Rh-catalyzed enantioselective diboration of simple alkenes: Reaction development and substrate scope

Article abstract of DOI:10.1021/jo051651m

The rhodium-catalyzed reaction between bis(catecholato)diboron and simple alkenes results in the syn addition of the diboron across the alkene. The resulting 1,2-bis(boronate) is subsequently oxidized to provide the 1,2-diol. In the presence of enantiomerically enriched Quinap ligand, high enantioselection in the diboration can be achieved. The reaction is highly selective for trans- and trisubstituted alkenes and can be selective for some monosubstituted alkenes as well. The development of this reaction is described as is the substrate scope and experiments that are informative about the reaction mechanism and competing pathways.

Full text of DOI:10.1021/jo051651m

Rh-Catalyzed Enantioselective Diboration of Simple Alkenes:
Reaction Development and Substrate Scope
Ste´phane Trudeau, Jeremy B. Morgan, Mohanish Shrestha, 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 August 5, 2005
The rhodium-catalyzed reaction between bis(catecholato)diboron and simple alkenes results in the
syn addition of the diboron across the alkene. The resulting 1,2-bis(boronate) is subsequently
oxidized to provide the 1,2-diol. In the presence of enantiomerically enriched Quinap ligand, high
enantioselection in the diboration can be achieved. The reaction is highly selective for trans- and
trisubstituted alkenes and can be selective for some monosubstituted alkenes as well. The
development of this reaction is described as is the substrate scope and experiments that are
informative about the reaction mechanism and competing pathways.
Introduction
organoboron precursors. Because of this remarkable
breadth, reactions that enable the synthesis of stereode-
fined carbon-boron bonds have significant value, and
this is evidenced by the central role that hydroboration
plays in contemporary organic synthesis.7 While stereo-
selective insertion processes8 also serve to create chiral
organoboron compounds, there are few other methods for
accessing these motifs in a selective fashion.
Stereospecific manipulation of carbon-boron bonds is
sufficiently well developed that a large number of deriva-
tives may be targeted through stereospecific replacement
of the boron atom.1 Amination,2 oxidation,3 catalytic4 and
stoichiometric cross-coupling,5 and carbenoid insertions6
all serve to create useful organic assemblies from common
The catalytic reaction of alkenes with diboron com-
pounds offers one route to organoboron reagents in a
conceptually straightforward fashion.9 This transforma-
tion furnishes two carbon-boron bonds, both of which
might be derivatized in a useful fashion. Along these
lines, it has been reported that alkene diboration may
be accomplished with the assistance of rhodium,10 plati-
num,11 gold,12 and silver13 complexes. Each of these
complexes is thought to catalyze diboration through a
(1) Reviews: (a) Brown, H. S.; Singaram, B. Acc. Chem. Res. 1988,
21, 287. (b) Organoboranes for Synthesis; Ramachandran, P. V., Brown,
H. C., Eds.; ACS Symposium Series 783; American Chemical Society:
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ranes; Matteson, D. S., Ed.; Springer: New York, 1995.
(2) (a) Brown, H. C.; Midland, M. M.; Levy, A. B. J. Am. Chem. Soc.
1973, 95, 2394. (b) Brown, H. C.; Kim, K. W.; Cole, T. E.; Singaram,
B. J. Am. Chem. Soc. 1986, 108, 6761. (c) Knight, F. I.; Brown, J. M.;
Lazzari, D.; Ricci, A.; Blacker, A. J. Tetrahedron 1997, 53, 11411. (d)
Fernandez, E.; Maeda, K.; Hooper, M. W.; Brown, J. M. Chem Eur. J.
2000, 6, 1840.
(3) (a) Zweifel, G.; Brown, H. C. Org. React. 1963, 13, 1. (b) Brown,
H. C.; Snyder, C.; Subba Rao, B. C.; Zweifel, G. Tetrahedron 1986, 42,
5505. (c) Kabalka, G. W.; Wadgaonkar, P. P.; Shoup, T. M. Organo-
metallics 1990, 9, 1316.
(4) Reviews: (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(b) Kohta, S.; Lahirir, K.; Kashinath, D. Tetrahedron 2002, 58, 9633.
