Nucleophilic Ring Opening of Cyclopropane Hemimalonates Using Internal Brønsted Acid Activation

Abstract

The reaction of cyclopropanes, geminally disubstituted with one carboalkoxy and one carbohydroxy group, undergoes ring-opening reactions with indole nucleophiles under catalyst-free, hyperbaric (13 kbar) conditions. An internal hydrogen bond is postulated as the mode of activation obviating the need for the Lewis acid catalyst normally used for such donor-acceptor cyclopropane chemistry. These conditions avoid decarboxylation and yield useful adducts with the carboxylic acid group intact for further elaboration.

A New Golden Age for Donor–Acceptor Cyclopropanes

“…Friedel–Crafts alkylations involving the ring‐opening reactions of D‐A cyclopropanes usually occur at the 3‐position of the indole moiety. Most recent studies in this field are based upon investigations performed by Kerr and co‐workers on the indole‐induced bond cleavage of D‐A cyclopropanes 13b,c. Subsequent studies by Johnson showed that control could be exerted over the stereocenter formed in this reaction by employing a pybox ligand (pybox*), which enforces a chiral environment upon the Lewis acid MgI 2 .…”

Ring Opening of Donor–Acceptor Cyclopropanes with N-Nucleo­philes

“…[137][138][139][140][141][142][143][144][145] In these cases, the chemoselectivity mainly depends upon the sites where substituents are located in the indole. However, reaction of 3-methyl-1H-indole (N-unsubstituted skatole) with a cyclopropane-1,1-dicarboxylate 1a under harsh conditions resulted in N-alkylation proceeding along with formal (3+2)-cycloaddition and leading to product 164 (Scheme 89).…”

Synthesis and Reactivity of Donor-Acceptor Substituted Aminocyclopropanes and Aminocyclobutanes

“…Interestingly, Kerr showed 14 years later that hydrolysis of one ester in the starting cyclopropane was enough to activate it with no need of a catalyst (Scheme 1.4) [54]. The reaction occurred under high pressure (13 kbar) and probably proceeded via intramolecular H-Bonding in cyclopropane 39.…”