Catalytic reductive desymmetrization of malonic esters

Diverse synthesis of α-tertiary amines and tertiary alcohols via desymmetric reduction of malonic esters

“…During this study and our previous exploration of ligand scaffolds 16 – 18 , prolinol- (e.g., L11 ), and pipecolinol-derived (e.g., L9 ) tetradentate ligands were found to give dominant hydrosilylation products of opposite configuration (Fig. 6 , 92 and 93 ).…”

“…Recently, we have accomplished the reductive desymmetrization of all-carbon- 16 , 17 and halogen-substituted 18 malonic esters using a series of dinuclear zinc complexes with a tetradentate ligand. It is envisioned that the inclusion of amino- and oxymalonic esters in this desymmetrization paradigm 19 , 20 would provide an expeditious and diverse synthesis of enantioenriched α-tertiary amines and tertiary alcohols, as these diester substrates ( 4 and 5 ) can be rapidly and modularly prepared from inexpensive amino-, bromo-, and ketomalonic esters ( 1 – 3 ) via facile substitution and addition reactions (Fig.…”

“…First, unlike inert alkyl and aryl groups, coordinating and/or acidic nitrogen/oxygen substituents can deactivate the bimetallic catalyst containing both a Lewis acidic and Brønsted basic zinc center 21 . Second, as the enantioselection of the desymmetrization boils down to the size difference between two α-substituents, a pair of carbon substituents of dinstinct sizes (e.g., phenyl vs methyl) were often prerequisite for a highly stereoselective hydrosilylation to quaternary stereocenters 16 , 17 . Comparably, a wide scope of amino- and oxymalonic esters would require catalysts to accommodate heteroatom substituents of diverse shapes and sizes, such as ethers, amides, and alkyl amines, to contrast different carbon sidechains (i.e., small carbon vs large heteroatom substituents and vice versa).…”

Gold‐Catalyzed Desymmetric Lactonization of Alkynylmalonic Acids Enabled by Chiral Bifunctional P,N ligands

“…Desymmetrization [26] of α,α‐disubstituted malonic acid derivatives is an efficient strategy to access quaternary stereocenters. Very recently, Huang and co‐workers applied this strategy in zinc‐catalyzed desymmetric hydrosilylation of malonic esters (Figure 2c) [27] . In our previous work, we reported the cyclization of dialkynoic acids with an achiral gold catalyst to synthesize spiro lactones [28] .…”

“…Very recently, Huang and co-workers applied this strategy in zinc-catalyzed desymmetric hydrosilylation of malonic esters (Figure 2c). [27] In our previous work, we reported the cyclization of dialkynoic acids with an achiral gold catalyst to synthesize spiro lactones. [28] To the best of our knowledge, the desymmetric lactonization of alkynylmalonic acids has not been reported.…”