Cyclopropanation/Carboboration Reactions of Enynes with B(C6F5)3

Article abstract of DOI:10.1021/jacs.5b09311

Stoichiometric reaction of B(C₆F₅)₃ with 1,6-enynes is shown to proceed via initial cyclopropanation and formal 1,1-carboboration. Depending on the substitution on the alkene moiety, subsequent ring-opening of the cyclopro

Full text of DOI:10.1021/jacs.5b09311

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Article
Cyclopropanation / Carboboration Reactions of Enynes with B(C6F5)3
Max M. Hansmann, Rebecca L. Melen, Matthias Rudolph, Frank Rominger,
Hubert Wadepohl, Douglas W. Stephan, and A. Stephen K. Hashmi
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.5b09311 • Publication Date (Web): 18 Nov 2015
Downloaded from http://pubs.acs.org on November 20, 2015
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Cyclopropanation / Carboboration Reactions of Enynes with
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Max M. Hansmann,*,a Rebecca L. Melen,b Matthias Rudolph,a Frank Rominger,a Hubert
Wadepohl,c Douglas W. Stephan*,d and A. Stephen K. Hashmi*,a,e
a) Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120
Heidelberg, Germany
b) School of Chemistry, Cardiff University, Main Building, Cardiff, CF10 3AT, Cymru/Wales, UK
c) Anorganisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120
Heidelberg, Germany
d) Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada
e) Chemistry Department, Faculty of Science, King Abdulaziz University (KAU), Jeddah 21589, Saudi Arabia.
ABSTRACT: Stoichiometric reaction of B(C6F5)3 with 1,6-enynes are shown to proceed via initial cyclopropanation and
formal 1,1-carboboration. Depending on the substitution on the alkene moiety, subsequent ring-opening of the cyclopro-
pane affords either cyclopentane or cyclohexane derivatives in which the C6F5 and B(C6F5)2 adopt a 1,4-positioning. Mech-
anistically this transformation involves π-activation of the alkyne moiety which triggers cyclopropanation, followed by
carboboration. Both the cyclopropanation and subsequent ring-opening are shown to be stereospecific. Both cyclopropa-
nation and 1,4-carboborated products were employed as Lewis acid components in frustrated Lewis pair activation of H2
and CO2.
INTRODUCTION
beta-carbon atom in a 1,1-carboboration reaction. Since
these findings the reactions of B(C6F5)3 with π-bonds has
been widely exploited in 1,1-carboboration.24,28-43 An ele-
gant report by Ingleson described a metal-free route to
1,2-carboborations of alkynes using Lewis acidic
boranes.44 More recently, Bourissou and coworkers have
The construction of C-C bonds by transition metal cataly-
sis is one of the main tools for the elaboration of molecu-
lar complexity providing diverse and atom-economic
protocols.1-2 Within this toolbox of synthetic strategies,
reactions of enynes have drawn considerable attention.
Since the pioneering work of Trost which exploited pal-
ladium catalyzed cycloisomerization reactions of 1,n-
enynes,3-4 several reports have described a variety of tran-
sition metals most significantly gold catalysts for related
enyne activations.5-13
described a related 1,2 carboboration using a borenium
45
reagent
while we have reported 1,2-carboborations of
allenyl ketones and esters.46 Erker and coworkers also
reported the reaction B(C6F5)3 with simple conjugated
enynes, affording both carboboration and cyclization to
give a facile route to a 2,3-dihydroborole.47-48 In related
work, Ingleson has described the reactions of 1,6 hex-
adiynes with BCl3 to give electrophilic boralative cy-
clization products.49
An alternative approach involving the use of main
group reagents has emerged over the last decade. Indeed
in a number of cases, such reagents have been shown to
mimic a variety of the aspects of transition metal reactivi-
ty.14 Perhaps the most prominent example is the splitting
of H2 by frustrated Lewis pairs (FLPs).15-17 However, FLPs
have also been exploited for the activation of olefins18 and
alkynes.19 These findings stimulated the study of Lewis
acids as π-activators of alkyne-derivatives for cyclization
reactions.20-24 In this regard, recent studies have described
stoichiometric reactions of B(C6F5)320-24 although Lewis
acid catalysts based upon the heavier group 13 elements
gallium or indium have also been reported.25-26
In seeking to extend the reactivity of B(C6F5)3 in fur-
ther reactions with enynes, targeting new avenues to
cyclization, we noted that for transition metal mediated
cyclizations of enynes, a number of experimental and
theoretical studies debated the nature of key intermedi-
ates, suggesting that cyclopropane, cyclobutane, cationic,
radical or carbene type intermediates may be involved.50-56
In this manuscript we explore the reactivity of a series of
enynes with B(C6F5)3, demonstrating the initial products
are derived from cyclopropanation and formal 1,1 carbob-
oration. Depending on substitution, further ring-opening
of the cyclopropane affords cyclopentane or cyclohexane-
derivatives which presents net 1,4-carboboration prod-
Berke27 and Erker28 independently showed that
reactions of B(C6F5)3 with alkynes resulted in delivery of
both C6F5 and B(C6F5)2 to an alkyne carbon with
concurrent migration of the alkyne substitutent to the
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ucts. The subsequent utility of these resulting products in The formation of 2a proceeds with the construction of 3
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FLP activation of H2 and CO2 are also probed.
