Iron-Catalyzed Cross-Coupling of Bis-(aryl)manganese Nucleophiles with Alkenyl Halides: Optimization and Mechanistic Investigations Lidie Rousseau, Alexandre Desaintjean, Paul Knochel, Guillaume Lefèvre

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Lidie Rousseau, Alexandre Desaintjean, Paul Knochel, Guillaume Lefèvre. Iron-Catalyzed Cross- Coupling of Bis-(aryl)manganese Nucleophiles with Alkenyl Halides: Optimization and Mechanistic Investigations. Molecules, MDPI, 2020, 25 (3), pp.723. ￿10.3390/molecules25030723￿. ￿cea-02476144￿

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Article Iron-Catalyzed Cross-Coupling of Bis-(aryl)manganese Nucleophiles with Alkenyl Halides: Optimization and Mechanistic Investigations

Lidie Rousseau 1,2, Alexandre Desaintjean 3, Paul Knochel 3 and Guillaume Lefèvre 1,*

1 Chimie ParisTech, PSL University, CNRS, Institute of Chemistry for Life and Health Sciences (i-CLeHS FRE2027), CSB2D, 75005 Paris, France; [email protected] 2 NIMBE, CEA, CNRS, Univ. Paris-Saclay, 91191 Gif-sur-Yvette, France 3 Department of Chemistry, Ludwig-Maximilians-Universitat München, Butenandstr. 5-13, Haus F, 81377 Munich, Germany; [email protected] (A.D.); [email protected] (P.K.) * Correspondence: [email protected]; Tel.: +33-1-85-78-41-70



Received: 15 January 2020; Accepted: 6 February 2020; Published: 7 February 2020


Abstract: Various substituted bis-(aryl)manganese species were prepared from aryl bromides by one-pot insertion of magnesium turnings in the presence of LiCl and in situ trans-metalation with MnCl in THF at 5 C within 2 h. These bis-(aryl)manganese reagents undergo smooth iron-catalyzed 2 − ◦ cross-couplings using 10 mol% Fe(acac)3 with various functionalized alkenyl iodides and bromides in 1 h at 25 ◦C. The aryl-alkenyl cross-coupling reaction mechanism was thoroughly investigated through paramagnetic 1H-NMR, which identified the key role of tris-coordinated ate-iron(II) species in the catalytic process.

Keywords: iron catalysis; cross-coupling; bis-(aryl)manganese; alkenyl halides; ate iron(II) complex

1. Introduction Transition-metal catalyzed cross-couplings are widely used in the development and production of pharmaceutical compounds [1]. The most versatile of them are palladium-catalyzed and nickel-catalyzed cross-couplings [2–5] as they tolerate a great variety of functionalities on both coupling partners. Yet, these metals have drawbacks such as toxicity [6,7] and high prices in the case of palladium [8]. That is one of the reasons why copper [9], iron [10–13], or cobalt [14] have been developed as alternative metal-catalysts. Organomanganese species pioneered by Cahiez [15] often considerably reduce the amount of side reactions such as homo-coupling [16,17] and have proven to be excellent nucleophiles in various types of reactions [18–24] including cross-couplings [25,26]. Organomanganese species then constitute an interesting alternative to usual cross-coupling partners such as organomagnesium [27], organozinc [28], and organo-boronic esters, which may have genotoxic properties [29,30]. Recently, we have developed a two-step preparation of functionalized bis-(aryl)manganese reagents by oxidative insertion of magnesium into the C-Br bond of aryl bromides, which is followed by a trans-metalation with MnCl 2LiCl [31]. Herein, we wish to report an effective one-pot preparation 2· of those functionalized bis-(aryl)manganese reagents (Ar Mn 2MgX 4LiCl, denoted as Ar Mn (1), 2 • 2• 2 Scheme1) starting from aryl bromides, which are followed by an iron-catalyzed cross-coupling of 1 with alkenyl iodides and bromides, and provide a range of polyfunctionalized alkenes (4, Scheme1). These bis-(aryl)manganese reagents are generally stable at RT (25 ◦C) for several hours, which makes them suitable reagents for mild cross-coupling reactions [32].

Molecules 2020, 25, 723; doi:10.3390/molecules25030723 www.mdpi.com/journal/molecules Molecules 2020, 25, 723 22 of of 12 Molecules 2020, 25, 723 2 of 12

Scheme 1. One-pot preparation of bis-(aryl)manganese reagents by in situ trans-metalation followed byScheme iron-catalyzed 1. One-pot cross-couplings preparation of with bis-(aryl)manganese alkenyl iodides andreagents bromides. by in situ trans-metalation followed by iron-catalyzed cross-couplings withwith alkenylalkenyl iodidesiodides andand bromides.bromides. 2. Results 2. Results In preliminary experiments, the bis-(aryl)manganese reagent 1a was conveniently prepared by treatingIn preliminary 4-bromoanisole experiments, (2a, 1.0 equiv.) the bis-(aryl)manganese in THF at −5 °C reagent with magnesium 1a was conveniently turnings and prepared LiCl (2.4 by treating 4-bromoanisole (2a, 1.0 equiv.) in THF at 5 C with magnesium turnings and LiCl (2.4 equiv.) equiv.)treating in 4-bromoanisole the presence of (MnCl2a, 1.02 (0.6 equiv.) equiv.) in withinTHF− at 1 ◦ −h.5 Titration°C with [31]magnesium with iodine turnings led to anda yield LiCl for (2.4 1a ofinequiv.) the87%. presence in Cross-coupling the presence of MnCl of2 (0.6MnClmethodologies equiv.)2 (0.6 equiv.) within involving 1within h. Titration 1 thoseh. Titration [31 bis] with-(aryl)manganese [31] iodine with lediodine to a speciesled yield to fora yieldwere1a of forthen 87%. 1a investigatedCross-couplingof 87%. Cross-coupling (see methodologies Supporting methodologies Information involving fileinvolving those forbis details).-(aryl)manganese those bis-(aryl)manganese species were species then investigated were then (seeinvestigated SupportingIn the absence (see Information Supporting of any iron fileInformation catalyst, for details). the file cross-coupling for details). of 1a with (Z)-ethyl 3-iodoacrylate (3a; 25 °C, 1 Inh) thetheproduced absenceabsence a of ofZ/ any Eany = iron50:50 iron catalyst, catalyst,mixture the ofthe cross-couplingthe cross-coupling desired cross-coupling of of1a 1awith with (Z )-ethyl(productZ)-ethyl 3-iodoacrylate 4a 3-iodoacrylate in 60% yield (3a ;(Table(3a 25;◦ 25C, 11,°C, h)entry 1 produced h) 1).produced Although a Z /aE Z =the/E50:50 = cross-coupling 50:50 mixture mixture of theofperformed the desired desired with cross-coupling cross-coupling FeBr2 gave producta moderateproduct4a 4ain yield in 60% 60% of yield 42%, yield (Table the (Table use1, ofentry1, entryFeCl 1).3 ,1). AlthoughFeBr Although3, or FeCl the the cross-coupling2 affordedcross-coupling the E performed performedisomer of with4a with in FeBr 54–64%FeBr2 2gave gave yielda a moderatemoderate (entries 2–5). yieldyield Using ofof 42%,42%, Fe(acac) the use2 provedof FeCl 3to,, FeBr be more3,, or or FeCl FeCleffective22 affordedaff ordedsince thethe yieldE isomer increas of ed4a4a intoin 54–64%67%54–64% (entry yieldyield 6). (entries(entriesOur best 2–5).2–5). result UsingUsing was Fe(acac)obtainedFe(acac)22 withproved Fe(acac) to be 3 moremore (>99% eeffectiveff purity)ective sincesinceas a catalyst, thethe yieldyield producing increasedincreased the toto 67%67%E isomer (entry(entry of 6). 6).4a Ourin a 79% best resultyield (entry was obtained 7). with Fe(acac)33 (>99%(>99% purity) purity) as as a a catalyst, catalyst, producing producing the the EE isomerisomer of of 4a inin a a 79% 79% yield yield (entry (entry 7). 7). Table 1. Catalyst screening of the reaction between the bis-(aryl)manganese reagent 1a and (Z)-ethyl 3-iodoacrylateTable 1.1. CatalystCatalyst (3a screening). of the reactionreaction betweenbetween the bisbis-(aryl)manganese-(aryl)manganese reagent 1a and (Z)-ethyl 3-iodoacrylate (3a).

Entry Catalyst (10 mol%) Yield (%) a Entry Catalyst (10 mol%) Yield (%) a b Entry1 1Catalystnone (10 mol%) none 60 Yield 60 (%)b a 2 FeBr 42 21 FeBrnone2 2 6042 b 3 FeCl3 54 32 FeClFeBr32 5442 4 FeBr3 57 43 FeBrFeCl3 5754 5 FeCl2 64 2 54 6FeClFeBr3 Fe(acac) 2 67 6457 65 7 Fe(acac)Fe(acac)FeCl2 32 (>99% purity) 79 6764 76 Fe(acac)Fe(acac)3 (>99%2 purity) 7967 a b Z E 4a a Yield of analytically pure product. b A / = 50:50 mixture of was obtained. 7 Yield of analytically pureFe(acac) product.3 (>99% Apurity) Z/E = 50:50 mixture of 4a was obtained. 79 a Yield of analytically pure product. b A Z/E = 50:50 mixture of 4a was obtained. Furthermore, the cross-coupling of 1a with (2-bromovinyl)trimethylsilane ((3b3b;; ZZ//EE == 10:90) gave the olefin olefinFurthermore, 4b in 98% the yield cross-coupling with complete of 1aE-selectivity with (2-bromovinyl)trimethylsilane (Z/E = 1:99)1:99) whereas whereas the yi yield (3beld; Zwithout /E = 10:90) iron gave salt wasthe olefin 24% ( Z4b/E in = 98%20:80,20:80, yield Table Table with 22,, entryentry complete 1).1). WhenWhen E-selectivity thethe electron-richelectron-rich (Z/E = 1:99) bisbis -(3,4-dimethoxyphenyl)manganese-(3,4-dimethoxyphenyl)manganesewhereas the yield without iron salt (was1b) 24%was (mixed mixedZ/E = 20:80,with with 3aTable3a,, the the 2, EE -acrylateentry-acrylate 1). When4c4c waswas the generated generated electron-rich in in 69% 69%bis -(3,4-dimethoxyphenyl)manganeseyield yield and and a Z a/ZE/ E= 69:31= 69:31 mixture mixture of productsof(1b products) was mixedwas was obtained with obtained 3a in, the 58% in E -acrylateyield 58% yieldwithout 4c withoutwas an generated iron an catalyst iron in catalyst69% (entry yield 2). (entry andThe tri-substituteda 2). Z/E The = 69:31 tri-substituted mixture bis-(3,4,5- of trimethoxyphenyl)manganesebisproducts-(3,4,5-trimethoxyphenyl)manganese was obtained in 58% (yield1c) underwent without (1c) underwent an smooth iron catalyst cross-coupling smooth (entry cross-coupling 2). with The 3b tri-substituted to with afford3b theto a bisEff-alkeneord-(3,4,5- the 4dEtrimethoxyphenyl)manganese-alkene in 80%4d (8%in 80%were (8%obtained were obtained(without1c) underwent a without catalyst, smooth a entry catalyst, cross-coupling 3). Additionally, entry 3). with Additionally, 1c 3b reacted to afford 1cwith reactedthe 3a E -alkeneand with 2- bromostyrene4d in 80% (8% ( 3cwere; Z/E obtained = 18:82) to without give the a acrylate catalyst, 4e entry and 4f3). ( ZAdditionally,/E = 1:99) in 57% 1c reactedand 82% with yield 3a whereas and 2- bromostyrene (3c; Z/E = 18:82) to give the acrylate 4e and 4f (Z/E = 1:99) in 57% and 82% yield whereas

