Phosphorus‐Containing Superbases: Recent Progress in the Chemistry of Electron‐Abundant Phosphines and Phosphazenes

Weitkamp, Robin F.; Neumann, Beate; Stammler, Hans‐Georg; Hoge, Berthold

doi:10.1002/chem.202101065

Cited by 37 publications

(28 citation statements)

References 240 publications

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“…No significant amount of ODN could be detected with RP HPLC. Using the stronger nonnucleophilic phosphazene base P2-Et [23] under similar conditions, no ODN was detected either. Therefore, we were confident to conclude that Dmoc linker and protecting group have to be oxidized before they can be cleaved with non-nucleophilic bases such as potassium carbonate and DBU.…”

Section: Ce-medmoc Phosphoramidites For Odn Synthesismentioning

confidence: 97%

aDim-aDmoc Protection for ODN Synthesis Allows Deprotection under Non-nucleophilic and Nearly Neutral Conditions

Chillar

Eriyagama

Yin

et al. 2022

Preprint

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Over a hundred non-canonical nucleotides have been found in DNA and RNA. Many of these modified nucleotides are sensitive toward nucleophiles and bases. Because known solid phase DNA and RNA synthesis technologies require strongly nucleophilic and basic conditions for deprotection and cleavage, there is no technology for the synthesis of DNAs and RNAs containing these sensitive nucleotides. The Dim-Dmoc technology has been developed to overcome the challenge. With Dim-Dmoc protection, oligodeoxynucleotide (ODN) deprotection has be achieved with sodium periodate oxidation followed by β-elimination induced by the weak base aniline. Some sensitive groups have been shown to be stable under the deprotection conditions. Besides serving as a base, aniline also serves as a nucleophilic scavenger for the side products of Dim-Dmoc deprotection, which prevents the side products from reacting with the deprotected ODN. For this reason, excess aniline is needed. In this article, we report the use of alkyl Dim (aDim) and alkyl Dmoc (aDmoc) protecting groups for ODN synthesis. With aDim-aDmoc protection, deprotection is demonstrated to be achievable with sodium periodate oxidation followed by the non-nucleophilic base potassium carbonate at pH 8. No scavenger for the side products of deprotection is needed. Over 10 ODNs with length ranging from 10-mer to 23-mer were synthesized, and importantly, the ODNs could be easily purified with RP HPLC. It was further demonstrated that the highly sensitive N4-acetylcytidine nucleoside could survive the oxidative deprotection conditions, and ODNs containing this sensitive nucleotide could be readily synthesized and purified without the need of any special cautions. Work on extending the method for the synthesis of sensitive RNAs such as those containing the biologically important ac4C is in progress.

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Section: Ce-medmoc Phosphoramidites For Odn Synthesismentioning

confidence: 97%

aDim-aDmoc Protection for ODN Synthesis Allows Deprotection under Non-nucleophilic and Nearly Neutral Conditions

Chillar

Eriyagama

Yin

et al. 2022

Preprint

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“…Phosphazenes are a family of non-ionic organic superbases that have been known to promote a wide variety of chemical transformation. [34][35][36][37][38][39][40][41] P1-t Bu is not the strongest base in this family but it was chosen as the catalyst of choice for this study due to its simple structure, relatively low costs and good tolerance to air and moisture. 34,36,39 Bulkier phosphazenes were considered unsuitable for this initial study, as the steric bulks of their structures render the imino nitrogen centres very poor s-Lewis donors, 41 but we will not rule them out of future investigations.…”

Section: Scheme 1 Catalytic 11-diboration Of Terminal Alkynesmentioning

confidence: 99%

Organosuperbase Catalyzed 1,1-Diboration of Alkynes

Doan

Ton

Khanh

et al. 2022

Preprint

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1,1-diboryl alkenes are versatile building blocks in organic synthesis and medicinal chemistry. There have been only a small number of established methods to prepare this class of compounds and most of them used transition metal catalysts, which are undesirable in the preparation of bioactive compounds. Herein, we report an unprecedented application of P1-tBu as an organocatalyst to promote 1,1-diboration reactions of unactivated aromatic as well as electron-deficient terminal alkynes. The strong basicity of this phosphazene enables the activation of reaction substrates while its steric bulk allows for high regio- and stereo-selectivity to be obtained. A combination of experimental and computational studies suggests interesting mechanistic insights for these phosphazene-catalyzed diboration reaction, which are also discussed in detail.