RESULTS AND DISCUSSION
C-C bonds affording 5 new stereocenters. However, de-
spite the molecular complexity generated in this reaction,
2a forms selectively with the phenyl ring in the endo posi-
tion with respect to the alkylborane on the cyclopropane
ring. In the reaction, we only ever observe two diasterom-
ers being formed as a 3:1 mixture at the α-position to bo-
ron. Nonetheless, the major diastereomer could be easily
separated by fractional crystallization giving clean prod-
uct on a preparative scale. This reaction stands in stark
contrast to typical 1,1-carboboration reactions of alkynes
which afford vinylboranes.29
Reaction of 1,6-enyne 1a in a 1:1 stoichiometric ratio with
B(C6F5)3 results in a rapid (< 10 min) and very clean trans-
formation, generating a 3.1:1 mixture of two diastereomers
1
as evidenced by in situ H/19F/13C NMR spectroscopy. 2D-
NMR studies allowed the clear assignment of the ob-
tained isomeric mixture of the diastereomers of 1,1-
carboborated product 2 which contains a cyclopropane
unit (Scheme 1). The 11B NMR spectrum shows a broad
resonance at δ ≈ 3 ppm, characteristic of an intramolecu-
lar Lewis acid/base adduct suggesting an interaction of
the B with a carbonyl fragment similar to that observed in
our previous studies.46 19F NMR spectroscopy shows two
sets of resonances at -132.3/-140.3 ppm (o-C6F5), -154.5/-
160.2 ppm (p-C6F5) and -163.1/-165.6 ppm (m-C6F5). These
are attributed to two distinct C6F5 groups resulting from a
carboboration reaction. Interestingly, the 13C NMR spec-
trum reveals a 13C-19F through space coupling indicated by
the resonance for C2 which appears as a triplet at 43.7
ppm with a coupling constant of 8.0 Hz (Figure 2) at
room temperature. Similar through space couplings have
been previously observed.57-58 This is assumed to result
from the close proximity of the C-H bond with the ortho-
fluorine atoms on the C6F5 ring. This is consistent with
the observation of five 19F NMR signals for each C6F5 ring
in 2a at -80 °C (Figure S1; SI) and further supported by
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(C6F5)2
B
B(C6F5)3
O
MeO2C
MeO2C
C6F5
(i)
MeO
Ph
CH2Cl2, rt
MeO2C
Ph
1a
2a 3.1:1 (dr)
(C6F5)2
B
O
B(C6F5)3
C6F5
MeO2C
MeO2C
(ii)
MeO
Me
CH2Cl2, rt
MeO2C
Me
1b
2b
3.2:1 (dr.)
(C6F5)2
B
B(C6F5)3
MeO2C
MeO2C
O
C6F5
Me
(iii)
MeO
CH2Cl2, rt
Me
MeO2C
Me
Me
13
19F/1H HETCOSY and C NMR studies at -80 °C revealing
1c
2c
3.8:1 (dr.)
the correlation of the F atom with the C2-H bond (Figure
S2, S4). The structural connectivity was confirmed by an
X-ray diffraction study (Figure 1) revealing intramolecular
coordination of the carbonyl moiety to the Lewis-acidic
boron center to generate the tricyclic 7/5/3- membered
ring system. In addition, the solid-state structure exhibits
a short C2···F distance of 2.820 Å, typical for through space
19F/13C interactions previously observed.57-58
(C6F5)2B
O
O
C6F5
Me
S
N
O
B(C6F5)3
(iv-vi)
O
S N
Me
Me
CH2Cl2, rt
Me
X
X = Me
2d
2e
X = Me
Br
1:1 (dr.)
