Asymmetric Michael Addition of Malonates to Enones Catalyzed by an α-d-Glucopyranoside-Based Crown Ether

Abstract

The chiral monoaza-15-crown-5 lariat ether annelated to methyl-4,6-O-benzylidene-α-D-glucopyranoside has been applied as a phase-transfer catalyst in several Michael addition reactions under mild conditions affording the adducts with good to excellent enantioselectivities. In the addition of α-substituted diethyl malonates to trans-chalcones, the substituents of the reactants had a significant impact on the yield and enantioselectivity. Among the reactions of substituted diethyl malonates, that of diethyl-2-acetoxymalonate gave the best results (up to 97% ee). New phase-transfer-catalyzed cyclopropanation reactions (MIRC reactions) of a few enones were also developed using diethyl 2-bromomalonate as the nucleophile. The corresponding chiral cyclopropane derivatives were formed with enantioselectivities up to 92% from 2-benzylidenemalononitrile starting materials, in up to 60% enantiomeric excess using 2-benzylidene-1,3-diphenyl-1,3-propanediones, and in up to 88% optical purity applying trans-chalcones as the starting materials.

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

“…It was noticed in 1 of our previous studies that the 4-methyl substitution increased significantly the enantioselectivity of this reaction under discussion using carbohydrate-based crown ethers. 31 To our surprise, depending on the substituent of the catalysts, much better results were achieved in this reaction ( Table 3, entries 10-15). Cyclopropane derivative 17b was obtained in good yields (81-90%) and with uniformly excellent enantiomeric excesses (99% ee, 96% ee, 98% ee, and 99% ee, respectively) in the presence of lariat ethers having hydroxypropyl side arm (2a, 2c, 2e, and 2f).…”

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

“…A few preliminary results have already been published. 21 Besides that, we used enones containing naphthalene, thiophene and pyridine rings as the aryl substituents (Table 3). …”

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

“…61 Previously, we found that a glucopyranoside-based macrocycle generated asymmetric induction in the reaction of chalcone 9a with diethyl acetoxymalonate (15). 46 It was a challenge for us to test the threitol-based lariat ethers in this reaction. In our experiments, the conjugate addition of diethylmalonate (15) to trans-chalcones 9a-f was carried in a mixture of THF-ether as the solvent in the presence of Na 2 CO 3 (used in 2-fold excess) employing 15 mol% of the crown ether at room temperature to afford the chiral Michael adducts 16a-f.…”

“…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.…”