Insigh in o he Key Fac o s ha In luence he Reac ion Pa hways
in he Silyl-P ins Cycliza ion o gem-Vinylsilyl Alcohols
Paula González-And és,aCa los Díez-Poza,aLau a F. Peña,a
Daniel Gónzalez-Pina do,bIs ael Fe nández,b,* and Asunción Ba be oa,*
a
Depa men o O ganic Chemis y, Facul y o Science, Uni e si y o Valladolid?, 47011 Valladolid, Spain
Phone: +34-983-423013
Fax: +34-983-423013
E-mail: [email p o ec ed]
b
Depa amen o de Química O gánica y Cen o de Inno ación en Química A anzada (ORFEO-CINQA), Facul ad de Ciencias
Químicas, Uni e sidad Complu ense de Mad id, 28040-Mad id, Spain
Phone: +34-3944312
E-mail: [email p o ec ed]
Manusc ip ecei ed: No embe 19, 2024; Re ised manusc ip ecei ed: Decembe 10, 2024;
Ve sion o eco d online: Janua y 2, 2025
Suppo ing in o ma ion o his a icle is a ailable on he WWW unde h ps://doi.o g/10.1002/adsc.202401437
© 2025 The Au ho (s). Ad anced Syn hesis & Ca alysis published by Wiley-VCH GmbH. This is an open access a icle unde
he e ms o he C ea i e Commons A ibu ion Non-Comme cial NoDe i s License, which pe mi s use and dis ibu ion in any
medium, p o ided he o iginal wo k is p ope ly ci ed, he use is non-comme cial and no modi ica ions o adap a ions a e made.
Abs ac : This wo k p o ides an in-dep h analysis
o he ac o s go e ning he di e en eac ion
pa hways in he acid-ca alyzed cycliza ion o gem-
inylsilyl alcohols wi h aldehydes. The s udy e al-
ua es he impac o bo h he ligands a ached o
silicon and he choice o he Lewis acid on he
eac ion ou come. Addi ionally, compu a ional s ud-
ies o e aluable insigh s in o he mechanism ha
con ol hese dis inc pa hways. The p ocess enables
he chemo- and s e eocon olled o ma ion o a
a ie y o s uc u al amewo ks, o e ing signi ican
po en ial o he gene a ion o a b oad ange o
molecula a chi ec u es.
Keywo ds: P ins cycliza ion; o ganosilanes; compu-
a ional s udies; Lewis acids; S e eocon ol
In oduc ion
The ine a o O ganic Syn hesis has he ex ao dina y
powe o eplica ing some o he mos ascina ing
molecules ha na u e p oduces. Some o hese sub-
s ances ha e changed ou e e yday li es by p o iding
candida es o pha maceu ical, ag icul u e, cosme ic,
o high- echnology applica ions, among o he s. Bu
p obably medical science is he ield ha has concen-
a ed mo e e o s in he sea ch o biologically ac i e
molecules. Mo eo e , O ganic Syn hesis has p o en
in aluable o cons uc ing analogues o de i a i es o
na u al p oduc s, which can some imes exhibi en-
hanced biological p ope ies compa ed o hei na u al
coun e pa s.
One o he mos abundan sca olds in biologically
ac i e compounds is he e ahyd opy an mo i ,[1,2] and,
he e o e, de eloping me hodologies o he p epa a-
ion o his s uc u al co e wi h a ange o subs i uen s
o e i s pe iphe y emains a key objec i e in O ganic
Syn hesis.[3,4] Addi ionally, he disco e y o me hod-
ologies ha , depending on he na u e o he subs a es
o ca alys s, may ollow di e en eac ion pa hways,
and he e o e may a o d he cons uc ion o s uc u -
ally di e se sca olds, is highly desi able. Such
me hods p o ide ample possibili ies o designing
s uc u al a ia ion in a ge molecules and enhance he
po en ial o no el d ug disco e y.
