US EPA

3860742 

Journal Article 

Substrate Range of the Titanium TADDOLate Catalyzed Asymmetric Fluorination of Activated Carbonyl Compounds 

Bertogg, A; Hintermann, L; Huber, DP; Perseghini, M; Sanna, M; Togni, A 

2012 

Yes 

Helvetica Chimica Acta
ISSN: 0018-019X 

95 

3 

353-403 

10.1002/hlca.201100375 

WOS:000301574200002 

The substrate range of the [TiCl2(TADDOLate)] (TADDOL=a,a,a',a'-tetraaryl-1,3-dioxolane-4,5-dimethanol)-catalyzed asymmetric a-fluorination of activated beta-carbonyl compounds has been investigated. Optimal conditions for catalysis are characterized by using 5 mol-% of TiCl2(naphthalen-1-yl)-TADDOLate) as catalyst in a saturated (0.14 mol/l) MeCN solution of F-TEDA (1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis-[tetrafluoroborate]) at room temperature. A series of a-methylated beta-keto esters (3-oxobutanoates, 3-oxopentanoates) with bulky benzyl ester groups (6090% ee) or phenyl ester (6788% ee) have been fluorinated readily, whereas a-acyl lactones were also readily fluorinated, but gave lower inductions (1346% ee). Double stereochemical differentiation in beta-keto esters with chiral ester groups raised the stereoselectivity to a diastereomeric ratio (dr) of up to 96.5?:?3.5. For the first time, beta-keto S-thioesters were asymmetrically fluorinated (6291.5% ee) and chlorinated (83% ee). Lower inductions were observed in fluorinations of 1,3-diketones (up to 40% ee) and beta-keto amides (up to 59% ee). General strategies for preparing activated beta-carbonyl compounds as important model substrates for asymmetric catalytic a-functionalizations are presented (>60 examples). 

Asymmetric catalysis; Catalysis; Fluorination; a; a; a'; a'-Tetraaryl[1; 3-dioxolane-4; 5-diyl]dimethanol; Fluoroorganic compounds; TADDOL; Titanium complexes