Prolinol diphenylprolinol

In the case of acetophenone reduction, it appears that amino alcohols that are sterically hindered at the carbon adjacent to the alcohol lead to much better results. A dramatic effect has been found in the case of prolinol and diphenylprolinol the enantiomeric excess increases from 50% to 97%. Cyclic amino alcohols where the nitrogen is in a 4- or 5-membered ring have exceptional catalytic properties and lead to very good enantiomeric excesses (Tables 16.1 and 16.2). Diphenylprolinol (4) is a very good choice because of its availability and performance. 

Prolinol or diphenylprolinol were found by Corey et al. [87] and Itsuno et al. [88] to catalyze the enantioselective diborane reduction of many ketones. Corey et al. developed this new route greatly, often called CBS reduction (from the names of the authors of Ref. [87]). An oxazaborolidine which is either formed in situ or can be preformed, is the actual catalyst. A mechanistic picture has been proposed [87]. 

Other cyclic alcohols apart from prolinol have been used to synthesise bicyclie oxazaphospholidines and derivatives. One important example is (5)-(—)-a,a-diphenylprolinol (51), which is nowadays commercially available (Scheme 3.22). 

Direct organocatalytic -benzylation of a, -unsaturated aldehydes using toluenes has been achieved under mild conditions of DCM/reflux, using f-butyldimethylsilyl-protected diphenylprolinol ees >99% arereported. Typically, the toluene needs to be activated by a base such as triethylamine, and typically also needs two nitro groups (or one nitro and another EWG) to stabilize the benzyl anion intermediate. Dual activation is essential without the prolinol, no reaction occurs, even with excess DMAP or DBU as base. 

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