Traceless Linkers-Only Disappearing Links in Solid-Phase Organic Synthesis?

Bräse, Stefan; Dahmen, Stefan

doi:10.1002/1521-3765(20000602)6:11<1899::aid-chem1899>3.0.co;2-m

Cited by 90 publications

(38 citation statements)

References 17 publications

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“…The methyl‐substituted tetrahydroquinolines 2 were further hydrogenated to the decahydroquinolines. Gratifyingly, traceless cleavage10 of the chiral auxiliary occurred in the course of the reaction. Optimization of the reaction conditions showed Rh/C as a catalyst, acetic acid as solvent at 150 bar and elevated temperatures to be optimal.…”

Section: Methodsmentioning

confidence: 99%

“…Whereas the known hydrogenation methods are limited to the formation of 1,2,3,4‐tetrahydroquinolines mostly with a stereocenter in the 2‐position only, our method was demonstrated to work for building up stereocenters in the 5‐, 6‐, 7‐ and 8‐positions of the tetrahydroquinoline ring system. Furthermore, the auxiliary can be cleaved tracelessly10 in a second hydrogenation step, resulting in the formation of the corresponding decahydroquinolines with up to 99% ee , containing up to 4 stereocenters. The development of efficient hydrogenation methods for the asymmetric formation of heterocyclic compounds is ongoing in our laboratories.…”

Section: Methodsmentioning

confidence: 99%

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Diastereoselective Hydrogenation of Substituted Quinolines to Enantiomerically Pure Decahydroquinolines

2010

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Abstract:The stereoselective hydrogenation of auxiliary-substituted quinolines was used to build up saturated and partially saturated heterocycles. In a first step, the formation and diastereoselective hydrogenation of 2-oxazolidinone-substituted quinolines to 5,6,7,8-tetrahydroquinolines is reported. In this unprecedented process, stereocenters on the carbocyclic quinoline ring were formed with a dr of up to 89:11. Platinum oxide as a catalyst and trifluoroacetic acid as a solvent were found to be optimal for high levels of chemo-and stereoselectivity in this step. In a second hydrogenation step, the completely saturated decahydroquinolines with 4 newly formed stereocenters were obtained with enantioselectivities of up to 99%. Rhodium on carbon as a catalyst and acetic acid as a solvent gave the best results for this hydrogenation and allowed a traceless cleavage of the chiral auxiliary. Thus, this new method allows an efficient stereoselective synthesis of valuable 5,6,7,8-tetrahydro-and decahydroquinoline products.Keywords: asymmetric synthesis; chiral auxiliaries; decahydroquinolines; heterocycles; hydrogenation Enantiomerically pure saturated or partially saturated heterocyclic compounds are important building blocks and fragments of many biologically active compounds like coniine, the poisonous alkaloid of hemlock, or the multiply substituted Lycopodium alkaloids.[1] The asymmetric hydrogenation of heteroaromatic substrates presents an attractive strategy for their preparation and the last years have seen many significant contributions to this field.[2] For example, several different approaches have been reported for the asymmetric hydrogenation of pyridines: e.g., Charette et al. developed a highly selective Ir-catalyzed homogeneous hydrogenation of pyridine ylides, [3d] Zhang and Lei used a sequential combination of heterogeneous and homogeneous hydrogenation,[3c] Rueping et al. reported an organocatalytic approach employing chiral Brønsted acids, using a Hantzsch ester as the reducing agent.[3b] Whereas all these methods employ chiral, enantiomerically pure catalysts, Glorius et al. developed an efficient hydrogenation of chiral oxazolidinone-substituted pyridines using achiral heterogenous hydrogenation catalysts like Pd(OH) 2 /C.[3e,f] In this latter reaction, the auxiliary was cleaved under the reaction conditions and fully saturated piperidines with up to 4 newly formed stereocenters and high ees (85-98%) were obtained. Significantly more methods have been reported for the asymmetric (partial) hydrogenation of quinolines. Since the aromatic stabilization of the second aromatic ring in bicyclic aromatics is somewhat lower, hydrogenation of the annulated ring is significantly facilitated. Most of these methods employ homogeneous iridium, rhodium or ruthenium complexes of chiral ligands [4a-n] together with molecular hydrogen or, alternatively, chiral Brønsted acids as organocatalysts [4o,p] in transfer hydrogenations (Scheme 1). [2] However, despite these advances in the area of asymmetric hydrogena...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diastereoselective Hydrogenation of Substituted Quinolines to Enantiomerically Pure Decahydroquinolines

2010

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“…An interesting modification of the Richter reaction is the use of ortho-ethynyl-substituted phenyltriazenes, in which the triazine fragment acts as a masked diazonium cation, for cyclization [82,83]. This method of synthesis was used for the creation of combinatorial libraries [84]. An obvious advantage of this approach for the Richter reaction is the possibility of separating the diazotization and cyclization stages, which makes it possible to avoid side reactions.…”

Section: + +mentioning

confidence: 99%

Methods for the synthesis of cinnolines (review)

Vinogradova

Балова

2008

Chem Heterocycl Comp

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This review analyses the principal approaches to the synthesis of the cinnoline nucleus, used as synthetic precursors of arenediazonium salts, arylhydrazones, and arylhydrazines, and also reductive methods for the synthesis of polycondensed derivatives of cinnoline. The mechanisms of the transformations and the possibilities and limitations of the various methods are discussed. Special attention is paid to methods based on the cyclization of derivatives of arenediazonium salts, which have been developed substantially in recent years.

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“…This section will not attempt to replicate these, but rather illustrate the evolution of the concept of the diversity linker unit. [2,3,[9][10][11][12][13][14][15][16][17] Reflecting their genesis in solid-phase peptide and oligonucleotide synthesis, early linker units typically possessed a polar functional group (e.g. OH, NH 2 , CO 2 H, etc.)…”

Section: Linker Cleavage Strategies: An Overviewmentioning

confidence: 99%

“…[1] Alternatively, the cleavage with sodium methoxide gives the corresponding methyl ester 5, and this resembles a very simple and trivial example of diversity cleavage. [13] Scheme 3.…”

Section: Linker Cleavage Strategies: An Overviewmentioning

confidence: 99%

Diversity Linker Units for Solid‐Phase Organic Synthesis

Scott

Steel

2006

Eur J Org Chem

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In recent years an ever‐increasing number of traditional solution‐phase reactions have been adapted for solid‐phase organic synthesis (SPOS) because of the ease of application of solid‐phase techniques to combinatorial chemistry and high‐throughput screening. To accommodate the growing number of reactions being attempted on solid supports, new linker units continue to be reported in the literature. Linker units are typically grouped according to the functionality left at the “cleavage site” in the target molecule, and are normally classified as traditional (polar functionality remains following cleavage) or traceless (hydrogen residue left after cleavage) linkers. As the field continues to expand, however, more advanced linker units have been reported, which utilise the cleavage step in SPOS to incorporate additional diversity into target libraries. These linker units have been termed “diversity” or “multifunctional” linker units, and in this microreview we introduce this aspect of the field, giving representative examples indicating key stages of development including the linker units recently designed in our laboratory. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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Traceless Linkers-Only Disappearing Links in Solid-Phase Organic Synthesis?

Cited by 90 publications

References 17 publications

Diastereoselective Hydrogenation of Substituted Quinolines to Enantiomerically Pure Decahydroquinolines

Diastereoselective Hydrogenation of Substituted Quinolines to Enantiomerically Pure Decahydroquinolines

Methods for the synthesis of cinnolines (review)

Diversity Linker Units for Solid‐Phase Organic Synthesis

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