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Rational perturbation of the fluorescence quantum yield in emission-tunable and predictable fluorophores (Seoul-Fluors) by a facile synthetic method involving C-H activation.

Choi EJ, Kim E, Lee Y, Jo A, Park SB - Angew. Chem. Int. Ed. Engl. (2014)

Bottom Line: Herein, we report a facile synthesis of emission-tunable and predictable Seoul-Fluors, 9-aryl-1,2-dihydrolopyrrolo[3,4-b]indolizin-3-ones, with various R(1) and R(2) substituents by coinage-metal-catalyzed intramolecular 1,3-dipolar cycloaddition and subsequent palladium-mediated CH activation.We also showed that the quantum yields of Seoul-Fluors are controlled by the electronic nature of the substituents, which influences the extent of photoinduced electron transfer.On the basis of this understanding, we demonstrated our design strategy by the development of a Seoul-Fluor-based chemosensor 20 for reactive oxygen species that was not accessible by a previous synthetic route.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry/Bio-MAX Institute, Seoul National University, Seoul 151-747 (Korea).

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Synthesis of lactam‐embedded indolizine core structures. The yields given are for the isolated product after four steps. [a] Ag2O was used to catalyze the 1,3‐dipolar cycloaddition. [b] [AuPPh3Cl] was used as a catalyst; DDQ was added for the oxidative aromatization. Boc=tert‐butoxycarbonyl.
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sch2: Synthesis of lactam‐embedded indolizine core structures. The yields given are for the isolated product after four steps. [a] Ag2O was used to catalyze the 1,3‐dipolar cycloaddition. [b] [AuPPh3Cl] was used as a catalyst; DDQ was added for the oxidative aromatization. Boc=tert‐butoxycarbonyl.

Mentions: We first introduced terminal alkynes instead of olefins to overcome the limited substrate scope of pyridine‐based dipoles and facilitated the 1,3‐dipolar cycloaddition of the terminal alkyne with the resulting azomethine ylide by the use of a coinage‐metal catalyst.6 This approach enabled the synthesis of Seoul‐Fluors containing diverse R2 substituents. To optimize the synthesis conditions for the lactam‐embedded indolizine core, we prepared the secondary amine 1 through a substitution reaction of propargyl amine with Boc‐protected 3‐bromopropan‐1‐amine. The resulting amine 1 was acylated with bromoacetyl bromide and treated with pyridine derivatives to generate pyridinium intermediates (Scheme 2). Without purification, the resulting pyridinium ion was converted by treatment with 1,8‐diazabicycloundec‐7‐ene (DBU) into an azomethine ylide, which underwent intramolecular [3+2] cycloaddition with the terminal acetylene. The tricyclic adducts underwent spontaneous aromatization to give lactam‐embedded indolizines 2–7 and 9 without the addition of oxidants, such as 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ), which was required in the previous synthetic method.4 In the case of the electron‐rich dimethylaminopyridine, we failed to synthesize the desired indolizine core by our previous method because of the inherently low reactivity of the electron‐rich dipole. However, we succeeded in synthesizing the cyclized adduct 8 with a dimethylamino group by a new synthetic route in the presence of chloro(triphenylphosphine)gold(I) as a catalyst. The addition of a catalytic amount of silver(I) oxide also improved the yield of the 1,3‐dipolar cycloaddition for pyridines containing weakly electron donating R2 substituents (products 6 and 7) or isoquinoline (product 9). Therefore, this new synthetic route not only expands the range of possible R2 substituents, but also improves the efficiency of the synthesis of Seoul‐Fluors. Under these conditions, we were able to synthesize lactam‐embedded indolizine cores with various R2 substituents.


Rational perturbation of the fluorescence quantum yield in emission-tunable and predictable fluorophores (Seoul-Fluors) by a facile synthetic method involving C-H activation.

Choi EJ, Kim E, Lee Y, Jo A, Park SB - Angew. Chem. Int. Ed. Engl. (2014)

Synthesis of lactam‐embedded indolizine core structures. The yields given are for the isolated product after four steps. [a] Ag2O was used to catalyze the 1,3‐dipolar cycloaddition. [b] [AuPPh3Cl] was used as a catalyst; DDQ was added for the oxidative aromatization. Boc=tert‐butoxycarbonyl.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4279899&req=5

sch2: Synthesis of lactam‐embedded indolizine core structures. The yields given are for the isolated product after four steps. [a] Ag2O was used to catalyze the 1,3‐dipolar cycloaddition. [b] [AuPPh3Cl] was used as a catalyst; DDQ was added for the oxidative aromatization. Boc=tert‐butoxycarbonyl.
Mentions: We first introduced terminal alkynes instead of olefins to overcome the limited substrate scope of pyridine‐based dipoles and facilitated the 1,3‐dipolar cycloaddition of the terminal alkyne with the resulting azomethine ylide by the use of a coinage‐metal catalyst.6 This approach enabled the synthesis of Seoul‐Fluors containing diverse R2 substituents. To optimize the synthesis conditions for the lactam‐embedded indolizine core, we prepared the secondary amine 1 through a substitution reaction of propargyl amine with Boc‐protected 3‐bromopropan‐1‐amine. The resulting amine 1 was acylated with bromoacetyl bromide and treated with pyridine derivatives to generate pyridinium intermediates (Scheme 2). Without purification, the resulting pyridinium ion was converted by treatment with 1,8‐diazabicycloundec‐7‐ene (DBU) into an azomethine ylide, which underwent intramolecular [3+2] cycloaddition with the terminal acetylene. The tricyclic adducts underwent spontaneous aromatization to give lactam‐embedded indolizines 2–7 and 9 without the addition of oxidants, such as 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ), which was required in the previous synthetic method.4 In the case of the electron‐rich dimethylaminopyridine, we failed to synthesize the desired indolizine core by our previous method because of the inherently low reactivity of the electron‐rich dipole. However, we succeeded in synthesizing the cyclized adduct 8 with a dimethylamino group by a new synthetic route in the presence of chloro(triphenylphosphine)gold(I) as a catalyst. The addition of a catalytic amount of silver(I) oxide also improved the yield of the 1,3‐dipolar cycloaddition for pyridines containing weakly electron donating R2 substituents (products 6 and 7) or isoquinoline (product 9). Therefore, this new synthetic route not only expands the range of possible R2 substituents, but also improves the efficiency of the synthesis of Seoul‐Fluors. Under these conditions, we were able to synthesize lactam‐embedded indolizine cores with various R2 substituents.

Bottom Line: Herein, we report a facile synthesis of emission-tunable and predictable Seoul-Fluors, 9-aryl-1,2-dihydrolopyrrolo[3,4-b]indolizin-3-ones, with various R(1) and R(2) substituents by coinage-metal-catalyzed intramolecular 1,3-dipolar cycloaddition and subsequent palladium-mediated CH activation.We also showed that the quantum yields of Seoul-Fluors are controlled by the electronic nature of the substituents, which influences the extent of photoinduced electron transfer.On the basis of this understanding, we demonstrated our design strategy by the development of a Seoul-Fluor-based chemosensor 20 for reactive oxygen species that was not accessible by a previous synthetic route.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry/Bio-MAX Institute, Seoul National University, Seoul 151-747 (Korea).

Show MeSH