Stepwise alkyne insertion in Au(i) acetylides: influence of the nuclearity

S epwise alkyne inse ion in Au(I) ace ylides: influence o he nuclea i y† Juan Cayuela-Cas illo, a F ancisco J. Fe n´ andez-de-C´ o do a, a Ma hew S. See, b Is ael Fe n´ andez * c and Pablo R´ ıos * a The eac ion be ween NHC-suppo ed (NHC =N-he e ocyclic ca bene) gold(I) ime hylsilylace ylide complexes wi h NHC gold(I) hyd oxide species ende s diffe en symme ical homobime allic Au complexes. These compounds eadily unde go mig a o y inse ion o DMAD (dime hyl ace ylenedica boxyla e) a 25 °C o gi e he co esponding bime allic enyne p oduc s. On he con a y, monome allic analogues equi e much mo e o cing condi ions (excess o DMAD and empe a u e $110 °C) o gi e he same ans o ma ion. Expe imen al and compu a ional s udies e eal ha he second me al agmen is esponsible o he enhanced nucleophilici y o he eac i e ca bon a om o he ace ylide C^C bond, which ini ially leads o a mo e a o able in e ac ion wi h DMAD in he a e- de e mining s ep o an unp eceden ed, s epwise mechanism whe e he labili y o he Au–C bonds plays an ins umen al ole. The enhanced eac i i y displayed by he bime allic species was le e aged in he inse ion o o he subs a es such as he e ocumulenes. In oduc ion Since he  s obse a ion ha ca ionic gold(I) complexes elec- ophilically ac i a e unsa u a ed C–C bonds upon binding, 1 he u iliza ion o gold(I) in homogeneous ca alysis has g own exponen ially o e he las couple o decades. The p-coo dina- ion ende s he sys em suscep ible o nucleophilic a ack and has led o a my iad o o ganic ans o ma ions. 2 This p ocess ypically equi es a acan posi ion a he ca ionic gold(I) species o coo dina ion o he p-subs a e, which would imply ha neu al, coo dina i ely sa u a ed gold(I) complexes a e, in p inciple, un eac i e, acco ding o his eac i i y pa e n. Howe e , ecen disco e ies ha e demons a ed ha hese ypes o gold compounds can also unde go elemen a y s eps ypical o ansi ion me als, such as oxida i e addi ion, educ i e elimi- na ion, and/o mig a o y inse ion. 3 In he la e case, only a ew examples ha e been published. 4 In 2007, Sadighi and co- wo ke s desc ibed he e e sible inse ion o diffe en in e nal alkynes in o he gold–uo ine bond o SIP AuF (SIP =1,3- bis(2,6-diisop opylphenyl)imidazolin-2-ylidene) o gi e he co esponding ans p oduc . 5 The p oposed mechanism in ol es uo ide displacemen by he alkyne ollowed by nucleophilic addi ion o he coo dina ed iple bond, hus explaining he ans o ien a ion. Con e sely, he  s example o asyn inse ion was epo ed by Amgoune and Bou issou, whe e phosphine-suppo ed gold(I) silyl species yielded b-silyl inyl- gold p oduc s in a s e eo- and egioselec i e manne . 6 No ably, eplacing he phosphine agmen wi h an NHC ligand ga e ise o he inse ion p oduc wi h opposi e egioselec i i y, p esumably due o s e ic ac o s. 7 None heless, he majo i y o he examples desc ibed in he li e a u e equi e elec on- decien alkynes such as DMAD o a success ul mig a o y inse ion e en , some o which a e summa ized in Fig. 1. Indeed, IP AuH (IP =1,3-bis(2,6-diisop opylphenyl)imidazol-2- ylidene) does no eac wi h 3-hexyne o diphenylace ylene, bu i cleanly eac s wi h DMAD, gi ing he co esponding inylgold complex wi h a ans a angemen o he es e g oups (Fig. 1A). 8 This is unusual gi en ha he es o he examples exhibi a cis geome y. Based on kine ic and compu a ional s udies, Miqueu, Amgoune and Bou issou p oposed a wo-s ep mechanism o he DMAD inse ion in o Au–Si bonds, whe e he alkyne  s coo dina es o gold (p-complex) ollowed by a conce ed cis inse ion s ep (Fig. 1B). Howe e , his species is accompanied by an app oxima ely equal amoun o he Au–P inse ion p oduc . This complex seems o be he esul o phosphine dissocia ion, Michael addi ion o DMAD, and a ack o he esul ing phosphonium enola e o he gold silyl agmen . 9 The non-innocen cha ac e o Au–P bonds in he inse ion o alkynes was also epo ed by Kuniyasu and Kambe o (Ph 3 P) AuSPh species. Ins ead o obse ing he expec ed Au–S inse ion a Ins i u o de In es igaciones Qu´ ımicas (IIQ), Depa amen o de Qu´ ımica Ino g´ anica, Cen o de Inno aci´ on en Qu´ ımica A anzada (ORFEO-CINQA), CSIC and Uni e sidad de Se illa, 41092 Se illa, Spain. E-mail: [email p o ec ed] b Depa men o Chemis y, Uni e si y o Cali o nia, Be keley, Be keley, CA, 94720, USA c Depa amen o de Qu´ ımica O g´ anica I and Cen o de Inno aci´ on en Qu´ ımica A anzada (ORFEO-CINQA), Facul ad de Qu´ ımicas, Uni e sidad Complu ense de Mad id, Mad id 28040, Spain. E-mail: is [email protected] †Elec onic supplemen a y in o ma ion (ESI) a ailable. CCDC 2372473–2372479, 2403953 and 2407558. Fo ESI and c ys allog aphic da a in CIF o o he elec onic o ma see DOI: h ps://doi.o g/10.1039/d4sc08227c Ci e his: Chem. Sci.,2025,16, 