Molecules 2020, 25, 723 3 of 12 Molecules 2020, 25, 723 3 of 12

66%3a and (Z/ 2-bromostyreneE = 72:28) and 80% (3c (;ZZ//EE == 53:47)18:82) were, to give respectively, the acrylate obtained4e and 4fwithout(Z/E = a 1:99)catalyst in 57%(entries and 4–5). 82% Inyield the whereas last experiment, 66% (Z/E 1c= 72:28)reacted and with 80% (E ()-1-iodoocteneZ/E = 53:47) were, (3d) respectively, to provide the obtained alkene without 4g in 87% a catalyst yield (entries(Z/E = 9:91) 4–5).Molecules Moleculeswhen InMolecules 2020 theMolecules 202077%, 25 last2020, ,25 723 ,2020yield 723, 25 experiment, ,, 72325 , (723Z/ E = 4:96)1c reactedwas obtained with ( Ewithout)-1-iodooctene a catalyst (3d (entry) to provide 6). Furthermore,3 of the3 of12 3 12 alkeneof 3 12of 12 bis 4g- in 87% yieldMoleculesMolecules (MoleculesZ 2020/EMolecules 2020,= 25 2020, ,9:91)25 723 ,2020 ,723 25, , 72325 when, 723 77% yield (Z/E = 4:96) was obtained without a catalyst3 of3 of12 3 12 of (entry 3 12of 12 6). (4-(trifluoromethoxyMolecules66%Molecules66% (Z66%/ E2020 ( Z=/ E2020(,72:28))phenyl)manganese Z25 =/,E 723,72:28) 25= ,and72:28) 723 and 80% and 80% (Z 80%/E ( Z=/ E(53:47)Z =/ E (53:47)1d = were,53:47)) reacted were, respectively,were, respectively, withrespectively, 3aobtained obtainedto obtainedprovide without without without thea catalyst aacrylate catalyst a catalyst (entries (entries 4h (entries3 4–5). of(Z 312 4–5)./of E 12 4–5).= 1:99) Furthermore,66%Molecules (bisZ/ E2020-(4-(trifluoromethoxy)phenyl)manganeseMolecules = 72:28), 25, 723 2020 and , 25 80%, 723 (Z/E = 53:47) were, respectively, obtained (1d) reacted without with a catalyst3a to (entries provide3 4–5).of 12 the 3 acrylate of 12 in 77% yield66%In 66%Inthe (entry (theZ66%In last(/ZE the66%Inlast /= E ( experiment, Z72:28)the7). = last/ experiment,E72:28)(Z =Thelast/ Eexperiment,72:28) and = experiment,and 72:28)reaction 80% and1c 80% 1c reactedand( Z 80% reacted(/1cZE 80% without/ = Ereacted1c( Z 53:47) =with / reactedE53:47)( Zwith =/ E 53:47) (were, withE= Fe(acac) )-1-iodooctene(were,53:47) Ewith)-1-iodooctene (were,respectively,E )-1-iodooctene respectively, (were,E)-1-iodooctene respectively,3 gave respectively, (3d (obtained a3d) obtainedtosimilar )( 3d to provideobtained ( )3dprovide to obtainedwithout) provide to withoutyield theprovide without the alkene a withoutbut thecatalystalkenea catalyst the alkenea 4g catalystmix alkenea4g (entries incatalyst (entriesin 87%4gof 87% (entries4ginthe yield 4–5). 87%(entriesin yield 4–5).two 87% yield4–5). isomers yield4–5). (74%,4h (Z/ EZ/=EIn(66% 1:99)Z= 66%In(/ theZE81:19, /(the=EZIn66%( Zlast9:91)(/= inZ E/ the66%EIn(last9:91)/ Z=E (77%= experiment,/ Z 72:28)the entryE= when last9:91)/ experiment, E(72:28) =whenZ =last9:91)/ E yieldexperiment,72:28) whenand 77% = 7). experiment, and72:28) 77%when 80% yield The1cand(entry 77%80% yield 1c reacted and77%( Z 80% reacted(yield(silicon-containing1c/ZZE (/80% / ZE yield=7).Ereacted 1c( / Z=53:47) E=(with / Zreacted4:96)E(=53:47) TheZwith/ E(4:96)=/ZE =53:47) /( were,withE was=4:96) reaction )-1-iodooctene( were,=53:47) Ewaswith )-1-iodooctene4:96) obtained ( were,respectively,Ewas obtained)-1-iodooctene respectively,( were,Ewas )-1-iodoocteneobtained respectively, withoutbis obtained withoutrespectively,-(aryl)manganese without(3d (obtained 3d)without obtainedto ) ( a Fe(acac)without3d to provide caobtained a( ) 3dprovide talystcato obtained withouta)talyst provide tocawithout a talyst(entry theprovide3ca withoutthe(entrygavetalyst alkeneawithout reagentthe (entrycatalyst alkenea6). catalyst (entry6).the a alkeneFurthermore,a 4g similarcatalyst Furthermore, 6). alkenea4g (entriesincatalyst 6).Furthermore, 1e (entriesin4g87% Furthermore, 87% could(entries4ginyield yield 4–5). 87%(entries in bis yield4–5). 87%bis- yieldalso4–5). but- bis yield4–5). -bis areact- mix (ZIn(/ZE /the=EIn 9:91)= thelast9:91) when lastexperiment, when experiment, 77% 77% yield yield1c reacted (1cZ (/ ZEreacted /=E 4:96)= with 4:96) withwas ( Ewas)-1-iodooctene obtained(E obtained)-1-iodooctene without without (3d ) (a 3dto caa ) provide catalysttotalyst provide (entry (entrythe thealkene 6). 6). alkeneFurthermore, Furthermore, 4g in4g 87% in 87% bisyield bis- yield- withof the 3a two, which(4-(trifluoromethoxyIn isomers (4-(trifluoromethoxythe((4-(trifluoromethoxy Zlast /producesEIn((4-(trifluoromethoxyZ = experiment,/the E9:91) (74%, = last9:91) when experiment, Z)phenyl)manganesewhen4i/)phenyl)manganese E 1c 77%(= Z)phenyl)manganese reacted77%/ 81:19,yieldE)phenyl)manganese =yield1c (1:99) withZreacted entry/ E(Z =/( E(4:96)in1d )-1-iodooctene= (with 7).1d 4:96)) 64%reacted was)( 1d reacted The( Ewas() 1d)-1-iodooctene obtainedreactedyield ) with silicon-containingobtainedreacted with (3d 3a(51%,with without) 3a to with without to provide3a ( 3dprovide Zto3a a)/ Eprovidecato a talystthe =theprovideca the57:43talyst acrylatealkenebis (entrytheacrylate-(aryl)manganese the(entry acrylatewere 4g 4h6).acrylatealkene in4h (Furthermore,6).Z 87% (/obtained 4hZEFurthermore, /4g= E4h ( yieldZ 1:99) =in/ E(1:99)Z 87%=/ E 1:99) =bis without reagentyield1:99) -bis - (4-(trifluoromethoxy((4-(trifluoromethoxyinZ /77%E(4-(trifluoromethoxy(in Z= / 77%E in9:91)yield = 77% 9:91)yield when (entry yield when (entry 77%)phenyl)manganese 7).(entry)phenyl)manganese 77%The 7).yield)phenyl)manganese The7). reactionyield (TheZ reaction/E ( reaction Z= / withoutE4:96) = without(4:96)1d was (without1d) Fe(acac)reacted was) ( obtained1dreacted Fe(acac)) obtainedreacted Fe(acac) 3with gave with without3 gave 3a with a3without 3a gavesimilarto a to provide 3asimilara aprovide cato similar yieldatalyst provideca yieldtalystthe but the(entryyield acrylate but a the(entryacrylate mix but a 6).acrylate mix of a Furthermore,4h6). mixthe 4hof (Furthermore,Z twothe (of/4hZE /the = Etwo (isomers Z 1:99)= /two E1:99) isomers bis= 1:99)isomers- bis- 1e could alsoin(Z /77%E = react 9:91)yield((4-(trifluoromethoxyZ/ Ewhen (entrywith = 9:91) 77% 7).3a when The ,yield which reaction 77% ()phenyl)manganeseZ/ Eyield produces= without 4:96) (Z/ Ewas = Fe(acac) 4:96) obtained4i (was(Z1d3 /gaveE) obtained reactedwithout= a1:99) similar with awithout ca in yieldtalyst 3a 64% to abut (entryprovideca yieldtalysta mix 6). theof(entry Furthermore, (51%, the acrylate two 6).Z Furthermore, isomers/ E4h = bis(Z57:43-/ E = 1:99) bis were- Fe(acac)3, inentry 77% yield8). Some (entry 7).good The reactionyields couldwithout be Fe(acac) achieved3 gave3 ain similar the absence yield but aof mix the of theiron two catalyst isomers (entries 2, (74%,(4-(trifluoromethoxy(4-(trifluoromethoxyin(74%, 77% in(4-(trifluoromethoxy(74%,Z /77%ZE (4-(trifluoromethoxy(74%,inyield /=E 77% Z 81:19,yield=/ E(entry81:19,Z yield=/E (entry 81:19, entry= )phenyl)manganese 7).entry(entry81:19,)phenyl)manganese The 7).entry7).)phenyl)manganese 7). The7). entryreactionThe)phenyl)manganese TheThe7). reaction silicon-containing 7).The reactionsilicon-containing withoutThe silicon-containing without (1dsilicon-containing (without1d) Fe(acac)reacted )( 1dreacted Fe(acac) ()1d reacted bisFe(acac)) with bis -(aryl)manganesereactedgave with-(aryl)manganese 3bis gave 3a with a-(aryl)manganese3 bis 3agave similar towith -(aryl)manganese a to provide3asimilar aprovide to3asimilar yield provideto yield reagent theprovide but reagent theyield acrylate buta reagenttheacrylate mix 1ebut reagentathe acrylate 1e mix couldof a 4hacrylate couldmixthe1e 4hof ( Z 1ecould thetwo also (of/4hZE also could/ the =two E 4h( isomers Zreact1:99) =also / two E(react1:99) isomersZ also=/ E reactisomers1:99) = react1:99) obtained without(74%,(74%, Z /ZE / Fe(acac)E= 81:19,= 81:19, entry 3entry, entry 7). 7). The The 8). silicon-containing Somesilicon-containing good yields bis 3bis-(aryl)manganese-(aryl)manganese3 could be achieved reagent reagent 1e in 1e could the could absence also also react react of the iron 4–8), whichwithin inwith77% could 77% 3a(74%,inwith yield 3a,77% in(74%,withyieldwhich, 77%3awhichZbe (entryyield /,E 3a(entry Zwhich yieldattributed=produces/, E which(entry81:19, produces7).= 7).(entry 81:19, Theproduces The entry7).produces reaction4i The7). entry reaction 4i(to ZThe7). (/reaction 4iZE the7). The/ withoutEreaction=(4i Z without1:99)The= / catalyticE(silicon-containingZ1:99) without/= Esilicon-containing in 1:99)Fe(acac)without= inFe(acac)64%1:99) 64% in Fe(acac)activity yield3 64%inFe(acac) gaveyield gave64% yield(51%, bisa gave (51%,similar ayield-(aryl)manganese3ofbis gavesimilar (51%, -(aryl)manganeseaZthe similar/ZE(51%, ayield / Esimilar= yieldmanganese(II) Z57:43=/ E butZyield57:43 /=butE yield a57:43were= mix buta reagentwere57:43 mix but reagent aofwereobtained mix of theobtainedawere mixthe1e oftwoobtaineditself. could1etwothe of obtained withoutisomers couldthe two withoutisomers also Fortwo withoutisomers also reactwithoutisomersexample, react with(74%,with 3a(74%, 3a, Zwhich/,3 E which Z=/3 E81:19, =produces3 81:19,produces entry entry 4i7). 4i( ZThe 7).(/ZE /The E=silicon-containing 1:99)= silicon-containing1:99) in in64% 64% yield yieldbis -(aryl)manganese (51%,bis (51%,-(aryl)manganese Z /ZE /E= 57:43= 57:43 reagent were reagentwere obtained1e obtained could1e could withoutalso without also react react manganesecatalyst (entriesFe(acac)(74%, Fe(acac)salts withFe(acac)Z/3 2,E(74%,,withFe(acac)proved entry =, 4–8),3a entry81:19, , 3a,Zwhich entry8)./, E , which8). which toentrySomeentry= Some 81:19,8).efficientlyproduces 8).Somegood7).produces could good SomeentryThe yieldsgood 4iyieldssilicon-containing good7). be catalyze(4i Z yields Thecould /attributedE( Zcouldyields =/ Esilicon-containing 1:99) couldbe= bese 1:99)couldachieved veralinachieved be to64%inbis achievedbe the-(aryl)manganese64% achievedcouplings inyield inthe catalytic yield bisthe inabsence(51%,-(aryl)manganese theabsence in(51%, the absenceofZactivity /ofabsence Eorgano Z reagent ofthe=/E the57:43 of=iron 57:43 theironof ofmagnesium 1e reagent catalystwerethe iron the couldcatalyst were iron catalyst manganese(II)obtained 1e (entriesalsocatalystobtained (entriescould react reagents(entries without2, (entriesalso 2,without react2, itself.2,with Fe(acac)withFe(acac)with 3a3, entry,3 ,3a whichentry, which 8). 8). producesSome Some produces good good 4i yields ( 4iZyields/ E( Z =could/ E 1:99)could = 1:99) be in be achieved 64% inachieved 64% yield inyield inthe(51%, the absence(51%, absence Z/E Z =/of E57:43 ofthe= the57:43 iron were iron catalystwere catalystobtained obtained (entries (entries without without2, 2, alkenylFor example, electrophiles4–8),with4–8), manganesewhich3aFe(acac)4–8), which, with4–8),Fe(acac)which which could 3 3awhich,could in entry,produces3 ,which couldentrythebe salts becould8). attributed past Some8).attributedbeproduces proved4i Somebeattributed ( [32]. Zgoodattributed/ E togood = 4ito to theyieldsThe1:99) (the eZto yieldscatalyticffi/ E theto catalyticbis incouldciently= the -benzo[d][1,3]dioxol-5-ylmanganese64%1:99)catalyticcould catalyticbeactivity yieldin activityachieved catalyzebe 64% achievedactivity (51%, ofactivity yield ofthe in the severalZ of the inmanganese(II)/E(51%, theof manganese(II)the absence= the 57:43 manganese(II)absence Z couplings/manganese(II)E wereof= 57:43 the ofitself. the obtaineditself.iron were iron ofitself.For catalyst Foritself. organomagnesium catalystexample,obtained without( For1fexample, For) (entries example,also (entriesexample, without reacted2, 2, 4–8), which could3 be attributed to the catalytic activity of the manganese(II) itself. For example, Fe(acac)Fe(acac)4–8),manganese4–8),Fe(acac)manganese which3Fe(acac)4–8),manganese, entry3 ,which entry saltswhich,could entry8).3 ,salts8). couldentrySomeproved salts Somebecould8). proved 8).attributedSomebe goodproved to good Somebeattributed efficiently to goodyieldsattributed yieldsefficiently togood to efficientlyyields could the to couldyieldscatalyze theto catalytic couldcatalyzebe the be catalyticcouldcatalyzeachieved seachieved catalyticbeveral activityseachievedbeveral seachievedactivity incouplingsveral inactivitythe couplingsof the in absence couplingstheof theabsencein oftheof manganese(II)the absence organo theof manganese(II)ofabsence organo ofthemanganese(II) theorgano magnesiumof iron theironofmagnesium catalystthe itself.magnesiumiron catalyst itself.iron catalyst reagentsForitself. (entriescatalyst reagents(entriesForexample, reagents For (entriesexample, with 2, (entriesexample, 2, with 2,with 2, withreagents 3a and withmanganese 3b alkenyl to saltsyield electrophilesproved the toE -alkenesefficiently in the catalyze4j pastand se [4k32veral]. in Thecouplings 78–84%bis-benzo[d][ of yield organo (entriesmagnesium1,3]dioxol-5-ylmanganese 9–10). reagents The with bulkier bis (1f-) alkenylmanganese4–8),4–8),manganesealkenyl manganesewhich4–8),alkenyl whichelectrophiles4–8),alkenylmanganese electrophiles whichsalts could saltselectrophileswhichcould proved electrophilessalts couldprovedbe salts becould inprovedattributed in toattributedthebe proved tothe efficiently in beattributed pastefficiently to theinpastattributed efficiently tothe [32].past toefficiently[32].the pastcatalyze the Theto [32].catalyze catalytic The thetocatalytic[32]. catalyzebis The the biscatalytic-benzo[d][1,3]dioxol-5-ylmanganesesecatalyze The veralse-benzo[d][1,3]dioxol-5-ylmanganese catalyticbisactivityveral activityse-benzo[d][1,3]dioxol-5-ylmanganesebis couplingsveral -benzo[d][1,3]dioxol-5-ylmanganeseseactivity couplings veral ofactivity couplings ofthe couplingstheof ofmanganese(II) oftheoforganomanganese(II) organo the ofmanganese(II) organo ofmanganese(II)magnesium organomagnesium magnesiumitself. itself. magnesium(1f ( itself.)1freagentsFor also )reagentsForitself. (1falso example, )reagents (Forreacted 1fexample,also reacted)reagentswithFor alsoexample, with reacted example, withreacted with also reacted with 3a and 3b to yield the E-alkenes 4j and 4k in 78–84% yield (entries 9–10). The bulkier mesitylmanganesewithalkenylmanganesemanganesealkenylwith 3aalkenylmanganesewith 3a electrophilesandmanganesewithalkenyl electrophiles and 3asalts1g 3b saltselectrophiles3aand 3breacted toproved electrophilesandsalts provedto3byield salts inyield3bprovedto in tothe yieldprovedtothewith tothe efficientlyin theyieldpast efficiently Etothe inpast -alkenes theE3b efficiently -alkenestothe [32].pastthe Eefficiently[32].to -alkenes past catalyze E The afford[32].catalyze-alkenes 4jThe 4j[32]. andcatalyzebis The and bis4j-benzo[d][1,3]dioxol-5-ylmanganesesecatalyze 4kThe 4l -benzo[d][1,3]dioxol-5-ylmanganeseveralse and4j bis4k veral within and-benzo[d][1,3]dioxol-5-ylmanganesesebis in4kcouplingsveral78–84% se-benzo[d][1,3]dioxol-5-ylmanganese couplings 78–84%4k inverala couplingssmall78–84%in yieldcouplings78–84% ofyield of organo20% yield(entriesorgano of (entriesyield organoofyield magnesium(entries organo magnesium 9–10).(entries 9–10).magnesium (91% magnesium9–10). (The1f ( 9–10).The)1freagents afteralso )reagentsbulkier (The 1falsobulkier )reagents( reactedThe1f also 18bulkier reacted )reagentswith alsobis bulkier withh, reactedbis- entrywith-reacted bis with -bis -11). Thisbis-mesitylmanganese methodwithmesitylmanganesealkenylalkenylwithmesitylmanganese also 3awithalkenylmesitylmanganese 3a electrophilesandalkenylwithmesitylmanganese proved electrophilesand3a 3belectrophiles3aand 3b1g toelectrophilesand to3b 1greactedyieldto 1g inyield3breacted totolerate inreacted the1gyieldtothe the in the 1greactedyieldpast with E with theinpast reacted-alkenesthe Ewith nitriles,-alkenesthe [32].pastthe 3bE[32].with -alkenes past3b Eto withTheto [32].-alkenes 4j toTheafford3b a4j[32]. andsinceafford ff bis3b toThe andordbis4j-benzo[d][1,3]dioxol-5-ylmanganese afford toThe4k 4l -benzo[d][1,3]dioxol-5-ylmanganese and 4j bis 4kafford4l4-(2-bromovinyl)benzonitrile with in and-benzo[d][1,3]dioxol-5-ylmanganese bis with inwith4k4l78–84%-benzo[d][1,3]dioxol-5-ylmanganese a 78–84%with4k4l in smalla withsmall a78–84%in a small yield 78–84%small20% ayield 20%small yield(entries 20% yield(entriesyield 20% (91%yield(entries yield (91% 9–10).yield(entries 9–10). after(91% after(91% 9–10). (91%(The1f 18 (after9–10).The)1f 18 3e alsoh, )bulkierafter after( The 1falsoh, entrybulkier18( Z) ( entryThereacted1f also/h,18 bulkierEreacted) 18 entry 11).alsobish,=bulkier reacted11). h,bis-98:2)entry - reacted entry 11).bis - 11).bis could- 11). mesitylmanganesewithmesitylmanganesewith 3a and3a and 3b to3b1g 1g yieldreactedto reacted yield the with the Ewith-alkenes 3bE-alkenes 3b to toafford 4j afford and4j 4land 4k4lwith within4k a 78–84% in smalla small78–84% 20% yield 20% yield yield(entries (91%(entries (91% 9–10).after after 9–10). 18 The 18 h, The h,entrybulkier entry bulkier 11). 11).bis - bis- Thisbe used method asThiswith aThis coupling also method3amesitylmanganeseThis method withandmesitylmanganeseThis provedmethod also3bmethod3a alsopartner to andproved also toyieldproved also3b tolerateproved 1gtowiththe proved toreacted1gtolerateyield Etolerate reacted-alkenesto 1d nitriles, toleratetothe withandnitriles, tolerate nitriles,Ewith -alkenes4j 3b 1enitriles, sinceand since3bto nitriles,in since afford to 4k good4j 4-(2-bromovinyl)benzonitrileaffordsince in and4-(2-bromovinyl)benzonitrile since 4l78–84% yields 4-(2-bromovinyl)benzonitrile with4k4l 4-(2-bromovinyl)benzonitrile within a yield78–84% small(entries a small (entries 20% yield 20% 12–13).yield 9–10).yield(entries 3e(91% 3e ( (91%ZMoreover,The (/ ZE3eafter9–10). /3e=E (3e afterbulkier Z98:2)= / (18E(98:2)Z Z The = /h, 18E could98:2) =entry couldbis=h,the bulkier98:2) entry-98:2) could coupling11). could 11).bis could- ThismesitylmanganesemesitylmanganeseThisbe methodusedThismesitylmanganesebe method usedmesitylmanganeseThisbe asmethod used aalso methodas couplingalso aas proved coupling also 1gaproved 1gcoupling alsoreacted proved partnerreacted 1gto proved topartner1greactedtolerate toleratewith partnerreactedto with tolerateto 3b withnitriles, tolerate 1d3b nitriles,towith andto1d3bafford nitriles, afford 1d3bsinceandto nitriles,1e since affordand toin4l 1e 4-(2-bromovinyl)benzonitrile sinceafford4lgoodwith in1e4-(2-bromovinyl)benzonitrile withsince 4l goodin 4-(2-bromovinyl)benzonitrile a yieldswith 4l good smalla 4-(2-bromovinyl)benzonitrile withsmallyields a (entriesyields small20% a 20% small(entries yield 20%(entries yield12–13). 20% yield(91%12–13). (91% yield12–13). Moreover, 3eafter(91% 3e afterMoreover, ((91%Z ( / 18Moreover,3eZEafter /18= E h,(3e afterZ 98:2) =the h, /entry 18E98:2)( Z entry =thecoupling/h, 18 Ecould98:2) =theentry 11).couldh,coupling 98:2)11). entry coupling could 11). could 11). generallybe used as beproceeds a used coupling as a withcoupling partner an partnerexcellent with with1d E 1d-selectivityand and1e 1ein in good when yields yields iodoalkenes (entries (entries 12–13). ar 12–13). eMoreover, used. Moreover, Total the coupling isomerization the coupling is generallybeThisThisbegenerally used methodusedbeThisgenerally method asusedThisgenerallybe proceeds asmethoda usedproceeds coupling aalso methodas coupling alsoproceeds aas proved couplingproceeds also withaproved couplingwithalsopartner proved partneran withto provedan toexcellentpartnertoleratewith excellent withtolerate an partnerto with anexcellent tolerateto 1d withnitriles, excellenttolerate E1d nitriles, -selectivityand withE -selectivityand1d nitriles, E1e 1dand-selectivitysince nitriles,1e in Esince -selectivityand in good1e when 4-(2-bromovinyl)benzonitrilesincegood in1e4-(2-bromovinyl)benzonitrilewhen since yieldsgoodin 4-(2-bromovinyl)benzonitrilewheniodoalkenesyields good iodoalkenes4-(2-bromovinyl)benzonitrilewhen yields (entries iodoalkenes (entriesyields iodoalkenes (entries ar12–13). (entries ear12–13). used.e 12–13).arused. Moreover,e ar 12–13). used.TotalMoreover, e3e Total used. 3e Moreover,(Z isomerizationTotal( /Moreover,Z3eE isomerization /Totalthe=E (3e Z98:2) =theisomerization/ couplingE(98:2)Z isomerization=thecoupling/ E could98:2) =the couldcoupling 98:2)is coupling couldis could is is generally proceeds with an excellent E-selectivity when iodoalkenes are used. Total isomerization observed observedgenerallybeforbegenerallyobserved used usedgenerallyZbeobserved-starting asusedbegenerallyobserved proceedsforas a usedproceeds for coupling a asZ coupling proceeds-startingfor Z aas -starting couplingproceeds for withiodoalkenesaZ coupling-starting with partnerZ partner-starting anwithiodoalkenes an iodoalkenesexcellent partnerwith excellent with anpartneriodoalkenes with excellentaniodoalkenes 1d(entries with excellent E 1d (entries-selectivityand withE (entries-selectivityand1d E1e 1d-selectivity(entriesand 1e inE 2, 2,(entries-selectivityand in good 1e2, 4,when 4,good in 1e4,when 7,2, 7, goodyields in 7, 8, 4,when 2,iodoalkenesyields 8,good 8, 10).iodoalkenes7,4,when yields 10).10).(entries8, 7, iodoalkenes (entriesAyields 10).8, iodoalkenesA similar (entriesA 10). similar Aar12–13). (entriessimilar ear12–13).similarA used. e tendency arused.12–13).similar tendencyeMoreover, ar12–13). used.Total Moreover, etendency tendencyTotal used. Moreover,tendency isomerizationTotalis Moreover, isomerizationis observed Totalthe observed theisomerizationis coupling observedisomerizationisthecoupling observed the observedcouplingfor isfor coupling is for is for is for bromoalkenes,is observedbromoalkenes,observedgenerallygenerallyobservedbromoalkenes, forobservedgenerallybromoalkenes, Zwithgenerallyobservedbromoalkenes, proceeds-startingfor proceedsfor Z proceeds-startingforthewithZ -starting withproceeds forwithZ -startingwith iodoalkeneswithexceptiontheZ -starting anthewithiodoalkenes an iodoalkenesexception excellent withthe exception excellentaniodoalkenesthe exceptionanexcellentiodoalkenes exceptionexcellentof E (entries(entries-selectivity of E (entries-selectivity of4-(2-bromovinyl)benzonitrile 4-(2-bromovinyl)benzonitrileE (entries-selectivityof4-(2-bromovinyl)benzonitrile E 2,(entries-selectivityof 4-(2-bromovinyl)benzonitrile 2,2, 4,when 4-(2-bromovinyl)benzonitrile 4,when7,2, 7, 7,8,4, when2,iodoalkenes 8, 10).iodoalkenes7, 8,4,when 10).8, 7, 10). iodoalkenes A 10). 8, iodoalkenesAsimilar 10). similar A Aar ear similarsimilarA used. e3e tendency arused.similar 3e tendencye ( ar Zused. Total3etendency(e/3e ZE Total tendencyused. /3e Etendency (= Z isTotalisomerization ( /Z= E(isomerization98:2),is observedZTotal/ E/98:2), observedE= isisomerization 98:2),= observedisomerizationiswhich, is 98:2),which,observed98:2), observedfor iswhich,for is which, for iswhich, for is for bromoalkenes,observedbromoalkenes,observed for forwithZ -startingwith Z -startingthe the iodoalkenesexception exception iodoalkenes of (entries of4-(2-bromovinyl)benzonitrile (entries4-(2-bromovinyl)benzonitrile 2, 4,2, 7,4, 8,7, 10).8, 10).A similarA similar 3e 3e tendency( Z (tendency/ZE /E= =98:2),is 98:2), observedis observedwhich, which, for for intriguingly,bromoalkenes,intriguingly,observedintriguingly, didbromoalkenes,intriguingly, with observedintriguingly,bromoalkenes, notfor thedid leadZ did-starting not exception didfornot to lead didwith notZleadisomerization -starting with iodoalkenestonot lead toisomerizationthe lead ofisomerization the to exception4-(2-bromovinyl)benzonitrile isomerizationiodoalkenesto exception isomerization (entries of of the ofthe 2,(entriestheof 4-(2-bromovinyl)benzonitrileofstarting 4, thestartingof4-(2-bromovinyl)benzonitrile 7, the starting 8,2, Z starting10). 4,bondZ bond7,bond ZA 8, whenbond Zsimilar when10). bond when3e when coupledA coupled( whentendencyZsimilar / coupledcoupledE 3e =withcoupled with98:2),3etendency( Z is nucleophile /with E( nucleophileZobservedwith with/ which,=E nucleophile 98:2),=is nucleophilenucleophile 98:2),observed 1dfor intriguingly, which,1d, ,which, 1d , 1dfor, 1d, intriguingly,bromoalkenes,bromoalkenes,intriguingly,entryintriguingly,bromoalkenes,entry 12,bromoalkenes,entryintriguingly, or12, did to 12, ordid awith not toslightor with didnot a tolead slight didwith thenotalead isomerization slightthewith tonot lead isomerizationexception to isomerizationthe exceptionlead isomerization tothe exception isomerization to exception isomerization whenof ofwhen of4-(2-bromovinyl)benzonitrile coupled whenof4-(2-bromovinyl)benzonitrilethe thecoupled of of4-(2-bromovinyl)benzonitrilestarting coupledthe startingof4-(2-bromovinyl)benzonitrile with the starting with Z starting1e bondZwith, entrybond1e Z, 1eentrybondwhen Z ,13.when entrybond In 13. whencoupled all coupled13.3eInwhen cases,3e all Incoupled( Z cases, all3e (with/coupledZE efficientwith/ cases,3eE(= Z nucleophileefficientwith/=E( 98:2), nucleophileZ efficientwith/98:2),E= transference nucleophile 98:2),= which, nucleophiletransference 98:2),which, transference1d which,1d, ,which, 1d, 1d, entrydid not 12, lead orentry to to a12, isomerizationslight or to a isomerization slight isomerization of the startingwhen when coupled coupledZ bond withwith when 1e 1e, entry coupled, entry 13. In 13. withall In cases, all nucleophile efficientcases, efficient transference1d, entry transference 12, or to ofentryintriguingly, intriguingly,entryofboth both entry12,intriguingly,of aryl 12,both intriguingly,entryofor aryl orboth12,to groups did aryl to a groups12, or didslight aaryl not toslightorgroups didnot afrom to groupsleadslight isomerizationdidfrom anotlead isomerization slight the fromtonot lead isomerizationthe to isomerization fromstarting lead isomerization thestartingto isomerizationthetostarting when isomerizationbis startingwhen bis-(aryl)manganese whencoupled-(aryl)manganese ofbis coupled whenofthe -(aryl)manganesebis thecoupled of-(aryl)manganesestarting withcoupled thestartingof with the starting 1e with Z starting1e,species entrybondZwith ,species entry1ebond Z ,species 1e entry13.bondwhen hasZ ,13.specieswhen entryhasInbond been In 13.all when coupled hasbeen all coupledcases,13.Inwhen hasobserved. beencases, all Incoupledobserved. been cases,all efficientwithcoupled observed. efficient withcases, observed. nucleophile efficientwith nucleophile transferenceefficientwith transference nucleophile nucleophiletransference transference1d 1d, , 1d ,1d , 1e ofa slight both aryl isomerizationofentry entryof bothgroups both ofentry12, aryl 12,both entryofor aryl orboth12, to groupsfrom aryl toa groups 12,or slight whenaaryl toslightorgroups theafrom to groups slightisomerizationfrom a coupledisomerization startingslight thefrom isomerizationthe fromstarting isomerization thestarting the withbisstarting when bis -(aryl)manganesestartingwhen bis-(aryl)manganese whencoupled-(aryl)manganese bis ,coupled when entry-(aryl)manganese bis coupled-(aryl)manganese withcoupled 13.with 1e with In 1e,species entrywith ,species allspecies entry1e ,speciescases, 1eentry13. has ,13.species entryhasIn been hasIn 13.all hasbeen e all ffi13.cases,In has beenobserved. beencases, cientall Inobserved. been cases, allefficient observed. observed.efficient cases, transference observed. efficient transferenceefficient transference transference transference of both aryl a a a groups fromof ofboth thebothofTable aryl Tablebothof starting aryl both Table2.groups aryl Iron-catalyzed2.groupsTable Iron-catalyzedaryl 2.groups bis Iron-catalyzedfrom 2.groups from -(aryl)manganeseIron-catalyzed thefrom couplingsthe from startingcouplings thestarting couplings the starting couplingsof bisstarting ofbisbis-(aryl)manganese bis-(aryl)manganese-(aryl)manganese ofbis-(aryl)manganese speciesbis of-(aryl)manganesebis-(aryl)manganese bis-(aryl)manganese-(aryl)manganese has (species1a been (species–1ag)– (agspecies 1awith) has observed.– (specieswith1ag has) –alkenylbeen gwith )hasalkenylbeen with has observed.alkenylbeen electrophiles observed. alkenylbeenelectrophiles observed. electrophiles observed. electrophiles (3a (–3ae).– ( e3a). –(3ae).– e). a Table 2. Iron-catalyzed couplings of bis-(aryl)manganese (1a–g) with a aalkenyl a electrophiles (3a–e). TableTable 2.Table Iron-catalyzed 2. Iron-catalyzed 2. Iron-catalyzed couplings couplings couplings of bis of-(aryl)manganese bis of-(aryl)manganese bis-(aryl)manganese (1a– (g1a) – (with g1aa ) – gwith )alkenyl with alkenyl alkenylelectrophiles electrophiles electrophiles (3a– (e3a). –(e3a).– e). Table 2. Iron-catalyzed couplings of bis-(aryl)manganese (1a–g a) with a alkenyl electrophiles (3a–e). TableTable 2. Iron-catalyzed 2. Iron-catalyzed couplings couplings of bis of-(aryl)manganese bis-(aryl)manganese (1a– (ga1a) – withg) with alkenyl a alkenyl electrophiles electrophiles (3a– (e3a). –e). Table 2. Iron-catalyzedTable 2. Iron-catalyzedTable 2. couplings Iron-catalyzed couplings of couplings bisof bis-(aryl)manganese-(aryl)manganese of bis-(aryl)manganese (1a (–1ag)– gwith) (1aa with–alkenylg) with alkenyl electrophiles alkenyl electrophiles electrophiles (3a–e). (3a (3a–e–).e ).

