Amide-directed alkenylation of sp2 C-H bonds catalyzed by a cationic Rh(I)/BIPHEP complex under mild conditions: Dramatic rate acceleration by a 1-pyrrolidinecarbonyl group

Article abstract of DOI:10.1021/ol802767s

(Chemical Equation Presented) A cationic rhodium(I)/BIPHEP complex catalyzes amide-directed regioselectlve alkenylatlons of olefinic or aromatic sp² C-H bonds in good yields under mild reaction conditions. The use of a 1-pyrrolidinecarbonyl gro

Full text of DOI:10.1021/ol802767s

ORGANIC
LETTERS
Amide-Directed Alkenylation of sp2 C-H
Bonds Catalyzed by a Cationic Rh(I)/
BIPHEP Complex Under Mild
2009
Vol. 11, No. 3
689-692
Conditions: Dramatic Rate Acceleration
by a 1-Pyrrolidinecarbonyl Group
Yu Shibata, Yousuke Otake, Masao Hirano, and Ken Tanaka*
Department of Applied Chemistry, Graduate School of Engineering, Tokyo UniVersity
of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received December 1, 2008
ABSTRACT
A cationic rhodium(I)/BIPHEP complex catalyzes amide-directed regioselective alkenylations of olefinic or aromatic sp2 C-H bonds in good
yields under mild reaction conditions. The use of a 1-pyrrolidinecarbonyl group as a directing group dramatically accelerates the reaction.
The chelation-assisted alkenylation of olefinic or aromatic
sp2 C-H bonds with alkynes catalyzed by transition-metal
complexes is a useful transformation in organic synthesis.1
Murai and co-workers reported the first carbonyl-directed
ortho-alkenylation of aryl ketones with alkynes by using a
ruthenium catalyst.2 After this pioneering work, a number
of chelation-assisted alkenylations of sp2 C-H bonds with
alkynes have been reported by using various chelation groups
and transition-metal catalysts.3-5 However, carbonyl-directed
alkenylations of sp2 C-H bonds with alkynes have been
reported in a limited number.2a,3,4,6-9 In particular, the use
of amide carbonyl groups as a chelation group is scarce.6-9
In this paper, we describe cationic rhodium(I)/BIPHEP
complex-catalyzed regioselective alkenylations of olefinic or
aromatic sp2 C-H bonds under mild reaction conditions by
a 1-pyrrolidinecarbonyl group as a directing group.
Recently, we have reported that a cationic rhodium(I)/H8-
BINAP complex catalyzes a codimerization of acrylate 1a and
diphenylacetylene (2a) leading to 1,3-diene 3aa at 80 °C
presumably through the formation of a rhodacyclopentene
intermediate followed by ꢀ-hydride elimination (eq 1).10
However, no conversion was observed in the reaction between
crotonate 1b and 2a under the same reaction conditions (eq 2).
(1) For recent reviews, see: (a) Kakiuchi, F.; Kochi, T. Synthesis 2008,
3013. (b) Davies, H. M. L.; Manning, J. R. Nature 2008, 451, 417. (c)
Campos, K. R. Chem. Soc. ReV. 2007, 36, 1069. (d) Alberico, D.; Scott,
M. E.; Lautens, M. Chem. ReV. 2007, 107, 174. (e) Godula, K.; Sames, D.
Science 2006, 312, 67. (f) Dyker, G., Ed. Handbook of C-H Transforma-
tions; Wiley-VCH: Weinheim, Germany, 2005. (g) Kakiuchi, F.; Chatani,
N. AdV. Synth. Catal. 2003, 345, 1077. (h) Miura, M.; Nomura, M. Top.
Curr. Chem. 2002, 219, 211. (i) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem.
ReV. 2002, 102, 1731. (j) Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698.
(2) (a) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai, S. Chem. Lett.
1995, 681. For the pioneering work on carbonyl-directed alkylations of aryl
ketones with alkenes by using a Ru catalyst, see: (b) Murai, S.; Kakiuchi,
F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature
1993, 366, 529.
(3) For ketone carbonyl-directed alkenylations of sp2 C-H bonds with
alkynes, see: (a) Kakiuchi, F.; Uetsuhara, T.; Tanaka, Y.; Chatani, N.;
Murai, S. J. Mol. Catal. A: Chem. 2002, 511, 182. (b) Harris, P. W. R.;
Rickard, C. E. F.; Woodgate, P. D. J. Organomet. Chem. 1999, 589, 168.
