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The development of reliable approaches to construct enantioenriched cyclic ketones bearing multiple stereocenters has attracted intense interest in synthetic chemistry, yet remains a challenging research area due to the difficulties in efficiently controlling the reaction enantioselectivity and diastereoselectivity. Desymmetrization of C2‐symmetric prochiral substrates has witnessed a practical and accessible strategy for creating more than one stereocenters in a single operation. In recent years, enantioselective desymmetrization of 1,3‐dicarbonyl compounds has been developed via transition‐metal‐catalyzed transformations for facile assembly of optically active cyclic ketones bearing congested stereocenters with diverse functionality. In this review, we would like to describe intramolecular enantioselective desymmetrization reactions of 1,3‐dicarbonyl derivatives, including C2‐functional group tethered 1,3‐diketones and 1,3‐diesters. This review is organized according to types of tethered groups, which aims to highlight the recent advances and briefly discuss about future perspectives in this domain. [ABSTRACT FROM AUTHOR]

A silver-catalyzed dearomative decarboxylative [3+2] spiroannulation of aryl oxamic acids with alkynes is described. The reaction provides reliable access to a range of azaspiro[4,5]trienones in moderate yields in aqueous media. In addition, the reaction exhibits a broad substrate scope and good functional group compatibility. [ABSTRACT FROM AUTHOR]

Highly enantioselective palladium-catalyzed dearomative reductive Heck reaction and domino Heck–Suzuki reaction of 2-CF3-indoles have been developed. Using Pd(OAc)2/(R)-Synphos as the catalyst and Et3SiH as a hydride source, a variety of indolines bearing a 2-trifluoromethyl quaternary stereocenter were obtained via a dearomative reductive Heck reaction. Alternatively, using Pd(dba)2/phosphoramidite as the catalyst and Ar4BNa as a coupling partner, structurally diverse indolines containing two vicinal carbon stereocenters were afforded through the domino dearomative Heck–Suzuki reaction. [ABSTRACT FROM AUTHOR]

Summary of main observation and conclusion: An enantioselective desymmetric nucleophilic α‐addition of cyclohexanone to propiolamide has been developed through a 6‐exo‐dig cyclization reaction. By employing simple and readily available L‐proline sodium salt as a bifunctional catalyst, a series of chiral 6,6‐bicyclic bridged products bearing morphan scaffold have been isolated in good yields and excellent enantioselectivities. Density functional theory (DFT) calculations elucidated the origins of the enantioselectivity and regioselectivity of this transformation. A salt bridge that links the amide carbonyl group with proline carboxylate in the transition state was proven to be the driving force for the induction of excellent enantioselectivity. A new enantioselective approach to morphan core is developed based on the desymmetric intramolecular α‐addition of cyclohexanone to propiolamide, which represents a new method for asymmetric ketone α‐vinylation reaction. α‐Carbonyl tertiary stereocenter is formed without racemization due to its unique bridged bicyclic structure. A very simple and readily available catalyst L‐Pro‐Na is used for this reaction. [ABSTRACT FROM AUTHOR]

Herein, a cobalt-catalyzed intramolecular enantioselective reductive Heck reaction is disclosed. Starting from N - ortho -iodoaryl-2-(trifluoromethyl)acrylamides, a plethora of chiral oxindoles bearing trifluoromethylated quaternary stereogenic centers at the C3-position are achieved in moderate to good yields (up to 88% yield) and good to excellent enantioselectivities (up to 94% ee) by employing zinc/silane as reducing agent. Other than the trifluoromethyl group, a number of chiral oxindoles bearing alkyl, aryl, and ester groups at C3-position were also obtained albeit in relatively lower enantioselectivities (68-78% ee).

An enantioselective copper-catalyzed 1,2-arylboration reaction of enamines has been developed by employing ( R )-xyl-BINAP as a chiral ligand. A number of chiral borate-containing 3,3'-disubstituted isoindolinones were obtained in moderate to good yields and good to excellent enantioselectivities from the reactions of N -( o -iodobenzoyl)enamines and bis(pinacolato)diboron (B 2 pin 2 ) under mild reaction conditions. Synthetic transformations of the products were conducted to demonstrate the practicality of this reaction.

Highly enantioselective palladium-catalyzed dearomative reductive Heck reaction and domino Heck-Suzuki reaction of 2-CF 3 -indoles have been developed. Using Pd(OAc) 2 /( R )-Synphos as the catalyst and Et 3 SiH as a hydride source, a variety of indolines bearing a 2-trifluoromethyl quaternary stereocenter were obtained via a dearomative reductive Heck reaction. Alternatively, using Pd(dba) 2 /phosphoramidite as the catalyst and Ar 4 BNa as a coupling partner, structurally diverse indolines containing two vicinal carbon stereocenters were afforded through the domino dearomative Heck-Suzuki reaction.

The extensively developed ene-type enantioselective cycloisomerization of classical 1,n-enynes provides an efficient approach to chiral cyclic 1,4-dienes. In contrast, the catalytic asymmetric heteroarenyne (heteroarene-alkyne) cycloisomerization involving the dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH-catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne-tethered indole substrates (formal 1,5- and 1,6-enynes). Based on this strategy, a variety of structurally diverse chiral spiro and fused indoline derivatives bearing quaternary stereocenters and exocyclic C=C bonds are afforded in moderate to excellent yields and excellent enantioselectivities (up to 98 % ee). The classical ene-type enantioselective 1,5-enyne cycloisomerization of N-vinylpropiolamides is also developed to afford chiral 2-pyrrolones in good to excellent ee values., (© 2021 Wiley-VCH GmbH.)