1.2:1 (dr.)
X
1d
1e 1f
, Br , NO2
NO2 2f 1.2:1 (dr.)
Scheme 1. Boron mediated cyclopropanation reactions of
1,6-enynes.
We were encouraged by this initial result and decided to
probe related cyclopropanation reactions. Treatment of
1,6-enynes with methyl- (1b) or dimethyl-substituted (1c)
olefins with stoichiometric quantities of B(C6F5)3 cleanly
gave diastereomeric mixtures of the cyclopropanation
products 2b and 2c in ratio of ca. 3.2:1 and 3.8 respective-
ly (Scheme 1). Interestingly, 2c proved to be remarkably
stable even at 60 °C for several days. In the case of the
cyclopropanation product 2b, a single crystal X-ray dif-
fraction study confirmed the structural assignment (see
SI) and reveals that coordination of the ester carbonyl
moiety to the Lewis acidic boron center yields a seven-
membered ring comparable to that observed for 2a.
Figure 1. Solid-state molecular structure of 2a. C: Black, N:
blue, O: red, F: pink, B: yellow-green, H: white.
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C6F5
F
1
2
3
4
5
6
7
C6F5
2
F
B
H
B(C6F5)3
MeO2C
F
MeO
Me
Me
(i)
MeO2C
O
O
F
B
C2
H
F
Ph
C6F5
1g
MeO
C6F5
2g 1:1.5 (E:Z)
MeO2C
O
O
Figure 2. 13C/19F through space coupling.
O
C6F5
B(C6F5)2
O
8
9
B(C6F5)3
S
N
S
N
(ii-iii)
Me
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Me
In a similar fashion the 1,6-enynes containing a para-
sulfonyl-amide (1d-f) react with B(C6F5)3 rapidly and high-
ly selectively to give the corresponding cyclopropana-
tion/carboboration products (2d-f). In contrast to 2a-c, 11B
NMR spectroscopy showed broad peaks around
δ ≈ 77 ppm, consistent with a trigonal planar boron cen-
ter. In these cases, while in situ NMR spectroscopy indi-
cated a quantitative conversion to the products, diaster-
omerically pure rac-(R,R,S)-2d-f were obtained on a pre-
parative scale by fractional crystallization in yields of 43%
(2d), 41% (2e) and 39% (2f). While these species were
challenging to crystalize, single crystals of 2d were isolat-
ed and X-ray data affirmed the formulation (Figure 3) and
the presence of a three coordinate boron center. It is
interesting to note that the diasteromeric ratios of the
products derived from these sulfonamide derived 1,6-
enynes (1d-f) were 1:1. This stands in contrast to the prod-
ucts derived from malonic acid 1,6-enynes (1a-c) and
suggests the selectivity in this reaction might involve a
chelate assisted carboboration mechanism in which the
coordination of the Lewis acidic borane to the Lewis basic
ester functionality directs the reaction yielding one dia-
stereoisomer in preference to the other.
R = Me 2h; 4:1 (E:Z)
Br 2i; 4:1 (E:Z)
R
R = Me 1h, Br 1i
R
BrC6H4CHO
Br
O
O
S
C6F5
N
(C6F5)2
B
Me
O
3
O
Si
O
B(C6F5)3
O
Si
O
C6F5
B(C6F5)2
(iv)
Me
Me
1j
2j 1.5:1 E/Z
C6F5
MeO2C
MeO2C
B(C6F5)3
MeO2C
MeO
(v-vi)
R
O
B
C6F5
C6F5
R
R = CF3 1k, OMe 1l
R = CF3 2k; 1:1 E:Z
2l
OMe ; 1:1 E:Z
O
O
O
C6F5
B(C6F5)2
O
S
N
B(C6F5)3
S
N
(vii)
1m
Br
Br
BrC6H4CHO
CF3
CF3
2m 1.9:1 E:Z
O
C6F5
O
S
N
(C6F5)2
B
O
Br
CF3
4
Br
Scheme 2. 1,4-carboboration reactions of 1,6-enynes.
