Photo-mediated ring contraction of saturated heterocycles

Saturated heterocycles are found in numerous therapeutics as well as bioactive natural products and are abundant in many medicinal and agrochemical compound libraries. To access new chemical space and function, many methods for functionalization on the periphery of these structures have been developed. Comparatively fewer methods are known for restructuring their core framework. Herein, we describe a visible light-mediated ring contraction of α-acylated saturated heterocycles. This unconventional transformation is orthogonal to traditional ring contractions, challenging the paradigm for diversification of heterocycles including piperidine, morpholine, thiane, tetrahydropyran, and tetrahydroisoquinoline derivatives. The success of this Norrish Type II variant rests on reactivity differences between photoreactive ketone groups in specific chemical environments. This strategy was applied to late-stage remodeling of pharmaceutical derivatives, peptides, and sugars.

Efficient Synthesis of Pharmaceutically Relevant Prochiral Heterocyclic Aminoketones

In this work, we report a practical method for alkylation of saturated heterocycles with chloroacetone yielding prochiral heterocyclic ketones, including previously not described molecules. The desired building blocks were obtained with high yields in hydrochloric salt forms, without the need for chromatographic purification.

Visible Light Mediated Selective Oxidation of Alcohols and Oxidative Dehydrogenation of N-Heterocycles Using Scalable and Reusable La-Doped NiWO4 Nanoparticles

Visible light-mediated selective and efficient oxidation of various primary/secondary benzyl alcohols to aldehydes/ketones and oxidative dehydrogenation (ODH) of partially saturated heterocycles using scalable and reusable heterogeneous photo redox catalyst in...

Alkynyl Prins and Alkynyl Aza-Prins Annulations: Scope and Synthetic Applications

This review focuses on alkynyl Prins and alkynyl aza-Prins cyclization­ processes, which involve intramolecular coupling of an alkyne with either an oxocarbenium or iminium electrophile. The oxocarbenium or iminium species can be generated through condensation- or elimination-type processes, to achieve an overall bimolecular annulation that enables the synthesis of both oxygen- and nitrogen-containing­ saturated heterocycles with different ring sizes and substitution patterns. Also discussed are cascade processes in which alkynyl Prins heterocyclic adducts react to trigger subsequent pericyclic reactions, including [4+2] cycloadditions and Nazarov electrocyclizations, to rapidly construct complex small molecules. Finally, examples of the use of alkynyl Prins and alkynyl aza-Prins reactions in the synthesis of natural products are described. The review covers the literature through the end of 2019.1 Introduction1.1 Alkyne-Carbonyl Coupling Pathways1.2 Coupling/Cyclization Cascades Using the Alkynyl Prins Reaction2 Alkynyl Prins Annulation (Oxocarbenium Electrophiles)2.1 Early Work2.2 Halide as Terminal Nucleophile2.3 Oxygen as Terminal Nucleophile2.4 Arene as Terminal Nucleophile (Intermolecular)2.5 Arene Terminal Nucleophile (Intramolecular)2.6 Cyclizations Terminated by Elimination3 Synthetic Utility of Alkynyl Prins Annulation3.1 Alkynyl Prins-Mediated Synthesis of Dienes for a [4+2] Cyclo­- addition­-Oxidation Sequence3.2 Alkynyl Prins Cyclization Adducts as Nazarov Cyclization Precursors3.3 Alkynyl Prins Cyclization in Natural Product Synthesis4 Alkynyl Aza-Prins Annulation4.1 Iminium Electrophiles4.2 Activated Iminium Electrophiles5 Alkynyl Aza-Prins Cyclizations in Natural Product Synthesis6 Summary and Outlook

Transition-metal-free C(sp3)–H/C(sp3)–H dehydrogenative coupling of saturated heterocycles with N-benzyl imines

A unique transition-metal-free C(sp3)–H/C(sp3)–H dehydrocoupling of N-benzylimines with saturated heterocycles is presented using 2-azaallyl anions as super electron donors to initiate the generation of hydrogen atom abstracting aryl radicals.