Enantioselective Hydrogenation of Imidazo[1,2‐a]pyridines

Abstract

The enantioselective synthesis of tetrahydroimidazo[1,2-a]pyridines by direct hydrogenation was achieved using a ruthenium/N-heterocyclic carbene (NHC) catalyst. The reaction forgoes the need for protecting or activating groups, proceeds with complete regioselectivity, good to excellent yields, enantiomeric ratios of up to 98:2, and tolerates a broad range of functional groups. 5,6,7,8-Tetrahydroimidazo[1,2-a]pyridines, which are found in numerous bioactive molecules, were directly obtained by this method, and its applicability was demonstrated by the (formal) synthesis of several functional molecules.

Recent developments in enantio- and diastereoselective hydrogenation of N-heteroaromatic compounds

“…The same group also reported the EH of pyrido-pyrimidones to form multiple stereocenters in adjacent rings leading to structurally complex motifs. 125 The previously reported conditions 122,123 were adopted for the hydrogenation, which showed complete chemoselectivity, with moderate to excellent diastereo-, and enantioselectivity (Scheme 50).…”

Enantioselective γ‐Addition of Pyrazole and Imidazole Heterocycles to Allenoates Catalyzed by Chiral Phosphine

“…For example, reduction of 3 m , followed by oxidation of the alcohol and cyclization led to the corresponding dimethylcarbamate 7 . Finally, compound 8 , a key intermediate of a muscarinic receptor M3 antagonist, as shown by Kaiser, was obtained after a sequence of reductions in 41 % yield over two steps (Scheme ).…”

“…Unsubstituted imidazoles,b enzimidazoles,a nd phenyl imidazoles were well tolerated, and gave the expected products 3m-3q in 55-77 %yield and 88-93 % ee. Fore xample,r eduction of 3m, followed by oxidation of the alcohol and cyclization led to the corresponding dimethylcarbamate 7.F inally,c ompound 8, akey intermediate [18] of amuscarinic receptor M3 antagonist, as shown by Kaiser, [19] was obtained after as equence of reductions in 41 %yield over two steps (Scheme 3). [16] Allenoates with functionalized g-substituents are compatible with the reaction conditions,a nd provide an easy access to chiral g-heteroaryl butenoates (Table 3).…”

Mechanistic Investigation of Well-Defined Cobalt Catalyzed Formal E-Selective Hydrophosphination of Alkynes

“…However, the sluggish progress in developing new metal catalysts is perhaps due to that the resultant trivalent vinyl phosphine is an excellent coordinating ligand, which is likely to poison the catalyst. Hence, the catalyst development for hydrophosphination reaction of unsaturated C–X (where X  C, O, N, S) bonds was not much explored − compared to the other hydro-functionalization reactions such as hydroboration, hydrosilylation, hydroamination, etc. ,− …”