Rh(I)-catalyzed carbonylative ring opening of diazabicycles with acyl anion equivalents

Article abstract of DOI:10.1021/ol7022054

A catalytic desymmetrization of strained alkenes by ring-opening of meso-diazabicycles with acyl anion nucleophiles is reported. Densely functionalized frans-1,2-hydrazinoacyl cyclopentene building blocks are obtained stereoselectively. The acyl anion equ

Full text of DOI:10.1021/ol7022054

ORGANIC
LETTERS
2
007
Vol. 9, No. 26
365-5367
Rh(I)-Catalyzed Carbonylative Ring
Opening of Diazabicycles with Acyl
Anion Equivalents
5
Frederic Menard, Christian Frederik Weise, and Mark Lautens*
DaVenport Research Laboratories, UniVersity of Toronto, 80 St. George Street,
Toronto, Ontario, Canada M5S 3H6
mlautens@chem.utoronto.ca
Received September 7, 2007
ABSTRACT
A catalytic desymmetrization of strained alkenes by ring-opening of meso-diazabicycles with acyl anion nucleophiles is reported. Densely
functionalized trans-1,2-hydrazinoacyl cyclopentene building blocks are obtained stereoselectively. The acyl anion equivalent is generated in
situ under very mild conditions from readily available organoboron precursors.
4
Acylation reactions are the focus of a growing interest and
expand the reaction beyond hydroformylation. The insertion
new reactions to desymmetrize meso substrates, the success
of rhodium catalysts to effect formal allylic substitutions of
1
5
of carbon monoxide into metal-carbon bonds is well
activated alkenes prompted us to explore the reactivity of
2
precedented with several metals, but rhodium is by far the
acyl-anion nucleophiles.
3
most versatile in terms of reactivity. In the development of
The generation of an acyl rhodium III is usually achieved
in two ways: (i) by the insertion into aldehydes and
1
b-f
(1) (a) Harada, Y.; Nakanishi, J.; Fujihara, H.; Tobisu, M.; Fukumoto,
anhydrides
or (ii) by the insertion of CO gas into an
Y.; Chatani, N. J. Am. Chem. Soc. 2007, 129, 5766. (b) Tanaka, K.; Shibata,
Y.; Suda, T.; Hagiwara, Y.; Hirano, M. Org. Lett. 2007, 9, 1215. (c) Hong,
Y. T.; Barchuk, A.; Krische, M. J. Angew. Chem., Int. Ed. 2006, 45, 6885.
1a
organometallic bond. The first approach generally requires
the presence of a chelating group on the aldehyde reactant
to prevent competing decarbonylation. The second approach
(d) Moxham, G. L.; Randell-Sly, H. E.; Brayshaw, S. K.; Woodward, R.
L.; Weller, A. S.; Willis, M. C. Angew. Chem., Int. Ed. 2006, 45, 7618. (e)
Tanaka, K.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 8078. (f) Tanaka, K.;
Fu, G. C. J. Am. Chem. Soc. 2002, 124, 10296.
usually necessitates high pressure apparatus, heating, or often
3f-h,6
both.
A drawback to these methods is that the nature of
(2) (a) Beller, M.; Krauter, J. G. E. In Applied Homogeneous Catalysis
with Organometallic Compounds, 2nd ed.; Cornils, B., Herrmann, W. A.,
Eds; Wiley-VCH: New York, 2002. Palladium: (b) Zeni, G.; Larock, R.
L. Chem. ReV. 2006, 106, 4644. Cobalt: (c) Struebing, D.; Beller, M. Top.
Organomet. Chem. 2006, 18, 165. (d) Klingler, R. J.; Chen, M. J.; Rathke,
J. W.; Kramarz, K. W. Organometallics 2007, 26, 352.
(4) (a) Cortez, G. A.; Schrock, R. R.; Hoveyda, A. H. Angew. Chem.,
Int. Ed. 2007, 46, 4534. (b) Cook, M. J.; Rovis, T. J. Am. Chem. Soc. 2007,
129, 9302. (c) Johnson, J. B.; Bercot, E. A.; Williams, C. M.; Rovis, T.
Angew. Chem., Int. Ed. 2007, 46, 4514. (d) Arai, K.; Lucarini, S.; Salter,
M. M.; Ohta, K.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2007,
129, 8103. (e) Berlin, J. M.; Goldberg, S. D.; Grubbs, R. H. Angew. Chem.,
Int. Ed. 2006, 45, 7591. (f) Bournaud, C.; Falciola, C.; Lecourt, T.; Rosset,
S.; Alexakis, A.; Micouin, L. Org. Lett. 2006, 8, 3581. (g) Cabrera, S.;
Arrayas, R. G.; Alonso, I.; Carretero, J. C. J. Am. Chem. Soc. 2005, 127,
17938.
