Z-Selective Hydrofunctionalization of Dienes

Olefins play a fundamental role in synthetic organic chemistry because they are useful building blocks that create molecules. However, geometry control (E- vs Z-) in olefin synthesis is of utmost importance because the olefin geometry has a tremendous impact on its physical, chemical and biological properties. Additionally, Z-olefins are less stable compared to their E-olefin counterparts; due to this difference, general methods to make olefins results in more cases of E-olefins production with relatively fewer Z-olefins caused by its instability. It has been reported that Z-olefins can be synthesized from dienes through a rhodium-catalyzed formate mediated transformation, with tolerance to several reducible functional groups.  With this successful method in hand, the focus is to make functionalized Z-alkenes while still maintaining tolerance to reducible functional groups under mild reaction conditions. Thus, this project presents the production of Z-olefins through rhodium-catalyzed hydrofunctionalization using the starting materials, dienes and aldehydes. This method requires an inert atmosphere and the reaction progress can be monitored by Nuclear Magnetic Resonance (NMR) using an internal standard to quantify the amount of product formed. In this process, it was observed that the starting material was consumed until more than 95% conversion. In addition, the possibility of using different dienes, such as diene esters and phenyl dienes, as well as different aldehydes could further broaden the scope of this method. The usefulness of this process can be applied to the production of complex molecules. For example, in the synthesis of a glucagon receptor antagonist, which is a drug that is used in the treatment of diabetes. Currently, there is a limited number of methods used to create Z-olefins; however, this proven procedure can be further implicated in other hydrofunctionalization experiments

Transition-Metal-Catalyzed Alkylations of Amines with Alkyl Halides: Photoinduced, Copper-Catalyzed Couplings of Carbazoles

N-alkylations of carbazoles with a variety of secondary and hindered primary alkyl iodides can be achieved by using a simple precatalyst (CuI) under mild conditions (0 °C) in the presence of a Brønsted base; at higher temperature (30 °C), secondary alkyl bromides also serve as suitable coupling partners. A Li[Cu(carbazolide)_2] complex has been crystallographically characterized, and it may serve as an intermediate in the catalytic cycle

Catalytic Asymmetric C-N Bond Formation: Phosphine-Catalyzed Intra- and Intermolecular γ-Addition of Nitrogen Nucleophiles to Allenoates and Alkynoates

Pin the amine on the gamma: A new method has been developed for the γ-addition of nitrogen nucleophiles to γ-substituted alkynoates or allenoates through intra- and intermolecular processes that are catalyzed by spirophosphine 1 (see scheme). An asymmetric version of this reaction affords enantioenriched pyrrolidines, indolines, and γ-amino-α,β-unsaturated carbonyl compounds

Stereodivergent, Multicomponent Metal-Catalyzed Couplings Generating Three Stereocenters: Combining Enantioselective Rh-Catalyzed Conjugate Addition and Ir-Catalyzed Allylic Alkylation

Stereodivergent dual catalysis has emerged as a powerful tool to selectively prepare all four stereoisomers in molecules containing two chiral centers from common starting materials. Most processes involve the use of two substrates, and it remains challenging to use dual catalyst approaches to generate molecules having three newly formed stereocenters with high diastereo- and enantioselectivity. Here we report a multicomponent, stereodivergent method for the synthesis of targets containing three contiguous stereocenters by the combination of enantioselective Rh-catalyzed conjugate addition and Ir-catalyzed allylic alkylation methodologies. Both cyclic and acyclic ,-unsaturated ketones undergo -arylation using aryl boron reagents to form an enolate nucleophile that can be subsequently allylated at the -position. The reactions proceed with generally >95% ee and with >90:10 dr. Epimerization at the -carbonyl center enables the preparation of any of the eight possible stereoisomers from common starting materials, as demonstrated for cyclohexanone products

Catalytic Enantioselective Benzylation Directly from Aryl Acetic Acids

The stability and wide availability of carboxylic acids make them valuable reagents in chemical synthesis. Most transition metal catalyzed processes using carboxylic acid substrates are initiated by a decarboxylation event that generates reactive carbanion or radical intermediates. Developing enantioselective methodologies relying on these principles can be challenging, as highly reactive species tend to react indiscriminately without selectivity. Furthermore, anionic or radical intermediates generated from decarboxylation can be incompatible with protic and electrophilic functionality, or groups that undergo trapping with radicals. We demonstrate that metal-catalyzed enantioselective benzylation reactions of allylic electrophiles can occur directly from aryl acetic acids. The reaction proceeds via a pathway in which decarboxylation is the terminal event, occurring after stereoselective carbon–carbon bond formation. The mechanistic features of the process enable enantioselective benzylation without the generation of a highly basic nucleophile. Thus, the process has broad functional group compatibility that would not be possible employing established protocols.<br /

Formic Acid Mediated Direct Z-Selective Reductive Coupling of Dienes and Aldehydes

We demonstrate that formic acid mediates the Rh-catalyzed, Z-selective coupling of dienes and aldehydes. The process is distinguished by broad tolerance towards reducible or electrophilic groups. Kinetic analysis suggests that generation of the catalytically active Rh-intermediate by ligand dissociation is the rate determining step. The rapid generation and trapping of Rh-allyl intermediates is key to preventing chain-walking isomerization events that plague related protocols. Insights gained through this study may have wider implications in selective metal-catalyzed hydrofunctionalization reactions.<br /

Phase Stability, Structural Evolution and Magnetic Properties of Sc(1-x)LuxVO3 (0.0 x 1.0).

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Catalytic Oxidative Benzylation of Amines Enabled by Direct Ionic Decarboxylation

We report a method for the decarboxylative alkylation of amines via the direct generation of a benzylic nucleophiles

Enantioselective Tertiary Electrophile (Hetero)Benzylation: Pd-Catalyzed Substitution of Isoprene Monoxide with Arylacetates

The enantioselective generation of quaternary carbon centers remains challenging but is of growing importance for the preparation of functional molecules. Transition metal catalyzed allylic alkylations of tertiary electrophiles have provided access to these substructures but remain generally incompatible with organometallic benzyl nucleophiles. In this study we demonstrate that electron-deficient arylacetates can serve as benzyl nucleophile surrogates to generate enantioenriched acyclic molecules containing a quaternary carbon center via a two-step substitution-decarboxylation process using isoprene monoxide. The reaction gives products typically in >90% ee using a commercially available catalyst system and tolerates an array of electron-withdrawing functional groups on the arylacetate moiety. The lactone intermediate generated by the initial substitution reaction can be used in further stereoselective transformations to prepare molecules with acyclic vicinal quaternary stereocenters

Enantio- and Z-Selective d-Hydroarylation of Aryldienes via Rh-Catalyzed Conjugate Addition

Metal-catalyzed enantioselective conjugate arylations of electron-poor alkenes are highly selective processes for C(sp2)–C(sp3) bond formation. d-Selective hydroarylations of electron-poor dienes are less well developed and reactions that deliver high enantioselectivity while giving single alkene isomer products are elusive. Here we report the Rh-catalyzed d-arylation of aryldienes that gives nearly exclusive Z-1,4-addition products (generally with >95:5 positional and geometrical selectivity). This remote functionalization provides access to chiral diarylated butenes from readily available precursors poised for further functionalization, including in the synthesis of bioactive molecules. Mechanistic studies suggest that protonolysis of a Rh-allyl intermediate generated by diene insertion into a Rh-aryl is the rate determining step and occurs by an inner-sphere proton transfer pathway