The corresponding reaction of the 1,6-enyne 1g featuring a
gem-disubstituted alkene, with B(C6F5)3 proceeds cleanly
in < 3 h to give quantitative formation of a 1:1.5 diaster-
omeric mixture of a new product. 2D NMR studies indi-
cated the generation of the unexpected 1,4-carboboration
product 2g as a mixture of E and Z isomers depending
upon the position of the C6F5 group on the newly generat-
ed alkene fragment (Scheme 2). The assignment of the E
or Z diastereomers were confirmed by NOE measure-
ments as well as 13C measurements in which only the E-
compound exhibited a through-space 13C/19F coupling59
between the ortho-C6F5 groups and the proximal
Figure 3. Solid-state molecular structure of 2d. C: Black, N:
blue, O: red, S: yellow, F: pink, B: yellow-green, H: white.
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Ingleson from the reaction of BCl3 with the terminal
diyne, 1,6-heptadiyne.49
1
2
3
4
5
6
7
8
Analogous reactivity of enynes 1h-i containing sulfon-
amide functionalities, the 1,6-cyclic silyl protected diol
enyne derivative 1j and the aryl-substituted enynes 1k-m
(Scheme 2) afforded the related E/Z-1,4-carboboration
11
products 2h-m. B NMR data were consistent with either
three-coordinate boron species which gave a broad peak
at δ > 60 ppm (2h-2j, 2m) or four-coordinate compounds
with a more sharp peak at δ ≈ 27 ppm (2k, 2l). While the
reaction of the para-brosyl amide derivative 2i could be
fractionally crystallized to give the diasteromerically pure
1,4-carboborated product (E)-2i, the para-tosyl amide
analog 2h proved to be more resistant to crystallization.
However, the corresponding para-bromobenzaldehyde 3
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adduct derived from 2h was readily isolated and showed a
11
sharp singlet in the B NMR spectrum at -8.5 ppm
.
In the
case of 2k and 2l, X-ray diffraction confirmed the nature
of the 1,4-carboboration products (Figure 4). In the reac-
tion of enyne 1m, the 1,4-carboboration product 2m was
formed as a 1:1.8 mixture of E/Z-isomers. In this case, X-
ray data was obtained for the para-bromobenzaldehyde
adduct of the (E)-isomer of 2m, 4 (Figure 6).
Figure 4. Solid-state molecular structure of compounds
2g and 2k. C: Black: N: blue: O: red, F: pink: B: yellow-
green, H: white.
Figure 5. Solid-state molecular structure of 4 (C6F5 groups on
boron removed for clarity). C: Black, N: blue, O: red, F: pink,
Br: brown, S: yellow, B: yellow-green, H: white.
methylene proton in the cyclopentane ring (see SI). A
single crystal X-ray diffraction study of the minor (E)-
isomer 2g confirmed the assigned connectivity and the
net 1,4- nature of the carboboration product (Figure 4). In
addition, the X-ray crystal structure clearly depicts the
bicyclic nature of 2g which comprises a cyclopentane ring
and a seven membered ring formed by coordination of
the ester fragment to boron. The structure also reveals the
short F-C separation of 2.90(1) Å between an ortho-F and
the methyl substituent on the cyclopentane ring, con-
sistent with the observed NOE and 13C NMR data. It is
important to note that the formation of 2g is an unusual
example of carboboration ultimately affording 1,4-
positioning of the boron and fluoroarene fragments. Very
recently, a net 1,4-chloroboration has been reported by
Further insight into the selectivity of these cyclopropa-
nation reactions with different olefin regioisomers was
probed employing the enynes 1n and 10 which are identi-
cal with the exception of the geometry (cis or trans) of the
alkene. The reaction of the trans-olefin 1n gave a 1:1.5
mixture of cyclopropanation products 2n (Scheme 4).
Although 2n formed as two diastereoisomers, one could
be selectively isolated and fully characterized at low tem-
peratures. However, it should be noted that this com-
pound was unstable in solution at room temperature and
showed an unselective reaction yielding a mixture of cy-
clopropanation ring opening products.
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(C6F5)2
B
1
2
3
4
5
6
O
C6F5
MeO2C
B(C6F5)3
MeO
MeO2C
MeO2C
Me
1:1.5 (dr.)