Wi hin he a ious a ailable me hodologies o
gene a ing oxygen- o ni ogen-con aining he e o-
cycles, he P ins cycliza ion has eme ged as one o he
mos e icien app oaches.[5,6] The cycliza ion in ol es
he acid-ca alyzed in amolecula addi ion o a π-dono
g oup ( ypically an alkene) o an oxoca benium ion
(gene a ed in si u by condensa ion o he hyd oxy
g oup o he s a ing alkenol wi h an aldehyde).
Se e al modi ica ions o he P ins cycliza ion ha e
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been de eloped by a ying he na u e o he π-dono o
accep o en i ies. In ecen yea s, ou esea ch has
ocused on explo ing a ious s a egies o syn hesiz-
ing oxa- and azacycles h ough silyl-P ins
cycliza ion,[7,8] wi h pa icula emphasis on using
alkenyl silanes as ac i a ed π-dono g oups. This
me hod, known as silyl-P ins cycliza ion, p esen s
mul iple bene i s, such as enhanced eac ion selec i i y
and a educ ion in he o ma ion o unwan ed by-
p oduc s.[9]
Wo h o no e is he ecen ly published disco e y o
a andem silyl-P ins cycliza ion-a yl mig a ion p o ocol
which occu s wi h he main enance o he silyl g oup
in he molecule and a yl mig a ion om silicon o he
neighbou ing ca bon.[10] An e en mo e in iguing
inding was ha he a yl mig a ion depended on he
na u e o he acid ca alys (TMSOT s BiCl3/
TMSCl)[11] (Scheme 1).
The mechanism ha we ha e p oposed o hese
ans o ma ions in ol es he ini ial o ma ion o an
oxoca benium ion which will hen unde go nucleo-
philic a ack by he inylsilyl g oup o gi e an α o
silicon ca boca ion I(which is mo e s able han he
co esponding β-silyl ca boca ion).[12] F om his com-
mon in e media e, depending on he na u e o he
Lewis acid coun e ion, he eac ion will e ol e wi h
ei he 1,2-a yl mig a ion om silicon o ca bon and
inal silyl ca ion apping by ime hylsilanol (when
TMSOT is used), o by di ec nucleophilic apping o
he e ia y ca boca ion (in he eac ion media ed by
BiCl3, TMSCl) (Scheme 2).
We en isioned ha a be e unde s anding o he
ac o s go e ning hese al e na i e pa hways was
equi ed o u he de elop his syn he ically use ul
ans o ma ion. We he ein p esen a deepe o e iew
o his in iguing me hodology, highligh ing he e ec s
o bo h he na u e o he silyl ligands and he Lewis
acid componen on he ou come o he cycliza ion
(Scheme 1). Mo eo e , compu a ional s udies ha e
been ca ied ou o gain mo e insigh in o he aspec s
in luencing he occu ence o he a yl mig a ion and
he high s e eocon ol obse ed.
Resul s and Discussion
Ou ini ial e o s ocused on explo ing he in luence
o he ligands a ached o silicon on he p ocess. To
his end, we pe o med u he expe imen s in ol ing
subs a es wi h di e en subs i uen s a he silicon
cen e . Bea ing in mind ha phenyldime hylsilyl
de i a i es 1ha e been p e iously demons a ed o
unde go selec i e a yl mig a ion, we hough ha i
would be in e es ing o in es iga e he beha iou o
alkenylsilyl alcohols bea ing ei he a diphenylalkylsilyl
g oup o a ialkylsilyl g oup.
Thus, we i s es ed he eac ion wi h aldehydes o
a model subs a e 4wi h wo phenyl g oups bonded o
silicon (diphenylme hylsilyl g oup). As expec ed, he
eac ion in he p esence o TMSOT p o ided he
adduc s o a andem P ins cycliza ion-a yl mig a ion
p o ocol. Howe e , he e a e wo key di e ences
compa ed o he eac ion wi h he analogous alcohol 1
bea ing he phenyldime hylsilyl g oup: (i) he eac ion
o he diphenylme hylsilyl de i a i e 4p oceeded
mo e slowly han he p eceden one, sugges ing ha
s e ic hind ance is in luencing his p ocess and (ii) he
eac ions now esul ed in an equimola mix u e o
epime s a C4 (5and 6) (Scheme 3).
