Asymmetric hydrovinylation of 1-vinylcycloalkenes. Reagent control of regio- and stereoselectivity

Article abstract of DOI:10.1021/ja301640e

1-Vinylcycloalkenes undergo highly regio- and enantioselective (>98% ee) 1,4-hydrovinylation (HV) when treated with ethylene (1 atm) at room temperature in the presence of [(S,S)-2,4-bis-diphenylphosphinopentane (BDPP)]CoCl ₂ (0.05 equiv) and methylaluminoxane. The minor 1,2-HV products, seen only in 1-vinylcyclohexene (～15%) and 1-vinylcycloheptene (2%), are formed as racemic mixtures. The corresponding Ni(II)-catalyzed HV reactions of these substrates give mostly the 1,2-adducts. Racemic 4-tert-butyl-1-vinylcyclohexene, when treated with Co[(S,S)-(BDPP)]Cl₂ and ethylene, undergoes a rare enantiodivergent reaction giving two diastereomers each in >98% ee.

Full text of DOI:10.1021/ja301640e

Communication
pubs.acs.org/JACS
Asymmetric Hydrovinylation of 1-Vinylcycloalkenes. Reagent Control
of Regio- and Stereoselectivity
Jordan P. Page and T. V. RajanBabu*
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, United States
*
S Supporting Information
ABSTRACT: 1-Vinylcycloalkenes undergo highly regio-
and enantioselective (>98% ee) 1,4-hydrovinylation (HV)
when treated with ethylene (1 atm) at room temperature
in the presence of [(S,S)-2,4-bis-diphenylphosphinopen-
tane (BDPP)]CoCl (0.05 equiv) and methylaluminoxane.
2
The minor 1,2-HV products, seen only in 1-vinyl-
cyclohexene (∼15%) and 1-vinylcycloheptene (2%), are
formed as racemic mixtures. The corresponding Ni(II)-
catalyzed HV reactions of these substrates give mostly the
1,2-adducts. Racemic 4-tert-butyl-1-vinylcyclohexene, when
treated with Co[(S,S)-(BDPP)]Cl and ethylene, under-
2
goes a rare enantiodivergent reaction giving two
diastereomers each in >98% ee.
ickel(II)-catalyzed asymmetric hydrovinylation (HV) of
N
1-vinylcycloalkenes is a powerful reaction that has been
used to install exocyclic methyl-bearing chiral centers with
exceptional enantio- and diastereoselectivity depending on the
1
nature of the starting diene (eqs 1−2). While excellent ligand-
dependent selectivity has been demonstrated even in a
1b
demanding chiral precursor such as 3, with a disparate
inherent substrate-specific stereochemical preference, an occa-
sional complication in the reaction was noted during the
attempted diastereoselective 1,2-hydrovinylation of the ster-
2
oidal substrate 5 (eq 3). Even though the formation of the
desired 1,2-adduct (6) is totally stereoselective (and control-
lable by the choice of the ligand), a minor product, 7, arising via
a highly selective 1,4-addition of ethylene is also formed. Since
configurationally well-defined 2-vinylcycloalkylidenes such as 7
could be potentially important intermediates for further
stereoselective transformations, we decided to explore ways of
optimizing such 1,4-hydrovinylation reactions of 1-vinyl-
cycloalkenes. We find that by using variations of a recently
Scheme 1. 1,2- vs 1,4-Hydrovinylation of 4-tert-Butyl-1-
vinylcyclohexene
3a
disclosed Co(II)-mediated HV protocol, it is possible to effect
highly regio- and enantioselective 1,4-hydrovinylation of 1-
4
vinylcycloalkenes. The results of this study are reported here.
Our studies started with an examination of Co(II)-catalyzed
hydrovinylation of 4-tert-butyl-1-vinylcyclohex-1-ene (8,
Scheme 1). After optimization of the reaction conditions
using various combinations of (L) CoCl /AlMe (L = DPPM,
2
2
3
5
DPPE, DPPP, and DPPB), temperatures, and solvents, it was
found that, in sharp contrast to the Ni(II)-catalyzed HV
8
experimentally it was advantageous to use methylaluminoxane,
1a
reaction (Scheme 1, 8 → 10), and a related Ru(II)-catalyzed
which can be easily weighed out, in place of the hydrocarbon
6
reaction, the (DPPP)CoCl /Me Al-mediated reaction gave
2
3
almost exclusively the 1,4-adducts as a mixture of cis (9a) and
trans (9b) isomers (81:17). We also recognized that
Received: February 26, 2012
Published: March 28, 2012
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©
2012 American Chemical Society
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dx.doi.org/10.1021/ja301640e | J. Am. Chem. Soc. 2012, 134, 6556−6559

