Stable Bicyclic Functionalized Nitroxides: The Synthesis of Derivatives of Aza-nortropinone–5-Methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octene 8-oxyls

Larisa N Grigor’Eva,Dmitrii G Mazhukin,Konstantin A Lomanovich,Alexsei Ya Tikhonov

doi:10.3390/molecules26103050

Abstract

In recent decades, bicyclic nitroxyl radicals have caught chemists’ attention as selective catalysts for the oxidation of alcohols and amines and as additives and mediators in directed C-H oxidative transformations. In this regard, the design and development of synthetic approaches to new functional bicyclic nitroxides is a relevant and important issue. It has been reported that imidazo[1,2-b]isoxazoles formed during the condensation of acetylacetone with 2-hydroxyaminooximes having a secondary hydroxyamino group are recyclized under mild basic catalyzed conditions to 8-hydroxy-5-methyl-3-oxo-6,8-diazabicyclo[3.2.1]-6-octenes. The latter, containing a sterically hindered cyclic N-hydroxy group, upon oxidation with lead dioxide in acetone, virtually quantitatively form stable nitroxyl bicyclic radicals of a new class, which are derivatives of both 2,2,6,6-tetramethyl-4-oxopiperidine-1-oxyl (TEMPON) and 3-imidazolines.

Highlights

Among various types of organic radicals, nitroxyl radicals (NRs) are the most stable, most robust, and best-studied class of paramagnetic species
NRs can participate in UV—or visible-light—excited photosynthesis owing to their ability to participate in light-induced hydrogen atom transfer processes [17,18,19]
We found that bicycle 5, encumbered with a sterically hindered N-OH group, can be oxidized by lead dioxide to form a stable NR (6a, 6c, or 6d) as the only reaction product

Summary

Introduction

Among various types of organic radicals, nitroxyl radicals (NRs) are the most stable, most robust, and best-studied class of paramagnetic species. Due to the asymmetry of all carbon atoms in 6c, the hfc constants for all the different types of hydrogen atoms differ from each other and are in the range from 0.095 to 0.217 mT for methylene protons in the carbonyl and decrease from 0.054 mT for protons of the CH2 group on the six-membered ring closest to the radical center down to ~0.001 mT for the most distant protons of the aliphatic ring (Supplementary Materials, Figure S14). Due to the asymmetry of all carbon atoms in 6c, the hfc constants for all the different types of hydrogen atoms differ from each other and are in the range from 0.095 to 0.217 mT5 offo1r1 methylene protons in the carbonyl and decrease from 0.054 mT for protons of the CH2 group on the six-membered ring closest to the radical center down to ~0.001 mT for the most distant protons of the aliphatic ring (Supplementary Materials, Figure S14). AAccccoording ttoooouurroobbseservrvataitoionns sanadndsimsimilairladradtaaitna tihnetlhiteerlaitteurraet,unroew, nwowe cawnepcraonpopsreoapmoescehanmisemchoafnbiassme-coaftablyaszee-dcaretaclyyczliezdatrioecnyocfliizmatidioanzooisfoixmaizdoalezso2is.oTxhaezomleesch2a.nTishme cmonecshisatsnoifstmhectornansissftosrmofatihoen torfa2nsinfotromaantionnteromf e2diantteo(2aHn -imntiedrmazeodleiaNte-o(x2iHd-eim2Hid-aImzo;lSechNe-moxeid1e), 2wHh-oImse; sSucbhseemqeue1n),t winhtorasme soulebcsuelqaureinntteinratrcatimonolewciutlharthineternaocltaioten awnitohntgheneenroaltaetde iannitohne greancetriaotnedcainnotchceurrebaoctthioant tchaencaorcbcounr abtootmh oaft tthheenciatrobnoengartooump aonf dthaet tnhietrcoanrebognroautopmaonfdthaet tihmeincaorgbroonuapt,otmhuosflethadeiinmgineiothgerrotuopt,htehpursoldeaudctinogf keintheetirctcootnhteroplr(obdicuycctliocfhkyidnerotixcycloamntirnoel (5biincytchleicfhorymdreorxcyalsaem) oinreto5tihnetpherofdourmcteorfctahseer)moordtoynthame picrocodnutcrtool f(4t-hpeyrrmidoodnyen-2a-mkeictocxoinmtreo3l (i4n-pthyerildaottneer-c2a-ksee)t.oxInimdeee3d,ininththeelactotnertrcoalseex).pIenrdimeeedn,t,inwthheencwonetrinoltreoxdpuecreimd eanctr, ywsthaelnlizwede isnatmropdluecoedf baiccryycsletal5ldizeindtsoamthpelereoafcbtiiocnyc, lwe 5itdhinshtoortht ehreeaaticntigon(6, 0w–i6th5 ◦sCho)rot fhethaitsinagq(u6e0o–u65s °sCol)uotifotnhiins 0a.q2u5NeouNsaOsoHlu, t5idonviirntu0a.l2ly5NquNanatOitHat,iv5edlyvtiurrtuneadllyinqtouaanstiintagtlievperlyodtuucrtn,epdyriindtoonae s3idn,gwlehpicrhodwuacst,ispoylraitdeodnaen3ddc,hwarhaicchterwizaesdisboylaNteMdRanspdecchtraorsaccotepryi.zed by NMR spectroscop3y. .Materials and Methods

General Information

Findings

Conclusions