On he o he hand, he P ins cycliza ion o
diphenylme hylsilyl alkenol 4wi h p-chlo obenzalde-
hyde, in he p esence o a mix u e o BiCl3and
TMSCl, p o ided he expec ed C4 halogena ed e ahy-
d opy an 7(no phenyl mig a ion is obse ed) wi h
Scheme 1. P e ious esul s and his wo k.
Scheme 2. P oposed mechanism.
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s e eoselec i i y compa able o i s phenyldime hylsilyl
analog 1[11] (Scheme 4).
Nex , we decided o es he cycliza ion using he
inylsilyl alcohol 8wi h h ee alkyl g oups bonded o
silicon. Al hough he highe mig a o y ap i ude o a yl
s alkyl g oups is well known, we easoned ha he
p esence o a p ima y alkyl g oup a ached o silicon,
wi h highe mig a o y ap i ude han he me hyl g oup,
could acili a e he mig a ion. Howe e , no mig a ion
was obse ed in he eac ion. Ins ead, he in e media e
e ia y ca ion Inow unde goes a compe i i e elimi-
na ion eac ion (9,10), a he han nucleophilic
addi ion, p obably due o he s e ic equi emen o he
nucleophile (TMSOH) (Scheme 5).
In line wi h his hypo hesis and wi h p e ious
esul s, he cycliza ion o he ialkylsilyl de i a i e 8
wi h p-chlo obenzaldehyde, media ed by BiCl3/
TMSCl, u nished he expec ed 4-cho o e ahyd opy -
an 11 in good yield and wi h excellen s e eocon ol
(Scheme 6).
These esul s demons a e ha he cycliza ion o
gem- inylsilyl alcohols, media ed by TMSOT , unde -
go a andem P ins cycliza ion-a yl mig a ion, p o ided
ha he silyl g oup is a ached o an a yl g oup.
Howe e , ega dless o he na u e o he ligands
a ached o silicon, when he ans o ma ion is medi-
a ed by BiCl3/TMSCl, he eac ion consis en ly ollows
a P ins cycliza ion pa hway.
To gain mo e insigh in o he pa hways leading o
he di e en ou comes o he ans o ma ion, Densi y
Func ional Theo y (DFT) calcula ions we e ca ied ou
a he dispe sion co ec ed PCM(dichlo ome hane)-
B3LYPD3/de 2-TZVPP//PCM(dichlo ome hane)-
B3LYP/de 2-SVP le el (see compu a ional de ails in
he Suppo ing In o ma ion). To his end, we in es-
iga ed he p ocess in ol ing he ini ially o med
oxoca benium ion INT0 (ha ing he SiMe2Ph moie y),
ypically de i ing om he eac ion o he alcohol
agmen o he LA-complexed aldehyde,[13,14] in he
p esence o ei he TMSOT o BiCl3/TMSCl (Fig-
u e 1). The ini ial in e media e INT0 is, as p e iously
p oposed (see abo e), ans o med in o he ca boca ion
INT1 h ough he in amolecula nucleophilic addi ion
o he inylsilyl agmen o he elec ophilic oxoca be-
nium. Depending on he con o ma ion o he subs i u-
en s a he silicon a om, wo possible ansi ion s a es
(TS1/TS1’) and in e media es (INT1/INT1’) we e
loca ed on he po en ial ene gy su ace. Ou calcula-
ions indica e ha he p ocess in ol ing he phenyl
g oup in close p oximi y o he e ahyd opy an ing
(i.e., TS1/INT1) is a o ed om bo h kine ic and
he modynamic poin s o iew. This is mainly due o
he occu ence o a s abilizing CH-π non-co alen
in e ac ion be ween he axial hyd ogen a oms in he
ing and he π-sys em o he phenyl g oup as con i med
by he NCIPlo me hod (see g eenish su ace in he
inse o Figu e 1).
