Alex C. Bissember

The Au(I)-catalyzed intramolecular hydroarylation of terminal alkynes under mild conditions: Application to the synthesis of 2H-chromenes, coumarins, benzofurans, and dihydroquinolines

Operationally simple Au(I)-catalyzed intramolecular hydroarylation (IMHA) reactions of terminal alkynes that proceed in high yield and under very mild conditions are described. These processes involve low catalyst loadings, mild reaction temperatures, and short reaction times, require no cocatalysts or additives, and allow for the generation of a number of important heterocyclic motifs from readily accessible starting materials.

A Versatile Approach to Ullmann C–N Couplings at Room Temperature: New Families of Nucleophiles and Electrophiles for Photoinduced, Copper-Catalyzed Processes

The use of light to facilitate copper-catalyzed cross-couplings of nitrogen nucleophiles can enable C-N bond formation to occur under unusually mild conditions. In this study, we substantially expand the scope of such processes, establishing that this approach is not limited to reactions of carbazoles with iodobenzene and alkyl halides. Specifically, we demonstrate for the first time that other nitrogen nucleophiles (e.g., common pharmacophores such as indoles, benzimidazoles, and imidazoles) as well as other electrophiles (e.g., hindered/deactivated/heterocyclic aryl iodides, an aryl bromide, an activated aryl chloride, alkenyl halides, and an alkynyl bromide) serve as suitable partners. Photoinduced C-N bond formation can be achieved at room temperature using a common procedure with an inexpensive catalyst (CuI) that does not require a ligand coadditive and is tolerant of moisture and a variety of functional groups.

Transition-Metal-Catalyzed Alkylations of Amines with Alkyl Halides: Photoinduced, Copper-Catalyzed Couplings of Carbazoles

N-alkylations of carbazoles with a variety of secondary and hindered primary alkyl iodides can be achieved by using a simple precatalyst (CuI) under mild conditions (0 °C) in the presence of a Bronsted base; at higher temperature (30 °C), secondary alkyl bromides also serve as suitable coupling partners. A Li[Cu(carbazolide)_2] complex has been crystallographically characterized, and it may serve as an intermediate in the catalytic cycle.

Photoinduced, Copper-Catalyzed Alkylation of Amides with Unactivated Secondary Alkyl Halides at Room Temperature

The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for SN2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

Applications of visible light photoredox catalysis to the synthesis of natural products and related compounds

Covering: 2008 to 2016The total synthesis of natural products and their derivatives continues to inspire organic chemists to identify and test new synthetic strategies and develop and explore novel methodology. In recent years, visible light photoredox catalysis has risen to prominence as a powerful technology that enables the selective formation of chemical bonds under mild reaction conditions. Herein we review applications of photoredox catalysis to the synthesis of natural products and related complex molecules, showcasing a range of powerful transformations that include: reductive couplings, photocycloadditions, intermolecular C-H functionalisation processes, fragmentations, and cyclisations.

New Method for the Rapid Extraction of Natural Products: Efficient Isolation of Shikimic Acid from Star Anise

A new, practical, rapid, and high-yielding process for the pressurized hot water extraction (PHWE) of multigram quantities of shikimic acid from star anise (Illicium verum) using an unmodified household espresso machine has been developed. This operationally simple and inexpensive method enables the efficient and straightforward isolation of shikimic acid and the facile preparation of a range of its synthetic derivatives.

Microwave-Assisted Trans-Halogenation Reactions of Various Chloro-, Bromo-, Trifluoromethanesulfonyloxy- and Nonafluorobutanesulfonyloxy-Substituted Quinolines, Isoquinolines, and Pyridines Leading to the Corresponding Iodinated Heterocycles†

Microwave irradiation of certain chloro-, bromo-, trifluoromethanesulfonyloxy- and nonafluorobutanesulfonyloxy-substituted quinolines in the presence of acetic anhydride and sodium iodide leads, via a trans-halogenation process, to the corresponding iodides in high yield. Related conversions involving pyridines and isoquinolines can also be achieved under similar conditions.

Synthesis of 2,3-Dihydro-4(1H)-quinolones and the Corresponding 4(1H)-Quinolones via Low-Temperature Fries Rearrangement of N-Arylazetidin-2-ones

N-Arylazetidin-2-ones of the general form 1, which are readily prepared by Goldberg–Buchwald-type copper-catalyzed coupling of N-unsubstituted azetidin-2-ones with the relevant aryl halide or using Mitsunobu cyclization processes, undergo smooth Fries-rearrangement in triflic acid at 0–18°C to give the isomeric 2,3-dihydro-4(1H)-quinolones (2). Dehydrogenation of the latter compounds using 10% Pd on C in 1.0 M aqueous sodium hydroxide/propan-2-ol mixtures at ca. 82°C provides the corresponding 4(1H)-quinolones (3).

Practical Isolation of Asperuloside from Coprosma quadrifida via Rapid Pressurised Hot Water Extraction

The valuable glycoside asperuloside was efficiently isolated in multigram quantities from Coprosma quadrifida employing a recently developed rapid pressurised hot water extraction (PHWE) method that utilises an unmodified household espresso machine. This study represents the first time C. quadrifida has been extracted and its major chemical components isolated and analysed. Our findings reveal that this species is a rich source of asperuloside (7.0 % yield w/w). Significantly, this represents one of the highest yields obtained of this glycoside from a Coprosma species, and the entire Rubiaceae family more generally.

Seven-membered rings

New synthetic methods continue to be developed to construct seven-membered heterocyclic compounds containing one, two, or three of the heteroatoms N, O, or S. The focus of much of the literature has been on aromatic systems containing at least 1 N atom and has often been driven by a desire to prepare these heterocycles in a stereocontrolled fashion, the search for new bioactives, and the synthesis of natural products. Prominent synthetic methods include transition metal-catalyzed, cycloaddition/annulation, cascade-type, and CeH functionalization processes. Review articles on the synthesis of seven-membered nitrogen heterocycles through the Ugi multicomponent reaction (17CHE382), synthetic approaches, and biological activities of benzodiazepines (17MOC453), the isolation, structure determination, medicinal properties, and total synthesis of marine natural products containing an oxepanyl ring (17MAD361), the synthesis and medicinal importance of benzoxepines (17LDD1086), methods for the synthesis of 1,2,3-, 1,2,4-, 1,2,5-, and 1,3,5-triazepines (17JCCS1023), and the isolation, biosynthesis, and biological activity of natural products that contain a sevenmembered ring with three or more heteroatoms (17JNP3060), as well as indole-fused azepines and analogs as anticancer lead molecules (17EJM244) have been published.