(5) (a) Suzuki, A.; Miyaura, N.; Abiko, S.; Itoh, M.; Brown, H. C.;
Sinclair, J. A.; Midland, M. M. J. Am. Chem. Soc. 1973, 95, 3080. (b)
Leung, T.; Zweifel, G. J. Am. Chem. Soc. 1974, 96, 5620. (c) Yamada,
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(7) Smith, K.; Pelter, A. In Comprehensive Organic Synthesis; Trost,
B. M., Ed.; Pergamon: Oxford, 1995; Vol. 8, p 703. For a review of
catalytic asymmetric hydroboration, see: Crudden, C. M.; Edwards,
D. Eur. J. Org. Chem. 2003, 4695.
(8) (a) Matteson, D. S. Tetrahedron 1998, 54, 10555. (b) Matteson,
D. S.; Majumdar, D. J. Am. Chem. Soc. 1980, 102, 7588. (c) Matteson,
D. S.; Ray, R. J. Am. Chem. Soc. 1980, 102, 7590.
(9) For reviews on catalytic diboration of unsaturated organic
compounds, see: (a) Ishiyama, T.; Miyaura, N. Chem. Rec. 2004, 3,
271. (b) Ishiyama, T.; Miyaura, N. J. Organomet. Chem. 2000, 611,
392. (c) Marder, T. B.; Norman, N. C. Top. Catal. 1998 5, 63.
(10) (a) Baker, R. T.; Nguyen, P.; Marder, T. B.; Westcott, S. A.
Angew. Chem., Int. Ed. Engl. 1995, 34, 1336. (b) Dai, C.; Robins, E.
G.; Scott, A. J.; Clegg, W.; Yufit, D. S.; Howard, J. A. K.; Marder, T. B.
Chem. Commun. 1998, 1983. (c) Nguyen, P.; Coapes, R. B.; Woodward,
A. D.; Taylor, N. J.; Burke, J. M.; Howard, J. A. K.; Marder, T. B. J.
Organomet. Chem. 2002, 652, 77.
(6) (a) Brown, H. C.; Imai, T. J. Am. Chem. Soc. 1983, 105, 6285.
(b) Matteson, D. S.; Majumdar, D. Organometallics 1983, 2, 1529. (c)
Sadhu, K.; M.; Matteson, D. S. Organometallics 1985, 4, 1687. (d)
Brown, H. C.; Singh, S. M. Organometallics 1986, 5, 994. (e) Brown,
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L.; Crudden, C. M. Chem. Commun. 1999, 611. (g) Ren, L.; Crudden,
C. M. Chem. Commun. 2000, 721. (h) O’Donnell, M. J.; Drew, M. D.;
Cooper, J. T.; Delgado, F.; Zhou, C. J. Am. Chem. Soc. 2002, 124, 9348.
10.1021/jo051651m CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/20/2005
9538
J. Org. Chem. 2005, 70, 9538-9544

Enantioselective Diboration of Simple Alkenes
TABLE 1. Survey of Chiral Ligands in the
Rh-Catalyzed Alkene Diboration Reaction
SCHEME 1. General Mechanism for
Transition-Metal-Catalyzed Reaction by Alkenes
and Diboron Compounds
entry
ligand
% yield syn:anti % ee syn (anti)
1
2
3
4
5
6
7
8
9
Binap (1)
25
37
<5
10
<5
24
<5
<5
<5
1.5:1
4.5:1
38 (84)
5 (55)
DIOP (2)
Chiraphos (3)
iPr-PHOX (4)
Josiphos (5)
Quinap (6)
Indane-Pybox (7)
MeO-Biphep (8)
H-MOP(9)
6.6:1
35:1
5
86
catalytic cycle that involves oxidative addition of the
diboron reagent to the metal,14 insertion of the alkene,15
and then reductive elimination of the organodiboron
product (Scheme 1).16,17 Significant reaction side products
are often observed that appear to arise from â-hydrogen
elimination of the intermediate organometallic complex.18
In an effort to develop an asymmetric variant of the
alkene diboration process, we initiated studies with chiral
transition-metal complexes.19 On the basis of the catalytic
cycle described above, exploratory experiments were
restricted to those involving bidentate chiral ligands in
combination with rhodium complexes since it was ex-
pected that bidentate ligands would render the analogous
four-coordinate d8 platinum diboryl intermediate inert
to olefin coordination and insertion reactions.20 These
initial experiments revealed that when chiral rhodium
complexes derived from Quinap are used, the reaction
exhibits remarkable enantioselection and good yields for
a number of prochiral alkene substrates and that with
this particular ligand structure the diboration process
operates relatively free from competitive side reactions.
While the diboron adduct may be conveniently oxidized
to the 1,2-diol, selective tandem reactions are also pos-
sible and include tandem cross-coupling/oxidation21 and
homologation/oxidation.22 In this manuscript we provide
the full details of the reaction development, document
the substrate scope, and provide a framework to forecast
stereoinduction in these reactions.
