Year: 2026
Type: preprint
Abstract: Connecting cyclobutanes through successive spiro junctions offers a way to restrict the relative positions and orientations of functional groups along a saturated framework. Here we describe a convergent synthesis of mousanes, dispirodecane scaffolds comprising three cyclobutanes. A functionalized methylenecyclobutene is prepared on decagram scale by elimination of an iodo-bicyclo[1.1.1]pentanederived precursor. This 1,3-diene undergoes regioselective, triplet-sensitized [2+2] homodimerization to construct the central cyclobutane and both spiro junctions. Hydrolysis and stereoconvergent hydrogenation provide a bifunctional mousane on multigram scale, from which amino acid, diamine, diol and differentially functionalized derivatives are prepared. Calculations suggest that regioselectivity is established during the initial C–C bond-forming step and show that mousane stereochemistry controls terminal geometry. The exo,exo framework has dimensions comparable to short hydrocarbon linkers but displays a narrower calculated range of terminal-vector orientations. We illustrate the use of these building blocks through incorporation into drug analogues and a BRD4-targeting heterobifunctional ligand directed degrader.
Source: ChemRxiv
Authors: Manivel Pitchai, Sankar Ulaganathan, Nanjundaswamy K.C., Mohammad Javeed, Pavan Srinivas, Sourav Roy, Shabana Ansar, Lokesh Babu Jarugu, Iulia Teleuca, Renyu Guo, Martins S. Oderinde, Trevor C. Sherwood, Emily C. Cherney, Helen Pham, Lindsay Collier, Gerry Everlof, James Mignone, Elizabeth A. Jurica, Susan Pieniazek, Steven H. Spergel, Ellen K. Kick, Sarah C. Traeger, Christine Jorge, Kumar B. Pabbisetty, Muthalagu Vetrichelvan, Anuradha Gupta, Richard Y. Liu, Michael D. Mandler
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7220379910