Ring closing metathesis reactions of α-methylene-β-lactams: application to the synthesis of a simplified phyllostictine analogue with herbicidal activity

Abstract

Michael. (2015) Ring closing metathesis reactions of α-methylene-β-lactams : application to the synthesis of a simplified phyllostictine analogue with herbicidal activity. Organic & Biomolecular Chemistry, Volume 13 (Number 28). pp. 7655-7663. Permanent WRAP url:http://wrap.warwick.ac.uk/70250 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-forprofit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. Ring closing metathesis (RCM) reactions of -methylene--lactams are used to construct strained 11-and 12-membered macrocycles that mimic key structural elements of phyllostictine A. The highest yield and stereoselectivity was achieved making 12-membered macrocycle Z-19 with use of a p-methoxyphenyl group on the lactam nitrogen. Interestingly, substrate concentration had an important influence on the stereochemical course of the reaction. A simplified analogue produced using this approach displays phytotoxic activity against Chlamydomonas reinhardtii suggesting that the -methylene--lactam subunit is responsible, at least in part, for the herbicidal activity of phyllostictine A .

A new direct synthesis of α-methylene- and α-alkylidene-β-lactams

“…7 Propiolamides were also useful starting materials affording various -methylene--lactams through PPh 3 -catalyzed cyclizations. 8 Finally, the cross-metathesis of -methylene--lactams, 9 as well as the ring closing metathesis reactions, 3 were also used successfully to prepare the corresponding -alkylidene derivatives. Thus, the synthesis of this class of molecules generally involves multistep sequences with costly and/or sensitive reagents, therefore it appeared interesting to develop a new, and more direct, approach.…”

One-pot conversion of carbamates of unsaturated β-aminoesters into unsaturated β-lactams by use of trimethylsilyl iodide

“…1 The activity of famous antibiotics such as penicillins, cephalosporins and carbapenems are attributed to the presence of the 2-azetidinone ring in these compounds. 2 Apart from clinical use, β-lactams can also serve as good synthons in the synthesis of many biologically active heterocycles. Several approaches have been developed for the synthesis of β-lactams including cyclization of β-aminoesters to α-methylene-β-lactams [3][4][5][6] , Grignard reaction on azetidin-2,3-diones followed by dehydration using PPh 3 /CCl 4 reagent 7 , rhodium catalyzed olefin cross metathesis 8 , thermal β-elimination of trans-3-allyl-3-sulfinyl-β-lactams 9 , copper-catalyzed carbonylative coupling of cycloalkanes and amides 10 , synthesis of optically active α-methylene β-lactams through lipase-catalyzed kinetic resolution 11 , synthesis of optically active spiro-β-lactams by cycloadditions to α-alkylidene-β-lactams 12 and other miscellaneous approaches such as ring contraction and radical processes 1 .…”

Asymmetric Synthesis of α-Alkylidene-β-Lactams through Copper Catalysis with a Prolinol-Phosphine Chiral Ligand

“…In this context, chiral α-alkylidene-β-lactams are attractive linchpin compounds since the C–C double bond serves as a platform for numerous transformations such as olefin metathesis, hydrogenation, Michael addition, etc. In addition, chiral α-alkylidene-β-lactams exhibit various biologic activities on their own . Although several synthetic methods have been developed for chiral α-alkylidene-β-lactams, − most of them require multistep sequences or the use of stoichiometric amounts of chiral reagents.…”