b b b b b b EntryEntry EntryAr 2MnAr 2MnArElectrophile2 MnElectrophile Electrophile Yield Yield (%)b Yield (%) (%) EntryEntry EntryAr 2MnAr 2MnArElectrophile2 MnElectrophile Electrophile Yield Yield (%)b Yield (%) (%) Entry Ar2Mn Electrophile Yield (%) Entry Ar2Mn Electrophile Yield (%) b b Entry Ar2Mn2 Electrophile Yield (%) b b Entry Ar2Mn2 Electrophile Yield (%) b b EntryEntry EntryAr MnAr 2MnArElectrophile2 MnElectrophile Electrophile Yield Yield (%) Yield (%) (%) b EntryEntry EntryAr MnAr 2MnArElectrophile2 MnElectrophile Electrophile Yield Yield (%) Yield (%) (%) b b b b b EntryEntry Ar 2MnAr 2MnElectrophile Electrophile Yield Yield (%)b (%) b EntryEntry Ar 2MnAr 2MnElectrophile Electrophile Yield Yield (%)b (%) b Entry ArEntry2Mn ElectrophileAr2Mn Electrophile Yield (%) Yield b (%) Entry ArEntry2Mn ElectrophileAr2Mn Electrophile Yield (%) Yield (%) b Entry Ar2Mn Electrophile Yield (%) Entry Ar2Mn Electrophile Yield (%) Entry Ar2Mn Electrophile Yield (%) b Entry Ar2Mn Electrophile Yield (%) b 1 1a 8 1e 1 1 1a1 1a 3b1a:3b Z/: EZ 3b=/E : =Z3b /E: Z=/ E = 8 8 1e8 1e 1e 4b:4b 98,: 98, Z4b/ EZ: 98,4b=/E 1:99 : = Z98, 1:99/E Z=/ 1:99E = 1:99 1 1 1a 1a 3b:3b Z10:90/: EZ =/E 10:90 = 10:90 8 8 1e 1e 3a 3a 3a 1 1 1a 1a10:90 3b: Z3b/E: Z= /E 4b= : 98, Z/E = 1:99 8 8 1e 1e 3a 4i: 4i64,: 64, Z4i/ EZ: 64,=/4iE 1:99 : = Z64, 1:99/E Z=/ 1:99E = 1:99 4b: 98,4b :Z 98,4b/E : = Z98, 1:99/E Z=c /1:99E = c1:99 c 1 1 1a1 1a 1a 10:9010:90 10:90 10:90 (24,(24, Z/ EZ(24, =/E 20:80) (24,=Z 20:80)/E Z= c/ 20:80)E = 20:80) 8 8 1e1e 1e 3a 3a 4i: 4i64,: 64, Z/ EZ =/E 1:99 = 1:99 1 1a1 3b1a:3b Z:/ EZ3b /=E : =Z3b /E: Z=/ E = 8 1e8 1e 3a 3a 4i: 64,4i: Z64,/E Z=c /1:99E = c1:99 c 4b: 98,4b Z: 98,/E =Z 1:99/cE =c 1:99 (51,(51, Z/ EZ(51, =/E 57:43) (51,=Z 57:43)/E Z= c/ 57:43)E = 57:43) 3b: Z/E = 10:90 (24,4b4b(24,: 98,Z:/ 98, E Z(24,Z =//E EZ20:80) =(24,4b/Z=E 20:80)/1:99E: = 98, Z= 1:99 / 20:80)E Z =/ E 20:80) = c1:99 c 3a 10:9010:90 10:90 3a 3a 4i: 64,4i Z: 64,/E =Z 1:99/Ec =c 1:99 10:90 c 3a 3a (51,4i:(51, 64, Z/ EZ =/E 57:43)4i =4i :57:43)1:99: 64,64, Z / E = c1:991:99c (24, Z/E = 20:80)c c (51, (51,Z/E Z= /57:43)E = 57:43) (24,(24, Z/ EZ(24, /=E 20:80) (24,=Z 20:80)/E Z= c/ 20:80)E = 20:80) c (51, Z/E = 57:43) c (51, Z(51,/E =Z 57:43)/E =c 57:43) c c 1 1a 3b: Z/E = 8 1e (51, Z/E = 57:43)(51, Z / E = 57:43) c 4b: 98, Z/E = 1:99 10:90 3a 4j: 4i78,4j: :64, 78,4j: Z78,/E = 1:99 2 2 21b 1b 1b 9 9 91f 1f 1f3b : Z3b/E: =Z3b /E: Z=/ E = 4j: 78, 2 1b 4c: 69,4c Z: 69,/E =Z 1:99/cE = 1:99 9 1f 3b: Z/E = 2 1b (24, 4cZ/: E69, = Z 20:80)/E =4c 1:99: 69, Z/E = 1:99 9 1f 4j: 4j78,: 78, 2 2 2 1b 1b 1b 3a 3a 3a 9 9 9 1f 1f 1f 3b:3b Z10:90/: EZ =/E 10:90 = 10:90 Z/E =Z 1:99/4jE :Z= 78,/ 4j1:99E : = 78, 1:99 c 2 1b3a 4c:4c 69,: 69, Z/ EZ =/E 1:99 = 1:99 9 1f10:90 3b: Z3b/E: Z= /E = Z/E = 1:99(51, Z4j/:E 78, = 57:43) 4c: 69,4cZ: 69,/4cE: = Z69,/1:99E Z=c /1:99E = c1:99 c 3b: Z/E = 10:90 2 2 1b 1b 3a 3a (58,(58, Z/ EZ(58, =/E 69:31) (58,=Z 69:31)/E Z= c/ 69:31)E = 69:31) 9 9 1f 1f 10:9010:90 10:90 Z/4jEZ :=/ 4jE78, 1:99 := 78, 1:994j Z : /78, E4j:= 78,1:99 2 1b2 1b 3a 3a c 9 1f9 3b1f:3b Z:/ EZ3b /=E : =Z3b /10:90E: Z=/ E =(39, Z(39,/E Z =Z /20:80)/EE Z= = /1:99 E20:80) =c 1:99 c c (58,4c: Z69,4c/E Z: =69,/E69:31) =Z 1:99/Ec =c 1:99 (39, Z/E = 20:80)(39, Z c/ E = 20:80) c (58,4c:(58, 69,Z/ E Z =//E 69:31) ==4c 69:31)1:99: 69, Z / E = c1:99c Z E 3a 3a (58, (58,Z/E Z= /69:31)E = 69:31) 10:9010:90 Z/E(39, =Z 1:99/E =/ c1:99= 20:80) 3a 3a 10:90 10:90(39, (39, ZZ//E EZ ==/ E 1:9920:80) = 20:80) Z /E =c 1:99c c c c (39, (39,Z/E Z= /20:80)E = 20:80) (58, Z(58,/E =Z 69:31)/E =c 69:31) c (58, Z/E = 69:31)(58, Z / E = 69:31) c c (39,(39, Z/ EZ(39, /=E 20:80) (39,=Z 20:80)/E Z= c/ 20:80)E = 20:80) c

