On the Lewis acid catalyzed cyclocondensation of silyloxydienes with .alpha.,.beta.-unsaturated aldehydes

Kerwin, James F.

doi:10.1021/jo00137a035

Cited by 41 publications

(12 citation statements)

References 2 publications

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“…[37][38][39] It has previously been employed in the synthesis of encoded libraries. 40 A heterocycle-forming variant is the aza-Diels-Alder reaction of imines with Danishefsky's diene 41,42 which has been used as a key step in the synthesis of e.g. natural productinspired libraries and in diversity-oriented synthesis.…”

Section: Development Of a Zncl 2 -Mediated Aza-diels-alder Reaction Omentioning

confidence: 99%

“…Based on the original report of Danishefsky et al using ZnCl 2 (ref. 41) as the catalyst we started our investigation of the aza-Diels-Alder reaction on CPG-coupled DNA. We initiated the imine formation of hexT-aldehyde conjugate 11 with 500 equivalents of aniline 12a in tetrahydrofuran/triethyl orthoformate (TEOF) for four hours followed by the addition of 500 equivalents of Danishefsky's diene 13 and 50 equivalents of ZnCl 2 .…”

Section: Development Of a Zncl 2 -Mediated Aza-diels-alder Reaction Omentioning

confidence: 99%

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Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions

et al. 2019

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Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions DNA-encoded compound libraries are a widely used technology for target-based small molecule screening. Initiating encoded compound synthesis with solid phase -coupled DNA barcodes does benefi t from choice of organic solvents. Screening of more than 50 metal salts and organic reagents for DNA compatibility suggested reactions for encoded compound synthesis. A ZnCl2-mediated aza-Diels-Alder reaction with Danishefsky's diene and diphenyl phosphate-promoted tetrahydroquinoline and pyrimidinone syntheses by Povarov and Biginelli reactions, respectively, showed a broad substrate scope and were well tolerated by a DNA oligonucleotide.DNA-encoded compound libraries are a widely used technology for target-based small molecule screening. Generally, these libraries are synthesized by solution phase combinatorial chemistry requiring aqueous solvent mixtures and reactions that are orthogonal to DNA reactivity. Initiating library synthesis with readily available controlled pore glass-coupled DNA barcodes benefits from enhanced DNA stability due to nucleobase protection and choice of dry organic solvents for encoded compound synthesis. We screened the compatibility of solid-phase coupled DNA sequences with 53 metal salts and organic reagents. This screening experiment suggests design of encoded library synthesis. Here, we show the reaction optimization and scope of three sp 3 -bond containing heterocyclic scaffolds synthesized on controlled pore glass-connected DNA sequences. A ZnCl 2 -promoted aza-Diels-Alder reaction with Danishefsky's diene furnished diverse substituted DNA-tagged pyridones, and a phosphoric acid organocatalyst allowed for synthesis of tetrahydroquinolines by the Povarov reaction and pyrimidinones by the Biginelli reaction, respectively. These three reactions caused low levels of DNA depurination and cover broad and only partially overlapping chemical space though using one set of DNA-coupled starting materials. † Electronic supplementary information (ESI) available: Synthesis and additional tables for screening experiments, reaction optimization experiments and reaction scope. Copies of HPLC traces and MALDI-MS spectra are shown for all discussed DNA conjugates. See a For each: 20 nmol DNA, 200 equiv. (transition) metal salt or organocatalyst A-H, 50 mL dry solvent, r.t., 22 h. b 50 mL of the indicated aqueous acid. c 5 equiv. of metal salt were used. hexT 7 ¼ 5 0 -AcN-(CH 2 ) 6 -TTT TTT-3 0 -CPG, TC 8 ¼ 5 0 -TTC CTC TCC T-3 0 -CPG, ATC 9 ¼ 5 0 -TTA CTA CCT A-3 0 -CPG, ATGC 10 ¼ 5 0 -GTC ATG ATC T-3 0 -CPG, ACN ¼ acetonitrile, MeOH ¼ methanol. This journal is View Article Online c 1000 equiv. of amine 12 were used. d Yb(OTf) 3 was used instead of ZnCl 2 . e The 2 nd step of the reaction was performed overnight at 35 C. 10mer ATGC ¼ 5 0 -GTC ATG ATC T-3 0 , ACN ¼ acetonitrile. This journal isFig. 7 Cheminformatics analysis: A ¼ PCA plot of the DA-1(red), P (blue) and B (green) lib...

