Ti-TADDOLate-Catalyzed, Highly Enantioselective Addition of Alkyl- and Aryl-Titanium Derivatives to Aldehydes

Article abstract of DOI:10.1016/S0040-4020(01)90475-2

Toluene-ether or toluene-hexane solutions of aryl and alkyl triisopropoxy titanium reagents (free of Li, Mg, or Zn salts) are prepared from the corresponding Li or Grignard reagents and ClTi(OⁱPr)3, with careful removal of salts (centrifugation of LiCl or of dioxane*MgX2, and addition of 12-crown-4).The solutions of the organotitanium compounds are combined with one equiv. of an aldehyde and 0.2 equiv. of (R,R)-diisopropoxy-(α,α,α',α'-tetraphenyl-2,2-dimethyl-1,3-dioxolane-4,5-dimethanolato) titanium (Ti-TADDOLate 3) at dry-ice temperature.Warming up to room temperature leads to nucleophilic addition to the (Si)-face of the aldehydes with enantioselectivities as high as 99.5 : 0.5 (products 4-33 in Scheme 4).Functional groups or protecting groups and branching in the Ti-R group and in the aldehyde must be remote from the reacting centers.Aryl groups can be added to aldehydes by this method. - In contrast to all the enantioselective R2Zn additions to aldehydes, in which only one R-group is actually transferred, a twice as economic use is made of the originally employed R-metal reagent in the method described here. - A procedure for multigram preparation of the spiro-Ti-TADDOLate (2) employed for the in situ generation of catalyst (3) is described, and details of the determination of enantiomer ratios (er) by GC and NMR methods are given (Tab. 2, 3).The mechanistic interpretation of Ti-TADDOLate-mediated nucleophilic additions as derived previously (ref.^4c) is also compatible with this monometallic variant of the method.