Synthesis of New Sulfonyloximes and Their Use in Free-Radical Olefin Carbo-oximation

New bifunctional reagents for free-radical carbo-oximation of olefins have been developed. In this process, a single reagent can act both as a trap for nucleophilic radicals as well as a source of electrophilic radical via an α-scission of an alkylsulfonyl radical. This strategy involving the addition of a C-centered electrophilic radical and an oxime across the double bond of an electron-rich alkene is initiated with a <i>t</i>-BuO radical following an unusual mechanism, supported by both experiments and density functional theory calculations

Free-Radical Carbocyanation of Cyclopropenes: Stereocontrolled Access to All-Carbon Quaternary Stereocenters in Acyclic Systems

Free-radical carbocyanation of cyclopropenes offers straightforward access to tetrasubstituted cyclopropanes in satisfying yields with moderate diastereoselectivity. The incorporation of various functional groups on the cyclopropane ring allows a subsequent base-mediated ring-opening reaction leading to functionalized acyclic systems having an all-carbon quaternary stereocenter

Total Synthesis of (±)-Eucophylline. A Free-Radical Approach to the Synthesis of the Azabicyclo­[3.3.1]­nonane Skeleton

The first total synthesis of eucophylline was reported in 10 steps and 10% overall yield. The naphthyridine core of eucophylline was prepared through the coupling between a strained azabicyclo­[3.3.1]­nonan-2-one and a trisubstituted benzonitrile, followed by a cyclization of the corresponding amidine. This coupling reaction was shown to proceed through a stable bicyclic chloroenamine intermediate. The azabicyclo­[3.3.1]­nonan-2-one skeleton was in turn accessible through a straightforward sequence including a free-radical three-component olefin carbo-oximation as a key step

Visible-Light-Mediated Addition of Phenacyl Bromides onto Cyclopropenes

Visible-light-promoted addition of α-bromoaceto­phenones onto the cyclopropene π-system in the presence of the <i>fac</i>-Ir­(ppy)₃ catalyst was shown to afford the corresponding 1­(4<i>H</i>)-naphthalenones. The <i>syn</i>-carboarylation of the cyclopropene is followed by a cyclopropane ring opening under the basic conditions, allowing the formation of two C–C bonds and the generation of 1­(4<i>H</i>)-naphthalenones bearing an all-carbon benzylic quaternary stereocenter

Free-Radical Carbo-alkenylation of Enamides and Ene-carbamates

The addition of xanthates and vinyldisulfones across the double bond of enamides and ene-carbamates provides access to the corresponding three-component adducts in good to excellent yields with a high level of diastereocontrol in cyclic systems. This strategy illustrates a complementary reactivity for these versatile olefins and extends their scope of application

One-Pot Synthesis and PEGylation of Hyperbranched Polyacetals with a Degree of Branching of 100%

The Brønsted acid-catalyzed polytransacetalization of hydroxymethylbenzaldehyde dimethylacetal (<b>1</b>), a commercially available AB₂-type monomer, led to hyperbranched polyacetals (HBPA’s) with a degree of branching (DB) around 0.5 by forming methanol as byproduct. In sharp contrast, the polyacetalization of the nonprotected homologue, namely, hydroxymethylbenzaldehyde (<b>2</b>), yielded HBPA’s with DB = 1, by forming water as byproduct, under the same acidic conditions. This major difference arises from the instability of the initially formed hemiacetal intermediates, which react faster than aldehyde moieties, driving the polyacetalization toward the quantitative formation of dendritic acetal units. This represents a rare example of defect-free hyperbranched polymer synthesis utilizing a very simple AB₂-type monomer. Brønsted acid catalysts included <i>p</i>-toluenesulfonic, camphorsulfonic, and pyridinium camphorsulfonic acids. Trapping of the water generated during polyacetalization of <b>2</b> was accomplished using molecular sieves regularly renewed, which allowed achieving polymers of relatively high molar masses. These HBPA’s with DB = 1 featuring multiple aldehyde functions at their periphery were further derivatized into PEGylated HBPA’s, using linear amino-terminated poly­(ethylene oxide)­s of different molar masses. This led to submicrometric sized HBPA’s with a core–shell architecture. Finally, HBPA derivatives could be readily hydrolyzed under acidic conditions (e.g., pH = 4), owing to the acid sensitivity of their constitutive acetal linkages