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Section: Development Of a Zncl 2 -Mediated Aza-diels-alder Reaction Omentioning

confidence: 99%

Section: Development Of a Zncl 2 -Mediated Aza-diels-alder Reaction Omentioning

confidence: 99%

Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions

et al. 2019

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“…Finally, the direct catalytic reductive cycloaddition of amides with Danishefsky's diene ( 6 ) was investigated. The established reaction conditions consist of the iridium‐catalyzed partial reduction of 1 t in CH 2 Cl 2 , switching the solvent to MeOH, and treating the presumed imine intermediate with anhydrous ZnCl 2 and Danishefsky's diene ( 6 ).…”

Section: Figurementioning

confidence: 99%

Iridium‐Catalyzed Reductive Alkylations of Secondary Amides

Han

et al. 2018

Angewandte Chemie

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Reported herein is the first direct, metal‐catalyzed reductive functionalization of secondary amides to give functionalized amines and heterocycles. The method is shown to have exceptionally broad scope with respect to suitable nucleophiles, which cover both hard and soft C nucleophiles as well as a P nucleophile. The reaction exhibits good chemoselectivity and tolerates several sensitive functional groups.

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“…Unfortunately, the endo/exo ratio (4:1) and yield (30%) remained unchanged. In 1986, Smith and co-workers disclosed the first total synthesis of the diterpenes (+)-jatropholone A (26) and B (27) by employing a high-pressure-induced Diels-Alder reaction to fuse the six-membered ring of the core jatropholone skeleton (Scheme 3). 15 Starting from pyrrolidine enamine 17, hydroxy diketone 19 was prepared in two steps.…”

Section: Scheme 1 Synthesis Of Cantharidin (4) By Daubenmentioning

confidence: 99%

“…Rewardingly, pressurizing (5 kbar) a neat, equimolar mixture of diene 20 and cycloheptenone 23 at ambient temperature for three days afforded the endo-Diels-Alder adduct 24 possessing the requisite regiochemistry of the jatropholone skeleton in high yield (80%). Six further transformations of the core structure, including methylation and desilylation of ketone 25, afforded the epimeric natural products (+)-jatropholone A (26) and B (27). Schmidt and co-workers reported the synthesis of 33, the bottom half of chlorothricolide (34) which is the aglycon of the macrolide antibiotic chlorothricin (Scheme 4).…”

Section: Scheme 1 Synthesis Of Cantharidin (4) By Daubenmentioning

confidence: 99%

High-Pressure Transformations in Natural Product Synthesis

Hugelshofer

Magauer

2014

Synthesis

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This review summarizes the application of high-pressure chemistry in natural product synthesis. By highlighting reactions that could not be promoted by conventional means but that proceed readily under high-pressure conditions, we intend to disclose the benefits of high-pressure-mediated reactions for organic transformations. The individual syntheses are classified by the reaction type of the key step and are discussed briefly.

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On the Lewis acid catalyzed cyclocondensation of silyloxydienes with .alpha.,.beta.-unsaturated aldehydes

Cited by 41 publications

References 2 publications

Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions

Screening of metal ions and organocatalysts on solid support-coupled DNA oligonucleotides guides design of DNA-encoded reactions

Iridium‐Catalyzed Reductive Alkylations of Secondary Amides

High-Pressure Transformations in Natural Product Synthesis

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