Alkoxy aluminum hydrides

A convenient route to highly enantiomerically enriched a-alkoxy tributylslannanes 17 involves the enanlioselective reduction of acyl stannanes 16 with chiral reducing agents10. Thus reaction of acyl stannanes with lithium aluminum hydride, chirally modified by (S)-l,l -bi-naphthalene-2,2 -diol, followed by protection of the hydroxy group, lead to the desired a-alkoxy stannanes 17 in optical purities as high as 98 % ee. 

A slightly more complex Scheme is required for preparation of an antihistaminic agent bearing a secondary amine, e. g., tofenacin (32). In the synthesis of tofenacin, alkylation of the benzhydrol (29) with ethyl bromoacetate affords the alkoxy ester (30) saponification followed by conversion to the methylamide gives (31), which is reduced with lithium aluminum hydride to complete the synthesis of 32. 10... 

Oxidation of oxyberberine (58) with lead tetraacetate effected 13-acetoxyl-ation to give 13-acetoxyoxyberberine (116), which was further oxidized to the 14-alkoxy-8,13-dioxo compounds 117 and 118 (Scheme 25). Reduction of 116 with lithium aluminum hydride followed by sodium borohydride afforded ( )-ophiocarpine (92) (78). 

Better reagents than lithium aluminum hydride alone are its alkoxy derivatives, especially di- and triethoxyaluminohydrides prepared in situ from lithium aluminum hydride and ethanol in ethereal solutions. The best of all, lithium triethoxyaluminohydride, gave higher yields than its trimethoxy and tris(/er/-butoxy) analogs. When an equimolar quantity of this reagent was added to an ethereal solution of a tertiary amide derived from dimethylamine, diethylamine, W-methylaniline, piperidine, pyrrolidine, aziridine or pyrrole, and the mixture was allowed to react at 0° for 1-1.5 hours aldehydes were isolated in 46-92% yields [95,1107], The reaction proved unsuccessful for the preparation of crotonaldehyde and cinnamaldehyde from the corresponding dimethyl amides [95]. 

Single-Source-Precursor CVD Alkoxy and SUoxy Aluminum Hydrides... 

The third contribution is particularly devoted to the concept of so-called single source precursors (SSPs). SSPs contain all the atoms of the different elements necessary for the deposition of the desired material in one single molecule. One motivation for using this concept is to simplify the accompanying gas-phase reactions and thus reduce the process parameters to be controlled and optimised. However, SSPs may offer a unique chance of depositing metastable materials that cannot be derived by other methods. M. Veith and S. Mathur provide such an example in their paper entitled Single-Source-Precursor CVD Alkoxy and Siloxy Aluminum Hydrides . 

Reduction of l,2,4-triazin-3-ones (84) with Raney nickel, zinc and acetic acid, lithium aluminum hydride, sodium borohydride, titanium(III) chloride, p-toluenethiol, hydrogen and a palladium catalyst, or electrochemically, produces 4,5-dihydro-l,2,4-triazin-3-ones (268) (78HC(33)189, p. 246, 80JHC1237), which may be further reduced to 1,4,5,6-tetrahydro-l,2,4-triazin-3-ones (269). l,2,4-Triazin-3-ones (84) with hydriodic acid and phosphorus yielded imidazoles (05LA(339)243). 3-Alkoxy-l,2,4-triazines (126) and sodium borohydride gave the 2,5-dihydro derivatives (270) (80JOC4594). 

The mechanism of diisobutylaluminum hydride reduction involves formation of a six-membered transition state with aluminum complexed to the carbonyl of the ester group, which is required for the delivery of the hydride from the electrophilic aluminum hydride to the carbonyl group. The alkoxy moiety is then displaced during workup resulting in the desired peptide aldehyde. This mechanism accounts for the fact that the reduction stops after the conversion of the ester into the aldehyde. 23 ... 

The reduction of quinazoline with lithium aluminum hydride gave a mixture of 1,2,3,4-tetrahydroquinazoline and Va-methyl- ,2-toluenediamine. 4-Aryloxy- and 4-alkoxy-quinazolines gave 1,2-di-hydro derivatives, while 2-chloro-4-phenyl- and 4-chloro-2-phenyl-quinazolines gave the corresponding 3,4-dihydroquinolines with reductive loss of halogen.1356... 

In 1951 Bothner-By first attempted asymmetric reductions based on the conversion of lithium aluminum hydride (LAH) into a chiral alkoxy derivative by reaction with (+)-camphor. Since this pioneering work, the use of chirally modified LAH reagents has been the focus of much attention. In 1979, the first virtually complete enantiofacial recognition of prochiral carbonyl compounds was accomplished by using LAH modified with optically pure 2,2 -dihydroxy-1,1 -binaphthyl and a simple alcohol (BINAL-H). Asymmetric reduction with chiral 2,5-dimethylborolane also gave alcohols in high optical yields." Recently, excellent results have been obtained using a chirally modified sodium borohydride... 

Hydrogenolysis using lithium aluminum hydride under reflux without any additives requires the presence of strongly electron-donating groups such as alkoxy, hydroxy, and amino groups at the ortho or para position to the carbonyl substituent in the aromatic system (equation 13). ... 

A recent report by Chan and Chong describes the enantioselective reduction of acylstannanes to the oi-alkoxy organostannanes by the chiral 2,2 -dihydroxy-l,l -binaphthyl modified lithium aluminum hydrides. Matteson has also described a possible route to such chiral organostannanes utilizing the chiral a-chloroboronic esters. ... 

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