3 3 1c 1c 10 1f1f 4j: 78, 2 1b3 3 1c3 1c 3b1c:3b Z/: EZ 3b=/E : =Z3b /E: Z=/ E = 10 9 10 1f10 1f 1f 1f 3b: Z/E = MoleculesMolecules 2020 2020, 25,, 257233b, 723: Z /E = 10:90 4k:4k 84,: 84, Z4k/ EZ: 84,4k=/E 1:99 : 4= Z84, 1:99/ofE 4 Z=12of/ 1:99E 12= 1:99 3 3Molecules Molecules1c 1c 2020 2020, 253b, ,:7233b 25Z10:90/:, E Z723 =/E 10:90 = 10:904c : 69, 4d Z:/ 80,E4d = Z: 80,4d1:99/E : = Z80, 1:99/ E Z=/ 1:99E = 1:99 10 10 1f 1f 3a 3a 3a 4k: 84, Z/E4 =of1:99 412 of 12 3 3 1c 1c10:90 3b: Z3b/E: Z= /E 4d=4d : 80,: 80, Z/EZ /=E 1:99= 1:99 10 10 1f 1f 3a 10:90 4k: 84, Z/E = 1:99 c 3a 4k: 84,4k :Z 84,/E =Z Z1:99/E/ E=c 1:99= 1:99c c 4d: 80, Z/E = 1:99 c (48, Z(48,/E(48, 4k (48,=Z 99:1)/:E 84,Z Zc=// E 99:1)E Z =/=E 99:1) 99:1)= 1:99 10:9010:90 (8,4d: Z80,4d/E :Z =80,4d/E1:99) : = Z80, 1:99/E cZ= /1:99E =c 1:99 c 3a 3a (48, Z/E = 99:1) 3 3 3 1c 1c 1c 3b: Z3b/E10:90: =Z /10:90E = (8, Z/(8,E =Z(8, 1:99)/E Zc=c/ 1:99)E = 1:99) 10 10 10 1f 1f 1f 3a 3a 3 3b1c: Z/E = 3b:(58, Z/E Z=(8, /E Z /=E 69:31)= 1:99) 10 1f 4k: 84,4k Z: 84,/E =Z 1:99c/E = 1:99 4k(48,:(48, 84, Z/ EZ /=/E 99:1) 4k== 1:9999:1): 84, Zc /E =c 1:99c 10:9010:90 4d: 80,4d Z: 80,/E =Z c1:99/E c= 1:99 (48, (48,Z/E Z= /99:1)E = 99:1) c 10:90 10:90 4d(8,: 80,(8,Z/ E ZZ (8,=//E E1:99) =4dZ= (8, 1:99)/1:99E: 80, Z= / 1:99) E Z =/E 1:99) =c 1:99 c 3a 3a 3a 3a (39, Z/E = 20:80) (48, Z(48,/E =Z 99:1)/E c= 99:1) c c c c (48, Z/E = 99:1)(48, Z /E = 99:1) c (8, (8,Z/ EZ /(8,=E 1:99) =Z(8, 1:99)/E Zc= / 1:99)E = 1:99) c

d 4l: 4l : d d 4 1c 11 1g 4l: d 4 4 4 1c 1c 1c 11 11 11 1g 1g 1g 3b: 3bZ/:E Z =/ E = 4l: d 4 1c 11 1g3b : 3bZ/:E Z3b=/E: 10:90Z= /E = 4l: 3a 4e: 57, Z/E = 1:99 10:90 20, Z/E = 21:79 3a 3a 3a 4e4e: 57,: 57,4eZ: Z57,//EE =Z= /1:991:99E = 1:99 10:9010:90 20, Z20,/E 20, Z= /21:79EZ =/ E21:79 = 21:79 3 1c 3a 4e: 57, Z/E = 1:9910 1f 10:90 20, Z/E = 21:79 3b: Z/E = c c e e (66,(66, Z/ZE/ E= 72:28)= 72:28) c c 91, Z/E = 5:9591, Z/Ee = 5:95e (66, (66,Z/E Z= /72:28)E = 72:28) c 91, Z91,/E4k Z= /5:95E: 84, = 5:95 Z /E =e 1:99 10:90 4d: 80, Z/E = (66,1:99 Z /E = 72:28) 3a (traces,91, ZZ//EE == 5:9550:50) c c (traces,(traces, Z/E Z =/ E50:50) = 50:50) c c (traces,(traces,(48, Z/E ZZ= /50:50)E == 50:50) 99:1) c c (8, Z/E = 1:99) c

5 5 5 1c 1c 1c 3c: 3cZ/:E Z =/ E = 12 12 12 1d 1d 1d 5 1c 3c: Z3c/E: Z= /E = 12 1d 18:8218:82 18:82 4f: 82, Z/E = 1:99 18:82 4f: 82,4f: Z82,/E Z= /1:99E = 1:99 4m4m: 74,: 74,Z/E Z =/ E98:2 = 98:2 4f: 82, Z/E = 1:99 4m: 4m74, :Z 74,/E Z= /98:2E = 98:2 c 3e: Z/E = 98:2 (80,(80, Z/E Z =/ E53:47) = 53:47) c c 3e: Z3e/E: Z= /98:2E = 98:2 c (80, Z/E = 53:47) c 3e: Z/E =(19, 98:2(19, Z /E Z =/ E73:27) = 73:27) c c (80, Z/E = 53:47) (19, Z(19,/E Z= /73:27)E = 73:27) c

6 1c 13 1e 6 6 1c 1c 4g: 4g: 4g: 13 13 1e 1e 6 1c3d 4g: 13 1e 3d 3d 87, 87,Z/E Z =/ E9:91 = 9:91 3d 87, Z87,/E Z= /9:91E = 9:91 4n: 4n66, : 66,Z/E Z =/ E70:30 = 70:30 c 4n: 66, Z/E = 70:30 (77, Z/E = 4:96) c c 3e: 3eZ/:E Z =/ E98:2 = 98:2 4n: 66, Z/E = 70:30 (77, (77,Z/E Z= /4:96)E = 4:96) c 3e: Z/E = 98:2 (77, Z/E = 4:96) 3e: Z/E = 98:2 c (41,(41, Z/E Z =/ E72:28) = 72:28) c c (41, Z(41,/E Z= /72:28)E = 72:28) c

7 7 1d 1d 7 7 1d 1d 4h: 4h77,: 77,Z/E Z =/ E1:99 = 1:99 3a 3a 4h: 77,4h :Z 77,/E Z= /1:99E = 1:99 3a 3a c (74,(74, Z/E Z =/ E81:19) = 81:19) c c (74, Z(74,/E Z= /81:19)E = 81:19) c a Fora For claritya clarity reasons, reasons, the the magnesium magnesium salt salt has has been been omitted. omitted. b Yield b Yieldb of analyticallyof analytically pure pure product. product. c In c In c Fora Forclarity clarity reasons, reasons, the themagnesium magnesium salt salthas hasbeen been omitted. omitted. Yield b Yield of analytically of analytically pure pure product. product. In c In parentheses,parentheses, yield yield and and Z/E Z/E ratio ratio obtained obtained without without catalysis. catalysis. d Yields d Yieldsd determined determined by byGC GC and and 1H-NMR. 1H-NMR.1 parentheses,parentheses, yield yield and and Z/E Z/Eratio ratio obtained obtained without without catalysis. catalysis. Yields d Yields determined determined by GC by GCand and H-NMR. 1H-NMR. e Aftere Aftere 18 18h. h. Aftere After 18 h. 18 h. 3. Discussion 3. Discussion3. Discussion3. Discussion In order to rationalize some of the mechanistic features of the transformations reported in the In orderIn orderIn toorder rationalizeto rationalizeto rationalize some some ofsome theof theofmechanistic themechanistic mechanistic features features features of theof theoftransformations thetransformations transformations reported reported reported in thein thein the first section, we focused our efforts on the coupling system involving various bis-(aryl)manganese firstfirst section,first section, section, we wefocused wefocused focused our our efforts our efforts effortson onthe the oncoupling thecoupling coupling system system system involving involving involving various various various bis -(aryl)manganesebis-(aryl)manganese bis-(aryl)manganese nucleophiles (bis-mesitylmanganese and bis-phenylmanganese) with (2-bromovinyl)-trimethylsilane nucleophilesnucleophilesnucleophiles (bis (-mesitylmanganesebis -mesitylmanganese(bis-mesitylmanganese and and bis and-phenylmanganese) bis-phenylmanganese) bis-phenylmanganese) with with (2-b with (2-bromovinyl)-trimethylsilane (2-bromovinyl)-trimethylsilaneromovinyl)-trimethylsilane (3b). This choice has been motivated by the low cross-coupling yields obtained with this electrophile (3b().3b This).(3b This ).choice This choice choicehas has been has been motivated been motivated motivated by theby the bylow thelow cros low cross-coupling cross-couplings-coupling yields yields yieldsobtained obtained obtained with with this with this electrophile this electrophile electrophile in the absence of the iron catalyst, which ascertains the requirement of an Fe-based catalysis for this in thein theabsencein theabsence absence of theof the ironof theiron catalyst, iron catalyst, catalyst, which which whichascertains ascertains ascertains the the requirement therequirement requirement of anof Fe-basedan of Fe-basedan Fe-based catalysis catalysis catalysis for forthis forthis this coupling (see Table 2, entries 1, 3, 9 and 11). couplingcouplingcoupling (see (see Table (see Table 2,Table entries 2, entries 2, entries 1, 3, 1, 9 3, and1, 9 3, and 11).9 and 11). 11). The bis-(mesityl)manganese reagent was prepared by adding MesMgBr (2.0 equiv.) into a TheThe bisThe -(mesityl)manganesebis -(mesityl)manganesebis-(mesityl)manganese reagent reagent reagent was was prepared was prepared prepared by byadding byadding addingMesMgBr MesMgBr MesMgBr (2.0 (2.0 equiv.) (2.0 equiv.) equiv.) into into a into a a 1 1 solutionsolution of ofMnCl MnCl2•LiCl2•LiCl2 (1.0 (1.0 equiv.) equiv.) in inTHF THF at at−5 −°C5 °C within within 1 h.1 h.H-NMR H-NMR1 showed showed no no free free MesMgBr MesMgBr solutionsolution of MnClof MnCl•LiCl2•LiCl (1.0 (1.0 equiv.) equiv.) in THFin THF at − at5 °C−5 within°C within 1 h. 1 H-NMRh. 1H-NMR showed showed no freeno free MesMgBr MesMgBr left. The spectra presented high signal-to-noise ratios and broad signals, due to the high left.left. Theleft. The spectraThe spectra spectra presented presented presented high high signal-to-noishigh signal-to-nois signal-to-noise ratiose ratiose ratiosand and broadand broad broadsignals, signals, signals, due due todue tothe to thehigh thehigh high paramagnetism of manganese(II) species, which could not be attributed to a specific molecule (Figure paramagnetismparamagnetismparamagnetism of manganese(II) of manganese(II) of manganese(II) species, species, species, which which whichcould could notcould not be notattributedbe attributed be attributed to a to specific a to specific a specific molecule molecule molecule (Figure (Figure (Figure 1a) [33]. High-spin organomanganese compounds are often reported to be NMR silent [34] or without 1a) 1a[33].) 1a[33]. High-spin) [33]. High-spin High-spin organomanganese organomanganese organomanganese compounds compounds compounds are areoften areoften reported often reported reported to be to NMRbe to NMR be silent NMR silent [34] silent [34] or [34]without or without or without NMRNMR characterization characterization at allat all[35–37]. [35–37]. Yet, Yet, after after addition addition of ofa catalytic a catalytic load load of ofFeCl FeCl2 (0.102 (0.102 equiv.) equiv.) to tothe the NMRNMR characterization characterization at all at [35–37].all [35–37]. Yet, Yet, after after addition addition of a of catalytic a catalytic load load of FeCl of FeCl (0.102 (0.10 equiv.) equiv.) to the to the II −II − 1 1 MesMes2Mn2Mn solution,2 solution, the the ate ate complex complex [Mes [Mes3Fe3Fe] 3was] wasII −detected detected by by H-NMR H-NMR1 from from the the three three signals signals at at127 127 MesMesMn2Mn solution, solution, the theate complexate complex [Mes [MesFe 3]Fe wasII]− was detected detected by byH-NMR 1H-NMR from from the thethree three signals signals at 127 at 127 ppmppm (s, (s,6H, 6H, meta meta-H-H of ofthe the Mes Mes group), group), 110 110 ppm ppm (s, (s,9H, 9H, para para-CH-CH3), 3and), and3 26 26ppm ppm (bs, (bs, 18 18H, H,ortho ortho-CH-CH3), 3), 3 ppmppm (s, 6H,(s, 6H, meta meta-H of-H the of theMes Mes group), group), 110 110 ppm ppm (s, 9H,(s, 9H, para para-CH-CH), and3), and 26 ppm26 ppm (bs, (bs, 18 H,18 orthoH, ortho-CH-CH), 3), as shown in Figure 1b. These signals attest to a strong paramagnetism, due to the high-spin (S = 2) as shownas shownas shown in Figurein Figurein Figure 1b. 1b.These 1b.These Thesesignals signals signals attest attest toattest ato strong ato strong a strongparamagnetism, paramagnetism, paramagnetism, due due to due theto thetohigh-spin thehigh-spin high-spin (S =( S2) = ( S2) = 2) configuration of this complex [38]. This proves a fast trans-metalation of the aryl groups from the configurationconfigurationconfiguration of thisof this ofcomplex this complex complex [38]. [38]. This [38]. This proves This proves proves a fa ast fa trans-metalationast fa trans-metalationst trans-metalation of theof the ofaryl thearyl groups aryl groups groups from from the from the the manganese toward the iron(II) center. A similar result was obtained while adding an excess of the manganesemanganesemanganese toward toward toward the theiron(II) theiron(II) iron(II) center. center. center. A similarA similar A similar resu result wasresult was ltobtained was obtained obtained while while addingwhile adding adding an anexcess excessan excessof theof theof the II –II – 1 1 MesMes2Mn2Mn solution2 solution onto onto Fe(acac) Fe(acac)3 (0.103 (0.103 equiv.) equiv.) as asan aniron(III) iron(III) precursor. precursor. [Mes [Mes3Fe3Fe] 3was] wasII –detected detected by by H- H-1 MesMesMn2Mn solution solution onto onto Fe(acac) Fe(acac) (0.103 (0.10 equiv.) equiv.) as an as iron(III)an iron(III) precursor. precursor. [Mes [MesFe 3]Fe wasII]– was detected detected by byH- 1H- NMR, showing that, when an iron(III) precursor is used, a first 1-electron reduction of the latter by NMR,NMR, NMR,showing showing showing that, that, when that, when anwhen iron(III)an iron(III)an iron(III) precursor precursor precursor is us ised, us is ed, aus first ed,a first 1-electrona first 1-electron 1-electron redu reduction reduction ofction theof thelatterof thelatter bylatter by by

