Titanium‐Catalyzed Stereoselective Geminal Heterodihalogenation of β‐Ketoesters.

Abstract

Oxocarboxylic acids and esters Oxocarboxylic acids and esters Q 0460Titanium-Catalyzed Stereoselective Geminal Heterodihalogenation of β-Ketoesters. -Monofluorination of β-ketoesters (I) and (IV) with Selectfluor proceeds smoothly in the presence of titanium catalysts to furnish the α-fluoroβ-ketoesters (II) and (V), resp., in moderate to good yields. The selectivity of mono-to difluorination reaches 10-30:1. The method can be extended to achieve an enantioselective heterodihalogenation. Thus, monofluorination in the presence of a chiral TiCl 2 ((R,R)-TADDOL) complex, followed by chlorination with NCS under analogous conditions furnishes the α-chloro-α-fluoro-β-ketoesters (III) and (VI) in moderate enantioselectivities. Changing the order of halogenation steps provides access to the corresponding stereoisomer. The introduction of a chiral auxiliary at the ester group does not significantly improve the selectivities. -(FRANTZ, R.; HINTERMANN, L.; PERSEGHINI, M.; BROGGINI, D.; TOGNI*, A.; Org. Lett. 5 (2003) 10, 1709-1712; Dep. Chem., Swiss Fed. Inst. Technol., ETH-Hoenggerberg, CH-8093 Zuerich, Switz.; Eng.) -Mischke 38-063 2003 Oxocarboxylic acids and esters

Recent Advances in Catalytic Enantioselective Fluorination of Active Methines

“…The stereochemical outcome is determined in the second fluorination with comparable yields and enantioselectivities (up to 57%) while utilizing the same enantiomeric form of the catalyst (Scheme 15) [23]. The stereochemical outcome is determined in the second fluorination with comparable yields and enantioselectivities (up to 57%) while utilizing the same enantiomeric form of the catalyst (Scheme 15) [23].…”

“…Togni and co-workers also demonstrated that Ru-Salen complex (23) are also suitable catalysts for electrophilic fluorination. The chiral Ru(II)-Salen complex catalyzed the asymmetric fluorination of -ketoesters with NFSI affording fluorinated compounds with high enantioselectivity (Scheme 12) [20].…”

Selectfluor and Its Analogs Electrophilic Fluorination for Preparing Alkyl Fluorides

“…The disadvantage is that monofluorinated products could not be selectively obtained under these conditions. The use of CpTiCl 3 as catalyst in acetonitrile solved this problem at least partially with amount of difluorinated compounds under 10% [53,54]. In the direct monofluorination of various acetoacetamides carried out in green solvent PEG-400 at 60 C without the use of base or metal catalyst, the selective formation of monofluorinated products was observed with a ratio greater than 30:1 [55].…”

Cu(I)‐catalyzed asymmetric chlorination of β‐keto esters in the presence of chiral phosphine‐schiff base type ligands

“…[2][3][4][5] The resulting chiral halogen-containing compounds have attracted much attention in various research fields such as biological and medicinal chemistry as well as material science. 6 The first enantioselective fluorination of b-keto esters was reported by Togni and coworkers [7][8][9] Following this pioneering work, Sodeoka and coworkers reported an efficient enantioselective fluorination of various acyclic and cyclic b-keto esters catalyzed by chiral BINAP-palladium complexes. [10][11][12][13][14] Other late transition metal complexes including Cu(II), Ni(II), and Zn(II), which are complementary to the palladium complexes, were also successfully applied to catalyze asymmetric halogenation reactions.…”