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“…58 A review of electron-abundant phosphines and phosphazenes as superbases was published very recently, highlighting the attractiveness of the topic. 59 Carbon-Centered Superbases: Phosphorus Ylides and Carbodiphosphoranes (Figure 2D,E)…”

Section: Basicity Computations In Solutionmentioning

confidence: 99%

“…Simple, easily synthesized monophosphazenyl phosphanes of low molecular weight such as P III (NR 2 ) 2 (NP(NR 2 ) 3 ), P III ( t Bu) 2 (NP(NR 2 ) 3 ), and P III (NR 2 ) 2 (NP t Bu 3 ) display not only basicities comparable or higher than those of the corresponding Schwesinger bases but a donor strength, measured as the Tolman electronic parameter (TEP) toward transition-metal centers, comparable to that of N-heterocyclic carbenes and Verkade’s base. , The aspect of designing extremely strong P-donor ligands instead of extremely strong P-bases is predominantly applied in related tris(imidazol-2-ylidenamino)phosphanes (IAP) in the Dielmann group and in P-ylidyl-substituted phosphanes (YPhos) in the Gessner group . A review of electron-abundant phosphines and phosphazenes as superbases was published very recently, highlighting the attractiveness of the topic …”

Section: General Strategies For the Molecular Design Of Superbasesmentioning

confidence: 99%

Design of Novel Uncharged Organic Superbases: Merging Basicity and Functionality

et al. 2021

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Conspectus One of the constant challenges of synthetic chemistry is the molecular design and synthesis of nonionic, metal-free superbases as chemically stable neutral organic compounds of moderate molecular weight, intrinsically high thermodynamic basicity, adaptable kinetic basicity, and weak or tunable nucleophilicity at their nitrogen, phosphorus, or carbon basicity centers. Such superbases can catalyze numerous reactions, ranging from C–C bond formation to cycloadditions and polymerization, to name just a few. Additional benefits of organic superbases, as opposed to their inorganic counterparts, are their solubility in organic reaction media, mild reaction conditions, and higher selectivity. Approaching such superbasic compounds remains a continuous challenge. However, recent advances in synthetic methodology and theoretical understanding have resulted in new design principles and synthetic strategies toward superbases. Our computational contributions have demonstrated that the gas-phase basicity region of 350 kcal mol–1 and even beyond is easily reachable by organosuperbases. However, despite record-high basicities, the physical limitations of many of these compounds become quickly evident. The typically large molecular weight of these molecules and their sensitivity to ordinary reaction conditions prevent them from being practical, even though their preparation is often not too difficult. Thus, obviously structural limitations with respect to molecular weight and structural complexity must be imposed on the design of new synthetically useful organic superbases, but strategies for increasing their basicity remain important. The contemporary design of novel organic superbases is illustrated by phosphazenyl phosphanes displaying gas-phase basicities (GB) above 300 kcal mol–1 but having molecular weights well below 1000 g·mol–1. This approach is based on a reconsideration of phosphorus(III) compounds, which goes along with increasing their stability in solution. Another example is the preparation of carbodiphosphoranes incorporating pyrrolidine, tetramethylguanidine, or hexamethylphosphazene as a substituent. With gas-phase proton affinities of up to 300 kcal mol–1, they are among the top nonionic carbon bases on the basicity scale. Remarkably, the high basicity of these compounds is achieved at molecular weights of around 600 g·mol–1. Another approach to achieving high basicity through the cooperative effect of multiple intramolecular hydrogen bonding, which increases the stabilization of conjugate acids, has recently been confirmed. This Account focuses on our efforts to produce superbasic molecules that embody many desirable traits, but other groups’ approaches will also be discussed. We reveal the crucial structural features of superbases and place them on known basicity scales. We discuss the emerging potential and current limits of their application and give a general outlook into the future.

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Phosphorus‐Containing Superbases: Recent Progress in the Chemistry of Electron‐Abundant Phosphines and Phosphazenes

Cited by 37 publications

References 240 publications

aDim-aDmoc Protection for ODN Synthesis Allows Deprotection under Non-nucleophilic and Nearly Neutral Conditions

aDim-aDmoc Protection for ODN Synthesis Allows Deprotection under Non-nucleophilic and Nearly Neutral Conditions

Organosuperbase Catalyzed 1,1-Diboration of Alkynes

Design of Novel Uncharged Organic Superbases: Merging Basicity and Functionality

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