Facile Electrophilic Iodination of Icosahedral Carboranes. Synthesis of Carborane Derivatives with Boron-Carbon Bonds via the Palladium-Catalyzed Reaction of Diiodocarboranes with Grignard Reagents

Zheng, Zhiping; Jiang, Wei; Zinn, Alfred A.; Knobler, Carolyn B.; Hawthorne, M. Frederick

doi:10.1021/ic00112a023

Cited by 170 publications

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“…Conversely, the B-H vertices exhibit slight nucleophilicity permitting derivatization by reactive electrophiles, leading, for example, to B-iodo derivatives. The latter, in combination with Pd-catalyzed cross-coupling reactions (2), facilitates synthesis of a diverse range of B-derivatives. This difference in reactivity makes the regioselective preparation of B-and/or C-derived carboranes possible without the need for complicated protecting group strategies or expensive reagents (for recent reviews, see refs.…”

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confidence: 99%

Synthesis and evaluation of transthyretin amyloidosis inhibitors containing carborane pharmacophores

Julius

Farha²,

Chiang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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110

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Carboranes represent a potentially rich but underutilized class of inorganic and catabolism-inert pharmacophores. The regioselectivity and ease of derivatization of carboranes allows for facile syntheses of a wide variety of novel structures. The steric bulk, rigidity, and ease of B-and C-derivatization and lack ofinteractions associated with hydrophobic carboranes may be exploited to enhance the selectivity of previously identified bioactive molecules. Transthyretin (TTR) is a thyroxine-transport protein found in the blood that has been implicated in a variety of amyloid related diseases. Previous investigations have identified a variety of nonsteroidal antiinflammatory drugs (NSAIDs) and structurally related derivatives that imbue kinetic stabilization to TTR, thus inhibiting its dissociative fragmentation and subsequent aggregation to form putative toxic amyloid fibrils. However, the cyclooxygenase (COX) activity associated with these pharmaceuticals may limit their potential as long-term therapeutic agents for TTR amyloid diseases. Here, we report the synthesis and evaluation of carborane-containing analogs of the promising NSAID pharmaceuticals previously identified. The replacement of a phenyl ring in the NSAIDs with a carborane moiety greatly decreases their COX activity with the retention of similar efficacy as an inhibitor of TTR dissociation. The most promising of these compounds, 1-carboxylic acid-7-[3-fluorophenyl]-1,7-dicarba-closo-dodecaborane, showed effectively no COX-1 or COX-2 inhibition at a concentration more than an order of magnitude larger than the concentration at which TTR dissociation is nearly completely inhibited. This specificity is indicative of the potential for the exploitation of the unique properties of carboranes as potent and selective pharmacophores.amyloid ͉ cyclooxygenase ͉ nonsteroidal antiinflammatory drug ͉ fibril T he dicarba-closo-dodecaboranes (carboranes) are icosahedral carbon-containing boron clusters with extraordinary characteristic properties (such as resistance to catabolism, kinetic inertness to reagents, strong hydrophobicity, and wellestablished chemistry) that afford the opportunity for their exploitation as novel hydrophobic pharmacophores. The three isomeric dicarbon carboranes, closo-1,2-C 2 B 10 H 12 , closo-1,7-C 2 B 10 H 12 , and closo-1,12-C 2 B 10 H 12 , commonly known as ortho-, meta-, and para-carborane, respectively, share approximately the same volume as a rotated phenyl ring. This, as well as their structural integrity, ease of substitution, and delocalized bonding, suggests their description as three-dimensional analogs of aromatic hydrocarbons (1), allowing their facile substitution for phenyl rings as rigid scaffolding in pharmacological agents. This rigid scaffolding can be easily and selectively derivatized through deprotonation of the slightly acidic C-H vertices by a strong base (alkyllithium reagents, Grignard reagents, etc.) affording a strongly nucleophilic carboranyl anion capable of reaction with a wide range of electrophiles, inclu...

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confidence: 99%

Synthesis and evaluation of transthyretin amyloidosis inhibitors containing carborane pharmacophores

Julius

Farha²,

Chiang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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110

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“…B-Iodo compounds undergo Pd-catalyzed cross-coupling reactions with alkyl [171][172][173][174][175][176] , aryl 123,126,139,[173][174][175][176][177][178] (e.g. 37) 123 hetaryl 177 , and acetylenyl 126,174,179 (e.g.…”

Section: N Phmentioning

confidence: 99%

“…39) 126 organometallic reagents. First demonstrated for iodocarboranes 175 , the reaction has also been applied to charged species derived from [B 12 [173][174][175]177,178 ), and para-carborane 6 (refs 126,175,179 …”

Section: N Phmentioning

confidence: 99%

“…Several types of organometallic compounds, including organic derivatives of Mg (refs 123,126,[171][172][173][175][176][177][178] ), Zn (refs 18,174,181 ), and B (ref. 182 ) have been used and the choice of the metal depends on the iodide structure and the type of organic residue.…”

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confidence: 99%

“…Cross-coupling reactions of boronic acids with B-iodocarboranes under Suzuki conditions are inefficient giving a large fraction of byproducts 182 . Pd(0) catalysts have been found to be more effective than Ni(0) complexes, and the use of CuI as co-catalyst has a beneficial effect on the reaction 126,173,180 .…”

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confidence: 99%

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Four Decades of Organic Chemistry of closo-Boranes: A Synthetic Toolbox for Constructing Liquid Crystal Materials. A Review

Kaszyński

1999

Collect. Czech. Chem. Commun.

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Introduction and transformations of organic functional groups to ten- and twelve-vertex closo-boranes and heteroboranes is reviewed in the context of preparation of liquid crystalline compounds. The review, containing 198 references, is designed as a synthetic manual for materials chemists and focuses on methods for engineering molecules with elongated shapes and variable dipole moments. Several underdeveloped aspects of closo-borane chemistry are identified.

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Transition‐Metal‐Promoted Functionalization of Carboranes

Qiu¹,

Xie²

2013

Advances in Organometallic Chemistry and Catalysis

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Facile Electrophilic Iodination of Icosahedral Carboranes. Synthesis of Carborane Derivatives with Boron-Carbon Bonds via the Palladium-Catalyzed Reaction of Diiodocarboranes with Grignard Reagents

Cited by 170 publications

References 0 publications

Synthesis and evaluation of transthyretin amyloidosis inhibitors containing carborane pharmacophores

Synthesis and evaluation of transthyretin amyloidosis inhibitors containing carborane pharmacophores

Four Decades of Organic Chemistry of closo-Boranes: A Synthetic Toolbox for Constructing Liquid Crystal Materials. A Review

Transition‐Metal‐Promoted Functionalization of Carboranes

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