Aluminium hydride selective reduction with

Lithium aluminium hydride LiAlH is a useful and conveuient reagent for the selective reduction of the carbonyl group and of various other polar functional groups. It is obtained by treatment of finely powdered lithium hydride with an ethereal solution of anhydrous aluminium chloride ... 

Since sulphones 204 are easily available compounds one would expect that they could be used as starting materials for the preparation of sulphoxides via the selective removal of one oxygen atom from the sulphonyl group (equation 112). Up to now, there is only one example reported of a direct reduction of a sulphone to a sulphoxide. The bicyclic dideuterio sulphone 205 after 24 h treatment with three-fold excess of diisobutyl aluminium hydride in boiling dichloromethane gave the corresponding sulphoxide 206 in 36% yield (equation 113). A two-step procedure for the selective reduction of sulphones to sulphoxides, which involves an initial reaction of sulphone 204 with aryldiazonium tetrafluoroborate 207 to form aryloxysulphoxonium salt 208 and its subsequent reduction (equation 114), was alluded to by Shimagaki and coworkers and... 

Brown, H. C., and Ch. J. Shoaf Selective Reductions. III. Further Studies of the Reaction of Alcohols with Lithium Aluminium Hydride as a Route to the Lithium Alkoxyaluminiumhydrides. J. Amer. chem. Soc. 

Nonmetallic systems (Chapter 11) are efficient for catalytic reduction and are complementary to the metallic catalytic methods. For example lithium aluminium hydride, sodium borohydride and borane-tetrahydrofuran have been modified with enantiomerically pure ligands161. Among those catalysts, the chirally modified boron complexes have received increased interest. Several ligands, such as amino alcohols[7], phosphino alcohols18 91 and hydroxysulfoximines[10], com-plexed with the borane, have been found to be selective reducing agents. 

Complete control of the diastereoselectivity of the synthesis of 1,3-diols has been achieved by reagent selection in a one-pot tandem aldol-reduction sequence (see Scheme l). i Anti-selective method (a) employs titanium(IV) chloride at 5°C, followed by Ti(OPr )4, whereas method (b), using the tetrachloride with a base at -78 °C followed by lithium aluminium hydride, reverses the selectivity. A non-polar solvent is required (e.g. toluene or dichloromethane, not diethyl ether or THF), and at the lower temperature the titanium alkoxide cannot bring about the reduction of the aldol. Tertiary alkoxides also fail, indicating a similarity with the mechanism of Meerwein-Ponndorf reduction. 

A recently published full account of another synthesis [69] of the same alkaloid starting from the /rans-cinnamic ester 264 represented a different approach (ACD -> ACDB) to ( )-lycorine (Scheme 42). An intramolecular Diels-Alder reaction of 264 in o-dichlorobenzene furnished the two diastereomeric lactones 265 (86%) and 266 (5%) involving the endo and exo modes of addition respectively. The transposition of the carbonyl group of 265 to 267 was achieved by reduction with lithium aluminium hydride, followed by treatment of the resulting diol with Fetizon s reagent, which selectively oxidised the less substituted alcohol to give isomeric 5-lactone 267. On exposure to iodine in alkaline medium 267 underwent iodolactonisation to afford the iodo-hydroxy y-lactone 268. The derived tetrahydropyranyl ether... 

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... 

The Leukart reaction has also been used in the conversion of dehydroepiandro-sterone into 17/3-formylamino-3/3-formyloxyandrost-5-ene, which on reduction with lithium aluminium hydride afforded 3/3-hydroxy-17/3-me thylaminoandrost-5-ene. Acylation with isocaproyl chloride then furnished the N-methyl-N-isocaproyl steroid (197), after selective ester hydrolysis of the initially formed ON-diacyl derivative. The amide (197) was further converted into its 3,5-cyclo-6-ketone via the 3,5-cyclo-6/3-alcohol and thence by reaction with hydrogen bromide into the corresponding 3/3-bromo-5a-6-ketone which upon dehydrobromination furnished a A2-5a-6-ketone and ultimately the 2-monoacetate of the 2/3,3/3-diol (198) after reaction with silver acetate and iodine. Hydrolysis to the 2/3,3/3-diol (198) gave a separable mixture of the 2/3,3/8-dihydroxy-5a- and -5/3-ketones.88... 

The ability of reagents to differentiate between functional groups is called chemo-selectivity and can be solvent-dependent. A nice clear-cut example is the reduction of the bifunetional eompound 11-bromoundecyl tosylate with Uthium aluminium hydride in different solvents as shown in Eq. (5-153) [695]. 

Selective reduction of functional groups can be achieved by chemical modification of the LiALH4 for example, lithium tri(t-butoxy)aluminium hydride [LiAIH(t-OBu)3] is a more selective reagent, and reduces aldehydes and ketones, but slowly reduces esters and epoxides. Nitriles and nitro groups are not reduced by this reagent. Carboxylic acids can be converted into the aldehyde via acid chloride with lithium tri(tert-butoxy) aluminium hydride at a low temperature (—78°C). The nitro compounds are not reduced under this condition. Thus, selective reduction of 3,5-dinitrobenzoic acid (6.45) to 3,5-dinitrobenzaldehyde (6.47) can be achieved in two steps. First, 6.45 is converted into 3,5-dinitrobenzoyl chloride (6.46) and then LiAlH(t-OBu)3 reduction of 6.46 gives 6.47. 

The reduction of the maleic anhydride adduct (303) with lithium aluminium hydride was previously reported to occur selectively to give the lactone (304). The lower selectivity now observed with sodium aluminium hydride (none at all with sodium borohydride) is interpreted as evidence for a complex (305) of the ester and anhydride carbonyl groups with a solvated lithium ion when lithium aluminium hydride is used, leading to selective reduction of the free carbonyl group.Sodium ions are considered not to form so stable a complex. 

Vinyloxiranes are reduced very selectively by diisobutyl-aluminium hydride (Eq. 168). Without regard to the configuration (exo,endo), the reduction of norborn-ane diepoxides with LiAlH proceeds in such a manner that the norbornane moiety remains intact in the reaction. (Eq. 168). ... 

For the synthesis of (+)-citronellol (6), the mixed pinenes were catalytically hydrogenated to give (-)-cis-pinane (7) which was pyrolysed to (-)-citronellene. Application of the Ziegler reaction with aluminium hydride proceeded selectively at the more reactive disubstituted double bond and following atmospheric oxidation and aqueous work-up, (+)-citronellol was isolated identical with that derived by the reduction of natural citronellal by the Ponndorf-Meerwein-Verley method (ref.9) as shown. 

Catalytic hydrogenation gives a mixture of partially reduced products (enamine and allylamine) and/or saturated amine depending on the conditions used . Partial reduction also occurs on treatment with lithium in ammonia . Dienamines are resistant to reduction by lithium aluminium hydride which therefore provides a means for selective reduction of a less reactive carbonyl group in polyfunctional molecules (Scheme 13). 

The selective reduction of the hetero-ring of benzo-1,3-azoles or the benzo-l,2-azoles has not been reported, though benzazolium salts can be easily reduced to 1,2-dihydro derivatives with sodium borohydride or lithium aluminium hydride. " ... 

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