Hydrogenolysis hydride reductions

Amines of the formula n 2n+ be prepared by the lithium aluminum hydride reduction of the corresponding amide, hydrogenolysis... 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

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. 

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. 

Halogenomethylpyrroles have been oxidized with lead(IV) salts or by chromium trioxide to yield the formylpyrroles, whilst catalytic hydrogenolysis or zinc-acetic acid reduction produces the 2-methylpyrroles (B-77MI30504). The methyl derivatives are also obtained by hydride reduction of trifluoromethyl-pyrroles and -indoles, and trifluoromethylindoles are converted into the carboxylic esters by ethanol under basic conditions (74JOC1836). 

The mixture 258 was converted to the unstable benzenesulfonyl aziridine 259 by treatment with an excess of benzenesulfonyl azide in benzene. Ace-tolysis of 259 with acetic acid and sodium acetate at room temperature for several days afforded the crystalline mixture of diastereoisomers represented by the formula 260. The aziridine rearrangement was regiospecific and 260 was the only product detected during this rearrangement. Lithium aluminium hydride reduction of 260 followed by acetylation yielded the mixture 261 in 85% yield. Selective hydrolysis of 261 afforded 262 in quantitative yield. The diastereoisomeric mixture 262 was converted into the diols 263 by hydrogenolysis. The diol mixture was oxidized with chromium trioxide... 

Because of the need for initial coordination with the catalyst, only benzylic or allylic C-X bonds can be reduced, but the X can be oxygen as well as nitrogen. We will come back to benzyl groups, and their hydrogenolysis, as a means for temporary protection of amines and alcohols later in the chapter. For the moment, though, we should take a broader look at catalytic hydrogenation as our second (after hydride reduction) important class of reductions. 

Scheme 75). The D/E ring system of these alkaloids has been constructed by the intramolecular [4 + 2]-cycloaddition of an oxadiene with an ot,P-unsaturated amide. Thermolysis of the diene 580 at 190°C in xylene produced a 4.5 1 mixture of the cis and trans- cycloadducts 581 and 582, respectively. They could be separated to provide cis-lactam (73%). Subsequent hydride reduction of 581 with aluminum hydride produced the tertiary amine 583. Acylation of 583 with trichloroacetyl chloride followed by a haloform cleavage gave the ester 584. Finally, hydrogenolysis of the iV-benzyl group provided the known bicyclic amine 585, which was previously converted to a mixture of 586 and 587. 

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