Achiral Precursors Research Articles

Stereoselective Catalysis Achieved through in Situ Desymmetrization of an Achiral Iron Catalyst Precursor.

Stereoselective catalysis is described that proceeds with catalyst control but without the need to synthesize preformed chiral catalysts or ligands. Iron-based catalysts were discovered to effect the stereoselective polymerization of lactides starting from a single achiral precursor and the proper choice of an achiral silanol additive. Spectroscopic analysis of the polymer revealed that the stereoselectivity originates from an enantiomorphic site rather than a chain end stereocontrol mechanism. Iron intermediates that are stereogenic at iron are proposed to form in situ as a result of desymmetrization that occurs from a change in the metal coordination number. The proposed mechanism is supported by a combination of spectroscopic measurements, model complexes, kinetic measurements, and DFT calculations.

ChemInform Abstract: Manipulating Simple Reactive Chemical Units: Fishing for Alkaloids from Complex Mixtures

AbstractReview: [26 refs.

ChemInform Abstract: Recent Advances in the Transition‐Metal‐Catalyzed Enantioselective Synthesis of Silicon‐Stereogenic Organosilanes

AbstractReview: [20 refs.

Manipulating Simple Reactive Chemical Units: Fishing for Alkaloids from Complex Mixtures

This Concept article describes how key C10 molecular scaffolds, too reactive to be obtained through classical multistep synthesis, were targeted in the most simple reaction conditions, reproducing those that may be encountered in living cells. The rationale was that small amounts of these reactive intermediates might be formed in situ from cheap and abundant reactants (i.e., glutaraldehyde and tetrahydropyridine) resulting, upon further rearrangement in "complex mixtures" from which natural substances would arise. From five types of mixtures, at least six full carbon skeletons of known natural substances were formed spontaneously. This work also led to the discovery of new plausible biosynthetic achiral precursors in the Nitraria metabolism.

ChemInform Abstract: The Total Syntheses of Basiliolide C, epi‐Basiliolide C, and Protecting‐Group‐Free Total Syntheses of Transtaganolides C and D.

The total syntheses of basiliolide C and previously unreported epi-basiliolide C are achieved by an Ireland–Claisen/Diels–Alder cascade. The development of a palladium catalyzed cross-coupling of methoxy alkynyl zinc reagents allows for the protecting-group-free syntheses of transtaganolides C and D. Syntheses of transtaganolides C and D are accomplished in a single operation to generate three rings, two all-carbon quaternary centers, and four tertiary stereocenters from a monocyclic, achiral precursor.

Recent Advances in the Transition‐Metal‐Catalyzed Enantioselective Synthesis of Silicon‐Stereogenic Organosilanes

AbstractAsymmetric catalysis is one of the most attractive and efficient ways of synthesizing chiral enantioenriched compounds from achiral precursors. Compared with the well‐investigated enantioselective preparation of carbon‐stereogenic compounds, the corresponding preparation of silicon‐stereogenic compounds is much less established. In particular, the available methods typically rely on the use of stoichiometric amounts of chiral reagents, and little progress has been made on catalytic enantioselective synthesis using prochiral organosilanes until recently. This Focus Review highlights recent advances in the catalytic enantioselective preparation of silicon‐stereogenic organosilanes under transition‐metal catalysis through desymmetrization of prochiral organosilanes including diorganodihydrosilanes and tetraorganosilanes.

Step-by-step strategy from achiral precursors to polyoxometalates-based chiral organic-inorganic hybrids.

Using two types of triol ligands, several novel asymmetrically triol-functionalized Anderson organic hybrids have been efficiently synthesized in high purity and good yields via a convenient two-step esterification reaction. These organic-inorganic hybrids are chiral and can be spontaneously resolved with suitable solvents. Their molecular and crystal structures have been confirmed by single-crystal X-ray diffraction studies. Stable solid-state chirality of the corresponding enantiopure crystals has also been confirmed definitively by CD spectra. Interestingly, these organic-inorganic hybrids possess a layer-by-layer structure, forming solvent-accessible nanoscale chiral channels via a 1D infinite helical chain substructure. TGA measurements indicated that the species of the central heteroatoms significantly effects the stability of these compounds.

Stochastic and empirical models of the absolute asymmetric synthesis by the Soai-autocatalysis.