(5) For a prime example of Rh-catalyzed desymmetrization: (a) Lautens,
M.; Fagnou, K.; Hiebert, S. Acc. Chem. Res. 2003, 36, 48. See also: (b)
McManus, H. A.; Fleming, M. J.; Lautens, M. Angew. Chem., Int. Ed 2007,
46, 433. (c) Tseng, N.-W.; Mancuso, J.; Lautens, M. J. Am. Chem. Soc.
2006, 128, 5338. (d) Menard, F.; Chapman, T. M.; Dockendorff, C.; Lautens,
M. Org. Lett. 2006, 8, 4569.
(
3) For Pauson-Khand reactions: (a) Struebing, D.; Beller, M. Top.
Organomet. Chem. 2006, 18, 165. (b) Bayden, A. S.; Brummond, K. M.;
Jordan, K. D. Organometallics 2006, 25, 5204. (c) Wender, P. A.; Croatt,
M. P.; Deschamps, N. M. J. Am. Chem. Soc. 2004, 126, 5948. For
hydroformylation reactions: (d) Thomas, P. J.; Axtell, A. T.; Klosin, J.;
Peng, W.; Rand, C. L.; Clark, T. P.; Landis, C. R.; Abboud, K. A. Org.
Lett. 2007, 9, 2665. (e) Kuil, M.; Soltner, T.; van Leeuwen, P. W. N. M.;
Reek, J. N. H. J. Am. Chem. Soc. 2006, 128, 11344. (f) Huang, J.; Bunel,
E.; Allgeier, A.; Tedrow, J.; Storz, T.; Preston, J.; Correll, T.; Manley, D.;
Soukup, T.; Jensen, R.; Syed, R.; Moniz, G.; Larsen, R.; Martinelli, M.;
Reider, P. J. Tetrahedron Lett. 2005, 46, 7831. For silylformylation: (g)
Zacuto, M. J.; Leighton, J. L. J. Am. Chem. Soc. 2000, 122, 8587. For
C-H functionalization: (h) Chatani, N.; Asaumi, T.; Ikeda, T.; Yorimitsu,
S.; Ishii, Y.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc. 2000, 122, 12882.
(6) Evans, P. A. In Modern Rhodium-Catalyzed Organic Reactions;
Wiley-VCH: Weinheim, Germany, 2005.
1
0.1021/ol7022054 CCC: $37.00
© 2007 American Chemical Society
Published on Web 11/17/2007

the acyl group cannot be varied easily. Consequently, a
catalytic protocol which could generate easily variable acyl
anion equivalents would be very useful.
By exploiting rhodium’s high affinity for CO and its
reactivity with boronic acids, it is possible to generate an
7
acyl-anion intermediate III (Scheme 1). However, the
The acylated cyclopentene 3a was obtained as the sole
product in excellent yield. The absence of 2a was surprising
14
as it is the only product formed in the absence of CO. Thus,
the outcome of the reaction is completely changed by using
a simple CO gas balloon instead of Ar.
Scheme 1. Proposed Ring Opening with Acyl Rhodium Species
Noteworthy features of the reaction are the exclusive
formation of the trans isomer of the acylated product, the
alkene in 3 does not isomerize to give the conjugated enone,
and the unusual mildness of the reaction conditions for an
intermolecular CO-insertion. The stereochemistry presum-
ably results from addition on the alkene taking place on the
exo face of bicycle 1. The present ring-opening of the diaza
compounds complements our previous work in the ring-
opening of oxa or aza bicycles, which always gave the 1,2-
cis ring-opened products with carbon nucleophiles.5
The important optimization results are summarized in
Table 1. It was found that a nonpolar, non-coordinating
reversible process of CO insertion/extrusion favors II over
III for thermodynamic reasons, and this is why high
pressures are usually required.8 Thus, in applying this
catalytic system to the desymmetrization of strained alkenes
I under ambiant conditions, it was unclear whether the
desired acylrhodation (pathway b) would occur preferentially
to the competing carborhodation (pathway a). Indeed, the
catalytic ring-opening of diazabicycles I with nucleophiles
a,b,15
Table 1. Optimization of the Ring Opening with Benzoyl
Aniona
9
10
toward IV is known with alkyls, aryl groups, and het-
eroatoms.11 Herein, we report the chemo- and diastereose-
lective reaction of diazabicycles with acyl rhodium species
toward V, which constitutes the first example of a Rh-
catalyzed allylic substitution with acyl anion equivalents.