4684 All publica ion cha ges o his a icle ha e been paid o by he Royal Socie y o Chemis y Recei ed 4 h Decembe 2024 Accep ed 8 h Feb ua y 2025 DOI: 10.1039/d4sc08227c sc.li/chemical-science 4684 |Chem. Sci.,2025,16,4684–4694 © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chemical Science EDGE ARTICLE Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online View Jou nal | View Issue p oduc (in ag eemen wi h hei p e ious esul s wi h Pd and P ), he zwi e ionic alkenylphospho us species depic ed in Fig. 1C was egioselec i ely ob ained, a ibu ed o a conce ed inne -sphe e a ack o PPh 3 o he alkyne moie y bound o gold. 10 Simila ly, S ockland J and co-wo ke s obse ed Z- inyl- gold o ma ion upon DMAD inse ion on gold(I) phosphi e compounds (Fig. 1D). 11 While all hese examples p o ide de ailed and use ul in o ma ion abou alkyne inse ion in o Au– X(X=H o he e oa om) bonds, hey a e all es ic ed o monome allic gold(I) complexes. Conside ing he ole o bime allic species in ca alysis, 12 especially in he case o digold complexes, 13 i seems necessa y o de elop dinuclea a chi ec- u es o s udy he ac o s go e ning his elemen a y s ep in o ganogold sys ems. To his end, bime allic gold ace ylides suppo ed by NHC ligands (NHC–Au–C^C–Au–NHC) we e chosen as pla o ms o his s udy. Dinuclea gold(I) ace ylides ha e been known o se e al decades, and hei pho ophysical p ope ies ha e been s udied in de ail because o he in e es in C n -b idged mul inuclea ino ganic species om he poin o iew o molecula elec onics and nonlinea op ical ma e ials. 14 Howe e , he eac i i y o dinuclea gold(I) ace ylides emains essen ially unde explo ed, which sha ply con as s wi h ligh e g oup 11 congene s such as Cu 2 C 2 , an ac i e ca alys o a numbe o e hynyla ion p ocesses (i.e., Reppe chemis y). 15 He ein, we p esen he p epa a ion and cha ac e iza ion o digold(I) ace ylides and hei eac i i y wi h DMAD. While a sub le modica ion on he ligand scaffold esul s in diffe en kine ics o inse ion, a p onounced dispa i y in eac ion a es is obse ed be ween bi- and monome allic complexes. A a ion- aliza ion o his diffe en beha io is p o ided based on Densi y Func ional Theo y (DFT) calcula ions, as well as an unp eceden ed, s epwise mechanism o he alkyne inse ion in o he Au–C bonds o he syn hesized complexes. In ligh o he enhanced eac i i y exhibi ed by he bime allic species, a a ie y o subs a es was also in es iga ed. Resul s and discussion Syn hesis and ini ial eac i i y s udies Ini ial syn he ic s udies we e ca ied ou wi h gold(I) species suppo ed by he IP ligand. The u iliza ion o IP AuX species is based on hei wide applicabili y, hei ease o p epa a ion, 16 and he s onge bond o NHCs wi h gold compa ed o phos- phine ligands. Simila o p e ious s udies epo ed o coppe (I) species, 17 he in oduc ion o a ime hylsilylace ylene agmen on gold would p o ide he C 2 agmen oge he wi h a lea ing g oup ha can be displaced by an app op ia e nucleophilic Au(I) syn hon. This app oach would cons i u e a modula syn he ic pa hway o bime allic Au(I)-based ace ylides, hus a oiding ace ylene gas 14 and opening he possibili y o de eloping unsymme ical complexes. S a ing om chlo ide complex 1 16 (Scheme 1), addi ion o LiC^CSiMe 3 in oluene esul ed in he p ecipi a ion o LiCl oge he wi h he o ma ion o a soluble alkynyl complex 3, which could be isola ed as a colo less solid in 91% isola ed yield. Diagnos ic e idence o he o ma ion o he desi ed p oduc was obse ed by NMR ( esonances a 0.05 and −25.8 ppm in he 1 H and 29 Si– 1 H HMBC spec a, espec i ely) and IR spec oscopy (n C^C =2054 cm −1 ). Addi ionally, c ys als o 3sui able o single-c ys al X- ay diff ac ion we e ob ained om a n-pen ane solu ion a −30 °C, allowing o he con - ma ion o he expec ed assignmen (see ESI†). F om complex 3, he o ma ion o a bime allic ace ylide was pu sued using IP AuOH 5 18 so ha he o ma ion o Me 3 SiOH ac s as a d i ing o ce in he ans o ma ion. Ini ially, no eac ion akes place a 25 °C acco ding o he 1 H NMR spec um o he eac ion Fig. 1 Examples o Au(I) complexes de i ed om DMAD inse ion. Scheme 1 Syn hesis o bime allic ace ylides 7and 8. Isola ed yields in pa en heses. Fig. 2 Solid-s a e s uc u e o bime allic ace ylide 7(50% p obabili y ellipsoids). H a oms a e omi ed and 2,6-diisop opylphenylg oups a e ep esen ed as capped s icks o cla i y. © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chem. Sci.,2025,16,4684–4694 | 4685 Edge A icle Chemical Science Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online mix u e. Howe e , hea ing he solu ion o 100 °C o 15 h led o he comple e consump ion o bo h eagen s in a o o a new symme ical species, in line wi h he expec ed bime allic complex 7(Scheme 1). S uc u al con ma ion came om single-c ys al X- ay diff ac ion analysis o colo less c ys als g own om diffusion o n-pen ane in o a benzene solu ion o 7 (Fig. 2). The solid-s a e s uc u e exhibi s an almos coplana o ien a ion o he IP imidazole ings (:N1–C2–C20 –N10= 12.7(3)°) and a linea a angemen along he ace ylide axis (:C2–Au1–C1 and :Au1–C1–C10=175°). The Au1–C1 and C1– C10bond dis ances (1.991(3) and 1.194(3) Å, espec i ely) all wi hin he ange obse ed o o he bime allic Au(I) ace ylides. 