233277-18-4Relevant academic research and scientific papers
Catalytic reductive desymmetrization of malonic esters
Xu, Pengwei,Huang, Zhongxing
, p. 634 - 642 (2021)
Desymmetrization of fully substituted carbons with a pair of enantiotopic functional groups is a practical strategy for the synthesis of quaternary stereocentres, as it divides the tasks of enantioselection and C?C bond formation. The use of disubstituted malonic esters as the substrate of desymmetrization is particularly attractive, given their easy and modular preparation, as well as the high synthetic values of the chiral monoester products. Here, we report that a dinuclear zinc complex with a tetradentate ligand can selectively hydrosilylate one of the carbonyls of malonic esters to give α-quaternary β-hydroxyesters, providing a promising alternative to the desymmetric hydrolysis using carboxylesterases. The asymmetric reduction features excellent enantiocontrol that can differentiate sterically similar substituents and high chemoselectivity towards the diester motif of substrates. Together with the versatile preparation of malonic ester substrates and post-reduction derivatization, the desymmetric reduction has enabled the synthesis of a diverse array of quaternary stereocentres with distinct structural features. [Figure not available: see fulltext.]
A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides
Huang, Zhongxing,Low, Kam-Hung,Zhang, Suihan,Zheng, Yin,Zi, Weiwei
, p. 1951 - 1961 (2022/02/09)
Enantioenriched tertiary alkyl halides are prevalent in bioactive molecules and can serve as versatile synthetic intermediates to construct complex structures. While conventional access to these motifs often hinges on stereoselective carbon-halogen or carbon-carbon bond formation reactions, desymmetric approaches using halogenated and prochiral tetrasubstituted carbons are largely elusive in comparison. Here, we report that a suite of dinuclear zinc catalysts with a prolinol- or pipecolinol-derived tetradentate ligand can reductively desymmetrize a large collection of easily available halomalonic esters to α-halo-β-hydroxyesters. These polyfunctionalized tertiary alkyl fluorides, chlorides, and bromides proved to be useful intermediates toward fluorinated drug analogs and polyhalogenated monoterpenes. The facile intramolecular epoxidation of the chiral chloride and bromide products has also enabled expeditious access to natural products containing tertiary alcohol motifs.
Chemoenzymatic synthesis of 2-substituted 2-fluoro-1,3-dioxygenated chiral building blocks
Narisano, Enrica,Riva, Renata
, p. 1223 - 1242 (2007/10/03)
A series of 2-substituted-2-fluoro-1,3-dioxygenated chiral building blocks are synthesized via a chemoenzymatic route using either (i) lipase catalyzed monohydrolysis of suitably functionalized malonic diesters, or (ii) lipase catalyzed monoacetylation of suitably functionalized 1,3-propanediols.
Lipase mediated preparation of differently protected homochiral 2-aryl- 2-fluoro-1,3-propanediols
Guanti, Giuseppe,Narisano, Enrica,Riva, Renata
, p. 1859 - 1862 (2007/10/03)
Lipase mediated asymmetric monohydrolysis of 2-aryl-2-fluoromalonic acid diesters or monoacetylation of 2-aryl-2-fluoro-1,3-propanediols affords chiral fiuorinated polyfunctionalized C3 synthons in excellent enantiomeric excess and acceptable chemical yields.