(11) (a) Iverson, C. N.; Smith, M. R., III Organometallics 1997, 16,
2757. (b) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem Commun.
1997, 689. (c) Marder, T. B.; Norman, N. C.; Rice, C. R. Tetrahedron
Lett. 1998, 39, 155. (d) Ishiyama, T.; Momota, S.; Miyaura, N. Synlett
1999, 1790. (d) Mann, G.; John, K. D.; Baker, R. T. Org. Lett. 2000, 2,
2105.
(12) Baker, R. T.; Nguyen, P.; Marder, T. B.; Westcott, S. A. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1336.
(13) Ram´ırez, J.; Corbera´n, R.; Sanau´, M.; Peris, E.; Fernandez, E.
Chem. Commun. 2005, 3056.
(14) Oxidative addition with Rh: (a) Dai, C.; Stringer, G.; Marder,
T. B.; Scott, A. J.; Clegg, W.; Norman, N. C. Inorg. Chem. 1997, 36,
272. (b) Nguyen, P.; Lesley, G.; Taylor, N. J.; Marder, T. B.; Pickett,
N. L.; Clegg, W.; Elsegood, M. R. J.; Norman, N. C. Inorg. Chem. 1994,
33, 4623. (c) Clegg, W.; Lawlor, F. J.; Marder, T. B.; Nguyen, P.;
Norman, N. C.; Orpen, A. G.; Quayle, A. J.; Rice, C. R.; Robins, E. G.;
Scott, A. J.; Souza, F. E. S.; Stringer, G.; Whittell, G. R. J. Chem. Soc.,
Dalton 1998, 301. Oxidative addition with Pt: (d) Iverson, C. N.; Smith,
M. R., III J. Am. Chem. Soc. 1995, 117, 4403. (e) Ishiyama, T.; Matsuda,
N.; Murata, M.; Ozawa, F.; Suzuki, A.; Miyaura, N. Organometallics
1996, 15, 713. (f) Lesley, G.; Nguyen, P.; Taylor, N. J.; Marder, T. B.;
Scott, A. J.; Clegg, W.; Norman, N. C. Organometallics 1996, 15, 5137.
(g) Ishiyama, T.; Matsuda, N.; Miyaura, N.; Suzuki, A. J. Am. Chem.
Soc. 1993, 115, 11018. (h) Clegg, W.; Lawlor, F. J.; Marder, T. B.;
Nguyen, P.; Norman, N. C.; Orpen, A. G.; Quayle, M. J.; Rice, C. R.;
Robins, E. G.; Scott, A. J.; Souza, F. E. S.; Stringer, G.; Whittell, G. R.
J. Organomet. Chem. 1998, 550, 183.
(15) For a documented alkene insertion into a Rh-B bond, see:
Baker, R. T.; Calabrese, J. C.; Westcott, S. A.; Nguyen, P.; Marder, T.
B. J. Am. Chem. Soc. 1993, 115, 4367.
(16) For the organometallic chemistry of transition-metal boryls,
see: Irvine, G. J.; Lesley, M. J. G.; Marder, T. B.; Norman, N. C.; Rice,
C. R.; Robins, E. G.; Roper, W. R.; Whittell, G. R.; Wright, L. J. Chem.
Rev. 1998, 98, 2685.
(17) For computational studies of the mechanism of alkene dibora-
tion, see: Cui, Q.; Musaev, D. G.; Morokuma, K. Organometallics 1997,
16, 1355.
(18) Competitive â-hydrogen elimination is catalyst and substrate
dependent, see ref 10.
(19) For a preliminary report, see: Morgan, J. B.; Miller, S. P.;
Morken, J. P. J. Am. Chem. Soc. 2003, 125, 8702. See also, ref 21.
(20) Bidentate ligands are known to inhibit the Pt-catalyzed dibo-
ration of alkynes and the Pd-catalyzed diboration of allenes. See ref
14f and Pelz, N. F.; Woodward, A. R.; Burks, H. E.; Sieber, J. D.;
Morken, J. P. J. Am. Chem. Soc. 2004, 126, 16328.