14 The cen osymme ic cha ac e o 7leads o a silen n C^C s e ch by IR spec oscopy, ye Raman measu emen s exhibi a s ong peak a 2012 cm −1 , in good ag eemen wi h phosphine- suppo ed analogues. 14 Reac i i y s udies we e conduc ed wi h 7 and alkynes wi h diffe en elec onic p ope ies (Scheme 2). An excess (4 equi .) o 3-hexyne did no eac wi h 7ae 16 h a 80 ° CinC 6 D 6 (Fig. S62†), which is in s a k con as o ha obse ed by Sadighi and co-wo ke s o Au–F species. 5 On he o he hand, ace ylene gas (1.5 ba ) cleanly eac s wi h 7unde simila (80 °C in C 6 D 6 ) eac ion condi ions o selec i ely yield he e minal alkyne complex IP AuCCH (9), 19 con med by an independen syn hesis using 1and MgB CCH (Fig. S63†). Al hough his eac ion has no been explo ed in de ail, he ini ial s eps o his ans o ma ion migh nd hei o igin in he acidi y o he ace ylene C–H bonds 20 and he inc eased elec on densi y o he p-sys em o 7. Indeed, a ela ed bime allic Au(I) ace ylide complex exhibi s up o ou T-shaped and o hogonal C–H/p in e ac ions be ween he iple bond and he C–H bond o ou CHCl 3 molecules. 14c The au ho s a ibu ed hese s ong in e - ac ions o he acidi y o he C–H bonds o he sol en and he elec on ichness o he alkyne p o ided by he dona ion o he gold a oms. The e o e, an elec on-decien alkyne such as DMAD was in es iga ed nex , based on he examples desc ibed in Fig. 1. Addi ion o DMAD o complex 7in C 6 D 6 a 25 °C esul ed in he p og essi e o ma ion o wo new se s o signals in he 1 H NMR spec um o he IP ligands in a 1 : 1 a io, consis en wi h he unsymme ical p oduc 10 (Scheme 2). These esonances a e accompanied by wo new single s a 3.1 and 3.5 ppm in eg a ing o 3 p o ons each, which sugges s he inco po a ion o 1 equi . o DMAD in o he unsymme ical s uc u e. The eac ion can be accele a ed by hea ing he mix u e o 60 °C, leading o he ull consump ion o 7in a o o he a o emen ioned signals o complex 10. Vapo diffusion o n- pen ane in o he eac ion mix u e a 25 °C affo ded colo less c ys als sui able o single-c ys al X- ay analysis. Fig. 3 shows he solid-s a e s uc u e o he inse ion p oduc 10, e ealing a bime allic enyne s uc u e wi h a cis o ien a ion o he IP Au agmen s and es e g oups, in line wi h he majo i y o exam- ples desc ibed in Fig. 1 (C–C bond dis ances (C1–C2 =1.20(1) Å, C2–C3 =1.442(8) Å, C3–C4 =1.34(1)) and angles (:C1–C2–C3 =173.9(8)°, :C2–C3–C4 =122.2(6)°)). Le e aging he syn he ic s a egy employed o he p epa a ion o 7(Scheme 1), he syn hesis o a diffe en bime allic Au(I) ace ylide complex was pu sued. In o de o e alua e he effec o he p-elec on densi y on he inse ion o DMAD, a minimal s uc u al modica ion was ca ied ou o modi y he elec onic p ope ies o he NHC ligand while keeping he s e ic demand a ound he AuCCAu moie y unal e ed. To his end, ace ylide 8was en isaged (Scheme 1). 21 Complex 8is iden ical o 7, ye he IP backbone has been eplaced by he sa u a ed e sion SIP , which would, in p inciple, inc ease he elec on densi y o he C^C bond. 21 The ime hylsilylace ylide gold(I) p ecu so 4was ob ained in e y good yield (88%) om he co esponding chlo ide complex 2. Then, bime allic assembly was ca ied ou by eac ion wi h SIP AuOH species 6upon hea ing, as depic ed in Scheme 1. Bime allic ace ylide 8was isola ed as colo less c ys als in 84% yield ae laye ing n-pen ane o e a THF solu ion o he complex a 25 °C. 1 H NMR analysis o he isola ed ma e ial ag ees well wi h he expec ed p oduc (Fig. S14†), and single- c ys al X- ay diff ac ion analysis allows i s iden ica ion in he solid s a e, as depic ed in Fig. 4. Simila o species 7, complex 8 possesses a coplana o ien a ion o he imidazole moie ies (:N1–C2–C20 –N10=1.8(2)°). Ne e heless, he longe C^C bond dis ance in he solid-s a e s uc u e (1.215(3) Å) and lowe n C^C s e ch (2003 cm −1 , Raman spec oscopy) compa ed o 7 Scheme 2 Explo a o y eac i i y s udies be ween ace ylide 7and alkynes. Fig. 3 Solid-s a e s uc u e o bime allic enyne 10 (50% p obabili y ellipsoids). H a oms a e omi ed and 2,6-diisop opylphenylg oups a e ep esen ed as capped s icks o cla i y. 4686 |Chem. Sci.,2025,16,4684–4694 © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chemical Science Edge A icle Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online poin o a sligh ly weake iple bond ( ide in a). 