(c) Kakiuchi, F.; Sato, T.; Tsujimoto, T.; Yamauchi, M.; Chatani, N.; Murai,
S. Chem. Lett. 1998, 27, 1053. (d) Londergan, T. M.; You, Y.; Thompson,
M. E.; Weber, W. P. Macromolecules 1998, 31, 2784.
(4) For ester carbonyl-directed alkenylations of sp2 C-H bonds with
alkynes, see: Trost, B. M.; Imi, K.; Davies, I. W. J. Am. Chem. Soc. 1995,
117, 5371.
10.1021/ol802767s CCC: $40.75
Published on Web 01/08/2009
2009 American Chemical Society

Interestingly, the reaction between crotonamide 1c and 2a
proceeded in quantitative yield, although a mixture of stereoi-
somers A, B, and C shown in Table 1 was generated (eq 3).
Table 1. Screening of Reaction Conditions for Rh-Catalyzed
Alkenylation of Alkenylamide 1c with Monoyne 2aa
To improve the stereoselectivity, the reaction of 1c and
2a was examined at ambient temperature as shown in Table
1. After screening of various diphosphine ligands (entries
1-8), we were pleased to find that the use of BIPHEP
furnished the desired diene 3ca in moderate yield (entry 4).
As the reaction proceeds at ambient temperature and isomer
A was obtained as a predominant stereoisomer, the reaction
may proceed through an amide carbonyl-directed C-H bond
activation pathway. The yields of 3ca are highly dependent
on dihedral angles of biaryldiphosphine ligands [dihedral
angle: H8-BINAP (entry 1) > BINAP (entry 2) > Segphos
(entry 3) > BIPHEP (entry 4),11 yield of 3ca: entry 1 <
entry 2 < entry 3 < entry 4]. The electronic nature of the
substituents on the phosphorus was also examined, which
revealed that the use of electron-rich Cy-BIPHEP completely
a [Rh(cod)2]BF4/ligand (0.0075 or 0.015 mmol), 1c (0.150 mmol), 2a
(0.165mmol),andCH2Cl2(1.5mL)wereused.b NMRyield.c [Rh(cod)2]BF4/ligand
(0.025 mmol), 1c (0.500 mmol), 2a (0.550 mmol), and CH2Cl2 (1.0 mL)
were used.
(5) For chelation-assisted alkenylations of sp2 C-H bonds with alkynes,
see: (a) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2008, 47, 4019. (b) Cheng, K.; Yao, B.; Zhao, J.; Zhang, Y. Org. Lett.
2008, 10, 5309. (c) Yotphan, S.; Bergman, R. G.; Ellman, J. A. J. Am.
Chem. Soc. 2008, 130, 2452. (d) Colby, D. A.; Bergman, R. G.; Ellman,
J. A. J. Am. Chem. Soc. 2008, 130, 3645. (e) Ueura, K.; Satoh, T.; Miura,
M. Org. Lett. 2007, 9, 1407. (f) Ueura, K.; Satoh, T.; Miura, M. J. Org.
Chem. 2007, 72, 5362. (g) Kuninobu, K.; Tokunaga, Y.; Kawata, A.; Takai,
K. J. Am. Chem. Soc. 2006, 128, 202. (h) Nakao, Y.; Kanyiva, K. S.; Oda,
S.; Hiyama, T. J. Am. Chem. Soc. 2006, 128, 8146. (i) Kuninobu, K.; Kawata,
A.; Takai, K. J. Am. Chem. Soc. 2005, 127, 13498. (j) Lim, S.-G.; Lee,
J. H.; Moon, C. W.; Hong, J. B.; Jun, C.-H. Org. Lett. 2003, 5, 2759. (k)
Lim, Y.-G.; Lee, K.-H.; Koo, B. T.; Kang, J.-B. Tetrahedron Lett. 2001,
42, 7609. (l) Satoh, T.; Nishinaka, Y.; Miura, M.; Nomura, M. Chem. Lett.
1999, 615. (m) Du¨rr, U.; Kisch, H. Synlett 1997, 1335. (n) Halbritter, G.;
Knoch, F.; Wolski, A.; Kisch, H. Angew. Chem., Int. Ed. Engl. 1994, 331603.
(6) Ru-catalyzed codimerizations of N,N-dimethylacrylamide and alkynes
at 80 °C were reported, and a mechanism, the formation of a ruthenacyclo-
pentene intermediate followed by ꢀ-hydride elimination, is proposed; see:
Mitsudo,T.;Zhang,S.-W.;Nagao,M.;Watanabe,Y.Chem.Commun.1991,598.
