Synthesis of PEG-supported organotrifluoroborates and their applications in palladium-catalyzed homo-coupling reactions.

A general synthetic route to water-soluble PEG-supported organotrifluoroborates has been developed. In the presence of air and catalytic amounts of Pd(OAc)2, the PEG-supported organotrifluoroborates undergo homo-coupling reactions smoothly at room temperature. No additional oxidizing agent, base, or phosphine ligands are required.

Boronated carbohydrate derivatives as potential boron neutron capture therapy reagents.

The treatment of cancer remains one of the most challenging problems for humanity. Boron neutron capture therapy is a binary approach for cancer treatment that is particularly attractive in treating high-grade gliomas and metastatic brain tumors. Among the types of boron-containing molecules used as boron neutron capture therapy agents, boronated carbohydrate derivatives have received significant attention because of their preferential uptake by growing tumor cells. This review provides a summary of the recent developments in the chemistry of carborane-containing carbohydrates.

The hydroarylation reaction--scope and limitations.

The synthetic potential of stereoselective, palladium-catalyzed hydro(het)arylation reactions of bi-, tri- and tetracyclic (hetero)alkenes in the presence of phospines and arsines as highly efficient ligands was studied. The mechanism of this reductive Heck reaction becomes more complex in the case of benzonorbornenes. Hydroarylation of diazabicyclo-[2.2.1]heptenes provides a stereoselective access to aryldiaminocyclopentanes. Electron-deficient arylpalladium complexes shift the reaction towards the product of a formal 1,2-hydrazidoarylation reaction of 1,3-cyclopentadiene by a stereoselective C-N cleavage. Due to steric reasons, rigid bicyclo[2.2.2]octenes react slower in hydroarylation reactions than the corresponding bicyclo[2.2.1]heptenes. The more flexible bicyclo[4.2.2]decene system already tends to undergo domino-Heck reactions, even under reductive conditions. When a tetracyclic cis-allylcyclopropane is carbopalladated in the presence of formates, the neighboring cyclopropane ring is attacked in the first reported example of a pi,sigma domino-Heck reaction.

Syntheses and characterization of polymer-supported organotrifluoroborates: applications in radioiodination reactions.

A novel strategy combining the advantages of polymer-supports and organotrifluoroborate chemistry for radiotracer preparation is reported.

Chemoselective bromodeboronation of organotrifluoroborates using tetrabutylammonium tribromide: application in (Z)-dibromoalkene syntheses.

Tetrabutylammonium tribromide (TBATB) has been found to be a unique bromodeboronation reagent for organotrifluoroborates. When compared to previously reported bromodeboronation methods, the mild and metal-free reaction conditions tolerate a wider range of functional groups. High regio- and chemoselectivity are observed in the presence of both unsaturated carbon-carbon bonds and aldehyde functional groups. An efficient synthetic route to (Z)-dibromoalkenes from terminal alkynes has been developed using the TBATB-mediated bromodeboronation as a key step.

Titanium(IV) halide mediated coupling of alkoxides and alkynes: an efficient and stereoselective route to trisubstituted (E)-alkenyl halides.

Alkoxide C-O bond cleavage occurs readily at room temperature in the presence of titanium(IV) halide. Capture of the resultant carbocation by alkynes provides an efficient route to trisubstituted (E)-alkenyl halides with high stereoselectivity.

Identification of a boron-containing intermediate in the boron tribromide mediated aryl propargyl ether cleavage reaction.

An alternate reaction mechanism for the boron tribromide mediated deprotection of aryl propargyl ethers based on the isolation of a key boron-containing byproduct is proposed. On the basis of the new mechanistic insight, we discovered that HBBr(2) x SMe(2) can also be used for cleaving aryl propargyl ethers.

Synthesis, biological evaluation and radiochemical labeling of a dansylhydrazone derivative as a potential imaging agent for apoptosis.

To develop a small molecule-based tracer for in vivo apoptosis imaging, dansylhydrazone (DFNSH) was synthesized in 93% yield in less than 30 min. The biological evaluation showed that DFNSH selectively binds to paclitaxel-induced apoptotic cancer cells. The high magnification fluorescent images demonstrate that DFNSH is localized within the cytoplasm of cells that bound Alexa 488 labeled annexin V on the plasma membrane. [(18)F]-DFNSH ([(18)F]-3) was synthesized and isolated in 50-60% radiochemical yields, based on [K/K(222)](18)F, with a synthesis time of 50 min (EOB). The straightforward preparation of fluorine-18 labeled 3 makes it a promising tracer for PET imaging of apoptosis.

