Crown ether derived from d-glucose as an efficient phase-transfer catalyst for the enantioselective Michael addition of malonates to enones

Abstract

A monoaza-15-crown-5 lariat ether derived from D-glucose (1) has been applied as chiral phase-transfer catalyst in the Michael addition of diethyl, dimethyl, diisopropyl and dibenzyl malonates to enones under mild conditions to afford the adducts in good to excellent enantioselectivities. In the reaction of diethyl malonate with substituted trans-chalcone, the adducts formed in enantioselectivities up to 89% ee. Among the reactions of substituted diethyl malonates, that of diethyl acetoxymalonate gave the best results (96% ee). The effect of the substituents of the chalcone was also investigated in reaction with diethyl acetoxymalonate. Among the chalcones substituted on the β side, the para-substituted compounds resulted in the highest enantioselectivities (88-97% ee). The substituents on the α-side of chalcone caused a decrease in the enantioselectivity, as compared to the unsubstituted case. The adducts having furyl or thiophenyl substituents were formed with >99% ee. The glucose-based catalyst also proved to be effective in the cases of diisopropyl and dibenzyl acetoxymalonates (including ee-s up to 99% ee). The reactions of diethyl acetoxymalonate with cyclic enones gave the corresponding Michael adducts in enantioselectivities up to 83%.-2 -The absolute configuration of one of the new Michael adducts was determined by CD spectroscopy.

Synthesis of d‐mannitol‐based crown ethers and their application as catalyst in asymmetric phase transfer reactions

“…25 In the presence of mannitol-based macrocycles, completion of the reaction required 10 to 14 days. Earlier, this reaction was carried out by using a glucopyranoside-based lariat ether as the catalyst leading to good optical purity.…”

“…Earlier, this reaction was carried out by using a glucopyranoside-based lariat ether as the catalyst leading to good optical purity. 25 In the presence of mannitol-based macrocycles, completion of the reaction required 10 to 14 days. The results are summarized in Table 1.…”

Synthesis of l‐threitol‐based crown ethers and their application as enantioselective phase transfer catalyst in Michael additions

“…The organic layer was washed with cold 10% HCl (3 x 10 ml) and then with water (10 ml), dried (Na 2 CO 3 and Na 2 SO 4 ), and concentrated. The crude product was purified by preparative TLC using silica gel and hexane-EtOAc 2.6 | General procedure for asymmetric model reactions using malonates [46][47][48] Unsaturated compound (1 mmol), substituted malonate (1.5 mmol) and the crown ether (0.15 mmol) were dissolved in a mixture of anhydrous THF (0.6 ml) and Et 2 O (2.4 ml) and dry Na 2 CO 3 (0.22 g, 2 mmol) was added. The reaction mixture was stirred at RT.…”

Crystal structure of diethyl 2-acetoxy-2-[3-(4-nitrophenyl)-3-oxo-1-phenylpropyl]malonate

“…Many phase-transfer-catalyzed methods that are simple and environmentally friendly have been developed for the Michael reaction (Shioiri, 1997). This new racemic compound was prepared in a phase-transfer reaction using a sugar-based crown ether as the catalyst (Rapi et al, 2016).…”