Photochemical Synthesis of Azaheterocycles

Abstract

Synthetic organic photochemistry is a field that continues to offer unique routes to organic structures not typically accessed from thermal reactions. In this review, the photochemical synthesis of five-, six-, seven-, and eight-membered-ring azaheterocycles, as well as some aza-macrocycles, is discussed. The discussion will focus on methods where heterocycle formation occurs during or as a result of a photochemical event. Reaction mechanisms will be discussed also, as these provide a rationale for understanding the synthetic results. 1 Introduction 2 Five-Membered Rings 2.1 Cyclization Reactions 2.2 Cycloadditions 2.3 From Aromatic and Vinyl Azides 2.4 earrangements 2.5 Other Individual Methods 3 Six-Membered Rings 3.1 Cyclization Reactions 3.2 Isocyanide Insertions 3.3 Cycloadditions 4 Seven-Membered Rings and Larger 5 Conclusion Key words azaheterocycles, photocycloaddition, photocyclization, photorearrangement, photocatalyst Dr. Tanoury began his career in the pharmaceutical industry in 1992 as a Medicinal Chemist at the Burroughs-Wellcome Company in North Carolina. In 1996, he moved to Sepracor, Inc. in Massachusetts to start a career as a process development chemist. He moved to Vertex Pharmaceuticals in 2001 where he is currently a Senior Scientific Fellow in the Process Chemistry Department. Prior to starting his industrial career, Dr. Tanoury was a graduate student under the direction of Professor Barry M. Trost, earning his Ph.D. from Stanford University in 1989. This was followed by a National Institutes of Health postdoctoral fellowship at Harvard University from 1989-1992 in the labs of Professor E. J. Corey. In addition to synthetic organic chemistry and developing chemical processes for the manufacture of API, Dr. Tanoury's interests include understanding and probing chemical reactions using state-ofthe-art technology, and studying reaction mechanisms and chemical properties (ground and excited state) using theoretical/computational methods.

Stereoselective Synthesis of 3,5‐Dihydroxypyrrolidin‐2‐ones Through a Photoinduced Multicomponent Reaction Followed by Dimerization

“…In this manuscript we have described a straightforward two step procedure for the synthesis of complex 3,5‐dihydroxypyrrolidin‐2‐ones. A photoinduced multicomponent reaction followed by an aldol condensation/intramolecular hemiaminal formation affords stereochemically defined five‐membered heterocycles 2 in moderate to good yields . The relatively simple building blocks employed (diazoketones, isocyanides and silanols) can be changed at will, in order to introduce different appendages to the core and to obtain symmetrical and unsymmetrical derivatives.…”

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“…It is always imperative in drug discovery to create efficient, convenient, rapid, and environmentally benevolent synthetic techniques for the functionalization and manufacture of heterocycles. Visible light photoredox catalysis is one of the most suitable approaches utilized today [13]. Following the photo excitation with visible light, metal complexes and the organic dyes tend to engage in single-electron transfer (SET) process entailing carbon-based molecules to attain the chemical transformation processes [14].…”

Recent Advances on Metal-Free, Visible-Light- Induced Catalysis for Assembling Nitrogen- and Oxygen-Based Heterocyclic Scaffolds

“…To create heterocyclic scaffolds, comprehensive photocatalytic strategies based on various metal complexes have been already disclosed [13,14,15,16,17,18,19,20]. However, their metal-free analogues play a significant role in terms of green chemistry [21] and medicine because of the high toxicity of many transition-metal complexes [22,23,24].…”