Organocatalytic Asymmetric Synthesis of Cyclic Compounds Bearing a Trifluoromethylated Stereogenic Center: Recent Developments

Abstract

The broad prospects of trifluoromethylated compounds in materials science, agricultural chemistry, and pharmaceutical chemistry have stimulated the rapid development of asymmetric organocatalytic transformations to access these biologically important compounds. Among all types of trifluoromethylated compounds, trifluoromethylated cyclic compounds with a C−CF3 stereogenic center have gained increasing attention in medicinal and organic chemistry because they are extensively found in many biologically active molecules, lead compounds, and listed drugs. This review attempts to summarize the developments in the organocatalytic asymmetric synthesis of cyclic compounds bearing a trifluoromethylated stereogenic center since 2012.magnified image

The Catalytic Asymmetric Construction of Trifluoromethylated Quaternary Carbon-Containing Thiochromans

“…In the field of pharmaceutical, agricultural, and synthetic chemistry, trifluoromethylated heterocyclic compounds have attracted a growing interest. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Because the introduction of trifluoromethyl group often enhanced the metabolic stability, lipophilicity, bioavailability, and binding selectivity of drug molecules. [35][36][37][38] Thus constructing optically active compounds incorporating both a trifluoromethyl moiety and a sulfur heterocyclic structure is biologically and synthetically useful, and still remains a challenge.…”

Asymmetric Fluorination Reactions promoted by Chiral Hydrogen Bonding‐based Organocatalysts

“…[12,14] However, in this review we are discussing asymmetric organocatalytic protocols focused on hydrogen bonding-based catalysts, such as (thio)ureas, [15] squaramides [16] chiral phosphoric acids [17] and chiral carboxylic acids [18] as the most representative chiral organocatalysts. [19] Although other reviews have covered many examples using some of these catalytic structures, [20] we are focusing our attention on those works in which direct fluorination takes place using a fluorinating agent, leaving aside the reactions where a fluorine atom is incorporated from the beginning as part of other reactants. With these statements in mind, we have been able to find a good number of essential examples in the literature catalyzed by these selected organocatalysts.…”

Diastereodivergent Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Ylides and β‐Fluoroalkyl Vinylsulfones: Low Copper(II) Catalyst Loading and Theoretical Studies

“…[5] Despite these tremendous advances,t he known synthetic methods still suffer from various problems,such as:1)high catalyst loading (at least 5mol %);2 )rarely using cheaper and more stable Cu II catalysts in contrast to Cu I catalysts; [6] 3) few examples of providing exo'-adducts as the major isomers; [7] 4) limited trifluomethylated starting materials. [8] In recent years,c onsiderable effort has been devoted to the asymmetric incorporation of fluorine atoms into organic molecules because such modifications can tune the physical, chemical, and biological properties of the corresponding nonfluorinated parent molecules. [9] Among various fluoroalkyl groups,t he trifluoromethyl group (CF 3 )h as received significant attention because of its similar size to the methyl group and its high electronegativity resulting in unique stereoelectronic properties,w hich may substantially increase the metabolic stability,l ipophilicity,a nd thus bioavailability of drug molecules.I ndeed, an umber of CF 3 -substituted pyrrolidines displaying interesting bioactivities have been reported, including the insecticide A, [10] suicide inhibitor B, [11] antibacterial agent C, [12] and hepatitis Cv irus inhibitor D [13] (Figure 1).…”