Insertion of an Alkene into an ester: Intramolecular oxyacylation reaction of alkenes through acyl C-O bond activation

Article abstract of DOI:10.1002/anie.201005767

Atom economy and esters: compatible now! The first catalytic insertion of a C-C bond into an acyl C-O bond was achieved using rhodium catalysts (see scheme). The products are β-alkoxy ketones with a fully substituted carbon center. Quinoline chelating groups were employed to stabilize the Rh-alkoxide intermediate.

Full text of DOI:10.1002/anie.201005767

Communications
DOI: 10.1002/anie.201005767
À
C O Activation
Insertion of an Alkene into an Ester: Intramolecular Oxyacylation
À
Reaction of Alkenes through Acyl C O Bond Activation**
Giang T. Hoang, Venkata Jaganmohan Reddy, Huy H. K. Nguyen, and Christopher J. Douglas*
b-Alkoxyketones are common intermediates in organic syn-
thesis. An unusual approach to this class of compounds could
=
be the insertion of a C C bond into an ester, a potentially
atom economical process (Scheme 1). This alkene “oxyacy-
Scheme 1. Alkene oxyacylation.
À
Scheme 2. Processes involving acyl C O activation.
lation” could be an alternative to the aldol reaction.[1] Atom
economy and ester manipulation, however, are rarely com-
patible: esters usually fragment after reactions with nucleo-
philes, or decarbonylate when activated with transition
À
approach was akin to stoichiometric acyl C O bond activa-
tion strategies[6–8] in which metal chelating groups were
metals.[2] In the rare cases when the acyl C O bond is
used.[6] We employed quinoline as a chelating group based
À
[9]
À
activated and decarbonylation is suppressed, the acyl metal
alkoxide complexes can undergo additional transforma-
tions,[3,4] but only with the expulsion of an alcohol
(Scheme 2a)[3b–f] or ketone (Scheme 2b).[3a] We are aware of
on our previous successes in acyl C C bond activation. We
designed an intramolecular reaction to avoid problems with
regioselectivity and to increase local concentrations of alkene.
Activation of 1a to I, followed by migratory insertion and
reductive elimination would provide 2a, containing a cyclic
ether with a ketone in a 1,3-relationship and a new fully
substituted carbon center.
À
one example where acyl C O activation provided products
containing the original atoms: Oheꢀs recent Pd-catalyzed
À
nitrile insertion into an acyl C O bond, followed by
rearrangement (Scheme 2c).[4] The challenge of productive
Here, we report the first example of alkene insertion into
À
À
acyl C O bond activation is accentuated by the frequent
the acyl C O bond of an ester. Beginning with 1a, we
reports of the reverse reaction: when acyl metal alkoxides are
accessed by other means, they readily undergo reductive
elimination to form esters.[5]
screened Rh complexes containing various counterions (Cl,
BF4, OTf), with [Rh(cod)2]OTf (cod = cyclooctadiene) pro-
viding encouraging results (Table 1, entries 1–3). A by-
product observed in our initial study was the phenol 3a,
resulting from a formal hydrolysis of 1a, though attempts to
rigorously exclude water did not decrease the formation of
3a. Switching to 1,2-dicholorethane as solvent, [Rh(cod)2]BF4
showed good conversion, but gave a 1:1 mixture of 2a:3a
(Table 1, entries 4, 5). The addition of bidentate phosphine
ligands, particularly dppp, was effective at maintaining high
conversion. Using the [Rh(cod)2BF4]/dppp catalyst system at
higher temperature suppressed the formation of 3a (Table 1,
entries 8–11).
We postulated that a chelating group would prevent
decarbonylation by stabilizing the acyl metal complex, I. Our
[*] G. T. Hoang, V. J. Reddy, H. H. K. Nguyen,[+] Prof. C. J. Douglas
Department of Chemistry, University of Minnesota
Twin Cities, 207 Pleasant St. SE, Minneapolis, MN 55455 (USA)
Fax: (+1)612-626-7541
E-mail: cdouglas@umn.edu
[+] UMN Undergraduate Research, 2009–2010.
[**] We acknowledge the donors of the ACS Petroleum Research Fund
for partial support (47565-G1). We thank UMN (start-up funds),
Prof. Gunda Georg for discussions, and Rosalind Douglas for
assistance with this manuscript.
Using the conditions from Table 1, entry 11, we examined
the scope of oxyacylation (Table 2). Both electron-donating
and electron-withdrawing substituents on the aromatic linker
gave products 2b–g in good yields (Table 2, entries 1–6),
although longer reaction times were required for electron-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201005767.
1882
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 1882 –1884