(7) Ru-catalyzed intramolecular alkenylations of crotonates and cro-
tonamide derivatives with alkynes at 110 °C were reported, although the
mechanism is not clear; see: Mori, M.; Kozawa, Y.; Nishida, M.; Kanamaru,
M.; Onozuka, K.; Takimoto, M. Org. Lett. 2000, 2, 3245.
shut down the reaction (entry 5). Prolonged reaction time
and high concentration improved the yield of 3ca to 94%
and lowered the catalyst loading to 5 mol% (entry 11).
Not only BIPHEP as a ligand but also a 1-pyrrolidinecarbonyl
group as a directing group are essential for this transformation.
Dimethylcarbamoyl (1d) and 1-piperidinecarbonyl (1e) groups
significantly decreased the reaction rate, and ester (1b) and
ketone (1f) carbonyl groups completely shut down the reaction
(Scheme 1). This observation may correlated with electron
densities of carbonyl oxygens (electron density: 1-pyrrolidinyl
Scheme 1
(8) Pd-catalyzed codimerizations of acrylate and acrylamide derivatives
with internal aryl alkynes at 100 °C were reported, and a mechanism, the
formation of a Pd hydride species followed by hydropalladation with the
alkyne, is proposed; see: Lindhardt, A. T.; Mantel, M. L. H.; Skrydstrup,
T. Angew. Chem., Int. Ed. 2008, 47, 2668.
(9) Ru-catalyzed co-oligomerizations of N-vinylamides with alkenes or
alkynes at 160-170 °C were reported, and a mechanism, the formation of
a Ru hydride species by activation of sp2 C-H bonds in alkenes or a ligand,
is proposed; see: Tsujita, H.; Ura, Y.; Matsuki, S.; Wada, K.; Mitsudo, T.;
Kondo, T. Angew. Chem., Int. Ed. 2007, 46, 5160.
690
Org. Lett., Vol. 11, No. 3, 2009

Table 2. Cationic Rhodium(I)/BIPHEP Complex-Catalyzed
Alkenylation of Alkenylamides 1 with Monoynes 2a
Table 3. Cationic Rhodium(I)/BIPHEP Complex-Catalyzed
Alkenylation of Benzamides 5 with Monoynes 2a
6/% yieldb
(E/Z)
7/
entry
5 (R1)
2 (R2, R3)
2a (Ph, Ph)
% yieldb
3/%
4/%
entry 1 (R1, R2)
1c 1c (Me, H)
2 (R3, R4)
2a (Ph, Ph)
yieldb (A/B/C) yieldb
1
2
3
5a (H)
5e (CF3)
78 (>99:1)
79 (>99:1)
93 (>99:1)
92 (>99:1)
76 (>99:1)f
60 (>99:1)f
81 (>99:1)
2a (Ph, Ph)
88 (89:8:3)
64 (>98:<1:<1)d
0 (-)
2c 1g (n-Pr, H) 2a (Ph, Ph)
5f (OMe) 2a (Ph, Ph)
5f (OMe) 2a (Ph, Ph)
5f (OMe) 2a (Ph, Ph)
5f (OMe) 2a (Ph, Ph)
5f (OMe) 2b [Ph, (CH2)3Me]
4c
5d
6e
7
3
4
5
6
7
8
9
1h (H, Me)
1i (H, H)
1j [-(CH2)4-] 2a (Ph, Ph)
1c (Me, H)
1c (Me, H)
1c (Me, H)
1c (Me, H)
2a (Ph, Ph)
2a (Ph, Ph)
0 (-)
80 (>99:<1:-)
0
<2
<2
0
2b [Ph, (CH2)3Me] 74 (>98:<1:<1) <5
2c [Ph, (CH2)3OTs] 80 (>98:<1:<1) <5
2d [Ph, (CH2)3Br] 73 (>98:<1:<1) <5
2e [Me, (CH2)4Me] 75 (>98:<1:<1)e 10e
8
9
10
11
5f (OMe) 2c [Ph, (CH2)3OTs] 40 (>99:1)f
5f (OMe) 2d [Ph, (CH2)3Br]
5f (OMe) 2e [Me, (CH2)4Me]
45 (>99:1)f
36 (87:13)f
5f (OMe) 2f (n-PrCt C, n-Pr) 20 (>99:1)f
0
10 1c (Me, H)
2f (n-PrCt C, n-Pr) 35 (>98:<1:<1)d
0
a [Rh(cod)2]BF4/BIPHEP (0.050 mmol, 10 mol %), 5 (0.500 mmol), 2
(0.550 mmol), and (CH2Cl)2 (1.0 mL) were used. b Isolated yield. c Catalyst:
5 mol %. d Catalyst: 2 mol %. e At 25 °C. f Conversion of 5f: 76% (entry
5), 60% (entry 6), 50% (entry 8), 46% (entry 9), 37% (entry 10), 32%
(entry 11).
