Alanes acetals

FIGU RE 1.31 Separation factors for all-(5)/all-(R)-enantiomers of Af-3,5-dinitrobenzoylated alanine peptides (DNB-Alan-OH) and chromatogram for the DNB-protected decaalanine peptide, DNB-Alaio-OH, on a l,4-hw(9-0-quinidinyl)phthalazine-based CSP (5 xm) with LC-ESI-MS. Experimental conditions Column dimension, 150 mm x 4 mm ID mobile phase, methanol-0.5 M ammonium acetate buffer (80 20 v/v) (pHa 6.0) flow rate, 1 mLmin temperature, 25°C injection volume, 50 xL MS negative mode, SIM (C. Czerwenka et ah. Anal. Chem., 74 5658 (2002).)... 

Concurrently, the butyltellurenyl bromide was obtained by the addition of a solution of bromine (0.16 g, 2.0 mmol) in benzene ( 10 mL) to the solution of dibutylditelluride (0.738 g, 2.0 mmol) in hexane cooled at 0°C under a nitrogen atmosphere. The mixture was stirred at 0°C for 10 min, then LiCl (0.196 g, 4.2 mmol) was added, the dark solution turned clear red and stirring was continued until LiCl was dissolved (10 min). The resulting solution was transferred to the flask containing the vinyl alane. The reaction was stirred for 2 h at room temperature and then a mixture of ice and water ( 60 mL) was added. The solids were filtered and the products extracted with hexane (3X70 mL) and ethyl acetate... 

Many more examples exist for reduction of the carhonyl only. Over an osmium catalyst [763] or platinum catalyst activated by zinc acetate and ferrous chloride [782] cinnamaldehyde was hydrogenated to cinnamyl alcohol. The same product was obtained by gentle reduction with lithium aluminum hydride at —10° using the inverse technique [609], by reduction with alane (prepared in situ from lithium aluminum hydride and aluminum chloride)... 

Acetals of aldehydes are usually stable to lithium aluminum hydride but are reduced to ethers with alane prepared in situ from lithium aluminum hydride and aluminum chloride in ether. Butyraldehyde diethyl acetal gave 47% yield of butyl ethyl ether, and benzaldehyde dimethyl acetal and diethyl acetal afforded benzyl methyl ether and benzyl ethyl ether in 88% and 73% yields, respectively [792]. 

High yields of amines have also been obtained by reduction of amides with an excess of magnesium aluminum hydride (yield 100%) [577], with lithium trimethoxyaluminohydride at 25° (yield 83%) [94] with sodium bis(2-methoxy-ethoxy)aluminum hydride at 80° (yield 84.5%) [544], with alane in tetra-hydrofuran at 0-25° (isolated yields 46-93%) [994, 1117], with sodium boro-hydride and triethoxyoxonium fluoroborates at room temperature (yields 81-94%) [1121], with sodium borohydride in the presence of acetic or trifluoroacetic acid on refluxing (yields 20-92.5%) [1118], with borane in tetrahydrofuran on refluxing (isolated yields 79-84%) [1119], with borane-dimethyl sulflde complex (5 mol) in tetrahydrofuran on refluxing (isolated yields 37-89%) [1064], and by electrolysis in dilute sulfuric acid at 5° using a lead cathode (yields 63-76%) [1120]. 

Several new aspects of organoalane chemistry have been described this year. Orthoesters react with alanes, prepared from a variety of allyl and propargyl halides, to give the corresponding 0,y-unsaturated acetals (Scheme 45). Interestingly reactions involving acetals rather than ortho esters lead exclusively to the formation of allenic ethers (160). ... 

Nucleophiles relevant for this chapter are hydride ion, O-atom- and N-atom-centered nucleophiles and C-nucleo-philes like organometallic compounds, ketene acetals, and ester enolates as well as electron-rich heterocycles. Reductions of 1,2,3-triazines and 2-methyl-l,2,3-triazin-2-ium salts by sodium borohydride in methanol and lithium alanate in ether to yield 2,5-dihydro-l,2,3-triazines have been reviewed in CHEC(1984) and CHEG-II(1996). The reaction is explained by nucleophilic attack of the hydride ion at C-5. Borohydride reductions of 1,2,3-triazine... 

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. 

L-3-(3-Deoxy-l,2 5,6-di-0-isopropylidene-a-D-allofuranos-3-yl)alanine (290) (R = R = H) has been synthesized by a route that involved the addition of the carbanion derived from methyl (methylthio)methyl sulphoxide to 3-C-cyano-methyl-3-deoxy-l,2 5,6-di-0-isopropylidene-a-D-allofuranose. Subsequent treatment of the resulting (glycosyl)enamino sulphoxide with acetic anhydride, base-catalysed ester-exchange, and reductive desulphurization afforded the A-acetyl-3-(glycos-3-yl)alanate (290) (R = Ac R = Me), which was hydrolysed to (290) (R = R = H) with base. 

Very similar to the trisacetoxy compound 17, which is simply obtained by dissolving sodium borohydride in acetic acid, the tris-tert-butoxy-alanate complex 18 is formed also on treatment of lithium alanate with tert-butyl alcohol. 

The synthesis of retronecine was completed using a 4-reaction sequence. The C3 hydroxyl group of 34 was converted to a mesylate which underwent j8-elimination to introduce the C1-C2 olefin. The acetal of 35 was hydrolyzed, and sodium borohydride reduction of the C7 ketone from the convex face provided 37. 1,2-Reduction of the unsaturated ester using alane finished the synthesis of retronecine (21). 

Propargylic lithium alanates or lithium borates react with allylic halides or with carbonyl compounds in a regioselective manner to furnish 1,1 -disubstituted allenes (Scheme The reaction between alkyl halides and aluminum metal is the basis of the oldest method for the synthesis of organoaluminum compounds. For example, propargylic bromides react with aluminum in ether giving organoaluminum compounds that on treatment with acetals yield solely a-allenic ethers (equation 1)." However, the reaction of simple alkyl halides with aluminum metal requires a long reaction time. 

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