Journal of the American Chemical Society
Communication
solutions of Me Al. Both the Ni(II) and Co(II) reactions are
highly regioselective in the formation of the respective 1,2- and
readily prepared via intramolecular cross-metathesis of an
enyne, is a compatible substrate giving 2,5-cis (14a) and 2,5-
3
9
1
1
,4-adducts with less than 4% of the isomeric products (9 and
0 respectively) formed in each case.
The scope of the reaction is illustrated with the examples
trans (14b) adducts in a ratio of 1:9 (entry 3). Conformation-
ally flexible 1-vinylcyclohexene (entry 4) also gave predom-
inantly the 1,4-adduct (15a), with up to 22% of the 1,2-HV
product. The Co(II)-catalyzed 1,4-hydrovinylations are partic-
ularly effective for 1-vinylcycloheptene (entry 5) and 1-
vinylcyclooctene (entry 6), under the typical reaction
conditions using DPPP as the ligand. Substrates 18, 20, and
shown in Table 1. Under the standard reaction conditions, the
hydrovinylation is highly chemoselective for the 1,3-diene
moiety, as shown by the reaction of the enantiopure substrate
1
1, which was prepared from commercially available
2
2, which gave exclusive 1,2-hydrovinylation under the Ni-
(
(
−)-perrilaldehyde (entry 2). The 1,4-adducts 12a and 12b
1a
catalyzed reaction conditions described in Scheme 1, gave
quantitative yields of the 1,4-adduct (1,4-HV vs 1,2-HV > 99:1)
in the Co(II)-mediated reactions (entries 7−9).
ratio of 4:1) are obtained in excellent yield. The allyl ether 13,
Table 1. Co(II)-Catalyzed 1,4-Hydrovinylation of 1-
Vinylcycloalkenes
Searching for a chiral, chelating bisphosphine ligand that
bears a structural similarity to 1,3-bis-diphenylphosphinopro-
pane (DPPP), we identified commercially available 2,4-bis-
diphenylphosphinopentane (BDPP), which serves admirably
well in an asymmetric version of the 1,4-HV reaction. Reactions
of two prototypical substrates, 1-vinylcyclohexene and 1-
vinylcycloheptene showing the optimized conditions, and the
a
10
possible side reactions, are shown in eq 4. The HV reactions
of 1-vinylcyclohexene and 1-vinylcycloheptene with the
BDPP)Co(II)-catalyst closely parallel the results obtained
(
with the corresponding (DPPP)Co(II)-complex, except for the
proportion of the 1,4-HV product, which is slightly more in the
former case (∼85%) than what was formed with the DPPP-
complex. The reactions using the (S,S)-BDPP ligand gave (S)-
1
5a and (S)-16a essentially as single enantiomers with <0.2% of
11
the (R)-isomers. Predictably, reaction with the (R,R)-BDPP
gave the enantiomeric products (R)-15a and (R)-16a in
comparable yields and selectivities. The configuration of (S)-
1
6a was confirmed by its conversion [(Ph P) RhCl, CH Cl ,
3 3 2 2
11
H2 (35 psi), followed by O , Me S] to (R)-2-ethyl-
3
2
cycloheptanone whose chiroptical properties have been
12
described in the literature. In sharp contrast to the high
selectivity observed for the 1,4-HV product, the corresponding
1
,2-HV adducts (15b and 16b) were formed nearly as racemic
mixtures.
As illustrated by the examples listed in Table 2, the
BDPP)CoCl -catalyzed asymmetric 1,4-hydrovinylation is a
(
2
broadly applicable reaction. Vinylcyclooctene, as compared to
the six- and seven-membered analogs, gives exclusively the 1,4-
adduct, which is formed in >99% ee (entry 3). 1,4-
Hydrovinylations of substrates 18, 20, and 22 (entries 4−6)
also proceed giving nearly quantitative yields of the respective
1
,4-adducts with >99% ee.
4
-tert-Butyl-1-vinylcyclohexene (8) is a chiral (racemic)
substrate capable of producing two sets of diastereomers each
from the 1,2- and 1,4-HV reactions, and the selectivity of the
reaction is highly dependent on the ligand. For example, the
high regio- (9:10 = 98:2) and diastereoselectivity (9a:9b =
81:17) in the formation of the products seen with the achiral
a
See Scheme 1 for typical procedure using (DPPP)CoCl as catalyst
2
b
and Supporting Information for further details. 1,4-HV:1,2-HV,
determined by GC and/or NMR. Rest starting material. 15b and
1
c
d
6b are 1,2-HV products.
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Journal of the American Chemical Society
Communication
Table 2. Co(II)-Catalyzed Asymmetric 1,4-Hydrovinylation
of 1-Vinylcycloalkenes
metal complexes should make these enantiopure skipped 1,4-
dienes valuable intermediates for further synthetic applications.
Such studies are in progress.
a
ASSOCIATED CONTENT
Supporting Information
■
*
S
Details of the experimental procedures, spectroscopic and
