Scope and Limitations of 2‑Deoxy- and 2,6-Dideoxyglycosyl Bromides as Donors for the Synthesis of β‑2-Deoxy- and β‑2,6-Dideoxyglycosides

It is shown that 2-deoxy- and 2,6-dideoxyglycosyl bromides can be prepared in high yield (72–94%) and engaged in glycosylation reactions with β:α selectivities ≥6:1. Yields of product are 44–90%. Fully armed 2-deoxyglycoside donors are viable, while 2,6-dideoxyglycosides require one electron-withdrawing substituent for high efficiency and β-selectivity. Equatorial C-3 ester protecting groups decrease β-selectivity, and donors bearing an axial C-3 substituent are not suitable. The method is compatible with azide-containing donors and acid-sensitive functional groups

Mechanism of Nucleophilic Activation of (−)-Lomaiviticin A

(−)-Lomaiviticin A (<b>1</b>) is a <i>C</i>₂-symmetric cytotoxin that contains two diazofluorene functional groups and which induces double-strand breaks (DSBs) in DNA. Evidence suggests DNA cleavage is initiated by hydrogen atom abstraction from the deoxyribose backbone. Here we demonstrate the formation of the vinyl radicals <b>1·</b> and <b>2·</b> from <b>1</b> by 1,7-addition of thiols to the diazofluorenes. These radicals can affect hydrogen atom abstraction from methanol and acetone. The first addition of thiol to <b>1</b> proceeds at a much greater rate than the second. The diazosulfide <b>5</b> formed en route to <b>1·</b> has been detected at −50 °C and undergoes decomposition to <b>1·</b> with a half-life of 110 min at −20 °C under air. These data, which constitute the first direct evidence for the generation of <b>1·</b> and <b>2·</b> from <b>1</b>, provide insights into the mechanism of DNA cleavage by <b>1</b>

Hydroaminoalkylation of Unactivated Olefins with Dialkylamines

Hydroaminoalkylation of Unactivated Olefins with Dialkylamine

Hydroaminoalkylation of Unactivated Olefins with Dialkylamines

Hydroaminoalkylation of Unactivated Olefins with Dialkylamine

Intermolecular Hydropyridylation of Unactivated Alkenes

A general method for the hydropyridylation of unactivated alkenes is described. The transformation connects metal-mediated hydrogen atom transfer to alkenes and Minisci addition reactions. The reaction proceeds under mild conditions with high site-selectivities and allows for the construction of tertiary and quaternary centers from simple alkene starting materials

Identification of a Novel Michael Acceptor Group for the Reversible Addition of Oxygen- and Sulfur-Based Nucleophiles. Synthesis and Reactivity of the 3-Alkylidene-3<i>H</i>-indole 1-Oxide Function of Avrainvillamide

The 3-alkylidene-3H-indole 1-oxide functional group found in the naturally occurring alkaloid avrainvillamide has been synthesized by a cross coupling−reductive condensation sequence and found to undergo reversible addition of oxygen- and sulfur-based nucleophiles

Regioselective Reductive Hydration of Alkynes To Form Branched or Linear Alcohols

The regioselective reductive hydration of terminal alkynes using two complementary dual catalytic systems is described. Branched or linear alcohols are obtained in 75–96% yield with ≥25:1 regioselectivity from the same starting materials. The method is compatible with terminal, di-, and trisubstituted alkenes. This reductive hydration constitutes a strategic surrogate to alkene oxyfunctionalization and may be of utility in multistep settings

Fragment Coupling Approach to Diaporthein B

Pimarane diterpenes are produced by a diverse array of plants, fungi, and bacteria. Many members of this family possess antimicrobial and antiproliferative activities. The pimarane diterpenes are characterized by a tricyclic carbon scaffold comprising three fused six-membered rings and at least three quaternary centers. Here, we describe two convergent, fragment-based strategies toward the synthesis of diaporthein B (3), one of the most highly oxidized pimarane diterpenes. The first approach provided access to the tricyclic carbon scaffold of the target and featured a highly diastereoselective fragment coupling, a novel carbonylative Stille cross-coupling to directly access an α-hydroxyketone from a vinyl iodide, and a tandem aldol cyclization–deprotection cascade. The second route utilized a diastereoselective 1,4-addition of a silyloxyfuran to an unsaturated ketone, followed by an epoxidation–ring opening sequence, to access a highly oxidized intermediate containing two elaborated cyclohexane rings. The chemistry developed herein may ultimately be useful in an eventual synthesis of this class of natural products

Synthesis of Ketones and Esters from Heteroatom-Functionalized Alkenes by Cobalt-Mediated Hydrogen Atom Transfer

Cobalt bis­(acetylacetonate) is shown to mediate hydrogen atom transfer to a broad range of functionalized alkenes; in situ oxidation of the resulting alkylradical intermediates, followed by hydrolysis, provides expedient access to ketones and esters. By modification of the alcohol solvent, different alkyl ester products may be obtained. The method is compatible with a number of functional groups including alkenyl halides, sulfides, triflates, and phosphonates and provides a mild and practical alternative to the Tamao–Fleming oxidation of vinylsilanes and the Arndt–Eistert homologation

Enantioselective Synthesis of Stephacidin B

We describe an enantioselective synthetic route to the antiproliferative alkaloid stephacidin B (1) proceeding in 18 steps and 4.0% yield from 4,4-(ethylenedioxy)-2,2-dimethylcyclohexanone (3). Key features of the synthetic sequence include the use of the Corey−Bakshi−Shibata (CBS) reduction to introduce asymmetry early in the synthetic route, use of the novel electrophile N-(tert-butoxycarbonyl)-5-(isopropylsulfonyloxymethyl)-2,3-dihydropyrrole in a stereoselective enolate alkylation, a diastereoselective Strecker-type addition of hydrogen cyanide to an N-Boc enamine substrate in the solvent hexafluoroisopropanol, platinum-catalyzed nitrile hydrolysis under neutral conditions, cyclization of an acylamino radical intermediate to form the diketopiperazine core of stephacidin B, and implementation of a convergent procedure for introduction of the key 3-alkylidene-3H-indole 1-oxide functional group in the final stage of the route to prepare the structure 2, previously proposed to be the fungal metabolite avrainvillamide (17 steps, 4.2% yield). We observed that synthetic (−)-2 dimerized in the presence of triethylamine to form (+)-stephacidin B (>95%). We also obtained evidence that 2 can form 1 under mild conditions, and that 2 reacts with nucleophiles, such as methanol, by conjugate addition