Diastereoselective Formation of Indanes from Arylboronate Esters Catalyzed by Rhodium(I) in Aqueous Media

Article abstract of DOI:10.1021/ol0260627

(Matrix Presented) R₁ = amide, ketone, ester, aldehyde R₂ = H, CO₂Me Arylboronate esters bearing a pendant Michael-acceptor alkene can add to norbornene and cyclize to give indane systems in yields ranging from 62% to 95%

Full text of DOI:10.1021/ol0260627

ORGANIC
LETTERS
2
002
Vol. 4, No. 12
105-2108
Diastereoselective Formation of Indanes
from Arylboronate Esters Catalyzed by
Rhodium(I) in Aqueous Media
2
Mark Lautens* and John Mancuso
DaVenport Chemical Laboratories, Department of Chemistry, UniVersity of Toronto,
80 St. George Street, Toronto, Ontario M5S 3H6, Canada
mlautens@chem.utoronto.ca
Received April 22, 2002
ABSTRACT
Arylboronate esters bearing a pendant Michael-acceptor alkene can add to norbornene and cyclize to give indane systems in yields ranging
from 62% to 95% with high diastereomeric excess (>20:1). The reaction is performed in an organic/aqueous emulsion and catalyzed using
2
[Rh(COD)Cl] with t-Bu-amphos chloride, a sterically bulky, electron-rich, water-soluble phosphine ligand.
2
3
4
4a
Aqueous transition metal catalysis is gaining in popularity
as a method for generating complex organic molecules with
reduced environmental impact. Water exhibits a combination
of properties difficult to emulate with organic solvents (i.e.,
polarity, H-bonding, basicity) and can provide a means for
catalyst recovery, reducing overall cost.
One of the goals of our investigation is to generate
arylrhodium species and react them with unactivated olefins
in aqueous media. Studies by several groups have shown
that arylrhodium species can be generated from arylmetal
precursors where the metal is boron, silicon, tin, bismuth,
5
or mercury. Typically, saturated products are obtained, but
in certain cases formation of the Heck product is a competing
1
3
b,6
process.
Methodologies to date focus on intermolecular processes
with the rhodium mediating the formation of one carbon-
carbon bond. Palladium chemistry is well-known for tandem
7
or “cascade” processes, whereby a single mole of catalyst
can effect the formation of several bonds within a single
substrate molecule, resulting in a complex and functionally
diverse product.
In an attempt to create a rhodium-based tandem reaction
process, we envisaged the trapping of an intermediate
(1) (a) Cornils, B.; Herrmann, W. A. Aqueous-Phase Organometallic
Catalysis; Wiley-VCH: Weinheim, Germany, 1998. (b) Horv a´ th, I. T.; Jo o´ ,
F. Aqueous Organometallic Chemistry and Catalysis; Kluwer Academic:
Dordrecht, The Netherlands, 1995. (c) Li, C.-J.; Chan, T.-H. Organic
Reactions in Aqueous Media; Wiley-Interscience: New York, 1997.
(
2) Selected recent references: (a) Murakami, M.; Igawa, H. Chem.
Commun. 2002, 4, 390. (b) Lautens, M.; Yoshida, M. Org. Lett. 2002, 4,
23. (c) Frost, C. G.; Wadsworth, K. J. Chem. Commun. 2001, 22, 2316.
(4) (a) Huang, T.; Meng, Y.; Venkatraman, S.; Wang, D.; Li, C.-J. J.
Am. Chem. Soc. 2001, 123, 7451. (b) Oi, S.; Moro, M.; Ito, H.; Honma,
Y.; Miyano, S.; Inoue, Y. Tetrahedron 2002, 58, 91.
1
Asymmetric additions: (d) Hayashi, T. Synlett 2001, Spec. Iss., 879. (e)
Sakuma, S.; Miyaura, N. J. Org. Chem. 2001, 66, 8944. (f) Itooka, R.;
Iguchi, Y.; Miyaura, N. Chem. Lett. 2001, 7, 722.
(5) (a) Larock, R. C.; Bernhardt, J. C. J. Org. Chem. 1977, 42, 180. (b)
Larock, R. C.; Hershberger, S. S. J. Org. Chem. 1980, 45, 3840.
(6) Lautens, M.; Roy, A.; Fukuoka, K.; Fagnou, K.; Martin-Matute, B.
J. Am. Chem. Soc. 2001, 123, 5358.
(3) (a) Oi, S.; Honma, Y.; Inoue, Y. Org. Lett. 2002, 4, 667. (b) Mori,
A.; Danda, Y.; Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am. Chem. Soc.
(7) For selected reviews on Pd cascade reactions, see: (a) Heumann,
A.; R e´ glier, M. Tetrahedron 1996, 52, 9289. (b) Grigg, R.; Sridharan, V.
J. Organomet. Chem. 1999, 576, 65.
2
001, 123, 10774. (c) Huang, T. S.; Li, C.-J. Chem. Commun. 2001, 22,
348.
2
1
0.1021/ol0260627 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/11/2002

