An organocatalytic reductive coupling and Lewis-acid-catalyzed annulative ring-opening strategy is developed as a two-step protocol for the stereoselective synthesis of dihydropyrans as the major products from the chiral formylcyclopropanes, CH acids, and Hantzsch ester. It is an efficient, catalytic, two-step protocol for the chiral synthesis of dihydropyrans and dihydrofurans. Structurally important and challenging functionally rich cyclopropanes containing cyclic-1,3-diones were synthesized in very good yields with excellent chemo-, enantio-, and diastereoselectivities from the readily available starting materials, chiral formylcyclopropanes, cyclic-1,3-diones, or CH acids and Hantzsch ester through an organocatalytic reductive coupling reaction at ambient conditions, especially without harming the cyclopropane ring. Chiral cyclopropanes containing cyclic-1,3-diones were stereospecifically transformed into dihydropyrans and dihydrofurans found in many bioactive natural products and drugs through an annulative ring-opening reaction by using Lewis-acid (BF·OEt) or cesium carbonate (CsCO) catalysis. Highly diastereo- and regioselective ring opening of cyclopropanes was explained through a stereospecific intimate ion pair pathway.

We developed a simple and practically feasible protocol for the chemoselective coupling of optically active functionally rich 2-aroylcyclopropanecarbaldehydes with various CH acids or active methylene compounds under 10 mol % of (s)-proline in the presence of Hantzsch ester as a hydrogen source through a three-component reductive alkylation reaction. The metal-free, organocatalytic selective reductive C–C coupling method has wide advantages/applications like no epimerization, no ring opening, high carbonyl control, and large substrate scope, generating only monoalkylated 2-aroylcyclopropanes, and the resulting chiral products can be synthons in medicinal to material chemistry. We have also shown the synthetic applications of chiral CH-acid-containing 2-aroylcyclopropanes 5 by transforming them into the interesting molecules of pyrimidine analogues 8, dimethyl cyclopropane-malonates 9, functionally rich dihydropyran 10, cyclopropane-alcohols 11, and cyclopropane-olefins 12/13. Many of these chiral products 5–13 can serve as excellent building blocks for the synthesis of value-added small molecules, natural products, pharmaceuticals, and their analogues.

Structurally complex cedrane scaffolds were synthesized in very good yields with high chemo-and diastereoselectivities in a sequential one-pot manner. A combination of intermolecular olefination, intramolecular Michael and Michael reactions or intermolecular olefination, intramolecular Michael and aldol reactions were used as the key steps from the readily available hydroxy-p-quinone butanals and phosphoranes with catalytic amounts of quinine at ambient temperatures for a few hours. This is a unique one-pot combination of coupling and annulation routes for the green synthesis of a library of tricyclic pseudo-terpenoids (cedrane scaffolds) with high selectivity and yields. Organocatalytic ring isomerization was highlighted through transforming one ring into another one by retrocyclization. We have discussed thoroughly mechanistic aspects of these tandem coupling/annulation and ring isomerization reactions based on control experiments and X-ray crystal structure analysis.

The Front Cover shows like the fungi, the organocatalytic multi‐catalytic one‐pot method also stands as a unique kingdom in the field of synthetic organic chemistry by simply making the impossible possible. We sincerely thank Mr. A. Vamshi Krishna, Ms. Revoju Sravanthi and Mr. Raghu Ghanapuram for the excellent cover design. More information can be found in the Research Article by D. B. Ramachary et al.