a [Rh(cod)2]BF4/BIPHEP (0.050 mmol, 10 mol %), 1 (0.500 mmol), 2
(0.550 mmol), and CH2Cl2 (entries 1-5) or (CH2Cl)2 (entries 6-10) (1.0
mL) were used. b Isolated yield. c Catalyst: 5 mol %. d Conversion of 1g:
71% (entry 2). Conversion of 1c: 38% (entry 10). e Isolated as a mixture of
3ce and 4ce.
> NMe2 > 1-piperidinyl . OMe or Et,12 yield of 3: 1-pyrro-
lidinyl > NMe2 > 1-piperidinyl . OMe or Et).
carbonyl-directed C-H bond activation pathway, the reaction
between benzamide 5a and monoyne 2a should proceed in
the presence of the same rhodium catalyst. Indeed, the desired
alkenylation proceeded at ambient temperature, and the
1-pyrrolidinecarbonyl group is again the best directing group
(Scheme 2).15,16
The scope of both alkenylamides 1 and monoynes 2 was
examined as shown in Table 2. Not only crotonamide (1c,
entry 1) but also 2-hexenylamide (1g, entry 2) and cyclic
alkenylamide (1j, entry 5) could participate in this reaction.13
However, methacrylamide 1h and acrylamide 1i could not
participate in this reaction (entries 3 and 4). With respect to
monoynes, the reactions of phenyl, alkyl, and functionalized
alkyl substituted unsymmetrical monoynes 2b-e with 1c
proceeded in good yields with high regioselectivity (entries
6-9). The reaction of 1c with 1,3-diyne 2f proceeded with
complete regioselectivity although it was sluggish (entry
10).14 Importantly, the present alkenylation is highly ste-
reoselective and isomer A was obtained as a predominant
isomer.
Scheme 2
If the present rhodium-catalyzed alkenylations of olefinic
sp2 C-H bonds with alkynes proceed through an amide
At elevated temperature, the reaction of 5a and 2a was
accelerated to give the desired alkenylation product 6aa in
(10) Shibata, Y.; Hirano, M.; Tanaka, K. Org. Lett. 2008, 10, 2829.
(11) Shimizu, H.; Nagasaki, I.; Saito, T. Tetrahedron 2005, 61, 5405.
(12) Kanner, C. B.; Pandit, U. K. Tetrahedron 1982, 38, 3597.
(13) The reaction of phenyl-substituted alkenylamide 1k with 2a
proceeded at 80 °C in quantitative yield, while the stereochemistry of the
product 3ka has not been determined.
(15) During preparation of this manuscript, ketone carbonyl-directed
alkenylations and alkylations of aryl ketones with diphenylacetylene, styrene,
and norbornene catalyzed by cationic Ir(I)/biaryldiphosphine complexes were
reported; see: (a) Tsuchikama, K.; Kasagawa, M.; Hashimoto, Y-k.; Endo,
K.; Shibata, T. J. Organomet. Chem. 2008, 693, 3939. Amide carbonyl-
directed asymmetric alkylations of a NH2-benzamide with norbornene
catalyzed by a Ir(I)/bisphosphine/Cp complex were reported; see: (b)
Aufdenbatten, R.; Diezi, S.; Togni, A. Monatsh. Chem. 2000, 131, 1345
.
(16) The corresponding Ir(I) complexes showed significantly low
(14) Ru-catalyzed Alder ene reactions of di- and triynes were reported;
see: Cho, E. J.; Lee, D. J. Am. Chem. Soc. 2007, 129, 6692.
catalytic activities in the present 1-pyrrolidinecarbonyl-directed sp2 C-H
bond alkenylations.