arylrhodium species with a strained olefin, such as nor-
8
bornene, to generate an alkylrhodium species that cannot
Table 1. Optimization Study for the Formation of Indane 4a
â-hydride eliminate (Scheme 1). The presence of a pendant
Scheme 1. Proposal for Tandem Reaction
entry
catalyst/ligand
conversion, %b
4:5c
1
2
3
4f
5f,g
6f,h
7f
[Rh(cod)Cl]2
13
>99
>99
>99 (95)
>99
69:31
27:73
e
>99:<1
96:4
>99:<1
>99:<1
[Rh(cod)Cl]2/1d
[Rh(cod)Cl]2/2
[Rh(cod)Cl]2/2
[Rh(cod)Cl]2/2
[Rh(cod)Cl]2/2
[Rh(cod)OH]2/2
>99
>99
a
cod ) 1,5-cyclooctadiene. Reactions run in 0.2 M degassed water under
nitrogen with 0.6 equiv of SDS and 1 equiv of Na2CO3 at 80 °C for 2 h.
b
1
c
Determined by H NMR. Isolated yield of 4 in parentheses. Determined
1
d
e
f
by H NMR. 8 mol % ligand used. Variable (see text). 1:1 water/toluene
olefin would allow intramolecular cyclization and eject the
product either via protodemetalation or â-hydride elimination
of the rhodium intermediate. In either case, in order for this
process to be an efficient methodology, the problem of
competitive hydrolytic deboronation of arylboronic acids by
rhodium in water would have to be minimized.
We have previously shown that arylboronic acids add to
substituted styrenes in water in the presence of a rhodium
catalyst, a water-soluble ligand (Figure 1, TPPDS, 1), and a
(degassed) was used as the solvent. g 1 equiv of norbornene used. h Reaction
run at rt for 14 h.
Adding a water-soluble ligand such as TPPDS (1) resulted
in a significant increase in the rate of consumption of the
boronate ester, although the ratio of products changed to
favor 5 (entry 2). Switching to a more electron-rich and bulky
water-soluble phosphine such as 2 showed similar conversion
rates; however, yields of 4 were irreproducible, ranging from
3
0% to 95% (entry 3).
This problem was resolved through the addition of an
organic cosolvent. With 2 as the ligand in a 1:1 mixture of
water and toluene (entry 4), excellent selectivity for the
cyclized product was observed. To prove that the improved
results were due to the amphos ligand, we repeated the
TPPDS experiment (entry 2, Table 1) in a 1:1 mixture of
toluene/water and obtained very little change in product
ratios. Thus we believe that ligand 2 is responsible for the
high activity/selectivity seen. SDS was added to ensure
proper mixing of both phases, resulting in an organic/aqueous
emulsion. Product 4 could be isolated in 95% yield in
diastereomeric excess of >20:1, and the stereochemical
configuration was assigned by 2D-NMR and NOE experi-
ments.
Figure 1. Water-soluble ligands and model substrate.
phase transfer agent (sodium dodecyl sulfate, SDS), to
generate stilbene derivatives resulting from a Heck-type
6
9
process. We now introduce t-Bu-amphos chloride (2) as a
superior ligand for the transmetalation of arylboron substrates
to arylrhodium intermediates in water. Ligand 2 effects
transmetalation at room temperature and greatly reduces the
problem of hydrolytic deboronation, presumably as a result
of its steric bulk and basic properties.
The use of only 1 equiv of norbornene still gave the desired
adduct with >95% selectivity (entry 5), indicating that this
reaction is attractive from an atom economy point of view.10
It was also possible to run the reaction at room temperature
(
entry 6) rather than at 80 °C, albeit with a longer reaction
The pinacol (pin) boronate ester 3 was selected as a model
substrate and tested with a catalytic amount of [Rh(cod)Cl]
in water with SDS and norbornene. Poor conversion was
seen (Table 1, entry 1), and a mixture of deboronated product
1
1
time (14 h). The use of [Rh(cod)OH]
2
exhibited activity
2
similar to that of the chloride dimer (entry 7), emphasizing
the likelihood that a hydroxorhodium(I) species is part of
the catalytic cycle.
5
and the desired indane 4 was obtained.
The scope of the reaction was investigated using other
norbornene and norbornadiene derivatives. Unstrained al-
kenes such as styrene and 3-sulfolene were also tested and
(
8) Oguma, K.; Miura, M.; Satoh, T.; Nomura, M. J. Organomet. Chem.
002, 648, 297.
9) (a) For preparation of t-Bu-amphos Cl (2) and account of its efficiency
2
(
for Pd-catalyzed Suzuki couplings in aqueous media, see: Shaughnessy,
K. H.; Booth, R. S. Org. Lett. 2001, 3, 2757. (b) Original amphos ligand:
Smith, R. T.; Baird, M. C. Inorg. Chim. Acta 1982, 62, 135.
(10) Trost, B. M. Science 1991, 254, 1471.
(11) Uson, R.; Oro, L. A.; Cabeza, J. A. Inorg. Synth. 1985, 23, 126.
2106
Org. Lett., Vol. 4, No. 12, 2002

