Alcohols with LiAIH

Boireau, G. Deberly, A. Toneva, R. Synlett 1993, 585. In this study, reduction with LiAIH(Ot-Bu)3 was shown to give primarily the trans-alcohol. 

Problem 17.8 What carbonyl compounds give the following alcohols on reduction with LiAIH Show all possibilities. 

The hydrogenation activity of the intermediate rhodium complex was lowered by the use of the corresponding unsaturated phosphites as substrates, although the pressure had to be increased to 34bar (Scheme 4.105) [11]. Alcohols yielded only by separate reduction of the aldehydes with LIAIH. The dominance for the formation of the branched aldehyde was not affected by branching ofthe substrate. Increasing the distance between phosphite and olefin caused the total loss of the regiodirecting effect. 

The benzyl group has been widely used for the protection of hydroxyl functions in carbohydrate and nucleotide chemistry (C.M. McCloskey, 1957 C.B. Reese, 1965 B.E. Griffin, 1966). A common benzylation procedure involves heating with neat benzyl chloride and strong bases. A milder procedure is the reaction in DMF solution at room temperatiue with the aid of silver oxide (E. Reinefeld, 1971). Benzyl ethers are not affected by hydroxides and are stable towards oxidants (e.g. periodate, lead tetraacetate), LiAIH, amd weak acids. They are, however, readily cleaved in neutral solution at room temperature by palladium-catalyzed bydrogenolysis (S. Tejima, 1963) or by sodium in liquid ammonia or alcohols (E.J. Rcist, 1964). 

Formation of an Alcohol The simplest reaction of a tetrahedral alkoxide intermediate is protonation to yield an alcohol. We ve already seen two examples of thi.s kind of process during reduction cif ketones and uldchydcs with hydride reagents such as NaBH, and LiAIH (Section 17.5), and during Qrignard reactions (Section 17.6). In the case of reduction, the nucleophile that adds to the carbonyl group is a hydride ion, H while in the case of Grignard reaction, the nucleophile is a carbanion, R ,C . ... 

Deoxygenation of aUyBc and benzyUc alcohols. Allylic and benzylic alcohols are conveniently reduced to the corresponding hydrocarbons in two steps. The alcohol is first converted into a pyridinium alkyl sulfate by reaction with sulfur trioxide-pyridine in THF at 0-3° (3-20 hours). Then lithium aluminum hydride (or LiAIH -AlClj, 3 1) in THF is added and the mixture stirred for I hour at 0° and then at 25° for 3-5 hours. Yields are high. In the case of allylic alcohols... 

Section 8-6 presents two u.seful reduction processes. Carbonyl compounds such as ketones and aldehydes arc useful precursors (starting materials) for the synthesis of alcohols. Either metal-catalyzed Ht addition or reaction with the hydride reagents NaBH and LiAIH converts aldehydes to primary alcohols. The same processes convert ketones to secondary alcohols. The.se hydride reductions are the lirst of many examples that you will. see of nucleophilic additions to the electrophilic carbons of carbonyl groups. This is one of the most important clas.ses of reactions in organic chemistry. 

Hexafluoroacetone is a reactive electrophile. It reacts with activated aromatic compounds (e.g., phenol), and can be condensed with olefins, dienes, ketenes, and acetylenes. It forms adducts with many compounds containing active hydrogen (e.g., H O or HCN). Reduction of HFA with NaBH or LIAIH affords the useful solvent hexafluorolsopropyl alcohol. The Industrial Importance of HFA arises largely from Its use In polymers and as an... 

Reduction of (160) with LiAlH or LiAIH -AIClj in molar ratio 3 I gave a ca. 50 50 ratio of cis- and trans-alcohols, whereas ca. 70 % cis-alcohol was formed with AIH3 or LiAl(OMe)3H. However, greater selectivity was exhibited in reductions of (157) where proportions of cis-alcohol ranged from ca. 75% with LiAlH to 100% with LiAl(OMe)3H. 

Similarly, reduction of both aromatic and aliphatic aldehydes and ketones where there is a chlorine (Cl) or bromine (Br) present elsewhere in the carbonyl-containing compound succeeds with sodium borohydride (NaBH,) and, occasionally, with lithium aluminum hydride (LiAIH,) at low temperatures. Catalytic reduction frequently leads to hydrogenolysis of the halogen, producing the halogen-free alcohol. 

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