Hydrogenolysis with Hydrides

Oxidative addition of aryl and alkenyl halides, and pseudohalides, followed by transmetallation with various metal hydrides generates Ar—M—FI species, reductive elimination of which results in hydrogenolysis of halides. In the main, Pd is used as an efficient catalyst for the hydrogenolysis. 

The phenolic OH group can be removed by Pd-catalysed hydrogenolysis of its triflate 522 with triethylammonium formate [261]. Naphthol can be converted to naphthalene by the hydrogenolysis of its triflate. The Ni-catalysed reduction of aryl mesylates 523 is possible using MeOH and Zn as the hydrogen donor [262]. Smooth removal of phenol groups as triflates and mesylates is not possible by any other means. 

Ketones and aldehydes are converted to alkenes by the hydrogenolysis of their enol triflates with formate. The steroidal enone 524 is converted to the dienol triflate 525 and then to the 1,3-diene 526 by the hydrogenolysis with tributylammonium formate 

Palladium Reagents and Catalysts, pp. 125-290, John Wiley, 1995. 

Tsuji (Ed), Perspectives in Organopalladium Chemistry for the XXI Century, pp. 1-124, Elsevier, 1999. 

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Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

Treatment of hydride 28 with dichlorocarbene, a process known to proceed with retention of configuration14, afforded the insertion product 27. Hydrogenolysis with BusSnH led to the monochloro derivative 26, which afforded the amine 24 of nearly identical... 

Another limitation is seen when extra strain is included in the compound to be reduced. Dehalogenation of 3,3-dichlorobicyclo[2.2.0]hexan-2-one with zinc/ammonium chloride in methanol gave, at best, a 25% yield of 3-chlorobicyclo[2.2.0]hexan-2-one (14) together with cyclohexenone and 6-chlorohex-5-enoic acid.128 The best results were achieved with the zinc/ acetic acid system, while addition of water, silver-promoted zinc reduction in methanol, tri-butyltin hydride reduction or hydrogenolysis with palladium in methanol did not result in formation of 14, but various other ring-opened products. 

Acyl halides can be reduced to aldehydes1206 by treatment with lithium tri-f-butoxyaluminum hydride in diglyme at -78°C,1207 R may be alkyl or aryl and may contain many types of substituents, including N02, CN, and EtOOC groups. The reaction stops at the aldehyde stage because steric hindrance prevents further reduction under these conditions. Acyl halides can also be reduced to aldehydes by hydrogenolysis with palladium-on-barium sulfate... 

The aminocarbonyl group attached to the C = C bond in 2-chloro-3.3,4,4,5.5-hexafluorocyc-lopent-l-enecarboxamide (8) activates the C-Cl bond to complete hydrogenolysis with lithium aluminum hydride the number of C-F bonds reduced is dependent on the amount the hydride used, while the amide group remains unaffected under milder conditions.131... 

Hydrogenolysis with Formate and Other Hydrides to Give Allenes and Internal Alkynes (Types II and IV)... 

Enamines may be reduced by sodium borohydride to give saturated amines, but only if a protonating species is available to convert the enamine initially into the iminium cation (lo). Steroidal g-amino-g,5-dienes are unreactive to sodium boro-hydride alone, but addition of acetic acid leads to rapid reduction via the iminium ion (10) to give gj -amino-A -steroids [224], The possibility that diborane was the reactive species in the NaBHd/HOAc system was excluded by the virtual non-reactivity of the enamine to externally generated diborane. Reduction of the iminium ion derivative (3) of a 6-formyl enol ether has been exploited in a variant of the Vilsmeier synthesis of 6-methyl steroids [22 ], the reduction product was the 6-aminomethyl enol ether (ii) which suffered hydrogenolysis with Raney nickel to give the 6-methylated enol ether (12). 

Alkylation of (a-tetralone)chromiumtricarbonyl 37 with MeLi and subsequent ionic hydrogenolysis with excess EtsSiH and CF3CO2H gave (1-endo-methyltetralin)-chromiumtricarbonyl (39) via stereoselective exo-hydride displacement on 38. On the other hand, the endo-acstate complex 40 was converted into (1-exo-methyltetralin)-chromiumtricarbonyl (41) via exo-methyl attack to the carbocation by treatment with MejAl (Sch. 23) [47]. 

Another regioselective hydrogenolysis of fluorine with hydrides takes place in perfluorotoluene, and electrolytically in pentafluorobenzoic acid (equations 25 and 26). ... 

Heated to 200° in vacuo, teloidine carbonate (XL) gave 3a,6a-oxido-tropan-7 -ol (XLIII) (47). As a variation 48), 6,7-ditosylteloidine (XLIV) was prepared from 6,7-ditosylteloidinone and solvolyzed in the presence of sodium methoxide to 0-7-tosyloscine. Alkaline hydrolysis or hydrogenolysis with lithium aluminum hydride then afforded oscine (XLIII) in good yield. 

The reaction of 1 with pseudouridine (12), a C-nucleoside, differs from the reaction with uridine in that a mixture of 2 - and 3 -chlorodeoxynucleosides are formed. Thus the reaction of 1 with 12, either neat or in acetonitrile, followed by hydrogenolysis with tri-/i-butyltin hydride and deblocking gives about equal amounts of 2 - and 3 -deoxypseudouridine, (13 and 14). ... 

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