Silylium-ion-promoted (5+1) cycloaddition of aryl-substituted vinylcyclopropanes and hydrosilanes involving aryl migration [original]

Cycloaddition

Silylium-Ion-Promoted (5++1) Cycloaddition of Aryl-Substituted

Vinylcyclopropanes and HydrosilanesInvolving Aryl Migration

TaoHe, Guoqiang Wang,Vittorio Bonetti, Hendrik F. T. Klare,and Martin Oestreich*

In memory of Professor Kilian MuÇiz (1970–2020)

Abstract: Atransition-metal-free (5++1) cycloaddition of aryl-

substituted vinylcyclopropanes (VCPs) and hydrosilanes to

affordsilacyclohexanes is reported. Catalytic amounts of the

trityl cation initiate the reaction by hydride abstraction from the

hydrosilane,and further progress of the reaction is maintained

by self-regeneration of the silylium ions.The new reaction

involves a[1,2] migration of an aryl group,eventually furnish-

ing 4- rather than 3-aryl-substituted silacyclohexane derivatives

as major products.Various control experiments and quantum-

chemical calculations support amechanistic picture where

asilylium ion intramolecularly stabilized by acyclopropane

ring can either undergo akinetically favored concerted

[1,2] aryl migration/ring expansion or engage in acyclopro-

pane-to-cyclopropane rearrangement.

Introduction

There is arich chemistry associated with substituted

vinylcyclopropanes (VCPs), especially because of their value

as C5 synthons for the construction of complex carbon

skeletons.[1] VCPs engage in adiverse set of bond reorganiza-

tions,[2] and transition-metal-catalyzed cycloadditions of

VCPs continue to attract considerable attention.[3] Aside

from those exciting synthetic applications,the parent VCP

1aroused interest in carbocation chemistry as its protonation

allowed the study of the stabilizing effect of the cyclopropyl

group on carbenium ions.[4] Thecyclopropylcarbinyl cation 2

is known to undergo various rearrangements (Scheme 1, top

left),[2,4] and we asked ourselves what would happen upon

treatment of 1with asilylium ion instead of astrong Brønsted

acid (Scheme 1, top right). Theanalogy lies in FlemingQsearly

notion of silylium ions being fat protons,[5] and the result

would likely be the carbenium ion 3further stabilized by the

b-silicon effect.[6] Assuming that the cyclopropane ring would

not be directly opened by the silylium ion,[7] the fate of 3

would not be predictable,and we expected new chemistry to

emerge.The plan was to initiate the reactions of the VCPs 4

and dihydrosilanes 5with catalytic amounts of trityl borate

Ph3C+[B(C6F5)4]@,relying on hydride abstraction (Corey

reaction[8])and, as such, self-regeneration of silylium

ions.[7,9,10] Thus,carbenium ion intermediates such as 6[11]

would be captured by hydride.Wechose the aryl-substituted

VCPs 4as model substrates and found several cyclic silanes

(7—9)asproducts (Scheme 1, bottom) but no simple alkene

hydrosilylation (4!10).[12] Thesix-membered-ring compound

7is the result of aformal (5++1) cycloaddition accompanied by

an unexpected migration of the aryl group.Wepresent here

the scope of the new reaction and its experimental and

quantum-chemical mechanistic analysis.

Results and Discussion

Using catalytic amounts of Ph3C+[B(C6F5)4]@as an

initiator,webegan our investigation with the reaction of 4a

and excess Et2SiH2(5a)inbenzene at ambient temperature

(Table 1). Themajor product was the 4-phenyl-1-silacyclo-

hexane 7aa along with small quantities of the 3-phenyl-1-

Scheme 1. Cyclopropyl-substitutedcarbenium ions and their potential

intermediacy in asilylium-ion-promoted (5++1) cycloaddition.