Results and Discussion
1. Reaction Development. A. Ligand Evaluation. On
the basis of the mechanism depicted in Scheme 1,
platinum complexes were avoided in exploratory studies
since chiral bidentate ligands were expected to prohibit
alkene coordination and insertion reactions that involve
d8 diboryl intermediates. Instead, an initial comparative
ligand analysis was conducted with a Rh(I) salt and
included a number of symmetric and nonsymmetric
bidentate ligands as well as a monodentate ligand
structure (Table 1). This survey was executed with trans-
â-methylstyrene and bis(catecholato)diboron [B2(cat)2] as
the reaction substrates. Each chiral ligand under ques-
tion was first treated with (cod)2RhBF4 followed by the
diboron reagent in THF at room temperature. Subse-
quently, the alkene was added and the reaction allowed
to stir for 12 h. Oxidative workup was accomplished by
(21) Miller, S. P.; Morgan, J. B.; Nepveux, F. J.; Morken, J. P. Org.
Lett. 2004, 6, 131.
(22) Kalendra, D. M.; Duen˜es, R. A.; Morken, J. P. Synthesis 2005,
1749.
J. Org. Chem, Vol. 70, No. 23, 2005 9539

Trudeau et al.
TABLE 2. Analysis of Transition-Metal Salts in the
TABLE 3. Examination of Solvent Effects in the
Rh-Quinap-Catalyzed Diboration of Alkenes
Asymmetric Alkene Diboration Reaction with (S)-Quinap
entry
Rh salt
% yielda
% eeb
entry
solvent
time (h) % yielda syn:antib % eeb
1
2
3
4
5
6
(nbd)Rh(acac)
(cod)Rh(acac)
(ethylene)Rh(acac)
(nbd)2RhBF4
(cod)2RhBF4
71
43
50
56
24
<5
93
93
92
95
86
1
2
3
4
5
6
7
8
9
THF
12
24
12
24
24
12
12
24
24
71
21
20
15
35
17
<5
<5
27
>50:1
34:1
93
90
92
87
87
89
CH2Cl2
dichloroethane
dimethoxyethane
toluene
>50:1
9.4:1
46:1
(cod)2IrBF4
ether
45:1
acetonitrile
acetone
a Isolated yield of purified material. b Determined by chiral GC
analysis.
1,4-dioxane
21:1
83
a Isolated yield of purified material. b Determined by GC analy-
treatment with basic hydrogen peroxide and the resulting
diol analyzed. As the results in Table 1 show, only a few
chiral ligands are able to furnish effective diboration
catalysts when combined with the rhodium salt. Modi-
fication of the metal with Quinap23 provides the highest
diastereo- and enantioselectivity; however, Binap also
provides an interesting reaction outcome wherein a
significant amount of the anti isomer is formed and
delivered in moderate enantiomeric excess.
sis on a permethylated â-cyclodextrin column.
sis of the transition-metal salt, the effect of reaction
solvent was surveyed. As depicted in Table 3, THF proved
to be the most effective solvent for the reaction; however,
toluene also afforded modest yields of reaction product.
Other solvents such as dichloromethane, ether, dimethox-
yethane, and dichloroethane provided the diboration
product in comparable optical purity although in dimin-
ished yields. Generally, the diboron reagent was much
less soluble in these other solvents.
B. Transition-Metal Salt. Due to the superior selectiv-
ity exhibited by Quinap, this ligand was selected for
further experimentation. As observed in Table 2, signifi-
cantly improved yield and selectivity could be achieved
by alteration of the transition-metal salt. Whereas the
reaction with (cod)2RhBF4 provided a mediocre yield in
the initial survey, when complexed with Quinap the
cationic (nbd)2RhBF4 and neutral (nbd)Rh(acac) provide
useful product yields and are the best of those examined.
In an effort to understand the nature of the transition-
metal-ligand complex that is formed under the reaction
conditions, (nbd)Rh(acac) was treated with Quinap and
the reaction examined by 31P NMR. While simply mixing
the ligand and the metal did not lead to a change in the
31P resonance of the Quinap ligand (-13 ppm), upon
addition of 3 equiv of B2(cat)2, association of Quinap with
the metal does occur and provides a number of species
2. Reaction Scope. A. 1,2-Disubstituted Alkenes.
Unfunctionalized 1,2-disubstituted alkenes participate in
the Rh-Quinap-catalyzed diboration reaction with the
trans alkene geometry reacting with excellent levels of
enantioselectivity. As depicted in Table 4, aromatic
substitution is tolerated but not required in the dibora-
tion reaction with both stilbene and a substituted styrene
providing high levels of enantiocontrol (entries 1 and 2).