1 H NMR analysis o he eac ion mix u e be ween 8and DMAD e eals p og essi e ans o ma ion o an unsymme ical species 11,as e idenced by he wo se s o imidazole and es e esonances in a 1 : 1 a io. Fu he cha ac e iza ion expe imen s o 11 a e in ag eemen wi h he inse ion o 1 equi alen o DMAD, simila o ha obse ed o complex 7(Fig. S20 and S21†) Kine ic s udies: ligand and nuclea i y effec s In o de o in es iga e u he de ails o he DMAD inse ion, kine ic s udies we e pe o med. Ini ial expe imen s we e con- duc ed in C 6 D 6 wi h pa en ace ylide 7unde pseudo- s -o de condi ions ([DMAD] $10 equi alen s), which indica e ha he eac ion is  s -o de wi h espec o he bime allic complex (see ESI†). De e mina ion o k obs a diffe en empe a u es (25, 30, 35 and 40 °C) and Ey ing analysis affo ded an ac i a ion en halpy DH ‡ =18.1 (±0.3) kcal mol −1 and a nega i e ac i a ion en opy DS ‡ =−15.0 (±1.0) cal mol −1 K −1 , he la e sugges ing an associa i e p ocess in he a e-de e mining s ep (Fig. 5). The ac i a ion Gibbs ee ene gy de e mined by his me hod is DG ‡ (298 K) =22.6 (±0.1) kcal mol −1 . Wi hin he pseudo- s o de egime, he de e mina ion o k obs was ca ied ou using diffe en concen a ions o DMAD. A linea co ela ion was obse ed ae plo ing k obs s. [DMAD] (Fig. S78†), indica ing ha he eac ion is  s o de in each componen and sug- ges ing a bimolecula mechanism ( ide in a). Thus, he second o de a e cons an could be de e mined, wi h a alue o k=3.9 ×10 −4 M −1 s −1 . Whe eas he ac i a ion pa ame e s abo e a e simila o hose obse ed o a conce ed inse ion mechanism o DMAD in a Au(I) complex, 9,10 compu a ional e idence sugges s his does no seem o be he case ( ide in a). Simila expe imen s we e conduc ed wi h bime allic ace ylide 8(see ESI†). Complex 8 engages in a slowe inse ion eac ion (Fig. 5A, pu ple ace), despi e he s onge s-dona ing cha ac e o he SIP ligand, which sugges s ha p-backbonding om Au(I) o he NHC ligands is playing a non-negligible ole. 22 ADG ‡ alue o 23.2 (±0.1) kcal mol −1 was ob ained om his kine ic analysis. These esul s a e in ag eemen wi h he spec oscopic and c ys allo- g aphic da a desc ibed abo e ega ding he s eng h o he C^C bond. The examples epo ed in he li e a u e o DMAD inse ion on Au(I) a e no app op ia e o compa ison due o he diffe en na u e o he ligands a ound he me al and he lack o bime- allic sys ems (Fig. 1). This p omp ed us o in es iga e he effec o he nuclea i y on sys ems ela ed o he syn hesized dinuclea ace ylides and compa e he impac ha one o wo gold a oms may ha e on he inse ion eac ion. To his end, non-a yl complexes 3and 4(p ecu so s o ace ylides 7and 8) and a oma ic alkynyl complex IP AuCCPh (12) we e examined in he inse ion o DMAD (Scheme 3). G a i yingly, monome allic complexes 3,4, and 12 inse DMAD in a simila ashion o he examples desc ibed abo e, yielding he co esponding Z-enyne p oduc s as he main species, as asce ained by mul inuclea NMR and single-c ys al X- ay diff ac ion s udies (see ESI†). Howe e , a mo e o cing expe imen al condi ions we e Fig. 4 Solid-s a e s uc u e o bime allic ace ylide 8(50% p obabili y ellipsoids). Mos o he H a oms a e omi ed and 2,6-diisop opylphe- nylg oups a e ep esen ed as capped s icks o cla i y. Fig. 5 Selec ed esul s om kine ic analysis. (A) Plo o [X] s. ime (X = 7o 8) a 25 °C. (B) Plo o ln[7] s. ime a diffe en T alues. (C) Ey ing plo o 7(ln(k obs /T) s. 1/T). © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chem. Sci.,2025,16,4684–4694 | 4687 Edge A icle Chemical Science Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online equi ed o he eac ions o each comple ion. In all cases, an excess o DMAD had o be added and he eac ion mix u es had o be hea ed up o 110 °C in oluene in o de o show e olu ion. Kine ic s udies we e ca ied ou wi h species 4unde pseudo-  s -o de condi ions ([DMAD] $10 equi alen s) in p-xylene- d 10 a 120 °C, indica ing ha he inse ion is  s o de in he Au(I) complex. 23 A his empe a u e, k obs alues simila o hose obse ed o bime allic complex 8a 25 °C we e ob ained (Table S2†), along wi h a DG ‡ (393 K) =30.6 (±0.3) kcal mol −1 . The e o e, hese esul s sugges ha he second NHC–Au ag- men in he bime allic ace ylides g ea ly acili a es he inse ion eac ion in compa ison o he monome allic analogues (Fig. 6). Ex ension o he scope Based on he supe io eac i i y displayed by bime allic ace y- lide complex 7,diffe en eac ion condi ions and subs a es we e explo ed (Table S1†). Fi s , DMAD and 3-hexyne we e in es iga ed unde mo e o cing eac ion empe a u es, namely 150 °C (mesi ylene as sol en ) and 120 °C ( oluene as sol en ) espec i ely. While he o me expe imen esul ed in he pa ial decomposi ion o he complex, he la e did no show any e olu ion by 1 H NMR spec oscopy. Simila ly, diphenylace ylene did no lead o any inse ion e en , as well as 1-phenylp op-1- yne (Ph–C^C–Me). Howe e , in oduc ion o elec on- wi hd awing g oups –COOMe on he pa a posi ions o he diphenylace ylene backbone esul ed in eac i i y wi h complex 7; howe e , mul iple uniden ied p oduc s we e obse ed e en a 25 °C. A simila ou come was ob ained when using me hyl 2- bu ynoa e (Me–C^C–COOMe) a 120 °C (Fig. S66 and S67†). Conside ing ha he acidi y o he me hyl g oup migh gi e ise o dep o ona ion p ocesses and subsequen side- eac ions, his agmen was eplaced by a phenyl ing in me hyl phenyl- p opiola e (Ph–C^C–COOMe). Hea ing his eac ion mix u e in oluene o 120 °C selec i ely yielded inse ion p oduc 16 (Scheme 4), as de e mined by NMR spec oscopy. In addi ion, he egioselec i i y o he inse ion eac ion was es ablished by single-c ys al X- ay diff ac ion analysis (see ESI†). Con e sely, monome allic de i a i e 12 did no show any e olu ion unde hese condi ions (10 equi . o alkyne and 120 °C), which, again, mani es s he benecial ole o he second me al in his ype o eac ion. As a ma e o ac , only bime allic compound 7 eac- ed wi h CS 2 o gi e he monoinse ion p oduc 17 (Scheme 4). The connec i i y o 17 was asce ained by X- ay diff ac ion s udies on c ys als g own om apo diffusion o die hyl e he in o a MeCN solu ion o he complex (Fig. 7). The o ma ion o aAu–S bond may be a d i ing o ce o his ans o ma ion, which mo i a ed he explo a ion o a diffe en , sul u - con aining subs a e. Indeed, when elec on-decien 4-( i- uo ome hyl)phenyl iso hiocyana e (10 equi .) was added o a oluene solu ion o 7, apid (30 min) con e sion o a new unsymme ical species was obse ed a 25 °C by 1 H NMR spec oscopy. Mul inuclea NMR and IR spec oscopy and combus ion analysis indica e ha he p oduc co esponds o Scheme 3 Reac i i y s udies be ween monome allic alkynyl complexes 3,4and 12 and DMAD. Fig. 6 Compa ison be ween bime allic complex 7and monome allic species 4: plo o [complex] s. ime. Scheme 4 Ex ension o he eac i i y scope o ace ylide species 7. Isola ed yields in pa en heses. 4688 |Chem. Sci.,2025,16,4684–4694 © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chemical Science Edge A icle Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online he monoinse ion de i a i e 18 (Scheme 4). Hea ing he eac- ion mix u e o 120 °C did no lead o clea , u he eac i i y as species 18 was s ill he main p oduc ae 17 h and he 19 F{ 1 H} NMR spec um e eals he p esence o nume ous esonances, which sugges s pa ial decomposi ion (Fig. S68†). Monome allic compound 12 also exhibi ed eac i i y wi h 4-( iuo ome hyl) phenyl iso hiocyana e, albei a 120 °C using a 10- old excess o eagen (when 1 equi . was employed, ca. 20% con e sion was obse ed ae 3 days a 120 °C). Un o una ely, he high solu- bili y o he p oduc in apola (n-pen ane o hexame hyldisi- loxane) and pola (MeCN o MeOH) sol en s p e en ed i s isola ion om he excess o iso hiocyana e, p ecluding i s u he cha ac e iza ion. None heless, mass spec ome y analysis (Fig. S45†) poin s o a p oduc wi h wo equi alen s o iso hiocyana e pe IP ligand. Las , CO 2 and N-N0-dicyclohex- ylca bodiimide we e also in es iga ed, bu hey did no eac wi h 7o 12 unde he expe imen al condi ions es ed. Mechanis ic s udies In o de o unde s and he ole o he second me al a om in he p ocess, he eac ion mechanism wi h DMAD was in es iga ed by means o expe imen al and compu a ional ools. Simple on ie molecula o bi al (FMO) analysis o pa en ace ylide 7 and DMAD was pe o med on DFT-op imized s uc u es 24 o ga he in o ma ion ela ed o he in e ac ion be ween bo h compounds. As depic ed in Fig. 8, he LUMO o DMAD consis s o an an ibonding combina ion o p o bi als o he iple bond, and he HOMO o 7is mos ly loca ed on he ace ylenic p-sys em wi h a clea con ibu ion o he adjacen gold a oms. Thus, in e ac ion be ween hese wo species would in ol e elec on densi y dona ion om he alkyne in 7 o DMAD (i.e., a Michael- ype nucleophilic addi ion), debili a ing he C^C bond o he o ganic agmen . This analysis sugges s ha blocking he p- sys em in 7should inhibi DMAD inse ion. Fo his eason, inuclea complex 19 was syn hesized by mixing 7and IP AuOT in THF as shown in Fig. 9 ( op). X- ay quali y c ys als o his ma e ial we e ob ained om he apo diffusion o n- pen ane in o a THF solu ion o 19 a −30 °C, which allowed o he de e mina ion o i s s uc u e in he solid s a e (Fig. 9, bo om). As expec ed, he hi d IP Au agmen es ablishes p- bonding wi h he iple bond, which leads o he bending o he AuCCAu axis, as judged by he :Au1–C1–C10and :Au10 –C10 – C1 angles ca. 164°. This de o ma ion is likely caused by he s e ic demand o he h ee IP ligands. No ably, a e y sligh elonga ion o he iple bond (1.226(5) Å) is obse ed compa ed o 7. Addi ion o DMAD o complex 19 does no show any e olu ion a 25 o 100 °C by 1 H NMR spec oscopy, in line wi h he