B(C6F5)3-Catalyzed Diastereoselective Formal (4 + 1)-Cycloaddition of Vinylcyclopropanes and Et2SiH2

Article abstract of DOI:10.1021/acs.orglett.1c01565

A formal (4 + 1)-cycloaddition of vinylcyclopropanes and Et2SiH2 to afford 3,4-disubstituted silolanes is reported. The reaction sequence commences with the known B(C6F5)3-catalyzed alkene hydrosilylation with dihydrosilanes. Cleavage of the remaining Si-H bond in the hydrosilylation product assisted by B(C6F5)3 leads to formation of a cyclopropane-stabilized silylium ion. The activated cyclopropane ring is then opened by the in situ-generated borohydride accompanied by ring closure to the silolane. The diastereoselectivity is rationalized by a mechanistic model.

Full text of DOI:10.1021/acs.orglett.1c01565

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Letter
B(C6F5)3‑Catalyzed Diastereoselective Formal (4 + 1)-Cycloaddition
of Vinylcyclopropanes and Et2SiH2
Peng-Wei Long and Martin Oestreich*
Cite This: Org. Lett. 2021, 23, 4834−4837
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ABSTRACT: A formal (4 + 1)-cycloaddition of vinylcyclopro-
panes and Et2SiH2 to afford 3,4-disubstituted silolanes is reported.
The reaction sequence commences with the known B(C6F5)3-
catalyzed alkene hydrosilylation with dihydrosilanes. Cleavage of
the remaining Si−H bond in the hydrosilylation product assisted
by B(C6F5)3 leads to formation of a cyclopropane-stabilized
silylium ion. The activated cyclopropane ring is then opened by the
in situ-generated borohydride accompanied by ring closure to the silolane. The diastereoselectivity is rationalized by a mechanistic
model.
Scheme 1. VCPs and Silicon Electrophiles: Different
Reaction Pathways Depending on Catalyst and Hydride
Source
inylcyclopropanes (VCPs) are regarded as versatile
building blocks in the field of chemical synthesis and
V
can react in diverse ways,1 serving as C3 and C5 synthons in
various cycloadditions in the presence of transition metals2 and
Lewis acids.3 However, there have been hardly any reports
about Lewis acid-catalyzed cycloaddition reactions of VCPs
and hydrosilanes. Our laboratory recently reported trityl-
cation-initiated, silylium-ion-promoted cycloadditions of VCPs
and dihydrosilanes.4,5 For aryl-substituted VCPs, silicon-
containing six-membered rings were obtained as a result of a
formal (5 + 1)-cycloaddition; a cis-configured cyclopropane-
stabilized silylium ion is the key intermediate in this skeletal
reorganization (R = Ph; Scheme 1, top).6 In turn, a benzyl
instead of an aryl group steered the reaction toward an
intramolecular Friedel−Crafts alkylation involving the inter-
mediacy of a trans-configured cyclopropane-stabilized silylium
ion (R = Bn; Scheme 1, top).7 For both, an initially formed β-
silicon-stabilized8 cyclopropylcarbinyl cation9 is not captured
by external hydride, that is, excess dihydrosilane, but instead
undergoes a 1,3-hydride shift from silicon to carbon to
generate either of the aforementioned cyclopropane-stabilized
silylium ions that can exist as interconverting cis- and trans-
diastereomers.6,7 However, the situation changes completely
with B(C6F5)3/hydrosilane combinations.10 The in situ-formed
borohydride [HB(C6F5)3]−, which is a better hydride donor
than hydrosilanes,11 traps the β-silicon-stabilized cyclopropyl-
carbinyl cation to yield the conventional hydrosilylation
product (Scheme 1, bottom left).5b,12 A new (4 + 1)-
cycloaddition has now been discovered under reaction
conditions similar to those of that B(C6F5)3-catalyzed
hydrosilylation (Scheme 1, bottom right). At higher concen-
tration, more catalyst loading or prolonged reaction time, the
hydrosilylation product is further converted into the
corresponding trans-configured cyclopropane-stabilized sily-
lium ion with [HB(C6F5)3]− as the counteranion. Ring
Received: May 7, 2021
Published: June 2, 2021
https://doi.org/10.1021/acs.orglett.1c01565
© 2021 American Chemical Society
Org. Lett. 2021, 23, 4834−4837
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Letter
opening by intermolecular attack of the borohydride13 (rather
than the intramolecular processes outlined before6,7) could
explain the diastereoselective formation of the trans-3,4-
disubstituted silolane. We present here a B(C6F5)3-catalyzed
formal (4 + 1) cycloaddition of VCPs and Et2SiH2.
extended to 14 days. Because of the minor quantities, the
silolane could not be obtained in analytically pure form.