Internal aliphatic alkenes are optimal reaction substrates
with trans-5-decene reacting in good yield and excellent
enantioselection. As demonstrated with entries 4 and 5,
protected hydroxyl functionality is tolerated in the form
of silyl ethers; notably, the coordinating functionality
present in both MOM ethers and benzyl ethers is
inconsequential to the reaction outcome, and good yields
and high selectivities result (entries 6 and 7). In contrast
to the reactions of trans alkenes, cis alkenes react with
varying levels of selectivity. While indene is converted
to the derived 1,2-diol in a selective fashion, cis-â-
methylstyrene provides low selectivity and favors the
opposite enantiomer of the reaction product. In contrast,
the Rh/Quinap-catalyzed hydroboration of cis-â-methyl-
styrene, as described by Brown, provides higher selection
and the same sense of induction as compared to indene.24
B. Monosubstituted Alkenes. These alkenes are attrac-
tive substrates for diboration reactions since the primary
and secondary C-B bonds may be differentially func-
tionalized in postreaction derivatization. As depicted in
Table 5, this alkene class is also the most challenging in
the Rh-Quinap-catalyzed diboration reaction. The reac-
tion rates are significantly higher than with trans
alkenes, and the reactions often reach completion in less
than 1 h. Simple R-olefins react with mediocre selectivity
(ca. 60% ee) when sterically undemanding functionality
with the dominant one resonating at 34.0 ppm (1JP-Rh
)
160 Hz). When the (nbd)Rh(acac)/Quinap-catalyzed reac-
tion is followed by 31P NMR, many new species are
apparent with none clearly dominant and none resonat-
ing at 34.0 ppm. In contrast, when (nbd)2RhBF4/Quinap-
catalyzed reaction is followed by 31P NMR, two species
dominate a handful of minor species, and the minor
compound of the pair can also be found in the NMR of
the (nbd)Rh(acac)/Quinap-catalyzed process (31P δ ) 67.9
1
ppm, JP-Rh ) 174.9 Hz). These experiments leave open
the possibility that both the neutral and the cationic
catalyst provide the same active catalyst under the
reaction conditions as one might suspect based on the
observations in Table 2.
C. Reaction Solvent. Sequential single-pot reaction
sequences that are initiated with asymmetric diboration
may be more facile if the diboration reaction can be
catalyzed in alternate solvents.21,22 Therefore, after analy-
(23) (a) Alcock, N. W.; Brown, J. M.; Hulmes, D. I. Tetrahedron:
Asymmetry 1993, 4, 743. (b) Lim, C. W.; Tissot, O.; Mattison, A.;
Hooper, M. W.; Brown, J. M.; Cowley, A. R.; Hulmes, D. I.; Blacker, A.
J. Org. Proc. Res. Dev. 2003, 7, 379.
(24) Doucet, H.; Fernandez, E.; Layszell, T. P.; Brown, J. B. Chem.
Eur. J. 1999, 5, 1320.
9540 J. Org. Chem., Vol. 70, No. 23, 2005

Enantioselective Diboration of Simple Alkenes
TABLE 4. Rh-Quinap-Catalyzed Diboration of
TABLE 5. Rh-Quinap-Catalyzed Diboration of
1,2-Disubstituted Alkenes
Monosubstituted Alkenes
a Configuration of reaction products determined by comparison
to authentic compounds. b Isolated yield of purified material; value
is an average of two experiments. c Determined by chiral GC,
HPLC, or SFC analysis. d (R)-Quinap was used for this experi-
ment.
a Configuration of reaction products determined by comparison
to authentic compounds. b Isolated yield of purified material; value
is an average of two experiments. c Determined by chiral GC or
SFC analysis. d In addition to the 1,2-diol, this reaction provided
17% 1-indanol.
diboration was examined with alternate diboron re-
agents. It was expected that with increased steric en-
cumbrance adjacent to the boron atom, improved facial
differentiation might result. As depicted in Scheme 2,
substituted bis(catecholato)diboron reagents were used
in place of B2(cat)2, and while reactivity was slightly
diminished, there was essentially no change in the level
of selectivity. It appears that even with diboron 10 in
Scheme 2 the substitution is too far removed from the
metal center to have a significant impact on selectivity.
C. 1,1-Disubstituted and Trisubstituted Alkenes. Table
6 describes the reaction outcome with 1,1-disubstituted
and trisubstituted alkenes, both of which provide a
tertiary C-B bond in the reaction intermediate. As
observed, the yields in these reactions often suffer and,
for 1,1-disubstituted alkenes where the steric bias of the
alkene prochiral faces is lessened, the selectivity is
expectedly low. With trisubstituted alkenes high enan-
tioselection results and the sense of asymmetric induction
is present at the allylic carbon (entries 1 and 2), and
styrene reacts in a notably nonselective fashion in the
Rh-Quinap-catalyzed diboration reaction. The outcome
with styrene stands in stark contrast to the selectivity
observed in the analogous Rh-Quinap-catalyzed hy-
droboration reaction (91.5% ee) for which aromatic alk-
enes are the only selective substrate class.24 Aliphatic
alkenes with an encumbered R-carbon in the form of a
quaternary center react with enhanced selectivity, pro-
viding product in the range of 93-96% ee (entries 4-7).