chromatographic data for key compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
rajanbabu.1@osu.edu
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial assistance for this research provided by the U.S.
National Institutes of Health (General Medical Sciences, R01
GM075107) is gratefully acknowledged.
REFERENCES
■
(
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011, 1654. For representative examples of hydroalkenylation of
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a
b
See eq 4 and Supporting Information for details. 1,4-HV/1,2-HV.
1
c
Determined by H NMR and/or GC. Major product. Determined by
chiral stationary phase GC. See Supporting Information for chromato-
grams. Assigned by analogy to products 16a and 21, whose
configurations were confirmed by comparison to known derivatives;
see text and Supporting Information for details. 9a:9b = 60:40.
Assignments (tentative) based on configurations of 16a and 21.
d
̈
For related Fe-catalyzed reactions, see: Ehlers, J.; Konig, W. A.; Lutz,
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e
(DPPP)-Co(II) complex (Scheme 1, Table 1, entry 1) shows
significant erosion when the [(S,S)-BDPP]Co(II) complex is
used (regioselectivity 9:10 = 87:13; diastereoselectivity 9a:9b =
6
2
011, 13, 6236 and references cited therein.
(5) Ligands: BDPP = bis-2,4-diphenylphosphinopentane; DPPM =
0:40). However, both diastereomers of the 1,4-adducts, 9a and
b, are formed with enantioselectivities exceeding 98% (entry 7,
diphenylphosphinomethane; DPPE = diphenylphosphinoethane;
DPPP = diphenylphosphinopropane; DPPB = diphenylphophinobu-
9
Table 2). The exceptionally high enantioselectivity in the
formation of the two diastereoisomeric products from a chiral
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tane; Cy
dioxalane-4,5-diylbismethylene) bis-diphenylphosphine.
6) A high pressure Ru(II)-catalyzed hydrovinylation of 1,3-dienes at
75 °C using (Cy P) Ru(CO)(H)(Cl)/HBF also gives mostly the 1,2-
3
P = tricyclohexylphosphine; DIOP = (2,2-dimethyl-1,3-
(
13
3
2
4
of efficient enantiodivergent parallel kinetic resolutions.
hydrovinylaion products, albeit in modest yields. See: He, Z.; Yi, C. S.;
Donaldson, W. A. Org. Lett. 2003, 5, 1567. Additionally, we noticed
that even the Co(II)-catalyzed reaction is highly dependent on the
ligand. For example, (+)-DIOP gave >90% yield of a mixture of
diastereomers of the 1,2-hydrovinylation (exocyclic) products (10a
and 10b), both of which were formed in low ee’s. 1-Vinylcyclohexene
also behaves similarly. See Supporting Information for details.
In summary, we have discovered a simple procedure for the
preparation of enantiopure 1-alkylidene-2-vinylcycloalkanes
from readily available 1-vinylcycloalkenes. The enhanced
reactivity of the trisubstituted double bond in electrophilic
reactions and the greater access of the monosubstitued alkene
to reagents such as dialkylboranes and catalytically competent
6
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Journal of the American Chemical Society
Communication
(
7) The 1,2- and 1,4-adducts are easiy distinguished by the chemical
shifts of the bis-allylic hydrogen. This proton appears as a ddd at δ
.93 in cis-9 and as broad singlet at δ 3.46 in trans-9. In both
2
diastereomers of 10 this signal appears as a multiplet at δ 2.70. Gas
chromatographic retention times for the 1,4-adducts on a methyl-
silicone column are significantly lower than those of the 1,2-adducts.
See Supporting Information for details.
(
1
(
6
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(
2
equiv of methylaluminoxane in CH Cl under an ethylene atmosphere
2
2
was added a CH Cl solution of the diene. The mixture was stirred for
2
2
6
−8 h at room temperature and was quenched by adding a
stoichiometric amount of methanol. Dilution with pentane and
filtration through silica afforded the product in excellent yields and
1
isomeric purity, as judged by both gas chromatography (GC) and H
NMR spectroscopy. The enantiomeric ratios of the products were
determined by chiral stationary phase GC on a cyclosil-B or a
cyclodex-B column, where baseline separations of the enantiomers
were observed. For exact conditions of analysis and the chromato-
grams of racemic and enriched samples, see Supporting Information.
(
11) See Supporting Information for experimental details and
analytical data, including gas chromatograms recorded on regular
and chiral stationary phase columns.
(
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