714
J. Am. Chem. Soc. 2000, 122, 714-715
reoselective with respect to the formation of a new 1,2-
disubstituted olefin (entry 8). Furthermore, the Ru-catalyzed
reaction is not impeded by either ether (entries 9-12 and 14) or
amide (entries 13 and 17) functionalites.7 1,7-Enynes also readily
participate in our ruthenuim-catalyzed cycloisomerization reaction
to produce six-membered carbocyclic rings (entries 15 and 16)8
and a piperidine (entry 17). The reaction shows modest to good
1,3-diastereoselectivity (entries 9-12 and 14). Ruthenium-
catalyzed cycloisomerization of enyne 13 affords 83-86% of only
the 1,4-diene with a 1.4:1 diastereoselectivity (entries 9 and 10)
in contrast to the Pd-catalyzed reaction9 wherein mixtures of the
1,3- and 1,4-dienes are obtained. Most notably, isomerization of
enyne 7 gave only 1,4-diene 8 (entries 4 and 5), whereas, the
palladium process gave only the 1,3-diene.
We also examined the regio- and diastereoselectivity utilizing
enyne 27. This substrate has been previously employed in the
Pd-catalyzed Alder-ene reaction to afford the 1,3-diene 29, an
intermediate in the synthesis of sterepolide.10 In contrast, the Ru-
catalyzed reaction affords the silyl enol ether 28 in 72% yield as
a single diastereomer (eq 1). The ability to form an enol silyl
Ruthenium-Catalyzed Cycloisomerizations of 1,6- and
1,7-Enynes
Barry M. Trost* and F. Dean Toste
Department of Chemistry, Stanford UniVersity
Stanford, California 94305
ReceiVed September 20, 1999
Transition metal catalysis offers the unique means by which
to achieve synthetic efficiency not normally accessible by
traditional methods.1 One example of this is the ene-type reaction
between an alkene and an alkyne (as the enophile). A variety of
transition metal catalysts have been reported to catalyze the
intramolecular coupling of alkenes and alkynes to produce cyclic
1,4-dienes.2,3 A few years ago, we reported that the intermolecular
version of this reaction can be catalyzed by cyclopentadienyl (1,5-
cyclooctadiene) ruthenium chloride complex.4 Our initial attempts
to develop the intramolecular version of the ruthenium-catalyzed
Alder-ene were thwarted by the fact that, with CpRu(COD)Cl as
a catalyst, only monosubstituted olefins participated in the reac-
tion. The requirement for the alkene substituent to be on the car-
bon attached to ruthenium (to allow for â-hydride elimination)
demands that the postulated metallacyclopentene intermediate
have a 1,3-bridging as in 1a or 1bsa type of bridging that cannot
be accommodated by short tethers. Our recent discovery that the
+
-
use of the cationic ruthenium catalyst CpRu(CH3CN)3 PF6
2
ether in the presence of a free hydroxyl group is, to our
knowledge, unprecedented. Furthermore, the fact that a silyl enol
ether is stable, even in the presence of a free hydroxyl group, is
a testament to the mildness of the conditions for the Ru-catalyzed
ene-type reaction.
When unsymmetrically trisubstituted olefins, such as 30, are
subjected to the Pd-catalyzed ene-type reaction, products of the
type 33 are obtained.11 In stark contrast to this selectivity, Ru-
catalyzed cycloisomerization of geranyl based 30 affords selec-
tively (8:1) the more substituted 1,4-diene 31 (eq 2). Switching
allowed for the participation of 1,2-disubstituted alkenes5 should
now permit cyclizations to normal ring sizes via a ruthenacycle
such as 1c in a process that may complement the selectivity
observed with Pd-catalyzed cycloisomerizations, enhancing the
scope of such reactions, and provide mechanistic insight into these
reactions.
