Stereodivergent Synthesis of Spiroaminals via Chiral Bifunctional Hydrogen Bonding Organocatalysis.

Spiroaminals represent novel structural motifs prevalent in diverse natural products and biologically active molecules. Achieving their enantioselective synthesis is a highly desirable and challenging task in synthetic endeavors due to their intricate molecular frameworks. Herein, we accomplished the first stereodivergent construction of spiroaminals using chiral bifunctional organocatalyzed intramolecular 1,2-addition followed by an oxa-Michael addition cascade in a high atom and step economical pathway. A proper modulation of the cinchona-derived squaramide catalysts efficiently provided access to all the possible stereoisomers with high yield, diastereoselectivity, and excellent enantioselectivity while displaying a broad substrate tolerance. Additionally, we validated the scalability of the reaction and demonstrated the synthesis of variable spiroaminal scaffolds, confirming the viability of our protocol.

An Intramolecular Umpolung Cascade Kukhtin-Ramirez Reaction/Michael Addition-Initiated Cyclization: Stereoselective Synthesis of Tetrasubstituted Cyclopropane Fused 1-Indanones.

Herein, we disclose a fascinating highly stereoselective P(NMe2)3 mediated intramolecular deoxygenative umpolung cascade Michael addition-initiated cyclopropanation with a diverse substrate adaptability. This methodology creates a new horizon for expedient access to valuable 6,5,3-fused scaffolds having an all-carbon quaternary stereocenter via Kukhtin-Ramirez (K-R) adduct formation, with excellent diastereoselectivity and yields under metal-free ambient conditions. A few functional group transformations have also been performed successfully. Additionally, an asymmetric catalytic attempt using (R)-(+)-H8-BINOL has delivered good enantioselectivity.

Umpolung Chemo- and Regioselective Cascade Addition of Diethylzinc to α-Diketones Followed by Intramolecular Michael Reaction: Stereoselective Synthesis of Highly Substituted 1- Indanones.

Herein we report an efficient stereoselective umpolung 1,2-addition of Et2Zn onto α-diketones followed by intramolecular cascade Michael cyclization. This strategy effectively delivers a broad range of substituted 1-indanones in excellent yields in a chemo- and regioselective fashion. Additionally, we performed a variety of synthetic transformations on the 1-indanone products. Furthermore, a hitherto-unexplored asymmetric variant of this methodology that provides up to 94:6 er using an easily accessible cinchona alkaloid ligand has been addressed.

Primary Aminothiourea-Catalyzed Enantioselective Synthesis of Rauhut-Currier Adducts of 3-Arylcyclohexenone with a Tethered Enone on the Aryl Moiety at the Ortho-Position.

An enantioselective synthesis of Rauhut-Currier (RC) adducts from 3-aryl cyclohexenone with a tethered enone moiety at the ortho-position on the aryl group is accomplished. This method provides a wide range of valuable synthetic building blocks having a unique [6-5-6] all-carbon-fused tricyclic skeleton. A primary amine-containing thiourea, a bifunctional organocatalyst, was found to be an efficient catalyst for this transformation. The primary amine counterpart of the catalyst possibly activates the aliphatic enone via dienamine formation (HOMO activation), whereas the thiourea counterpart activates the tethered enone (LUMO activation). Considering the difficulty in achieving an RC reaction of ß,ß-disubstituted (alkyl and aryl) enones, this method would be significantly rewarding.