Radical chain repair: The hydroalkylation of polysubstituted unactivated alkenes.

The concept of repair is widely used by nature to heal molecules such as proteins, lipids, sugars, and DNA that are damaged by hydrogen atom abstraction resulting from oxidative stress. We show that this strategy, rather undocumented in the field of synthetic organic chemistry, can be used in a radical chain reaction to enable notoriously intractable transformations. By overcoming the radical chain inhibitor properties of substituted alkenes, the radical-mediated hydroalkylation of mono-, di-, tri-, and even tetrasubstituted unactivated olefins could be performed under mild conditions. With a remarkable functional group tolerance, this reaction provides a general coupling method for the derivatization of olefin-containing natural products.

Synthesis and Size-Dependent Properties of [12], [16], and [24]Carbon Nanobelts.

The synthesis and X-ray crystal structure of the first member of the carbon nanobelt family is reported. [12]Carbon nanobelt ([12]CNB) was originally obtained from a nickel-mediated reductive coupling reaction of a dodecabrominated macrocyclic precursor, albeit only in 1% yield. The present article reports on the development of this synthetic strategy and its extension to the preparation of the [16] and [24]CNB analogues. In particular, our extensive investigations on the final belt-forming, nickel-mediated reaction led to the development of a new ligand system that provides [12]CNB in up to 7% yield, contributing to the commercialization of [12]CNB. The belt structures of [12], [16], and [24]CNB were characterized by NMR, UV-vis, and Raman spectroscopy as well as mass spectrometry and X-ray crystallography. The fluorescence of the CNBs in solution displayed a remarkable dependence on the ring size, ranging from a broad red emission ([12]CNB) to a narrow-band blue emission ([24]CNB), while both features are observed for [16]CNB.

Synthesis of a carbon nanobelt.

The synthesis of a carbon nanobelt, comprising a closed loop of fully fused edge-sharing benzene rings, has been an elusive goal in organic chemistry for more than 60 years. Here we report the synthesis of one such compound through iterative Wittig reactions followed by a nickel-mediated aryl-aryl coupling reaction. The cylindrical shape of its belt structure was confirmed by x-ray crystallography, and its fundamental optoelectronic properties were elucidated by ultraviolet-visible absorption, fluorescence, and Raman spectroscopic studies, as well as theoretical calculations. This molecule could potentially serve as a seed for the preparation of structurally well-defined carbon nanotubes.

Catechols as Sources of Hydrogen Atoms in Radical Deiodination and Related Reactions.

When used with trialkylboranes, catechol derivatives, which are low-cost and low toxicity, are valuable hydrogen atom donors for radical chain reactions involving alkyl iodides and related radical precursors. The system 4-tert-butylcatechol/triethylborane has been used to reduce a series of secondary and tertiary iodides, a xanthate, and a thiohydroxamate ester. Catechol derivatives are right in the optimal kinetic window for synthetic applications, as demonstrated by highly efficient radical cyclizations. Cyclizations leading to the formation of quaternary centers can be performed in an all-at-once process (no slow addition of the hydrogen atom donor) at standard concentrations. The H-donor properties of catechol derivatives can be fine-tuned by changing their substitution pattern. In slow radical cyclization processes, an enhanced ratio of cyclized/uncyclized products was obtained by using 3-methoxycatechol instead of 4-tert-butylcatechol.

Repairing the thiol-ene coupling reaction.

Thiol-ene coupling (TEC) reactions emerged as one of the most useful processes for coupling different molecular units under reaction mild conditions. However, TEC reactions involving weak CH bonds (allylic and benzylic fragments) are difficult to run and often low yielding. Mechanistic studies demonstrate that hydrogen-atom transfer processes at allylic and benzylic positions are responsible for the lack of efficiency of the radical-chain process. These competing reactions cannot be prevented, but reported herein is a method to repair the chain process by running the reaction in the presence of triethylborane and catechol. Under these reaction conditions, a unique repair mechanism leads to an efficient chain reaction, which is demonstrated with a broad range of anomeric O-allyl sugar derivatives including mono-, di-, and tetrasaccharides bearing various functionalities and protecting groups.

Lewis acid-water/alcohol complexes as hydrogen atom donors in radical reactions.

Water or low molecular weight alcohols are, due to their availability, low price and low toxicity ideal reagents for organic synthesis. Recently, it was reported that, despite the very strong BDE of the O-H bond, they can be used as hydrogen atom donors in place of expensive and/or toxic group 14 metal hydrides when boron and titanium(III) Lewis acids are present. This finding represents a considerable innovation and uncovers a new perspective on the paradigm of hydrogen atom transfers to radicals. We discuss here the influence of complex formation and other association processes on the efficacy of the hydrogen transfer step. A delicate balance between activation by complex formation and deactivation by further hydrogen bonding is operative.

Role of equilibrium associations on the hydrogen atom transfer from the triethylborane-methanol complex.

The triethylborane-methanol system used in radical deoxygenation and dehalogenation processes has been investigated. Unambiguous evidence for the formation of a complex between triethylborane and methanol is provided. It was shown that the complexation process is exothermic (ΔH° ≈ -7.6 kcal mol(-1)) while being entropically disfavored (ΔS° ≈ -24 cal mol(-1) K(-1)). This study demonstrates that only very small quantities of complex (1-2%) are present in most of the reported conditions used in dehalogenation and deoxygenation processes. Recalculating the rate constant for the hydrogen transfer to a secondary alkyl radical with this concentration suggests a value in the 10(6) M(-1) s(-1) range for the complex itself, indicating a much more important activation of the O-H bond than previously thought. The importance of solvent effects is also highlighted. The formation of a larger amount of complex by the addition of methanol is accompanied by its deactivation via hydrogen bonding. These observations open new opportunitites for the future preparation of more effective hydrogen atom donors involving borane complexes.

Radical chain reduction of alkylboron compounds with catechols.

The conversion of alkylboranes to the corresponding alkanes is classically per-formed via protonolysis of alkylboranes. This simple reaction requires the use of severe reaction conditions, that is, treatment with a carboxylic acid at high temperature (>150 °C). We report here a mild radical procedure for the transformation of organoboranes to alkanes. 4-tert-Butylcatechol, a well-established radical inhibitor and antioxidant, is acting as a source of hydrogen atoms. An efficient chain reaction is observed due to the exceptional reactivity of phenoxyl radicals toward alkylboranes. The reaction has been applied to a wide range of organoboron derivatives such as B-alkylcatecholboranes, trialkylboranes, pinacolboronates, and alkylboronic acids. Furthermore, the so far elusive rate constants for the hydrogen transfer between secondary alkyl radical and catechol derivatives have been experimentally determined. Interestingly, they are less than 1 order of magnitude slower than that of tin hydride at 80 °C, making catechols particularly attractive for a wide range of transformations involving C-C bond formation.

Role of catechol in the radical reduction of B-alkylcatecholboranes in presence of methanol.

Mechanistic investigations on the previously reported reduction of B-alkylcatecholboranes in the presence of methanol led to the disclosure of a new mechanism involving catechol as a reducing agent. More than just revising the mechanism of this reaction, we disclose here the surprising role of catechol, a chain breaking antioxidant, which becomes a source of hydrogen atoms in an efficient radical chain process.