Lithium aluminium hydride diastereoselective reductions

Enantiomerically pure /J-keto sulfoxides are prepared easily via condensation of a-lithiosulfinyl carbanions with esters. Reduction of the carbonyl group in such /J-keto sulfoxides leads to diastereomeric /J-hydroxysulfoxides. The major recent advance in this area has been the discovery that non-chelating hydride donors (e.g., diisobutylaluminium hydride, DIBAL) tend to form one /J-hydroxysulfoxide while chelating hydride donors [e.g., lithium aluminium hydride (LAH), or DIBAL in the presence of divalent zinc ions] tend to produce the diastereomeric /J-hydroxysulfoxide. The level of diastereoselectivity is often very high. For example, enantiomerically pure /J-ketosulfoxide 32 is reduced by LAH in diethyl ether to give mainly the (RR)-diastereomer whereas DIBAL produces exclusively the (.S R)-diastereomer (equation 30)53-69. A second example is shown in... 

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. 

Stereoselectivity in reductions of acyclic oximes depends on the configuration of C=N bond. ( )-Isomer of oxime 89 produced syn-hydroxylamine 90 in excellent stereoselectivity in reaction with phenyldimethylsilane-trifluroacetic acid while giving anti-product in the reaction with lithium aluminium hydride. Stereoselectivity in reductions of (Z)-isomers of 89 was substantially lower in both cases (equation 62) . It can be assumed that the rules of stereoselectivity established in diastereoselective reduction of ketones can be applied to reduction of oximes as well. 

A related strategy was used to prepare D-allosamine (134). Cycloaddition of the dipole derived from nitroacetal (129) to (S )-vinyl dioxolane (74) afforded a mixture of erythro/threo isoxazolines 130 131 (Scheme 6.72). The erythro isoxazoline was subjected to hydroxylation as described above, to give 4-hydroxyisoxazoline 132 with high diastereoselectivity. Lithium aluminium hydride reduction furnished a single diastereomer of aminodiol 133, which could be deprotected to give the hydrochloride salt of D-allosamine (134) (141). 

In other reports, /i-cyclodcxtrins have been used to induce asymmetry in borohydride reduction of ketones,166 a diastereoselective reduction has been controlled167 by a real lyltricarbonyl iron lactone tether , a phosphinamide has been combined with a dioxaborolidine unit as an activated, directed catalyst for ketone reduction,168 reductive amination using benzylamine-cyanoborohydride converts 3-hydroxy ketones into syn-1,3-amino alcohols,169 l-(3,4-dimethoxyphenyl)-2-(2-methoxyphenoxy)propan-l-one has been reduced diastereoselectively,170 and production of chiral alcohols via (i) Itsuno-Corey and Brown procedures171 and (ii) lithium aluminium hydride modified by chiral nucleophiles172 has been reviewed. 

The chiral, reactive 2(3// )-quinazolinone 406 underwent diastereoselective reduction with lithium tri(fer7-butoxy)-aluminium hydride at —60°C to generate the 1,4-dihydro derivative 407 <2003JOC754>, while nickel boride reduction of the 2-thioxoquinazoline 408 gave the 2,3-dihydro-4(177)-quinazolinone 409 <2003JHG677>. 

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