Asymmetric induction during electron transfer mediated photoreduction of carbonyl compounds: role of zeolites

Photochemistry of 17 aryl alkyl ketones included within cation exchanged zeolites has been examined. In solution five of the 17 ketones undergo intramolecular hydrogen abstraction reaction even in the presence of a chiral amine and the rest are photoreduced to the corresponding alcohol. Within zeolites all 17 ketones yielded in presence of a chiral amine, the corresponding alcohol as the major product. When a chiral amine was used as the coadsorbent within alkali ion exchanged zeolites, enantiomerically enriched alcohol was formed in all cases. The best chiral induction was obtained with phenyl cyclohexyl ketone (enantiomeric excess: 68%). 1H-13C Cross Polarization Magic Angle Spinning (CP-MAS) experiments, with a model ketone (perdeuterated acetophenone) and chiral amine (pseudoephedrine) included within MY zeolites, suggested that the cation brings the reactant and the chiral amine closer. The role of the cation in such a process is also revealed by the computation results. The results presented here highlight the importance of a supramolecular structure in forcing a closer interaction between a reactant and a chiral inductor that could be used to achieve asymmetric induction in photoproducts.     

Inducing Propeller Chirality in Triaryl Boranes with Chiral Amines

Stabilization of chiral propeller conformations in triaryl compounds is challenging due to generally low racemization barriers. Nonetheless, it was recently found that chiral conformational preferences can be induced to triaryl boranes by incorporating point-chiral alkylether chains to the aryl blades and subsequently locking the structure with ammonia. A four-point interaction, meaning that the cooperative effects of Lewis-adduct formation and three hydrogen bonds, was proposed as stabilizing mechanism. Herein, it was shown that three such strong interactions suffice to introduce a preferential propeller handedness. Although DFT calculations predict no noteworthy preferences for either P- or M-chiral propellers for some of the investigated triarylborane–amine adducts that were prepared with chiral primary amines, vibrational circular dichroism (VCD) spectroscopic characterizations revealed that there is indeed a measurable excess of one propeller handedness. Furthermore, the steric demand of the amine was found to play a key role in the induction process and especially in preventing blade rotations.     

Catalytic asymmetric epoxidation of cyclic enones

A highly enantioselective epoxidation of cyclic enones with hydrogen peroxide has been developed that is catalyzed by chiral primary amine salts.     

Asymmetric synthesis of axially chiral biaryls via desymmetrization of 2,2',6,6'-tetrahydroxybiphenyl using 1,4-Di-O-benzyl-L-threitol as a chiral template

Sequential etherification of 2,2',6,6'-tetrahydroxybiphenyl (1) with 1,4-di-O-benzyl-L-threitol under Mitsunobu conditions gives desymmetrized biphenyldiol 9 of S-axial chirality exclusively. Cyclization of 9 with 1,omega-dibromoalkanes followed by removal of the chiral auxiliary yields (S)-2,2'-biphenyldiols 14 with alkylenedioxy bridges at the 6 and 6' positions. (S)-6,6'-Dialkyl- and -diphenyldiols 20 are obtained in an efficient manner via Pd(0)-catalyzed cross-coupling of bis(triflate) derivative 17 with organozinc reagents. Bis(triflate) 17 also serves as an intermediate for asymmetric synthesis of axially chiral biphenyldicarboxylic acid 23, terphenylcarboxylic acid 28, lactone 26, and lactam 30.     

Highly Enantioselective Aldol Reactions between Acetaldehyde and Activated Acyclic Ketones Catalyzed by Chiral Primary Amines

Highly enantioselective cross‐aldol reactions between acetaldehyde and activated acyclic ketones are reported for the first time. Various acyclic ketones, such as saturated and unsaturated keto esters, reacted with acetaldehyde in the presence of a chiral primary amine and a Brønsted acid to afford optically enriched tertiary alcohols in good yields and with excellent enantioselectivities. Trifluoromethyl ketones were tolerable under the reaction conditions, thereby affording the trifluoromethyl carbinol in good‐to‐excellent yields and enantioselectivities. Structural modification of the chiral amines from the same chiral source switched the stereoselectivity of the products. The utility of aldol chemistry was demonstrated in the brief synthesis of functionally enriched δ‐lactones. Theoretical calculations on the transition‐state structure indicated that the protonated tertiary amine could effectively activate the carbonyl group of a keto ester to promote the addition process through hydrogen‐bonding interaction and, simultaneously, provide an appropriate attacking pattern for the approach of the keto ester to the enamine, which is formed from acetaldehyde and the chiral catalyst, on a particular face, resulting in high enantioselectivity.     