2n
1n
Me
7
8
9
MeO2C
MeO
C6F5
Me
10
11
12
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O
B(C6F5)2
MeO2C
MeO2C
B(C6F5)3
2o
+
C6F5
Me
MeO2C
MeO
1o
Me
O
B(C6F5)2
5
Scheme 3. Cyclopropanation and 1,4-carboboration of
E/Z-olefin derived enynes.
In contrast to the reaction of the E-olefin 1n with B(C6F5)3,
the equivalent reaction of the Z-configured enyne sub-
strate 1p afforded two 1,4-carboboration products with no
evidence for cyclopropanation. However 2D NMR analysis
were not consistent with the expected mixture of E/Z-
isomers as seen previously for 1g-m (Scheme 2) but rather
a 1:1 mixture of the 1,4-carboboration products based on 5-
membered (2o) and new 1,4-carboboration product based
upon a 6-membered ring (5) (Scheme 3). In addition,
unlike 2g-m which were formed as a mixture of E/Z iso-
mers, it should be highlighted that both compounds 2o
and 5 were formed as single diastereomers. While 5 was
found to be thermally stable, 2o decomposes in solution
at room temperature. The formulations of the two prod-
ucts were confirmed by solid-state structure determina-
tions (Figure 6) which show intramolecular coordination
of the ester oxygen atom to the Lewis acidic borane.
Based on the reactivity described above for 1g-m, the
formation of 2o was expected however, the formation of
the 6-membered compound 5 represents a new pathway
for the cyclopropane opening mechanism. The differing
reaction pathways for the E/Z-olefin configured enynes
confirmed the stereospecific nature of the cyclopropana-
tion and ring-opening processes. Furthermore these ob-
servations exclude a radical mechanism and preclude
conformational equilibration of the intermediates.
Figure 6. Solid-state molecular structures of 2o and 5. C:
Black, N: blue, O: red, F: pink, B: yellow-green, H: white.
O
O
O
C6F5
O
1. B(C6F5)3
2. H2O
S
N
S
N
B(C6F5)2
OH2
1p
6
Me
Me
C6F5
MeO2C
MeO
B(C6F5)3
MeO2C
MeO2C
O
B(C6F5)2
1q
7
Scheme 4. Carboboration reactions with terminal olefin
derived enynes.
Following these studies, the reactions of the monosubsti-
tuted terminal alkene derived precursors 1p and 1q with
B(C6F5)3 were probed. These proceed less cleanly than
previous examples, giving mixtures of carboboration
products. Nonetheless, in the case of 1p, subsequent to
the reaction with B(C6F5)3 addition of water gave single
crystals of the 1,4-carboboration product 6 as a water
adduct which was confirmed by solid-state structure de-
termination (Scheme 4, see SI). In contrast, the reaction
of 1q with B(C6F5)3 afforded the six-membered cyclohex-
ane derived 1,4-carboboration product 7 as an intramo-
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lecular chelate (Scheme 4, Figure 7). Thus, while the reac- the sample of 2r’ to room temperature (see Figure S6, SI)
1
2
3
4
tions of substituted enynes are largely selective in the
products generated (cyclopropanation vs. carboboration),
the unsubstituted alkene fragments afford rather unselec-
tive reactions.
confirming that the cyclopropanation product is formed
en route to the 1,4-carboboration product. (E)-2r was
found to be configurationally stable and did not undergo
thermal isomerization to (Z)-2r.
5
6
7
O
O
S
N
8
9
R1
1m; R1 = Br; R2 = CF3
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R2
1
2
1r
; R = NO2; R = H
B(C6F5)3
(C6F5)2B
O
(C6F5)2B
O
C6F5
C6F5
O
O
S
N
S
N
+
Figure 7. Solid-state molecular structure of 7. C: Black, N:
blue, O: red, F: pink, B: yellow-green, H: white.
R1
2m'
2r'
R1
R2
2m''
2r''
R2
Mechanistic Considerations. In order to understand
the outcomes of these cyclopropanation/carboboration
reactions, mechanistic studies were undertaken. Time
dependent multinuclear NMR studies of the reaction of
1,6-enyne 1m with B(C6F5)3 revealed the formation of two
intermediates 2m’ and 2m’’ in a mixture of diastereoiso-
slow
fast
C6F5
O
C6F5
B(C6F5)2
O
O
O
S
N
S
N
B(C6F5)2
1
mers. These species gave rise to H NMR signals at 1.49
and 1.12 ppm (2m’), and 1.40 and 0.70 ppm (2m’’) which
could be assigned to the characteristic cyclopropane pro-
tons showing the formation of the two corresponding
diastereomeric cyclopropanation products (Scheme 5).
