Iron-catalyzed hydroboration of vinylcyclopropanes

Article abstract of DOI:10.1021/acs.orglett.7b02691

An iron-catalyzed hydroboration of vinylcyclo-propane with HBpin is first reported for the preparation of valuable homoallylic organoboronic esters. The iron catalysts enable efficient and regioselective C-C cleavage of vinyl-cyclopropanes, stereoselectively delivering E-alkenes with good stereospecific selectivity at an allylic position. This protocol exhibits mild conditions with good functional group tolerability. The chiral homoallylic organoboronic esters could be further converted into chiral polysubstituted tetrahydrofuran and tetrahydropyran.

Full text of DOI:10.1021/acs.orglett.7b02691

Letter
pubs.acs.org/OrgLett
Iron-Catalyzed Hydroboration of Vinylcyclopropanes
Chenhui Chen, Xuzhong Shen, Jianhui Chen, Xin Hong, and Zhan Lu*
Department of Chemistry, Zhejiang University, Hangzhou 310027, China
S
* Supporting Information
ABSTRACT: An iron-catalyzed hydroboration of vinylcyclo-
propane with HBpin is first reported for the preparation of
valuable homoallylic organoboronic esters. The iron catalysts
enable efficient and regioselective C−C cleavage of vinyl-
cyclopropanes, stereoselectively delivering E-alkenes with good
stereospecific selectivity at an allylic position. This protocol
exhibits mild conditions with good functional group
tolerability. The chiral homoallylic organoboronic esters
could be further converted into chiral polysubstituted tetrahydrofuran and tetrahydropyran.
vinylcyclopropane gave an anti-Markovnikov selective product
lkyl boronic acid derivatives are a very important class of
Aorganic compounds in chemistry. Due to their chemical with 97/3 rr.5a The hydroborations of substituted VCPs with
1
BH3 have been reported to afford a mixture of regioisomers.5
stability and easy elaboration, organoboronic acid derivatives
Additionally, the alkenes could not survive in these trans-
formations. These results decreased the utility of this
transformation. So far, it is highly desirable for the development
of new strategies for highly selective hydroboration of
vinylcyclopropanes.
As a continuation of our interest in earth-abundant
transition-metal-catalyzed transformations,6 herein we describe
an iron-catalyzed Markovnikov-type hydroboration of vinyl-
cyclopropanes to afford homoallylic organoboronic esters via
selective C−C bond cleavage (Scheme 1c).
The 1-phenyl-2-(1′-phenyl)vinyl cyclopropane 1a was
chosen as a model substrate. The reaction of 1a with HBpin
using OPPA as a ligand and FeCl2 as a precatalyst did not afford
hydroboration products (Table 1, entry 1).6f Using Pybox·
FeCl2 or PDI·FeCl2 as precatalysts which used to be suitable for
hydroboration of alkenes and NaHBEt3 as a reductant, the
reaction did not occur (entries 2 and 3). The iron complex
OIP·FeCl2 was found to be a good precatalyst for hydro-
boration of 1a, delivering the homoallylic organoboronic ester
2a in 90% yield with 12/1 E/Z via a C−C bond cleavage
process4,7 (entry 4). This protocol was a good supplement for
the synthesis of polysubstituted homoallylic organoboronic
esters which were difficult to obtain using boromethylation of
allylic compounds.8 Using bromide as a counterion, the
reaction afforded 2a in 88% isolated yield with 15/1 E/Z
(entry 5). The yield decreased when 1 equiv of 1a was used
(entry 6). The reaction could be completed in 10 min (entries
7 and 8). The control experiments without NaBHEt3, or
precatalyst, or ligand were carried out and did not afford the
desired products (entries 9−11). Various reductants have also
been screened, however, to afford traces of products (see Table
S1). The standard conditions were identified as racemic
are considered to be useful synthetic building blocks for the
preparation of intricate molecules. Thus, the development of
new methodologies for the highly efficient and selective
synthesis of diversified organoboronic acid derivatives is
continuously desirable. Late transition-metal-catalyzed olefin
hydroboration is one of the most direct, efficient, and atom-
economic transformations in organoboron chemistry.2 Re-
cently, the catalysts involving earth-abundant transition metals3
such as iron, cobalt, nickel, copper, and manganese have
emerged with high activity and selectivity for alkene hydro-
boration (Scheme 1a).
