Diboron-Assisted Palladium-Catalyzed Transfer Hydrogenation of N-Heteroaromatics with Water as Hydrogen Donor and Solvent

Abstract

A Pd-catalyzed transfer hydrogenation of various N-heteroaromatic compounds with B2pin2 as a mediator and environmentally benign water as both solvent and hydrogen donor has been disclosed. This reaction proceeded under ambient temperature with a broad range of N-heteroaromatic compounds among which imidazo[1,2-a]pyridine derivatives were for the first time selectively reduced to 5,6,7,8-tetrahydroimidazo[1,2-a]pyridines, which are the core structural motifs of an inhibitor of human O-GlcNAcase. Mechanistic studies suggested that the new protons in products are from water and Pd-H might be the key intermediate with B2pin2 as the H2O activator.

Catalytic Reductions Without External Hydrogen Gas: Broad Scope Hydrogenations with Tetrahydroxydiboron and a Tertiary Amine

“…Doubling the amount of pyrrolidine appeared to lead to a slightly incomplete reaction (entry 9), and even on a lower scale water was less effective (entry 11). Absence of B 2 (OH) 4 , or pyrrolidine, or Pd/C led to practically no reaction (entries [12][13][14].…”

“…Previously, phenol triflates have been reduced with a combination of a Pd catalyst, phosphine ligand, and an amine (with or without an acid additive), with formate often serving as a source of hydrogen atoms. [25][26][27][28] Under the conditions described here, the triflate derivative of 4-acetaminophen [29] was reduced in high yield to acetanilide (14). By comparison to the easy reducibility of this triflate, the tosylate and mesylate derivatives underwent reduction in only 5% and 22% yields, respectively (as assessed by 1 H NMR).…”

“…[13] The combination of (pinB) 2 and H 2 O has been the focus of several reduction protocols. In the presence of Pd(OAc) 2 , quinolines, quinoxalines, and imidazo [2,1a] pyridines were reduced (with or without added base), [14] and imidazo [2,1a]pyridines with added PCy 3 . [15] Aldehydes and ketones were reduced in the presence of DBU, without Pd(OAc) 2 , [16] but with Pd (OAc) 2 and Cs 2 CO 3 a quinoline and a pyridine underwent ring reduction, and benzonitrile was reduced to benzylamine.…”

Efficient Water Reduction with sp3‐sp3 Diboron(4) Compounds: Application to Hydrogenations, H–D Exchange Reactions, and Carbonyl Reductions

“…[2][3][4] Similarly,w ater was used as ah ydride source in palladiumcatalyzed enantioselective reductive Heck reactions employing either B 2 (OH) 4 or B 2 cat 2 . [2][3][4] Similarly,w ater was used as ah ydride source in palladiumcatalyzed enantioselective reductive Heck reactions employing either B 2 (OH) 4 or B 2 cat 2 .…”

“…[1] Furthermore,s everal groups have demonstrated that the combination of either B 2 (OH) 4 or B 2 pin 2 with water generates ap alladium hydride species,w hich can be applied to the selective hydrogenation of unsaturated bonds. [2][3][4] Similarly,w ater was used as ah ydride source in palladiumcatalyzed enantioselective reductive Heck reactions employing either B 2 (OH) 4 or B 2 cat 2 . [5] There has been ag rowing focus on the use of isolated sp 2 -sp 3 diboron(4) compounds ( Figure 1).…”