While the cyclopropanation intermediates 2m’ and 2m’’
are formed rapidly, the rate of subsequent ring-opening
for each diastereomer to give (E/Z)-2m differs significant-
R1
R1
R2
(E)-2m
(E)-2r
R2
(Z)-2m
(Z)-2r
Scheme 5. 1,4-carboboration reaction pathway via cyclo-
propane intermediates.
1
ly. Kinetic data obtained from time dependent H/19F
NMR analysis (Figure S5, SI) shows that 2m’’ undergoes
ring-opening to form (Z)-2m more rapidly than 2m’, re-
sulting in a changing E/Z ratio of 2m over the course of
the reaction. Ultimately this affords a ratio of 1.9:1 with
the major isomer being (E)-2m (Figure 8). The differing
rates of ring-opening are consistent with a consideration
of the stereochemistry of the transition state in which a
cyclopropane orbital interacts with the unoccupied p-
orbital at boron. Steric repulsion of aryl/C6F5 groups (Fig-
ure 9) are expected to slow down ring-opening to form
the (E)-2m isomer.
Further support for the proposition of a cyclopropane
intermediate was provided by the reaction of the enyne 1r
with B(C6F5)3 (Scheme 5). In this case, both colorless and
orange crystals could be obtained from the reaction. The
orange crystals proved to be the 1,4-carboboration prod-
uct (Z)-2r containing a trigonal planar Lewis acidic boron
as confirmed by X-ray diffraction (Figure 10). Conversely,
low temperature 2D NMR studies of the colorless crystals
confirmed it to be the cyclopropane intermediate 2r’. The
conversion of 2r’ to (E)-2r could be observed by warming
Figure 8. Kinetic data obtained from the reaction of 1r with
B(C6F5)3 determined by 1H NMR integration.
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H
C6F5
(C6F5)2B
(C6F5)2B
1
2
3
C6F5
C6F5
C6F5
C6F5
Me
C6F5
Me
B
B
H2
[HPtBu3]
C6F5
Ts
N
Ts
N
H
PtBu3
H
Me
4
5
6
7
8
9
10
11
12
13
14
C6F5
2d
PtBu3
8
Ar
2m''
fast
Ar
2m'
CO2
slow
PtBu3
O
H
C6F5
O
(C6F5)2B
C6F5
Me
C6F5
H
B(C6F5)2
B(C6F5)2
Ts
N
Ar
Ar
Me
10
(E)-2m
(Z)-2m
O
Figure 9. Stereochemical rational for differential rates of
cyclopropane opening.
O
C6F5
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
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60
S
N
H2
PtBu3
H
B
O
O
C6F5
S
N
Me
C6F5
C6F5
B(C6F5)2
Me
2i
9
Br
[HPtBu3]
Br
PtBu3
CO2
O
O
C6F5
S
N
PtBu3
O
B
Me
O
C6F5
C6F5
11
Br
Scheme 7. H2 and CO2 activation with cyclopropana-
tion/carboboration products.
Overall the enyne/B(C6F5)3 reaction can be considered as
arising through the initial Lewis acid alkyne activation (I,
Scheme 6) analogous to that previously described for
propargyl esters.21 While such π-alkyne boron complexes
have not been observed, weak van der Waals interactions
of boranes with olefins have been detected.60 The alkyne
activation triggers the nucleophilic attack of the activated
alkyne by the alkene prompting the 5-exo cyclization (II)
and subsequent cyclization to the cyclopropyl cation (III).
The experiments performed with Z- and E-configured
alkenes indicate a concerted cyclopropanation mecha-
nism without the step-wise formation of II. The positive
charge on the α-carbocation in III prompts migration of a
C6F5 group affording the cyclopropanation product as a
mixture of diastereoisomers in which there has been a net
1,1-carboboration reaction. The subsequent cyclopropane
ring-opening reaction to give the E/Z five- or six-
membered ring products depends markedly on the nature
of the substitution as seen for the reactions of 1g-1s with
B(C6F5)3. Thus while mono- or di-substitution in 7-
position on the alkene moiety affords stable cyclopropyl
compounds (1a-1h), the absence of this substitution
prompts stereospecific ring-opening affording either cy-
clopentane or cyclohexane derived alkylboranes (Scheme
6). It is noteworthy that there is precedence for methylcy-
clopropane boron derivatives undergoing ring-openings,61
and indeed such compounds have been used in homoal-
Figure 10. Solid-state molecular structure of 2r. C: Black, N:
blue, O: red, F: pink, S: yellow, B: yellow-green, H: white.
