Rh-catalyzed enantioselective hydrogenation of vinyl boronates for the construction of secondary boronic esters

Article abstract of DOI:10.1021/ol060735u

Rh-catalyzed hydrogenation of prochiral vinyl boronates occurs in an enantioselective fashion in the presence of the chiral ligand Walphos 1. This transformation provides access to chiral secondary organoboronates that are not available from alkene hydrob

Full text of DOI:10.1021/ol060735u

ORGANIC
LETTERS
2006
Vol. 8, No. 11
2413-2415
Rh-Catalyzed Enantioselective
Hydrogenation of Vinyl Boronates for
the Construction of Secondary Boronic
Esters
Wesley J. Moran and James P. Morken*
Department of Chemistry, Venable and Kenan Laboratories,
The UniVersity of North Carolina at Chapel Hill,
Chapel Hill, North Carolina 27599-3290
morken@unc.edu
Received March 25, 2006
ABSTRACT
Rh-catalyzed hydrogenation of prochiral vinyl boronates occurs in an enantioselective fashion in the presence of the chiral ligand Walphos
1. This transformation provides access to chiral secondary organoboronates that are not available from alkene hydroboration reactions. The
chiral reaction products should be useful in organic synthesis, and preliminary experiments suggest that they may participate in one-pot
amination and homologation reactions.
Controlled construction of secondary organoboron derivatives
is a difficult problem in organic synthesis, and yet, because
the boron atom may be replaced with a variety of functional
groups, solutions to this problem have important ramifica-
tions for the preparation of chiral compounds.1 Alkene
hydroboration is the most common route to alkylboron
derivatives. However, aside from styrenes, hydroboration of
1-alkenes does not deliver secondary organoboron com-
pounds.2 Hydroboration of 1,2-disubstituted alkenes is
similarly ineffective because this substrate class generally
suffers from low position selectivity. In fact, the R-halo-
boronic ester strategy developed by Matteson is the only
general route to such compounds in a nonracemic fashion.3
In this report we describe a catalytic enantioselective route
to versatile secondary boronic esters that are not available
from other catalytic reactions. Attractive features of this
process are that the reaction proceeds under mild conditions
and operates on readily available substrates that are prepared
in an efficient, inexpensive fashion.4
As part of a program aimed at the development of catalytic
asymmetric processes for the generation of chiral reactive
intermediates, we recently described the hydrogenation of
vinylbis(boronic esters).5 This transformation provides an
alternative to enantioselective alkene diboration as a route
to the production of chiral alkyl-1,2-bis(boronic esters). In
a similar fashion, it was imagined that hydrogenation of
vinylboronic esters might provide an alternative to alkene
hydroboration for the synthesis of chiral secondary organo-
(1) (a) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Syntheses Via Boranes; Wiley-Interscience: New York, 1975. (b)
Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988, 21, 287.
(2) For recent reviews of catalytic hydroboration, see: (a) Crudden, C.
M.; Edwards, D. Eur. J. Org. Chem. 2004, 4695. (b) Beletskaya, I.; Pelter,
A. Tetrahedron 1997, 53, 4957.
(4) (a) Takagi, J.; Takashi, K.; Ishiyama, T.; Miyaura, N. J. Am. Chem.
Soc. 2002, 124, 8001. (b) Morrill, C.; Funk, T. W.; Grubbs, R. H.
Tetrahedron Lett. 2004, 45, 7733.
(3) Review: Matteson, D. S. Tetrahedron 1998, 54, 10555.
(5) Morgan, J. B.; Morken, J. P. J. Am. Chem. Soc. 2004, 126, 15338.
10.1021/ol060735u CCC: $33.50
© 2006 American Chemical Society
Published on Web 05/05/2006