exhibited no reactivity. The ratio of boronate ester to alkene
was kept at 1:2, except in cases where the presence of excess
alkene could interfere with purification.
The use of boronate esters with pendant enone and
acrylamide moieties were also tolerated giving exo-adducts
9 (entry 4) and 10 (entry 5), respectively. A boronate ester
containing an R,â-unsaturated aldehyde moiety (entry 6)
showed extensive intermolecular coupling under the standard
reaction conditions. In this case, a good yield of the product
The results in Table 2 showed that the reaction gave high
1
1 could be achieved if the reaction was conducted at room
Table 2. Tandem Reactions with a Variety of Boronate Esters
and Alkenes
temperature with slow addition of the substrate to the reaction
mixture.
An example of a postsynthetic modification to yield
functionalized tricyclic systems is shown in Figure 2.
Figure 2. Oxidative cleavage of 6 to yield diquinane 12.
Ozonolysis of 6 followed by reductive workup with NaBH
4
gave the diquinane 12 in quantitative yield. Compound 12
bears five stereocenters, three of which are created in the
coupling step.
The catalytic cycle is believed to follow the path shown
n
in Scheme 2, whereby the active catalyst is L Rh(OH) (I),
Scheme 2. Proposed Catalytic Cycle
a
Ratio of boronate ester to alkene is 1:2. b Isolated by column chroma-
c
tography. Diastereomeric excess is >20:1 for all entries. Ratio of boronate
ester to alkene is 1:1.2. Slow addition of boronate ester to reaction mixture
d
over 12 h at rt.
diastereoselectivity with various substrates of >20:1. The
relative stereochemical configurations of products 6-11 were
assigned on the basis of the spectroscopic data of 4.
Norbornadiene (entry 1) gave the exo-adduct 6 in excellent
1
2
yield. A substituted norbornadiene only reacted at the
unsubstituted olefin (entry 2) to give product 7, and a
functionalized norbornene gave pentacycle 8 in high yield
(
entry 3).
which transmetalates with II to give the arylrhodium(I)
species III. Carborhodation of the alkene ensues to give IV
in which the rhodium is presumably coordinated to the
(12) Stereochemistry of 6 proved by hydrogenation, which gives only
product 4.
Org. Lett., Vol. 4, No. 12, 2002
2107

internal pendant olefin. Carbocyclization then occurs via a
-exo-trig process to generate the rhodium(I) enolate V.
Protodemetalation of V by water generates the product VI
and regenerates I, which can re-enter the catalytic cycle.
We are currently investigating the use of heterocyclic
arylboronate esters, as well as evaluating alternative alkene
coupling partners to replace norbornyl olefins.
5
Acknowledgment. We thank NSERC (Canada), the
Merck Frosst Centre for Therapeutic Research, and the
University of Toronto for financial support. We also thank
K. Fagnou for helpful discussions.
To the best of our knowledge, this is the first example of
tandem carbocyclization process utilizing a water-soluble
rhodium catalyst system. Utilizing water as cosolvent poses
an obvious advantage due to its environmental and economic
benefits. In addition, the use of the t-Bu-amphos chloride
ligand prevents hydrolytic deboronation; therefore yields can
be based on the boronate ester, improving atom economy
and reducing cost, as the boronate ester is typically the more
expensive coupling partner.
Supporting Information Available: General procedures
1
and spectroscopic data for compounds 4 and 6-12 and H
NMR, COSY, and ROESY spectra for compound 4. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL0260627
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Org. Lett., Vol. 4, No. 12, 2002