In he p esence o TMSOT , in e media es INT1/
INT1’ hen unde go a 1,2-phenyl mig a ion ia TS2/
TS2’ (wi h a low ba ie o only ca. 4–5 kcal/mol) o
p oduce he silyl ca ion in e media es INT2/INT2’,
which a e TMSOT apping (by he eadily o med
TMSOH) leads o he obse ed inal p oduc s. Once
again, he pa hway leading o he isome INT2’ ( ia
TS2’) is kine ically dis a o ed o e he analogous
p ocess leading o INT2, which is consis en wi h he
expe imen ally obse ed p e e ed o ma ion o he
Scheme 3. E ec o he ligands on silicon: diphenylme hylsilyl
g oup and TMSOT .
Scheme 4. E ec o he ligands on silicon: diphenylme hylsilyl
g oup and BiCl3/TMSCl.
Scheme 5. E ec o he ligands on silicon: ialkylsilyl g oup
and TMSOT .
Scheme 6. E ec o he ligands on silicon: ialkylsilyl g oup
and BiCl3/TMSCl.
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e ahyd opy an whe e he phenyl and R g oups a e
placed in an i- ela i e posi ion. On he o he hand, in
he p esence o BiCl3/TMSCl, he o ma ion o BiCl4
-
as he sou ce o chlo ide can be assumed. In e es ingly,
we ound ha he P ins-cycliza ion and chlo ide
apping occu in a conce ed manne wi h a lowe
ba ie (ΔΔG¼6 ca. 5 kcal/mol) han ha compu ed o
he o ma ion o INT1/INT1’ (i.e., he analogous
coun e anion-non-assis ed p ocess). This is he e o e
consis en wi h he exclusi e o ma ion o e ahyd o-
py ans 3in he p ocesses media ed by BiCl3/TMSCl.
In addi ion, he ba ie compu ed o his conce ed
cycliza ion/ apping eac ion is lowe (ΔΔG¼6 =
2.1 kcal/mol) o he p ocess in ol ing Cl-TS1, whe e
he phenyl g oup is again placed close o he
e ahyd opy an ing. This can be again asc ibed o he
occu ence o simila CH-π non-co alen in e ac ions
in his saddle poin . This is also consis en wi h he
p e e ed o ma ion o he p oduc whe e he Cl and R
subs i uen s a e placed in syn- ela i e posi ion (despi e
being he modynamically less s able han i s an i-
coun e pa , see Figu e 1) and indica es ha hese
weak in e ac ions a e key in he selec i i y o he
p ocess, ega dless o he condi ions (TMSOT s
BiCl3/TMSCl) used in he expe imen s.
The di e gen ou comes obse ed in his p ocess
p omp ed us o ques ion whe he hey can solely be
a ibu ed o he na u e o he Lewis acid coun e ion o
o he ac o s migh also be a play. To explo e his
u he , we decided o s udy he cycliza ion using o he
halides as coun e ions. Ini ially, we examined he
cycliza ion eac ion o alcohol 1wi h cinnamaldehyde,
in he p esence o bismu h ib omide, which could
play he dual ole o Lewis acid and sou ce o b omide.
Howe e , an un esol ed mix u e was ob ained unde
hese condi ions (Table 1, en y 1) and he combina ion
o ca aly ic BiB 3wi h s oichiome ic TMSB did no
yield imp o ed esul s (Table 1, en y 2). Fo una ely,
eac ion media ed by TMSB in dichlo ome hane a
oom empe a u e a o ded he desi ed 4-b omo e ahy-
d opy an in good yield, al hough wi h some insepa-
able by-p oduc s (Table 1, en y 3). By lowe ing he
empe a u e o 78°C, we we e able o a oid his
p oblem (Table 1, en y 4) and he desi ed compound
was ob ained in high yield and as a single p oduc .