MoleculesMolecules 2020 2020, 25,, 25723, 723 4 of4 of12 12 MoleculesMoleculesMolecules 2020Molecules 2020, 25 2020, ,723 25 2020,, 25723,, 723 25, 723 4 of4 12of4 12of4 12of 12 MoleculesMoleculesMolecules 2020Molecules 2020, 25 ,2020 ,25 723, 2020723, 25 ,, 72325, 723 4 of4 of12 4 12 of 4 12of 12

4l: d 4l: d 4 4 1c 1c 11 11 1g 1g 3b: Z/E = 3b: Z/E = d d Molecules 2020, 25, 723 4l: 4l: d4l : d 4 of 12 4 4 4 1c 1c 1c 3a 4e: 4e57,: 57,Z/E Z =/E 1:99 = 1:99 11 11 111g 1g 1g 10:9010:90 20, 20,Z/E Z =/E 21:79 = 21:79 4l : 4 1c 3a 11 3b1g: Z3b/E: 3b Z= /:E 3bZ =/ E: Z =/ E = d d 4l: 4ld : d 4l: 4l : 4 4 1c 1c 4e : 57,4e :Z 4e57,/E: 57,Z= /1:99E Z =/ cE1:99 = 1:99 11 11 1g 1g10:90 10:90 3b10:90: Z3b /E: Z= /E 20,= Z20,/E 20,Z= /21:79E Z =/ E21:79e = 21:79 4 4 1c 1c 3a 3a 3a 3a (66,(66, Z/E Z =/E 72:28) 4e= 72:28): 57, Z /c E = 1:9911 11 1g 1g 3b3b: Z:/ EZ /=E = 10:90 91,91,Z/E Z =/E 5:95 =20, 5:95 Z/ Ee = 21:79 4e: 57,4e: Z57,/E Z= /1:99E = 1:99 20, Z20,/E Z= /21:79E = 21:79 3a 3a 4e:4e 57,: 57, Z/ EZ /=E 1:99 = 1:99c c 10:9010:90 10:90 10:90 20,20, Z/ EZ /=E 21:79 = 21:79e e 3a 3a (66, (66,Z/E(66, Z= /72:28)E Z =/ E72:28) = 72:28) c c 91, Z91,/E Z91,= /5:95EZ =/ E5:95 = 5:95c e e (66, Z/E = 72:28) (traces,(traces, Z/E Z =/E 50:50)91, = 50:50)Z/ E = c5:95 c e (66, (66,Z/E ZTable=c /72:28)E c= 72:28) c2. Cont. 91, Z91,/Ee Z = /e5:95E = 5:95 e (66,(66, Z/ EZ /=E 72:28) = 72:28) 91,91,Z/EZ /=E 5:95 = 5:95 c c (traces,(traces, (traces,Z/E(traces, Z= /50:50)E Z =/ E50:50) Z = / E50:50) = c50:50) c c c b (traces,(traces, (traces,Z/ EZ(traces, /=E 50:50) =Z 50:50)/E Z= c / 50:50)E c= 50:50)b Entry Ar2Mn Electrophile Yield (%) Entry Ar2Mn Electrophile Yield (%)

5 1c 12 1d 5 1c 3c: 3cZ/:E Z =/E = 12 1d 18:82 5 5 5 1c 1c 1c 3c: Z3c18:82/E: 3cZ= /:E Z =/ E = 4f: 82, Z/E = 1:99 12 12 121d 1d 1d 5 1c 3c: Z/E = 4f: 82, Z/E = 1:99 12 1d 4m4m: 74,: 74,Z/E Z =/E 98:2 = 98:2 5 1c5 5 1c 1c 12 12 121d 1d 1d 5 5 1c 1c 3c18:82:3c Z:/ EZ18:82 3c/=E 18:82: =Z3c /E18:82: Z= /E =4f : 82,4f :Z 82,4f/E: 82,Z= /1:99E Z =/ Ec1:99 = 1:99 12 12 1d1d 3e: Z/E = 98:2 (80, Z/E = 53:47)4f: 82, Z/cE = 1:99 3e: Z/E = 98:2 4m: 74, 4mZ/E: 74,= 98:2 Z/cE = 98:2 3c: Z/E = 18:82 (80, Z/E = 53:47) (19, 4mZ/E: 74,= 73:27)4m Z/E: 74, = 98:2 Zc/E = 98:2 18:8218:82 18:82 18:82 4fZ: 82,4fE: Z82,/E Z= /1:99E = 1:99 (19, Z/E = 73:27) 4f4f:4f 82,:: 82,82, Z/ EZ /=E 1:99 = 1:991:99c c c 3e: Z3e/E: 3eZ= /98:2:E Z =/ E98:2 = 98:2 4m: 4m74,: Z74,/E Z= /98:2E = 98:2 (80, (80,Z/E(80, Z= /53:47)E Z =/ E53:47) = 53:47) c 3e: Z/E =4m 98:24m: 74, : 74, Z/ 4mEZ /=E :98:2 = 74, 98:2c Z /cE =c 98:2 (80, Z/E =c 53:47) 3e Z E (19, (19,Z/E(19, Z= /73:27)E Z =/ E73:27) = 73:27) c (80, Z/E = 53:47) c c 3e:: Z3e//E: Z= /98:2E98:2 = 98:2 (19, Z/E = 73:27) c (80, Z/E(80, = 53:47) (80,Z/E Z= c / 53:47)E c= 53:47) 3e:3e Z:/ EZ /=E 98:2 = 98:2 (19, Z/E = 73:27)c c (80, Z/E = 53:47) (19,(19, Z/ EZ(19, /=E 73:27) =(19,Z 73:27)/E Z= c / 73:27)E c= 73:27)

6 1c 13 1e 6 1c 4g: 4g: 13 1e 3d 6 6 1c1c 3d 87, Z/E = 9:91 13 13 1e 1e 6 6 6 1c 1c 1c 87, Z/E = 9:914g : 4g: 4g: 4g13: 13 13 1e 1e 1e 3d 4n: 66, Z/E = 70:30 6 6 1c 1c 3d 3d 3d 87, Z/E 87,= 9:91 Z/E c = 9:91 4g: 13 13 1e 1e 4n: 66, Z/E = 70:30 6 6 1c 1c (77,4g: Z 87,87,/E =Z 4:96)//E87, == 9:91 Z9:91 /4gEc := 9:914g13 : 13 1e 1e 3e: Z/E = 98:2 (77, Z/E = 4:96) 4g: 3e: Z/E = 98:2 3d3d 3d 3d 87, Z87,/E Z= /9:91Ec = 9:91 4n: 66,4n :Z 4n66,/E4n: 66,Z=: /70:30E 66,Z =/ Ec70:30Z =/ E70:30 = 70:30 (77,87,87, ZZ/ EZ/E /=E =9:91 = 4:96)9:91 c c 3e: Z/E = 98:2 (41, Z/E = 72:28)4n: 66, Z/cE = 70:30 (77, Z/E(77, = 4:96) Z/E = 4:96)c c 3e: Z3e/E: 3eZ= /98:2:E Z =/ E98:2 = 98:2 (41, Z/E = 72:28) (77, Z/E(77, = 4:96) Z/E = 4:96) 3e: Z/E = 98:2 4n: (41,66,4n: Z66,Z/E/ E Z= /=70:30E 72:28)= 70:30 c c 4n4n: 66,: 66, Z/ EZ /=E 70:30 = 70:30c c c (77,(77, Z/ EZ(77, /=E 4:96) =(77,Z 4:96)/E Zc= /4:96) Ec = 4:96) c 3e:3e Z:/ EZ 3e/=E 98:2: =Z3e 98:2/E : Z= /98:2E =(41, 98:2 (41,Z /E(41, Z= /72:28)E(41, Z =/ E72:28) Z =/ E72:28) = 72:28) c c (41,(41, Z/ EZ(41, /=E 72:28) =(41,Z 72:28)/E Z=c /72:28)Ec = 72:28)c