Table 1: Optimization of reaction conditions.[a]
Table 2: Reaction scope.[a]
Entry
Substrate
Product
Yield
[%][b]
1[c]
79
Entry Catalyst
L
Solvent
T [oC] Yield of
2a (3a)
1
2
3
4
5
6
7
8
[Rh(PPh3)3Cl]
–
–
–
–
–
PhMe
PhMe
PhMe
DCE
130
130
130
110
110
130
130
90
–
–
[{Rh(C2H4)2Cl}2]
[Rh(cod)2]OTf
[Rh(cod)2]OTf
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
[Rh(cod)2]BF4
2[c]
60[d]
20% (37%)[b]
complex mixture
40% (40%)[b]
–
DCE
dppe DCE
dppb DCE
dppp DCE
dppp DCE
dppp DCE
40%[b]
25% (25%)[b]
65% (32%)[b]
82%[c]
3
65
9
110
130
10
11[d]
dppp DCE/PhMe 150
85%[c]
[a] Entries 1–5: Rh catalyst 20 mol%, 0.1m 1a, 24 h, entries 6–11:
[Rh(cod)2]BF4 (10 mol%), ligand (12 mol%), 0.05m 1a, 24 h. [b] Deter-
mined by 1H NMR spectroscopy. [c] Yield after chromatography. [d] Con-
ditions used for further substrate evaluation. Legend: dppe=1,2-
bis(diphenylphosphino)ethane, dppp=1,3-bis(diphenylphosphino)pro-
pane, dppb=1,4-bis(diphenylphosphino)butane, DCE=1,2-dichloro-
ethane.
4
78
5
90
donating groups (entries 1, 2). In the presence of another
À
ester group, acyl C O bond activation occurred exclusively
6
7
8
81
–
for the 8-quinoline carboxylate ester, leaving the other ester
untouched (Table 2, entry 4). Substitution at the 6-position of
the aromatic linker accelerated the reaction, presumably due
to the restricted rotation of the acyl group (Table 2, entries 5,
6). Replacing alkene substituents with Et and CH2OBn
provided products 2i and 2j in good yield (Table 2, entries 8,
9). An alkene substituent is required for oxyacylation to
occur; for R = H (1h), oxyacylation product 2h was not
observed, possibly due to facile b-hydride elimination
(Table 2, entry 7).
78
Chromans could also be formed (Table 2, entry 10). For
allylic ether 1l, we observed oxyacylation at 1308C, but at
higher temperatures (1508C) the product from Claisen
rearrangement was formed predominantly (Table 2,
entry 11).
9
51
85
Based on the above results, we propose the following
reaction mechanism (Scheme 3). Coordination to the quino-
À
line nitrogen directs rhodium to insert into the acyl C O
bond, forming intermediate I. Migratory insertion of the
alkene into the metal–oxygen bond,[10] followed by reductive
elimination provides 2a. A by-product observed in this
reaction was phenol 3a, which we presume is a decomposition
product from intermediate I. Hartwig et al. reported similar
decomposition of related rhodium alkoxide complexes.[11]
When the reaction temperature was increased, oxyacylation
product 2a was favored and the formation of 3a was
minimized (Table 1, entires 8–11), suggesting that migratory
insertion to form II is turnover-limiting.
10
11
25[e]
[a] Conditions: [Rh(cod)2]BF4 (10 mol%), dppp (12 mol%), PhMe/
DCE=8:2, 1508C, 24 h. [b] Yield after chromatography. [c] 36 h.
[d] 14% recovered 1c, 70% 2c based on recovered starting material
(brsm). [e] 1308C, 50% recovered 1l, 50% 2l brsm.
In conclusion, we have reported the first direct insertion
À
of an alkene into an acyl C O bond to provide b-alkoxy
ketones bearing a fully substituted carbon center. Decarbon-
Angew. Chem. Int. Ed. 2011, 50, 1882 –1884
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
1883

