Highly enantioselective gem-chlorofluorination of active methylene compounds was carried out by using a copper(II) complex of a chiral spiro pyridyl monooxazoline ligand. This reaction yielded α-chloro-α-fluoro-β-keto esters and α-chloro-α-fluoro-β-keto phosphonates with up to 92% ee. The resulting dihalo β-keto ester was converted into various α-fluoro-α-heteroatom-substituted carbonyl compounds via nucleophilic substitution without loss of optical purity. A fully protected β-amino acid with a gem-chlorofluoromethylene function was also synthesized.
Testing the waters: An architecture‐based system for transition‐metal catalysis consisting of a self‐assembled amphiphilic pincer palladium complex bearing hydrophilic and hydrophobic chains has been developed. Self‐assembly of the bilayer vesicles of the complex, concentration of the organic substrates within the hydrophobic region of the bilayer membrane, and catalytic transformation of the substrate all occur sequentially in water (see scheme).
A novel optically active 2-(oxazolinyl)pyridine ligand (Spymox) having a spiro binaphthyl backbone was synthesized from an a,a-disubstituted a-amino acid (H-Bin-OH), and successfully used in palladium-catalyzed asymmetric allylic alkylations to afford the corresponding alkylated products with 99% ee. Development of new chiral ligands for asymmetric synthesis is an important research subject in synthetic organic chemistry. Recently, optically active spiro compounds have attracted significant attention as a new class of chiral ligands because their rigid spiro structure can result in a fairly rigid transition-state geometry during the course of asymmetric metal catalysis. 1 However, there are few reports on the successful development of spiro chiral ligands, especially which have spiro structure on their side arm, because of the difficulty involved in the preparation of these ligands in optically pure form. 2,3 Herein, we have designed chiral spiro 2-(oxazolinyl)pyridine (Spymox) as a novel N,N-bidentate ligand. 4 Spymox was efficiently synthesized from 2-picolinic acid and H-Bin-OR, 5 which is an a,a-disubstituted a-amino acid with an axial chiral binaphthyl backbone (Scheme 1). Surprisingly, no report have been appeared on the application of this unique artificial amino acid to asymmetric catalysis, though chiral aamino acids have been frequently used as synthons for numerous chiral ligands 6 and organocatalysts. 7 In this paper, we discuss the concise synthesis of spymox and its successful application to palladium-catalyzed asymmetric allylic alkylations. 8The synthesis of Spymox (1) is shown in Scheme 2. H-[(R)-Bin]-OEt (3) was synthesized from (R)-2,2¢-bis(bromomethyl)-1,1¢-binaphthyl (2) and ethyl isocyanoacetate using a phase-transfer catalyst in 84% yield. This procedure is much more concise than the previous report using glycine tert-butyl ester Schiff base. 5 The amido alcohol 4 was obtained by the condensation of 3 with 2-picolinoyl chloride, followed by reduction of the ethyl ester with LiBH 4 . After chlorination of the primary alcohol with SOCl 2 , the oxazoline ring was formed under basic conditions to afford (R)-1 with 45% yield (25% overall yield).Scheme 2 Reagents and conditions: (a) CNCH 2 CO 2 Et (1.2 equiv), n-Bu 4 N + HSO 4 -(20 mol%), K 2 CO 3 (10 equiv), MeCN, reflux, 18 h; (b) concd HCl, EtOH, r.t., 6 h; (c) 2-picolinoyl chloride·HCl (1.1 equiv), Et 3 N (4 equiv), CH 2 Cl 2 , r.t., 4 h; (d) LiBH 4 (5 equiv), THF, r.t., 12 h; (e) SOCl 2 (10 equiv), CHCl 3 , reflux, 6 h; (f) 2.5 N aq NaOH (10 equiv), 1,4-dioxane, 60°C, 20 h.The asymmetric induction of Spymox was evaluated by using it in the palladium-catalyzed asymmetric alkylation of racemic 1,3-diphenyl-2-propenyl acetate (5a). 9 Fortunately, the palladium complex of (R)-1 catalyzed the alkylation of 5a with dimethyl malonate to afford the desired product 6a with 99% ee. As sumarized in Table 1, excellent enantioselectivities were observed in a variety of solvents, including highly polar solvents and protic solvents. Notably, the use of ter...
Amphiphilic pincer palladium complexes bearing hydrophilic and hydrophobic side chains on the planar NCN palladium pincer backbone were designed and prepared via the ligand introduction route. The complexes self-assembled under aqueous conditions to form vesicles with bilayer membranes containing palladium species. The catalytic activity of the vesicles in the Miyaura-Michael reaction in water was investigated.
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