[*] Dr.T.He, Dr.G.Wang, V. Bonetti, Dr.H.F.T.Klare,

Prof. Dr.M.Oestreich

Institut ffrChemie, Technische Universit-tBerlin

Strasse des 17. Juni 115, 10623 Berlin (Germany)

E-mail:m[email protected]

Homepage:http://www.organometallics.tu-berlin.de

Supportinginformation and the ORCID identification number(s) for

the author(s) of this article can be found under:

https://doi.org/10.1002/anie.202004320.

T2020 The Authors. Published by Wiley-VCH Verlag GmbH &Co.

KGaA. This is an open access article under the terms of the Creative

Commons Attribution Non-Commercial License, which permits use,

distribution and reproduction in any medium, provided the original

work is properly cited, and is not used for commercial purposes.

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International Edition: doi.org/10.1002/anie.202004320

German Edition: doi.org/10.1002/ange.202004320

12186 T2020 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim Angew.Chem.Int. Ed. 2020,59,12186 –12191

silacyclohexane 8aa and 3-benzyltetrahydrosilole 9aa (en-

try 1). Thearene solvent influenced the product distribution,

and the formation of 9aawas reduced in 1,2-dichlorobenzene

and chlorobenzene (entries 2and 3). Proceeding with chlor-

obenzene,welooked into the variation of other parameters

(entries 4–6). Neither alower catalyst loading (1.0 instead of

2.0 mol%) nor less dihydrosilane (5.0 to 1.5 equiv) had an

effect on the reaction outcome.Aslight decrease in yield and

asomewhat less favorable product ratio was detected with

equimolar quantities of the reactants (entry 7). Thesix-

membered 7aa did form in 90%yield under the optimized

reaction conditions.

We then probed the substrate scope under the optimized

protocol (Scheme 2). Electronic and steric modifications of

the substituent on the aryl group were examined with 4a–k.

Theparent VCP 4ayielded 7aain 75%yield on a0.25 mmol

scale and in 80%yield on a7.0 mmol scale.Substrates

bearing,for example,electron-donating 4-methyl (4b), 3,5-

dimethyl (4e), and 4-tert-butyl (4f)groups reacted smoothly,

affording the desired products 7ba,7ea,and 7fa,respectively,

in moderate yields.Itisworthy of note that amethyl group in

the ortho position, as in 4d,did not affect the reactivity

compared with 4band 4c.Halogen atoms were tolerated well

in this reaction, as shown for the cases with fluorine (4g),

chlorine (4hand 4i), and bromine (4jand 4k)inthe para or

meta positions.The preparation of the ortho-substituted

regioisomers had failed. Abulkier b-naphthyl group as in 4l

was also compatible with the reaction conditions although

alower yield was obtained. Conversely,the biphenyl-sub-

stituted 4m hardly converted into the desired product 7ma.

We believe that the aryl substituents in 4l and 4m are more

likely to engage in electrophilic aromatic substitution with

silylium-ion intermediates,[13] thereby consuming the silylium

ion to result in either decomposition or low conversion. A

triethylsilyl group,asin4n,did not interfere with the (5++1)

cycloaddition. Theyields of the isolated products were

generally low because of the challenging purification of these

nonpolar compounds;yields refer to analytically pure mate-

rial and come close to those determined by 1HNMR

spectroscopy with less rigor.Wealso note here that the

reaction of aVCP with acyclohexyl, instead of the phenyl

group,led to acomplex reaction mixture (not shown).

Aside from the dihydrosilane used above,weasked

ourselves whether tertiary hydrosilanes would also participate

in this reaction. We had recently shown that silylium ions can

indeed cleave Si@C(sp3)bonds.[14] This dealkylation corre-

sponds to an exchange of an alkyl group between aquaternary

silane and asilylium ion. Therefore,intermediates with no Si@

Hbond available anymore could potentially still engage in the

Table 1: Optimization of the trityl-cation-initiated (5++1) cycloaddition.[a]

Entry Initiator

(mol%)

Dihydrosilane

(equiv)

Solvent Yield [%][b]

