Oxidative Heterocycle Formation Using Hypervalent Iodine(III) Reagents
TL;DR: This chapter focuses on the general application of hypervalent iodine(III) reagents in the de novo synthesis and in the late stage functionalization of heterocyclic compounds.
Abstract: Hypervalent iodine(III) reagents have been widely exploited in a diverse array of synthetic transformations. This chapter focuses on the general application of hypervalent iodine(III) reagents in the de novo synthesis and in the late stage functionalization of heterocyclic compounds.
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TL;DR: A sulfur-iodine exchange protocol of diaryliodonium salts with inorganic sulfur salt was developed and five- to eight-membered sulfur-containing heterocycles were achieved.
109 citations
TL;DR: The present review, classified according to the types of synthetic methods involved, encompasses all recent developments in the field of transition-metal-free iodine(iii)-catalyzed/mediated direct functionalizations of heterocycles with representative examples and insightful mechanistic discussions.
Abstract: Late stage functionalization (LSF) through direct X-H manipulations (X = C, N) enables synthetic chemists to accelerate the diversification of natural products, agrochemicals and pharmaceuticals allowing rapid access to novel bioactive molecules without resorting to arduous de novo synthesis. LSF does not only allow tapping of the hitherto unexplored chemical space but also renders the synthetic sequence more straightforward, atom economical and cost-effective. In this regard, the recent decade has witnessed the emergence of hypervalent iodine(iii) reagents as a powerful synthetic tool owing to their easy availability, mild reaction conditions, remarkable oxidizing properties and high functional group tolerance. Iodine(iii) reagents have tremendous applications in the regio- and chemo-selective late-stage functionalization of a diverse variety of heterocycles through an exciting range of transformations, such as oxidative amination, cross-dehydrogenative coupling (CDC), fluoroalkylation, azidation, halogenation and oxidation. The present review, classified according to the types of synthetic methods involved, encompasses all these recent developments in the field of transition-metal-free iodine(iii)-catalyzed/mediated direct functionalizations of heterocycles with representative examples and insightful mechanistic discussions.
53 citations
TL;DR: Various atom-economical applications of diaryliodonium salt methodologies that have been reported recently for the synthesis of functionalized molecules are focused on.
Abstract: Diaryliodonium salt, as a stable and easily prepared reagent, has become one of the most efficient arylation reagents in organic synthesis. In traditional methods, this reagent is generally applied as a single arylation source and the regenerated aryl iodide is a waste of resources. In the past five years, transition-metal-catalyzed utilization of both aryl groups in diaryliodonium salts has been well demonstrated. The purpose of the present review is to focus on various atom-economical applications of diaryliodonium salt methodologies that have been reported recently for the synthesis of functionalized molecules. The presentation is organized according to the structures of the diaryliodonium salts and the reaction components.
51 citations
TL;DR: The methodology is unprecedented among metal‐free methods in terms of amine scope, the ability to transfer both electron‐withdrawing and electron‐donating aryl groups, and efficient use of resources, as excess substrate or reagents are not required.
Abstract: A transition metal-free N-arylation of primary and secondary amines with diaryliodonium salts is presented. Both acyclic and cyclic amines are well tolerated, providing a large set of N-alkyl anilines. The methodology is unprecedented among metal-free methods in terms of amine scope, the ability to transfer both electron-withdrawing and electron-donating aryl groups, and efficient use of resources, as excess substrate or reagents are not required.
46 citations
TL;DR: This method provides a concise and highly valuable pathway for the synthesis of enantiopure aminophosphine ligands in large-scale through diastereoselective metal-free intramolecular radical oxidative C-H amination with chiral phosphamide as the auxiliary group.
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TL;DR: This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry, and are more atom- and step-economical than previous methods.
Abstract: The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry.
1,838 citations
TL;DR: An overview of the historical and recent advances in the synthesis and applications of diaryliodonium salts is provided.
