The increasing demand to produce enantiomerically pure pharmaceuticals, agrochemicals, flavors, and other fine chemicals has advanced the field of asymmetric catalytic technologies.1,2 Among all asymmetric catalytic methods, asymmetric hydrogenation utilizing molecular hydrogen to reduce prochiral olefins, ketones, and imines, have become one of the most efficient methods for constructing chiral compounds.3 The development of homogeneous asymmetric hydrogenation was initiated by Knowles4a and Horner4b in the late 1960s, after the discovery of Wilkinson’s homogeneous hydrogenation catalyst [RhCl(PPh3)3]. By replacing triphenylphosphine of the Wilkinson’s catalystwithresolvedchiralmonophosphines,6Knowles and Horner reported the earliest examples of enantioselective hydrogenation, albeit with poor enantioselectivity. Further exploration by Knowles with an improved monophosphine CAMP provided 88% ee in hydrogenation of dehydroamino acids.7 Later, two breakthroughs were made in asymmetric hydrogenation by Kagan and Knowles, respectively. Kagan reported the first bisphosphine ligand, DIOP, for Rhcatalyzed asymmetric hydrogenation.8 The successful application of DIOP resulted in several significant directions for ligand design in asymmetric hydrogenation. Chelating bisphosphorus ligands could lead to superior enantioselectivity compared to monodentate phosphines. Additionally, P-chiral phosphorus ligands were not necessary for achieving high enantioselectivity, and ligands with backbone chirality could also provide excellent ee’s in asymmetric hydrogenation. Furthermore, C2 symmetry was an important structural feature for developing new efficient chiral ligands. Kagan’s seminal work immediately led to the rapid development of chiral bisphosphorus ligands. Knowles made his significant discovery of a C2-symmetric chelating bisphosphine ligand, DIPAMP.9 Due to its high catalytic efficiency in Rh-catalyzed asymmetric hydrogenation of dehydroamino acids, DIPAMP was quickly employed in the industrial production of L-DOPA.10 The success of practical synthesis of L-DOPA via asymmetric hydrogenation constituted a milestone work and for this work Knowles was awarded the Nobel Prize in 2001.3k This work has enlightened chemists to realize * Corresponding author. 3029 Chem. Rev. 2003, 103, 3029−3069

New Chiral Phosphorus Ligands for Enantioselective Hydrogenation

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

/pdf/introduction-of-fluorine-and-fluorine-containing-functional-1i8kwiad20.pdf

Introduction of Fluorine and Fluorine-Containing Functional Groups

: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Organic chemists have always been fascinated by the cyclopropane subunit.1 The smallest cycloalkane is found as a basic structural element in a wide range of naturally occurring compounds.2 Moreover, many cyclopropane-containing unnatural products have been prepared to test the bonding features of this class of highly strained cycloalkanes3 and to study enzyme mechanism or inhibition.4 Cyclopropanes have also been used as versatile synthetic intermediates in the synthesis of more functionalized cycloalkanes5,6 and acyclic compounds.7 In recent years, most of the synthetic efforts have focused on the enantioselective synthesis of cyclopropanes.8 This has remained a challenge ever since it was found that the members of the pyrethroid class of compounds were effective insecticides.9 New and more efficient methods for the preparation of these entities in enantiomerically pure form are still evolving, and this review will focus mainly on the new methods that have appeared in the literature since 1989. It will elaborate on only three types of stereoselective cyclopropanation reactions from olefins: the halomethylmetal-mediated cyclopropanation reactions (eq 1), the transition metal-catalyzed decomposition of diazo compounds (eq 2), and the nucleophilic addition-ring closure sequence (eqs 3 and 4). These three processes will be examined in the context of diastereoand enantiocontrol. In the last section of the review, other methods commonly used to make chiral, nonracemic cyclopropanes will be briefly outlined.

Stereoselective Cyclopropanation Reactions

The Golden Age of Transfer Hydrogenation

Bis(isonitrile) iron(II) complexes bearing a C2-symmetric diamino (NH)2P2 macrocyclic ligand efficiently catalyze the hydrogenation of polar bonds of a broad scope of substrates (ketones, enones, and imines) in high yield (up to 99.5 %), excellent enantioselectivity (up to 99 % ee), and with low catalyst loading (generally 0.1 mol %). The catalyst can be easily tuned by modifying the substituents of the isonitrile ligand.