In con as wi h he slow eac ion a es obse ed
wi h pu e TMSCl (which made necessa y he addi ion
o BiCl3), he high eac i i y o TMSB ob ia es he
need o addi ional coca alys s, such as BiB 3. Mo e-
o e , unde TMSB ac i a ion, he use o low empe -
Figu e 1. Compu ed eac ion p o ile o he p ocess in ol ing he ini ially o med oxoca benium in e media e INT0 in he p esence
o TMSOT o BiCl3/TMSCl. Rela i e ee ene gies (ΔG, a 298 K) and bond dis ances a e gi en in kcal/mol and angs oms,
espec i ely. The inse shows he con ou plo s o he educed densi y g adien isosu aces (densi y cu o o 0.04 a.u.) o INT1
whe e he g een su aces indica e a ac i e non-co alen in e ac ions. All da a ha e been compu ed a he PCM(dichlo ome hane)-
B3LYPD3/de 2-TZVPP//PCM(dichlo ome hane)-B3LYP/de 2-SVP le el.
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a u e is equi ed o ge selec i e eac ions. Once
selec ed he op imal condi ions o his eac ion
(Table 1, en y 4), we nex s udied he scope o he
p ocess using di e en aldehydes. The esul s a e
shown in Table 2.
The eac ion is gene al o a ylic aldehydes (ei he
elec on- ich o elec on-poo ) as well as o inylic
aldehydes. In addi ion, di e en subs i uen s (including
a ylic g oups) a e ole a ed on he ca binol ca bon.
Howe e , he use o highly eac i e aldehydes (i.e.,
alkylic aldehydes o p-ni obenzaldehyde) esul ed in
complex mix u es om which i was di icul o isola e
he co esponding 4-b omo e ahyd opy ans. In e es -
ingly, he eac ion again occu s wi h di ec apping o
he in e media e α-silyl e ahyd opy anyl ca ion Iby
he halide (i.e., p oduc s o 1,2-phenyl mig a ion we e
no obse ed). Fu he mo e, excellen dias e eoselec-
i i y owa ds a single dias e eome is ob ained in all
he examples when he eac ion was pe o med a
78°C (12a–12j). The ela i e con igu a ion o he
e ahyd opy anyl p oduc s was de e mined by he
coupling cons an s in 1H-NMR and NOESY expe i-
men s. Mo eo e , con i ma ion o ha s uc u e was
achie ed by means o single-c ys al X- ay di ac ion
o compound 12b (Figu e 2).
To comple e ou s udy, and also mo i a ed by he
signi icance o luo ina ed compounds in pha maceu -
ical and adiological applica ions, we decided o
in es iga e whe he he same eac ion pa hway ob-
se ed wi h chlo ide and b omide me al Lewis acids is
also ollowed when luo ide is used as he coun e ion.
Fo ha pu pose, we choose BF3·OE 2as he ac i a o .
The esul s a e shown in Table 3.
As demons a ed, and in con as wi h he beha iou
o o he me al halide Lewis acids, when luo ide is he
coun e ion he eac ion seems o ollow a andem silyl-
P ins cycliza ion/phenyl mig a ion pa hway. This
migh sugges ha a ious ac o s, including s e ic
hind ance and bond s eng h, play a c i ical ole in
de e mining he eac ion ou come. The eac ion wi h
BF3·OE 2is e ec i e o bo h elec on- ich and
elec on-poo a oma ic aldehydes, as well as o inylic
aldehydes and e en he highly eac i e alkylic alde-
hydes. Addi ionally, a ylic subs i uen s a ached o he
ca binol a e well ole a ed, yielding he desi ed p oduc
in mode a e yields.
Acco ding o ou DFT calcula ions (Figu e 3), he
conce ed P ins-cycliza ion/ luo ide- apping (wi h
BF4
-as luo ide sou ce) also p oceeds wi h a lowe
ba ie han he non-assis ed p ocess. This leads o he
o ma ion o he F-3-syn/an i in e media es wi h no
Table 1. Op imiza ion o b omide-based Lewis acids.