Vinylcyclopropane (VCP) as a simple and useful synthon has
been used for an impressive range of synthetic applications,
particularly for the construction of all-carbon rings.4 Hydro-
boration of VCP has the potential to afford organoboronates
containing cyclopropanes or alkenes available for further
elaboration (Scheme 1b). The hydroboration of simple
Scheme 1. Hydroboration of Vinylcyclopropanes
Received: August 29, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02691
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Condition Optimizations
b
b
entry
cat.
t (h)
yield (%)
Z/E
1
2
3
4
5
OPPA + FeCl2
Pybox·FeCl2
PDI·FeCl2
DMiPOIP·FeCl2
DMiPOIP·FeBr2
DMiPOIP·FeBr2
DMiPOIP·FeBr2
DMiPOIP·FeBr2
FeBr2
3
<2
<2
<2
90
93
56
97(87)
85
0
−
−
−
12/1
15/1
13/1
12/1
12/1
−
3
3
3
3
c
6
3
7
8
9
0.5
0.17
3
d
10
DMiPOIP·FeBr2
−
3
0
−
−
11
3
0
a
Using HBpin (0.5 mmol), 1a (1.0 mmol), [Fe] (5 mol %), NaBHEt3
b
(15 mol %), and toluene (1 mL). Yields and ratio of E/Z were
determined by 1H NMR analysis based on HBpin, and isolated yield in
c
d
the parentheses. Alkene/HBpin = 1/1. Without NaBHEt3.
Figure 1. Substrate scope.a a Standard conditions: HBpin (0.5 mmol),
1 (1.0 mmol), DMiPOIP·FeBr2 (0.025 mmol), NaBHEt3 (0.075 mmol),
toluene (1 mL), rt, 30 min. Isolated yield and the ratio of E/Z.
b DMiPOIP·FeBr2 (0.05 mmol). c 3 h. d 10 h. e HBpin (0.5 mmol), 1 (0.5
mmol).
vinylcyclopropane (1.0 mmol), HBpin (0.5 mmol), OIP·FeBr2
(5 mol %), and NaBHEt3 (15 mol %) in a solution of toluene
(0.5 M) for 0.5 h.
Under the optimized conditions, the scope of various
substituents on alkene was first explored in Figure 1. The
substrates with a methyl group at the para- or meta-position on
the phenyl ring could be delivered to 2b−2c in 82−85% yields
with 11/1−15/1 E/Z. More sterically hindered substrate 1d (2-
methyl phenyl) could be converted into 2d in 49% yield with
excellent E/Z selectivity. Various aryl rings with electron-
donating and electron-withdrawing substituents were amenable
to this protocol, delivering 2e−l in 56−93% yields. The
polycyclic rings and heterocyclic rings were also tolerable to
provide 2m−2p in 65−88% yields. The reaction of alkyl-
substituted VCP could be carried out to give 2q in 53% yield.
The VCPs attached with bioactive molecules could also be
converted into corresponding products 2r−2t in 86−88%
yields with excellent E/Z. It should be noted that the reaction
could be carried out on a gram scale to afford 2e and 2n in 91%
and 85% yield, respectively.
of stereospecific hydroboration of VCP was next studied in
Figure 2. Using DMtBOIP-FeBr2 as a chiral precatalyst, the
The generality of cyclopropanes was next examined. For a
functionalized aryl moiety, both electron-donating (1aa−1ac)
and electron-withdrawing (1ad−1ag) substituents can be
incorporated, particularly with a fluoro group at the para-,
meta-, or ortho-position (64−95% yields). 1-Naphthyl, 2-
naphthyl, 2-furyl, and 2-thienyl cyclopropanes could be
delivered to the corresponding products 2ah−2al in 48−99%
yields. The reaction of monosubstituted cyclopropane gave
2am in 65% yield with 3/1 E/Z. The 1°-, 2°-, or 3°-alkyl
cyclopropanes were suitable for this catalytic system, affording
2an−2as in 84−99% yields with 4/1−10/1 E/Z. The reaction
of 2,2-dimethyl-1-(1′-phenylvinyl) cyclopropane afforded 2at in
64% yield with >20/1 E/Z.
a
Figure 2. Stereospecific hydroboration of vinylcyclopropanes.a
-
Standard conditions: HBpin (0.25 mmol), 1 (1.0 mmol), [Fe]
(0.0125 mmol), NaBHEt3 (0.0375 mmol), toluene (0.5 mL), rt, 0.5 h.