Absolute asymmetric synthesis (AAS) is the preparation of pure (or excess of one) enantiomer of a chiral compound from achiral precursor(s) by a chemical reaction, without enantiopure chiral additive and/or without applied asymmetric physical field. Only one well-characterized example of AAS is known today: the Soai-autocatalysis. In an attempt at clarification of the mechanism of this particular reaction we have undertaken empirical and stochastic analysis of several parallel AAS experiments. Our results show that the initial steps of the reaction might be controlled by simple normal distribution ("coin tossing") formalism. Advanced stages of the reaction, however, appear to be of a more complicated nature. Symmetric beta distribution formalism could not be brought into correspondence with the experimental observations. A bimodal beta distribution algorithm provided suitable agreement with the experimental data. The parameters of this bimodal beta function were determined by a Pólya-urn experiment (simulated by computer). Interestingly, parameters of the resulting bimodal beta function give a golden section ratio. These results show, that in this highly interesting autocatalysis two or even perhaps three catalytic cycles are cooperating. An attempt at constructing a "designed" Soai-type reaction system has also been made.

A homochiral Cu(i) coordination polymer based on achiral precursors and its photocatalytic properties.

A homochiral three-dimensional framework material, [Cu(7)(4-bpt)(6)(CN)(H(2)O)] (1) (4-bpt = 3,5-bis(4-pyridyl)-1,2,4-triazole), has been successfully synthesized by solvothermal reaction, which is generated through an unusual spontaneous asymmetrical crystallization from achiral precursors, and its photocatalytic properties in degradation of organic dyes are also investigated.

Spontaneous resolution of P and M helical copper(ii) MOFs built from achiral precursors

Enantiomorphic P and M helices have been synthesized by the self-assembly of achiral precursors via spontaneous resolution.

Homochiral 3D coordination polymer with unprecedented three-directional helical topology from achiral precursor: synthesis, crystal structure, and luminescence properties of uranyl succinate metal-organic framework.

A luminescent homochiral uranyl succinate coordination polymer with unprecedented three-directional helices was synthesized hydrothermally via spontaneous symmetry breaking, and fully characterized. Its homochirality has been confirmed by singe crystal X-ray diffraction and solid state circular dichroism (CD) spectra. The polymer exhibited a Stokes shift greater than 180 nm.

Spontaneous symmetry breaking of Co(II) metal-organic frameworks from achiral precursors via asymmetrical crystallization.

The racemic conglomerate (1P-NH3 + 1M-NH3) and enantioenriched bulk samples (1P-H2O or 1M-NH3) of Co(II) metal–organic frameworks were obtained from achiral precursors under different solvothermal conditions. The bulk homochirality was generated through asymmetrical crystallization in the absence of any chiral additives confirmed by single crystal X-ray diffraction and CD spectroscopy.

Formation of a novel ferromagnetic end-to-end cyanate bridged homochiral helical copper(II) Schiff base complex via spontaneous symmetry breaking.

A homochiral helical coordination polymer of copper(II) has been synthesized using achiral precursors via spontaneous symmetry breaking and has been confirmed by single crystal X-ray diffraction and solid-state CD spectroscopy. The variable temperature magnetic measurements indicate the presence of weak ferromagnetic exchange interactions mediated by end-to-end cyanate bridges (J = +0.12 cm(-1)).

Emergence of single-molecular chirality from achiral reactants.

The synthesis of enantiopure molecules from achiral precursors without the need for pre-existing chirality is a major challenge associated with the origin of life. We here show that an enantiopure product can be obtained from achiral starting materials in a single organic reaction. An essential characteristic of this reaction is that the chiral product precipitates from the solution, introducing a crystal–solution interface which functions as an asymmetric autocatalytic system that provides sufficient chiral amplification to reach an enantiopure end state. This approach not only provides more insight into the origin of life but also offers a pathway to acquire enantiopure compounds for industrial applications.

The total syntheses of basiliolide C, epi-basiliolide C, and protecting-group-free total syntheses of transtaganolides C and D.

The total syntheses of basiliolide C and previously unreported epi-basiliolide C are achieved by an Ireland-Claisen/Diels-Alder cascade. The development of a palladium catalyzed cross-coupling of methoxy alkynyl zinc reagents allows for the protecting-group-free syntheses of transtaganolides C and D. Syntheses of transtaganolides C and D are accomplished in a single operation to generate three rings, two all-carbon quaternary centers, and four tertiary stereocenters from a monocyclic, achiral precursor.

Synthesis and Biological Activity of 25-Hydroxy-2-methylene-vitamin D3 analogues monohydroxylated in the A-ring.

