Catalytic enantioselective hydrogenation of vinyl bis(boronates)

Article abstract of DOI:10.1021/ja044396g

Catalytic enantioselective hydrogenation of prochiral vinylmetallic reagents can provide an attractive alternative to hydrometalation and bismetalation of alkenes. In this contribution, the first highly enantioselective hydrogenation of vinyl boronic esters is described. The chiral reduction products are versatile intermediates for chemical synthesis. Copyright

Full text of DOI:10.1021/ja044396g

Published on Web 11/03/2004
Catalytic Enantioselective Hydrogenation of Vinyl Bis(boronates)
Jeremy B. Morgan and James P. Morken*
Department of Chemistry, The UniVersity of North Carolina at Chapel Hill,
Chapel Hill, North Carolina 27599-3290
Received September 15, 2004; E-mail: morken@unc.edu
New catalytic methods for the generation of reactive enantio-
Table 1. Asymmetric Hydrogenation of Vinyl Bis(boronate) 1
merically enriched molecules are important for chemical synthesis.
Of particular interest are methods that enable domino reaction
sequences for the introduction of functional group complexity. In
this respect, reactions that furnish reactive and stereogenic carbon-
metal bonds are particularly useful for the generation of stereo-
chemically intricate structures. While processes such as alkene
1
2
hydrometalation and bismetalation have been developed to create
such intermediates, these processes are often plagued with low
substrate scope and, for hydrometalation, may provide regioisomer
3
mixtures. An alternative method for generating stereogenic carbon-
metal bonds is the hydrogenation of prochiral vinylmetallic species
4
(
Scheme 1). This reaction may circumvent many of the problems
inherent in alkene metalation reactions, and since vinyl-metal
compounds are readily available, asymmetric hydrogenation may
provide an attractive complement to current methods for the
a
See Supporting Information for ligand structures. b Isolated yield of
3
synthesis of enantioenriched sp hybridized organometallics. Herein,
purified material.
we report the first highly enantioselective hydrogenation of vinyl-
metallic substrates which, in this case, provides access to enantio-
of 2 mol % of rhodium salt and 4 mol % Walphos (Table 2). While
Walphos-W001 ligand leads to high asymmetric induction for
aromatic substrates, lower enantioselectivity is observed with
aliphatic substituents on the diborylalkene. Accordingly, the family
of Walphos ligands was reevaluated with aliphatic substrates
5
merically enriched alkyl 1,2-bis(boronates).
Scheme 1
Table 2. Rh-Walphos-Catalyzed Asymmetric Hydrogenation of
Recently, our laboratory reported the preparation of enantio-
merically enriched alkyl 1,2-bis(boronates) by the catalytic asym-
metric diboration of alkenes. Although this reaction is highly
Vinyl Bis(boronates)a
6
selective with most trans-alkene substrates, the majority of mono-
substituted olefins do not provide high asymmetric induction. Since
a number of reaction sequences, such as tandem diboration/Suzuki
7
coupling/oxidation, may be enabled by the sequential transforma-
tion of sterically differentiated C-B bonds, the selective diboration
of 1-alkenes is a particularly attractive goal. While current efforts
are directed at solving this problem, as suggested above, an alternate
approach to the product alkyl-1,2-bis(boronates) is the hydrogena-
tion of vinyl 1,2-bis(boronates). These prochiral substrates are
readily available by diboration of alkyne precursors using com-
mercially available catalysts and reagents.8
Initial experiments probed the reactivity of vinyl bis(boronates)
toward group 9 hydrogenation catalysts. In these experiments, E-1,2-
bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)styrene (1) was sub-
ject to asymmetric hydrogenation with 5 mol % catalyst at 15 bar
2
H in dichloroethane (DCE), followed by basic peroxide oxidation.
In general, it was found that rhodium complexes were superior to
their iridium analogues. The most promising ligands are depicted
in Table 1 wherein (R,R)-Walphos-W0019 provided the most
selective catalyst and afforded 73% ee and 82% yield in DCE. Upon
examination of other solvents, it was found that toluene provides
significantly higher selectivity (93% ee) with comparable yields.
Under optimized conditions, excellent yields and high enantio-