Poly(arylene vinylene) Synthesis via a Precursor Step-Growth Polymerization Route Involving the Ramberg–Bäcklund Reaction as a Key Post-Chemical Modification Step

The synthesis of conjugated copolymers based on poly­(fluorene vinylene) [<b>PFV</b>] and poly­(fluorene vinylene-<i>co</i>-carbazole vinylene) [<b>PFVCV</b>] was achieved via a previously unexplored precursor three-step synthetic route involving the Ramberg–Bäcklund reaction. The resulting π-conjugated (co)­polymers proved highly soluble in common organic solvents, such as DCM, THF, or CHCl₃. The solution step-growth polymerization between 2,7-bis­(bromomethyl)-9,9′-dihexyl-9<i>H-</i>fluorene [<b>F-Br</b>] and 2,7-bis­(mercaptomethyl)-9,9′-dihexyl-9<i>H-</i>fluorene [<b>F-SH</b>] was carried out under basic conditions at 100 °C in a mixture of MeOH and THF. The resulting polysulfides were then subjected to an oxidation reaction using <i>m-</i>CPBA, which was followed by the Ramberg–Bäcklund reaction in the presence of CF₂Br₂/Al₂O₃–KOH, thus achieving the desired <b>PFV</b>. Similarly, <b>PFVCV</b> could be synthesized through the same three-step sequence employing, in this case, 2,7-bis­(mercaptomethyl)-9-(tridecan-7-yl)-9<i>H</i>-carbazole (<b>C-SH</b>) and <b>F-Br</b>. Conjugated polymers with apparent molecular weights up to 15 kg mol^–1 and exhibiting promising optical features were obtained following this convenient synthetic strategy

Polyaldol Synthesis by Direct Organocatalyzed Crossed Polymerization of Bis(ketones) and Bis(aldehydes)

Synthesis of polyaldols consisting of β-keto alcohol monomer units is described. These polymers were obtained by direct step-growth polymerization of purposely designed bifunctional enolizable bis­(ketone) monomers playing the role of nucleophilic donors, and activated nonenolizable bis­(aldehyde)­s serving as electrophilic acceptors. Monofunctional ketone and aldehyde homologues were first synthesized as models to establish the aldol reaction conditions using reaction partners at stoichiometry. A bifunctional organocatalytic system consisting of pyrrolidine in conjunction with acetic acid allowed performing polyaldolizations of stoichiometric amounts of the bis­(aldehyde) and the bis­(ketone) in solution in THF, DMSO, or DMF, at room temperature. However, polar solvents and/or prolonged reaction time induced further aldol reactions between aldol units of polymer chains, as indicated by the relatively broad molecular weight distribution of related polyaldols observed by size exclusion chromatography. Analysis by NMR spectroscopy confirmed the formation of β-keto alcohol units, but also evidenced that the latter were also partly dehydrated into conjugated ketones via a crotonization reaction (from 20 to 33% depending on the structure of the initial monomers)

Eosin-Mediated Alkylsulfonyl Cyanation of Olefins

Eosin-Y (EY)-mediated alkylsulfonyl cyanation of olefins was shown to afford alkylsulfonyl nitriles in good yields. On the basis of transient absorption spectroscopy, the reaction was shown to proceed via photoinduced electron transfer from ³EY* to an O-cyanated derivative of the photocatalyst, formed in situ, with generation of the corresponding sulfinate that is oxidized by EY^•.+ into a sulfonyl radical. Addition of the latter on the olefin, followed by a radical cyano group transfer, then furnished the nitrile along with a RSO₂ radical sustaining the radical chain