Lithium aluminum hydride reduction, alcohols from, with carbonyl compounds

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

The reaction of complex hydrides with carbonyl compounds can be exemplified by the reduction of an aldehyde with lithium aluminum hydride. The reduction is assumed to involve a hydride transfer from a nucleophile -tetrahydroaluminate ion onto the carbonyl carbon as a place of the lowest electron density. The alkoxide ion thus generated complexes the remaining aluminum hydride and forms an alkoxytrihydroaluminate ion. This intermediate reacts with a second molecule of the aldehyde and forms a dialkoxy-dihydroaluminate ion which reacts with the third molecule of the aldehyde and forms a trialkoxyhydroaluminate ion. Finally the fourth molecule of the aldehyde converts the aluminate to the ultimate stage of tetraalkoxyaluminate ion that on contact with water liberates four molecules of an alcohol, aluminum hydroxide and lithium hydroxide. Four molecules of water are needed to hydrolyze the tetraalkoxyaluminate. The individual intermediates really exist and can also be prepared by a reaction of lithium aluminum hydride... 

Chiral Ligand of L1A1H4 for the Enantioselective Reduction of Alkyl Phenyl Ketones. Optically active alcohols are important synthetic intermediates. There are two major chemical methods for synthesizing optically active alcohols from carbonyl compounds. One is asymmetric (enantioselective) reduction of ketones. The other is asymmetric (enantioselective) alkylation of aldehydes. Extensive attempts have been reported to modify Lithium Aluminum Hydride with chiral ligands in order to achieve enantioselective reduction of ketones. However, most of the chiral ligands used for the modification of LiAlHq are unidentate or bidentate, such as alcohol, phenol, amino alcohol, or amine derivatives. 

Two unselective approaches to the two alkaloids are illustrated in Scheme 50. A straightforward synthesis by King relied on acid-induced intramolecular Mannich reaction of ammoketone 396, prepared from 5-aminopentanal diethyl acetal and pent-3-en-2-one, to give a mixture of ( )-394 (55%) and ( )-395 (20%) (367). The synthesis by Pilli et at. involved a one-pot trimethylsilyl triflate-catalyzed condensation between pent-3-en-2-one and the acyliminium ion derived fium JV-Boc-2-ethoxypiperidine (397) (368,369). Under the reaction conditions, the intermediate 398 underwent spontaneous V-deprotection and cyclization to give a 5.5 1 mixture of ( )-394 and ( )-395 (67%). In the same Scheme is also shown the much shorter stereoselective synthesis of ( )-394 by Beckwith et al, who used a radical-mediated cyclization on the V-acylated 2,3-dihydropyridin-4-one 399 to give the bicyclic product 400 as the sole diastereomer (91%) (370). Compound 400 was readily converted into the target alkaloid by reduction of both carbonyl groups with lithium aluminum hydride followed by reoxidation of the secondary alcohol at C-2. 

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