lack o a ailabili y o he C^C bond in 19 (Fig. S64†). Howe e , his obse a ion also implies ha a po en ial equi- lib ium 19 47+ IP AuOT does no seem o be aking place Fig. 7 Solid-s a e s uc u e o complex 17 (50% p obabili y ellipsoids). H a oms a e omi ed and 2,6-diisop opylphenylg oups a e ep e- sen ed as capped s icks o cla i y. Only one diso de componen o he s uc u e is shown. Fig. 8 F on ie molecula o bi als o DMAD (A, LUMO) and 7(B, HOMO). Fig. 9 (Top) Syn hesis o inuclea species 19. (Bo om) Solid-s a e s uc u e o 19 (50% p obabili y ellipsoids). H a oms and i- fluo ome hanesul ona e anion we e omi ed, and 2,6-diisop opyl- phenylg oups we e ep esen ed as capped s icks o cla i y. © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chem. Sci.,2025,16,4684–4694 | 4689 Edge A icle Chemical Science Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online since ee ace ylide 7 eadily eac s wi h DMAD. ESI-MS suppo s his hypo hesis since he mass spec um only exhibi s a pa en ion peak wi h he expec ed m/zand iso ope dis ibu ion pa e n (Fig. S44†). On he o he hand, he 1 H NMR spec um o 19 a 25 °C e eals only one se o esonances o all h ee IP ligands (Fig. S39†), sugges ing apid exchange be ween he pand s-bonding modes o he ace ylide agmen . Va iable empe a u e 1 H NMR spec a we e acqui ed in THF-d 8 om 25 ° C o−95 °C (Fig. S42†), and coalescence phenomena we e obse ed a app oxima ely −75 °C. Un o una ely, no slow exchange was obse ed wi hin he empe a u e ange de e - mined by he sol en , which p ecluded he ex ac ion o a a e cons an . None heless, a ansi ion s a e connec ing he s uc- u e depic ed in Fig. 9 and a gem-digold ace ylide species was ound leading o a a he low ba ie o 3.6 kcal mol −1 , which is consis en wi h he obse ed as exchange (Fig. S93†) and ha p oposed by Widenhoe e and co-wo ke s. 25 These ndings highligh he labile cha ac e o he Au–C bonds in his ype o complexes, which seems o be an essen ial ea u e in he mechanism p oposed o he inse ion o DMAD ( ide in a). The mechanism o he eac ion be ween 7and DMAD was also explo ed by DFT me hods. S a ing om 7and DMAD as ene gy e e ence, he  s s ep o he mechanism in ol es he o ma- ion o he an de Waals encoun e complex 7$DMAD, which lies 3.0 kcal mol −1 abo e he sepa a e eac an s due o en opic easons. F om his poin , ini ial app oaches in ol ed app oxi- ma ion o DMAD o diffe en egions o he ace ylide complex ia elaxed po en ial ene gy su ace scans o nd a conce ed inse ion p ocess (e.g. o ma ion o Au–C and C–C bonds in he same s ep), simila o hose p oposed by Amgoune and Bou - issou 9 o Kuniyasu and Kambe. 10 All ou a emp s we e ui less in his ega d; howe e , hey led o a diffe en , unp eceden ed s epwise mechanism depic ed in Fig. 10. In he  s s ep o his eac ion p ole, he HOMO o complex 7in e ac s wi h he LUMO o DMAD ia TS1, a saddle poin loca ed 19.5 kcal mol −1 abo e he ene gy e e ence. This eac ion is he a e- de e mining s ep o he en i e p ocess, wi h an ac i a ion Gibbs ene gy close o ha de e mined expe imen ally (22.6 kcal mol −1 ). Likewise, he en halpy diffe ence o his ba ie (15.9 kcal mol −1 ) is close o he alue de e mined by 1 H NMR spec oscopy (18.2 kcal mol −1 ). This key saddle poin , TS1, is associa ed wi h bo h he app oach o DMAD and he o ma- ion o wha will be he single C–C bond in he enyne s uc u e o 10. In his species, he C/C bond- o ming dis ance is 2.05 Å, and DMAD is no longe linea based on C(O)–C–C angles o z134°, implying a ma ked sp 2 hyb idiza ion o he ca bon a oms (Fig. 11, op). This ansi ion s a e leads o In 1- ans, which consis s o a s,p–digold complex, simila o hose e- po ed by Widenhoe e , 25 Nolan 26 and Echa a en. 27 Based on his s uc u e, his ini ial s ep can be iewed as he DMAD- p omo ed displacemen o one IP Au moie y om i s s-bond wi h he C 22− agmen o he p-coo dina ion in In 1- ans. The geome y o he la e species can be ega ded as a zwi e ionic s uc u e wi h a ca ionic IP Au g oup bound o he iple C^C bond (Fig. 10, pu ple a ow) and ea u ing a dicoo dina e, sp 2 ca banion (g een a ow). F om In 1- ans, he ca ionic [IP Au] + moie y can mig a e o his sp 2 ca bon a om o yield he inse ion p oduc . Howe e , his s ep would affo d he E-enyne complex Fig. 10 Compu ed Gibbs ene gy p ofile in benzene o he eac ion be ween 7and DMAD. Rela i e Gibbs ene gies compu ed a 298 K and 1 M a e gi en in kcal mol −1 . The Gibbs ene gy o 7+ DMAD has been aken as ze o ene gy. En halpy alues (a 298 K and 1 a m) a e highligh ed in g een. All da a ha e been compu ed a he SMD-M06L-D3/de 2-TZVPP//SMD-M06L-D3/6-31G(d,p)&SDD(+ ) le el. 4690 |Chem. Sci.,2025,16,4684–4694 © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chemical Science Edge A icle Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online ins ead o he obse ed Zisome . Expec edly, his mig a ion is 10 kcal mol −1 mo e ene gy demanding (DG ‡ =5.4 kcal mol −1 , Fig. S91†) han he analogous mig a ion leading o he Z- p oduc ( ide in a) in acco dance wi h he expe imen al obse a ions. The e o e, an isome iza ion s ep om In 1- ans is necessa y. This akes place h ough TS2, lying 1.1 kcal mol −1 abo e he ene gy e e ence, whe e a linea C(O)–C–C(C) a angemen (178.3 °C) is obse ed, which e ol es o In 1-cis, 1.5 kcal mol −1 mo e s able han i s ans isome . This species possesses bo h es e g oups in a cis o ien a ion, and places bo h gold a oms in close con ac (Au/Au dis ance o 3.11 Å) whe e me alophilic in e ac ions migh be p esen . 