Stereoselective Synthesis of Hydrindane and Hydroazulene Derivatives by Transannular Cyclization of Nine- and Ten-Membered Carbocycles
- 14 September 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 86 (19), 13684-13692
- https://doi.org/10.1021/acs.joc.1c01751
Abstract
Treatment of cis-fused bicyclic diene dicarboxylates with Li/naphthalene triggers a tandem ring-opening and transannular cyclization process that stereoselectively yields hydroazulenes and hydrindanes derivatives. Cyclononadienyl diesters, which can be isolated after the ring-opening step by judicious choice of the reaction conditions, undergo a tandem conjugate addition/intramolecular Michael addition upon treatment with chiral lithium amides to give bicyclic beta-amino esters in a process where 4 contiguous stereocenters are formed with high diastereocontrol. A concise route toward the highly enantioenriched AEF ring core of the aconitine-type alkaloids has been developed as an application of this methodology. The starting cis-fused bicyclic dicarboxylates are easily prepared in one step by reductive alkylation of diisopropyl phthalate (Na/THF, followed by the appropriate bis-electrophiles).Keywords
Funding Information
- European Regional Development Fund
- Ministerio de Economàa y Competitividad (CTQ2017-84354-P)
- Xunta de Galicia (ED431C 2018/16, ED431G2019/03)
This publication has 28 references indexed in Scilit:
- Studies on transannulation reactions across a nine-membered ring: the synthesis of natural product-like structuresOrganic & Biomolecular Chemistry, 2011
- Recent applications of intramolecular Diels–Alder reactions to natural product synthesisChemical Society Reviews, 2009
- A Tandem Conjugate Addition/Cyclization Protocol for the Asymmetric Synthesis of 2-Aryl-4-aminotetrahydroquinoline-3-carboxylic Acid DerivativesOrganic Letters, 2009
- Transannulation Reactions in the Synthesis of Natural ProductsSynthesis, 2009
- Dearomatization−Bis-alkylation of Aromatic and Heteroaromatic Diesters Promoted by Me3SnLi via a Stanna−Brook RearrangementOrganic Letters, 2006
- The conjugate addition of enantiomerically pure lithium amides as homochiral ammonia equivalents: scope, limitations and synthetic applicationsTetrahedron: Asymmetry, 2005
- Diverse Methods for Medium Ring SynthesisAccounts of Chemical Research, 1998
- Free radical-mediated macrocyclisations and transannular cyclisations in synthesisContemporary Organic Synthesis, 1997
- Stereoselective α-alkylation of α,β-unsaturated esters utilizing conjugate addition of nitrogen nucleophiles (R2NLi)Journal of the Chemical Society, Chemical Communications, 1987
- Proton couplings in cyclohexaneJournal of the American Chemical Society, 1968