Multicomponent reactions (MCRs) are fundamentally different from two-component reactions in several aspects. Among the MCRs, those with isocyanides have developed into popular organic-chemical reactions in the pharmaceutical industry for the preparation of compound libraries of low-molecular druglike compounds. With a small set of starting materials, very large libraries can be built up within a short time, which can then be used for research on medicinal substances. Due to the intensive research of the last few years, many new backbone types have become accessible. MCRs are also increasingly being employed in the total synthesis of natural products. MCRs and especially MCRs with isocyanides offer many opportunities to attain new reactions and basic structures. However, this requires that the chemist learns the “language” of MCRs, something that this review wishes to stimulate.

Multicomponent Reactions with Isocyanides.

In this review, we highlight the use of organic photoredox catalysts in a myriad of synthetic transformations with a range of applications. This overview is arranged by catalyst class where the photophysics and electrochemical characteristics of each is discussed to underscore the differences and advantages to each type of single electron redox agent. We highlight both net reductive and oxidative as well as redox neutral transformations that can be accomplished using purely organic photoredox-active catalysts. An overview of the basic photophysics and electron transfer theory is presented in order to provide a comprehensive guide for employing this class of catalysts in photoredox manifolds.

Organic Photoredox Catalysis

The chemistry of heterocyclic carbenes has experienced a rapid development over the last years. In addition to the imidazolin-2-ylidenes, a large number of cyclic diaminocarbenes with different ring sizes have been described. Aside from diaminocarbenes, P-heterocyclic carbenes, and derivatives with only one, or even no heteroatom within the carbene ring are known. New methods for the synthesis of complexes with N-heterocyclic carbene ligands such as the oxidative addition or the metal atom template controlled cyclization of β-functionalized isocyanides have been developed recently. This review summarizes the new developments regarding the synthesis of N-heterocyclic carbenes and their metal complexes.

Heterocyclic Carbenes: Synthesis and Coordination Chemistry

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

Benjamin H. Rotstein,†,‡ Serge Zaretsky,† Vishal Rai,†,§ and Andrei K. Yudin*,† †Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario Canada, M5S 3H6 ‡Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, and Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, Massachusetts 02114, United States Department of Chemistry, Indian Institute of Science Education and Research (IISER) Bhopal, Indore By-pass Road, Bhauri, Bhopal 462 066, MP India

Small Heterocycles in Multicomponent Reactions

Über zweistufige Redoxsysteme, X1) Tetrathio-äthylene und ihre höheren Oxidationsstufen

Mit Elektronendonatoren tetrasubstituierte Athylene und ihre formalen Dissoziationsprodukte, die zugehorigen nucleophilen Carbene, reagieren mit allen bisher benutzten Elektrophilen zum gleichen Typus von Produkten. Durch Einsatz reaktiver Azide (z. B. Tosylazid) last sich eindeutig zwischen Athylen- und Carbenreaktion unterscheiden, wie am Beispiel der entsprechenden Benzthiazolderivate gezeigt wird. Als Nebenreaktionen sind Redoxvorgange zu berucksichtigen.

