Enantioselective Cyclopropanation of 2‐Cyano‐3‐arylacrylates Using Carbohydrate‐Based Crown Ethers

Abstract

Enantioenriched, highly functionalized cyclopropane derivatives were prepared by a simple and green approach using monosaccharide-based chiral crown ethers as phase transfer catalysts. The Michael-initiated ring closure (MIRC) reactions of diethyl bromomalonate with 2-cyano-3-phenylacrylate took place with complete diastereoselectivity in the presence of chiral lariat ethers derived from carbohydrates and enantiose-lectivity up to 87 % ee was achieved. Among the catalysts tested, the monoaza-15-crown-5 lariat ether having a methyl βd-glucopyranoside unit and a 2-(3,4-dimethoxyphenyl)ethyl group on the nitrogen generated the highest asymmetric induction (87 % ee). In the reactions of analogous 2-cyano-3arylacrylates, enantioselectivity was in the range of 8-91 % ee.

d-Idose-Based Monoaza-15-Crown-5 Lariat Ethers: Synthesis of an Elusive d-Hexose and Application of Derived Macrocycles in Enantioselective Syntheses

“…When 2-cyano-3-arylacrylates (21a-d) were used in the MIRC reaction (Scheme 7) instead of benzylidenemalononitrile (18), neither the side arm nor the anomeric configuration significantly influenced the results, although the ee values were higher than in the previous cyclopropanation. The products 21a-d were obtained with complete diastereoselectivity, just as previously observed [3]. It seems that in the case of the crown ethers in which the position of the anomeric methyl group was axial (Table 3, entries 1-2), the reaction times were shorter compared to the β-analogues (Table 3, entries 3-5).…”

“…As in a previous publication [3], we investigated if the substitution of the aromatic ring had any positive or negative effects on the enantioselectivity. Thus, the Scheme 6.…”

“…As in a previous publication [3], we investigated if the substitution of the aromatic ring had any positive or negative effects on the enantioselectivity. Thus, the cyclopropanation of chloro-substituted arylacrylates (21b-d) was examined using crown ether 1c as the catalyst.…”

“…Enantioselective phase transfer catalysis [1,2] is a widely applied concept, the goal being the simple and efficient synthesis of enantioenriched or enantiopure compounds, which omits the oftentedious procedure of the post-reaction resolution of stereoisomers. Crown ethers that contain one or more asymmetric centers can promote enantioselective reactions [3]. Their usage as selector molecules in chiral stationary phases has been prevalent in recent years as well [4].…”

Synthesis of cyclopropanes through gold-catalyzed [2 + 1] cycloaddition of allenamides with sulfoxonium ylides

“…5 Other transition metal-free reactions include the use of bases, Lewis acids, and various ylides that can also form cyclopropanes. 6 However, despite its great underlying potential, cyclopropanation with the formation of carbene as the key intermediate has some limitations. For example, diazo compounds as carbene precursors are limited due to their poor stability and high explosiveness.…”