Org. Lett., Vol. 11, No. 3, 2009
691

diynes.18,19 However, slow addition of 1,6-diynes and/or a
large excess of aryl ketones were necessary to obtain high
product yields. Pleasingly, the use of benzamide 5a is also
effective in the dienylation with 1,6-diyne 9 to give the
desired dienylation product 10 in high yield without employ-
ing slow addition of 9 and using excess 5a (eq 5).20
Scheme 3
improved yield (Table 3, entry 1). The scope of both
benzamides 5 and monoynes 2 was then examined as shown
in Table 3. The use of electron-deficient 4-trifluoromethyl-
substituted benzamide 5e did not affect the product yield
(entry 2), but that of electron-rich 4-methoxy-substituted
benzamide 5f improved the product yield (entry 3) and
allowed the reaction to be conducted at lower catalyst
loadings (5 mol %, entry 4; 2 mol %, entry 5) or ambient
temperature (25 °C, entry 6). Like the alkenylations of
alkenylamide 1c with unsymmetrical monoynes 2b-f, those
of benzamide 5f with 2b-f proceeded with high regio- and
stereoselectivity (entries 7-11), although the reactions with
2c-f were sluggish (entries 8-11).
A possible mechanism for the alkenylation of benzamide
5 with monoyne 2 is shown in Scheme 3. Benzamide 5 reacts
with rhodium to give rhodium hydride D through 1-pyrro-
lidinecarbonyl-directed C-H bond activation. Insertion of
monoyne 2 followed by reductive elimination of rhodium
furnishes alkenylation product 6. Importantly, double alk-
enylation products 8 were not generated in the all of entries
shown in Table 3. The steric repulsion between the amide
group and the alkenyl group may deter the formation of
plausible intermediate E leading to 8.
In conclusion, we have demonstrated that a cationic
rhodium(I)/BIPHEP complex catalyzes 1-pyrrolidinecarbo-
nyl-directed regioselective alkenylations of olefinic or aro-
matic sp2 C-H bonds in good yields under mild reaction
conditions. Future studies will focus on further catalyst
tuning, expanding the scope, and elucidation of the precise
reaction mechanism.
Acknowledgment. This work was supported in part by a
Grant-in-Aid for Scientific Research (Nos. 20675002 and
19028015) from JSPS, Japan. We thank Takasago Int. Co.
for the gift of H8-BINAP and Segphos.
Supporting Information Available: Experimental pro-
cedures and compound characterization data (PDF). This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL802767S
(18) (a) Tanaka, K.; Otake, Y.; Wada, A.; Hirano, M. Org. Lett. 2007,
9, 2203. After our publication, the same reaction was independently reported
by another research group, see: (b) Tsuchikama, K.; Kuwata, Y.; Tahara,
To access the electronic effect on the present alkenylation,
a competition experiment was conducted between benza-
mides 5e and 5f at ambient temperature, which revealed that
electron-rich amide 5f preferentially reacted with 2a (eq 4).
According to this observation and a lack of the catalytic
activity of electron-rich Cy-BIPHEP as a ligand (Table 1,
entry 5), the electrophilic metalation of sp2 C-H bonds by
cationic rhodium(I) species may be involved in the catalytic
cycle.17
Y.; Yoshinami, Y.; Shibata, T. Org. Lett. 2007, 9, 3097
.
(19) Dienylations of sp2 C-H bonds with alkynes have been developed
by using various transition-metal complexes; see: (a) Aubert, C.; Betschmann,
P.; Eichberg, M. J.; Gandon, V.; Heckrodt, T. J.; Lehmann, J.; Malacria,
M.; Masjost, B.; Paredes, E.; Vollhardt, K. P. C.; Whitener, G. D.
Chem.sEur. J. 2007, 13, 7443. (b) Aubert, C.; Gandon, V.; Geny, A.;
Heckrodt, T. J.; Malacria, M.; Paredes, E.; Vollhardt, K. P. C. Chem.sEur.
J. 2007, 13, 7466, and references cited therein.
(20) The reaction of alkenylamide 1c with 1,6-diyne 9 also proceeded
in high yield, while the stereochemistry of the product 11 has not been
determined.
We have recently reported the cationic rhodium(I)/Segphos
complex-catalyzed ortho-dienylation of aryl ketones with 1,6-
(17) Electron-deficient cationic Rh(I) complexes efficiently catalyze
arylation reactions of sp2 C-H bonds; see: (a) Yanagisawa, S.; Sudo, T.;
Noyori, R.; Itami, K. J. Am. Chem. Soc. 2006, 128, 11748. (b) Nambo, M.;
Noyori, R.; Itami, K. J. Am. Chem. Soc. 2007, 129, 8080.
692
Org. Lett., Vol. 11, No. 3, 2009