Zum Problem der nucleophilen Carbene

Durch regioselektive Alkylierung des 1-tert-Butyl-1,4-dihydro-5-H-tetrazol-5-ons (7) erhalt man die 1,4-Dialkyltetrazolone 8b und c. Der elektronenstosinduzierte Zerfall des bekannten, einfachsten Tetrazolons 8a verlauft im Sinne einer [3+2]Cycloeliminierung in Methylazid und Methylisocyanat. Die Photolyse der Tetrazolone 8 in Acetonitril oder Pentan ergibt unter Stickstoffabspaltung 1,2-Dialkyldiaziridinone 24, von denen 24c in reiner Form isoliert wird. Besonders reaktive Alkylierungsmittel wie Fluorsulfonsaure-methylester, Trimethyloxonium-tetrafluoroborat oder tert-Butylalkohol/Tetrafluoroborsaure in Ether alkylieren 1-Methyl-5-(methylthio)1H-tetrazol (9a) bevorzugt an N-3, Dimethylsulfat reagiert zu etwa gleichen Teilen mit N-3 oder N-4. In der so erhaltenen Mischung der Salze 10a und 11a wird nur 11a durch Triethylamin in Acetonitril am Schwefel entmethyliert, wobei das leicht abtrennbare Tetrazolthion 5a entsteht. 1-tert-Butyl-1,4-dihydro-5H-tetrazol-5-thion (18b) wird durch Diazomethan uberwiegend am Schwefel, durch 2-Diazopropan aber in ungefahr gleichen Umfang am Schwefel oder an N-4 zum Tetrazolthion 5c alkyliert. Neben den durch [3+2] Cycloeliminierung in Methylazid und Methylisothiocyanat entstandenen Fragment-Ionen beobachtet man beim elektronenstosinduzierten Zerfall des einfachsten Tetrazolthions 5a auch Ionen, die sich auf eine Stickstoffabspaltung von dem Molekul-Ion zuruckfuhren lassen. Die Photolyse der Tetrazolthione 5 in Alkanen oder Acetonitril bei +20 bis -40°C spaltet Stickstoff ab und ergibt hohe Ausbeuten an Carbodiimiden 30 und Schwefel.



Synthesis and Photolysis of 1,4-Dialkyl-1,4-dihydro-5H-tetrazol-5-ones ans -thiones. A Novel Approach to Diaziridinones and Carbodiimides1)



The regioselective alkylation of the 1-tert-butyl-1,4-dihydro-5H-tetrazol-5-one (7) produced the 1,4-dialkyltetrazolones (8b) and c. The electron impact induced decomposition of the known, most simple tetrazolone 8a proceeded via a [3+2] cycloelimination into methyl azide and methyl isocyanate. On photolysis in acetonitrile or pentane, the tetrazolones 8 lost nitrogen and formed 1,2-cyanate. On photolysis in acetonitrile or pentane, the tetrazolones 8 lost nitrogen and formed 1,2-dialkyldiaziridinones 24, of which 24c was isolated in pure from. Very reactive alkylating reagents, e.g. methyl fluorosulfonate, trimethyloxonium tetrafluoroborate, or tert-butyl alcohol/tetrafluoroboric acid in ether, preferentially alkylated N-3 of 1-methyl-5-(methylthio)-1H-tetrazole (9a); dimethyl sulfate reacted almost equally at N-3 or N-4. In the mixture of the salts 10a and 11a obtained in this way, only 11a was demethylated at the sulfur atom by triethylamine in acetonitrile affording the easily separable tetrazolethione 5a. Diazomethane methylated 1-tert-butyl-1,4-dihydro-5H-tetrazole-5-thione (18b) predominantly at the sulfur atom. In contrast, 2-diazopropane gave approximately equal fractions of S-alkylation and N-4-alkylation producing the tetrazolethione 5c. Besides fragment ions resulting from [3+2]cycloelimination products, in the electron impact induced decomposition of the most simple tetrazolethione Sa, ions were observed which correspond to loss of nitrogen from the molecular ion. On photolysis in alkanes or acetonitrile in the temperature range between +20 and −40°C the tetrazolethiones lost nitrogen furnishing high yields of sulfur and the carbodiimides 30.

Helmut Quast

Papers

Über zweistufige Redoxsysteme, X1) Tetrathio-äthylene und ihre höheren Oxidationsstufen

Zum Problem der nucleophilen Carbene

Synthese und Photolyse von 1,4‐Dialkyl‐1,4‐dihydro‐5H‐tetrazol‐5‐onen und ‐thionen: Neue Wege zu Diaziridinonen und Carbodiimiden1)

Heterocyclische Ylide, II1) Ylide durch Decarboxylierung von N-Methyl-carbonsäurebetainen des Pyridins, Chinolins und Isochinolins

Über zweistufige Redoxsysteme, XII1) Synthese und Polarographie von Quartärsalzen der Phenanthroline, des 2,7‐Diazapyrens sowie der Diazoniapentaphene