Combining multi-catalysis and multi-component systems for the development of one-pot asymmetric reactions: stereoselective synthesis of highly functionalized bicyclo[4.4.0]decane-1,6-diones

We have developed a direct amine/acid-catalyzed stereoselective hydrogenation of a variety of Wieland-Miescher (W-M) ketones, Hajos-Parrish (H-P) ketones and their analogs with organic hydrides (Hantzsch esters) as the hydrogen source. This astonishingly simple and biomimetic approach was used to construct highly functionalized chiral bicyclo[4.4.0]decane-1,6-diones in a diastereoselective fashion. This is an example of the development of a new technology by the combination of multiple catalysts and components in one pot to deliver highly functionalized chiral molecules.     

Isopropylidene glycerol hydrogen phthalate as a resolving agent: a study of its diastereomeric salts with (S)- and (R)-1-phenylethylamine

An insight into the mechanism of the highly efficient resolution of 1-phenylethylamine with enantiomerically pure isopropylideneglycerol hydrogen phthalate is provided by comparison of physicochemical and X-ray crystallographic data of the two diastereomeric salts formed by the amine with the S acid. In the nearly identical structures of these salts, the different disposition of the isopropylidene glycerol moiety stands out drawing attention to the critical role played by the chiral part of the acid in the discrimination between the amine enantiomers.     

Mechanisms and kinetics of noncatalytic ether reaction in supercritical water. 2. Proton-transferred fragmentation of dimethyl ether to formaldehyde in competition with hydrolysis

Noncatalytic reaction pathways and rates of dimethyl ether (DME) in supercritical water are determined in a tube reactor made of quartz according to liquid- and gas-phase 1H and 13C NMR observations. The reaction is studied at two concentrations (0.1 and 0.5 M) in supercritical water at 400 degrees C and over a water-density range of 0.1-0.6 g/cm3. The supercritical water reaction is compared with the neat one (in the absence of solvent) at 0.1 M and 400 degrees C. DME is found to decompose through (i) the proton-transferred fragmentation to methane and formaldehyde and (ii) the hydrolysis to methanol. Formaldehyde from reaction (i) is consecutively subjected to four types of redox reactions. Two of them proceed even without solvent: (iii) the unimolecular proton-transferred decarbonylation forming hydrogen and carbon monoxide and (iv) the bimolecular self-disproportionation generating methanol and carbon monoxide. When the solvent water is present, two additional paths are open: (v) the bimolecular self-disproportionation of formaldehyde with reactant water, producing methanol and formic acid, and (vi) the bimolecular cross-disproportionation between formaldehyde and formic acid, yielding methanol and carbonic acid. Methanol is produced through the three types of disproportionations (iv)-(vi) as well as the hydrolysis (ii). The presence of solvent water decelerates the proton-transferred fragmentation of DME; the rate constant is reduced by 40% at 0.5 g/cm3. This is caused by the suppression of low-frequency concerted motion corresponding to the reaction coordinate for the simultaneous C-O bond scission and proton transfer from one methyl carbon to the other. In contrast to the proton-transferred fragmentation, the hydrolysis of DME is markedly accelerated by increasing the water density. The latter becomes more important than the former in supercritical water at densities greater than 0.5 g/cm3.     

Remarkable Differences in Reactivity between Benzothiazoline and Hantzsch Ester as a Hydrogen Donor in Chiral Phosphoric Acid Catalyzed Asymmetric Reductive Amination of Ketones

Described herein are differences in behavior between a Hantzsch ester and a benzothiazoline as hydrogen donors in the chiral phosphoric acid catalyzed asymmetric reductive amination of ketones with p‐anisidine. The asymmetric reductive amination of ketones with a Hantzsch ester as a hydrogen donor provided the corresponding chiral amines exclusively, regardless of the structures of the ketones, whereas a similar transformation with a benzothiazoline provided chiral amines and p‐methoxyphenyl‐protected primary amines in variable yields, depending on the structures of both the ketones and benzothiazolines. Because a benzothiazoline has an N,S‐acetal moiety that is vulnerable to p‐anisidine, the primary amine can be formed through transimination of the benzothiazoline with p‐anisidine followed by reduction of the resulting aldimine with remaining benzothiazoline.     