Abstract: The recent groundbreaking developments in the application of diaryliodonium salts in cross-coupling reactions has brought this class of previously underdeveloped reagents to the forefront of organic chemistry. With the advent of novel, facile, and efficient synthetic routes to these compounds, many more applications can be foreseen. Herein we provide an overview of the historical and recent advances in the synthesis and applications of diaryliodonium salts.
835 citations
TL;DR: Concerted metalation-deprotonation (CMD) is now proposed to be the turnover limiting step and DFT calculations conducted on this system agree with a stepwise C-N bond reductive elimination/N-O bond oxidative addition mechanism to afford the desired heterocycle.
Abstract: Directing groups that can act as internal oxidants have recently been shown to be beneficial in metal-catalyzed heterocycle syntheses that undergo C−H functionalization. Pursuant to the rhodium(III)-catalyzed redox-neutral isoquinolone synthesis that we recently reported, we present in this article the development of a more reactive internal oxidant/directing group that can promote the formation of a wide variety of isoquinolones at room temperature while employing low catalyst loadings (0.5 mol %). In contrast to previously reported oxidative rhodium(III)-catalyzed heterocycle syntheses, the new conditions allow for the first time the use of terminal alkynes. Also, it is shown that the use of alkenes, including ethylene, instead of alkynes leads to the room temperature formation of 3,4-dihydroisoquinolones. Mechanistic investigations of this new system point to a change in the turnover limiting step of the catalytic cycle relative to the previously reported conditions. Concerted metalation−deprotonation ...
810 citations
TL;DR: It is shown here how the structure of the C−O Bond Formation following C−H Bond Oxidation following Baeyer−Villiger-type Reaction and Wacker-type Cyclization influenced the formation of the S−N Bond Formation.
Abstract: II.2.1. Homogeneous Systems 2166 II.2.2. Heterogeneous Systems 2168 II.3. Hydride Transfer Reduction 2169 II.3.1. Homogeneous Systems 2169 II.3.2. Heterogeneous Systems 2171 II.4. Hydrosilylation 2172 III. C−O Bond Formation 2173 III.1. Epoxidation of Unfunctionalized Olefins 2173 III.1.1. Homogeneous Catalysis 2173 III.1.2. Heterogeneous System 2176 III.2. Dihydroxylation of Olefins 2178 III.2.1. Homogeneous Systems 2178 III.2.2. Heterogeneous System 2178 III.3. Ring Opening of Meso Epoxides 2180 III.4. Kinetic Resolution 2180 III.4.1. Terminal Epoxides 2180 III.4.2. Secondary Alcohols 2181 IV. C−H Bond Oxidation 2181 IV.1. Allylic and Benzylic Oxidation 2181 IV.2. Baeyer−Villiger-type Reaction 2181 IV.3. Wacker-type Cyclization 2182 V. S−O Bond Formation 2182 VI. C−N Bond Formation 2183 VI.1. Hydroboration/Amination 2183 VI.2. Enolate Amination 2183 VI.3. Aza-Claisen Rearrangement 2183 VI.4. Azide Synthesis 2184 VI.5. Aminohydroxylation 2184 VI.6. Aziridine Synthesis 2184 VI.7. C−N Bond Formation via S−N Bond Formation 2185
809 citations
TL;DR: An external-oxidant-free process to access the isoquinolone motif via cross-coupling/cyclization of benzhydroxamic acid with alkynes is described, pointing out the important involvement of a N-O bond as a tool for C-N bond formation and catalyst turnover.
Abstract: An external-oxidant-free process to access the isoquinolone motif via cross-coupling/cyclization of benzhydroxamic acid with alkynes is described. The reaction features a regioselective cleavage of a C-H bond on the benzhydroxamic acid coupling partner as well as a regioselective alkyne insertion. Mechanistic studies point out the important involvement of a N-O bond as a tool for C-N bond formation and catalyst turnover.
677 citations