The 20R- and 20S-isomers of 25-hydroxy-2-methylene-vitamin D3 and 3-desoxy-1α,25-dihydroxy-2-methylene-vitamin D3 have been synthesized. Two alternative synthetic routes were devised for preparation of the required A-ring synthons, starting from the chiral compound derived from the (-)-quinic acid and, alternatively, from the commercially available achiral precursor, monoprotected 1,4-cyclohexanedione. The A-ring dienynes were coupled by the Sonogashira process with the respective C,D-ring fragments, the enol triflates derived from the protected (20R)- or (20S)-25-hydroxy Grundmann ketones. All four compounds possessed significant in vivo activity on bone calcium mobilization and intestinal calcium transport. The presence of a 2-methylene group increased intestinal calcium transport activity of all four analogues above that of the native hormone, 1α,25-dihydroxyvitamin D3. In contrast, bone calcium mobilization was equal to that produced by 1α,25-dihydroxyvitamin D3 in compounds having a (20S)-configuration or diminished to one-tenth that of 1α,25-dihydroxyvitamin D3 in compounds with a (20R)-configuration.

Homochiral imidazole-based dicarboxylate metal complexes with SrSi2 topology: synthesis, crystal structures, and properties

Two new complexes with homochiral frameworks, {Co3(EIDC)2(H2O)5}n (1) and {Zn3(EIDC)2(H2O)4}n (2) (H3EIDC = 2-ethyl-1H-imidazole-4,5-dicarboxylic acid), have been synthesized from achiral starting precursors via spontaneous resolution and fully characterized by elemental analyses, IR, circular dichroism, photoluminescence (PL) spectroscopy, single-crystal X-ray diffraction, and thermogravimetric analysis. X-ray diffraction data revealed that 1 and 2 have SrSi2 topologies and that both are homochiral metal–organic frameworks. Compound 1 is constructed by left-handed chiral chains; however, right-handed chains constitute the homochiral framework of 2. Variable temperature magnetic susceptibility measurements of 1 indicate strong antiferromagnetic interactions between the magnetic Co centers. Compound 2 exhibited weak blue PL in the solid state at room temperature.

A combination of the "pillaring" strategy and chiral induction: an approach to prepare homochiral three-dimensional coordination polymers from achiral precursors.

Utilizing enantiopure camphorsulfonic acid as a chiral induction agent, 3D homochiral complexes were obtained from achiral 2D layers and MoO4(2-) pillars. This methodology combines the "pillaring" strategy with chiral induction, providing a new way to synthesize homochiral 3D coordination polymers intentionally from achiral precursors.

Recent Developments in Gene Chemistry

The recent adavancement in the field of nucleic acid, nucleotide, and nucleoside has revolutionized modern day biological and chemical research. The knowledge of synthetic chemistry is essential to prepare modified nucleic acids as potent therapeutic agents and as tools for molecular biology. On the other hand with the help of combinatorial chemistry nucleic acid/peptide libraries are generated and then specific members are enriched and mutated to obtain the most promising chiral catalyst for achieving the desired asymmetric transformations which include regio- and stereoselective transformations of achiral precursors in typical carbon-carbon bond forming and DNAphosphorylation reactions.

Hydrothermal Synthesis and Characterization of a Novel 3D Chiral Inorganic-Organic Hybrid Cadmium(II) Framework With Achiral 1,4-Naphthalenedicarboxylic Acid Ligand

Using the achiral 1,4-naphthalenedicarboxylic acid (H2L) ligand and corresponding cadmium(II) salts, under hydrothermal conditions, a novel 3D chiral inorganic-organic hybrid complex with the formula [Cd(μ6-L)(DMF)]n has been isolated and characterized by single-crystal X-ray diffraction, FT-IR, TGA, and luminescent analysis. The crystal crystallizes in the chiral space group P212121, a = 6.7180(10) Å, b = 13.507(2) Å, c = 15.229(2) Å, Z = 4, the flack parameter is near zero (–0.02(4)). Two kinds of 1D infinite right-handed Cd-O-Cd helical chains can be observed, which are further interlinked into 1D infinite Cd-O-Cd linkage in a unique arrangement way. Solid-state luminescent spectrum of 1 also has been investigated indicating the strong emission band centered at 494 nm upon excitation at 370 nm. The result also represents a good example of the construction of those chiral inorganic-organic hybrid frameworks containing infinite M-O-M linkage using the achiral precursor. Supplementary materials are available for this article. Go to the publisher's online edition of Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry to view the supplemental file.