Total Synthesis of Lissodendoric Acid A.

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A . These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis.

Enantioselective nickel-catalyzed Mizoroki-Heck cyclizations of amide electrophiles.

Amide cross-couplings that rely on C-N bond activation by transition metal catalysts have emerged as valuable synthetic tools. Despite numerous discoveries in this field, no catalytic asymmetric variants have been disclosed to date. Herein, we demonstrate the first such transformation, which is the Mizoroki-Heck cyclization of amide substrates using asymmetric nickel catalysis.

Studies Pertaining to the Emerging Cannabinoid Hexahydrocannabinol (HHC).

We report studies pertaining to two isomeric hexahydrocannabinols (HHCs), ()-HHC and ()-HHC, which are derivatives of the psychoactive cannabinoids Δ- and Δ-THC. HHCs have been known since the 1940s, but have become increasingly available to the public in the United States and are typically sold as a mixture of isomers. We show that ()-HHC and ()-HHC can be prepared using hydrogen-atom transfer reduction, with ()-HHC being accessed as the major diastereomer.

Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene.

Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical synthesis. We report a concise total synthesis of the manzamine alkaloid lissodendoric acid A, which hinges on the development of a regioselective, diastereoselective, and stereospecific trapping of a fleeting cyclic allene intermediate.

Hydrazone and Oxime Olefination via Ruthenium Alkylidenes.

We describe the development of an efficient method for the olefination of hydrazones and oximes. The key design approach that enables this transformation is tuning of the energy/polarity of C=N π-bonds by employing heteroatom functionalities (NR , OR). The resulting hydrazones or oximes facilitate olefination with ruthenium alkylidenes.

Catalytic, transannular carbonyl-olefin metathesis reactions.

Transannular carbonyl-olefin metathesis reactions complement existing procedures for related ring-closing, ring-opening, and intermolecular carbonyl-olefin metathesis. We herein report the development and mechanistic investigation of FeCl-catalyzed transannular carbonyl-olefin metathesis reactions that proceed a distinct reaction path compared to previously reported ring-closing and ring-opening protocols. Specifically, carbonyl-ene and carbonyl-olefin metathesis reaction pathways are competing under FeCl-catalysis to ultimately favor metathesis as the thermodynamic product.

Interrupted carbonyl-olefin metathesis via oxygen atom transfer.

Some of the simplest and most powerful carbon-carbon bond forming strategies take advantage of readily accessible ubiquitous motifs: carbonyls and olefins. Here we report a fundamentally distinct mode of reactivity between carbonyls and olefins that differs from established acid-catalyzed carbonyl-ene, Prins, and carbonyl-olefin metathesis reaction paths. A range of epsilon, zeta-unsaturated ketones undergo Brønsted acid-catalyzed intramolecular cyclization to provide tetrahydrofluorene products via the formation of two new carbon-carbon bonds.

Design, synthesis and biological evaluation of GPR55 agonists.

GPR55, a G protein-coupled receptor, is an attractive target to alleviate inflammatory and neuropathic pain and treat osteoporosis and cancer. Identifying a potent and selective ligand will aid to further establish the specific physiological roles and pharmacology of the receptor. Towards this goal, a targeted library of 22 compounds was synthesized in a modular fashion to obtain structure-activity relationship information.

Formation and in situ reactions of hypervalent iodonium alkynyl triflates to form cyanocarbenes.

The conversion of readily available silylalkynes, iodobenzene diacetate, and azide anions was utilized to form and react cyanocarbenes. A copper(II)-catalyzed reaction was found to react in a different manner. Both of these methods benefit from the formation and in situ reaction of hypervalent iodonium alkynyl triflates in O-H insertion reactions.

Synthesis of hypervalent iodonium alkynyl triflates for the application of generating cyanocarbenes.

The procedures described in this article involve the synthesis and isolation of hypervalent iodonium alkynyl triflates (HIATs) and their subsequent reactions with azides to form cyanocarbene intermediates. The synthesis of hypervalent iodonium alkynyl triflates can be facile, but difficulties stem from their isolation and reactivity. In particular, the necessity to use filtration under inert atmosphere at -45 °C for some HIATs requires special care and equipment.