7aa8aa 9aa

12.0 5.0 PhH 80 <511

22.0 5.0 o-C6H4Cl281 <58

32.0 5.0 PhCl 90 <56

41.0 5.0 PhCl 90 <56

51.0 3.0 PhCl 90 <55

61.0 1.5 PhCl 90 <55

71.0 1.0 PhCl 75 95

[a] All reactions were performed with 4a (0.25 mmol) and the indicated

amounts of the initiator Ph3C+[B(C6F5)4]@and Et2SiH2(5a)under argon

atmosphere in the indicated arene solvent (2.5 mL, 0.1m)atroom

temperature. Conversion was greater than 95%for each entry as

determined by 1HNMR spectroscopy using CH2Br2as an internal

standard. [b] Yields determined by 1HNMR spectroscopy using CH2Br2

as an internalstandard.

Scheme 2. Scope I: Variation of the aryl group in the VCPs 4in the

(5++1) cycloadditonwith Et2SiH2.Unless otherwise noted, all reactions

were performed on 0.25 mmol scale, and conversion was greater than

95%for each entry.Conversions and yields were determined by

1HNMR spectroscopy using CH2Br2as an internalstandard. Yields

determined by 1HNMR spectroscopy using CH2Br2as an internal

standard. Yields of analytically pure material obtained after flash

chromatography on silica gel are given within parentheses. [a] Yield of

isolated product on a7.0 mmol scale. [b] Ph3C+[B(C6F5)4]@(2.0 mol%)

and Et2SiH2(5.0 equiv) were used. [c] 82% 4m was recovered.

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self-regeneration of silylium ions.[7,9,10] Thereactions sum-

marized in Scheme 3demonstrate the feasibility of the

approach. Et3SiH (5b)yielded the same product 7aa as

Et2SiH2(5a)did in the reaction with 4a.Inturn, Me2PhSiH

(5c)underwent preferential dearylation, and EtMe2SiH (5d)

showed that demethylation is favored over abstraction of an

ethyl group.The observations are in line with those previously

made.[14,15]

To gain insight into the reaction mechanism, aseries of

control experiments was designed (Schemes 4–6). We had

recently shown that silylium ions promote the ring-opening

hydrosilylation of cyclopropanes.[7] If the (5++1) cycloaddition

begins with chemoselective ring opening of the cyclopropyl

group in 4,instead of the generation of the cyclopropyl-

stabilized carbenium-ion intermediates 6(cf.Scheme 1,

bottom), the a-substituted styrene derivatives 11 will be

likely intermediates.Hence,weprepared 11a and subjected it

to the standard procedure (Scheme 4, top). The endo

cyclization did occur but without migration of the phenyl

group,and 8aadid form exclusively with no trace of 7aa.This

finding makes the ring-opening preceding functionalization of

the alkene in the VCP unlikely.However,wealso found that

silylium ions can promote the isomerization of acyclopropyl

group into an allyl group.[7] We therefore prepared the 1,4-

diene 12aas another possible intermediate (Scheme 4,

bottom). When reacted with either 5a or 5b it was again

8aa,with no migration of the phenyl group,that was formed

exclusively.[16] These results hint that transposition of the

phenyl group occurs during the ring opening of cyclopropane.

We then turned towards the intermediates 13 with the

cyclopropane ring still intact, that is,the alkene hydrosilyla-

tion products 13aa and 13ab of 4a with 5a and 5b,

respectively (Scheme 5). Theassumed intermediate 13aa,

with aSi

@Hbond, underwent the ring expansion to 7aa

quantitatively with migration of the phenyl group when

treated with 1.0 mol%ofthe trityl borate Ph3C+[B(C6F5)4]@

in the absence of an external hydrosilane (Scheme 5, top).

Thesame result was obtained in the presence of 5b (not

shown). We concluded from this result that intramolecular

hydrosilylation of the cyclopropyl group is interlinked with

the aryl migration. Consequently,repeating this pair of

reactions with presilylated cyclopropane substrate 13ab with

no Si@Hbond led to the expected outcomes (Scheme 5,

bottom). Thetrityl-cation-promoted ring expansion of 13ab

into 7aain the presence of 5blikely involves the dealkylation

of quaternary silanes recently described by us.[14] Hence,

13aa!7aa with no hydrosilane and 13ab!7aa with addi-

tional hydrosilane pass through the same silylium-ion inter-

mediate.