En y Lewis Acid Sol en Condi ions P oduc (yield)
1 BiB 3CH2Cl2 , 2 h UCM[b]
2 BiB 3/TMSB [a] CH2Cl2 , 2 h UCM[b]
3 TMSB CH2Cl2 , 2 h 12j (74)[c]
4 TMSB CH2Cl278°C, 2 h 12j (82)
[a] 0.4 equi . o BiB 3and 1.2 equi . o TMSB we e used.
[b] UCM s ands o un esol ed complex mix u e.
[c] The p oduc could no be sepa a ed om o he by-p oduc s.
Table 2. Scope o he silyl-P ins cycliza ion o gem- inylsilyl
alcohols 1wi h TMSB .
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signi ican selec i i y. F om hese in e media es, a
simul aneous mig a ion o he luo ide and phenyl
g oups h ough he C-Si bond akes place o p oduce
he obse ed e ahyd opy ans. This p ocess he e o e
can be iewed as a ype I dyo opic eac ion acco ding
o he o iginal de ini ion by M. Ree z.[15,16] Mo eo e ,
he dyo opic eac ion in ol ing F-TS2mig is kine ically
a o ed o e he analogous p ocess in ol ing F-
TS2mig’(ΔΔG¼6 ca. 2 kcal/mol)). This ac , oge he
wi h he highe he modynamical s abili y o he
co esponding eac ion p oduc , F-2-an i, a e espon-
sible o he high s e eoselec i i y obse ed expe imen-
ally.
Since one o he added alues o silicon-con aining
compounds is hei abili y o unde go a a ie y o
unc ional g oup ans o ma ions unde mild condi-
ions, we ul ima ely chose o u he in es iga e he
po en ial o he silyla ed e ahyd opy ans ob ained
om his p ocess. To his end, we examined wo
dis inc silicon con e sion s a egies. We i s es ed
he p o odesilyla ion o adduc s om ei he he
cycliza ion-mig a ion o he cycliza ion-nucleophilic
apping p ocesses. As shown in Scheme 6, eac ion o
b omode i a i e 12b wi h TBAF in THF ga e he
co esponding desilyla ed e ahyd opy an 14 in good
yield and wi h comple e e en ion o he con igu a ion
a C4 (Scheme 7).
Howe e , p o odesilyla ion o e ahyd opy ans 2a
o 13b, in which silicon is a ached o a e y c owded
qua e na y cen e ,[17,18] yielded desilyla ed e ahyd o-
py ans 15 and 16 as a nea ly equimola mix u e o
dias e eoisome s (wi h ei he e en ion o in e sion o
he con igu a ion a C4) (Scheme 8).
Despi e an icipa ing po en ial s e ic hind ance chal-
lenges in he Fleming-Tamao oxida ion o a silicon-
subs i u ed qua e na y ca bon, we p oceeded o e al-
ua e he con e sion o he silyl g oup o a hyd oxyl in
4-phenyl-4-silyl e ahyd opy ans 2a and 13 b. A -
emp s o oxidize disilane 2 a unde a ious condi ions,
Figu e 2. X- ay c ys al s uc u e o 12 b; displacemen ellip-
soids a 50% p obabili y. H a oms a e omi ed o cla i y. Colo
key: C (g ey), O ( ed), Si (yellow), B (o ange). CCDC:
2391410.
Table 3. Scope o he silyl-P ins cycliza ion o gem- inylsilyl
alcohols 1wi h BF3·OE 2.
Scheme 7. P o odesilyla ion p ocess o 4-b omo-4-silyl e ahy-
d opy an 12b.
