Hydrogenation of fluoroarenes: Direct access to all- cis -(multi)fluorinated cycloalkanes

Abstract

All-c-multifluorinated cycloalkanes exhibit intriguing electronic properties. In particular, they display extremely high dipole moments perpendicular to the aliphatic ring, making them highly desired motifs in material science. Very few such motifs have been prepared, as their syntheses require multistep sequences from diastereoselectively prefunctionalized precursors. Herein we report a synthetic strategy to access these valuable materials via the rhodium-cyclic (alkyl)(amino)carbene (CAAC)-catalyzed hydrogenation of readily available fluorinated arenes in hexane. This route enables the scalable single-step preparation of an abundance of multisubstituted and multifluorinated cycloalkanes, including all--1,2,3,4,5,6-hexafluorocyclohexane as well as cis-configured fluorinated aliphatic heterocycles.

Hydrogenation of (Hetero)aryl Boronate Esters with a Cyclic (Alkyl)(amino)carbene–Rhodium Complex: Direct Access to cis‐Substituted Borylated Cycloalkanes and Saturated Heterocycles

“…[9] Herein, we report am ethod for the selective hydrogenation of substituted aryl boronate esters with ac yclic (alkyl)(amino)carbene (CAAC)-ligated rhodium complex. [10][11][12][13][14] This approach enables the hydrogenation of aryl and heteroaryl boronate esters with retention of the boronate ester functional group (Scheme 1b). Hence,i toffers as traightforward, chemo-, and stereoselective strategy to access elusive,d iversely substituted cis-borylated cycloalkanes that are difficult to prepare by conventional methods.…”

Die selektive Arenhydrierung bietet einen direkten Zugang zu gesättigten Carbo‐ und Heterocyclen

“…Dazu gehçren die Hydrierung von Benzol zu Cyclohexan (1) [1] oder Cyclohexen (2) [2] in der Nylon-Herstellung und die Hydrierung von Thymol zu (racemischem) Menthol (rac-3)i m Symrise-Mentholprozess. 6) [8] und Piperidinen (z. [5] Zudem gewinnt die Verwendung der Arenhydrierung fürdie Synthese gesättigter funktioneller Moleküle in der Feinchemie an Bedeutung.S o ermçglichte die enantioselektive Hydrierung von Chinolinen einen effizienten Zugang zu Te trahydrochinolinalkaloiden wie (À)-Galipinin (4).…”

“…[3] Weiterhin ist die Arenhydrierung ein wichtiger Schritt in der Verwertung von Plattformchemikalien aus Biomasse wie Furfural [4] und, zusammen mit der Dehydrierung,z entral beim Betrieb von flüssigen organischen Wasserstoffträgern (LOHCs). [9] Das erstgenannte Motiv (6)ist wegen der hohen Polaritätvon Interesse fürd ie Materialwissenschaft;d as zweite (7)k ombiniert zwei zentrale Motive der medizinischen Chemie.A ußerdem ist die chemo-und enantioselektive Hydrierung von Pyridinen der Schlüsselschritt der effizienten Synthese (7 Stufen, 38 %G esamtausbeute) eines Wikstoffkandidaten gegen Ty p-2-Diabetes (8). [6] Die von der Stoltz-Gruppe entwickelte Synthese von (À)-Jorunnamycin Aund (À)-Jorumycin (5)ist ein beeindruckendes aktuelles Beispiel.…”

Hydrogenation of (Hetero)aryl Boronate Esters with a Cyclic (Alkyl)(amino)carbene–Rhodium Complex: Direct Access to cis‐Substituted Borylated Cycloalkanes and Saturated Heterocycles

“…[8] Thec ontrol of stereoselectivity in the catalytic hydrogenation of substituted arenes is another major challenge,ascis and trans stereoisomers are usually formed. [10][11][12][13][14] This approach enables the hydrogenation of aryl and heteroaryl boronate esters with retention of the boronate ester functional group (Scheme 1b). [10][11][12][13][14] This approach enables the hydrogenation of aryl and heteroaryl boronate esters with retention of the boronate ester functional group (Scheme 1b).…”

“…[16,17] CAACs have found use as ancillary ligands in rhodium-catalyzed arene hydrogenations of aromatic ketones,phenols,fluoroarenes,and silylarenes. [11][12][13] We commenced our studies with the synthesis of the ortho-dimethyl-substituted CAAC-Rh complex ( Me CAAC)Rh(COD)Cl. [18] Ther elated aldiminium salt was deprotonated with lithium diisopropylamide (LDA), and then treated with [Rh(COD)Cl] 2 to afford the air-a nd moisturestable ( Me CAAC)Rh(COD)Cl complex in moderate yield (Scheme 2).…”