benzofurans and cyclopropane

Topics: Benzofurans; Bridged Bicyclo Compounds; Carbon; Cyclobutanes; Cyclohexanes; Cyclopentanes; Cyclopropanes; Nucleosides; Spiro Compounds

Herein, we describe an unprecedented (3 + 3) cycloaddition reaction of the donor-acceptor cyclopropanes with quinone esters toward the construction of chroman scaffolds in moderate to good yields. Interestingly, the strategy is also adjustable toward a (3 + 2) cycloaddition by just switching the Lewis acid to furnish benzofuran scaffolds. Based on the choice of Lewis acid used, the same set of precursors has been used to deliver the benzopyran and benzofuran derivatives.

Topics: Benzofurans; Benzoquinones; Catalysis; Cycloaddition Reaction; Cyclopropanes; Esters; Lewis Acids; Molecular Structure

Engineered hemoproteins have recently emerged as promising systems for promoting asymmetric cyclopropanations, but variants featuring predictable, complementary stereoselectivity in these reactions have remained elusive. In this study, a rationally driven strategy was implemented and applied to engineer myoglobin variants capable of providing access to 1-carboxy-2-aryl-cyclopropanes with high trans-(1R,2R) selectivity and catalytic activity. The stereoselectivity of these cyclopropanation biocatalysts complements that of trans-(1S,2S)-selective variants developed here and previously. In combination with whole-cell biotransformations, these stereocomplementary biocatalysts enabled the multigram synthesis of the chiral cyclopropane core of four drugs (Tranylcypromine, Tasimelteon, Ticagrelor, and a TRPV1 inhibitor) in high yield and with excellent diastereo- and enantioselectivity (98-99.9% de; 96-99.9% ee). These biocatalytic strategies outperform currently available methods to produce these drugs.

Topics: Adenosine; Benzofurans; Catalysis; Cyclopropanes; Escherichia coli; Molecular Structure; Myoglobin; Protein Engineering; Stereoisomerism; Ticagrelor; Tranylcypromine

An efficient MgI2-catalyzed annulation between donor-acceptor cyclopropane and N-tosylaziridinedicarboxylate to access highly substituted 2H-furo[2,3-c]pyrrole bearing two rings and four stereocenters, including one quaternary carbon stereocenter, has been developed. This methodology can be used for the synthesis of biologically active compounds like IKM-159. This work also offers an insight into the mechanism of the annulation process.

Topics: Aziridines; Benzofurans; Catalysis; Cyclopropanes; Lewis Acids; Molecular Structure; Oxidation-Reduction; Pyrroles; Pyrrolidinones

A synthetic method for bicyclic heterocycles, such as indole, benzofuran and chromene derivatives bearing a chiral cyclopropane at the 2-position, was established using isomerization of a terminal olefin and enamide-ene or diene metathesis. This route can also be applied to chiral 2-cyclopropylquinoline synthesis (both cis and trans).

Topics: Alkenes; Benzofurans; Benzopyrans; Cyclopropanes; Indoles; Molecular Structure; Quinolines; Stereoisomerism