When comparable quaternary centers are one carbon
removed from the alkene, the selectivity is substantially
diminished as demonstrated in entries 8-10.
In an effort to improve the stereoselection with mono-
substituted alkenes, the (nbd)Rh(acac)/Quinap-catalyzed
J. Org. Chem, Vol. 70, No. 23, 2005 9541

Trudeau et al.
SCHEME 2. Rh-Quinap-Catalyzed Diboration of 1-Decene with Substituted Diboron Reagents
TABLE 6. Rh-Quinap-Catalyzed Diboration of
transition metals are problematic in the alkene dibora-
tion reaction. For instance, alkenes that contain allylic
ethers or contain aryl halides or triflates do not cleanly
provide the 1,2-bis(alkylboronate) upon treatment with
B2(cat)2 and the Rh-Quinap combination. As depicted in
Scheme 4, allylic ethers are converted to the correspond-
ing allylboronate when subjected to the asymmetric
diboration reaction conditions. This transformation pro-
ceeds whether the allylic oxygen atom is protected as an
ester, an aryl ether, or a silyl ether. While this transfor-
mation has been documented for Pd catalysts with bis-
(pinacolato)diboron,25 it is heretofore unknown with Rh
catalysts. Substrates containing aryl halides and triflates
provide either low reaction yields or the product of alkene
hydroboration when subject to the alkene diboration
reaction (data not shown).
1,1-Disubstituted and Trisubstituted Alkenes
3. Stereochemical Model. Experiments that provide
insight into the mechanism of the rhodium-Quinap-
catalyzed asymmetric diboration have not yet rigorously
established one series of elementary steps as that re-
sponsible for diboration catalysis. However, available
observations are consistent with a mechanism involving
oxidative addition, olefin insertion, and reductive elimi-
nation as described for the nonasymmetric processes
presented in Scheme 1. The first compelling evidence for
such a cycle is that the reaction products from the Rh-
Quinap-catalyzed diboration arise from net syn addition
across the alkene. In contrast, the anti diastereomer
which arises during Rh-Binap-catalyzed diboration of
trans-â-methylstyrene provides evidence that alternate
pathways may operate. The origin of the anti diastere-
omer that is produced with Rh-Binap was elucidated by
examination of this catalyst with indene as the substrate.
As depicted in Scheme 5, this experiment provides a
mixture of the expected 1,2-diol but also cis-1,3-in-
danediol (13) and 1-indanol (14) as the reaction products.
A reasonable sequence of events that would lead to such
an outcome involves coordination and insertion of the
alkene with a bis(boryl)rhodium complex to give 15.
Reductive elimination from 15 would give the observed
1,2-diol 12, while â-hydrogen elimination from 15 would
give 16. Intermediate 16 might undergo reinsertion/
reductive elimination to give 1,3-diol 13, or it might
dissociate the allylboronate to give a hydrido(boryl)-
rhodium complex which could affect hydroboration of the
starting alkene to furnish 14.26
a Configuration of reaction products determined by comparison
to authentic compounds. b Isolated yield of purified material; value
is an average of two experiments. c Determined by chiral GC or
SFC analysis.
SCHEME 3. Selective Diboration of a Diene
Substrate
is identical to that observed with trans-disubstituted and
monosubstituted alkenes.
The reactivity characteristics observed in the tables
above suggest that one might observe selective transfor-
mation of the less substituted olefin in a diene substrate.
To probe such a possibility the diboration reaction in
Scheme 3 was executed. As anticipated, steric effects
dominate the reaction outcome and the trisubstituted
alkene is essentially untouched in the diboration product.
The product 1,2-diol may be isolated in good yield and
high enantiomeric excess.
Relative to the Rh-Binap-catalyzed reaction, the dibo-
ration of indene with the (nbd)Rh(acac)/Quinap catalyst
(25) (a) Ishiyama, T.; Ahiko, T.; Miyaura, N. Tetrahedron Lett. 1996,
37, 6889. (b) Ahiko, T.; Ishiyama, T.; Miyaura, N. Chem. Lett. 1997,
811.
