Organoaluminum reagents additions

Organoaluminum reagents are inexpensive and readily available in large quantities. However, only a few examples of conjugate additions using trialkylaluminum nucleophiles have been reported. 

The asymmetric synthesis of / -branched carboxylic acid derivatives was accomplished by conjugate addition of mixed organoaluminum reagents to optically active Arabinose-derived c -unsaturated A-acyloxazolidinones (Scheme 47). Efficient stereocontrol was achieved using different optically active bicyclic oxazolidinones, yielding (.R)- or ( -configured / -branched carboxylic acid derivatives.136a... 

Organoaluminum reagents have been used in the copper-catalyzed conjugate addition to enones with some success. Iwata and co-workers (182) demonstrated that dimethoxyphenyl oxazoline (247) provides modest selectivities in the copper-catalyzed conjugate addition of trimethylaluminum to 3,4,4-trimethylcyclohexadi-enone to provide the adduct in 68% ee, Eq. 145. The use of TBSOTf is crucial to attain high conversion and selectivity in this process. Woodward and co-workers (183) subsequently reported that a Cu(I) complex of thiocarbamate 248 provides modest facial discrimination in the addition of trimethylaluminum to a linear enone to afford 245b in 51% ee, Eq. 146. The authors note that this catalyst system decomposes under the reaction conditions at ambient temperature. 

Enantioselective conjugate addition to construct a cyclic quaternary center has been a particular challenge. Alexandre Alexakis has also shown (Angew. Chem. Int. Ed. 2005,44, 1376), as illustrated by the conversion of 9 to 13, that Cu -catalyzed organoaluminum reagents work effectively in this context. 

Additional evidence that reduction is not the role of R AlCla.. in catalyst formation is provided by the observation that the complexes [Bu4N] [Mo(CO)5X] and [R4N] [Mo(CO)5COR L in which the molybdenum is in a low oxidation state, require an organoaluminum reagent for catalytic activity (44, 45). In these examples, the function of the organoaluminum is most likely the removal of CO ligands to make available sites for olefin coordination. Molybdenum hexacarbonyl alone is reported to be a disproportionation catalyst in this case expulsion of the CO groups is attained thermally at 98 °C (46). 

Small quantities of organoaluminum distillation residues and waste solutions may be destroyed by slow addition of a 25% isopropanol solution in a hydrocarbon solvent. Safety procedures for handhug large volumes of organoaluminum reagents can be obtained from commercial vendors. 

As already discussed in this chapter, aluminum, in addition to its well-known high oxygenophilicity (Al-O = 511 3 kJ mol ), has exceedingly high affinity toward fluorine this is evident from the bond strengths in several metal-fluorine diatomic molecules Al-F, 663.6 6.3 kJ moFh Li-F, 577 + 21 kJ mol" Ti-F, 569 + 34 kJ moF Si-F, 552.7 + 2.1 kJ moF Sn-F, 466.5 + 13 kJ moF and Mg-F, 461.9 + 5.0 kJ moF [76]. Organoaluminum reagents seem, therefore, quite suitable for fluorine-assisted selective alkylation of fluoro epoxides, which also represents the experimental demonstration of the intervention of pentacoordinate chelate complexes of trialkyl-aluminums as plausible intermediates [63]. 

Yamamoto and Maruoka investigated the reaction of chiral acetals with organoaluminum reagents. Unprecedented regio- and stereochemical control was observed in the addition of trialkylaluminums to chiral a,/3-unsaturated acetals derived from optically pure tartaric acid diamide [83]. The course of the reaction seemed to be highly influenced by the nature of substrates, solvents, and temperature. These findings provide easy access to optically active a-substituted aldehydes (84), /3-substituted aldehydes (85), a-substituted carboxylic acids (86), or allylic alcohols (87). Because optically pure RJi)- and (5,5)-tartaric acid diamides are both readily available, this method enables the predictable synthesis of both enantiomers of substituted aldehydes, carboxylic acids, and allylic alcohols from a,/3-unsaturated aldehydes (Sch. 54). 

SITE SELECTIVE AND STEREOSELECTIVE ADDITIONS OF NUCLEOPHILES MEDIATED BY ORGANOALUMINUM REAGENTS... 

The silyl organoaluminum reagent (52) was prepared either by the addition of activated aluminum to a tetrahydrofuran solution of chlorotrimethylsilane, or by the treatment of sodium tetrakis(trimethyl-silyl)aluminate with aluminum chloride. Alternatively, ate complex (53) may be prepared by the addition of methyllithium to tris(trimethylsilyl)aluminum. ... 

The conversion of intermediate (72) to the natural product (73) was accomplished by exposure of a 1 1 complex of (72) and the hindered organoaluminum reagent (1 MAD) to methyllithium (57% yield). This is a fascinating result, not only because attempted methyllithium addition failed, but dso bKause the required configuration of the C-1 position was 3 with regard to the proton substituent and, therefore. 

The efficient activation of oxime sulfonates by organoaluminum reagents enables the intramolecular cyclization of alkenic oxime mesylates, which involves the electrophilic addition of the intermediate ni-trilium ion to the double bond. This results in the direct formation of a wide variety of structurally diverse carbocyclic and heterocyclic systems. Four distinct cyclization modes, i.e. endo(B)-endo, endo(B)-exo, exo(B)-endo and exo(B)-exo are possible, as shown in Scheme 4P The values in parentheses refer to the yields obtained using SnCU. 

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