Hydrazones reductive cleavage

Chiral hydrazines, supported on Merri-field resin, were reacted with various aldehydes, affording the corresponding hydrazones. These compounds allowed stereoselective preparation of a-branched amines, through 1,2-addition of both aromatic and aliphatic nucleophiles to the C=N double bond of the hydrazones. Reductive cleavage released the desired amine from the resin. Moderate to good enantiomeric excesses (50-86%) were achieved. 

Reduction, carboxyl groups, 56,83 Reduction of a,0-unsaturated p-toluene-sulfonyl-hydrazones to alkenes, 59,42 Reductive alkylation, 56,52 Reductive cleavage, 56, 101 Resolution of amines, 55,80, 83 Rexyn 201,55,4 Rhodium(III) oxide, 57, 1 Ring contraction, 56, 107 Ring expansion of cycloalkanones to cycloalkenones, 59, 113... 

Enantioselective synthesis of R R2CHNH2.1 Alkyllithiums add stereoselec-tively to the C=N bond of SAMP hydrazones (2) of aldehydes. Reductive cleavage of the N—N bond of the products (3) affords either (R)- or (S)-4 with recovery of... 

The N-N bond of polystyrene-bound hydrazines, which are prepared by reaction of organolithium compounds with resin-bound hydrazones [457], can be cleaved by treatment with borane to yield a-branched, primary amines (Entry 9, Table 3.23). An additional example of reductive cleavage to yield amines is shown in Entry 10 (Table 3.23), in which a resin-bound a,a-disubstituted nitroacetic ester undergoes decarboxylation and reduction to the primary amine upon treatment with lithium aluminum hydride. 

The initial step in the reduction in acid solution of azines, hydra-zones, and substituted hydrazones has been suggested to be a hydrogenolysis of the nitrogen-nitrogen bond.91 The aldimine and ketimine thus formed are usually, but not always, reduced further at the potential necessary for the reductive cleavage this depends on the nature of the substituents. The general reduction scheme for a hydrazone is shown in Scheme 8. 

Direct transition from level 2 to level 0 can be achieved by way of the Wolff-Kishner reaction (treatment of the respective hydrazones with alkali), a classical pathway for the reduction of carbonyl compounds. At the same time, a direct conversion of aldehydes and ketones into alkenes is also feasible via reductive cleavage of their tosylhydrazones under the action of MeLi, the Shapiro reaction (Scheme 2.63). "... 

Compound (1) and its enantiomer provide a variation on the same theme of stereospecific reductive amination. In this case, reduction of a chiral cyclic hydrazone (derived from an a-keto acid and (1)) with Aluminum Amalgam in wet DME proceeds with high stereoselectivity. Reductive cleavage of the N-N bond and ester hydrolysis complete the procedure, which produces a-amino acids with high optical purity (eq 4). The source of chirality is recovered by conversion of the resulting indoline-2-methanol back into (1). ... 

The procedure involves the transformation of carbonyl compounds to the corresponding SAMP or RAMP hydra-zones, metalation, trapping of the intermediate azaenolates with various electrophiles, and either hydrazone cleavage (carbonyl compounds) or hydrazone reduction/N-N bond cleavage (amines). 

Reductive cleavage of 2,4-dinitrophenylhydrazones. Certain 2,4-dinitrophenyl> hydrazones of 3-ketosteroids can be cleaved under mild conditions if the nitro groups are reduced to amino groups by chromous chloride. Thus when the 2,4-DNP of 4,5a-dihydrocortisone 21-acetate in methylene chloride was shaken in a separatory funnel with chromous chloride and dilute hydrochloric acid for 15 min., workup of the organic layer afforded the ketone in 94% yield. Use of a water-immiscible solvent protects the released ketone an inert atmosphere if required can be provided with dry ice. Cortisone 2,4-DNP was cleaved in only 3-5 hrs. and the yield was 60%. DN P derivatives of A -diene-S-ones were completely resistant to hydrolysis. Contributed by Leon Mandell... 

Benzenesulfonamide, Ar,AT-dibromo-4-methyl-(TsNBr2) bromohydrination with, 287 Benzenesulfonamides reductive cleavage, 247 synthesis of drugs, 301, 307-308 Benzenesulfonic acids. See Sulfonic acids Benzenesulfonic acid, 4-methyl-, esters (tosylates) alkyl a-synthons, 16, 24, 47, 93 fragmentation of, 89 rearrangement of, 32 reductive cleavage of, 114, 202-203 —, 4-methyl-, hydrazide (tosylhydrazine) hydrazones of fragmentation, 89 reduction, 109... 

In efforts to increase the reactivity of simple 1-aza-1,3-butadienes toward typical electron-deficient dienophiles, Ghosez and co-workers found that the a,/3-unsaturated hydrazone 1 behaves as a well-defined electron-rich diene in regioselective, normal (HOMOd,ene controlled) Diels-Alder reactions with a number of representative dienophiles. Reductive cleavage of the nitrogen-nitrogen bond concurrent with reduction of the carbon-carbon double bond has provided substituted piperidines, and aro-matization with elimination of dimethylamine has provided substituted pyridines (Scheme 9-1). Similar reactions of simple or functionalized a, -unsaturated oximes failed to provide an observable [4 -t- 2] cycloaddition. It remains to be determined whether this process is general for a,/3-unsaturated hydrazones capable of tautomerization. 

The preparation and a Diels-Alder reaction of (lE)-l,3-dimethoxybutadiene have been described. Dimethyl maleate and dimethyl fumarate each react with the hydrazone (92) to give the adduct (93) reductive cleavage of the N-N bond then gives the tetrahydropyridine (94) (Scheme 50). ... 

In 1999, Enders used this method in an iterative fashion to synthesize fl ti-l,3-polyols (Scheme 2.33). The sequence required two diastereoselective alkylations at the a- and a -positions of the hydrazone before cleavage of the chiral auxiliary using an aqueous solution of oxalic acid in ether. The reduction of the resulting ketone followed by a Barton-McCombie deoxygenation furnished the corresponding acetal 17, which was converted to the iodide intermediate 18 upon three additional steps. The latter was then used as an... 

One of the most successful classes of chiral auxiliaries for asymmetric synthesis is that of Enders proline-based hydrazines, namely (S)-l-amino-2-methoxymethylpyrrolidine (SAMP, 74) and its (R)-enantiomer RAMP (Scheme 11.11) [68]. Enders has reported that chiral hydrazones such as 75 undergo diastereoselective additions with organolithium reagents. The facile removal of the auxiliary by reductive cleavage of the N-N bond enables it as a versatile tool for the synthesis of a wide range of chiral secondary amines [69, 70]. As shown in Scheme 11.11, the secondary amine 77 was thus prepared in 73 % overall yield and 93 % ee [69]. 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

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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