boron compounds.6 Importantly, in this approach the position
selectivity of the chiral organoboron product is controlled
during construction of the hydrogenation substrate and should
ultimately allow access to a broad array of secondary
organoboronates in a regiodefined fashion.
Table 2. Rh/Walphos 1-Catalyzed Hydrogenation of
Vinylboronic Estersa
Many catalytic reactions proceed by transmetalation of
vinyl groups from boron to Rh(I), and this elementary step
has been observed in the Rh-catalyzed addition of aryl-
boronates to enones.7 For this reason, it was initially
considered that Rh-catalyzed hydrogenation of vinyl boronic
esters might suffer from significant competitive side reac-
tions. Likely because the hydrogenation reactions were
carried out in the absence of exogenous base, transmetalation
appears not to be a problem and very high yields of saturated
organoboron derivatives may be obtained from this route.
A sample of the many ligands examined is depicted in Table
1 where it can be seen that the Walphos 18 and Walphos 8
Table 1. Effect of Chiral Ligand on the Rh-Catalyzed
Hydrogenation of Vinylboronic Esters
a All reactions were conducted for 12 h in a stainless steel bomb
immersed in a Cryocool. b Isolated yield after passage of the reaction mixture
though a silica gel plug. In general, the reaction products are >95% pure
by spectroscopic analysis. c Enantiomeric excess determined after conversion
to the derived alcohol by treatment with NaOH/ H2O2.
ligands are uniquely selective for this transformation.
Whereas only moderate selectivity was observed under the
conditions for the initial ligand survey (35 atm H2, room
temperature), executing the reaction at lower temperatures
led to a significant improvement in enantioselectivity when
Walphos 1 was the chiral modifiying ligand. The optimal
reaction conditions are presented in Table 2 where it can be
observed that very high levels of selectivity and excellent
product yield may be obtained. Interestingly, both coordinat-
ing and noncoordinating functionality may be present in the
substrate and the selectivity is similar. Entries 8 and 9
demonstrate that the reaction of chiral substrates is controlled
by the catalyst alone and that resident chirality does not
significantly alter the reaction outcome.
An attractive feature of the vinylboronate hydrogenation
reaction is that the immediate reaction product is pure enough
for use directly in other transformations. The experiment in
Scheme 1 demonstrates this feature where, after the asym-
Scheme 1
(6) (a) Matteson, D. S.; Bowie, R. A. J. Am. Chem. Soc. 1965, 87, 2587.
(b) Matteson, D. S.; Bowie, R. A.; Srivastava, G. J. Organomet. Chem.
1969, 16, 33. (c) Suginome, M.; Nakamura, H.; Ito, Y. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2516. (d) Hupe, E.; Marek, I. Knochel, P. Org. Lett.
2002, 4, 2861. (e) Gamsey, S.; DeLaTorre, K.; Singaram, B. Tetrahedron:
Asymmetry 2005, 16, 711. For a previous approach to catalytic asymmetric
reduction of vinylboronates, see: (f) Ueda, M.; Saitoh, A.; Miyaura, N. J.
Organomet. Chem. 2002, 642, 145. For vinylsilanes: (g) Lautens, M.;
Zhang, C.; Crudden, C. M. Angew. Chem., Int. Ed. Engl. 1992, 232. (h)
Murakami, M.; Oike, H.; Sugawara, M.; Suginome, M.; Ito, Y. Tetrahedron
1993, 19, 3933.
metric hydrogenation, the alkylboronic ester is treated with
BCl3 and then benzyl azide.9 This reaction sequence directly
provides chiral secondary amine 2 in good yield and excellent
enantiomeric excess.
(7) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052.
(8) Sturm, T.; Weissensteiner, W.; Spindler, F. AdV. Synth. Catal. 2003,
345, 160.
(9) (a) Chlorination: (a) Jego, J. M.; Carboni, B.; Vaultier, M.; Carrie´,
R. J. Chem. Soc., Chem. Commun. 1989, 142. (b) Brindley, P. B.; Gerrard,
W.; Lappert, M. F. J. Chem. Soc. 1956, 824. (c) Amination: Brown, H.
C.; Midland, M. M.; Levy, A. B. J. Am. Chem. Soc. 1973, 95, 2394.
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Org. Lett., Vol. 8, No. 11, 2006