Diazabicyles 1 are attractive key substrates because of their
b
12
entry
catalyst
solvent
THF
dioxane
CH2Cl2
time (h)
yield (%)
easy preparation and stability. Additionally, the ring-opened
1
3
hydrazine is well recognized as an amine precursor. In a
test reaction, 2.0 equiv of phenylboronic acid and 1.0 equiv
of bicyclic hydrazine 1a were mixed with 10 mol % of
rhodium(I) complex in the stated solvent at 23 °C, under a
CO atmosphere (eq 1).
1
2
3
4
5
6
7
8
9
[Rh(CO)2acac]
[Rh(CO)2acac]
[Rh(CO)2acac]
[Rh(CO)2acac]
[Rh(CO)2acac]
[Rh(CO)2acac]
[Rh(CO)2Cl]2
[Rh(cod)Cl]2
[Rh(cod)OH]2
[Rh(cod)OH]2
[Rh(cod)2]OTf
[Ir(cod)Cl]2
48
48
72
48
16
20
20
20
20
20
20
20
20
20
38
50
74
70
92
95
92
95
91
92
4
toluene
benzene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
toluene/H2O
(7) This concept was recently recognized by Castanet to generate 1,4-
diketones from enones: (a) Chochois, H.; Sauthier, M.; Maerten, E.;
Castanet, Y.; Mortreux, A. Tetrahedron 2006, 62, 11740. (b) Askın, O.;
Dege, N.; Artok, L.; Tuerkmen, H.; Cetinkaya, B. Chem. Commun. 2006,
c
10
3
1
187. (c) Sauthier, M.; Castanet, Y.; Mortreux, A. Chem. Commun. 2004,
1
1
1
1
2
3
520.
trace
0
0
(
8) For carbonyl insertion/extrusion studies, see: (a) Krug, C.; Hartwig,
Pd2(dba)3
Cu(OAc)2
J. F. J. Am. Chem. Soc. 2002, 124, 1674. (b) Beck, C. M.; Rathmill, S. E.;
Park, Y. J.; Chen, J.; Crabtree, R. H.; Liable-Sands, L. M.; Rheihold, A. L.
Organometallics 1999, 18, 5311.
14
a
(
9) Pineschi, M.; Del Moro, F.; Crotti, P.; Macchia, F. Org. Lett. 2005,
, 3605.
10) Racemic: (a) John, J.; Sajisha, V. S.; Mohanlal, S.; Radhakrishnan,
All reactions were performed using 1b (0.135 mmol) with the listed
catalyst (10 mol % in Rh), ligand (12 mol %), PhB(OH)2 (2.0 equiv), and
solvent (0.07 M). b Isolated yield. c Without phosphine ligand.
7
(
K. V. Chem. Commun. 2006, 3510. Asymmetric: (b) Bertolini, F.; Macchia,
F.; Pineschi, M. Tetrahedron Lett. 2006, 47, 9173. (c) Menard, F.; Lautens,
M. Unpublished work.
(
11) Luna, A. P.; Cesario, M.; Bonin, M.; Micouin, L. Org. Lett. 2003,
solvent is needed in the presence of water to obtain high
yields (entries 1-6). Rhodium is the metal of choice to effect
5
, 4771.
(12) Diels, O.; Bolm, J. H.; Knoll, W. Justus Liebigs Ann. Chem. 1925,
4
43, 242. 1b is a free-flowing powder, making for easy handling. Its
preparation on scale is convenient, involving simple filtration of the reaction
mixture to obtain analytically pure material.
(14) When the same reaction was conducted under an argon atmosphere,
2a was obtained in >70% yield (see ref 10c). This observation suggests
that when CO is present, it coordinates to Rh(I) preferentially to 1, and
that only when the acyl rhodium species is formed is the alkene 1 allowed
to bind and react.
(
13) (a) Poulsen, T. B.; Alemparte, C.; Jørgensen, K. A. J. Am. Chem.
Soc. 2005, 127, 11614. (b) Ding, H.; Friestad, G. K. Org. Lett. 2004, 6,
37. (c) Evans, D. A.; Britton, T. C.; Dorow, R. L.; Dellaria, J. F.
Tetrahedron 1988, 44, 5525.
6
(15) Lautens, M.; Dockendorff, C. Org. Lett. 2003, 5, 3695.