Highly Enantioselective Transfer Hydrogenation of Ketones with Chiral (NH)2P2 Macrocyclic Iron(II) Complexes

The enantioselective formation of a quaternary stereogenic center coinciding with a hydroxylation process is a very rare reaction from a homogeneous catalysis point of view. Indeed, to our knowledge, no asymmetric transition-metal-catalyzed direct hydroxylation has been reported before. We describe here our initial study concerning the enantioselective alpha-hydroxylation of various beta-ketoesters catalyzed by Lewis-acidic complexes. Specifically, it was found that the Ti complex [TiCl(2)((R,R)-1-Np-TADDOLato)(MeCN)(2)] affords the hydroxylated products in high yield and enantioselectivities up to 94% enantiomeric excess when using 2-(phenylsulphonyl)-3-(4-nitrophenyl)oxaziridine as the oxidizing agent. Chiral enantiopure compounds of the latter type have been used previously in stoichiometric asymmetric hydroxylation reactions. We also show that, in a complementary approach with H(2)O(2) as the oxidant, the Ru(II) complex [RuCl(OE(2))((S,S)-PNNP)]PF(6) catalyzes the same type of transformation in a case of substrates showing a very substantial extent of enolization under reaction conditions; being, however, unreactive toward only weakly enolized beta-ketoesters.

https://www.pnas.org/content/pnas/101/16/5810.full.pdf

Expanding the scope of asymmetric electrophilic atom-transfer reactions: Titanium- and ruthenium-catalyzed hydroxylation of β-ketoesters

Ruthenium(II) Complexes with Chiral Tetradentate P2N2 Ligands Catalyze the Asymmetric Epoxidation of Olefins with H2O2

Enantioselective Ficini Reaction: Ruthenium/PNNP‐Catalyzed [2+2] Cycloaddition of Ynamides with Cyclic Enones

Complexes of the general formula [MXH2(dppp)2]n+ (M = Ru, Os; X = H, Cl, CO; dppp = 1,3-bis(diphenylphosphino)propane) have been prepared and characterized, and the effect of the donor/acceptor properties of X on their structure and acidity has been studied. The five-coordinate complexes [MCl(dppp)2]+ (M = Ru (1a), Os (1b)) react with H2 gas in CH2Cl2 to give the complexes [MCl(η2-H2)(dppp)2]+ (M = Ru (2a), Os (2b)) containing elongated dihydrogen ligands. The molecular structure of 2b has been determined by X-ray crystallography (monoclinic, space group P21/n with a = 13.314(7) A, b = 18.63(2) A, c = 23.20(2) A, β = 94.58(6)°, and Z = 4). Chlorohydride [OsH(Cl)(dppp)2] (3b) reacts with H2 gas in the presence of Na[BPh4] forming [OsH3(dppp)2]+ (4b). Protonation of [OsH2(dppp)2] (5b) with HBF4·Et2O also gives 4b. A combination of X-ray crystallography (monoclinic, space group P21/n with a = 13.392(3) A, b = 25.306(7) A, c = 21.247(7) A, β = 91.15(2)°, and Z = 4) and 1H and 31P NMR studies indicate that 4b ...

Antonio Mezzetti

Papers

Highly Enantioselective Transfer Hydrogenation of Ketones with Chiral (NH)2P2 Macrocyclic Iron(II) Complexes

Expanding the scope of asymmetric electrophilic atom-transfer reactions: Titanium- and ruthenium-catalyzed hydroxylation of β-ketoesters

Ruthenium(II) Complexes with Chiral Tetradentate P2N2 Ligands Catalyze the Asymmetric Epoxidation of Olefins with H2O2

Enantioselective Ficini Reaction: Ruthenium/PNNP‐Catalyzed [2+2] Cycloaddition of Ynamides with Cyclic Enones

Heterolytic H2 Activation by Dihydrogen Complexes. Effects of the Ligand X in [M(X)H2{Ph2P(CH2)3PPh2}2]n+ (M = Ru, Os; X = CO, Cl, H)