Diastereoselective Synthesis of β-Lactams by Ligand-Controlled Stereodivergent Intramolecular Tsuji-Trost Allylation.

J Org Chem

Department of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands.

Published: August 2020

The diastereoselective synthesis of highly substituted β-lactams by intramolecular Tsuji-Trost allylation is reported. Judicious selection of the ligand on palladium allows selective access to either the isomer (in generally good to excellent yield with very high diastereomeric excess) or isomer (with yields and diastereoselectivity ranging from modest to excellent depending on the substrate). The reaction proceeds under exceedingly mild conditions (rt, no additives) with a broad range of substrates, which are readily accessible by the Ugi reaction.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418107PMC
http://dx.doi.org/10.1021/acs.joc.0c00575DOI Listing

Publication Analysis

Top Keywords

diastereoselective synthesis
8
intramolecular tsuji-trost
8
tsuji-trost allylation
8
synthesis β-lactams
4
β-lactams ligand-controlled
4
ligand-controlled stereodivergent
4
stereodivergent intramolecular
4
allylation diastereoselective
4
synthesis highly
4
highly substituted
4

Similar Publications

The endoperoxide scaffold is found in numerous natural products and synthetic substances of pharmaceutical interest. The main challenge to their synthetic access remains the preparation of chiral compounds due to the weakness of the peroxide bond, which limits the scope of available or applicable methods. Here, we demonstrate how peroxycarbenium species can be trapped by silylated nucleophiles with high enantioselectivities and diastereoselectivities when applicable, using a chiral imidophosphorimidate (IDPi) as a catalyst.

View Article and Find Full Text PDF

An unusual chiral-at-metal mechanism for BINOL-metal asymmetric catalysis.

Nat Commun

January 2025

State Key Laboratory of Coordination Chemistry, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, China.

Chiral binaphthols (BINOL)-metal combinations serve as powerful catalysts in asymmetric synthesis. Their chiral induction mode, however, typically relies on multifarious non-covalent interactions between the substrate and the BINOL ligand. In this work, we demonstrate that the chiral-at-metal stereoinduction mode could serve as an alternative mechanism for BINOL-metal catalysis, based on mechanistic studies of BINOL-aluminum-catalyzed asymmetric hydroboration of heteroaryl ketones.

View Article and Find Full Text PDF

Synthesis of Enantiopure - and -Fused Octahydroisoindole-1-Phosphonic Acids from Octahydroisoindolones.

J Org Chem

January 2025

Centro de Investigaciones Químicas-IICBA, Universidad Autónoma del Estado de Morelos. Av. Universidad 1001, 62209 Cuernavaca, Morelos, Mexico.

Phosphonic analogs of octahydroisoindole-1-carboxylic acids are bicyclic proline derivatives of interest in drug design and enzymatic mechanism studies. Here we report the stereoselective synthesis of the - and -fused octahydroisoindole system using oxazoloisoindolone lactam and 1,2-cyclohexanedicarboxylic anhydride as advanced chiral precursors, respectively, yielding enantiopure octahydroisoindolone intermediates with the desired stereochemistry at the ring junction. Finally, using these intermediates, the target (1,3a,7a)- and (1,3a,7a)-octahydroisoindole-1-phosphonic acids and their enantiomers were obtained with complete stereocontrol via highly diastereoselective addition of trimethyl phosphite to chiral -acyliminium ions as the key step.

View Article and Find Full Text PDF

Secondary Alkylation of Arenes via the Borono-Catellani Strategy.

J Am Chem Soc

January 2025

Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, and TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan 430072, China.

A modular platform technology for the synthesis of α-aryl carbonyl derivatives via Borono-Catellani-type secondary alkylation of arenes is presented. This practical method features a broad substrate scope regarding aryl boronic acid catechol esters, secondary alkyl bromides, and diversified terminating reagents (e.g.

View Article and Find Full Text PDF

Domino Knoevenagel-cyclization reactions of styrene substrates, containing an -(-formyl)aryl subunit, were carried out with -substituted 2-cyanoacetamides to prepare tetrahydro-4-pyrano[3,4-]quinolone and hexahydrobenzo[]phenanthridine derivatives by competing IMHDA and IMSDA cyclization, respectively. The diastereoselective IMHDA step with α,β-unsaturated amide, thioamide, ester and ketone subunits as a heterodiene produced condensed chiral tetrahydropyran or thiopyran derivatives, which in the case of Meldrum's acid were reacted further with amine nucleophiles in a multistep domino sequence. In order to simplify the benzene-condensed tricyclic core of the targets and get access to hexahydro-1-pyrano[3,4-]pyridine derivatives, a truncated substrate was reacted with cyclic and acyclic active methylene reagents in diastereoselective Knoevenagel-IMHDA reactions to prepare novel condensed heterocyclic scaffolds.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!