As shown in Scheme 6, aseries of deuterium-labeling

experiments was performed to further elucidate the mecha-

nism. Thedeuterium incorporation was confirmed and

estimated by 1Hand 2HNMR spectroscopy (see the Support-

ing Information for details). When either 4a or the presily-

lated 13ab were reacted with Et3SiD ([D1]5b), deuterium

atoms were found at C3 and C4 of the rearranged product

Scheme 3. Scope II:Variation of the hydrosilane 5in the (5++1)

cycloadditonwith aVCP. Yields determined by 1HNMR spectroscopy

using CH2Br2as an internal standard. Yields of analytically pure

material obtained after flash chromatography on silica gel are given

within parentheses.

Scheme 4. Control experiments I: Verification of ring opening of the

cyclopropyl group in VCPs prior to engagementofthe alkene unit.

Scheme 5. Control experiments II:Cyclization experiments with presily-

lated cyclopropane intermediates, that is, alkene hydrosilylation prod-

ucts of VCPs.

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[D]7aa[Eq. (1) and Eq. (3)].Asshown in Scheme 5(top), no

additional hydrosilane is required to convert 13aa into 7aa.

However,when this reaction was performed in the presence

of Et3SiD ([D1]5b), deuterium incorporation was mainly

found at C3 but hardly any at C4 of [D]7aa [Eq. (2)].To

exclude downstream deuteration at C4, we subjected 7aa to

the reaction conditions but did not detect any deuteration in

the benzylic position [Eq. (4)].Consequently,C

@Hbond

formation occurs only during the migration/ring-enlargement

sequence.

To elucidate the mechanistic details of this reaction,

density-functional theory (DFT) calculations at the M062X/

cc-PVTZ//M062X/6–311G(d,p) level[17] were performed on

the model reaction of 4aand 5awith Ph3C+[B(C6F5)4]@as the

initiator (Scheme 7; see the Supporting Information for

computational details and Figures S74–S79 for the free-

energy profile and the optimized structures).[18] Thesolvent

effect was taken into consideration using apolarizable

continuum model (PCM)[19] with benzene as asolvent for

both geometry optimizations and single-point energy calcu-

lations.Benzene was chosen over chlorobenzene because all

byproducts did form in benzene.The initiation step involving

hydride transfer from Et2SiH2to Ph3C+readily occurs over an

activation barrier of 17.4 kcalmol@1.[20] Theresulting hydro-

gen-substituted silylium ion [Et2HSi(benzene)]+can associate

with the C=Cdouble bond in 4a to form the b-silicon-

stabilized carbenium ion Iwith [B(C6F5)4]@as the counter-

anion. This association has been calculated to be exergonic by

16.1 kcalmol@1with respect to the ion pair [Et2HSi-

(benzene)]+[B(C6F5)4]@.Insolution phase,the intermolecu-

larly alkene-stabilized silylium ion IQis predicted to be more

stable than other donor-stabilized silylium ions such as the

corresponding benzene-, chlorobenzene-, hydrosilane-, or

cyclopropyl-stabilized systems (see Tables S1–S3). Therefore,

Iwas selected as the energy reference in the following

discussion. Theion Ithen undergoes an intramolecular

[1,3] hydride shift from the silicon atom to the benzylic

carbon atom to arrive at the benzene-stabilized silylium ion II

over abarrier of 16.1 kcalmol@1(Scheme 7). Subsequent

reorganization of II forms the intramolecularly stabilized

silylium ions III (arene stabilization) or IV (cyclopropane

stabilization in cis-ortrans-configuration), and the corre-

sponding barriers for the formation of these species are 1.5,

6.2, and 6.4 kcalmol@1(relative to II). As aconsequence of the

low free-energy difference between these intermediates,they

Scheme 6. Control experiments III:Deuterium-labeling of the hydro-

silane.

