Chloro -0“,0“’ titanium aldol reaction

The aldol reactions of titanium enolates have been the best studied of all the transition metal enol-ates."- In many cases they show higher stereoselectivity and chemoselectivity in their reactions than lithium enolates and are easily prepared using inexpensive reagents. They also promote high levels of diastereofacial selectivity in reactions of chiral reactants. The Lewis acidity of the titanium metal center can be easily manipulated by variation of the ligands (chloro, alkoxy, amino, cyclopentadienyl, etc.) attached to titanium, which leads to enhanced selectivity in appropriate cases. Moreover, the incorporation of chiral ligands on titanium makes possible efficient enantioselective aldol reactions. 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

The Duthaler aldol reaction [21] utilizes the transmeta-lation of relatively stable lithium enolates of tert-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-0-isopropylidene-a-D-glucofuranos-3-0-yl)titanate. The so-obtained titanium enolate adds to the re-side of aldehydes and can be converted under acid or basic conditions into its corresponding acid. As often performed for the Braun aldol reaction, recrystallization of the primary aldol product is used as a convenient way for purification and improvement of selectivities. 

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See also in sourсe #XX -- [ ]

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