Parallel Synthesis of Tamoxifen and Derivatives on Solid Support via Resin Capture

Brown, Steven W.; Rw, Armstrong

doi:10.1021/jo9711807

Cited by 107 publications

(35 citation statements)

References 15 publications

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“…[344] They separated cis-diol 88 from cis/trans mixtures using polystyrene resin 90 functionalized with boronic acid groups (Scheme 60). [346] Aronov and Gelb described a procedure to ™catch∫ alcohols and ™release∫ amines (Scheme 62). Separation of cis-diols from a cis/trans mixture.…”

Section: Catch-and-releasementioning

confidence: 99%

Modern Separation Techniques for the Efficient Workup in Organic Synthesis

Tzschucke

Märkert

Bannwarth

et al. 2002

Angew. Chem. Int. Ed.

339

133

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The shift of paradigm in combinatorial chemistry, from large compound libraries (of mixtures) on a small scale towards defined compound libraries where each compound is prepared in an individual well, has stimulated the search for alternative separation approaches. The key to a rapid and efficient synthesis is not only the parallel arrangement of reactions, but simple work-up procedures so as to circumvent time-consuming and laborious purification steps. During the initial development stages of combinatorial synthesis it was believed that rational synthesis of individual compounds could only be achieved by solid-phase strategies. However, there are a number of problems in solid-phase chemistry: most notably there is the need for a suitable linker unit, the limitation of the reaction conditions to certain solvents and reagents, and the heterogeneous reaction conditions. Further disadvantages are: the moderate loading capacities of the polymeric support and the limited stability of the solid support. In the last few years several new separation techniques have been developed. Depending on the chemical problem or the class of compounds to be prepared, one can choose from a whole array of different approaches. Most of these modern separation approaches rely on solution-phase chemistry, even though some of them use solid-phase resins as tools (for example, as scavengers). Several of these separation techniques are based on liquid-liquid phase separation, including ionic liquids, fluorous phases, and supercritical solvents. Besides being benign with respect to their environmental aspects, they also show a number of advantages with respect to the work-up procedures of organic reactions as well as simplicity in the isolation of products. Another set of separation strategies involves polymeric supports (for example, as scavengers or for cyclative cleavage), either as solid phases or as soluble polymeric supports. In contrast to solid-phase resins, soluble polymeric supports allow reactions to be performed under homogeneous conditions, which can be an important factor in catalysis. At the same time, a whole set of techniques has been developed for the separation of these soluble polymeric supports from small target molecules. Finally, miscellaneous separation techniques, such as phase-switchable tags for precipitation by chemical modification or magnetic beads, can accelerate the separation of compounds in a parallel format.

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Section: Catch-and-releasementioning

confidence: 99%

Modern Separation Techniques for the Efficient Workup in Organic Synthesis

Tzschucke

Märkert

Bannwarth

et al. 2002

Angew. Chem. Int. Ed.

339

133

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“…Scheme 14 illustrates a more recent example of product phase-switching in the synthesis of a tamoxifen array library. 61 Solution-phase Suzuki reaction of the alkenyl bis-boronates 76 with a variety of aryl halides led to the formation of the desired mono-aryl products 77 plus contaminating deboronated products and bis-aryl coupled products. Only the desired mono aryl products 77 containing a remaining boronate ester could be phase-switched to a polymer-bound aryl iodide 78.…”

Section: Scheme 12mentioning

confidence: 99%

Phase-trafficking reagents and phase-switching strategies for parallel synthesis

Flynn

1999

Med. Res. Rev.

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“…[8] Armstrong has developed an alkyne diboration/crosscoupling sequence for the synthesis of tamoxifen derivatives. [9] However, new synthetic schemes that allow more flexible structural modifications of the aryl groups, which are believed to be important (essential) for antiestrogenic activity, are still in high demand.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Carbometalation/Cross‐Coupling Sequence across Alkynyl(2‐pyridyl)silanes Leading to a Diversity‐Oriented Synthesis of Tamoxifen‐Type Tetrasubstituted Olefins

2004

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A general synthetic scheme for tamoxifentype tetrasubstituted olefins based on the novel Cucatalyzed carbomagnesation across alkynyl(2-pyridyl)silane has been developed. A wide array of electronically and structurally diverse tetrasubstituted olefins can be prepared in a regiocontrolled, stereocontrolled, and diversity-oriented manner. Noteworthy features are that (i) the three aryl groups, which are believed to be important (essential) for anti-estrogenic activity, can be varied at will because they all stem from readily available aryl iodides, and (ii) any stereo-and regioisomers can, in principle, be prepared by simply changing the order use of the aryl iodides in the sequence.

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Parallel Synthesis of Tamoxifen and Derivatives on Solid Support via Resin Capture

Cited by 107 publications

References 15 publications

Modern Separation Techniques for the Efficient Workup in Organic Synthesis

Modern Separation Techniques for the Efficient Workup in Organic Synthesis

Phase-trafficking reagents and phase-switching strategies for parallel synthesis

Catalytic Carbometalation/Cross‐Coupling Sequence across Alkynyl(2‐pyridyl)silanes Leading to a Diversity‐Oriented Synthesis of Tamoxifen‐Type Tetrasubstituted Olefins

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