We then subjected several homologues of VCP 1a having
longer and shorter alkyl chains to the general procedure (1b−e
with n = 4 to 0; Scheme 2). VCP 1b (n = 4) with a 4-
On the basis of our previous work,12a we started the
investigation with the reaction of VCP 1a and Et2SiH2 in
toluene with double the amount of B(C6F5)3 (1.0 versus 0.50
mol %). The conventional hydrosilylation product 3a was
obtained as the major product along with the cycloadduct 2a
(Table 1, entry 1). We examined the effect of different
Scheme 2. Substrate Scope I: Variation of the Internal
a
Substituent
a
Table 1. Optimization of Reaction Conditions
yield
b
b
entry B(C6F5)3 (mol %)
solvent
c (M) 2a (%)
3a (%)
1
2
3
4
5
6
7
8
1.0
3.0
5.0
7.0
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
PhCl
1
1
1
1
26
34
82
78
73
37
61
70
80
75
52
58
<5
47
67
52
13
<5
<5
45
25
8
<5
<5
<5
24
43
46
a
Reactions were performed on a 0.2 mmol scale according to the
optimized procedure (Table 1, entry 9). Unless otherwise noted, the
formation of side products was not observed. Yields are of analytically
pure material obtained after flash chromatography on silica gel. The
relative configuration was confirmed by NMR spectroscopic analysis
10
1
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
1.0
0.1
0.5
2
1
1
1
1
1
1
b
(see the Supporting Information for details). 73% yield along with
9
<5% of the hydrosilylation product obtained at a 1 mmol scale.
c
d
Formation of a tricyclic byproduct in 13% yield.7 Formation of the
10
11
12
13
14
PhF
ring-opened hydrosilylation product in 9% yield.12a Formation of the
e
CH2Cl2
benzene
n-hexane
toluene
conventional hydrosilylation product 3e in 73% yield.6,12a
c
phenylbutyl group furnished the silolane 2b in 61% yield. The
model substrate 1a (n = 3) afforded 2a in 69% yield on a 1
mmol scale. Conversely, VCPs 1c (n = 2) and 1d (n = 1) with
less methylene groups in their carbon chains reacted in
significantly lower yields of 40% for 2c and 30% for 2d.
Byproducts were a previously observed tricylic compound7 in
the case of 1c (13% yield; see Tables S1 and S2) and the ring-
opened hydrosilylation product12a in the case of 1d (9% yield;
see Table S3). The phenyl-substituted VCP 1e (n = 0) gave
the conventional hydrosilylation product 3e in 73% yield (not
shown).6,12a
To assess the functional-group tolerance, a variety of VCPs
1f−n (n = 3) decorated with electronically modified aryl
groups were converted into the corresponding silolanes 2f−n
(Scheme 2). As for the parent VCP 1a, isolated yields were
consistently good, ranging from 60 to 75%. Larger aryl groups
such as naphthyl or biphenyl-4-yl groups as in 1o−q were not
detrimental, except for a biphenyl-2-yl group as in 1r.
The effect of an additional substituent on the cyclopropane
ring was probed in the reaction of several trans-disubstituted
VCPs 1s−v derived from 1a (Scheme 3). Substrates trans-1s−
u with different linear alkyl chains as the R group did undergo
the formal (4 + 1) cycloaddition in good yields yet with
complete loss of the stereochemical information. Silolanes 2s−
u were obtained as diastereomeric mixtures, and the reactions
were generally less clean. VCP trans-1v with R = Ph converted
into the ring-opened hydrosilylation product (not shown).12a
As outlined above, the proportion of the silolane 2a
increased with longer reaction times (Table 1, entry 14).
a
Unless otherwise noted, all reactions were performed on a 0.1 mmol
b
1
scale for 12 h. Yields were determined by H NMR spectroscopy
using CH2Br2 as an internal standard. The reaction time was 90 h.
c
amounts of the catalyst on the product distribution (entries 2−
5). The ratio of the two products shifted toward the silolane 2a
at higher catalyst loadings. While 2a did form exclusively with
more than 5.0 mol % of B(C6F5)3, the global yield slightly
decreased. The concentration was also crucial, and the
formation of the silolane 2a was found to be favored over 3a
with less solvent (entries 6−8). Solvents other than toluene
were tested with 5.0 mol % of B(C6F5)3 at a 1 M substrate
concentration (entries 9−13). The selectivity in favor of the
formal (4 + 1) cycloaddition further improved in polar aprotic
solvents, such as halogenated arenes and CH2Cl2 (entries 9−
11); the proportion of the hydrosilylation product was
substantial in benzene (entry 12). Conversely, almost none
of the cycloadduct formed in hydrocarbon solvents, such as n-
hexane (entry 13).