D. Allylic Ethers. Substrates with functionality that
may participate in oxidative addition reactions with
9542 J. Org. Chem., Vol. 70, No. 23, 2005

Enantioselective Diboration of Simple Alkenes
SCHEME 4. Reaction of an Allylic Ether under Rh-Catalyzed Diboration Conditions
SCHEME 5. Rh-Binap-Catalyzed Diboration of
Indene
FIGURE 1. Correlation between %ee Quinap ligand and %ee
SCHEME 6. Crossover in Rh-Quinap-Catalyzed
Diboration of Deuteriostyrne and Protiostyrene
diboration product.
SCHEME 7. Predictive Model for
Rh-Quinap-Catalyzed Alkene Diboration
provides less 1-indanol (4:1 12:14) and no 1,3-diol 13.
This observation suggests that â-hydrogen elimination
pathways are less operative with this catalyst. To further
substantiate this claim, a mixture of styrene and styrene-
d8 was subjected to the Rh-Quinap-catalyzed diboration.
Mass spectral analysis of the resulting 1,2-diol 17 showed
that in addition to 17-D8 a small amount of 17-D7H1 is
also present. Production of 17-D7H1 is consistent with
the observations above wherein â-hydrogen elimination/
hydroboration compete with alkene diboration. As ex-
pected, nonlabeled compound 17-H8 was also present;
however, it was not possible to determine the amount of
17-D1H7 present as this compound has the same mass
as the 13C isotopomer of 17-H8, Scheme 6. Collectively,
the observations with indene and labeled styrene suggest
that â-hydrogen elimination/hydroboration processes, at
the very most, only provide a minor pathway toward
generation of the reaction product.27
a near-perfect correlation exists between the optical
purity of the ligand and that of the product. These
experiments are highly suggestive of a catalyst which is
monomeric with a single ligand structure on the metal.
Stereochemical models for the Rh-Quinap-catalyzed
alkene diboration reaction are depicted in Scheme 7.
These models are based on the assumption that the
mechanism in Scheme 1 operates and are also based on
the crystallographic analysis of the Quinap ligand coor-
dinated to ruthenium and palladium centers.29 In model
A it is suggested that after oxidative addition of B2(cat)2
to Rh(I) the alkene coordinates to the Rh(III) center
opposite the weaker trans-effect atom (nitrogen) and
insertion occurs into the equatorial Rh-B bond as it is
weakened by the strong trans-influence phosphine
ligand.30 In model B the anionic boryl ligand is trans to
the less basic atom of the Quinap ligand, leading to a
As described above, NMR analysis of metal-ligand
complexes has not proven informative. As an alternative
means to learn more about the nature of the active
catalyst in alkene diboration reactions we studied the
relationship between ligand enantiopurity and product
enantiopurity.28 As depicted in Figure 1, nonlinear effects
are absent in the Rh-Quinap-catalyzed diboration and
(26) Dissociation of a hydrido(boryl)rhodium structure from 16
implies that an allylboronate should be generated. We have not
detected this compound, although it is reasonable to anticipate that it
might be protonated rapidly upon aqueous oxidative workup.
(27) At this point we have been unable to rule out a mechanism
involving insertion of an alkene into a Rh(I) boryl complex followed
by oxidative addition to B2(cat)2 and reductive elimination of the bis-
(boronate) product. Crossover experiments would provide this informa-
tion; however, we have found that B2(cat)2 and B2(4-t-BuCat)2 undergo
noncatalyzed exchange of the catechol ligands, thereby precluding this
experiment.
(28) For reviews, see: (a) Blackmond, D. G. Acc. Chem. Res. 2000,
33, 402. (b) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. 1998, 37,
2922.
(29) (a) Alcock, N. W.; Brown, J. M.; Hulmes, D. I. Tetrahedron:
Asymmetry 1993, 4, 743. (b) Faller, J. W.; Grimmond, B. J. Organo-
metallics 2001, 20, 2454.
J. Org. Chem, Vol. 70, No. 23, 2005 9543

Trudeau et al.
more stable and perhaps more populated coordination
geometry. Since the Quinap ligand provides a pseudo-
C2-symmetric steric environment about the metal center,
both models A and B lead to the same set of stereochem-
ical predictions. If quadrant diagrams31 are used to
demarcate the steric environment surrounding the coor-
dinated alkene, then the lower left quadrant is occupied
by the equatorial phenyl group of the PPh2 element in
model A and the top right quadrant is occluded by the
isoquinoline in model B. On the basis of these diagrams
it can be predicted that trans- and trisubstituted alkenes
should react in a selective fashion and favor the observed
product enantiomer. Similarly, indene and 2-methylin-
dene should react selectively assuming that regioselective
alkene insertion occurs to provide the more stable ben-
zylic C-Rh bond. With monosubstituted and 1,1-disub-
stituted alkenes the initial insertion might be expected
to provide the less hindered primary C-Rh bond. One
would therefore predict less enantiofacial control in
reactions of monosubstituted and 1,1-disubstituted alk-
enes since there is not an obvious steric bias between the
quadrants which are opposite the chiral ligand. This
model does not readily predict the low level of stereose-
lection with styrene nor does it provide a rationale for
the turnover in selectivity with dihydronaphthalene
relative to indene.
