Reductive cleavage with lithium aluminum hydride

An aldehyde synthesis introduced by Staab involves condensation of an acid chloride with imidazole to form an imidazolide (1) and reductive cleavage with lithium aluminum hydride to the aldehyde (2) and imidazole. In a one-step process... 

The trithiocarbonates may prove useful as intermediates for the synthesis of sugar dithiols from epoxides. Ring opening by reductive cleavage with lithium aluminum hydride gives excellent results with aliphatic and ahcyclic trithiocarbonates. When both carbon atoms are secondary, the product is a iraws-dithiol for example, cyclohexene oxide, which is converted into a irans-trithiocarbonate, gives, on reduction, cyclo-hexane-1,2-dithiol. The reaction has been used in the cyclitol series for the preparation of 1,2-dithio-neo-inositol and 1,2-dithio-ir-inositol, from 1,2-anhydro-alZo-inositol. The inositol trithiocarbonates show pronounced Cotton effects in their optical rotatory-dispersion spectra. 

The previously published method for the liberation of the diol from the resolved 1,1 -b1naphthyl-2,2 -diyi hydrogen phosphate entailed esterification with diazomethane and reductive cleavage with lithium aluminum hydride. The procedure presented here is felt to be safer in that it circumvents hazards associated with using diazomethane and lithium aluminum hydride on a large scale. 

Thiocarbamates, upon treatment with 5-BuLi followed by addition of various electrophiles, lead to the formation of -substituted products in excellent yields and with high stereoselectivities with inversion of configuration, e.g., eq 48. Reductive cleavage with lithium aluminum hydride and zinc chloride occurs without loss of enantiomeric purity and provides good yields of the corresponding thiols. 4... 

These eryt/ira-nitroaldols are attractive precursors to 1,2-amino alcohols (3). The conversion can be effected with retention of configuration by reduction to 2 (H, and neutral Raney nickel) followed by silyl ether cleavage with lithium aluminum hydride in ether. A one-step reduction of 1 to a 1,2-amino alcohol can be effected with lithium aluminum hydride, but with loss of configurational purity and some C—C bond cleavage. 

Conditions for auxiliary removal have to be carefully chosen to avoid partial racemization of the newly formed stereogenic center. Such complications arise under reductive cleavage conditions (lithium aluminum hydride/diethyl ether) as well as basic hydrolysis employing potassium hydroxide in ethanol. However, treatment with lithium hydroxide in aqueous tetra-hydrofuran appears to effect clean cleavage whilst avoiding this complication713. 

Since double bonds may be considered as masked carbonyl, carboxyl or hydroxymethylene groups, depending on whether oxidative or reductive methods are applied after cleavage of the double bond, the addition products from (E)-2 and carbonyl compounds can be further transformed into a variety of chiral compounds. Thus, performing a second bromine/lithium exchange on compound 4, and subsequent protonation, afforded the olefin 5. Ozonolysis followed by reduction with lithium aluminum hydride gave (S)-l-phenyl-l,2-ethanediol in >98% ee. 

Remarkable solvent effects on the selective bond cleavage are observed in the reductive elimination of cis-stilbene episulfone by complex metal hydrides. When diethyl ether or [bis(2-methoxyethyl)]ether is used as the solvent, dibenzyl sulfone is formed along with cis-stilbene. However, no dibenzyl sulfone is produced when cis-stilbene episulfone is treated with lithium aluminum hydride in tetrahydrofuran at room temperature (equation 42). Elimination of phenylsulfonyl group by tri-n-butyltin hydride proceeds by a radical chain mechanism (equations 43 and 44). 

The reduction of a stannaphosphene with lithium aluminum hydride has been reported to give the stannylphosphine.92 An excess of hydride leads to cleavage of the phosphorus-tin single bond.104... 

Usually alcohols accompany aldehydes in reductions with lithium aluminum hydride [1104] or sodium bis 2-methoxyethoxy)aluminum hydride [544], or in hydrogenolytic cleavage of trifluoroacetylated amines [7772]. Thus terr-butyl ester of. -(. -trifluoroacetylprolyl)leucine was cleaved on treatment with sodium borohydride in ethanol to rerr-butyl ester of A7-prolylleucine (92% yield) and trifluoroethanol [7772]. During catalytic hydrogenations over copper chromite, alcohols sometimes accompany amines that are the main products [7775]. 

Reduction of oxetanes can usually be achieved with lithium aluminum hydride in THF. The reaction is almost general, though polyalkyl substitution may decrease the rate to an impractical level. As is to be expected with a strong nucleophile, ring cleavage occurs generally between the oxygen atom and the least substituted a-carbon atom (equation 46)... 

An efficient synthesis of ( )-quebrachamine is based on the construction of a suitable precursor via ring cleavage of an a-diketone monothioketal (810) (80JCS(P1)457). This monothioketal, available from 4-ethoxycarbonylcyclohexanone ethylene ketal, was fragmented to the dithianyl half ester (811) with sodium hydride in the presence of water. Reaction of (811) with tryptamine and DCC provided an amide which was converted to the stereoisomeric lactams (812) on hydrolysis of the dithiane function. Reduction of either the a- or /3-ethyl isomer with lithium aluminum hydride followed by conversion of the derived amino alcohol to its mesylate produced the amorphous quaternary salt (813). On reduction with sodium in liquid ammonia, the isomeric salts provided ( )-quebrachamine (814 Scheme 190). 

By lithium aluminum hydride. The reaction at several dpi-sulfides with lithium aluminum hydride has been shown to proceed with reductive ring cleavage to give thiols as their lithium mercaptidea in about 75% yields. The secondary thiols, rather than the corresponding 1 -thiols, wore obtained from the reduction of propylene sulfide and 1-hexene sulfide ... 

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. 

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