Methylalumination asymmetric

Although the application of carboalumination to the synthesis of natural products is still in its infancy, a few preliminary results shown in Scheme 1.50 [167,168,171,172] suggest that it promises to become a major asymmetric synthetic reaction, provided that (i) the singularly important case of methylalumination can be made to proceed with S90% ee, and (ii) satisfactory and convenient methods for enantiomeric and diastereo-meric separation/purification can be developed. In this context, significant increases in ee in the synthesis of methyl-substituted alkanols from around 75 % to 90—93 % achieved through some strategic modifications are noteworthy (Scheme 1.50) [168]. Shortly before the discovery of the Zr-catalyzed enantioselective carboalumination, a fundamentally discrete Zr-catalyzed asymmetric reaction of allylically heterosubstituted alkenes proceeding via cyclic carbozirconation was reported, as discussed later in this section. 

Scheme 8.39. Asymmetric methylalumination reaction accelerated by addition of water.

Asymmetric methylalumination of alkenes bears fruit because chiral zirconium 136 was discovered to be an effective catalyst (Scheme 6.120) [152]. In initial attempts, the reaction proceeded in higli yield but with moderate to high ee (65-85%). More promising results were obtained by re-examining conditions that involved a proper choice of solvent CH3CHCI2. 

Negishi coupling reactions can be combined with asymmetric carboalumination, a process that was also discovered by the Negishi group (Scheme 5-87). The asymmetric induction of this zirconium-catalyzed enantioselective methylalumination process ( ZACA ) stems from a chiral zirconium catalyst precursor, namely dichlorobis(neomenthylindenyl)zirconium [(NM aZrCb]. The stereoinduction is very high. 

Zr-Catalyzed Asymmetric Methylalumination of Ordinary Unactivated Alkenes... 

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