Synthesis of Arrays Using Low Molecular Weight MPEG-Assisted Mitsunobu Reaction

Figlus, Marek; Wellaway, Natalie; Cooper, Anthony W. J.; Sollis, Steven L.; Hartley, Richard C.

doi:10.1021/co100091n

Cited by 14 publications

(2 citation statements)

References 33 publications

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“…Multiple attempts to solve these problems have been reported . Phosphine‐containing resins allow easy separation of phosphine oxide side products by filtration and these could be regenerated by silanes, but a stable, easy separable and recyclable alternative to DEAD is an important goal. For example, Lipshutz and co‐workers reported di‐ p ‐chlorobenzylazodicarboxylate (DCAD), which in CH 2 Cl 2 generates a readily separable hydrazine byproduct .…”

Section: Resultsmentioning

confidence: 99%

Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction

Polezhaev

Maciulis

Chen

et al. 2016

Chemistry A European J

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Reaction of 3,6-disubstituted-1,2,4,5-tetrazines with water and PEt forms the corresponding 1,4-dihydrotetrazine and OPEt . Thus PEt , as a stoichiometric reductant, reduces water, and the resulting two reducing equivalents serve to doubly hydrogenate the tetrazine. A variety of possible initial interactions between electron-deficient tetrazine and electron-rich PR , including a charge transfer complex, were evaluated by density functional calculations which revealed that the energy of all these make them spectroscopically undetectable at equilibrium, but one of these is nevertheless suggested as the intermediate in the observed redox reaction. The relationship of this to the Mitsunobu reaction, which absorbs the components of water evolved in the conversion of alcohol and carboxylic acid to ester, with desirable inversion at the alcohol carbon, is discussed. This enables a modified Mitsunobu reaction, with tetrazine replacing EtO CN=NCO Et (DEAD), which has the advantage that dihydrotetrazine can be recycled to tetrazine by oxidation with O , something impossible with the hydrogenated DEAD. For this tetrazine version, a betaine-like intermediate is undetectable, but its protonated form is characterized, including by X-ray structure and NMR spectroscopy.

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Section: Resultsmentioning

confidence: 99%

Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction

Polezhaev

Maciulis

Chen

et al. 2016

Chemistry A European J

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“…There are also ongoing attempts to develop direct methods for the alkylation of amines with alcohols. Among them, there are development of the advanced reaction conditions for the well-known Mitsunobu reaction 49 that allows basic amine usage 50 and a novel Ru-based catalyst system for hydrogen borrowing reaction, proposed by GSK in 2009 51 . Therefore, it is not surprising, that representation of this reagent class on the market is comparable with secondary amines.…”

Section: Alkylation Agentsmentioning

confidence: 99%

A Close-up Look at the Chemical Space of Commercially Available Building Blocks for Medicinal Chemistry

Zabolotna

Volochnyuk

Ryabukhin

et al. 2021

J. Chem. Inf. Model.

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The ability to efficiently synthesize desired compounds can be a limiting factor for chemical space exploration in drug discovery. This ability is conditioned not only by the existence of well-studied synthetic protocols but also by the availability of corresponding reagents, so-called building blocks (BB). In this work, we present a detailed analysis of the chemical space of 400K purchasable BB. The chemical space was defined by corresponding synthons -fragments contributed to the final molecules upon reaction. They allow an analysis of BB physicochemical properties and diversity, unbiased by the leaving and protective groups in actual reagents. The main classes of BB were analyzed in terms of their availability, rule-of-two-defined quality, and diversity. Available BBs were eventually compared to a reference set of biologically relevant synthons derived from ChEMBL fragmentation, in order to illustrate how well they cover the actual medicinal chemistry needs. This was performed on a newly constructed universal generative topographic map of synthon chemical space, allowing to visualize both libraries and analyze their overlapping and library-specific regions.

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Catalytic Variants of Phosphine Oxide‐Mediated Organic Transformations

Marsden

2013

Sustainable Catalysis

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Synthesis of Arrays Using Low Molecular Weight MPEG-Assisted Mitsunobu Reaction

Cited by 14 publications

References 33 publications

Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction

Tetrazine Assists Reduction of Water by Phosphines: Application in the Mitsunobu Reaction

A Close-up Look at the Chemical Space of Commercially Available Building Blocks for Medicinal Chemistry

Catalytic Variants of Phosphine Oxide‐Mediated Organic Transformations

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