Copper-Catalyzed Conjugate Addition of Carbonyls as Carbanion Equivalent via Hydrazones

Abstract

Copper-catalyzed conjugate addition is a classic method for forming new carbon−carbon bonds. However, copper has never showed catalytic activity for umpolung carbanions in hydrazone chemistry. Herein, we report a facile conjugate addition of hydrazone catalyzed by readily available copper complexes at room temperature. The employment of mesitylcopper(I) and electron-rich phosphine bidentate ligand is a key factor affecting reactivity. The reaction allows various aromatic hydrazones to react with diverse conjugated compounds to produce 1,4-adducts in yields of about 20 to 99%.

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

“…Of note,c opper was recently demonstrated to be ac ompetent catalyst in the hydrazone Michael addition chemistry above. [61] Carbon dioxide (CO 2 )i sr apidly gaining interest as aC 1 unit, and its reaction with Grignard reagents represents one of the classic ways to make carboxylic acids.A mong various efforts in exploring CO 2 fixation for fine-chemical synthesis, Yu,L an and Li et al collaboratively disclosed as treamlined synthesis of arylacetic acids by simply exposing either aldehyde (9.18 to 9.21)orketone (9.22 and 9.23)hydrazones to CO 2 atmosphere with as lightly altered Ru-catalysis protocol (Scheme 9C). [62] In addition to the activated double-bond electrophiles, nonpolar olefins were also amenable in the domain of hydrazone addition reactions.Inearly 2020, an anti-Markovnikov conjugate addition of hydrazones to terminal olefins was successfully implemented, introducing av ast array of highly functionalized alkyl fragments to 1,3-dienes (9.24 and 9.25)and 1,3-enynes (9.26 to 9.28,S cheme 9D).…”

“…In many cases, Ru showed similar catalytic performance to Fe ( 9.1 , 9.2 , 9.6 and 9.7 ); however, the former could deliver a broader reaction scope, especially when handling hydrazones derived from non‐aromatic precursors ( 9.11 , 9.13 to 9.17 ). Of note, copper was recently demonstrated to be a competent catalyst in the hydrazone Michael addition chemistry above [61] …”

Copper-Catalyzed Intramolecular Aldehyde–Ketone Nucleophilic Additions for the Synthesis of Chromans Bearing a Tertiary Alcohol Motif

“…Recently, Li and co-workers have successfully developed Umpolung strategy for metal catalyzed carbonyl (including aromatic aldehyde, aliphatic aldehydes, and aromatic ketone) derived hydrazones and achieved ruthenium or iron catalyzed intermolecular nucleophilic addition of hydrazones to carbonyl compounds in good yields (Scheme e). This strategy has not been employed in intramolecular additions of the challenging dicarbonyl compounds, which derive two types of hydrazones and greatly increase the difficulty of the intramolecular reaction.…”

Regiospecific deoxygenative deuteration of ketones via HOME chemistry

“…Inspired by the classical Wolff–Kishner reduction, 12 our group recently pioneered a conceptual design of using hydrazones as organometallic equivalents (HOME), 13 in which various classical reactions based on organometallic reagents such as nucleophilic addition, 14 conjugate addition, 15 and cross-coupling 16 reactions have been accomplished by this strategy without using stoichiometric organometallic reagents. 17 In addition, we recently reported a ruthenium-catalyzed deoxygenation for ketones, 18 in which the selective cleavage of C–O double bonds proceeds via the Wolff–Kishner type reduction but under mild conditions.…”