In-Situ Bromination Enables Formal Cross-Electrophile Coupling of Alcohols with Aryl and Alkenyl Halides.

Although alcohols are one of the largest pools of alkyl substrates, approaches to utilize them in cross-coupling and cross-electrophile coupling are limited. We report the use of 1° and 2° alcohols in cross-electrophile coupling with aryl and vinyl halides to form C(sp3)-C(sp2) bonds in a one-pot strategy utilizing a very fast (<1 min) bromination. The reaction's simple benchtop setup and broad scope (42 examples, 56% ± 15% ave yield) facilitates use at all scales. The potential in parallel synthesis applications was demonstrated by successfully coupling all combinations of 8 alcohols with 12 aryl cores in a 96-well plate.

Nickel-Catalyzed Addition of Aryl Bromides to Aldehydes To Form Hindered Secondary Alcohols.

Transition-metal-catalyzed addition of aryl halides across carbonyls remains poorly developed, especially for aliphatic aldehydes and hindered substrate combinations. We report here that simple nickel complexes of bipyridine and PyBox can catalyze the addition of aryl halides to both aromatic and aliphatic aldehydes using zinc metal as the reducing agent. This convenient approach tolerates acidic functional groups that are not compatible with Grignard reactions, yet sterically hindered substrates still couple in high yield (33 examples, 70% average yield). Mechanistic studies show that an arylnickel, and not an arylzinc, adds efficiently to cyclohexanecarboxaldehyde, but only in the presence of a Lewis acid co-catalyst (ZnBr2).

Synthesis of Spirocyclic Diphosphite-Supported Gold Metallomacrocycles via a Protodeauration/Cyclization Strategy: Mechanistic and Binding Studies.

A spirocylic diphosphite was used to generate P-metalated bimetallic complexes through protodeauration reactions involving LAuC6H4tBu (L = JohnPhos, tBuXPhos) and metallomacrocycles through protodeauration/cyclization using tBuC6H4AuP^PAuC6H4tBu precursors (P^P = flexible diphosphine). While the synthesis of the bimetallic complexes followed a stepwise process, generation of the metallomacrocycles was highly complex because of a series of reversible ligand redistribution reactions. The self-assembly was monitored, and key intermediates were identified by NMR spectroscopy and high-resolution mass spectrometry. The mechanistic investigation showed that using flexible diphosphine linkers was critical to the selective synthesis of metallomacrocycles because rigid diphosphines generated intractable mixtures of linear and cyclic compounds. The X-ray structure of a 32-membered metallomacrocycle revealed that the compound crystallized in an unsymmetrical collapsed form that was held together by two supported aurophilic interactions while the flexible diphosphines were folded along opposite sides of the metallomacrocycle. The solution structure was consistent with a symmetric species, which suggested interconversion between an open and collapsed form and/or rapid twisting of a collapsed form. The 32-membered metallomacrocycle was used to bind estrogen primarily through the formation of AuP-O-···H-OR hydrogen bonds.

Resolved P-metalated nucleoside phosphoramidites.

The synthesis of resolved P-metalated nucleoside phosphoramidites is described. These rare compounds were initially prepared with gold as the metal center; however, the gold can be removed using basic phosphines or solid-supported triphenylphosphine. Treatment of the free nucleoside phosphoramidite with a platinum source generated a unique platinated dinucleoside species with a diastereomeric ratio of >99:1.

Acid, silver, and solvent-free gold-catalyzed hydrophenoxylation of internal alkynes.

A range of arylgold compounds have been synthesized and investigated as single-component catalysts for the hydrophenoxylation of unactivated internal alkynes. Both carbene and phosphine-ligated compounds were screened as part of this work, and the most efficient catalysts contained either JohnPhos or IPr/SIPr. Phenols bearing either electron-withdrawing or electron-donating groups were efficiently added using these catalysts. No silver salts, acids, or solvents were needed for the catalysis, and either microwave or conventional heating afforded moderate to excellent yields of the vinyl ethers.