Metal-promoted [3+2] and [4+2] cycloaddition reactions
thesisposted on 29.06.2018 by Eric A. Allart
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Dicobalt complexes have been extensively used in synthetic chemistry to protect triple bonds, to form new carbon/carbon bonds using the Nicholas reaction and to form polycyclic molecules using the Pauson-Khand reaction. Using these dicobalt complexes, the formation of new carbon-heteroatom bonds was developed through [3+2] and [4+2] cycloaddition reactions via a stabilised dipole intermediate. Initial work carried out makes use of cyclopropanes substituted with a metal-alkyne complex towards the synthesis of tetrahydrofurans and pyrrolidines in good yields and with acceptable diastereoselectivity. The initial aim of the work described hereafter was to improve and expand the previous work carried out within the group. An alternative route using dihydrofurans as a cyclopropane surrogate was explored as well as other methods to form the cyclopropane in a-position to the alkyne. To extend the scope of the methodology, [4+2] cycloaddition reactions have been explored, using Nicholas carbocation. Various precursors have been prepared using a Knoevenagel condensation or an ene reaction. For the first time in synthetic chemistry, a novel [4+2] dipolar cycloaddition reaction from a cyclobutane has been developed. This reaction has opened a new way for the synthesis of six-membered heterocycles in a totally diastereoselective fashion using cyclobutane cores as precursors. A wide range of aldehydes was used as trapping reagents to form tetrahydropyrans in good yields up to 95% and with a good to total diastereoselectivity proven by nOe and X-Ray analyses. The use of other reagents such as ketones, imines and alkenes has been investigated· towards the formation of new six-membered rings as an extension of the methodology.