selectivities are obtained with an in situ generated catalyst composed
a
Identity of major enantiomer determined by correlation to authentic
materials. b Isolated yield of purified material. c Enantiomeric excess de-
termined by chiral GC analysis. Experiment at 30 bar H2.
d
15338
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J. AM. CHEM. SOC. 2004, 126, 15338-15339
10.1021/ja044396g CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
wherein it was found that Walphos-W008 in DCE solvent provided
increased selectivity with these compounds.
Table 3. Effect of Ligand:Metal Ratio on Asymmetric
Hydrogenation of 1
Platinum-catalyzed diboration of terminal alkynes provides ready
access to 1,2-bis(boryl)alkenes which were used as substrates in
Table 2.8 To minimize both solvent consumption and the number
of manipulations required to obtain the saturated 1,2-bis(boryl)-
alkane, we attempted a domino one-pot alkyne diboration/
hydrogenation sequence (Scheme 2). Since platinum complexes are
well-known as hydrogenation catalysts, an elevated loading of the
Rh-Walphos catalyst was employed in the hydrogenation step to
minimize competitive nonselective hydrogenation by the achiral
c-e
entry
mol % ligand
mol % Rh
% yield
% ee
configuration
1
2
3
1.6
2.0
4.0
2.0
2.0
2.0
90
83
84
52
37
93
R
R
S
platinum-based diboration catalyst. In addition, (Ph
3 2
P) Pt(ethylene)
asymmetric induction. 31P NMR experiments directed at under-
standing precatalyst stoichiometry remain inconclusive.
In conclusion, we have described the asymmetric hydrogenation
of prochiral vinyl bis(boronates). The reaction products are versatile
intermediates which should prove useful in the assembly of a
number of functional substructures.
was used instead of (Ph P) Pt for the diboration step to minimize
3
4
10
superfluous achiral phosphine in the reaction vessel. Upon
subjection of the alkyne to catalytic diboration, followed by catalytic
hydrogenation and oxidation, styrenediol was isolated in 66% yield
based on diboron and 91% ee. This level of selectivity is only
slightly lower than that observed for the reduction of the purified
vinyl bis(boronate).
Acknowledgment. We are grateful to Solvias for a generous
donation of ligands under their University Ligand Kit program.
J.B.M. thanks the Wellcome Trust and Eli Lilly for graduate
fellowships. This work was supported by the NIH (GM 59417).
J.P.M. is a fellow of the Alfred P. Sloan foundation and thanks
AstraZeneca, Bristol-Myers Squib, DuPont, GlaxoSmithKline, and
the Packard Foundation for support.
Scheme 2. Single-Pot Diboration/Hydrogenation/Oxidation of
Phenylacetylene
Supporting Information Available: Procedures, characterization
data, enantiomeric purity data, and structure proofs. This material is
available free of charge via the Internet at http://pubs.acs.org.
As alluded to above, an attractive feature of stereogenic carbon-
metal bonds is the diversity of functional groups that may be
obtained simply by altering reaction “workup” sequences. While
oxidative workup conveniently delivers 1,2-diols from 1,2-bis-
References
(
1) For recent reviews of catalytic hydroboration, see: (a) Crudden, C. M.;
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(
boronate) intermediates, a homologation/oxidation workup was
11
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6
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4
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(
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8
2
Preliminary observations suggest that a simple 1:1 ligand:metal
complex is not the sole participating entity in the hydrogenation
reaction. As depicted in Table 3, the reaction selectivity is
remarkably dependent on the ligand:metal ratio. A catalyst derived
from an equimolar ratio of Walphos-W001 and rhodium salt
provided the product in low enantioselection (entry 2). Surprisingly,
the product obtained from this reaction possessed the configuration
opposite to that obtained in the initial ligand survey. It was found
that addition of excess ligand is required for optimal enantioselec-
tivity (entry 3), whereas a substoichiometric amount of ligand (entry
1
(
(
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1) allows access to the opposite enantiomer with a modest level of
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J. AM. CHEM. SOC.
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