Asymmetric synthesis of α-trifluoromethoxy ketones with a tetrasubstituted α-stereogenic centre via the palladium-catalyzed decarboxylative allylic alkylation of allyl enol carbonates

Abstract

The palladium-catalyzed asymmetric decarboxylative allylic alkylation of trifluoromethoxy allyl enol carbonates afforded enantioenriched α-trifluoromethoxy allyl ketones that feature a tetrasubstituted α-stereogenic center in excellent yield and high enantioselectivity. The method was further extended to the asymmetric synthesis of α-difluoromethoxy and α-methoxy allyl ketones, which proceeded under similar catalytic conditions.

Enantioselective Benzylation and Allylation of α-Trifluoromethoxy Indanones under Phase-Transfer Catalysis

“…All the substrates, α-OCF3-indanones 1, were prepared by following a reported procedure. [46] General Procedure: A mixture of the indanone (1.0 equiv) and KOH (3.0 equiv) in MeOH (0.4 M) was stirred for 15 min at 0 °C, and PhI(OAc)2 (1.1 equiv) was added in 4-5 portions during 5 min. The mixture was stirred at the same temperature for 1 h, then warmed to room temperature and stirred overnight.…”

“…The reaction was run according to the general procedure, and the product is consistent with previously reported characterization data. [46] Eluent (n-hexane/ethyl acetate = 15/1). Colorless oil; 11.0 mg; 43% yield.…”

“…[45] We developed a strategy for the synthesis of chiral, non-racemic α-OCF3-ketones with a tetrasubstituted carbon center via a Pd-catalyzed enantioselective Tsujiallylation reaction with high enantioselectivity (Scheme 1c). [46,47] Very recently, Liu and co-workers reported the Pd-catalyzed enantioselective intramolecular trifluoromethoxylation reaction of alkenes using CsOCF3 to furnish OCF3-compounds with a chiral stereogenic center (Scheme 1d). [48] While these methods have broad substrate scopes with high enantioselectivity, all the methods require transition metal catalysts.…”

Enantioselective Benzylation and Allylation of α-Trifluoromethoxy Indanones under Phase-Transfer Catalysis

“…Later, Shen and co-workers reported a method to construct chiral trifluoromethoxyl compounds by the Ni-catalyzed enantioselective Suzuki–Miyaura coupling of secondary benzyl bromides in good to high enantioselectivity (Scheme 1b) [44]. We developed a strategy for the synthesis of chiral, non-racemic α-OCF 3 -ketones with a tetrasubstituted carbon center via a Pd-catalyzed enantioselective Tsuji-allylation reaction with high enantioselectivity (Scheme 1c) [45,46]. Very recently, Liu and co-workers reported the Pd-catalyzed enantioselective intramolecular trifluoromethoxylation reaction of alkenes using CsOCF 3 to furnish OCF 3 -compounds with a chiral stereogenic center (Scheme 1d) [47].…”

Palladium(II)‐Catalyzed Enantioselective Aminotrifluoromethoxylation of Unactivated Alkenes using CsOCF3 as a Trifluoromethoxide Source

“…[1] Therefore,m uch efforts have been devoted to the synthesis of chiral organofluorines during the last few decades. [2] Compared to reported methods for the synthesis of optically active F-and CF 3 containing compounds, [3] thed evelopment of methodologies for the preparation of chiral OCF 3 -containing molecules lags far behind, [4] which is possibly attributed to the nature of easy decomposition of the OCF 3 anion [5] and limited OCF 3 reagents. [6] Very recently,T ang and co-workers reported the sole example of the asymmetric trifluoromethoxylation reaction through an organocatalytic process,e mploying stable trifluoromethyl arylsulfonates (TFMS) as ap recursor for AgOCF 3 (Scheme 1a).…”