From evolution to green chemistry: rationalization of biomimetic oxygen-transfer cascades

Thermodynamic electron-transfer potentials from biology textbooks elucidate the sequence of electron-transfer events in the respiratory chain in mitochondria. In this study, thermodynamic and kinetic oxygen-transfer potentials have been defined and predicted for oxidants and substrates using density functional theory, aiming to rationalize multiple oxygen-transfer events in chemical catalysis, particularly in current developments of the Sharpless dihydroxylation. Key transition states for competing mechanisms in a recent dihydroxylation method containing the olefin, osmium tetraoxide, methyltrioxorhenium(VII), a chiral tertiary amine, and the green terminal oxidant hydrogen peroxide have been investigated rigorously. The calculations show the amine to function as an oxygen-transfer mediator between rhenium peroxides and osma-2,5-dioxolanes, in addition to its role as a carrier of chiral information. Unique mechanistic and stereoelectronic patterns in this oxygen-transfer cascade explain the unexpected failure of reactivity predictions using simpler models such as Marcus theory.     

A tripeptide-like prolinamide-thiourea as an aldol reaction catalyst

A tripeptide-like prolinamide-thiourea catalyst with (S)-proline, (1S,2S)-diphenylethylenediamine and (S)-di-tert-butyl aspartate as building blocks provides the products of the reaction between ketones and aromatic aldehydes in high to quantitative yields and high stereoselectivities (up to 99:1 dr and 99% ee). Both the chiral centers of the diamine unit are essential, while the thiourea hydrogen originating from the amine and the amide hydrogen play a predominant role for the catalyst efficiency.     

Visible‐Light‐Promoted Asymmetric Cross‐Dehydrogenative Coupling of Tertiary Amines to Ketones by Synergistic Multiple Catalysis

Reported herein is an unprecedented photocatalytic asymmetric cross‐dehydrogenative coupling reaction between tertiary amines and simple ketones, and it proceeds by synergistic multiple catalysis with substoichiometric amounts of a hydrogen acceptor. This process is enabled by a simple chiral primary amine catalyst through the coupling of a catalytic enamine intermediate and an iminium cation intermediate in situ generated from tetrahydroisoquinoline derivatives by coupled Ru/Co catalysis.     

One‐Pot Synthesis of Chiral N‐Arylamines by Combining Biocatalytic Aminations with Buchwald–Hartwig N‐Arylation

The combination of biocatalysis and chemo‐catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral‐amine‐producing biocatalysts with a Buchwald–Hartwig cross‐coupling reaction, affording a variety of α‐chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual‐enzyme biocatalytic hydrogen‐borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.     

Hydrogen-bonded extended structure of the 1:3 adduct of a C3 symmetric cobalt(III) complex with a tripod-ligand involving three imidazolate groups and hydroquinone or resorcinol

The assembly reaction arising from hydrogen bonding between a chiral C3 symmetric cobalt(III) complex and a tripod-ligand involving three imidazolate groups [tris[2-(((2-methylimidazolato-4-yl)methylidene)amino)ethyl]amine]cobalt(III) and either hydroquinone or resorcinol gave the 1:3 adducts, with 3D extended structures showing the template effect of the complex.     

Liquid chromatographic enantiomer separation of racemic amine using chiral crown ether stationary phase

Direct enantioseparation of racemic amine, amino-thiophene-2-yl-acetonitrile (TAN), on chiral crown ether stationary phase [Crownpak CR (+)] is described in this study. The elution behavior and the effect of acid additives on resolution of racemic amine, TAN, is intensely investigated. Moreover, the chiral recognition mechanism in this specific system is proposed based on computational methods with the density functional theory. Diastereomeric complexation of the ammonium ion of racemic amine inside the cavity of chiral crown ether appears essential for the chiral discrimination. The pH of the mobile phase containing acid additives also acts as an important factor for the chiral recognition.     

A Structural Study of Tautomerism and Hydrogen-Bonding in Supramolecular Assemblies

The synthesis and X-ray structures of four new crystalline materials incorporating ’dimers’ assembled from two different units possessing complementary hydrogen bonding motifs are reported; namely, phthalimide and 3-iminoisoindolinone or 2-guanidinobenzimidazole (or selected methylated derivatives) and 2-guanidinobenzoxazole. The bonding within each dimer involves a triplet of hydrogen bonds. The extended supramolecular structures are compared with each other as well as with two related structures described previously. The effect of using complementary DAD/ADA motifs that are not symmetrical on the respective supramolecular structures is also examined as is the prospect of incorporating different tautomeric components into the supramolecular structures. The presence of a very short, proton-transferred hydrogen bond within the respective triplets is also discussed.     

