Enantioselective hydroalumination

Hydroalummation of Functional Croups 63 2.4.1.2 Enantioselective Hydroalumination of Alkenes... 

In addition to the enhanced rate of hydroalumination reactions in the presence of metal catalysts, tuning of the metal catalyst by the choice of appropriate ligands offers the possibility to influence the regio- and stereochemical outcome of the overall reaction. In particular, the use of chiral ligands has the potential to control the absolute stereochemistry of newly formed stereogenic centers. While asymmetric versions of other hydrometaUation reactions, in particular hydroboration and hydrosi-lylation, are already weU established in organic synthesis, the scope and synthetic utiHty of enantioselective hydroalumination reactions are only just emerging [72]. 

To date, synthetically useful enantioselective hydroalumination is limited to the asymmetric reductive ring-opening reaction of bicycHc ethers. In spite of the fact that further studies are necessary to get a detailed understanding of the reaction mechanism, this reaction provides a new route to various cycloalkenol derivatives, which are useful intermediates in the preparation of biologically active compounds. 

The mechanism for this nickel-catalyzed enantioselective hydroalumination was initially thought to proceed via a nickel-catalyzed hydroalumination followed by the elimination of the organoaluminum with cleavage of the oxygen bridge. However, this seems unlikely in the light of recent evidence (Scheme 11). 

It was not until 1995 that a synthetically useful enantioselective hydroalumination was first described.123 The early attempts to develop enantioselective hydroalumination used chiral phosphines such as prophos, chiraphos 26, and BINAP 23 as ligands. The most successful of these was BINAP with ee s of 56% being obtained (entry 1, Table 11). 

Oxabenzonorbornadienes 124 also undergo enantioselective hydroaluminations. However, milder conditions were later developed as reactions in toluene typically resulted in the formation of naphthalene and naphthol as byproducts and the ee s were typically 60%. In the presence of THF, the reaction gave the ring-opened product in significantly better yield (88%) and ee (98%) (entry 1, Table 13). A number of oxabenzonorbornadienes were shown to undergo... 

Metal catalyzed hydrometalations, specifically hydroboration and hydrosi-lylation, are particularly attractive due to the potential for enantiocontrol by the use of chiral ligands coordinated to the metal center. While the first metal catalyzed hydroalumination was described more than 40 years ago, the first synthetically useful enantioselective hydroalumination was described in 1995 and the scope and synthetic utility of this reaction are only just emerging. 

An enantioselective hydroalumination of a prochiral olefin was first reported by GiacomeUi and coworkers. The authors surveyed a number of chiral amines in the nickel catalyzed hydroalumination of 1,1-disubstituted alkenes. Of the amines examined, N,N-dimethylmenthylamine (DMMA) in combination with triisobutylalane and catalytic amounts of Ni(mesal)2 (mesal = methylsaHcyHde-neimine) (5) effected the hydroalumination of 2,3,3-trimethylbutene which, fol-... 

Use of the chiral pool typically requires a series of subsequent transformations to achieve the substitution pattern desired and sometimes may be limited by the availability of only one enantiomer. Microbial oxidations of benzene derivatives have provided an excellent route to cyclohexadienediols in enantiomerically pure form. Although this provides only one enantiomer, synthetic methods have been devised to circumvent this problem [36]. Far fewer methods exist for the enantioselective synthesis of cycloheptenes for which there exists no reaction analagous to the Diels-Alder process [37,38,39,40,41,42]. The enantioselective hydroalumination route to dihydronapthalenols may prove to be particularly important. Only one other method has been reported for the enantioselective synthesis of these compounds microbial oxidation of dihydronaphthalene by P. putida generates the dihydronaphthalenol in >95% ee and 60% yield... 

Highly enantioselective hydroalumination was realized in 1995 in the reaction of 174 with 1-BU2AIH (DIBAL, 175) promoted by the catalyst generated in situ from (/f)-BINAP (58) (21 mol%) and Ni(COD)2 (14 mol%) at -78°C, which gave 176 with 97% ee in 97% yield through the ring-opening of the initially formed adduct 177 (Scheme 2.20) [99]. 

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