Fluorine/fluoroalkyl 1, 3-diketone compound, and method for synthesizing multi-chiral compound with fluorine/alkyl fluorine quaternary carbon center by using same

Abstract

The invention relates to a method for synthesizing a multi-chiral compound with a fluorinated / fluoroalkyl quaternary carbon center by using fluorine / fluoroalkylated 1, 3-diketone as a prochiral substrate and application of the multi-chiral compound, and belongs to the field of chemical synthesis. According to the invention, an N-heterocyclic carbene organic small molecule catalyst is used for catalyzing 2-bromo unsaturated aldehyde and the prochiral 1, 3-diketone substrate to be subjected to a desymmetrical organic cascade reaction under a mild condition, and a spiro indole compound containing trifluoromethyl quaternary carbon and having five continuous chiral centers can be constructed at the same time. The method has good substrate universality, trifluoromethyl is replaced by fluorine atoms, difluoromethyl and monofluoromethyl, and the target product can be obtained with excellent yield and stereoselectivity. Preliminary tests show that the reported chiral spiro indole compound containing the fluorinated / fluoroalkylated quaternary carbon center has relatively good antibacterial activity and has the potential of being applied to industrial production.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a method for synthesizing polychiral compounds with fluorine / fluoroalkyl quaternary carbon centers using fluorine / fluoroalkylation of 1,3-diketone as a prochiral substrate and its application to the preparation of chiral A method for spiro indole compounds. Background technique [0002] Introducing fluorine atoms into the drug structure is a common method for new drug design. About 20%-25% of drug molecular structures contain fluorine. Common fluorine-containing functional groups include fluorine atom F, trifluoromethyl CF 3 , Difluoromethyl CF 2 H, a fluoromethoxy CH 2 F and other structures. Generally speaking, the introduction of fluorine atoms will change the lipophilicity, hydrogen bonding, metabolic stability, bioavailability, etc. of the compound. Asymmetric catalysis is the most important method for the preparation of chiral fluorides, which has received extensive at...

AI Technical Summary

Problems solved by technology

The most challenging of all chiral fluorinated molecular structures is the construction of fluorinated / fluorinated alkyl-containing quaternary carbon centers, in which the simultaneous construction of multiple chiral centers including fluorinated / fluoroalkylated quaternary carbon centers is complex Molecular structure is particularly important, but no effective solution has been reported so far. The development and synthesis of such compounds with complex stereostructures containing fluorine / fluoroalkyl quaternary carbon will provide new opportunities for the discovery and development of synthetic chemistry and fluorine-containing drugs. opportunity

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