We note here that the product distribution was also
dependent on the reaction time (entry 1 versus entry 14);
longer reaction times led to more of 2a at the expense of 3a,
indicating that the conventional hydrosilylation product 3a can
be further converted into the silolane 2a (see the mechanistic
analysis). We also tested other dihydrosilanes, such as Ph2SiH2
and Me(Ph)SiH2, under the optimized reaction conditions of
entry 9. However, predominant formation of the hydro-
silylation products was seen, even when the reaction time was
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Letter
(not shown).12a Cleavage of the Si−H bond in 3 mediated by
B(C6F5)3 with intramolecular assistance by the cyclopropyl
moiety14 yields cyclopropane-stabilized silylium ions that can
exist as trans- or cis-adducts; the trans configuration is
energetically more favorable by 2.7 kcal mol−1 for R = Ph6
and 5.3 kcal mol−1 for R = Bn,7 respectively, according to
earlier computations (see Scheme 1, top). The activated
cyclopropane ring is then opened by the in situ-generated
borohydride accompanied by cyclization to the silolane. The
intermolecular delivery of the hydride is related to the known
intramolecular Friedel−Crafts reaction (see Scheme 1, top).7
The transition state TS also explains the relative configuration
of silolanes trans-2. The situation is different with VCPs having
an additional substituent at the cyclopropyl group (Scheme 5,
bottom). A third stereocenter is generated in the hydro-
silylation step yet with no diastereocontrol, for example, d.r. =
50:50 for 1u → 3u. The resulting mixture of epimers can form
various cyclopropane-stabilized silylium ions in the subsequent
Si−H bond heterolysis (not shown), eventually leading to a
mixture of trans- and cis-silolanes 2.
To conclude, the present work enriches the diverse
chemistry of VCPs when reacted with hydrosilanes in the
presence of the trityl cation6,7 or B(C6F5)3.12a The formation
of cyclopropane-stabilized silylium ions is common to several
of these reactions but the fate of these intermediates can be
different depending on substituents and hydride source. The
new formal (4 + 1) cycloaddition also passes through that key
intermediate in trans configuration. In contrast to previous
cases (see Scheme 1),6,7 it is captured intermolecularly by in
situ-generated [HB(C6F5)3]−, and its trans relationship
translates into the relative configuration of the formed
silolane.15,16 We believe that, at this stage of our mechanistic
understanding, further transformations can be developed.
Scheme 3. Substrate Scope II: Variation of the
Cyclopropane Substitution Pattern
a
a
See caption of Scheme 2 for further details.
Hence, we subjected an independently prepared sample of the
hydrosilylation product 3a12a to the reaction conditions
(Scheme 4, top). Exclusive formation of the silolane 2a in
high yield was seen, showing that the skeletal rearrangement is
downstream of the alkene hydrosilylation. A deuterium-
labeling experiment provided evidence that the in situ-formed
borohydride is intimately involved in the ring-opening of the
cyclopropyl group (3a-d1 → 2a-d1, Scheme 4, bottom).
a
Scheme 4. Control Experiments
ASSOCIATED CONTENT
* Supporting Information
■
sı
a
Yield was determined by 1H NMR spectroscopy using CH2Br2 as an
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.1c01565.
b
internal standard. The deuteration grades were estimated by 1H
NMR spectroscopy.
General procedures, experimental details, and character-
ization and spectral data for all new compounds (PDF)
On the basis of our previous experimental findings and
quantum-chemical calculations (see Scheme 1, top),6,7
a
AUTHOR INFORMATION
Corresponding Author
plausible reaction mechanism for this formal (4 + 1)
cycloaddition can be proposed (Scheme 5, top). B(C6F5)3-
catalyzed hydrosilylation of VCPs 1 proceeds as reported to
hydrosilanes 3 with a cyclopropyl group at the β carbon atom
■
Martin Oestreich − Institut fur Chemie, Technische
̈
Universität Berlin, 10623 Berlin, Germany; orcid.org/
0000-0002-1487-9218; Email: martin.oestreich@tu-
berlin.de
Scheme 5. Mechanistic Picture
Author
Peng-Wei Long − Institut fur Chemie, Technische Universität
̈
Berlin, 10623 Berlin, Germany; orcid.org/0000-0003-
4740-1541
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c01565
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
P.-W.L. thanks the China Scholarship Council for a
predoctoral fellowship (2019−2023), and M.O. is indebted
■
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Letter
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