Bisoxazoline-Catalyzed Asymmetric Nucleophilic Addition of Diethyl Zinc to Fluorinated Alkyl Ketones: Enantiofacial Control by Changing the Bisoxazoline Substituent
Abstract:Bisoxazoline (BOX)-catalyzed asymmetric nucleophilic addition of diethyl zinc to fluorinated alkyl ketones successfully afforded enantioenriched fluorinated alkyl tertiary alcohols. The effect of the size of the substituent on the oxazoline ring on the stereoselectivity of the reaction was investigated. Furthermore, the enantioselectivity could be reversed by altering the BOX bridge structure while retaining the C-4 substituent on the oxazoline ring.
“…[7] Jacobsen has recently reported au nique catalytic method for the asymmetric difluorination of alkenes to generate difluoromethylated stereocenters. [8] Asymmetric copper-catalyzed borylations represent ap owerful tool for the synthesis of optically active organoboron compounds. [9] We and other groups have reported the asymmetric synthesis of allylboron compounds via the asymmetric boryl substitution of allylic compounds (Scheme 1a).…”
The first catalytic enantioselective γ-boryl substitution of CF -substituted alkenes is reported. A series of CF -substituted alkenes was treated with a diboron reagent in the presence of a copper(I)/Josiphos catalyst to afford the corresponding optically active γ,γ-gem-difluoroallylboronates in high enantioselectivity. The thus obtained products could be readily converted into the corresponding difluoromethylene-containing homoallylic alcohols using highly stereospecific allylation reactions.
“…[7] Jacobsen has recently reported au nique catalytic method for the asymmetric difluorination of alkenes to generate difluoromethylated stereocenters. [8] Asymmetric copper-catalyzed borylations represent ap owerful tool for the synthesis of optically active organoboron compounds. [9] We and other groups have reported the asymmetric synthesis of allylboron compounds via the asymmetric boryl substitution of allylic compounds (Scheme 1a).…”
The first catalytic enantioselective γ-boryl substitution of CF -substituted alkenes is reported. A series of CF -substituted alkenes was treated with a diboron reagent in the presence of a copper(I)/Josiphos catalyst to afford the corresponding optically active γ,γ-gem-difluoroallylboronates in high enantioselectivity. The thus obtained products could be readily converted into the corresponding difluoromethylene-containing homoallylic alcohols using highly stereospecific allylation reactions.
The regioselectivity of addition of organomagnesium reagents to trifluoromethylated α‐bromoenones is reported. Alkyl and aryl Grignard reagents undergo 1,4‐ and/or 1,2‐addition but, in contrast to non‐fluorinated α‐bromoenones, the former direction is dominant for these fluorinated analogs. The high 1,4‐regioselectivity observed in most cases reflects the influence of the trifluoromethyl group on the direction of nucleophilic attack.
“…For example, Sasaki et al described the use of bis(oxazoline) 32 for the enantioselective addition of Et 2 Zn to trifluoromethyl ketones.A lthough compound 33 was obtained with good selectivity,t he selectivity significantly decreased for the alkynyl substrate (Scheme 21). [41] Recently,t he Hoveyda group introducedaseries of aminophenol catalysts for the catalytic stereoselectivea ddition of organoboron reagents. [42] The features of the catalysis included high catalytic activity (turnover number/frequency) and broad substrate scope.…”
Section: Addition Of Organometallic Reagentsmentioning
Enantioenriched CF 3 -substituted tertiary alcohols have been applied in ab road range of chemical disciplines, including medicinal chemistry and agrochemistry. The widely prescribed anti-HIV pharmaceutical efavirenz is one particular example of the application of these chiral building blocks. Because the typical synthetic route to this small drug molecule involves the stoichiometric use of ac hiral promoter,s ignificant effort has been devoted to the development of catalytic alternatives for accessing this building block.I n this Focus Review,w es ummarize the catalytic asymmetric synthesis of CF 3 -substituted tertiary propargylic alcohols based on three retrosynthetic approaches, namely one trifluoromethylation approacha nd two building-block strategies.T he general challenges that are involved in the construction of aC F 3 -substituted tetrasubstituted stereogenic carbon speciesa re highlighted and possible future directions in the field are discussed.
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