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
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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.
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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.
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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).
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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.
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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.
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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.
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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.
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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
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