Study On The Asymmetric Synthesis Of 3-Amino Disubstituted Oxindoles

As a core structure of many natural products and bioactive compounds, oxindoles have become one of the most heated topics for synthetic chemists and pharmacologists in recent years. Optical 3-amino disubstituted oxindoles, which is one important kind of 3,3’-disubstituted oxindoles, have been considered a lot in pharmaceutical research. However comparing with other types of 3,3’-disubstituted oxindoles, there are still fewer related research about them.We developed a zinc-mediated addition of methyl and terminal alkynes to chiral N-tert-butanesulfinyl ketimines in mild conditions and obtained methylation and alkynylation products in high yields and good to excellent diastereoselectivities. Subsequent convenient cleavage of sulfinyl protecting group under acid environment can provide 3-amino disubstituted oxindoles directly.Besides, we first synthesized 3-((N-Boc)-imido)-oxindoles and accomplished the addition of 1,3-dicarbonyl compounds to these imines.We also carried out an asymmetric Strecker reaction using TMSCN as CN-source. Both methods offered 3-(N-Boc)-3-disubstituted oxindole in high yields and good to excellent stereoselectivities. The latter products could be converted into acyl amides and amino acid methl esters with oxindole as the core via further elaboration.These methods we developed not only are important complements to the strategies of asymmetric syntheses for 3-amino disubstituted oxindoles, but also provide compounds having potential values in the fields of drug screening and syntheses of unnatrural amino acids and natural products or analogues with complex structures.