Synthesis of Pyrazolesulfoximines Using α-Diazosulfoximines with Alkynes.

Sulfoximines and pyrazoles are both important motifs in medicinal compounds. Here we report the synthesis and reactivity of sulfoximine diazo compounds as new reagents for the incorporation of sulfoximines. The use of N-silyl sulfoximines enabled formation of monosubstituted diazo compounds. Their application is demonstrated in a [3 + 2] cycloaddition with alkynes to form pyrazole sulfoximines in a new combination of these important chemotypes. Further derivatization of the pyrazole sulfoximines is demonstrated, including silyl deprotection to form unprotected pyrazolesulfoximines.

When is an Imine Directing Group a Transient Imine Directing Group in C-H Functionalization?

'Transient' C-H functionalization has emerged in recent years to describe the use of a dynamic linkage, often an imine, to direct cyclometallation and subsequent functionalization. As the field continues to grow in popularity, we consider the features that make an imine directing group transient. A transient imine should be i) formed dynamically in situ, ii) avoid discrete introduction or cleavage steps, and iii) offer the potential for catalysis in both the directing group and metal. This concept article contrasts transient imines with pioneering early studies of imines as directing groups for the formation of metallacycles and the use of preformed imines in C-H functionalization. Leading developments in the use of catalytic additives to form transient directing groups (as aldehyde or amine) are covered including selected highlights of the most recent examples of catalytic imine directed C-H functionalization with transition metals.

Dual Copper- and Aldehyde-Catalyzed Transient C-H Sulfonylation of Benzylamines.

This study reports the first example of using a dual catalytic system with copper(II) acetate and 2-hydroxynicotinaldehyde to achieve transient C(sp2)-H sulfonylation of benzylamines with sulfinate salts via a dynamically formed imine directing group. Manganese(IV) oxide was identified as an effective oxidant and base. Computational density functional theory investigations suggest that the transient directing group lowers the energy barrier for an acetate-mediated, turnover-limiting C-H activation step and subsequent combination of the cupracycle with a RSO2 radical.

Mechanistic studies of reactive oxygen species mediated electrochemical radical reactions of alkyl iodides.

Mechanistic studies of a reactive oxygen species mediated electrochemical radical reaction of alkyl iodides are described. Hydroxyl radicals and ozone are identified to be the active species involved in the formation of alkyl radicals under mildly reducing potential (-1.0 V vs. Ag QRE) in buffered acidic conditions (pH 3.6).

Electrochemical radical reactions of alkyl iodides: a highly efficient, clean, green alternative to tin reagents.

An electrochemical 'redox-relay' system has been developed which allows the generation of C-centered radicals. Intermolecular 'tin-like' radical reactions can subsequently be conducted under the most benign of conditions. The yields and efficiency of the processes are competitive and even superior in most cases to comparable conditions with tributyltin hydride. The use of air and electricity as the promotor (instead of a tin or other reagent) combined with the aqueous reaction media make this a clean and 'green' alternative to these classic C-C bond forming processes.

Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Radical Anion Cascade Triene Cyclization: Biomimetic Total Syntheses of Austalide Natural Products.

The first total synthesis of five austalide natural products, (±)-17 S-dihydroaustalide K, (±)-austalide K, (±)-13-deacetoxyaustalide I, (±)-austalide P, and (±)-13-deoxyaustalide Q acid, was accomplished via a series of biomimetic transformations. Key steps involved polyketide aromatization of a trans, trans-farnesol-derived ß,δ-diketodioxinone into the corresponding ß-resorcylate, followed by titanium(III)-mediated reductive radical cyclization of an epoxide to furnish the drimene core. Subsequent phenylselenonium ion induced diastereoselective cyclization of the drimene completed the essential carbon framework of the austalides to access (±)-17 S-dihydroaustalide K, (±)-austalide K, and (±)-13-deacetoxyaustalide I via sequential oxidations. Furthermore, (±)-13-deacetoxyaustalide I could serve as a common intermediate to be derivatized into other related natural products, (±)-austalide P and (±)-13-deoxyaustalide Q acid, by functionalizing the cyclic lactone moiety.

Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Cationic Polyene Cyclization: Total Syntheses of (+)-Hongoquercin A and B and Related Meroterpenoids.

(+)-Hongoquercin A and B were synthesized from commercially available trans, trans-farnesol in six and eleven steps, respectively, using dual biomimetic strategies with polyketide aromatization and subsequent polyene functionalization from a common farnesyl-resorcylate intermediate. Key steps involve Pd(0)-catalyzed decarboxylative allylic rearrangement of a dioxinone ß,δ-diketo ester to a ß,δ-diketo dioxinone, which was readily aromatized into the corresponding resorcylate, and subsequent polyene cyclization via enantioselective protonation or regioselective terminal alkene oxidation and cationic cyclization of enantiomerically enriched epoxide to furnish the tetracyclic natural product cores. Analogues of the hongoquercin were synthesized via halonium-induced polyene cyclizations, and the meroterpenoid could be further functionalized via saponification, hydrolytic decarboxylation, reduction, and amidation reactions.

Sequential Ketene Generation from Dioxane-4,6-dione-keto-dioxinones for the Synthesis of Terpenoid Resorcylates.

Trapping of the ketene generated from the thermolysis of 2-methyl-2-phenyl-1,3-dioxane-4,6-dione-keto-dioxinone at 50 °C with primary, secondary, or tertiary alcohols gave the corresponding dioxinone ß-keto-esters in good yield under neutral conditions. These intermediates were converted by palladium(0)-catalyzed decarboxylative allyl migration and aromatization into the corresponding ß-resorcylates. These transformations were applied to the syntheses of the natural products (±)-cannabiorcichromenic and (±)-daurichromenic acid.