One‐Pot Organocatalytic Asymmetric Synthesis of 3‐Nitro‐1,2‐dihydroquinolines by a Dual‐Activation Protocol

Generally, amine‐catalyzed enantioselective transformations rely on chiral enamine or unsaturated iminium intermediates. Herein, we report a protocol involving dual activation by an aromatic iminium and hydrogen‐bonding. An enantioselective aza‐Michael–Henry domino reaction of 2‐aminobenzaldehydes with nitroolefins has been developed through this protocol using primary amine thiourea catalysts to provide a variety of 3‐nitro‐1,2‐dihydroquinolines in moderate yields and with up to 90 % ee. The mechanism for the catalytic enantioselective reaction was confirmed by ESI mass spectrometric detection of the reaction intermediates. The products formed are substructures found in skeletons of important biological and pharmaceutical molecules.     

Deuterium isotope effect on 13C chemical shifts of tetrabutylammonium salts of Schiff bases amino acids

Deuterium isotope effects on 13C chemical shift of tetrabutylammonium salts of Schiff bases, derivatives of amino acids (glycine, L-alanine, L-phenylalanine, L-valine, L-leucine, L-isoleucine and L-methionine) and various ortho-hydroxyaldehydes in CDCl3 have been measured. The results have shown that the tetrabutylammonium salts of the Schiff bases amino acids, being derivatives of 2-hydroxynaphthaldehyde and 3,5-dibromosalicylaldehyde, exist in the NH-form, while in the derivatives of salicylaldehyde and 5-bromosalicylaldehyde a proton transfer takes place. The interactions between COO- and NH groups stabilize the proton-transferred form through a bifurcated intramolecular hydrogen bond.     

Ab initio study of hydrogen bonding and proton transfer in 3:1 FH:NH3 and FH:collidine complexes: structures and one- and two-bond coupling constants across hydrogen bonds

Ab initio EOM-CCSD calculations have been performed on 3:1 FH:NH3 complexes at their own optimized MP2/6-31+G(d,p) geometries and at the optimized geometries in the hydrogen-bonding regions of corresponding 3:1 FH:collidine complexes. The isolated gas-phase equilibrium 3:1 FH:NH3 complex has an open structure with a proton-shared Fa-Ha-N hydrogen bond, while the isolated equilibrium 3:1 FH:collidine complex has a perpendicular structure with an Fa-Ha-N hydrogen bond that is on the ion-pair side of proton-shared. The Fa-N coupling constant ((2h)J(Fa-N)) for the equilibrium 3:1 FH:NH3 complex is large and negative, consistent with a proton-shared Fa-Ha-N hydrogen bond; (2h)JFb-Fa is positive, reflecting a short Fb-Fa distance and partial proton transfer from Fb to Fa across the Fb-Hb-Fa hydrogen bond. In contrast, (2h)JFa-N has a smaller absolute value and (2h)JFb-Fa is greater for the 3:1 FH:NH3 complex at the equilibrium 3:1 FH:collidine geometry, consistent with the structural characteristics of the Fa-Ha-N and Fb-Hb-Fa hydrogen bonds. Coupling constants computed at proton-transferred 3:1 FH:collidine perpendicular geometries are consistent with experimental coupling constants for the 3:1 FH:collidine complex in solution and indicate that the role of the solvent is to promote further proton transfer from Fa to N across the Fa-Ha-N hydrogen bond, and from Fb to Fa across the two equivalent Fb-Hb-Fa hydrogen bonds. The best correlations between experimental and computed coupling constants are found for complexes with perpendicular proton-transferred structures, one having the optimized geometry of a 3:1 FH:collidine complex at an Fa-Ha distance of 1.80 A, and the other at the optimized 3:1 FH:collidine geometry with distances derived from the experimental coupling constants. These calculations provide support for the proposed perpendicular structure of the 3:1 FH:collidine complex as the structure which exists in solution.     

A new class of structurally rigid tricyclic chiral secondary amine organocatalyst: highly enantioselective organocatalytic Michael addition of aldehydes to vinyl sulfones

A new class of chiral secondary amine organocatalyst was rationally designed as an efficient catalyst to catalyze the elusive Michael addition of aldehydes to vinyl sulfones. High yield and excellent enantioselectivities could be obtained at room temperature without having to resort to high catalyst loading, anhydrous solvents, and low temperatures. Efficient control of enamine conformation and face shielding as well as the rigid nature of the tricyclic skeleton, with an inherent chiral pocket, provide a well-organized chiral environment to effect this elusive reaction efficiently.