C O M M U N I C A T I O N S
Table 3. Ni-Catalyzed Allylic Substitution of Alkenesa
mixture through a pad of silica gel and treatment with tetracyanoethylene
(TCNE) cleanly and completely removed the major 1,3-diene byproduct
(E-3a) via [4+2] cycloaddition (giving 12). The desired coupling product
(2a) was not affected by TCNE treatment and was isolated in 81% yield
(1.18 g) in >98% purity.
Scheme 1. Gram-Scale Allylic Substitution Reaction of Ethylene
In summary, we report the first examples of catalytic allylic
substitution of simple alkenes. This method accommodates a wide
range of allylic alcohol derivatives and nonactivated terminal alkenes,
such as ethylene and propylene, affording synthetically valuable 1,4-
dienes. High selectivity for substitution at the 2-position of alpha olefins
is generally observed, favoring 1,4-diene products with a 1,1-disubstituted
alkene. Further investigation of the reaction mechanism and the develop-
ment of a mediator-free (i.e., without Et3SiOTf) process are underway.
a Isolated yield; E/Z selectivity >98:2 in all cases. b Propylene pressure 1
atm (balloon); toluene (0.2 M). c 5 mol % Ni(cod)2, 10 mol % PCy2Ph.
d Yield of free alcohol after treatment with 1 N HCl. e Et3SiOTf added over
4 h. f Yield includes trace amounts of regioisomers (total <8%).
ethylene (Table 2) afforded a mixture of 4a, 5, and 6 in an unselective
manner (52:20:28). The use of PCy2Ph in place of P(o-anisyl)3 dramatically
improved the selectivity for the 1,1-disubstituted product (4a, Table 3,
entry 1, 77% yield, >98% selectivity), but higher boiling (i.e., not a gas at
STP) monosubstituted alkenes (alpha olefins) such as 1-octene gave the
corresponding product in low yield (approx 20%) under the same
conditions. A solution to this problem was ultimately found by changing
three reaction parameters: Increasing the initial substrate concentration,
using a combination of PCy2Ph and P(OPh)3, and mixing 1b with the
nickel complex prior to addition of alkene. Under these conditions, many
alpha olefins gave the coupling products 4 in good yield and with excellent
selectivity, including the more sterically demanding vinylcyclohexane
(Table 3, entries 2-6).11 The opposite regioselectivity was observed in
the case of styrene, with 7 being a sole coupling product (entry 7). It is
worthy of note that, in the case of all aliphatic olefins, C-C bond formation
occurs at the more substituted position of the alkene.
Acknowledgment. Support for this work was provided by the
NIGMS (GM-63755). We are grateful to Dr. Li Li for mass spectrometric
data. R.M. thanks JSPS Postdoctoral Fellowships for Research Abroad
for financial support.
Supporting Information Available: Experimental procedures and data
for all new compounds. This material is available free of charge via the Internet
References
(1) Trost, B. M.; Lee. C. B. In Catalytic Asymmetric Synthesis II; Ojima, I.,
Ed.; Wiley-VCH: New York, 2000; Chapter 8E, pp 593-650.
(2) Trost, B. M. Tetrahedron 1977, 33, 2615.
(3) Braun, M.; Meier, T.; Laicher, F.; Meletis, P.; Fiden, M. AdV. Synth. Catal.
2008, 350, 303.
(4) Zhao, X.; Liu, D.; Xie, F.; Zhang, W. Tetrahedron 2009, 65, 512.
(5) (a) Yasui, H.; Mizutani, K.; Yorimitsu, H.; Oshima, K. Tetrahedron 2006,
62, 1410. (b) Son, S.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 2756. (c)
Porcel, S.; Lo´pez-Carrillo, V.; Garc´ıa-Yebra, C.; Echavarren, A. M. Angew.
Chem., Int. Ed. 2008, 47, 1883. (d) Nishikata, T.; Lipshutz, B. H. J. Am.
Chem. Soc. 2009, 131, 12103.
(6) Oppolzer, W. Angew. Chem., Int. Ed. 1989, 28, 38.
(7) Catalytic intermolecular ASRs of conjugated alkenes leading to 1,4-dienes have
been reported: (a) Tsukada, N.; Sato, T.; Inoue, Y. Chem. Commun. 2001,
237. (b) Tsukada, N.; Sato, T.; Inoue, Y. Chem. Commun. 2003, 2404.
