Asymmetric Catalysis Of The Key Intermediate And Their Derivatives Of Indoxacarb

Indoxacarb is an highly efficient pesticide with low toxicity developed by DuPont.(S)-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylic acid ester has been identified as the key intermediate for the synthesis of chiral insecticide Indoxacarb.The catalytic enantioselective hydroxylation of prochiralβ-keto esters represents the most straightforward and efficient strategy for the synthesis of enantioenrichedα-hydroxyβ-keto esters.With the aim of development efficient and highly enantioselective hydroxylation catalyst,in this thesis our strategy is the design and synthesis of a series of salan ligands,the corresponding Zr(IV)-salan complexes were used in the catalyticα-hydroxylation ofβ-keto esters.The details are as follows:1、By using(1S,2S)-1,2-diaminocyclohexane,(1S,2S)-1,2-diphenylethylenediamine or L-prolinamide as the chiral source,a series of salan ligands were prepared through the reduction amination between chiral diamine and salicylaldehyde derivatives.2、The corresponding Zr(IV)-salan complexes were prepared and investigated in enantioselective hydroxylation ofβ-keto esters.By using 5.0 mol%catalyst,(S)-5-Chloro-2-hydroxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylic acid ester,which is the key intermediate for the synthesis of chiral agrochemical Indoxacarb,was obtained in 99%yield and 99%ee under room temperature,to the best of our knowledge,this result represents the best yield and enantioselectivity reported so far for this important molecule.3、Spectroscopic methods including high resolution mass spectrometry(HRMS)and ~1H NMR,nonlinear effect as a mechanistic probe and product analysis combined with DFT calculations were employed to gain mechanistic insights into the hydroxylation ofβ-keto ester by Zr(IV)-salan complex and cumene hydroperoxide.We have shown that(1)a Zr(IV)-salan complex was generated in stiu as the active catalyst responsible for the chiral induction,(2)the amine hydrogen atom(s)on the salan ligands was indispensable which could activate alkyl hydroperoxides through hydrogen bonding,the formation of hydrogen bond would also be helpful in stabilizing the stereo-controlled transition state,controlling the enantioselectivity and improving the reactivity.and(3)the cumene hy-droperoxide attack the enolate form of theβ-keto ester accompanying a heterolytic O-O bond cleavage pathway.