The Studies On Ring Expansion Of 1-cyanocyclopropane 1-esters For The Synthesis Of Fully Substituted Furans

Substituted cyclopropanes and their derivatives as key structural units exist in large numbers of natural products and pharmaceutically active compounds. Cyclopropanes and their derivatives easily undergo a variety of ring-opening reactions under the influence of a variety of conditions. Among them, donor-acceptor cyclopropanes have been broadly used as valuable building blocks for the construction of various chain, carbo-and heterocyclic systems due to their intrinsic ring strain and straightforward synthesis. Generally, the ring-opening of the donor-acceptor cyclopropanes can give easily a 1,3-dipolar intermediate which affords formal cycloaddition with various dipoles to structure various uncyclic and cyclic skeletons. As a part of our continuous research toward the development of new cyclic compounds and structural diversities, using the polysubstituted cyclopropane as essential building blocks, we report our efforts towards the synthesis of fully substituted 2-aminofuran derivatives, 4-cyanofuran-3-carbonate derivatives, and 2-(2,4,5-triarylfuran-3-yl)acetonitrile compounds. Additionally, these selective reactions of 1-cyanocyclopropane 1-esters were also investigated.Part 1:Fully substituted 2-aminofuran derivatives and 4-cyanofuran-3-carbonate derivatives were synthesized by the opening-ring and closing-ring reaction of polysubstituted cyclopropane in the presence of different basic agents. Fully substituted 2-aminofuran derivatives were obtained in 63-86% yield from substituted 1-cyanocyclopropane 1-esters in the presence of iodine and triethylamine under refluxing in toluene solution. The replacement of triethylamine with potassium carbonate gave 4-cyanofuran-3-carbonate derivatives in 75-90% yield. We synthesized thirty-three new products by optimising the reaction conditions. All target compounds were characterized by NMR, IR, and LC-MS spectroscopy. The single crystal structures of seven polysubstituted furans were confirmed by X-ray diffraction method.Part 2:A new DABCO-mediated [3+2] cycloaddition reaction was developed from readily available donor-acceptor cyclopropanes and substituted benzaldehydes. This approach provided a straightforward and efficient way to construct polysubstituted 2-(2,4,5-triarylfuran-3-yl)acetonitrile scaffolds in high yields. Seventeen new products were synthesized by the optimising reaction conditions. All target compounds were characterized by NMR, IR, and LC-MS spectroscopy. The single crystal structures of three products were confirmed by X-ray diffraction method.Part 3:Based on these special reactivity patterns, cyclopropanes and their derivatives have been recognized to be powerful building blocks in organic syntheses. These selective reactions of 1-cyanocyclopropane 1-esters were also investigated. The deesterification of substituted 1-cyanocyclopropane 1-esters was carried out in the presence of iodine and triethylamine under refluxing in the mixture solvents of DMF and toluene. And selective hydrolysis of substituted 1-cyanocyclopropane 1-esters afforded 1-carbamoylcyclopropane-l-carboxylates in the presence of hydroxylamine hydrochloride and sodium acetate. Twenty new products were synthesized by the optimising reaction conditions. All products were characterized by NMR, IR, and LC-MS spectroscopy. The single crystal structures of seven products were confirmed by X-ray diffraction method.