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howe e , yielded only complex p oduc mix u es. By
con as , he luo osilane de i a i e 13b demons a ed
g ea e ease o oxida ion, p oducing he desi ed 4-
phenyl-4-hyd oxy e ahyd opy ans as a mix u e o C4
epime s when ea ed wi h MCPBA and KF[19]
(Scheme 9). In e es ingly, e ahyd opy an analogs o
compound 17, bea ing a yl g oups in C2 and C4, ha e
been epo ed o exhibi signi ican umo g ow h
inhibi ion in a ious human cell lines.[20]
Conclusion
A deep examina ion o he ac o s con olling he
di e en eac ion pa hways o he Lewis acid-ca alyzed
silyl-P ins cycliza ion o gem- inylsilyl alcohols wi h
aldehydes is p o ided. The in luence on he eac ion
ou come o bo h he na u e o he Lewis acid and he
silicon ligands has been p o en. In addi ion, compu a-
ional analysis p o ides a c i ical insigh in o he
mechanism accoun ing o he di e en pa hways. Ou
me hodology allows he cons uc ion o s uc u ally
Figu e 3. Compu ed eac ion p o ile o he p ocess in ol ing he ini ially o med oxoca benium in e media e INT0 in he p esence
o BF3as he ac i a o . Rela i e ee ene gies (ΔG, a 298 K) and bond dis ances a e gi en in kcal/mol and angs oms, espec i ely.
All da a ha e been compu ed a he PCM(dichlo ome hane)-B3LYPD3/de 2-TZVPP//PCM(dichlo ome hane)-B3LYP/de 2-SVP
le el.
Scheme 8. P o odesilyla ion o 4-phenyl-4-silyl e ahyd opy -
ans 2a and 13b.
Scheme 9. Fleming-Tamao oxida ion o 4-phenyl-4-silyl e a-
hyd opy an 13b.
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di e se sca olds, p esen ing conside able p omise o
he c ea ion o an a ay o a ge s.
Expe imen al Sec ion
Expe imen al de ails, cha ac e iza ion da a o all new com-
pounds, copies o 1H and 13C{1 H} NMR spec a o new
compounds and X- ay c ys allog aphic da a o compound 12 b
can be ound in he Suppo ing In o ma ion.
CCDC-2391410 con ains he supplemen a y c ys allog aphic
da a o his pape . These da a can be ob ained ee o cha ge
om he Camb idge C ys allog aphic Da a Cen e ia www.
ccdc.cam.ac.uk/s uc u es
Lewis Acid P omo ed Cycliza ion o gem-Vinylsilyl
Alcohols
A solu ion o he homoallylic alcohol (1 equi .) and he
co esponding aldehyde (1.2 equi .) in d y dichlo ome hane is
cooled o he co esponding empe a u e (unde ni ogen). Then,
he Lewis acid is d opwise added. The mix u e is s i ed while
moni o ed by TLC. When s a ing ma e ials a e consumed, i is
hyd olyzed wi h NaOH (aq) 2 M. o sa . NaHCO3. Phases a e
hen sepa a ed, ex ac ing he aqueous phase h ee imes wi h
dichlo ome hane. The o ganic phases a e combined and d ied
o e anhyd ous MgSO4. The sol en is hen e apo a ed unde
educed p essu e. The c ude mix u e is analyzed by NMR and
hen pu i ied by column ch oma og aphy in silica gel, using
mix u es o hexane-e hyl ace a e, yielding he co esponding
e ahyd opy ans.
Acknowledgemen s
We a e g a e ul o inancial suppo om g an s TED2021-
131705BC21, PID2021-125909OBI00, PID2022-
139318NBI00 and RED2022-134331-T, unded by MICIU/
AEI/10.13039/501100011033 and Nex Gene a ionEU/PRTR. We
also acknowledge E. Cuella o X- ay analysis (Depa men o
Ino ganic Chemis y, Uni e si y o Valladolid, Spain). L. F.-P.,
P. G.-A. and D. G.-P. acknowledge p edoc o al ellowships
unded by ei he he “Jun a de Cas illa y León”, he Uni e si y
o Valladolid o he Comunidad de Mad id.
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