Communications
À
Keywords: acylation · aldol reaction · C O activation ·
homogeneous catalysis · rhodium
.
[1] a) B. M. Trost, C. S. Brindle, Chem. Soc. Rev. 2010, 39, 1600;
b) B. Schetter, R. Mahrwald, Angew. Chem. 2006, 118, 7668;
Angew. Chem. Int. Ed. 2006, 45, 7506.
[2] a) Y.-S. Lin, A. Yamamoto in Activation of Unreactive Bonds
and Organic Synthesis (Ed.: S. Murai), Springer, Berlin, 1999,
pp. 161 – 192; b) A. Yamamoto, Adv. Organomet. Chem. 1992,
34, 111.
À
[3] Catalysis using acyl C O activation: a) A. Ooguri, K. Nakai, T.
Kurahashi, S. Matsubara, J. Am. Chem. Soc. 2009, 131, 13194;
b) H. Tatamidani, K. Yokota, F. Kakiuchi, N. Chatani, J. Org.
Chem. 2004, 69, 5615; c) H. Tatamidani, F. Kakiuchi, N. Chatani,
Org. Lett. 2004, 6, 3597; d) L. Gooßen, J. Paetzold, Angew.
Chem. 2002, 114, 1285; Angew. Chem. Int. Ed. 2002, 41, 1237;
e) R. Kakino, I. Shimizu, A. Yamamoto, Bull. Chem. Soc. Jpn.
2001, 74, 371; f) N. Chantani, H. Tatamidani, Y. Ie, F. Kakiuchi, S.
Murai, J. Am. Chem. Soc. 2001, 123, 4849.
Scheme 3. Mechanistic hypothesis for oxyacylation.
[4] M. Murai, K. Miki, K. Ohe, Chem. Commun. 2009, 3466.
[5] E.-I. Negishi, C. Coperet, S. Ma, T. Mita, T. Sugihara, J. M. Tour,
J. Am. Chem. Soc. 1996, 118, 5904, and references therein.
[6] a) D. B. Grotjahn, C. Joubran, Inorg. Chim. Acta 2004, 357, 3047;
b) D. B. Grotjahn, C. Joubran, Organometallics 1995, 14, 5171.
[7] K. Nagayama, I. Shimizu, A. Yamamoto, Bull. Chem. Soc. Jpn.
1999, 72, 799.
[8] a) Y. Yamamoto, X.-H. Han, Angew. Chem. 2000, 112, 2041;
Angew. Chem. Int. Ed. 2000, 39, 1965; b) T. Yamamoto, S.
Miyashita, Y. Natto, S. Komiya, T. Ito, A. Yamamoto, Organo-
metallics 1982, 1, 808.
[9] a) M. T. Wentzel, V. J. Reddy, T. K. Hyster, C. J. Douglas,
Angew. Chem. 2009, 121, 6237; Angew. Chem. Int. Ed. 2009,
48, 6121; b) A. M. Dreis, C. J. Douglas, J. Am. Chem. Soc. 2009,
131, 412.
[10] a) R. M. Trend, Y. K. Ramtohul, B. M. Stoltz, J. Am. Chem. Soc.
2005, 127, 17778; b) J. P. Wolfe, M. A. Rossi, J. Am. Chem. Soc.
2004, 126, 1620; c) T. Kondo, F. Tsunawaki, R. Sato, Y. Ura, K.
Wada, T.-A. Mitsudo, Chem. Lett. 2003, 32, 24.
ylation was suppressed by the use of a quinoline chelating
group. Our results demonstrate that ester manipulation can
indeed be atom economical. Current efforts focus on discov-
ering other directing groups to expand the utility of this
methodology.
Experimental Section
Representative procedure: In a nitrogen-filled glove box, a 1 dram
reaction vial (Chemglass, polytetrafluoroethylene-lined cap) was
charged with [Rh(cod)2]BF4 (0.01 mmol, 0.1 equiv), 1,3-bis(diphenyl-
phosphino)propane (0.012 mmol, 0.12 equiv), and DCE (0.4 mL).
The mixture was stirred at room temperature for 1 h and then
transferred to a 1 dram vial containing ester 1a (30.6 mg, 0.1 mmol,
1 equiv) and toluene (1.6 mL). The reaction mixture was maintained
at 1508C for 24 h. The mixture was then removed from the glove box
and concentrated. The crude product was purified by flash column
chromatography (gradient, EtOAc:Hex) to afford the product 2a
(26 mg, 0.085 mmol, 85%).
[11] a) P. Zhao, J. F. Hartwig, Organometallics 2008, 27, 4749; b) P.
Zhao, C. D. Incarvito, J. F. Hartwig, J. Am. Chem. Soc. 2006, 128,
9642.
Received: September 14, 2010
Published online: January 18, 2011
1884
www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 1882 –1884