Alane epoxides

Especially in the early steps of the synthesis of a complex molecule, there are plenty of examples in which epoxides are allowed to react with organometallic reagents. In particular, treatment of enantiomerically pure terminal epoxides with alkyl-, alkenyl-, or aryl-Grignard reagents in the presence of catalytic amounts of a copper salt, corresponding cuprates, or metal acetylides via alanate chemistry, provides a general route to optically active substituted alcohols useful as valuable building blocks in complex syntheses. 

Scheme 4.10 gives some examples of application of alkyne carboalumination in synthesis. The reaction in Entry 1 was carried out as part of a synthesis of the immunosuppressant drug FK-506. The vinyl alane was subsequently transmetallated to a cuprate reagent (see Chapter 8). In Entry 2, the vinyl alane was used as a nucleophile for opening an epoxide ring and extending the carbon chain by two atoms. In Entries 3 to 5, the vinyl alane adducts were converted to vinyl iodides. In Entry 6, the vinyl alane was converted to an ate reagent prior to reaction with formaldehyde. 

Reagents of choice for reduction of epoxides to alcohols are hydrides and complex hydrides. A general rule of regioselectivity is that the nucleophilic complex hydrides such as lithium aluminum hydride approach the oxide from the less hindered side [511, 653], thus giving more substituted alcohols. In contrast, hydrides of electrophilic nature such as alanes (prepared in situ from lithium aluminum hydride and aluminum halides) [653, 654, 655] or boranes, especially in the presence of boron trifluoride, open the ring in the opposite direction and give predominantly less substituted alcohols [656, 657,658]. As far as stereoselectivity is concerned, lithium aluminum hydride yields trans products [511] whereas electrophilic hydrides predominantly cis products... 

Julia S, Guixer J, Masana J, Rocas J, Colonna S, Annuziata R, Molinari HJ (1982) Synthetic enzymes , highly stereoselective epoxidation of chal-cone in a triphasic toluene-walcr-pol y (S )-alan i ne system. J Chem Soc [Perkin 1] 1317... 

The disilyl derivative of all-cix-1,2-epoxycyclopentane-3,5-diol 5 7 was treated with diethyloctynylalane to afford after cleavage of the silylether function the triol 58. This triol was convered via the acetonide to the benzyl ether 59. Hydrolysis with aqueous trifluoroacetic acid yielded the diol benzylether 60 which could be prepared by an alternative route as well. This route proceeds via the monotrityl epoxide 61 and benzylation to the trityl benzylether 62 and then reaction with diethyl octynyl alane to the diolbenzylether 60 and the isomeric 1,3-diol. 

Alkyaylailom aUeyeUe epoxuUs. Alkynyldiethyl alanes (2 eq.) react with alicyclic epoxides (1 eq.) to form, after hydrolysis, / -hydroxyacctylcnes in fair to excellent yields ... 

Alane (AIH3) and its derivatives have also been utilized in the reduction of carboxylic acids to primary alcohols. It rapidly reduces aldehydes, ketones, acid chlorides, lactones, esters, carboxylic acids and salts, tertiary amides, nitriles and epoxides. In contrast, nitro compounds and alkenes are slow to react. AIH3 is particularly useful for the chemoselective reduction of carboxylic acids containing halogen or nitro substituents, to produce the corresponding primary alcohols. DIBAL-H reduces aliphatic or aromatic carboxylic acids to produce either aldehydes (-75 °C) or primary alcohols (25 C) Aminoalu-minum hydrides are less reactive reagents and are superior for aldehyde synthesis. ... 

With mono- or asymmetrically dialkylated ethylene oxides one obtains, in general, after hydrolysis of the products of alkylation, 2-substituted or 2,2-disubstituted primary alcohols. Only one alkyl group of the trialkyl alanes reacts with the epoxide function (124), e.g.,... 

When dialkyl alanes are used in place of trialkyl alanes, the result is generally a mixture of alcohols, with R partly replaced by H. In certain special instances triisobutylalane, for example, reacts with epoxides and H2 or RH is split off. 1,2-Epoxycyclododecane and l,2-epoxycyclodeca-5,9-diene give, after hydrolysis, l-hydroxycyclododeca-2-en (125) and 1-hydroxy-cyclododeca-2,5,9-triene (125) ... 

S, .S. .S )-Tri(isopropanol)arnine (14) is an efficient ligand for zirconium catalysts for cnantio-selective ring opening of epoxides with silyl azides (Section C.). It can be obtained either by the reaction of the commercially available starting materials ( + )-(5)-l-amino-2-propanol [(S)-alan-inol] and (-)-(5)-propylene oxide18, or directly from pure (iS)-propylene oxide and ammonia ... 

The synthesis of 188 from epoxide 189 was done as shown in Scheme 25. Epoxide opening with a propargyl alane reagent [124], protection-deprotection of the alcohol functions, and Redal reduction led to the -allylic alcohol 194, also obtained by another route [116]. Asymmetric epoxidation-Redal epoxide opening [60-62] followed by silylation and debenzylation led to intermediate triol 195. Selective six-membered acetal formation and primary alcohol oxidation then furnished building block 188. 

Reduction of hexamethyl-Dewar-benzene epoxide with lithium aluminium hydride affords a mixture of the tricyelie alcohol (424) and the ketone (425) in equal proportions. Use of alane as the reducing agent, followed by an aqueous basic work-up... 

Danishefsky has reported a modified route to /ra 5-fused butyrolactones (53) involving attack on a c/j-epoxide (51) by the acetylenic alane (52), followed by acid catalysed hydrolysis and lactonization other anions were found to be unsuitable. Similar fused lactones are available from a -epoxycyclohexanones by sequential Wittig-Horner reaction and acid-catalysed cyclization. 

Abstract The use of organoaluminum-based Lewis acids (A1R X3 R = alkyl, alkynyl, X = halide or pseudohalide) in the period 2000 to mid-2011 is overviewed with a focus on (1) stoichiometric reactions in which one of the organoaluminum substituents is transferred to the substrate (e.g., the opening of epoxides, 1,2-additions to carbonyl compounds, coupling with C-X, and Reissert chemistry) and (2) asymmetric, often catalytic, reactions promoted by Lewis acid catalysts derived from organoaluminum species (e.g., use of auxiliaries with alanes, Diels-Alder, and related cycloaddition reactions, additions to aldehydes and ketones, and skeletal rearrangement reactions). 

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