Abstract:Azido 18 F-arenes are important and versatile building blocks for the radiolabeling of biomolecules via Huisgen cycloaddition ("clickc hemistry") for positron emission tomography (PET). However,r outine access to such clickable agents is challenged by inefficient and/or poorly defined multistep radiochemical approaches.Ahigh-yielding direct radiofluorination for azido 18 F-arenes was achieved through the development of an ortho-oxygen-stabilizedi odonium derivative (OID). This OID strategy addresses an unmet n… Show more
“…2 , product 8 ) in 90% yield 68 . The remaining alkynyl group, after deprotection, undergoes triazole formation with benzyl azide 69 and isoquinolinone formation upon Rh-catalyzed C-H activation 70 to give triaryl fluoromethane products ( 9 , 10 ) with complete retention of optical purity. Fig.…”
Ynones are a unique class of structural motifs that show remarkable chemical versatility. Chiral ynones, particularly those possessing an α-stereogenic center, are highly attractive templates for structural diversification. So far, only very limited examples have been reported for asymmetric α-functionalization of ynones. Asymmetric double α-functionalization of ynones remains elusive. Here we describe a streamlined strategy for asymmetric α-difunctionalization of ynones. We developed a gold-catalyzed multicomponent condensation reaction from a simple ynone, an amine, and an electrophilic alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and isolable intermediate. This intermediate can undergo asymmetric fluorination catalyzed by a chiral phosphoric acid derivative. Chiral ynones with an α-quaternary carbon and containing a fluorine and an alkyne can be synthesized in high yield and high ee. The synthetic utility of this method is demonstrated by the synthesis of enantioenriched tri(hetero)arylmethyl fluorides.
“…2 , product 8 ) in 90% yield 68 . The remaining alkynyl group, after deprotection, undergoes triazole formation with benzyl azide 69 and isoquinolinone formation upon Rh-catalyzed C-H activation 70 to give triaryl fluoromethane products ( 9 , 10 ) with complete retention of optical purity. Fig.…”
Ynones are a unique class of structural motifs that show remarkable chemical versatility. Chiral ynones, particularly those possessing an α-stereogenic center, are highly attractive templates for structural diversification. So far, only very limited examples have been reported for asymmetric α-functionalization of ynones. Asymmetric double α-functionalization of ynones remains elusive. Here we describe a streamlined strategy for asymmetric α-difunctionalization of ynones. We developed a gold-catalyzed multicomponent condensation reaction from a simple ynone, an amine, and an electrophilic alkynylating reagent to generate a 1,2-dialkynyl enamine, a key stable and isolable intermediate. This intermediate can undergo asymmetric fluorination catalyzed by a chiral phosphoric acid derivative. Chiral ynones with an α-quaternary carbon and containing a fluorine and an alkyne can be synthesized in high yield and high ee. The synthetic utility of this method is demonstrated by the synthesis of enantioenriched tri(hetero)arylmethyl fluorides.
“…[ 18 F]3‐Fluorobenzaldehyde has been prepared in variable yield (7%‐52%) yield (Table , entry 3) . [ 18 F]3‐Fluorobenzyl azide (entry 4) and [ 18 F]4‐fluorobenzyl azide (entries 5‐7) have been prepared in good nonisolated yields. Isolated yields for the 4‐fluoro isomers ranged from low to moderate (entries 5‐7).…”
Over the last 2 decades or so, hypervalent iodine compounds, such as diaryliodonium salts and aryliodonium ylides, have emerged as useful precursors for labeling homoarenes and heteroarenes with no-carrier-added cyclotron-produced [ F]fluoride ion (t = 109.8 min). They permit rapid and effective radiofluorination at electron-rich as well as electron-deficient aryl rings, and often with unrestricted choice of ring position. Consequently, hypervalent aryliodine compounds have found special utility as precursors to various small-molecule F-labeling synthons and to many radiotracers for biomedical imaging with positron emission tomography. This review summarizes this advance in radiofluorination chemistry, with emphasis on precursor synthesis, radiofluorination mechanism, method scope, and method application.
“…[81,132,133,[135][136][137][138][139][140][141][142][143] It is noteworthy that [ 18 F]FPEB synthesized by the SCIDYm ethod was fully automated, thereby resulting in asubstantial improvement (3-10 fold) in the RCY and molar activity compared with the traditional S N Ar method. [81,132,133,[135][136][137][138][139][140][141][142][143] It is noteworthy that [ 18 F]FPEB synthesized by the SCIDYm ethod was fully automated, thereby resulting in asubstantial improvement (3-10 fold) in the RCY and molar activity compared with the traditional S N Ar method.…”
Positron emission tomography (PET) is a molecular imaging technology that provides quantitative information about function and metabolism in biological processes in vivo for disease diagnosis and therapy assessment. The broad application and rapid advances of PET has led to an increased demand for new radiochemical methods to synthesize highly specific molecules bearing positron-emitting radionuclides. This article provides an overview of commonly-used labeling chemistry in the examples of clinically relevant PET tracers, and highlights most recent development and breakthroughs over the past decade with focus on 11C, 18F, 13N, and 15O.
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