The Lack Of Electronic Vinyl Cyclopropane Reaction And Open-loop Of The Formyl Cyclopropane Series

Natural products-based strategy for lead discovery provides an efficient access to new medicines and agrochemicals.Many biologically active natural products have similar skeletons(so-called "privileged structures" or "pharmacophores"),which are difficult to construct efficiently employing current synthetic methods,thus it is very important to develop novel methods and strategies for HECCS(Highly Efficient Construction of Complex Skeletons).Domino reaction is one of the most important and efficient methods for HECCS in contemporary organic synthesis.As versatile building blocks in modern organic syntheses,activated cyclopropanes have attracted many interests in the field of nucleophilic ring-opening domino reactions.As a 5-carbon synthon,vinylcyclopropanes can undergo nucleophilic ring-opening with 1,3-or 1,5-mode.However,there are very limited reports taking advantage of the 1,5-mode ring-opening by nucleophilic addition which may be selected as a potential candidate to develop new domino reactions for HECCS.In the research of novel carbon-carbon and carbon-heteroatom bonds-forming reactions,N-heterocyclic carbenes(NHCs) have been efficiently applied as organocatalysts in a large number of umpolung chemical transformations. As a 4-carbon synthon,activated formylcyclopropanes can undergo NHC-catalyzed ring-opening based redox esterification and amidation processes,which encourage us to further explore the domino ring-opening reactions of formylcyclopropanes.We have developed three novel organic synthetic methods based on the domino ring-opening reactions of an activated vinylcyclopropane and di-activated formylcyclopropanes.Firstly,in the presence of DABCO·6H₂O,an activated vinylcyclopropane reacted with substituted benzaldehydes to affordα-methylene-γ-butyrolactones via a 1,5-mode ring opening process.Secondly,NHCs catalyzed the reaction of formylcyclopropane 1,1-diesters with salicylaldehydes via a domino redox esterification/Knoevenagel condensation process to give coumarins in moderate to excellent yields.Thirdly,we have demonstrated a novel domino ring-opening/redox amidation/cyclization reaction between 2-chloro-1H-indole-3- carboaldehydes and formylcyclopropane 1,1-diesters,which provides an efficient and direct access to a 6-5-6 tricyclic hydropyrido[1,2-α]indole skeleton,additionally, this method can be applied for the construction of the tetracyclic core skeleton of the natural product tronocarpine.