Aside from amination and oxidation, the capacity of chiral
organoboronic esters to participate in C-C bond-forming
reactions is also a noteworthy trait. The direct conversion
of vinyl boronate 1 to 3 can be accomplished as depicted in
Scheme 2.10 For this transformation, a solvent-swap of
relative to an alkyl substituent is clear when comparing
boronate 4 (84% conversion) to similarly sized alkene 5
(<10% conversion). One might ascribe this difference to the
π-acceptor properties14 of the boron atom. However, the low
reactivity observed with methyl methacrylate argues against
the solitary importance of this feature. Alternatively, one
might ascribe the enhanced reactivity of vinyl boronates to
inductive donation from boron to carbon.15 However, an
inductively withdrawing phenyl ring (7) provides levels of
reactivity comparable to that of the vinyl boronate (70%
conversion) albeit no enantioselection (<5% ee). Clearly,
the nature of the boronate’s involvement in the reaction is
not simple and more detailed experiments are required to
understand the nature of this reaction.
Scheme 2
In conclusion, we have documented a highly enantio-
selective catalytic asymmetric hydrogenation of vinyl bor-
onates, which in many cases provides products that are
unattainable from hydroboration reactions. Further examina-
tion of the scope and utility of this process is in progress.
toluene for THF is required, but the unpurified hydrogenation
mixture may be used directly and provides the R-chiral
alcohol 3 in high yield and enantiomeric excess.
Vinyl boron compounds may exhibit unique reactivity
relative to that of typical alkene substrates (i.e., omniphilic
reactivity in cycloadditions).11 A priori one might anticipate
that in the Rh-catalyzed hydrogenation the boronic ester
oxygen atoms may coordinate to the cationic metal center
and provide transition state organization.12 Experiments in
Table 2 suggest that this is not the case. Substrate functional-
ity of varying Lewis basicity, and presumably varying ability
to compete with a putatively coordinating boronate, all
provide similar enantioselection. This argument is consistent
with the minimal basicity13 of boronate oxygen atoms, which
arises from nO f pB orbital overlap. Alternatively, one might
consider the electronic properties of the boronic ester as an
important element in the reaction. To probe these effects,
the alkenes in Scheme 3 were compared in the Rh/Walphos-
catalyzed hydrogenation. The activating effect of the boronate
Acknowledgment. This work was supported by the NIH
(GM 59417). We thank Solvias for a generous donation of
Walphos ligands under the University Ligand Kit Program.
Supporting Information Available: Complete experi-
mental procedures, characterization data (1H and 13C NMR,
IR, and mass spectrometry), enantiomeric purity data (chiral
GC, SFC), and structure proofs (authentic syntheses). This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL060735U
(10) (a) Ren, L.; Crudden, C. M. Chem. Commun. 2000, 721. (b) Sadhu,
K. M.; Matteson, D. S. Organometallics 1985, 4, 1687.
(11) Singleton, D. A.; Martinez, J. P.; Watson, J. V. Tetrahedron Lett.
1992, 33, 1017.
(12) Coordination of a Lewis acid to a pinacol boronate oxygen has been
detected by NMR; see: Kennedy, J. W. J.; Hall, D. G. J. Am. Chem. Soc.
2002, 124, 11586.
(13) Pola, J.; Jakoubkova´, M.; Va´clav, C. Collect. Czech. Chem. Commun.
1979, 44, 3688.
Scheme 3. Conversion at 10 min in Isolated Experimentsa
(14) (a) Exner, O.; Bose, R. Collect. Czech. Chem. Commun. 1974, 39,
2234. (b) Kiplinger, J. P.; Crowder, C. A.; Sorensen, D. N.; Bartmess, J. E.
J. Am. Soc. Mass Spectrom. 1994, 5, 169.
(15) The Pauling electronegativites for boron and carbon are 2.04 and
2.55, respectively (Allred, A. L. J. Inorg. Nucl. Chem. 1961, 17, 215). Based
on chemical shift data for a boronic ester (No¨th, H.; Vahrenkamp, H. J.
Organomet. Chem. 1968, 12, 23) the electronegativity of this group is 1.96
according to the modified Dailey-Shoolery equation. See: (a) Narasimhan,
P. T.; Rogers, M. T. J. Am. Chem. Soc. 1960, 82, 34. (b) Ohashi, O.; Kurita,
Y.; Totani, T.; Watanabe, H.; Nakagawa, T.; Kubo, M. Bull Chem. Soc.
Jpn. 1962, 35, 1317.
a Reagents and conditions: 5 mol % Rh(nbd)2BF4, 8 mol %
Walphos 1, 35 atm H2, -35 °C.
Org. Lett., Vol. 8, No. 11, 2006
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