28 These in e ac- ions migh be in ol ed in he s abiliza ion o In 1-cis, unlike analogous in e media es whe e he e is only one me al (Fig. S92†). Despi e ha , a diffe en , almos isoene ge ic con o me In 2 was loca ed, which p eo ganizes he molecule o he nal [IP Au] + mig a ion s ep. The mos no iceable change in his s uc u e is he o a ion o he DMAD agmen om In 1-cis (whe e bo h es e g oups we e loca ed in a plane pe pendicula o he [IP Au] + moie y) o In 2 (whe e he DMAD backbone and he gold a om a e in he same plane). This a angemen acili a es he ansi ion me al agmen mig a ion om he C^C bond o he sp 2 a om h ough TS3, only 1.7 kcal mol −1 abo e he eagen s. This saddle poin in ol es a 5-membe ed me allacycle and di ec ly affo ds he Z-enyne species 10, 32.9 kcal mol −1 mo e s able han ace ylide 7+ DMAD eac an s. No su p isingly, an analogous mechanism was also ound o monome allic species 12 (Fig. S92†), whe e he app oach o DMAD is also he a e-de e mining s ep. None- heless, he Gibbs ee ene gy ba ie equi ed o his key s ep is compa a i ely much highe (DG ‡ =27.4 kcal mol −1 ), in good ag eemen wi h he mo e o cing expe imen al condi ions equi ed o he eac ion o occu . Mo eo e , he egioselec i i y obse ed o complex 16 is in ag eemen wi h he p oposed mechanism (see Fig. S94†). While he a o emen ioned compu ed p oles a e consis en wi h he expe imen al esul s, u he compu a ional analysis was ca ied ou o unde s and he ac o s behind he obse ed enhanced eac i i y o he bime allic sys em, i.e., why he second IP Au agmen acili- a es he inse ion eac ion o he ex en desc ibed abo e. To his end, we  s applied he Ac i a ion S ain Model (ASM) 29 o eac i i y o compa e he ini ial s ep in ol ing he addi ion o DMAD o bo h he pa en bime allic complex 7and i s mono- me allic coun e pa 12. This analysis decomposes he elec- onic ene gy (DE) in o wo e ms, namely he s ain (DE s ain ) ha esul s om he dis o ion o he indi idual eac an s and he in e ac ion (DE in ) be ween he de o med eac an s along he eac ion coo dina e dened, in his case, by he C/C bond- Fig. 11 (Top) Rep esen a ion o he ansi ion s a e o he a e-de e mining s ep o each mechanism, whe e he dashed line (chemical figu e) and he g een do s (3D image o TS1) ep esen he key C/C dis ance ha changes along he eac ion coo dina e. The dis o ion o he DMAD molecule is e iden since i is no longe linea (:C(O)–C–Cz134° and C^C=1.28 Å s. 175° and 1.21 Å in ee DMAD). In addi ion, a sligh dis o ion is obse ed in he :Au–C^C angle (165.9° s. 178.3° in 7)”. (Bo om) Compa a i e ac i a ion s ain analysis (a) and ene gy decom- posi ion analysis (b) o he eac ion o DMAD wi h 7(solid lines) and 12 (dashed lines) along he eac ion coo dina e p ojec ed on o he C/C bond- o ming dis ance. All da a ha e been compu ed a he ZORA-M06L-D3/DZP//SMD-M06L-D3/6-31G(d,p)&SDD(+ ) le el. © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chem. Sci.,2025,16,4684–4694 | 4691 Edge A icle Chemical Science Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online o ming dis ance. Fig. 11a shows he co esponding Ac i a ion S ain Diag ams (ASDs) om he ini ial s ages o he ans- o ma ion up o he espec i e ansi ion s a es. F om he da a in Fig. 11a, i becomes e iden ha he lowe ba ie compu ed o he eac ion in ol ing 7does no o igina e om he s ain e m, which is ac ually less des abilizing o he eac ion in ol ing he monome allic complex, bu exclusi ely om he s onge in e ac ion be ween he de o med eac an s along he en i e eac ion coo dina e. The o igin o he compu ed s onge in e ac ion o he 7+ DMAD eac ion can be u he analyzed by means o he Ene gy Decomposi ion Analysis (EDA) me hod. 30 This app oach in ol es decomposing he in e ac ion DE in be ween he eac an s in o he ollowing, physically meaning ul ene gy e ms: he classical elec os a ic in e ac ion (DV els a ), he Pauli epulsion (DE Pauli ) a ising om he epulsion be ween occupied closed-shell o bi als o bo h de o med eac- an s, he o bi al in e ac ion (DE o b ) ha accoun s o cha ge ans e and pola iza ion, and he dispe sion in e ac ions (DE disp ) coming om dispe sion o ces. As depic ed