of new methods for enantioselective reactions that generate stereogenic centres within molecules are a cornerstone of organic synthesis. Typically, metal catalysts bearing chiral ligands as well as chiral organocatalysts have been employed for the enantioselective synthesis of organic compounds. In this review, we highlight the recent advances in main group catalysis for enantioselective reactions using the p-block elements (boron, aluminium, phosphorus, bismuth) as a complementary and sustainable approach to generate chiral molecules. Several of these catalysts benefit in terms of high abundance, low toxicity, high selectivity, and excellent reactivity. This minireview summarises the utilisation of chiral p-block element catalysts for asymmetric reactions to generate value-added compounds.     

Optically active [(η-C5H5)Ru{(R)-Ph2PCH(CH3)CH2PPh2}(Olefin)]PF6 complexes: Influence of the stereogenic metal atom on the enantioface selection

The synthesis and characterization of optically active olefinic complexes of the type [(η-C₅H₅)Ru{Ph₂PCH(CH₃)CH₂PPh₂}(CH₂CHR″)]PF₆ (R″  H, CH₃, C₆H₅, COOCH₃), in which the metal is a stereogenic center, are reported. The enantioface discrimination of the prochiral olefin is influenced by the chiral ligand and by the stereogenic metal atom. The chiral center at the metal appears to be optically labile. The rates of the epimerization at the metal and of the olefin enantioface depend on the structure of the coordinated olefin.     

Enantioselective reductions by chirally modified alumino- and borohydrides

Fifty years after the first report on the reduction of carbonyl compounds using chiral LiAlH₄-derived hydrides (Bothner-By, A. A. J. Am. Chem. Soc. 1951, 73, 846), the field of enantioselective aluminohydride and borohydride reagents modified by chiral additives is reviewed. The first section deals with the preparation, scope, limits, mechanism of action and synthetic applications of chiral aluminohydrides, classified according to the chemical nature of the stereogenic modifier. The second covers the field of chiral borohydrides, which have been further classified according to the boron sources, namely metal borohydrides (via reaction with chiral additives or in the presence of chiral catalysts), or chiral boranes (by reduction with alkyllithiums or metal hydrides).     

Asymmetric conjugate additions of chiral phosphonamide anions to alpha,beta-unsaturated carbonyl compounds. A versatile method for vicinally substituted chirons

Reactions of anions derived from chiral nonracemic allyl, crotyl, and cinnamyl bicyclic C(2)-symmetrical phosphonamides with alpha, beta-unsaturated cyclic ketones, esters, lactones, and lactams take place at the gamma-position of the reagents. The products are diastereomerically pure or enriched beta-substituted carbonyl compounds. The method also provides easy access to vicinal substitution of as many as three stereogenic centers including in some cases quaternary carbon atoms, in a one-pot sequence.     

Chiral nonracemic late-transition-metal organometallics with a metal-bonded stereogenic carbon atom: development of new tools for asymmetric organic synthesis

Transition-metal-catalyzed cross-coupling reactions and the Heck reaction have evolved into powerful tools for the construction of carbon-carbon bonds. In most cases, the reactive organometallic intermediates feature a carbon-transition-metal sigma bond between a sp(2)-hybridized carbon atom and the transition metal (Csp(2)--TM). New, and potentially more powerful approach to transition-metal-catalyzed asymmetric organic synthesis would arise if catalytic chiral nonracemic organometallic intermediates with a stereogenic sp(3)-hybridized carbon atoms directly bonded to the transition metal (C*sp(3)--TM bond) could be formed from racemic or achiral organic substrates, and subsequently participate in the formation of a new carbon-carbon bond (C*sp(3)-C) with retention of the stereochemical information. To date, only a few catalytic processes that are based on this concept, have been developed. In this account, both "classical" and recent studies on preparation and reactivity of stable chiral nonracemic organometallics with a metal-bonded stereogenic carbon, which provide the foundation for the future design of new synthetic transformations exploiting the outlined concept, are discussed, along with examples of relevant catalytic processes.     

Efficient Kinetic Resolution of Sulfur‐Stereogenic Sulfoximines by Exploiting CpXRhIII‐Catalyzed C−H Functionalization

Chiral sulfoximines with stereogenic sulfur atoms are promising motifs in drug discovery. We report an efficient method to access chiral sulfoximines through a C?H functionalization based kinetic resolution. A rhodium(III) complex equipped with a chiral Cp^x ligand selectively participates in conjunction with phthaloyl phenylalanine in the C?H activation of just one of the two sulfoximine enantiomers. The intermediate reacts with various diazo compounds, providing access to chiral 1,2‐benzothiazines with synthetically valuable substitution patterns. Both sulfoximines and 1,2‐benzothiazines were obtained in high yields and excellent enantioselectivity, with s‐values of up to 200. The utility of the method is illustrated by the synthesis of the key intermediates of two pharmacologically relevant kinase inhibitors.     

碳水化合物含磷配体在不对称催化中的应用*

糖类化合物价廉易得,具有天然手性结构,糖环上的多个羟基经过修饰,可以连接多种官能团。近年来手性糖类化合物的合成与应用研究引起了人们的广泛关注,尤其是在不对称合成和催化中的应用研究已成为有机化学中非常活跃的领域。碳水化合物含磷手性配体在不对称催化反应中的应用研究进展十分迅速,本文综述了近年来碳水化合物含磷手性配体与金属形成络合物作为催化剂,在不对称催化氢化、不对称烯丙位取代和不对称氢甲酰化等反应中的研究进展。     

Synthesis of P-chiral phosphines via chiral metal template promoted asymmetric furan Diels-Alder reaction

The organoplatinum complex containing ortho-metalated (S)-(1-(dimethylamino)ethyl)-naphthalene as the chiral auxiliary has been used to promote the asymmetric [4+2] Diels-Alder reaction between phenyldivinylphosphine and 2-diphenylphosphinofuran. The reaction was complete in 6 days at room temperature, with the formation of four isomeric diphosphino-substituted oxanorbornene metal complexes in the ratio of 4:2:2:1. Only the exo-cycloaddition products were formed. The formation of stereogenic carbon centers within the oxanorbornene skeleton are highly stereoselective, with all four cycloadducts adopting the same absolute configurations. However, the stereocontrol at the external phosphorus stereogenic center is less efficient (S_p:R_p = 2:1 for the template cycloadducts). The chiral naphthylamine auxiliary could be removed chemoselectively by treatment with concentrated hydrochloric acid, and further ligand liberation of the dichloro complexes with aqueous cyanide gave the diphosphino-substituted oxanorbornene ligands. Hydrogenation of the double bonds in the cycloadduct stabilizes the phosphorus stereogenic center of the free diphosphine ligand which otherwise undergoes inversion of absolute configuration.