TY - JOUR
T1 - Enantio- and Z-selective synthesis of functionalized alkenes bearing tertiary allylic stereogenic center
AU - Ge, Luo
AU - Sinnema, Esther G.
AU - Pérez, Juana M.
AU - Postolache, Roxana
AU - Reis, Marta Castiñeira
AU - Harutyunyan, Syuzanna R.
N1 - Funding Information:
Acknowledgments Funding: Financialsupport from the European Research Council (grantno.773264, LA COPAROM),TheNetherlandsOrganizationforScientificResearch(NWO-VICI),andtheChina ScholarshipCouncil(CSC,toL.G.)isacknowledged.Authorcontributions:L.G.designedthe project.L.G.andE.G.S.developedallthemethodologiesandcarriedoutalltheexperiments describedinthemanuscript.J.M.P ., R.P ., andM.C.R.wereinvolv ed intheinitialoptimizationsof Mn-catalyzedhydrophosphinationofalkenes.L.G.andE.G.S.preparedthemanuscript.Allthe authorscommentedonthemanuscript.S.R.H.conceivedtheidea,acquiredthefunding,and directedtheresearch.Competinginterests:Theauthorsdeclarethattheyhav enocompeting interests.Dataandmaterialsavailability:Alldataneededtoevaluatetheconclusionsinthe paperarepresentinthepaperand/ortheSupplementaryMaterials.Crys tallogr aphicdatafor one of the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre, under deposition no. CCDC 2085291 (1i).
Publisher Copyright:
Copyright © 2023 The Authors, some rights reserved;
PY - 2023/1
Y1 - 2023/1
N2 - Olefins are ubiquitous in biologically active molecules and frequently used as building blocks in chemical transformations. However, although many strategies exist for the synthesis of stereodefined E-olefines, their thermodynamically less stable Z counterparts are substantially more demanding, while access to those bearing an allylic stereocenter with an adjacent reactive functionality remains unsolved altogether. Even the classic Wittig reaction, arguably the most versatile and widely used approach to construct Z-alkenes, falls short for the synthesis of these particularly challenging yet highly useful structural motives. Here, we report a general methodology for Z-selective synthesis of functionalized chiral alkenes that establishes readily available alkene-derived phosphines as an alternative to alkylating reagents in Wittig olefination, thus offering previously unidentified retrosynthetic disconnections for the formation of functionalized disubstituted alkenes. We demonstrate the potential of this method by structural diversification of several bioactive molecules.
AB - Olefins are ubiquitous in biologically active molecules and frequently used as building blocks in chemical transformations. However, although many strategies exist for the synthesis of stereodefined E-olefines, their thermodynamically less stable Z counterparts are substantially more demanding, while access to those bearing an allylic stereocenter with an adjacent reactive functionality remains unsolved altogether. Even the classic Wittig reaction, arguably the most versatile and widely used approach to construct Z-alkenes, falls short for the synthesis of these particularly challenging yet highly useful structural motives. Here, we report a general methodology for Z-selective synthesis of functionalized chiral alkenes that establishes readily available alkene-derived phosphines as an alternative to alkylating reagents in Wittig olefination, thus offering previously unidentified retrosynthetic disconnections for the formation of functionalized disubstituted alkenes. We demonstrate the potential of this method by structural diversification of several bioactive molecules.
UR - http://www.scopus.com/inward/record.url?scp=85146364173&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adf8742
DO - 10.1126/sciadv.adf8742
M3 - Article
C2 - 36638168
AN - SCOPUS:85146364173
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 2
M1 - eadf8742
ER -