5366
Org. Lett., Vol. 9, No. 26, 2007

the desired transformation, but the reaction is not sensitive
to the rhodium source, as long as it is a neutral complex
was inferior when electron-withdrawing substituents were
present on the arylboronic acid moiety (38-77%, entries 16-
18). The likely cause is a decreased rate of CO insertion
step to form the acyl intermediate II for electron withdrawing
groups. Alkenylboronic acids also reacted well, but slow
addition of the boronic acid was required to minimize the
competitive dibenzylidene acetone formation (entry 20).16
It is remarkable that even in low-yielding reactions (15-
18), none of the potentially competing arylated product 2
(entries 6-11). The presence of a phosphine ligand is not
essential to the reaction (entries 9 and 10), yet it was found
to help turnover for boronic acid partners less reactive than
simple phenyl. It is proposed that the bidentate phosphine
ligand creates a reserVoir of inactive rhodium complex in
solution. Thus, in view of the widespread use of BINAP
ligands, it was kept as a constant parameter. As optimized
1
7
2
conditions, [Rh(CO) acac] was chosen as a stable precatalyst
was observed.
To date, attempts to render this reaction enantioselective
with a 10:1 mixture of toluene and water as solvent mixture.
The most informative results from a scope study are
summarized in Table 2.
1
8
did not lead to satisfactory results. The rate of the
phosphine-free catalyst is apparently much faster than that
3
1
of a ligand-bound complex. P NMR studies showed that
phosphine ligands are displaced by CO under the reported
1
9
conditions. Ongoing mechanistic investigations are aimed
at addressing this issue and extending the reaction to other
Table 2. Scope of the Acyl Rhodium(I)-Catalyzed Ring
Openinga
2
0
systems.
In summary, we reported the early results of a catalytic
desymmetrization of strained alkenes via a formal allylic
substitution reaction with acyl anion nucleophiles. The
catalytic generation of acyl anion equivalents under very
simple and mild conditions obviates the typical use of high
pressures of CO and high reaction temperatures. The reaction
allowed the rapid synthesis of trans-1,2-hydrazinoacyl cy-
clopentenes 3, which are not easily accessible stereoselec-
tively by other means. The densely functionalized products
obtained should prove to be of great value as building blocks
in organic synthesis.
b
entry
1
R
product
yield (%)
1
2
3
1a
1b
1b
1c
1d
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
Ph
Ph
Ph
Ph
Ph
3a
3b
3b
3c
3d
4
5
6
7
8
92
91
94
e
c
4
5
93
93
96
84
91
84
94
91
88
83
83
83
77
57
38
39
e
Acknowledgment. We gratefully acknowledge NSERC
(Canada), Merck-Frosst, and the University of Toronto for
financial support, as well as Solvias AG for gifts of rhodium
catalysts. F.M. thanks the Ontario government for a post-
graduate scholarship (OGS). F.C.W. thanks Prof. C. Schneider
6
7
8
9
4-MeO-C6H4-
3-MeO-C6H4-
2-Me-4-MeO-C6H3-
2-Me-C6H4-
3-Me-C6H4-
4-Me-C6H4-
2-naphthyl
3-Me3Si-C6H4-
3-vinyl-C6H4-
4-Cl-C6H4-
4-F-C6H4-
4-CF3-C6H4-
4-Ac-C6H4-
3-thiophenyl-
1,2-(E)-styryl
10
11
12
13
14
15
16
17
18
19
20
9
(Universit a¨ t Leipzig) and the DAAD (Germany).
10
11
12
13
14
15
16
17
18
Supporting Information Available: Experimental pro-
cedures and characterization data for new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL7022054
d
63
(16) Such a synthesis of symmetrical ketones was reported with
organomercurials and rhodium under a CO atmosphere: Larock, R. C.;
Hershberger, S. S. J. Org. Chem. 1980, 45, 3840.
a
Unless otherwise noted, all reactions were performed using 1 (0.135
mmol) with Rh catalyst (10 mol %), (R)-, or rac-BINAP (12 mol %) in a
0:1 toluene/H2O biphasic solvent mixture (0.07 M), under a CO gas
atmosphere (balloon) for 20 h. Isolated yield. Reaction on 1 mmol scale.
Portion-wise addition of boronic acid, CsF was added (1.2 equiv).
(
17) Even after heating, the mass balance consisted mainly of unreacted
starting material.
18) Though the arylation product 2 is formed with significant enantio-
meric enrichment under the same conditions (89:11 er), the acylated product
was nearly racemic (55:45 er).
1
b
c
(
d
e
Reaction time was 24 h.
3
(
(
19) This phenomenon was also observed by others (see ref 3f).
20) In preliminary experiments, oxabicycle 19 reacted, but only the
aromatized ketone 20 was isolated:
The nature of the hydrazine protecting groups was found
to be insignificant on the reaction outcome (entries 1-5).
The reaction worked best with electron-rich and electroneu-
tral arylboronic acids (83-96%, entries 1-14). The yield
Org. Lett., Vol. 9, No. 26, 2007
5367