Experimental Section
Representative Procedure for the Catalytic Dibora-
tion of trans-â-Methylstyrene. An oven-dried 20 mL vial
equipped with a stir bar was charged with 3.7 mg (12.5 µmol)
of (bicyclo[2.2.1]hepta-2,5-diene)-(2,4-pentanedionato)rhodium-
(I) [(nbd)Rh(acac)], 5.5 mg (12.5 µmol) of (S)-Quinap, and 0.5
mL of THF under an inert atmosphere of argon in a drybox.
The resultant yellow solution was stirred for 5 min. After this
time 65.4 mg (0.28 mmol) of bis(catecholato)diboron was added
to the solution under argon. The solution turned immediately
from yellow to dark brownish-red. The solution was allowed
to stir for 5 min. After this time 29.5 mg (0.25 mmol) of trans-
â-methylstyrene was added to the solution under argon. The
vial was sealed with a screw cap and removed from the drybox,
where the solution was allowed to stir for 14 h at ambient
temperature. After this time the mixture was cooled to 0 °C
and 0.4 mL of 3 M NaOH and then 0.4 mL of 30% H2O2 were
added (dropwise with caution) under nitrogen. The solution
was allowed to stir at ambient temperature for 3 h. The
solution was then quenched with 0.5 mL of saturated aqueous
Na2S2O3 and 5 mL of 1 M NaOH. The mixture was extracted
with ethyl acetate (3 × 10 mL), and the combined organic
layers were washed with brine (1 × 10 mL). The organic layers
were then dried over anhydrous MgSO4 and filtered, and the
solvent was removed by rotary evaporation. The crude material
was purified by silica gel chromatography (1:1 hexanes:ethyl
acetate) to provide 27.2 mg (71%) of pure (1R,2R)-1-phenyl-
propane-1,2-diol. Rf ) 0.24 (silica gel, 1:1 hexanes:ethyl
acetate). IR (neat, ν cm-1): 3384, 1455, 1038. 1H NMR: δ 7.25-
7.42 (5H, m), 4.36 (1H, d, J ) 7.6 Hz), 3.85 (1H, qd, J ) 7.2
Hz, 6.4 Hz), 2.44 (2H, br s), 1.05 (3H, d, J ) 6.4 Hz). 13C
NMR: δ 141.0, 128.5, 128.2, 126.8, 79.5, 72.2, 18.8. HRMS
(FAB) Calcd for C9H16NO2 (M + NH4)+: 170.1181. Found:
170.1177. Chiral GLC (â-dex, Supelco, 140 °C, 20 psi): major
isomer (1R,2R) 51.6 min; minor isomer (1S,2S) 49.7 min.
Conclusion
The enantioselective diboration of alkenes can be
catalyzed by chiral rhodium-Quinap complexes, and the
reaction is effective for a number of alkene substrates.
The sense and levels of stereoinduction can be predicted
in a reliable fashion for many alkene substrates. Current
experiments are aimed at gaining a better understanding
of the reaction mechanism and developing improved
ligand structures based on the stereochemical hypotheses
developed herein.
Acknowledgment.
(NIGMS: R01-GM59417) is gratefully acknowledged.
Support from the NIH
Supporting Information Available: Complete experi-
mental procedures, characterization data (1H and 13C NMR,
IR, and mass spectrometry), enantiomeric purity data (chiral
GC, HPLC, SFC), and structure proofs (authentic syntheses).
This material is free of charge via the Internet at http:
//pubs.acs.org.
(30) For an excellent discussion of the steric and electronic properties
of amines in relation to phosphines, see: Togni, A.; Venanzi, L. M.
Angew. Chem., Int. Ed. Engl. 1994, 33, 497.
(31) Gladyz, J. A.; Boone, B. J. Angew. Chem,. Int. Ed. Engl. 1997,
36, 551.
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9544 J. Org. Chem., Vol. 70, No. 23, 2005