Amine radical cations are highly useful reactive intermediates in amine synthesis. They have displayed several modes of reactivity leading to some highly sought-after synthetic intermediates including iminium ions, α-amino radicals, and distonic ions. One appealing method to access amine radical cations is through one-electron oxidation of the corresponding amines under visible light photoredox conditions. This approach and subsequent chemistries are emerging as a powerful tool in amine synthesis. This article reviews synthetic applications of amine radical cations produced by visible light photocatalysis.1977

Synthesis of the C À Cb onds of ketones relies upon one high-availability reagent (carboxylic acids) and one lowavailability reagent (organometallic reagents or alkyliodides). We demonstrate here ak etone synthesis that couples two different carboxylica cid esters,N -hydroxyphthalimide esters and S-2-pyridyl thioesters,t of orm aryl alkyl and dialkyl ketones in high yields.The keys to this approach are the use of anickel catalyst with an electron-poor bipyridine or terpyridine ligand, aT HF/DMA mixed solvent system, and ZnCl 2 to enhance the reactivity of the NHP ester.The resulting reaction can be used to form ketones that have previously been difficult to access,s uch as hindered tertiary/tertiary ketones with strained rings and ketones with a-heteroatoms.The conditions can be employed in the coupling of complex fragments, including a2 0-mer peptide fragment analog of Exendin(9-39) on solid support. Scheme 1. Strategies in ketone synthesis.

Cascade reactions represent a class of ideal organic reactions because they empower efficiency, elegance, and novelty. However, development of cascade reactions remains a daunting task for synthetic chemists. Radicals are known to be well suited for cascade reactions. Compared with widely used carbon-based radicals, nitrogen-based radicals, such as neutral aminyl radicals and protonated aminyl radicals (amine radical cations), are underutilized, although they are behind some notable synthetic methods such as the Hofmann-Löffler-Freytag reaction. The constraint on their usage is generally attributed to the limited number of available stable precursors. Since amine radical cations offer increased reactivity and selectivity in chemical transformations compared with neutral aminyl radicals, their generation is of utmost importance. Recently, a surge of reports has been revealed using visible light photoredox catalysis. It has been demonstrated that amines can act as an electron donor in a reductive quenching cycle while the amine itself is oxidized to the amine radical cation. Although a number of methods exist to generate amine radical cations, the photochemical formation of these species offers many practical advantages. In this Account, we discuss our journey to the development of annulation reactions with various π-bonds and electrophilic addition reactions to alkenes using photogenerated amine radical cations. Various carbocycles and heterocycles are produced by these reactions. In our annulation work, we first show that single electron photooxidation of cyclopropylanilines to the amine radical cations triggers ring opening of the strained carbocycle, producing distonic radical cations. These odd-electron species are shown to react with alkenes and alkynes to yield the corresponding cyclopentanes and cyclopentenes in an overall redox neutral process. Further development of this annulation reaction allows us to achieve the [4 + 2] annulation of cyclobutylanilines with alkynes. In our work on electrophilic addition reactions to alkenes, we reveal that photogenerated amine radical cations are capable of undergoing the electrophilic addition reactions to alkenes to form a variety of indoles and indolines. This chemistry represents a rare oxidative C-N bond-forming reaction using visible light. Conclusions drawn from observational results and proposed mechanisms are outlined in this Account. Additionally, open discussion of our successes and deficiencies in our experiences will give readers helpful insights as to how these species tend to react. The overall utility of photogenerated amine radical cations has yet to reach its full potential. With our current results, we anticipate more new transformations can still be derived from the ring opening processes of cyclopropylanilines and cyclobutylanilines under visible light photocatalysis. Additionally, since utilizing photogenerated amine radical cations in C-N bond-forming reactions has practically been absent in literature, we are confident more new reactions have ye...

Visible-light mediated photoredox reactions have recently emerged as a powerful means for organic synthesis and thus have generated significant interest from the organic chemistry community. Although the reaction mechanisms have been probed by a number of techniques such as NMR, fluorescence quenching, and laser flash photolysis and various degree of success has been achieved, mechanistic ambiguity still exists (for instance, the involvement of the chain mechanism is still under debate) due to lack of structural information about the proposed and short-lived intermediates. Herein, we present the detection of transient amine radical cations involved in intermolecular [3+2] annulation reaction of N-cyclopropylaniline (CPA, 1) and styrene 2 by electrospray ionization mass spectrometry (ESI-MS) in combination with online laser irradiation of the reaction mixture. In particular, the reactive CPA radical cation 1+·, the reduced photocatalyst Ru(I)(bpz)3 +, and the [3+2] annulation product radical cation 3+· are all successfully detected and confirmed by high resolution MS. More importantly, the post-irradiation reaction with an additional substrate, the isotope-labeled CPA following photolysis of 1, 2 and Ru catalyst provide strong evidences to support the chain mechanism in the [3+2] annulation reaction. Furthermore, the key step of the proposed chain reaction, the oxidation of CPA 1 to amine radical cation 1+· by product radical cation 3+· (generated using online electrochemical oxidation of 3) is successfully established. Additionally, the coupling of ESI-MS with online laser irradiation has been successfully applied to probe the photostability of photocatalysts.

We report the first example of intermolecular [4+2] annulation of cyclobutylanilines with alkynes enabled by visible light photocatalysis. Monocyclic and bicyclic cyclobutylanilines successfully undergo the annulation with terminal and internal alkynes to generate a wide variety of amine-substituted cyclohexenes including new hydrindan and decalin derivatives with good to excellent diastereoselectivity. The reaction is overall redox neutral with perfect atom economy.