(8) There are far fewer ways to make 1,4-dienes with good regio- and stereocontrol
than there are to make 1,3- and 1,5-dienes: (a) Trost, B. M.; Probst, G. D.; Schoop,
A. J. Am. Chem. Soc. 1998, 120, 9228. (b) Wilson, S. R.; Zucker, P. A. J.
Org. Chem. 1988, 53, 4682. (c) Hilt, G.; du Mesnil, F.-X.; Lu¨ers, S. Angew.
Chem., Int. Ed. 2001, 40, 387. (d) Moreau, B.; Wu, J. Y.; Ritter, T. Org. Lett.
2009, 11, 337. (e) Morten, C. J.; Jamison, T. F. Tetrahedron 2009, 65, 6648.
(9) (a) Ogoshi, S.; Oka, M.-a.; Kurosawa, H. J. Am. Chem. Soc. 2004, 126, 11802.
(b) Ogoshi, S.; Haba, T.; Ohashi, M. J. Am. Chem. Soc. 2009, 131, 10350.
(10) (a) Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2005, 127, 14194. (b) Ho,
C.-Y.; Ng, S.-S.; Jamison, T. F. J. Am. Chem. Soc. 2006, 128, 5362. (c)
Schleicher, K. D.; Jamison, T. F. Org. Lett. 2007, 9, 875. (d) Ho, C.-Y.; Jamison,
T. F. Angew. Chem., Int. Ed. 2007, 46, 782. (e) Ho, C.-Y.; Ohmiya, H.;
Jamison, T. F. Angew. Chem., Int. Ed. 2008, 47, 1893Reviews: (f) Ng, S.-S.;
Ho, C.-Y.; Schleicher, K. D.; Jamison, T. F. Pure Appl. Chem. 2008, 80, 929.
(g) Ho, C.-Y.; Schleicher, K. D.; Chan, C.-W.; Jamison, T. F. Synlett 2009, 2565.
(11) Methyl acrylate did not undergo allylation with 1b.
(12) The mechanism of intramolecular ASR of olefins has been thoroughly
investigated. (a) Go´mez-Bengoa, E.; Cuerva, J. M.; Echavarren, A. M.;
Martorell, G. Angew. Chem., Int. Ed. Engl. 1997, 36, 767. (b) Ca´rdienas,
D. J.; Alcam´ı, M.; Coss´ıo, F.; Me´ndez, M.; Echavarren, A. M. Chem.sEur.
J. 2003, 9, 96. A similar olefin insertion step has also been studied in
reactions involving cationic metal hydrides. (c) Mecking, S.; Keim, W.
Organometallics 1996, 15, 2650. (d) DiRenzo, G. M.; White, P. S.;
Brookhart, M. J. Am. Chem. Soc. 1996, 118, 6225. (e) Joseph, J.;
RajanBabu, T. V.; Jemmis, E. D. Organometallics 2009, 28, 3552.
(13) NMR experiments revealed that, in contrast to cinnamyl methyl carbonate, cinnamyl
methyl ether does not undergo oxidative addition to Ni(0) in the absence of
Et3SiOTf. Yamamoto, T.; Ishizu, J.; Yamamoto, A. J. Am. Chem. Soc. 1981,
103, 6863.
Figure 1. Proposed mechanism of Ni-catalyzed allylic substitution of olefins
(L ) organophosphine; triflate (TfO-) omitted for clarity).
Although more detailed studies are required, we propose the
mechanism delineated in Figure 1, in which methyl carbonate 1b is
used as a representative substrate.12 The Ni(0) complex reacts with 1b
without the assistance of Et3SiOTf,13 affording allyl nickel complex 8.
The methoxy group is removed upon reaction with Et3SiOTf, generating
cationic allylnickel complex 9, poised for olefin coordination. Migratory
insertion (giving 10) orients the alkene substituent R away from the Ni,
and (PhO)3P-facilitated10d ꢀ-H elimination and reductive elimination
provide the 1,4-diene product and regenerate the catalyst.
As a demonstration of the scalability of this transformation, the ASR
of ethylene was conducted on 10-mmol scale. Filtration of the reaction
JA101186P
9
J. AM. CHEM. SOC. VOL. 132, NO. 20, 2010 6881