in Fig. 11b, which g aphically shows he e olu ion o he EDA e ms along he eac ion coo dina e om he ini ial s ages o he p ocesses up o he espec i e ansi ion s a es, he s onge (i.e., mo e s abilizing) in e ac ion be ween he eac an s compu ed o he eac ion in ol ing he bime allic sys em mainly esul s om bo h s onge elec os a ic and o bi al in e ac ions, pa icula ly a he ansi ion s a e egion. Fo ins ance, a he same consis en C/C bond- o ming dis ance o 2.1 Å, DV els a = −65.5 kcal mol −1 and DE o b =−64.1 kcal mol −1 o he eac ion in ol ing 7, whe eas much lowe alues we e compu ed o he analogous DMAD + 12 eac ion (DV els a =−53.2 kcal mol −1 and DE o b =−46.8 kcal mol −1 ). The s onge elec os a ic in e ac- ions can be asc ibed o he s onge pola iza ion induced by he IP Au agmen in 7compa ed o he phenyl g oup in 12,as con med by he highe nega i e NBO-cha ge compu ed a he ca bon a om adjacen o he eac i e ca bon (−0.55e s. −0.14e, o 7and 12, espec i ely). 31 In u n, he o igin o he mo e s abilizing DE o b can be ound by applying he Na u al O bi al o Chemical Valence (NOCV) 32 ex ension o he EDA me hod. Wi hin his app oach, he main o bi al in e ac ions con ibu ing o he o al DE o b e m can be isualized and also quan ied. As expec ed om ou ini ial FMO analyses ( ide sup a), he EDA-NOCV me hod iden ies he elec on ow om he p(HOMO) o he me al complex o he p*(LUMO) o DMAD as he main o bi al in e ac ion in his ans o ma ion (Fig. 12). No ably, his p(HOMO) /p*(LUMO) molecula o bi al in e ac ion is signican ly s onge , i.e., mo e s abilizing, o he p ocess in ol ing he bime allic sys em (see he co esponding s abilizing ene gies compu ed a a consis en C/C bond- o ming dis ance o 2.1 Å). The e o e, he ASM- EDA(NOCV) analysis sugges s ha he enhanced eac i i y o he bime allic sys em, compa ed o i s monome allic coun e - pa , nds i s o igin in he signican pola iza ion induced by he IP Au agmen on o he eac i e C^C bond which esul s in s onge elec os a ic and o bi al (p(HOMO) /p*(LUMO)) in e ac ions wi h he DMAD eac an and ul ima ely, in he obse ed lowe addi ion ba ie . Conclusions In summa y, a modula syn he ic s a egy o he p epa a ion o bime allic Au(I) ace ylides has been desc ibed. Whe eas only symme ical digold complexes ha e been explo ed in his wo k, his ou e opens he doo o he de elopmen o unsymme ical de i a i es o he e obime allic species, which is cu en ly an ongoing esea ch di ec ion in ou labo a o y. The syn hesized symme ical digold ace ylides and monome allic alkynyl analogues selec i ely inse DMAD o yield he co esponding Z enyne p oduc s; howe e , much mo e o cing condi ions a e necessa y when only one me al is employed (110 °C s. 25 °C). This p onounced dispa i y has been s udied in de ail h ough expe imen al and compu a ional me hods, leading o a s ep- wise mechanism, which diffe s om p e iously epo ed examples o inse ion on gold(I) complexes. Two key aspec s o his mechanism a e e iden : (1) he p esence o a second gold agmen s abilizes bo h he ansi ion s a e and in e media e species due o he inc eased elec on dona ion o he alkyne agmen (al hough au ophilic con ac s migh also play a ole in some o hem (e.g. In 1-cis)). This supply o elec on densi y acili a es he ini ial in e ac ion wi h DMAD and subsequen ly keeps he ca ionic IP Au moie y bound o he p-sys em. (2) Ce ain labili y o he Au–C bonds is necessa y so ha DMAD can displace one IP Au agmen om s o p-coo dina ion, and ease he mig a ion o Au om sp o sp 2 ca bon a oms. The balance o hese wo aspec s accoun s o he mild condi ions obse ed o he inse ion eac ion in he bime allic complexes and p o ides new knowledge o he ole ha wo me als play in he case o digold-media ed o ganic ans o ma ions. Da a a ailabili y The da a suppo ing his a icle ha e been included as pa o he ESI.†Deposi ion numbe s 2372473–2372479 ( o complexes 3,7,8,10,13,15 and 19), 2407558 ( o complex 16) and 2403953 ( o complex 17) con ain he supplemen a y c ys allog aphic da a o his pape . These da a can be ob ained ee o cha ge ia www.ccdc.cam.ac.uk/da _ eques /ci , o by emailing Fig. 12 Con ou plo s o he NOCV de o ma ion densi ies (isosu - ace alue o 0.001 a.u.) and he associa ed ene gies DE( ) (a a consis en C/C bond- o ming dis ance o 2.1 Å) o he main o bi al in e ac ion occu ing in he eac ion o DMAD wi h 7(le ) and 12 ( igh ). The elec onic cha ge flows om ed o blue. All da a we e compu ed a he ZORA-M06L-D3/DZP//SMD-M06L-D3/6-31G(d,p) &SDD(+ ) le el. 4692 |Chem. Sci.,2025,16,4684–4694 © 2025 The Au ho (s). Published by he Royal Socie y o Chemis y Chemical Science Edge A icle Open Access A icle. Published on 13 Feb ua y 2025. Downloaded on 6/3/2025 9:52:40 AM. This a icle is licensed unde a C ea i e Commons A ibu ion-NonComme cial 3.0 Unpo ed Licence. View A icle Online