Boron trihalide mediated alkyne-aldehyde coupling reactions: a mechanistic investigation.

A boron trihalide mediated alkyne-aldehyde coupling reaction leading to stereodefined 1,3,5-triaryl-1,5-dihalo-1,4-pentadienes is described. The study led to the discovery of a direct substitution of hydroxyl groups by stereodefined alkenyl moieties using alkenylboron dihalides. During the investigation, it was also discovered that, at low temperatures, the reaction of BCl3 with alkynes produces monovinylboron dichloride rather than the reported divinylboron chloride. A modified reaction mechanism for the boron trichloride mediated alkyne-aldehyde coupling reaction is now proposed. The reaction temperature and mode of addition have been found to have dramatic affects on the stereochemistry of the diene products.

Boron trihalide mediated haloallylation of aryl aldehydes: reaction and mechanistic insight.

The reaction of aryl aldehydes with allylsilanes in the presence of boron trihalides produces haloallylated products. Mechanistic details are presented.

Generation of cations from alkoxides: allylation of propargyl alcohols.

The reaction of alkoxides with boron trichloride results in the generation of cations in the absence of Brønsted acids. The absence of a Brønsted acid can make a difference in subsequent transformations such as allylation reactions.

The synthesis and use of boronated amino acids for boron neutron capture therapy.

The treatment of cancer remains one of the most challenging problems for humanity. Boron neutron capture therapy (BNCT) is a binary approach for cancer treatment that is particularly attractive in treating high-grade gliomas and metastatic brain tumors. Among types of boron-containing molecules used as BNCT agents, boronated amino acids have received significant attention for their preferentially uptake by growing tumor cells. This review emphasizes the synthesis of boronated amino acids.

Substitution of hydroxyl groups with alkynyl moieties using alkynylboron dihalides: an efficient approach to secondary alkylacetylene derivatives.

The reaction of alkynylboron dihalides with benzylic, allylic, and propargylic alcohols provides an efficient route to internal acetylenes. Isomerization of the product alkynes does not occur under the reaction conditions.

Lewis acid mediated reactions of aldehydes with styrene derivatives: synthesis of 1,3-dihalo-1,3-diarylpropanes and 3-chloro-1,3-diarylpropanols.

[reaction: see text] The reactions of aryl aldehydes with styrene derivatives, mediated by various boron Lewis acids, were investigated. 1,3-Dihalo-1,3-diarylpropanes were obtained in high yields with boron trihalides, while 3-chloro-1,3-diarylpropanols were obtained in good to excellent yields with phenylboron dichloride. Reactions involving nonenolizable aliphatic aldehydes, trans-cinnamaldehyde, and beta-substituted styrenes were also investigated for the first time.

Palladium-catalyzed, stereoselective rearrangement of a tetracyclic allyl cyclopropane under arylation.

The first example of a pi,sigma domino-Heck reaction under concomitant rearrangement of the tetracyclic allylcyclopropane endo,exo-bishomobarrelene (5) is reported; the stereoselective reaction proceeds via an intramolecular insertion of a primarily-formed carbopalladation intermediate into a strained cyclopropane C-C sigma-bond, giving 9.

Substitution of benzylic hydroxyl groups with vinyl moieties using vinylboron dihalides.

[reaction: see text] Substitution of benzylic hydroxyl groups with vinyl moieties using vinylboron dihalides has been achieved. The reaction provides a novel method for preparing stereodefined alkenyl halides.

Alkenylation of allylic alcohols using alkenylboron dihalides: a formal transition-metal free Suzuki reaction.

Carbon-carbon bond formation via substitution of an allylic hydroxide with stereodefined alkenyl groups using alkenylboron dihalides in the absence of transition metals.

Synthesis of 1-amino-3-[(dihydroxyboryl)methyl]- cyclobutanecarboxylic acid as a potential therapy agent.

A novel boronated aminocyclobutanecarboxylic acid (1) was synthesized for potential use in boron neutron capture therapy. Starting from the readily available 3-(bromomethyl)cyclobutanone ketal (4), several synthetic routes to 1 were evaluated. After several unsuccessful attempts with traditional synthetic methods, a novel synthetic strategy to generate the new boronated cyclic amino acid was developed. The tolerance of the hydantoin group to the selenoxide elimination reaction conditions in the preparation of alkenyl compound 7 proved to be the key step in the new strategy.