Palladium-Catalyzed Aerobic Dehydrogenation of Cyclic Hydrocarbons for the Synthesis of Substituted Aromatics and Other Unsaturated Products

Abstract

Catalytic dehydrogenation of saturated or partially saturated six-membered carbocycles into aromatic rings represents an appealing strategy for the synthesis of substituted arenes. Particularly effective methods have been developed for the dehydrogenation of cyclohexanones and cyclohexenes into substituted phenol, aniline, and benzene derivatives, respectively. In this Perspective, we present the contributions of our research group to the discovery and development of palladium-based catalysts for aerobic oxidative dehydrogenation methods, including general methods for conversion of cyclohexanones and cyclohexenones into substituted phenols and a complementary method for partial dehydrogenation cyclohexanones to cyclohexenones. The mechanistic basis for chemoselective conversion of cyclohexanones to phenols or enones is presented. These results are presented within the context of recent methods developed by others for the synthesis of aryl ethers, anilines and other substituted arenes. Overall, Pd-catalyzed dehydrogenation methods provide a compelling strategy for selective synthesis of aromatic and related unsaturated molecules.

Chemoselective α,β‐Dehydrogenation of Saturated Amides

“…Pioneering work by Kingsbury and Cram on the concerted thermal elimination of alkyl sulfoxides [7] later inspired similar work on selenoxide elimination. [8] TheS aegusa-Ito oxidation [9] is another well-known and often employed route to dehydrogenated carbonyl systems but is atwo-step procedure.Despite the original use of stoichiometric palladium, notable efforts have been made to develop efficient catalytic reactions based on much greener oxidants by the groups of Stahl [10] and others. [11] Although reliable,these methods often involve two steps or are limited to (cyclic) ketones.O ther important contributions include the work of Nicolaou and co-workers, who reported the use of 2-iodoxybenzoic acid (IBX) to oxidise ketones to the corresponding a,b-enones.…”

Unified Synthesis of 1,2-Oxy-aminoarenes via a Bio-inspired Phenol-Amine Coupling

“…When R 1 = H, the benzoxazole is obtained from ortho-iminophenol 4 by cyclization and dehydrogenation, demonstrating that the Cu catalyst used to oxygenate 1 can also dehydrogenate 5. 48 Alternatively, when R 1 = CO 2 Me, dehydrogenation of 6 cannot occur, and the benzoxazinone is obtained by lactonization (see Scheme S1). For obtaining the unsubstituted The scope of the C-N bond formation was explored with phenol 1 and a range of 1 amines (Scheme 6).…”

Enantioselective Total Syntheses of Pallambins A–D

“…One‐step methods for the direct dehydrogenation of ketones were investigated first. However, oxidation of ketone 14 with IBX, and other methods such as palladium‐catalyzed dehydrogenation, did not give any 24 . Therefore, two‐step methods, such as silyl enol ether formation/Saegusa reaction, selenoxide and sulfoxide elimination reactions, as well as bromination/dehydrobromination, were tested .…”