The ratio of E/Z is better than 10/1. Isolated yield. b 3.0 h.
stereospecific reaction of various racemic vinylcyclopropanes
with HBpin afforded the corresponding chiral homoallylic
boronic esters in 39−97% yields with 77−90% ee. The highly
enantiopure S-2a (98.8% ee) could be obtained via recrystalliza-
tion from ethanol. The absolute configuration was confirmed
by X-ray diffraction of S-2a.9
To control the absolute stereochemistry of products, a
stereospecific variant of this reaction was explored. The scope
The chiral homoallylic organoboronic ester 2a could be
further derivatized (Scheme 2). The lithiation followed by
B
DOI: 10.1021/acs.orglett.7b02691
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
with 33% ee (see SI). This indicated the reaction was
stereospecific. To demonstrate the plausible mechanism, the
reaction of VCP with deuterium labeled DBpin was performed
under standard conditions. The reaction of 1o with a phenyl
substituent or 1as with a tert-butyl substituent afforded D-2o
(eq 4) or D-2as (eq 5) with 66% or 85% deuteration of one
hydrogen on the methyl group, respectively. Incomplete
deuteration of D-2o is consistent with the intermediacy of an
iron hydride species which would be generated from β-hydride
elimination of the iron−carbon intermediate. The added
hydrogen atom on the methyl group in D-2as might be
introduced from initial activator NaBHEt3. Due to steric and
electronic effects, the iron−carbon intermediate from the
reaction of 1o did undergo β-hydride elimination to regenerate
the iron hydride species more easily than that from the reaction
of 1as. The 1a could react with BH3 directly affording the anti-
Markovnikov-type hydroboration products 10 in 64% yield
with 1.4/1 dr (eq 6) which indicates that the iron catalyst plays
a significant role in controlling the regioselectivity.
Scheme 2. Further Derivatizations
A proposed mechanism is shown in Scheme 3. On the basis
of previously reported literatures, we assume that an iron−
bromination of 2a afforded 3. The fluoridation followed by
palladium-catalyzed cross-coupling reaction gave 4 in 76%
yield. The oxidation of 2a with peroxide delivered 5 in 89%
yield. The reaction of 2a with lithiated CH2Br2 followed by
oxidation produced 6 in 91% yield. Additionally, the chiral
polysubstituted tetrahydrofuran 7 and tetrahydropyran 8 could
be obtained in 99% and 87% yield, respectively, through the
intramolecular iodoetherification reaction.3h,p,10
Scheme 3. Proposed Mechanism
During careful analysis of side products of the reaction, side-
product diene 9 was isolated and identified in the reaction of 1e
which illustrated that the primary alkyl iron complex should be
formed following β-hydride elimination to afford the diene and
regenerate the iron hydride species (eq 1). The reaction of
hydride complex is involved as an active species for the
transformation. First, the iron−hydride complex A is generated
from OIP-FeBr2 in the presence of NaBHEt3. The complex A
then undergoes alkene coordination with VCP followed by
alkene insertion into the iron−hydride bond to afford the
tertiary alkyl iron complex C. The selective β-carbon
elimination of complex C affords primary alkyl iron complex
D which might undergo β-hydride elimination to provide side-
product dienes.11 Finally, a ligand exchange of the complex D
with HBpin gives the homoallylic boronic ester and regenerates
iron−hydride complex A.
In summary, we have developed an iron-catalyzed
Markovnikov-selective hydroboration reaction of vinylcyclo-
propanes with HBpin via regio- and stereoselective C−C bond
cleavage. This novel protocol affords an efficient strategy for
furnishing polysubstituted homoallylic boronic esters in
moderate to good yields with good toleration of functional
groups. The stereospecific reaction is also demonstrated,
delivering chiral boronic esters with moderate to excellent ee.
The chiral homoallylic organoboronic esters could be further
converted into chiral polysubstituted tetrahydrofuran and
tetrahydropyran. More mechanistic studies and asymmetric
transformation of VCP will be explored in our laboratory.
diene 9 under standard conditions did not occur (eq 2) which
could rule out the diene intermediate. Besides, the catalytic
amount of diene 9 did not affect the hydroboration reaction of
1e (eq 3). In the absence of HBpin, the reaction of 1a afforded
a hydrogenation product in a traceless amount with 88%
recovery of 1a (see Supporting Information (SI)). The reaction
of chiral 1a (29% ee) was carried out under the standard
conditions with an achiral catalyst to afford the chiral product
C
DOI: 10.1021/acs.orglett.7b02691
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b02691.
■
S
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Experimental procedures and characterization data for all
new compounds (PDF)
Crystallographic data (CIF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: luzhan@zju.edu.cn.
ORCID
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Xin Hong: 0000-0003-4717-2814
Zhan Lu: 0000-0002-3069-079X
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support was provided by the National Basic Research
Program of China (2015CB856600), NSFC (21472162,
21772171), “Thousand Youth Talents Plan”, and Zhejiang
University.
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