7 1d 7 7 1d 1d 3a 4h4h:4h 77,:: 77, 77,Z/EZ Z /=/EE 1:99 = 1:991:99 7 7 7 1d 1d 1d 3a 7 1d 3a c 4h(74,: 77,Z Z4h/E/E:= 77,= 81:19)1:99 Z/cE = 1:99 7 7 1d 1d (74, 4hZ/E: 77,= 81:19) 4hZ/E: 77, = 1:99 Zc/E = 1:99 7 7 1d1d 3a 3a 3a 3a (74, Z/E = 81:19) a 4h: 77,4h: Z77,/E Z= /1:99E = 1:99 b c For clarity reasons, the magnesium3a 3a 4h salt4h: 77,: has77, Z/ EZ been/=E 1:99 = 1:99c omitted. c c Yield of analytically pure product. In parentheses, a 3a 3a (74, (74,Z/E(74, Z= /81:19)E Z =/ E81:19) = 81:19) c b c Fora clarity reasons, the magnesium salt (74,hasd Z been/E = 81:19) omitted. Yieldb of analytically1 pure product.e Inc For clarity reasons, the magnesium salt has beenc omitted.c Yield of analytically pure product. In yield and Z/E ratio obtained without(74, catalysis.(74, Z/ EZ(74, /=E 81:19) =(74,Z 81:19)/E Yields Z= c / 81:19)E c= 81:19) determined by GC and H-NMR. After 18 h. a db 1 c parentheses, Forparentheses,a Forclaritya For claritya For clarity reasons,yield clarity yieldreasons, andreasons, andthe reasons, Z/E the magnesiumZ/E ratio the magnesium ratio themagnesium obtained magnesiumobtained salt saltwithouthas saltwithout hasbeen salt has been catalysis. omitted.has beencatalysis. omitted. been omitted. omitted.Yields Yieldd Yieldsb Yield b determinedofYield bdeterminedanalytically ofYield analyticallyof analyticallyof byanalytically bypureGC GCpure and product. pureand product. H-NMR.pure 1 H-NMR.product. product. In c In c In c In ae a a a For clarity reasons, the magnesium salt has beendb omitted.bd db b Yield of analytically1 pure1 c1product.c c c In parentheses, AfterFore Forparentheses,After clarity parentheses, 18clarityFor parentheses,18h. clarity reasons,h. yield reasons, yield andreasons, yield the and yield Z/Ethe magnesiumand Z/E ratiomagnesiumthe and Z/E ratio magnesium obtainedZ/E ratio obtained ratio salt obtained salt withouthasobtained salthas withoutbeen beenhaswithout catalysis. omitted.without been omitted.catalysis. catalysis. omitted. catalysis. YieldsYield Yield Yields YieldsofdeterminedYield d of analyticallyYields determined analytically ofdetermined analytically determined by pure GCby pure byGCand product. pure GC by product.and H-NMR. GC and product.H-NMR. and H-NMR.In In1H-NMR. In 3. Discussione e parentheses,e parentheses, yield yield and and Z/E Z/E ratio ratio obtained obtained without without catalysis. dcatalysis.d d Yields d Yields determined determined by GCby1 GCand1 and 1H-NMR. 1H-NMR. parentheses, Afterparentheses, After 18 After eh. 18After yieldh.18 yield h.18 and h. and Z/E Z/E ratio ratio obtained obtained without without catalysis. catalysis. Yields Yields determined determined by by GC GC and and H-NMR. H-NMR. 3. Discussion3. Discussione Aftere Aftere 18After 18 eh. After h. 18 h. 18 h. In order to rationalize some of the mechanistic features of the transformations reported in the 3. Discussion3. Discussion3. Discussion3. Discussion In Inorder order to torationalize rationalize some some of ofthe the mechanistic mechanistic features features of ofthe the transformations transformations reported reported in inthe the first section,3. 3.Discussion Discussion3. we Discussion3. Discussion focused our efforts on the coupling system involving various bis-(aryl)manganese firstfirst section,In section,orderIn Inorder we orderInto we order rationalizefocusedto focusedtorationalize rationalizeto rationalizeour oursome efforts some efforts someof sometheonof on of thethemechanistic theof mechanisticcoupling the mechanisticcoupling mechanistic featuressystem systemfeatures features involvingfeaturesof involving theof of thetransformations theof transformationsvarious the transformationsvarious transformations bis bis-(aryl)manganese reported-(aryl)manganese reported reported reported in thein inthe thein the nucleophiles (bis-mesitylmanganeseIn order to rationalize andsome bisof -phenylmanganese)the mechanistic features of with the transformations (2-bromovinyl)-trimethylsilane reported in the nucleophilesfirstnucleophilesfirst Insection,firstIn ordersection,first order Insection, we(ordersection,tobis ( to webisrationalize-mesitylmanganesefocused rationalize we-mesitylmanganese tofocused we rationalizefocused ourfocused some our effortssome our efforts someofour efforts of theandon efforts the and of onthemechanistic bis themechanistic on thebis-phenylmanganese)coupling on-phenylmanganese)themechanistic coupling the coupling coupling featuressystem features system features system involving ofsystem of withtheinvolving withthe involvingof transformations (2-b involvingthetransformations (2-bvariousromovinyl)-trimethylsilane transformations variousromovinyl)-trimethylsilane various bisvarious -(aryl)manganesebis reported -(aryl)manganesebis reported -(aryl)manganesebis reported-(aryl)manganese in inthe the in the first section, we focused our efforts on the coupling system involving various bis-(aryl)manganese (3b). Thisfirst(nucleophiles3bfirst(3bnucleophiles). choice section,This).firstnucleophiles section, Thisnucleophiles choicesection, has choice we(bis we (-mesitylmanganesefocusedhas beenbis wefocused(has-mesitylmanganesebis been (-mesitylmanganesefocused bisbeen motivated -mesitylmanganeseour motivated our motivated efforts ourefforts efforts andonby on byandthe thebis thetheandon -phenylmanganese)low couplingbis and lowthecouplinglow -phenylmanganese)bis cros -phenylmanganese)biscoupling cros cross-couplings-coupling-phenylmanganese) systems-coupling system system involving yieldsinvolving with yields involvingwith (2-bobtained yieldswith variousobtained (2-bwithromovinyl)-trimethylsilane various (2-bromovinyl)-trimethylsilane various(2-b obtained romovinyl)-trimethylsilanewith bis withromovinyl)-trimethylsilanebis-(aryl)manganese this-(aryl)manganese bis this -(aryl)manganeseelectrophile with electrophile this electrophile nucleophiles (bis-mesitylmanganese and bis-phenylmanganese) with (2-bromovinyl)-trimethylsilane in the absencenucleophilesin(3bnucleophiles inthe().3b theThisnucleophiles (absence).3b This(absence). of3b choice This). the choice( Thisbis of( choicebis -mesitylmanganese has ironofthe -mesitylmanganesechoice( bisthehas beeniron -mesitylmanganesehas catalyst, ironbeen has catalyst, motivatedbeen catalyst, motivatedbeen motivatedwhich whichmotivated andbywhich and theby bisascertains and ascertains bybis the-phenylmanganese)lowascertains -phenylmanganese)bythe bislow cros the -phenylmanganese)low cros thes-couplinglow crosthe s-coupling therequirement cros s-couplingrequirement requirements-coupling yields with withyields ofyields (2-bwithobtained (2-bof anyields obtainedromovinyl)-trimethylsilane an Fe-based(2-bromovinyl)-trimethylsilane obtained ofFe-based obtained romovinyl)-trimethylsilanewith an with Fe-basedcatalysisthis with catalysis thiswith electrophile this electrophile thisfor electrophile for catalysis this electrophile this for this (3b). This choice has been motivated by the low cross-coupling yields obtained with this electrophile (couplingin3b( couplingthe3b).in This ).( theinabsence3b This thein ). (seeabsencechoice This the (seechoiceabsence Table ofabsence choice Table has theof has 2, theofbeeniron entries2,has been theof ironentries catalyst, motivatedthe beeniron motivated catalyst, 1,iron catalyst,motivated3,1, 9 3,catalyst,which and 9by whichand by the 11).which ascertainsthe by11). whichlow ascertains lowthe ascertains cros low crosascertains s-couplingthe cross-coupling therequirement s-couplingthe requirement the requirement yields requirement yields ofyields obtained anobtainedof Fe-basedofan obtained anofFe-based with anFe-based with Fe-based catalysisthis with this catalysis electrophile catalysis thiselectrophile catalysisfor electrophile forthis for this for this this coupling (see Tablein the 2absence, entries of the 1, 3,iron 9 andcatalyst, 11). which ascertains the requirement of an Fe-based catalysis for this incoupling inthecoupling theThe incouplingabsenceThe theabsence coupling (seebis absencebis -(mesityl)manganese(see Table -(mesityl)manganese of(see ofTablethe (see the Table 2,of iron entries Tabletheiron2, entriescatalyst,2, iron catalyst,entries 2, 1, entries catalyst,3, 1, 9reagent which 3, 1, and whichreagent 93, 1, and 9 11).which3, ascertainsand 9 was11).ascertains andwas 11). ascertainsprepared 11). prepared the the requirement therequirementby by requirementadding adding of MesMgBr ofan MesMgBr an Fe-basedof Fe-based an Fe-based (2.0 (2.0catalysis catalysisequiv.) equiv.) catalysis forinto for intothis thisfora a this The bis-(mesityl)manganesecouplingcoupling (see2 (see Table Table 2, entries 2, entries reagent 1, 3, 1, 9 3, wasand 9 and 11). prepared 11). by adding1 MesMgBr (2.0 equiv.) into a solution couplingsolutioncouplingsolutionTheThe of(seebis The of(seeMnCl -(mesityl)manganesebis TheTableMnCl -(mesityl)manganesebisTable •LiCl-(mesityl)manganesebis 22,•LiCl-(mesityl)manganese 2,entries entries(1.0 (1.0 equiv.) 1, equiv.) 1,3, 3,9reagent and9in reagentand inTHF reagent11). THF 11).wasreagent at wasat− 5prepared was −°C 5 prepared was°C withinprepared within prepared by 1 by h.adding1 byh.addingH-NMR 1byH-NMRadding MesMgBradding MesMgBrshowed MesMgBrshowed MesMgBr (2.0 no (2.0 nofreeequiv.) (2.0 free equiv.) (2.0MesMgBr equiv.) MesMgBr intoequiv.) into ainto a into a a 1 left. The ThespectraThe bis2 -(mesityl)manganesebispresented-(mesityl)manganese2 high signal-to-nois reagent reagent wase was ratiosprepared prepared and by 1 broad byadding1 1adding signals,1 MesMgBr MesMgBr due (2.0to (2.0 theequiv.) equiv.)high into into a a of MnClsolution2left.solutionLiClThesolution TheThe solutionofbis (1.0 MnClbisof-(mesityl)manganesespectra -(mesityl)manganeseofMnCl equiv.) MnClof•LiCl MnCl2•LiClpresented •LiCl(1.02 in•LiCl (1.0 equiv.) THF(1.0 equiv.) (1.0 high reagentequiv.) reagentin atequiv.) THFsignal-to-noisin 5inTHFwas at◦THFwasinC −atTHF5preparedwithin °C−preparedat5 −at°Cwithine5 −°Cratioswithin5 1by°Cwithin 1by h. withinaddingh. and1 adding h.H-NMR H-NMR1 h.broad H-NMR1 MesMgBrh. H-NMRMesMgBr H-NMR showedsignals, showed showed (2.0 noshowed (2.0due noequiv.)free equiv.)no nofree toMesMgBr nofree free theMesMgBr intofree intoMesMgBr highMesMgBr aMesMgBr a left. • solutionsolution of MnClof MnCl2•LiCl2•LiCl (1.0 (1.0 equiv.) equiv.)− in THFin THF at −at5 °C−5 °Cwithin within1 11 h. 1 1h.H-NMR 1H-NMR showed showed no nofree free MesMgBr MesMgBr The spectrasolutionparamagnetismleft.solutionparamagnetismleft. Theleft. presented Theleft.of spectra ofTheMnCl MnClspectraThe ofspectra2 •LiCl ofmanganese(II) high2spectrapresented•LiCl manganese(II) presented (1.0presented signal-to-noise(1.0 presentedequiv.) equiv.)high species,high species,inhighsignal-to-nois in THFhighsignal-to-nois THF whichsignal-to-nois which at ratios signal-to-nois at−5 could− °C5 ecould °C andwithinratiose notwithin ratiosenot broadbe ratiose 1 andbeattributed ratiosh. 1 attributedand h. H-NMRbroad and signals,H-NMR broadand tobroad signals, toashowedbroad specific showedasignals, due specificsignals, signals, todueno molecule no theduemoleculefree tofreedue highMesMgBrtoduethe MesMgBr (Figureto the (Figurehighto paramagnetismthe highthe high high left.1aparamagnetismleft.) [33]. Theleft. paramagnetismThe High-spinleft. spectraThe spectraThe ofspectra manganese(II)organomanganesepresentedspectra presented of manganese(II)presented presented high high species, highsignal-to-nois compounds signal-to-noisspecies,high whichsignal-to-nois signal-to-nois which could aree eratios often couldnotratiose be ratiosreportede notand attributedratiosand be broadand attributed broad toand be broadto signals, NMRabroad signals,specific to signals, silenta specificsignals,due moleculedue [34] todue molecule toorduethe without the(Figureto high tothehigh (Figurethe high high of manganese(II)1aparamagnetism) [33].paramagnetism High-spin species, of organomanganese manganese(II) of which manganese(II) could species, compounds species, not which be which could attributedare often could not bereported not attributed to be aattributed to specific be to NMR a specific to silent a molecule specific molecule [34] ormolecule without (Figure(Figure (Figure 1a)[ 33]. paramagnetismparamagnetism of manganese(II) of manganese(II) species, species, which which could could not not be attributedbe attributed to a to2 specific a specific molecule molecule (Figure (Figure paramagnetismNMR1aparamagnetism)NMR 1a[33].) 1acharacterization [33]. )High-spincharacterization1a [33].) High-spin [33]. High-spin of High-spin of manganese(II)organomanganese manganese(II) organomanganese at organomanganeseatall allorganomanganese [35–37]. [35–37]. species, species, Yet, compounds Yet, aftercompounds which afterwhichcompounds additioncompounds couldaddition arecould areoften not of arenot often of abe are reportedcatalyticoften bea attributed catalytic often reportedattributed reported reported loadto loadbe to ofto NMRabeto specificofaFeCl beNMRtospecific FeCl NMRbesilent (0.10 NMR silent2 molecule (0.10 moleculesilent[34] equiv.) silent[34] equiv.)or [34] without (Figureor [34] to(Figure withoutor tothe withoutor the without II − 1 High-spinMes2 organomanganeseMn1a) 1asolution,[33].) [33]. High-spin High-spin the ate organomanganese complex organomanganese compounds [Mes3Fe ]compounds are IIwas compounds− often detected reportedare are byoften oftenH-NMR 1reportedto reported be from to NMR be tothe NMRbe 2three silentNMR silent 2signals silent [34 [34]] [34]at oror 127 without withoutor without NMR 1aNMR1a)Mes NMR[33].) [33]. NMRcharacterization2Mn High-spinNMR characterization High-spin solution, characterization characterization organomanganese theorganomanganese at ate all at complex [35–37].allat all[35–37].at all[35–37]. Yet,[Mes[35–37]. compounds compoundsYet, after 3Yet,Fe after Yet, ]addition after was addition afterare additionaredetected often addition ofoften a of reportedcatalytic aofreportedby catalytic aof catalyticH-NMR a catalytictoload tobe load be of NMRfromload NMRFeCl ofload FeClofsilentthe silentFeCl(0.10of three2 FeCl(0.10 [34] equiv.)[34](0.10 signals2 or equiv.)(0.10 or without equiv.) withoutto equiv.) atthe to 127 theto theto the ppm2 (s,NMR 6H,NMR2 characterization meta characterization-H of the Mes at all group),at [35–37].all [35–37]. 1103 Yet,II ppm− Yet,3II after− II(s, after− II 9H,addition− addition para-CH of1 a3of ),catalytic1 aand 1catalytic 261 ppmload load of(bs,2 FeClof2 18 FeCl H,2 (0.10 ortho2 (0.10 equiv.)-CH equiv.)3), to theto the characterizationNMRMesNMRppmMesMn Mescharacterization 2 (s,characterizationMn Messolution, 6H,Mn at solution,2Mn all metasolution, [solution, 35the-H – the ate of37at the at theallate].complex theall Yet,ate[35–37]. complexMes [35–37]. atecomplex after group), complex[Mes Yet, [Mes Yet, addition Fe[Mes after 110 3after[MesFe] was ppmFeaddition] addition3wasFe] detected of (s,was] detecteda 9H,was of catalyticdetected of apara detected bycatalytica catalytic -CHbyH-NMR by loadH-NMR3), byload H-NMRand load H-NMRfrom of of26 from FeClof FeClppm thefromFeCl from the2 three (bs,(0.10(0.10 the (0.10three 18the signalsthreeequiv.) H, equiv.) threesignals ortho signals atto signals -CH to127 theat to the 127 at3 the), 127at Mes127 2Mn 2 II − II3 − II − 1 1 1 MesasppmMes shownppm2 Mn(s,Mesppm2Mn 6H, (s,Messolution, 2in Mn solution,(s,6H, metaFigure Mn 6H,solution, meta-H solution,metathe -H1b.ofthe ate -H the of Thesetheate complex theofMes the complexate the Messignals atecomplexgroup), MesII complexgroup),[Mes [Mesgroup), attest 1103 Fe[Mes3 Fe110 [Mesppm ]toII 1103]wasFe −ppma was strong(s,Fe]ppm detected was 9H,(s,detected] was(s,9H, paramagnetism,paradetected 9H, 1detectedparaby-CH bypara -CHH-NMR 3 1),byH-NMR-CH and3 ),byH-NMR and3 ),26 fromH-NMR anddue fromppm26 26 toppmthefrom (bs,theppmthe fromthree (bs, thethree18high-spin (bs, theH,18threesignals signals 18 orthoH,three H,orthosignals (-CHat S orthosignals at=127-CH 32)127), -CHat 3 ), 127at 3), 127 solution,as the shownateppmcomplex in (s, Figure 6H, meta 1b. [Mes -HThese 3ofFe the signals] Mes− was group),attest detected to 110 a strong ppm by (s,paramagnetism, H-NMR9H, para-CH from3), dueand the to26 the threeppm high-spin (bs, signals 18 H, (S ortho at= 2) 127 -CH ppm3), (s, ppmppm (s, 6H,(s, 6H, meta meta-H -Hof theof the Mes Mes group), group), 110 110 ppm ppm (s, 9H,(s, 9H, para para-CH-CH3), and3), and 26 ppm26 ppm (bs, (bs, 18 H,18 orthoH, ortho-CH-CH3), 3), ppmconfigurationasppm configurationshownas (s, asshown (s, 6H,shownas 6H,in shown meta Figurein metaof inFigure of-Hthis Figure -Hin thisof1b. complexFigure ofthe 1b.Thesecomplex the 1b. MesThese Mes1b. These signals [38].group), These group),[38].signals Thissignals attest This signals110 provesattest110 ppm provesattestto ppm attestato (s,stronga to a (s,fa a9H,strong stato fa9H, strong sttrans-metalation aparaparamagnetism, strongtrans-metalationpara paramagnetism,-CH paramagnetism,-CH 3paramagnetism,), 3and), and 26 of due26 ppm ofthe dueppm tothe due aryl (bs, theto (bs,duearyl tothe18high-spingroups 18 thetogroups H,high-spin H,the orthohigh-spin orthofrom high-spin from(-CHS -CH =(the S32) ), the(=3 S), 2) =( S 2) = 2) 6H, meta-H of theas shown Mes group),in Figure 1101b. These ppm signals (s, 9H, attestpara to-CH a strong3), and paramagnetism, 26 ppm (bs, due 18 to H, theortho high-spin-CH3 ),(S as= 2) shown asmanganeseconfigurationas manganeseshownconfiguration shownasconfiguration shownconfiguration in toward inFigure towardofFigure in thisof Figure the1b.ofthis complex 1b. thethis ofTheseiron(II) complex These1b.thisiron(II) complex These signalscomplex[38]. center.signals [38].center. signals This[38]. attest AThis[38].attest provesAsimilarThis attestto similarprovesThis to aproves stronga resuto provesstrongfa resuaast lt fastrong a trans-metalation paramagnetism, stwasltfa aparamagnetism,trans-metalationwasst fa obtained trans-metalationstparamagnetism, obtainedtrans-metalation while ofwhiledue due theof addingto ofthedue addingaryl tothe theof the arylto high-spin groupsthe an arylthehigh-spin an groupsexcessaryl high-spingroupsexcess from groups ( ofSfrom ( =Softhefrom 2)= the( from S2)the = the 2) the in Figure1b.2 configuration Theseconfiguration signals of thisof attest this complex complex to3 a strong[38]. [38]. This paramagnetism,This proves proves a fa ast fa trans-metalationst trans-metalation due to the3 II high-spinof– theof the aryl aryl groups ( Sgroups= 2)1from configurationfrom the the configurationMesmanganeseconfigurationMesmanganeseMnmanganese2Mn manganesesolution solution toward of toward of thisontotoward this onto thetoward complex Fe(acac) thecomplexiron(II) Fe(acac) the iron(II) the iron(II) [38]. center. (0.10iron(II)[38].3 (0.10center. This equiv.)center.This Aequiv.) center. proves similar Aproves assimilarA as ansimilarA a resuan iron(III)similarfaa stfaresuiron(III)lt st trans-metalation resuwas trans-metalationlt resu precursor.waslt obtained precursor.waslt obtained was obtained obtained [Meswhile [Mesof while oftheFe while adding3theFe ]whilearyl adding II was]aryl –adding was groups an detectedaddinggroups detectedexcessan an excessfrom anexcess from byof excessby theH-of the1 H- ofthe theof the NMR,2 manganese showingmanganese2 that, toward towardwhen the an the iron(II) iron(III)3 iron(II)3 center. precursor center. A similarA is similar used, resu aresu ltfirst waslt 1-electronwas obtained obtained 3redu whileII while–ction3II adding– II –addingofII –the an latter anexcess excess1 by of1 1theof 1the of this complexmanganeseMesmanganeseNMR,MesMnMes2Mn Messolutionshowing [Mn38 towardsolution2 Mn].toward solution This solutiononto that, the onto the provesFe(acac) ontowheniron(II) iron(II)Fe(acac)onto Fe(acac) an aFe(acac) center.(0.10 iron(III) fastcenter.3 (0.10 equiv.) (0.10 trans-metalationA3 equiv.)(0.10 Asimilarprecursor equiv.)similar as equiv.) an as resu iron(III)asan resu is anasiron(III)lt us ltwasaniron(III)ed, was precursor.iron(III) of aobtained precursor.first theobtained precursor. 1-electron arylprecursor. [Meswhile while groups[Mes Fe[Mes adding redu 3[MesaddingFe] wasFe from]ction 3 wasFean] detected anwas ]excess ofdetected the wasexcess thedetected manganese detected bylatterof of thebyH- the byby H- by H- H- toward II – II – II – 1 1 1 MesNMR,Mes2MnMesNMR,2 Mnshowing Messolution2 Mnsolution showing2Mn solution that, ontosolution onto whenthat, Fe(acac) onto Fe(acac) onto whenan Fe(acac) 3iron(III) Fe(acac) (0.103 an(0.10 3iron(III) equiv.)(0.10 equiv.)precursor3 (0.10 equiv.) asprecursor equiv.) as an anis iron(III)as usiron(III) anased, is iron(III)an usa precursor.iron(III) firsted, precursor. a precursor.1-electron first precursor. [Mes 1-electron [Mes 3 reduFe[Mes3Fe [Mes] IIction 3 was]reduFe– was3Fe] detectedof ctionwas detected] the was detectedof latter detectedtheby by H-latterby 1 H-by by H-by H- the iron(II) NMR, center.NMR, showing Ashowing similarthat, whenthat, result when an iron(III) an was iron(III) obtainedprecursor precursor is whileused, is usa addinged,first a 1-electron first an1-electron excess reduction redu of ctionof the the Mesof latter the Mnlatterby solutionby NMR,NMR, showing showing that, that, when when an aniron(III) iron(III) precursor precursor is us ised, us ed,a first a first 1-electron 1-electron redu reductionction of theof the latter2 latter by by NMR, NMR, showing showing that, that, when when an an iron(III) iron(III) precursor precursor is isus used,ed, a firsta first 1-electron 1-electronII redu reductionction of ofthe the latter1 latter by by onto Fe(acac)3 (0.10 equiv.) as an iron(III) precursor. [Mes3Fe ]− was detected by H-NMR, showing that, when an iron(III) precursor is used, a first 1-electron reduction of the latter by the nucleophile can take place, affording an iron(II) species. This is in agreement with recent reports by Neidig [39] and by some of us [40] regarding the reduction of iron(III) salts by Grignard reagents as MeMgBr and PhMgBr. Accordingly, all the mechanistic studies discussed thereafter were performed using an iron(II) precursor. Upon addition of the electrophile 3b ((2-bromovinyl)trimethylsilane) to a mixture of FeCl2 and II Mes2Mn at 25 ◦C, the signals corresponding to [Mes3Fe ]− were observed to slowly decrease, affording II [Mes2BrFe ]−, characterized by new signals at 128 ppm (s, 4H, meta-H of the Mes group), 104 ppm (s, 6H, para-CH3), and 29 ppm (bs, 12 H, ortho-CH3) (see Figure1c) (this tricoordinate ate species also presents a high-spin S = 2 configuration) [38]. The same reaction was run at 25 ◦C for 1 h, then quenched, and analyzed by GC-MS, which proved formation of the desired cross-coupling product with a low conversion (ca. 20%). This is in fair agreement with the result given in Table2, entry 11 (due to the high Molecules 2020, 25, 723 5 of 12 the nucleophile can take place, affording an iron(II) species. This is in agreement with recent reports by Neidig [39] and by some of us [40] regarding the reduction of iron(III) salts by Grignard reagents as MeMgBr and PhMgBr. Accordingly, all the mechanistic studies discussed thereafter were performed using an iron(II) precursor. Upon addition of the electrophile 3b ((2-bromovinyl)trimethylsilane) to a mixture of FeCl2 and Mes2Mn at 25 °C, the signals corresponding to [Mes3FeII]− were observed to slowly decrease, affording [Mes2BrFeII]−, characterized by new signals at 128 ppm (s, 4H, meta-H of the Mes group), 104 ppm (s, 6H, para-CH3), and 29 ppm (bs, 12 H, ortho-CH3) (see Figure 1c) (this tricoordinate ate species also Moleculespresents2020 a ,high-spin25, 723 S = 2 configuration) [38]. The same reaction was run at 25 °C for 1 h,5 then of 12 quenched, and analyzed by GC-MS, which proved formation of the desired cross-coupling product with a low conversion (ca. 20%). This is in fair agreement with the result given in Table 2, entry 11 paramagnetism(due to the high of paramagnetism the NMR-analyzed of the solution NMR-analyzed and due tosolution the presence and due of non-deuteratedto the presence solvents of non- (THFdeuterated solutions solvents of organometallics), (THF solutions NMR of organometallics), monitoring of the NMR coupling monitoring product of formation the coupling could product not be eformationfficiently performed).could not be efficiently performed).

