Cyclopropanation Reactions of Semi-stabilized and Non-stabilized Diazo Compounds

Abstract

The cyclopropane ring is present in a large number of bio­active molecules as its incorporation often greatly alters their physiochemical properties. The synthesis of such motif is therefore of interest. Diazo compounds are versatile and powerful reagents that can be used in a broad range of reactions, including cyclopropanation processes. However, in case of unstable diazo reagents such as the donor-substituted­ variants, their inherent toxicity and instability have hampered their effective synthesis and utilization. Herein, we report the recent­ advances devoted to the safe and facile production of these potentially hazardous species and their subsequent application in cyclopropanation reactions, allowing the synthesis of more complex cyclopropylated motifs.1 Introduction2 Halomethylmetal-Mediated Cyclopropanations3 Cyclopropanations through Metallic- or Free Carbenes3.1 Transition-Metal-Catalyzed Decomposition of Diazo Compounds3.2 Metal-Free Decomposition of Diazo Compounds4 Michael Induced Ring Closure (MIRC) Reactions4.1 Sulfur Ylides4.2 1,3-Dipolar Cycloadditions5 Conclusion

Predicting Absolute Rate Constants for Huisgen Reactions of Unsaturated Iminium Ions with Diazoalkanes

“…Combination of the iminium hexafluorophosphates 1 a , 2 a , or 3 a with 1.5 equivalents of diphenyldiazomethane ( 4 ) in different solvents and subsequent workup with aqueous phosphate buffer gave 2,2,3‐triphenylcyclopropanecarbaldehyde ( 5 a ) in variable yields and enantioselectivities. As shown in Table , the reaction of 1 a with 4 afforded good yields of the cyclopropanecarbaldehyde 5 a in dichloromethane, DMF, and acetonitrile, but not in methanol and THF solutions.…”

Iron catalysts with N-ligands for carbene transfer of diazo reagents

“…[21][22][23][24][25][26] Frequently, the cleavage of the cyclopropyl carbon-carbon bond is also a way, in which active drug molecules produce their pharmacological effects. 16 The cyclopropanation reaction, which takes place by transferring the carbene unit from the diazo compound to the double bond, 27 can occur with a specific diastereoselectivity and, if conducted in the presence of a chiral promoter, a pair of enantiomers are obtained for each diastereomer (Scheme 1). The reaction selectivity can be modulated by using the opportune metal catalyst and, also in the case of ironpromoted reactions, the choice of the ligand that coordinates the metal center is crucial for enhancing both the chemo-and stereoselectivity (diastereo-and enantioselectivity) of the process.…”

“…This experimental approach is of particular interest when the high reactivity of the required diazo reagents (such as monosubstituted, low-molecular weight alkyl-, aryl diazo compounds, diazoacetonitrile) prevents their safe handling in a laboratory. 46 Many papers have been published on the use of stable diazoprecursors 14,27 since V. K. Aggarwal and co-authors 47 first described the transformation of N-tosylhydrazones salts (RCH=NNTsNa) into diazo compounds (RCHN 2 ) by the Bamford-Stevens reaction 48 and their iron-porphyrin-catalyzed reaction with alkenes to form cyclopropanes. Besides all the diazo-precursors employed, Diazald is one of the most interesting reagents because it is able to generate the simplest diazo compound: diazomethane (CH 2 N 2 ).…”

Voraussage absoluter Geschwindigkeitskonstanten von Huisgen‐ Reaktionen ungesättigter Iminium‐Ionen mit Diazoalkanen

“…Umsetzung der Iminium‐hexafluorphosphate 1 a , 2 a oder 3 a mit 1.5 Äquiv. Diphenyldiazomethan ( 4 ) in verschiedenen Lösungsmitteln und nachfolgende Aufarbeitung mit wässrigem Phosphatpuffer ergab 2,2,3‐Triphenylcyclopropancarbaldehyd ( 5 a ) in unterschiedlichen Ausbeuten und Enantioselektivitäten. Wie in Tabelle gezeigt, lieferte die Reaktion von 1 a mit 4 in Dichlormethan, DMF oder Acetonitril gute Ausbeuten des Cyclopropancarbaldehyds 5 a , aber nicht in Methanol‐ oder THF‐Lösung.…”