We initially examined the reaction of the 1,5-enyne 3 (Table
1, entry 1). Subjecting it to 10% 2 and 30% camphorsulfonic
acid (CSA) in 2-butanone at 60 °C led to the 1,4-diene 4 which
was isolated in 68% yield. Further experimentation revealed that
the acid cocatalyst could be omitted and the temperature lowered
to room temperature. Under these latter conditions, the 1,4-diene
4 was isolated in 80% yield (Table 1, entry 2). Use of an electron-
deficient alkyne has no deleterious effect on the course of the
reaction (entries 3, 11, and 12). Unlike the intermolecular version,
the reaction proceeds in the presence of branching at the allylic
carbon (entries 4 and 5). The formation of the ene-type product
in such a case contrasts to the regioselectivity observed with Pd
catalysis. When employing a trisubstituted olefin 9 from which a
new quaternary center is generated in the product, solvent choice
proved critical and had to be switched from the less polar acetone
(entry 6) to the more polar DMF (entry 7). In contrast to the
titanium-catalyzed reaction,3b the Ru-catalyzed reaction is ste-
to the neryl-based enyne 32 completely reverses the selectivity
to afford 33 with a 17:1 selectivity. This is the first example in
which regioselectivity is dependent on the geometry of the starting
olefin. Examination of the proposed ruthenacycle intermediates
provides a possible explanation for this phenomenon. Much like
in the titanacycles,3b the substituent situated in a pseudoequatorial
position as in 34 and 35 places a hydrogen proximal to the metal
(1) Trost, B. M. Science 1991, 254, 1471; Trost, B. M. Angew. Chem., Int.
Ed. Engl. 1995, 34, 259.
(6) For alternative Ru-catalyzed transformations of 1,6-enynes see: (a)
Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1999, 121, 9725. (b) Nishida,
M.; Adachi, N. Onozuka, K.; Matsumura, H.; Mori, M. J. Org. Chem. 1998,
63, 9158. (c) Chatani, N.; Morimoto, T.; Muto, T.; Murai, S. J. Am. Chem.
Soc. 1994, 116, 6049. For a general review of Ru-catalyzed reactions see:
(d) Murahashi, S.-I.; Takaya, H.; Naota, T. Chem. ReV. 1998, 98, 2599.
(7) For cycloisomerization leading to; Furans: Trost, B. M.; Edstrom, E.
D.; Carter-Petillo, M. B. J. Org. Chem. 1989, 54, 4489. Pyrrolidines: Trost,
B. M.; Chen, S.-F. J. Am. Chem. Soc. 1986, 108, 6053 and ref 3b.
(8) Attempts to utilize a 1,8-enyne resulted in only 20% conversion to the
seven-membered ring.
(2) For reviews see: Trost, B. M.; Krische, M. J. Synlett 1998, 1. Ojima,
I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV. 1996, 96, 635.
(3) (a) Pd: Trost, B. M.; Tanoury, G. J.; Lautens, M.; Chan, C.;
MacPherson, D. T. J. Am. Chem. Soc. 1994, 116, 4255 and references therein.
(b) Ti: Sturla, S. J.; Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc.
1999, 121, 1976. (c) Ni-Cr: Trost, B. M.; Tour, J. M. J. Am. Chem. Soc.
1987, 109, 6268. (d) Co (mediated): Krafft, M. E.; Wilson, A. M.; Dasse, O.
A.; Bonaga, L. V. K.; Cheung, Y. Y.; Fu, Z.; Shao, B.; Scott, J. L. Tetrahedron
Lett. 1998, 38, 5911.
(4) (a) Trost, B. M.; Indolese, A. F.; Muller, T. J. J. Treptow, B. J. Am.
Chem. Soc. 1995, 117, 615. (b) Trost, B. M.; Muller, T. J. J.; Martinez, J. J.
Am. Chem. Soc. 1995, 117, 1888.
(9) Trost, B. M.; Lautens, M.; Chan, C.; Jebaratnam, D. J.; Mueller, T. J.
Am. Chem. Soc. 1991, 111, 636.
(10) Trost, B. M.; Chung, J. Y. L. J. Am. Chem. Soc. 1985, 107, 4586.
(11) Trost, B. M.; Phan, L. T. Tetrahedron Lett. 1993, 34, 4735.
(5) Trost, B. M.; Toste, F. D. Tetrahedron Lett. 1999, 40, 7739.
10.1021/ja993401r CCC: $19.00 © 2000 American Chemical Society
Published on Web 01/15/2000