1 FigureFigure 1.1. 1H-NMRH-NMR spectra spectra (recorded (recorded at 25at ◦25C in°Cd 8in-THF) d8-THF) of a 0.08 of a M 0.08 solution M solution of (a) Mes of2 Mn,(a) Mes (b) Mes2Mn,2 Mn(b) +Mes0.102Mn equiv. + 0.10 FeCl equiv.2,(c) MesFeCl22Mn, (c)+ Mes0.102Mn equiv. + 0.10 FeCl equiv.2 + 1.0 FeCl equiv.2 +3b 1.0,( dequiv.) FeCl 3b2 +, 3.0(d) equiv.FeCl2 + MesMgBr 3.0 equiv.+ 10MesMgBr equiv. 3b + .10 equiv. 3b.

TheThe same observations observations were were made made while while performing performing the the coupling coupling of 3b of 3bwithwith MesMgBr MesMgBr as a assole a II II solenucleophilic nucleophilic partner partner in a Kumada-type in a Kumada-type reaction reaction using usingFeCl2, FeClas [Mes2, as3Fe [MesII]− and3Fe [Mes]− and2BrFe [MesII]− were2BrFe also]− weredetected also under detected these under cross-coupling these cross-coupling conditions conditions(Figure 1d, (Figure in the absence1d, in the of absencemanganese, of manganese, the signals II theof [Mes signals2BrFe ofII [Mes]− shifted2BrFe to ]131,− shifted 106, and to 131, 30 ppm). 106, and These 30 ppm).series of These experiments, series ofexperiments, therefore, confirm therefore, that II II confirmboth [Ar that3FeII] both− and [Ar [Ar3Fe2BrFe]− IIand]− ate [Ar complexes2BrFe ]− ateare complexespart of a coupling are part ofcatalytic a coupling cycle catalytic and [Ar cycle3FeII]− andcan II [Arbe involved3Fe ]− can in bethe involvedactivation in step the of activation the electrop stephile. of theThe electrophile. following catalyti The followingc cycle (Scheme catalytic 2) can cycle be (Schemesuggested,2) can which be suggested, echoes recent which reports echoes recentby Neidig reports on by the Neidig Fe-catalyzed on the Fe-catalyzed alkyl-alkenyl alkyl-alkenyl coupling Moleculescouplingreactions 2020 reactions[39],, 25, and723 [by39 ],ourselves and by ourselves on the benzyl-alkenyl on the benzyl-alkenyl coupling coupling[26]. [26]. 6 of 12

II – [Ar3Fe ]

ArMnBr Br Cross-coupling TMS

Ar Ar2Mn TMS II – [Ar2BrFe ]

Scheme 2. ProposedProposed catalytic catalytic cycle cycle for for the the ar aryl-alkenylyl-alkenyl cross-coupling between Ar2Mn and an alkenyl alkenyl bromide under Fe-catalytic conditions.

II Thanks to the steric hindrance inin thethe orthoortho positions,positions, thetheate ate[Mes [Mes33FeFeII]−– speciesspecies remains remains stable stable for for hours at 25 °C◦C[ [38,41].38,41]. Thus, Thus, the the use use of of a a mesityl mesityl nucleophile nucleophile in in the the mechanistic mechanistic experiments experiments discussed discussed II earlier preventsprevents any any degradation degradation of theof the Fe catalystFeII catalyst toward toward lower lower oxidation oxidation states. Instates. order In to delineateorder to delineatethe influence the ofinfluence the formation of the of lowerformation oxidation of lowe statesr oxidation on the system, states additional on the investigationssystem, additional were, investigationstherefore, carried were, out therefore, using PhMgBr carried as out a less usin hinderedg PhMgBr nucleophile as a less hindered [42]. nucleophile [42]. First, [Ph3FeII]− was generated at −20 °C by stoichiometric trans-metalation between FeCl2 and 3.0 equiv. of PhMgBr, and characterized by its 1H-NMR signals at 116 and −41 ppm. As we recently reported, [Ph3FeII]– is stable for more than 1 h at this temperature [40,41]. Its fate upon addition of an excess of the electrophile 3b (10 equiv.) was then monitored by paramagnetic 1H-NMR. [Ph3FeII]− reacted rapidly, as attested by the decrease of its resonances (ca. 75% of the starting [Ph3FeII]− reacted after 10 min). The reaction was quenched after 1 h, and the GC-MS confirmed formation of the cross- coupling product, which confirms that [Ph3FeII]− was able to react with 3b in a cross-coupling process, akin to [Mes3FeII]−. Moreover, several transient resonances in the −15/−5 ppm area could also be detected in the course of the reaction (see Figure 2). These elusive resonances quickly disappeared, and were not detected after 30 min at −20 °C. These signals echo the formation of (η2-alkene)n-Fe0 intermediates, as recently reported by Deng, which exhibit similar resonances [43]. This suggests that Fe0 species are formed in situ by 2-electron reductive elimination from [Ph3FeII]−, which is in agreement with a recent report by some of us demonstrating that the evolution of [Ph3FeII]− led to the formation of a distribution of Fe0 and FeI oxidation states (identified as (η4-arene)2Fe0 and [(η6- − arene)FeI(Ph)2] , “arene” being an aromatic ligand present in the bulk medium (e.g., C6H6 or C6H5- C6H5 coming from the oxidation of PhMgBr). Fe0 being preponderantly formed [40,41]). Those Fe0 intermediates would then be trapped by alkene ligands present in the bulk medium, which leads to the observed resonances.

Figure 2. 1H-NMR spectrum (recorded at −20 °C in d8-THF) of a 0.08 M solution of [Ph3FeII]− followed by addition of 3b (10 equiv.). Spectrum recorded 20 min after addition of 3b.

Then, the reactivity of the low valent Fe0 and FeI oxidation states in the reaction medium was investigated. Following one of our recent procedures, reduction of FeII into a distribution of Fe0 and FeI species was performed, by fast trans-metalation between FeCl2 and PhMgBr (2.0 equiv.) at room temperature [40,41]. After 10 min, 1.0 equiv. of MesMgBr was added. The 1H-NMR spectrum showed no signal in the 100–150 ppm area, which attests to the absence of any Mes-FeII species, which shows that all the starting FeII was reduced by PhMgBr (Figure 3a).

Molecules 2020, 25, 723 6 of 12

II – [Ar3Fe ]

ArMnBr Br Cross-coupling TMS

Ar Ar2Mn TMS II – [Ar2BrFe ]

Scheme 2. Proposed catalytic cycle for the aryl-alkenyl cross-coupling between Ar2Mn and an alkenyl bromide under Fe-catalytic conditions.

Thanks to the steric hindrance in the ortho positions, the ate [Mes3FeII]– species remains stable for hours at 25 °C [38,41]. Thus, the use of a mesityl nucleophile in the mechanistic experiments discussed earlier prevents any degradation of the FeII catalyst toward lower oxidation states. In order to delineate the influence of the formation of lower oxidation states on the system, additional Moleculesinvestigations2020, 25 ,were, 723 therefore, carried out using PhMgBr as a less hindered nucleophile [42]. 6 of 12 First, [Ph3FeII]− was generated at −20 °C by stoichiometric trans-metalation between FeCl2 and 3.0 equiv. of PhMgBr, and characterized by its 1H-NMR signals at 116 and −41 ppm. As we recently II First, [Ph3FeII –]− was generated at 20 ◦C by stoichiometric trans-metalation between FeCl2 and reported, [Ph3Fe ] is stable for more than− 1 h at this temperature [40,41]. Its fate upon addition of an 3.0 equiv. of PhMgBr, and characterized by its 1H-NMR signals at 116 and 41 ppm. As we recently excess of the electrophile 3b (10 equiv.) was then monitored by paramagnetic 1H-NMR. [Ph3FeII]− II − reported, [Ph3Fe ]− is stable for more than 1 h at this temperature [40,41]. Its fate upon additionII − of an reacted rapidly, as attested by the decrease of its resonances (ca. 75% of the starting [Ph3Fe ] reacted 1 II excessafter 10 of min). the electrophileThe reaction3b was(10 quenched equiv.) was after then 1 h, monitoredand the GC-MS by paramagnetic confirmed formationH-NMR. of [Phthe3 cross-Fe ]− II reacted rapidly, as attested by the decrease of itsII − resonances (ca. 75% of the starting [Ph Fe ]− reacted coupling product, which confirms that [Ph3Fe ] was able to react with 3b in a cross-coupling3 process, after 10 min). The reaction was quenched after 1 h, and the GC-MS confirmed formation of the akin to [Mes3FeII]−. Moreover, several transient resonances in the −15/−5 ppm area could also be II cross-couplingdetected in the product,course of which the reaction confirms (see that Figure [Ph3 Fe2). These]− was elusive able to resona react withnces3b quicklyin a cross-coupling disappeared, II process, akin to [Mes3Fe ]−. Moreover, several transient resonances in the 15/ 5 ppm area2 could also0 and were not detected after 30 min at −20 °C. These signals echo the formation− − of (η -alkene)n-Fe beintermediates, detected in theas recently course of reported the reaction by Deng, (see Figurewhich2 ex).hibit These similar elusive resonances resonances [43]. quickly This disappeared,suggests that 2 0 and0 were not detected after 30 min at 20 ◦C. These signals echo the formation of (IIη− -alkene)n-Fe Fe species are formed in situ by 2-electron− reductive elimination from [Ph3Fe ] , which is in intermediates, as recently reported by Deng, which exhibit similar resonances [43]. This suggests that agreement with a recent report by some of us demonstrating that the evolution of [Ph3FeII]− led to the Fe0 species are formed in situ by 2-electron reductive elimination from [Ph FeII] , which is in agreement formation of a distribution of Fe0 and FeI oxidation states (identified3 as (−η4-arene)2Fe0 and [(η6- II with a recent report− by some of us demonstrating that the evolution of [Ph Fe ] led to the formation arene)FeI(Ph)2] , “arene” being an aromatic ligand present in the bulk medium3 − (e.g., C6H6 or C6H5- of a distribution of Fe0 and FeI oxidation states (identified as (η4-arene) Fe0 and [(η6-arene)FeI(Ph) ] , C6H5 coming from the oxidation of PhMgBr). Fe0 being preponderantly2 formed [40,41]). Those 2Fe−0 “arene”intermediates being anwould aromatic then ligandbe trapped present by inalkene the bulk ligands medium present (e.g., in Cthe6H bulk6 or Cmedium,6H5-C6H which5 coming leads from to 0 0 the oxidationobserved resonances. of PhMgBr). Fe being preponderantly formed [40,41]). Those Fe intermediates would then be trapped by alkene ligands present in the bulk medium, which leads to the observed resonances.

1 II Figure 2. 1H-NMRH-NMR spectrum (recorded atat −20 °CC in dd8-THF) ofof aa 0.080.08 MM solutionsolution of of [Ph [Ph3FeFeII]]− followedfollowed − ◦ 8 3 − by addition of 3b (10 equiv.). SpectrumSpectrum recordedrecorded 2020 minmin afterafter additionaddition ofof 3b3b..

0 I Then, the reactivity of the low valentvalent FeFe0 and FeI oxidation states in the reaction medium was II 0 investigated. Following one of our recentrecent procedures,procedures, reductionreduction ofof FeFeII intointo aa distributiondistribution ofof FeFe0 and I FeI species was performed, by fast trans-metalation between FeCl2 and PhMgBr (2.0 equiv.) at room 1 temperature [[40,41].40,41]. After 10 min, 1.0 equiv. of MesMgBr waswas added.added. The 1H-NMRH-NMR spectrum spectrum showed II no signal in the 100–150 ppm area, which attests toto thethe absenceabsence ofof anyany Mes-FeMes-FeII species, which shows II that all the starting FeII was reduced by PhMgBr (Figure3a). Moleculesthat all the2020 starting, 25, 723 Fe was reduced by PhMgBr (Figure 3a). 7 of 12

1 Figure 3. 1H-NMRH-NMR spectra spectra (recorded (recorded at 25 °C◦C in d8-THF)-THF) of of a a 0.08 0.08 M M solution solution of ( a) FeCl 2 ++ 2.02.0 equiv. equiv. PhMgBr, ++ 1.01.0 equiv.equiv. MesMgBr MesMgBr after after 10 10 min min agitation agitation at RT.at RT. (b) ( Sameb) Same tube, tube,+ 3.0 + equiv.3.0 equiv.3b, after 3b, after 30 min. 30 min. The addition of 3.0 equiv. of the electrophile 3b to the in situ generated solution of Fe0 and FeI 1 speciesThe led addition to a color of 3.0 change equiv. of of the the sample, electrophile which 3b turned to the from in situ dark generated brown to solution yellow. Theof Fe0H-NMR and FeI spectrumspecies led showed to a color that, change after of 30 the min, sample, ca. 20% which of the turned iron from contained dark brown in the solutionto yellow. was The converted 1H-NMR II intospectrum [Mes 3showedFe ]− (Figure that, after3b). 30 The min, presence ca. 20% ofof the3b ,iron therefore, contained allows in the a re-oxidationsolution was ofconverted the reduced into 0 I II Fe[Mesand3Fe/IIor]− (Figure Fe species 3b). toThe the presence Fe oxidation of 3b, therefore, state, the allows latter beinga re-oxidation trapped of by the trans-metalation reduced Fe0 and/or with FeI species to the FeII oxidation state, the latter being trapped by trans-metalation with MesMgBr to afford [Mes3FeII]−. The re-oxidation of low iron oxidation states by 3b to the FeII stage was also confirmed by the observation of bis(trimethylsilyl)butadienes TMS-CH=CH-CH=CH-TMS (TMS- (CH)4-TMS, E/E; Z/E; Z/Z) in GC-MS, after catalytic reactions involving 10 mol% of FeCl2, PhMgBr, and 3b as coupling partners. Formation of TMS-(CH)4-TMS undoubtedly comes from the sacrificial monoelectronic reduction of the electrophile that permits re-oxidation of the low Fe0 and/or FeI oxidation states. TMS-(CH)4-TMS, moreover, also appears as a suitable ligand for Fe0 oxidation state, and a (η4-TMS-(CH)4-TMS)Fe0 complex might, thus, contribute to the group of high field resonances in the in the −15/−5 ppm area (Figure 2). Quantity of detected TMS-(CH)4-TMS represents ca. 10% of the quantity of a detected coupling product, which shows that this off-cycle sacrificial reduction pathway is not preponderant. By comparison, no traces of TMS-(CH)4-TMS were detected when using mesityl nucleophiles (conditions of Figure 1), attesting that no sacrificial 1-electron reduction of 3b by oxidation states lower than FeII formed in situ occurred. Scheme 3 presents a summary of the competitive reactions that were observed in this work during the Fe-catalyzed coupling of Ph2Mn with (2-bromovinyl)-trimethylsilane (3b), taking into account the possibility of an off-cycle process involving in situ formed low iron oxidation states.

