Catalytic Transfer Hydrodebenzylation with Low Palladium Loading

Abstract

A highly‐efficient catalytic system for hydrodebenzylation reaction is described. The cleavage of O‐benzyl and N‐benzyl protecting groups was performed using an uncommonly low palladium loading (0.02–0.3 mol%; TON up to 5000) in a relatively short reaction time. The approach was used for a variety of substrates including pharmaceutically important precursors, and gram‐scale deprotection reaction was shown. Transfer conditions together with easy‐to‐make Pd/C catalyst are the key features of this debenzylation scheme.magnified image

Role of the Bromide on the Hydrodebenzylation of 2,4,6,8,10,12‐Hexabenzyl‐2,4,6,8,10,12‐hexaazaisowurtzitane (HBIW)

“…Among chloride, bromide and iodide, bromide showed the best catalytic performance in terms of both kinetic and yield. The affinity between halide anion and the palladium increased in the following order: Cl<Br<I [32] . The medium interaction between bromide and palladium facilitated the absorption of HBIW and the desorption of the intermediate on the surface of the palladium [33] .…”

“…The affinity between halide anion and the palladium increased in the following order: Cl < Br < I. [32] The medium interaction between bromide and palladium facilitated the absorption of HBIW and the desorption of the intermediate on the surface of the palladium. [33] More interestingly, HBr exhibited a better catalytic performance than KBr in terms of yield, and it seems that H + can also improve the catalytic performance in terms of yield.…”

Ru-gC3N4 Catalyzed Hydrodebenzylation of Benzyl Protected Alcohol and Acid Groups Using Sodium Hypophosphite as a Hydrogen Source

“…Protection and de-protection of alcohol and acid groups is an important methodology in the field of fine chemicals and pharmaceutical industries. Researchers prefer this pathway to control side reactions during chemical transformations in these fields [1,2]. The most conventional used protection technique is the preparation of benzyl ether and ester during various drug syntheses [3,4].…”

“…There are several catalytic systems reported for the hydrodebenzylation protocol and some of the latter use transition metal catalysts. The major catalytic methods used for this reaction through the past few decades are Pd [2,[9][10][11][12][13][14], Pt [15], Rh [16], Ru [17][18][19], Raney Ni [20,21], Ni [22][23][24], Cu [25], Co [26], and on occasion bimetallic [13,14,17,[27][28][29]. The majority of these metal catalysts were applied as homogeneous catalysts and several as heterogeneous.…”

“…The latter depends on the on metal loading and causes serious handling issues even in lab scale reactions. The most commonly used hydrogen donors for the hydrodebenzylation or transfer hydrogenation reactions are sodium borohydride [24], lithium aluminum hydride [26], 2-propanol [11,29], formic acid [2], alkali metal formates [30], sodium hypophosphite [10], supercritical ethanol [31], and molecular hydrogen. Most of these hydrogen sources have been used with the Pd metal catalyst.…”