B(C6F5)3
2
1
B(C6F5)3
R
R
R
R
6
R'
(C6F5)3B
R'
I
7
R
R
via
R'
II
C6F5
migration
(C6F5)2B
(C6F5)2B C6F5
C6F5
R'
R
R
R
R'
R
III
ring-
opening
C6F5
R
C6F5
R
R'
R
B(C6F5)2
R
B(C6F5)2
R'
Scheme 6. Proposed Mechanism for the cyclopropana-
tion/carboboration reactions.
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lylation reactions.62 Similarly, cyclopropanes have been
AUTHOR INFORMATION
Corresponding Authors
1
2
3
4
shown to undergo ring-openings on exposure to B/P
FLPs,63 nonetheless, the cyclopropanations described
herein are to our knowledge the first mediated by a bo-
ron-based Lewis acid.
hashmi@hashmi.de
hansmann@oci.uni-heidelberg.de
dstephan@chem.utoronto.ca
5
Small molecule activation. The potential utility of these
cyclopropanation/carboboration products in FLP reactivi-
ty was subsequently probed. Combination of the diaster-
omerically pure of the cyclopropane derivative 2d or the
1,4-carboboration product 2i with the bulky phosphine
tBu3P showed no adduct formation. Upon addition of H2,
NMR data were consistent with the clean activation of H2
in both cases, affording the corresponding phosphonium
hydridoborate species 8 and 9, respectively (Scheme 7).
The spectroscopic data for these products (see SI) are
consistent with that previously observed for closely
related FLPs.64 Similarly, reactions of these FLPs with CO2
(10 bar) cleanly afforded the zwitterionic phosphonium
borate 10 and 11 (Scheme 7). Again, NMR and IR data (see
SI) for these compounds are analogous to previously re-
ported FLP-CO2 adducts.65
6
7
8
9
Funding Sources
NSERC of Canada, Fonds der Chemischen Industrie for a
Chemiefonds and the Studienstiftung des deutschen Volkes
supported this research
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60
ACKNOWLEDGMENT
NSERC of Canada is thanked for financial support. D.W.S. is
grateful for the award of a Canada Research Chair. M.M.H. is
grateful to the Fonds der Chemischen Industrie for a
Chemiefonds scholarship and the Studienstiftung des
deutschen Volkes. R.L.M is thankful for a Humboldt Fellow-
ship.
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CONCLUSION
In summary, the present study has revealed that reac-
tions of B(C6F5)3 with 1,6-enynes proceed via cyclopropa-
nation and concurrent 1,1-carboboration. Subsequent
ring-opening reactions are observed depending on the
nature of the olefin substitution and these affording ei-
ther cyclopentane or cyclohexane derivatives in which the
C6F5 and B(C6F5)2 fragments are 1,4-disposed. Thus this
chemistry exploits the ability of the Lewis acid B(C6F5)3 to
activate alkyne fragments, providing new routes to substi-
tuted cyclic organic molecules. The resulting cyclopro-
pane and 1,4-carboration products are also shown herein
to participate in FLP activations of H2 and CO2.
It is interesting to note that cyclopropanation products
are typically derived from transition metal mediated reac-
tions of enynes.5-12 In addition, Pd-mediated borylative
enyne cyclisations have been used to install (pinacola-
to)boron fragments for subsequent cross couplings.66-68
The present work illustrates the ability of the main group
Lewis acid B(C6F5)3 to effect related cyclizations while
providing an avenue for the installation of a both C6F5 and
B(C6F5)2 fragments. It is noteworthy that Erker and
coworkers have exploited carboboration products in
cross-couplings.28,69 Thus the present chemistry affords a
strategy for the synthesis of highly substituted cyclopro-
panes, cyclopentanes and cyclohexanes with concurrent
carboboration. The potential of this and related chemistry
in the synthesis of functionalized complex organic mole-
cules and FLPs continues to be of interest in our laborato-
ries.
ASSOCIATED CONTENT
Supporting Information. Including synthetic and spectro-
scopic and crystallographic data have been deposited. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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