Scheme 7. Initiation and catalytic cycle of the silylium-ion-promoted (5++1) cycloaddition of 4a and 5a (see the SupportingInformation for

calculated structures of relevant intermediatesand transitionstates). Foreach reaction step, the Gibbs free reaction energies and barriers (labeled

with an asterisk) in kcalmol@1were computed with the M06-2X functional.

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are all energetically accessible and likely in equilibrium with

each other.The cyclopropane-stabilized IV can convert into

the b-silicon-stabilized carbenium ion Vthrough aconcerted

[1,2] phenyl shift/ring-expansion transition state (path a). Of

the two configurations of IV,cis-IV gives the lowest

[1,2] phenyl shift/ring-expansion transition state cis-TSIV–V

with asmall activation barrier of 9.7 kcalmol@1(see Fig-

ure S75 for further analysis of structural details of cis-TSIV–V

and trans-TSIV–V).[21] The[1,2] phenyl shift in cis-IV is driven

by the ring expansion of the highly strained bicyclo[3.1.0]hex-

2-silyl cation cis-IV into the six-membered-ring silylium ion

V.[22] Subsequent hydride transfer from 5a to Vaffords the

C(sp3)@H/silylium ion complex VI with abarrier of 15.9 kcal

mol@1.Finally,the association of another molecule of 4awith

Et2HSi+regenerates Iand releases 7aa,that is the major

product obtained experimentally.The [1,3] hydride shift with

an activation barrier of 16.1 kcalmol@1is the rate-limiting step

(I!II), which is consistent with the rapid reaction rate at

room temperature (see Figure S85).

Thedeuterium incorporation in the benzylic position of

7aa (Scheme 6) could be attributed to the formation of the

benzylic cation 7aa+by an intramolecular [1,2] hydride shift

in V(see Figure S84). Such aprocess is endergonic by

4.7 kcalmol@1with an activation barrier of 14.6 kcalmol@1

(relative to V). Further deuteride transfer from [D1]5b to

7aa+forms [D]7aa and regenerates the donor-stabilized

silylium ion. Thecorresponding barrier of this process is

13.9 kcalmol@1.

The[1,2] aryl migration/ring expansion cis-IV!Vof path

aisincompetition with the cyclopropane-to-cyclopropane

rearrangement trans-IV!trans-VII (9.7 versus 13.1 kcal

mol@1;Scheme 7).[21] Theformation of that bicyliccation is

the result of synchronous C2–C4 bond making and C4–C6

bond breaking in trans-IV.Acompeting hydride transfer from

5ato either C4 or C3 of trans-VII furnishes 8aa(path b) and

9aa (path c), respectively.The reaction outcome with 7aa as

the major product and 8aa and 9aa as byproducts is in

accordance with the free-energy difference of those two

barriers (DDG*=3.4 kcalmol@1), making this (5++1) cyclo-

addition akinetically controlled process.

Conclusion

We have disclosed here atransition-metal-free (5++1)

cycloaddition of VCPs and hydrosilanes that is promoted by

the self-regeneration of silylium ions.[7,9,10] Thenew reaction

also involves a[1,2] migration of an aryl group,eventually

furnishing 4- rather than 3-aryl-substituted silacyclohexane

derivatives.Based on various control experiments and

quantum-chemical calculations,reaction mechanisms that

rationalize the formation of the three products have been

proposed. Thebranching point is an intramolecularly cyclo-

propane-stabilized silylium ion that can either undergo

akinetically favored, concerted [1,2] aryl migration/ring

expansion or engage in acyclopropane-to-cyclopropane

rearrangement. That bond reorganization represents

astraightforward and atom-economic access to silacyclohex-

ane derivatives,which are potentially relevant to medicinal

applications.[23]

Acknowledgements

Thework was funded by the Deutsche Forschungsgemein-

schaft (DFG,German Research Foundation) under Germa-

nyQsExcellence Strategy (EXC 2008/1-390540038). G.W.

thanks the China Scholarship Council for apostdoctoral

fellowship (2019–2020). All theoretical calculations were

performed at the High-Performance Computing Center

(HPCC) of Nanjing University.M.O.isindebted to the

Einstein Foundation (Berlin) for an endowed professorship.

