Rh-Catalyzed Desymmetrization of ?-Quaternary Centers by Isomerization-Hydroacylation.
ABSTRACT: We describe a Rh-catalyzed desymmetrization of all-carbon quaternary centers from ?,?-bis(allyl)aldehydes by a cascade featuring isomerization and hydroacylation. This desymmetrization competes with two other novel olefin functionalizations that are triggered by C-H bond activation, including carboacylation and bisacylation. A BIPHEP ligand promotes enantioselective formation of ?-vinylcyclopentanones. Mechanistic studies support irreversible and enantioselective olefin-isomerization followed by olefin-hydroacylation.
Project description:Enantioselective syntheses of (-)-alloyohimbane and (-)-yohimbane was accomplished in a convergent manner. The key step involved a modified mild protocol for the enantioselective enzymatic desymmetrization of meso-diacetate. The protocol provided convenient access to an optically active monoacetate in multi-gram scale in high enantiomeric purity. This monoacetate was converted to (-)-alloyohimbane. Reductive amination of the derived aldehyde causes the isomerization leading to the trans-product and allows the synthesis of (-)-yohimbane.
Project description:We report a dynamic kinetic resolution (DKR) of chiral 4-pentenals by olefin hydroacylation. A primary amine racemizes the aldehyde substrate via enamine formation and hydrolysis. Then, a cationic rhodium catalyst promotes hydroacylation to generate ?,?-disubstituted cyclopentanones with high enantio- and diastereoselectivities.
Project description:A general protocol for the hydroacylation of styrenes from aliphatic carboxylic acids is reported. These reactions proceed via ?-scission of a phosphoranyl radical that is accessed by photoredox catalysis, followed by addition of the resulting acyl radical to the styrenyl olefin. We show that phosphine tunability is critical for efficient intermolecular coupling due to competitive quenching of the photocatalyst by the olefin. Primary, secondary, and structurally rigid tertiary carboxylic acids all generate valuable unsymmetrical dialkyl ketones.
Project description:Tandem olefin metathesis sequences are known to be versatile for the generation of natural product scaffolds and have also been used for ring opening of strained carbo- and heterocycles. In this paper we demonstrate the potential of these reactions for the desymmetrization of 7-azabicycloalkenes.We have established efficient protocols for the desymmetrization of different 7-azabicycloalkenes by intra- and intermolecular tandem metathesis sequences with ruthenium based catalysts.Desymmetrization of 7-azabicycloalkenes by olefin metathesis is an efficient process for the preparation of common natural product scaffolds such as pyrrolidines, indolizidines and isoindoles.
Project description:Ex-changing places: a highly enantioselective desymmetrization of 1,2-diols has been developed in which the catalyst utilizes reversible covalent bonding to the substrate to achieve both high selectivity and rate acceleration (see scheme, PMP=pentalmethylpiperidine, TBS=tert-butyldimethylsilyl). Induced intramolecularity is responsible for the enhanced rate, thus allowing the reaction to be performed at room temperature.
Project description:The enantioselective desymmetrization of carboxylic acids by chiral Brønsted base catalysis is reported, leading to bridged bicyclic lactones with up to 94% ee. Crystallographic analysis of a substrate-catalyst complex suggests an origin of stereocontrol, reminiscent of functional Brønsted bases in biological settings, and enabled reaction optimization. The products contain an all-carbon quaternary stereocenter and can be derivatized to functionalized cyclopentanes.
Project description:The desymmetrization of meso-compounds is a useful synthetic method, as illustrated by numerous applications of this strategy in natural product synthesis. Cu-catalyzed allylic desymmetrizations enable the enantioselective formation of carbon-carbon bonds, but these transformations are limited in substrate scope and by the use of highly reactive premade organometallic reagents at cryogenic temperatures. Here we show that diverse meso-bisphosphates in combination with alkylzirconium nucleophiles undergo highly regio-, diastereo- and enantio-selective Cu-catalyzed desymmetrization reactions. In addition, C2-symmetric chiral bisphosphates undergo stereospecific reactions and a racemic substrate undergoes a Cu-catalyzed kinetic resolution. The reaction tolerates functional groups incompatible with many common organometallic reagents and provides access to a broad range of functionalized carbo- and hetero-cyclic structures. The products bear up to three contiguous stereogenic centers, including quaternary centers and spirocyclic ring systems. We anticipate that the method will be a useful complement to existing catalytic enantioselective reactions.
Project description:In this work we developed C(2)-symmetric chiral nucleophilic catalysts which possess a pyrrolidinopyridine framework as a catalytic site. Some of these organocatalysts effectively promoted asymmetric desymmetrization of meso-diols via enantioselective acylation.
Project description:The rhodium-catalyzed enantioselective desymmetrization of symmetric ?,?-unsaturated amides via carbonyl-directed catalytic asymmetric hydroboration (directed CAHB) affords chiral secondary organoboronates with up to 98% ee. The chiral ?-borylated products undergo palladium-catalyzed Suzuki-Miyaura cross-coupling via the trifluoroborate salt with stereoretention.
Project description:A highly enantioselective method for desymmetrization of meso-epoxides using thiols is reported. This is the first example of epoxide activation achieved using metal BINOL phosphates. The reaction has a broad scope in terms of epoxide substrates and aromatic thiol nucleophiles. The resulting ?-hydroxyl sulfides are obtained in excellent yield and enantioselectivity.