Herein, we report a practical two‐step synthetic route to α‐arylpyrrolidines through Suzuki–Miyaura cross‐coupling and enantioselective copper‐catalyzed intramolecular hydroamination reactions. The ...excellent stereoselectivity and broad scope for the transformation of substrates with pharmaceutically relevant heteroarenes render this method a practical and versatile approach for pyrrolidine synthesis. Additionally, this intramolecular hydroamination strategy facilitates the asymmetric synthesis of tetrahydroisoquinolines and medium‐ring dibenzo‐fused nitrogen heterocycles.
An enantioselective copper‐catalyzed intramolecular hydroamination reaction can be used jointly with the Suzuki–Miyaura cross‐coupling to yield a diverse array of α‐arylpyrrolidine scaffolds that contain pharmaceutically relevant heteroarenes with excellent enantiomeric purity under mild conditions. Furthermore, this intramolecular hydroamination strategy is applicable to the asymmetric syntheses of six‐ to nine‐membered benzo‐fused nitrogen heterocycles.
Conjugate addition of carbon nucleophiles to electron‐deficient olefins is one of the most powerful methods for forming carbon–carbon bonds. Despite great achievements in controlling the selectivity, ...variation of the carbon nucleophiles remains largely underexplored, with this approach relying mostly on organometallic reagents. Herein, we report that naturally abundant carbonyls can act as latent carbon nucleophiles for conjugate additions through a ruthenium‐catalyzed process, with water and nitrogen as innocuous byproducts. The key to our success is homogeneous ruthenium(II) catalysis, combined with phosphines as spectator ligands and hydrazine as the reducing agent. This chemistry allows the incorporation of highly functionalized alkyl fragments into a vast array of electron‐deficient olefins under mild reaction conditions in a reaction complementary to the classical organometallic‐reagent‐based conjugate additions mediated or catalyzed by “soft” transition metals.
Hidden talents: Carbonyls can act as latent carbon nucleophiles for conjugate additions through a ruthenium‐catalyzed process. The reaction relies on homogeneous ruthenium(II) catalysis combined with phosphines as spectator ligands and hydrazine as the reducing agent. This method enables the incorporation of highly functionalized alkyl fragments into a vast array of electron‐deficient olefins under mild reaction conditions. EWG=electron‐withdrawing grop
Umpolung Addition of Aldehydes to Aryl Imines Chen, Ning; Dai, Xi‐Jie; Wang, Haining ...
Angewandte Chemie International Edition,
May 22, 2017, Volume:
56, Issue:
22
Journal Article
Peer reviewed
Open access
One of the classical ways to synthesize amines involves the coupling of carbonyl compounds and imines, either through enolate chemistry or acyl‐based carbanion equivalents. We herein report an ...alternative strategy that is based on the use of aldehydes as alkyl carbanion equivalents in a reductive coupling with aryl imines. A wide array of secondary amines can be synthesized in moderate to high yields. This reaction is mediated by hydrazine and catalyzed by ruthenium(II) complexes, and it tolerates various functional groups, such as esters, amides, and nitriles.
Hydrazine mediates the reductive coupling of aldehydes and aryl imines in the presence of a ruthenium(II) precatalyst and a bidentate phosphine ligand. This alternative approach to amine synthesis involves aldehyde‐derived alkyl carbanion equivalents, enables the synthesis of a wide array of secondary amines in moderate to good yields, and tolerates various functional groups.
A highly regio- and enantioselective synthesis of 1,2-diamine derivatives from γ-substituted allylic pivalamides using copper-catalyzed hydroamination is reported. The N-pivaloyl group is essential, ...in both facilitating the hydrocupration step and suppressing an unproductive β-elimination from the alkylcopper intermediate. This approach enables an efficient construction of chiral differentially protected vicinal diamines under mild conditions with broad functional group tolerance.
Natural availability of carbonyl groups offers reductive carbonyl coupling tremendous synthetic potential for efficient olefin synthesis, yet the catalytic carbonyl cross-coupling remains largely ...elusive. We report herein such a reaction, mediated by hydrazine under ruthenium(ii) catalysis. This method enables facile and selective cross-couplings of two unsymmetrical carbonyl compounds in either an intermolecular or intramolecular fashion. Moreover, this chemistry accommodates a variety of substrates, proceeds under mild reaction conditions with good functional group tolerance, and generates stoichiometric benign byproducts. Importantly, the coexistence of KO
Bu and bidentate phosphine dmpe is vital to this transformation.
A palladium‐catalyzed direct β‐C−H arylation of ketones was developed under mild conditions in water, featuring commercially available arylboronic acids as nucleophilic aryl sources and ...o‐iodoxybenzoic acid as the oxidant. The method provides a concise route to access β‐arylated ketones. Preliminary studies indicated that direct asymmetric β‐C−H arylation of ketones could be achieved by this strategy.
Radical measures: A radical coupling reaction, which is proposed to proceed through in situ chlorination of a hydroxy group by Me3SiCl, is used to form quaternary carbon centers with amino groups in ...α position. The reaction can be scaled up and is used in an efficient six‐step total synthesis of (±)‐9,10‐diepi‐stemoamide (see scheme, Cp=cyclopentadienyl, EWG=electron‐withdrawing group).
Iridium‐catalyzed direct dehydroxylation of alcohols with hydrazine was developed through a combination of the oxidation of alcohols and the Wolff–Kishner reduction. This protocol is simple to ...perform and highly efficient for a series of primary, benzylic and allylic alcohols.
Iridium‐catalyzed direct dehydroxylation of alcohols with hydrazine is developed through a combination of the oxidation of alcohols and Wolff–Kishner reduction. This protocol is simple to perform and highly efficient for a series of primary alcohols, especially benzylic and allylic ones.
A long-standing scientific challenge in the field of alcohol deoxygenation has been direct catalytic sp3 C–O defunctionalization with high selectivity and efficiency, in the presence of other ...functionalities, such as free hydroxyl groups and amines widely present in biological molecules. Previously, the selectivity issue had been only addressed by classic multistep deoxygenation strategies with stoichiometric reagents. Herein, we propose a catalytic late-transition-metal-catalyzed redox design, on the basis of dehydrogenation/Wolff–Kishner (WK) reduction, to simultaneously tackle the challenges regarding step economy and selectivity. The early development of our hypothesis focuses on an iridium-catalyzed process efficient mainly with activated alcohols, which dictates harsh reaction conditions and thus limits its synthetic utility. Later, a significant advancement has been made on aliphatic primary alcohol deoxygenation by employing a ruthenium complex, with good functional group tolerance and exclusive selectivity under practical reaction conditions. Its synthetic utility is further illustrated by excellent efficiency as well as complete chemo- and regio-selectivity in both simple and complex molecular settings. Mechanistic discussion is also included with experimental supports. Overall, our current method successfully addresses the aforementioned challenges in the pertinent field, providing a practical redox-based approach to the direct sp3 C–O defunctionalization of aliphatic primary alcohols.
Chemistry has always had as a target the conversion of molecules into valuable materials. Nevertheless, the aim of past synthesis has primarily focused on achieving a given transformation, regardless ...of the environmental impact of the synthetic route. Given the current global situation, the demand for sustainable alternatives has substantially increased. Our group focuses on developing selective chemical transformations that benefit from mild conditions, improved atom economy, and that can make use of renewable feedstocks as starting materials. This account summarizes our work over the past two decades specifically regarding the selective removal, conversion, and addition of functional groups that can, later on, be applied at a late stage for the modification of complex molecules.
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