Conflict of interest

Theauthors declare no conflict of interest.

Keywords: cycloaddition ·density-functional calculations ·

ring expansion ·silylium ions ·small-ring systems

[1] a) T. Hudlicky,J.W.Reed, Angew.Chem. Int. Ed. 2010,49,

4864–4876; Angew.Chem. 2010,122,4982–4994;b)J.E.

Baldwin, Chem. Rev. 2003,103,1197–1212.

[2] Z. Goldschmidt, B. Crammer, Chem. Soc.Rev. 1988,17,229–

267.

[3] a) G. Fumagalli, S. Stanton, J. F. Bower, Chem. Rev. 2017,117,

9404–9432;b)L.Souillart, N. Cramer, Chem. Rev. 2015,115,

9410–9464;c)Y.Gao,X.-F.Fu, Z.-X. Yu, Top. Curr.Chem.

2014,346,195–231;d)M.Rubin, M. Rubina, V. Gevorgyan,

Chem. Rev. 2007,107,3117–3179;e)S.C.Wang,D.J.Tantillo, J.

Organomet. Chem. 2006,691,4386–4392.

[4] a) G. A. Olah, D. P. Kelly,C.L.Jeuell, R. D. Porter, J. Am.

Chem. Soc. 1970,92,2544–2546;b)G.A.Olah, C. L. Jeuell,

D. P. Kelly,R.D.Porter, J. Am. Chem. Soc. 1972,94,146–156;

c) G. A. Olah, P. W. Westerman, J. Am. Chem. Soc. 1973,95,

7530–7531;d)J.F.Wolf,P.G.Harch, R. W. Taft, W. J. Hehre, J.

Am. Chem. Soc. 1975,97,2902 –2904;e)H.Mayr,G.A.Olah, J.

Am. Chem. Soc. 1977,99,510 –513;f)K.B.Wiberg,D.Shobe,

G. L. Nelson, J. Am. Chem. Soc. 1993,115,10645–10652.

[5] I. Fleming, Chem. Soc.Rev. 1981,10,83–111.

[6] a) J. B. Lambert, Y. Zhao,R.W.Emblidge,L.A.Salvador,X.

Liu, J.-H. So,E.C.Chelius, Acc.Chem. Res. 1999,32,183–190;

for asummary of the chemistry of silyl-substituted carbocations,

see:b)H.-U.Siehl, T. Mgller in The Chemistry of Organic

Silicon Compounds,Part 2 (Eds.: Z. Rappoport, Y. Apeloig),

Wiley,Chichester, 1989,pp. 595–701.

[7] A. Roy,V.Bonetti, G. Wang,Q.Wu, H. F. T. Klare,M.

Oestreich, Org.Lett. 2020,22,1213–1216.

[8] J. Y. Corey, J. Am. Chem. Soc. 1975,97,3237–3238.

[9] a) J. B. Lambert, Y. Zhao,H.Wu, J. Org.Chem. 1999,64,2729 –

2736;b)V.J.Scott, R. C¸ elenligil-C¸etin, O. V. Ozerov, J. Am.

Chem. Soc. 2005,127,2852–2853;c)R.Panisch, M. Bolte,T.

Mgller, J. Am. Chem. Soc. 2006,128,9676–9682;d)K.Mgther,

M. Oestreich, Chem. Commun. 2011,47,334–336;e)K.

Mgther,J.Mohr, M. Oestreich, Organometallics 2013,32,

6643–6646;f)O.Allemann,S.Duttwyler, P. Romanato,K.K.

Baldridge, J. S. Siegel, Science 2011,332,574 –577;g)B.Shao,

A. L. Bagdasarian, S. Popov,H.M.Nelson, Science 2017,355,

1403–1407.

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