Raney nickel, reductive cleavage

Reductive N-N cleavage of hydrazines. A diastcreoselective synthesis of chiral a-amino aldehydes (4) from glyoxal involves an intermediate dimethylhydrazone (1), which reacts with an alkyllithium to provide an or-substituted N. N -dimcthylhydrazine (2). The mildest method for cleavage of hydrazines to primary amines (3) involves hydrogenolysis catalyzed by Raney nickel at 30-50. This Raney nickel reductive cleavage is markedly improved by sonication and proceeds at atmospheric pressure of H2 at 20 in CHjOH in yields of 66-84% with no raccmization or debenyzlation.1... 

The methods discussed above all require chemically aggressive reagents. Freudenberg and his co-workers,41 however, found that benzyl ethers can also be cleaved by catalytic hydrogenation alkyl benzyl ethers can be converted into toluene and an alcohol by hydrogenation under very mild conditions in presence of platinum metals or Raney nickel reductive cleavage of aryl benzyl ethers is best carried out in presence of palladium-charcoal. 

Scott Denmark of the University of Illinois reports (J. Org. Chem. 68 8015,2003) a hetero intramolecular Diel-Alder reaction of a nitro alkene 5, followed by intramolecular dipolar cycloaddition of the resulting nitronate 6, to give the tricycle 7. Raney nickel reduction effected cleavage of the N-0 bonds and reductive amination of the liberated aldehyde, to give, after acetylation, the angularly substituted cis-decalin 8. 

The 1,2,5-thiadiazole ring is susceptible to reductive cleavage by a number of reagents including zinc and mineral acids,sodium and alcohol,and Raney nickel. Reduction occurs at the N—S bond (also the site of cleavage of 1,2,3- and 1,2,4-thiadiazoles) with formation of hydrogen sulMe and regeneration of the NCCN portion of the molecule in a reduced form. This property has been employed as a method of structure proof of 1,2,5-thiadiazoles in a number of cases. 

Hydrodesulfnrisation of benzothiophenes is conveniently achieved using Raney nickel. Reduction of the hetero-rings of both benzofuran and benzothiophene giving 2,3-dihydro derivatives, notably with retention of the snlfur in the latter case, can be achieved using triethylsilane in acidic solution, or with hydrogen over colloidal rhodium. Reductive cleavage of benzofuran to 2-hydroxystyrene is caused by lithium with 4,4 -di-f-butylbiphenyl (DTBB). ... 

Treatment of the reduced adduct with pronase and subsequent reduction with Raney nickel led to the release and isolation of trans-/3-methylstrene 39. Raney nickel is known to cleave carbon-sulfur bonds specifically (777). Furthermore, the expected product from cleavage of the carbon-sulfur bond of the reduced adduct is 1-phenyl-1-propanol however, under the conditions of the Raney nickel reduction, 1-phenyl-1-propanol is dehydrated to trans-/3-methylstyrene (770). This result suggests that the amino acid residue is cysteine. The finding that the total number of cysteine residues detected with 5,5 -dithiobis(2-nitro-benzoic acid) decreases by one in the denatured, 1-phenylcyclopropylamine-... 

Isothiazoles are reductively desulfurized by Raney nickel, e.g. as in Scheme 31 (72AHC(l4)l). 1,2,5-Thiadiazoles are subject to reductive cleavage by zinc in acid, sodium in alcohol, or Raney nickel, e.g. Scheme 32 (68AHC(9)107). 

Another mode of reductive ring cleavage is observed for 4-phenylazetidin-2-ones. These undergo N(l)—C(4) bond fission on hydrogenolysis in the presence of Raney nickel to yield the corresponding 3-phenylpropanamides (75S547 p. 583). 

The reductive cleavage of the N-O bond in the isoxazolidine 162 unmasks the 1,3-amino alcohol moiety. Thus, isoxazolidines can be viewed as direct precursors of 7-amino alcohols. The reductive cleavage of the cycloadduct proved difficult. W2 Raney-Ni and nickel boride were both ineffective. In contrast, nickel-aliminium alloy in an alkaline medium efficiently reduced the N-O bond at room temperature in the presence of a base (Equation 27) <1997TA109>. 

Open-chain aliphatic ethers are completely resistant to hydrogenolysis. Cyclic ethers (for epoxides, see p. 83) may undergo reductive cleavage under strenuous conditions. The tetrahydrofuran ring was cleaved in vigorous hydrogenations over Raney nickel [420] and copper chromite [420] to give, ultimately, alcohols. 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

Reductions of these ring systems are common. Most often, active hydrogen techniques are employed to cleave weak heteroatom-heteroatom bonds. Reductions of the glycoluril derivatives are less common due to the lack of such a weak bond. Some recent examples include reactions by Chan et al. <2003TL395> who employed Raney nickel and hydrogen to effect cleavage of an N-O bond in their synthesis of new heterocyclic compounds via 1,3-dipolar cycloaddition chemistry (Equation 15). 

Reduction of alkylated aldehyde-derived SAMP-hydrazones, followed by reductive N —N cleavage of the resulting hydrazines with Raney nickel, furnishes /(-substituted primary amines in good chemical yields and without racemization in 94-99% ee (see Table 5)31. 

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