Scheme 3. Proposed catalytic cycle and side reactions for the aryl-alkenyl cross-coupling between

Ph2Mn and an alkenyl bromide under Fe-catalytic conditions.

Kinetic studies will further be pursued in order to determine the global kinetics of the aryl- alkenyl cross-coupling reaction, and to examine the possibility for the low Fe0 and FeI oxidation states involved in a cross-coupling catalytic cycle, in addition to the off-cycle sacrificial reduction of the alkenyl electrophile evidenced herein. Such studies will also help analyze the mechanism of the

Molecules 2020, 25, 723 7 of 12

Figure 3. 1H-NMR spectra (recorded at 25 °C in d8-THF) of a 0.08 M solution of (a) FeCl2 + 2.0 equiv. PhMgBr, + 1.0 equiv. MesMgBr after 10 min agitation at RT. (b) Same tube, + 3.0 equiv. 3b, after 30 min.

The addition of 3.0 equiv. of the electrophile 3b to the in situ generated solution of Fe0 and FeI species led to a color change of the sample, which turned from dark brown to yellow. The 1H-NMR spectrumMolecules 2020 showed, 25, 723 that, after 30 min, ca. 20% of the iron contained in the solution was converted7 into of 12 [Mes3FeII]− (Figure 3b). The presence of 3b, therefore, allows a re-oxidation of the reduced Fe0 and/or FeI species to the FeII oxidation state, the latter being trapped by trans-metalation with MesMgBr to II II affordMesMgBr [Mes to3Fe affIIord]−. The [Mes re-oxidation3Fe ]−. The of re-oxidation low iron oxidation of low iron states oxidation by 3b states to the by Fe3bII tostage the Fewasstage also confirmedwas also confirmed by the observation by the observation of bis(trimethylsilyl)butadienes of bis(trimethylsilyl)butadienes TMS-CH=CH-CH=CH-TMS TMS-CH=CH-CH=CH-TMS (TMS- (CH)(TMS-(CH)4-TMS,4 E-TMS,/E; Z/E;/ EZ;/Z)/ Ein; ZGC-MS,/Z) in GC-MS, after catalytic after catalyticreactions reactions involving involving 10 mol% 10of FeCl mol%2, PhMgBr, of FeCl2, andPhMgBr, 3b as andcoupling 3b as partners. coupling Formation partners. of Formation TMS-(CH) of4-TMS TMS-(CH) undoubtedly4-TMS undoubtedlycomes from the comes sacrificial from 0 monoelectronicthe sacrificial monoelectronic reduction of the reduction electrophile of the that electrophile permits thatre-oxidation permits re-oxidationof the low Fe of0 theand/or low FeFeI I 0 oxidationand/or Fe states.oxidation TMS-(CH) states.4-TMS, TMS-(CH) moreover,4-TMS, also moreover, appears as also a suitable appears ligand as a suitablefor Fe0 oxidation ligand for state, Fe 4 0 andoxidation a (η4-TMS-(CH) state, and4 a-TMS)Fe (η -TMS-(CH)0 complex4-TMS)Fe might, thus,complex contribute might, to thus, the contributegroup of high to the field group resonances of high field resonances in the in the 15/ 5 ppm area (Figure2). Quantity of detected TMS-(CH) -TMS in the in the −15/−5 ppm area (Figure− − 2). Quantity of detected TMS-(CH)4-TMS represents ca. 10%4 of therepresents quantity ca. of 10% a detected of the quantity coupling of product, a detected which coupling shows product, that this which off-cycle shows sacrificial that this reduction off-cycle pathwaysacrificial is reduction not preponderant. pathway is notBy comparison, preponderant. no By traces comparison, of TMS-(CH) no traces4-TMS of TMS-(CH)were detected4-TMS when were usingdetected mesityl when nucleophiles using mesityl (conditions nucleophiles of (conditions Figure 1), attesting of Figure 1that), attesting no sacrificial that no 1-electron sacrificial 1-electronreduction II ofreduction 3b by oxidation of 3b by states oxidation lower states than lower FeII formed than Fe in situformed occurred. in situ occurred. SchemeScheme 33 presents presents a summarya summary of theof the competitive competitive reactions reactions that werethat observedwere observed in this workin this during work duringthe Fe-catalyzed the Fe-catalyzed coupling coupling of Ph2Mn of with Ph2 (2-bromovinyl)-trimethylsilaneMn with (2-bromovinyl)-trimethylsilane (3b), taking (3b into), taking account into the accountpossibility the of possibility an off-cycle of processan off-cycle involving process in invo situlving formed in lowsitu ironformed oxidation low iron states. oxidation states.

Scheme 3. ProposedProposed catalytic catalytic cycle cycle and and side reactions for the aryl-alkenyl cross-coupling between

Ph22MnMn and and an an alkenyl alkenyl bromide bromide under under Fe-catalytic Fe-catalytic conditions. conditions.

Kinetic studiesstudies willwill further further be be pursued pursued in orderin order to determine to determine the globalthe global kinetics kinetics of the aryl-alkenylof the aryl- alkenylcross-coupling cross-coupling reaction, reaction, and to and examine to examine the possibility the possibility for thefor the low low Fe 0Feand0 and Fe FeI Ioxidation oxidation states involvedinvolved in in a a cross-coupling catalytic catalytic cycle, cycle, in in addition addition to to the the off-cycle off-cycle sacrificial sacrificial reduction of of the alkenyl electrophile evidenced herein. Such Such studies studies will will also also help help analyze analyze the the mechanism of of the activation of the C-X bond of the alkenyl halide. Isomerization toward the sterically more stable E coupling products may suggest the implication of an iron-based radical activation of the alkenyl halide, as observed in the case of alkyl electrophiles [44], albeit formation of the Csp2-centered radical is generally more energetically-demanding. Additionally, it cannot be excluded in an alternative scenario that isomerization of the C=C bond occurs after the coupling step, akin to the observations made by Jacobi von Wangelin for the iron-catalyzed isomerization of Z-olefins to their E analogues [45].

4. Materials and Methods

4.1. Materials and Instruments All reactions, except otherwise noted, were carried out in flame-dried glassware equipped with magnetic stirring under an argon atmosphere using standard Schlenk techniques. To transfer solvents or reagents, syringes were used, which were purged three times with argon prior to use. After purification by flash column chromatography, products were concentrated using a rotary Molecules 2020, 25, 723 8 of 12 evaporator and, subsequently, dried under high vacuum. Indicated yields are isolated yields of 1 compounds estimated to be >95% pure, as determined by H-NMR (25 ◦C) and capillary GC. To examine the reaction progress of the performed reactions, GC-analysis of quenched hydrolyzed and iodolyzed reaction aliquots relative to an internal standard was used. For this purpose, small amounts of the reaction mixture were hydrolyzed using a saturated aqueous solution of NH4Cl, subsequently extracted with EtOAc, dried over MgSO4 and gaschromatographically quantified. To monitor the process of directed metalations and oxidative insertion reactions, small amounts of the reaction mixture were iodolyzed. A small quantity of iodine was dissolved in freshly distilled THF (0.50 mL), charged with the reaction mixture, and added to a solution of Na2S2O3. The mixture was extracted with EtOAc, dried over MgSO4, and was then gas chromatographically measured. To determine the concentration of the different synthesized metallic reagents, iodometric titration was used. For this purpose, a known amount of iodine was charged with freshly distilled THF (1.00 mL) to give a deep red solution. The metallic reagent was added dropwise at 2 ◦C to the iodine solution until the red coloration went colorless. The concentration of the organometallic reagent could be calculated via the consumed volume of the reaction mixture and the amount of used iodine. Thin layer chromatography (TLC) was implemented on alumina plates coated with SiO2 (Merck 60, F-254, Merck, Darmstadt, Germany). To visualize the spots of the different products, UV light was used. Flash column chromatography was performed using SiO2 (0.04–0.06 mm, 230–400 mesh) from Merck. 1H-NMR, 13C-NMR, 19F-NMR, and 2D-NMR spectra were recorded on VARIAN Mercury 200, BRUKER ARX 300, VARIAN VXR 400 S, and BRUKER AMX 600 instruments (Bruker, Billerica, MA, USA). Chemical shifts are reported as δ-values in ppm relative to tetramethylsilane. The following abbreviations were used to characterize signal multiplicities: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and bs (broad singlet). Mass spectroscopy: High resolution (HRMS) and low resolution (MS) spectra were recorded on a FINNIGAN MAT 95Q instrument (now Thermo Fisher company, Waltham, MA, USA). Electron impact ionization (EI) was conducted with an ionization energy of 70 eV.For coupled gas chromatography/mass spectrometry, a HEWLETT-PACKARD HP 6890 /MSD 5973 GC/MS system was used. Molecular fragments are reported starting at a relative intensity of 10%. 1 1 Infrared spectra (IR) were recorded from 4500 cm− to 650 cm− on a PERKIN ELMER Spectrum BX59343 instrument (Perkin Elmer, Wellesley, MA, USA). For detection, a SMITHS DETECTION DuraSamplIR IIDiamond ATR sensor (Smiths Detection, Hemel Hempstead, UK) 1 was used. Wavenumbers are reported in cm− starting at an absorption of 10%. Melting points (m.p.) were determined on a BÜCHI B-540 melting point apparatus (BÜCHI LabortechnikAG, Flawil, Switzerland) and are uncorrected. Compounds decomposing upon melting are indicated by (decomp.). Gas chromatography was executed with machines of type Agilent Technologies 7890A GC-Systems with 6890 GC inlets, detectors (Agilent, Santa Clara, CA, USA), a GC oven, and a column of type HP 5 (Hewlett-Packard, 5% phenylmethylpolysiloxane; length: 10 m, diameter: 0.25 mm, film thickness: 0.2 µm). Gas chromatography-Mass spectra were recorded on a networking system called Hewlett-Packard 6890/MSD 5973 GC/MS (Hewlett Packard, Palo Alto, CA, USA) with a column of type HP 5 (Hewlett-Packard, 5% phenylmethylpolysiloxane; length: 10m, diameter: 0.25 mm, film thickness: 0.2 µm).

4.2. Chemicals, Solvents, and Typical Procedures All chemicals were purchased from commercial sources and were used without any further purification unless otherwise noted. Molecules 2020, 25, 723 9 of 12

THF was continuously refluxed and freshly distilled from benzophenone ketyl under nitrogen. The freshly distilled THF was stored over a molecular sieve (4 Å) under argon. Solvents for column chromatography were distilled prior to use.

4.2.1. Typical Procedure for the One-Pot Preparation of Bis-(aryl)manganese Reagents 1a–g A dry and argon-flushed Schlenk-tube, equipped with a magnetic stirring bar and a rubber septum, was charged with LiCl (0.610 g, 14.4 mmol, 2.4 equiv.), heated to 450 ◦C under high vacuum, and then cooled to room temperature. After being switched to argon, the same procedure was applied after MnCl2 was added (453 mg, 3.60 mmol, 0.6 equiv.). After cooling to room temperature, magnesium turnings were added (0.350 g, 14.4 mmol, 2.4 equiv.), which was followed by freshly distilled THF (12 mL). After the reaction mixture was cooled to 5 C, the aryl bromides 2a–g were then added − ◦ dropwise using 1 mL syringes (6.0 mmol, 1.0 equiv., addition time: 1 min) and the reaction mixture was stirred until a complete conversion of the starting material was observed. The reaction progress was monitored by GC-analysis of hydrolyzed and iodolyzed aliquots. When the metalation was completed, the concentration of the bis-(aryl)manganese species was determined by titration against iodine in freshly distilled THF. The black solutions of the aryl reagents 1a–g were then separated from the magnesium turnings using a syringe and, subsequently, transferred into another pre-dried and argon-flushed Schlenk-tube, which was cooled to 5 C. After a titration − ◦ against iodine in freshly distilled THF was performed, the reagent was ready to use for Cross-Couplings.

4.2.2. Typical Procedure for the Cross-Coupling Reactions of Bis-(aryl)manganese Reagents 1a–g with Different Electrophiles 3a–e A pre-dried and argon-flushed Schlenk-tube equipped with a magnetic stirring bar and a rubber septum was charged with Fe(acac)3 (35 mg, 0.10 mmol, 10 mol%), the corresponding electrophile (3a–e, 1.0 mmol, 1.0 equiv.), tetradecane as internal standard (50 µL) and freshly distilled THF (1.0 mL) as solvent. The reaction mixture was cooled to 0 ◦C and the bis-(aryl)manganese solution (1a–g, 0.6 equiv.) was added dropwise whereupon a color change to dark brown could be recognized. After the addition was complete, the reaction mixture was stirred for a given time at room temperature and the completion of the cross-coupling reaction was monitored by GC-analysis of hydrolyzed aliquots. Thereupon, a saturated aqueous solution of NH4Cl was added and the aqueous layer was extracted with EtOAc (3 100 mL). The combined organic layers were dried over MgSO , filtered, and concentrated under × 4 reduced pressure. Purification of the crude products by flash column chromatography afforded the desired cross-coupling reaction products (4a–k, 4m, 4n).

4.3. Studies on the Catalytically Active Species and Catalytic Cycle All the samples were prepared in a recirculating JACOMEX inert atmosphere (Ar) drybox and vacuum Schlenk lines. Glassware was dried overnight at 120 ◦C before use. NMR spectra were obtained using a Bruker DPX 400 MHz spectrometer (Bruker, Billerica, MA, USA). Chemical shifts for 1H-NMR spectra were referenced to solvent impurities (herein, THF). NMR tubes were equipped with a J. Young valves were used for all 1H-NMR experiments and catalytic tests. The GC-MS analysis was performed using n-decane as an internal standard. The reaction media aliquots were quenched by the addition of distilled water under air. The organic products were extracted using DCM, and injected into the GC-MS. Mass spectra were recorded on a Hewlett-Packart HP 5973 mass spectrometer (Hewlett Packard, Palo Alto, CA, USA) via a GC-MS coupling with a Hewlett-Packart HP 6890 chromatograph (Hewlett Packard, Palo Alto, CA, USA) equipped with a capillary column HP-5MS (50 m 0.25 mm × × 0.25 µm, Hewlett Packard, Palo Alto, CA, USA). Ionisation was due to an electronic impact (EI, 70 eV).

5. Conclusions In summary, various functionalized bis-(aryl)manganese species have been readily prepared in one-pot conditions from the corresponding aryl bromides by inserting magnesium in the presence of Molecules 2020, 25, 723 10 of 12

LiCl and in situ trans-metalation with MnCl in THF at 5 C within 2 h. These bis-(aryl)manganese 2 − ◦ reagents have been allowed to undergo smooth iron-catalyzed cross-couplings using 10 mol% Fe(acac)3 and various functionalized alkenyl iodides and bromides at 25 ◦C for 1 h. Mechanistic investigations 1 II carried out by H-NMR showed that ate-iron(II) species [Ar3Fe ]− are formed by trans-metalation of the bis-(aryl)manganese reagent with the iron catalyst, and that they can react with alkenyl bromides to afford the expected cross-coupling product. Low-valent Fe0 and FeI oxidation states can also be formed by the reduction of the ate-iron(II) catalyst under these conditions. This leads to the sacrificial reduction of the alkenyl electrophile via an off-cycle pathway, which partly regenerates the FeII oxidation state, where the latter is able to enter a new catalytic cycle.

Supplementary Materials: The following are available online. Additional synthesis and characterization (NMR, IR, HRMS, m.p.) data are available online. Author Contributions: Conceptualization, G.L. and P.K. Methodology, A.D. and L.R. Writing—original draft preparation, G.L., L.R., and A.D. Writing—review and editing, G.L. and P.K. Supervision, G.L. and P.K. Project administration, G.L. and P.K. Funding acquisition, G.L. and P.K. All authors have read and agreed to the published version of the manuscript. Funding: This work was supported by the CNRS, Chimie ParisTech (Paris), and LMU (Munich) in the framework of the International Associated Laboratory IrMaCar. Acknowledgments: We thank the DFG (SFB749) for financial support, and Albemarle (Germany) and BASF (Ludwigshafen, Germany) for the generous gift of chemicals. G.L. also thanks the ANR research program (project JCJC SIROCCO). Aurélien Adenot (CEA Saclay) is warmly thanked for his kind technical assistance. Conflicts of Interest: The authors declare no conflict of interest.

References and Notes

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Sample Availability: Samples of all the compounds described in this article are available from the authors.

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