C−O Hydrogenolysis Catalyzed by Pd-PMHS Nanoparticles in the Company of Chloroarenes

Abstract

Catalytic Pd(OAc) 2 and polymethylhydrosiloxane (PMHS), in conjunction with aqueous KF, and a catalytic amount of an aromatic chloride, effects the chemo, regio, and stereoselective deoxygenation of benzylic oxygenated substrates at room temperature in THF. Preliminary mechanistic experiments suggest the process to involve palladium-nanoparticle catalyzed hydrosilylation followed by C-O reduction. The chloroarene additive appears to facilitate the hydrogenolysis process through the slow controlled release of HCl.In the early 1990's, Tour1 and Crabtree2 independently reported on how dispersing palladium throughout a siloxane polymer matrix raises the catalytic activity of the metal. Originally termed Pd-colloids, in 2004 Chauhan 3 unequivocally showed that by mixing Pd(OAc) 2 with polymethylhydrosiloxane (PMHS) formed polysiloxane-encapsulated Pd-nanoclusters.We had previously reported that Pd(OAc) 2 /PMHS in the presence of aqueous KF rapidly hydrodehalogenated chloroarenes.4 Despite PMHS' ability to reduce ketones to alcohols, 5 this system chemoselectively dechlorinated 4-(4-chlorophenyl)-2-butanone (eq 1). In contrast, when 4'-chloroacetophenone was placed under the same conditions, it was fully reduced to ethylbenzene (eq 2).(1) (2) Since transfer hydrogenolysis of activated C-O bonds by PMHS are known, 6 we were not entirely surprised by this result, until we examined the reactivity of acetophenone. After being exposed to the Pd(OAc) 2 /PMHS/KF (aq) conditions for 24 hours, the acetophenone afforded no visible amounts of ethyl benzene, stopping instead at 1-phenylethanol ( Empirically, the presence of a chloro group was influencing the reactivity of the benzylic ketone/alcohol. Yet, GC monitoring of the 4'-chloroacetophenone reduction indicated the intermediacy of acetophenone. Thus the chloro group of 4-chloroacetophenone was not directly enhancing its reactivity. An investigation was undertaken to uncover why in situ generated acetophenone undergoes full deoxygenation, while subjecting acetophenone starting material to the "same" reduction conditions stopped at the alcohol. Through experimentation, we found that by simply starting the reaction in the company of chlorobenzene, acetophenone was quantitatively reduced to ethylbenzene after 1 hour at room temperature. Moreover, 10 mol % chlorobenzene 7 proved equally effective at facilitating the reaction.To the best of our knowledge this is the first example of chlorobenzene serving as a productive additive in Pd-mediated reductions.8 , 9 ,10 To explore this curious finding further, we surveyed a variety of chlorides and related additives against the reaction of acetophenone with Pd (OAc) 2 /PMHS/KF (aq) .Where chlorobenzene efficiently facilitated deoxygenation, among bromobenzene, iodobenzene, and phenyl nonaflate (entries 2-4, 8) only PhBr showed any effectiveness as an additive with its reaction affording ethylbenzene in 22% yield. With PhI and PhONf, the reductions stopped at 1-phenylethanol. It was also noted that relative to chlorobenzene, P...

Efficient Palladium‐Catalyzed CO Hydrogenolysis of Benzylic Alcohols and Aromatic Ketones with Polymethylhydrosiloxane

“…The corresponding benzylic alcohols and secondary alcohol analogues could also be converted into their respective methylene hydrocarbons by the PdCl 2 /PMHS system. In this context, Maleczka et al [10] has reported very recently an important and effective catalytic system with PdA C H T U N G T R E N N U N G (OAc) 2 (5 mol%) and PMHS (2.5 equiv.) It is a by-product of the organosilicon industry and an inexpensive hydrosilane that can be employed as the stoichiometric reducing agent in organic synthesis.…”

Polymethylhydrosiloxane

“…84 Mild deoxygenation of aryl ketones to the corresponding methylene compounds has been achieved using PMHS, fluoride ion, and catalytic Pd in the presence of aryl chlorides. 85 The aryl chloride is thought to facilitate the hydrogenolysis process through slow release of HCl. The same conditions could be used for Odebenzylation of other species, including benzyl ethers, benzyl esters (as lactones), tertiary benzyl alcohols, or tertiary benzyl epoxides.…”

“…In the latter two cases, chiral integrity at the benzylic position was retained. 85 The carbonyl group of amides can also be reduced using PMHS to provide the corresponding amine species. In the presence of an iron carbonyl catalyst, a variety of aromatic, aliphatic, heteroaromatic, and heterocyclic amides were smoothly reduced to the corresponding amines (eq 41).…”

Concise access toward chiral hydroxy phenylpropanoids: formal synthesis of virolongin B; kigelin; kurasoin A; 4-hydroxysattabacin, and actinopolymorphol A

“…12 Many catalytic systems are being optimized to selectively cleave CAO bonds in a molecule demonstrating not only the efficacy of catalytic systems but also highlighting the importance of the CAO bond breaking strategy. 13 To realize the synthesis of the natural compound, kigelin, (2) we targeted synthesis of key chiral intermediate 13 and for the synthesis of key compound 13 we needed to synthesise isoelemicine 11 which was synthesized as reported in the literature. 14 Synthetic procedure commenced with the allyation of phenol 8a to get compound 9 which on Claisen rearrangement gave the phenolic compound 10.…”