1488
J. Am. Chem. Soc. 1997, 119, 1488-1489
Ru-Catalyzed Rearrangement of Styrenyl Ethers.
Enantioselective Synthesis of Chromenes through
Zr- and Ru-Catalyzed Processes
Scheme 1
Joseph P. A. Harrity, Michael S. Visser,
John D. Gleason, and Amir H. Hoveyda*
Department of Chemistry, Merkert Chemistry Center
Boston College, Chestnut Hill, Massachusetts 02167
ReceiVed October 23, 1996
The present studies arose from our interest in the enantiose-
1
lective synthesis of 2-substituted chromenes, a structural unit
2
found within a myriad of medicinally important agents. In this
Table 1. Ru-Catalyzed Rearrangement of the Styrenyl Ether of
context, extensive efforts by us to use the Zr-catalyzed kinetic
1
-Cyclohepten-2-ol
3
resolution of unsaturated pyrans to obtain nonracemic chromenes
led to uncharacteristically low levels of selectivity (∼10% ee
at 60% conversion). Alternatively, as shown in Scheme 1, we
envisioned that styrenyl allylic ethers, possess alkenes with
appropriate electronic attributes4 so that, with the Grubbs
5
metathesis catalyst (PCy3)2Cl2RudCHCHdCPh2 (3), they
might undergo a net skeletal rearrangement to yield the desired
6
isomeric heterocyclic products. Importantly, rearrangement
substrates would be synthesized in the nonracemic form by the
Zr-catalyzed kinetic resolution.7
Previous reports suggest that Ru-catalyzed ring-closing met-
atheses can be influenced by thermodynamic factors; we thus
8
a
Conditions: (A) 5 mol % of 3, CH Cl , 22 °C, Ar atmosphere,
10-14 h; (B) same as A, except under 1 atm of C H . Isolated yields.
2 4
2
2
b
selected 4 as our initial case study. We surmised that strain
energy of the seven-membered ring would serve as the driving
force for the formation of the less-strained chromene. When 4
is treated with 5 mol % of 3, as shown in entry 1 of Table 1,
RudCH2. This modification is perhaps effective since
larger amounts of the external alkene are present, leading to
the formation of the more reactive (toward styrenyl ether)
5
is obtained in 44% yield. In addition, dimer 6 is isolated in
6% yield (mixture of alkene isomers). Products from inde-
9
LnRudCH2.
5
The catalytic cycle may also commence with reaction of 3
with the carbocyclic olefin. Several observations, however,
imply that terminal alkene of styrene reacts first. For example,
the intermolecular variant (cross-metathesis) of this process
is inoperative; treatment of an equimolar mixture of 11 and 12
with 5 mol% 3 leads to <2% reaction. Without 11, under
pendent rupture of the cycloheptene, or any of the derived
dimeric adducts, were not detected. Under more dilute condi-
tions (entry 2), 5 becomes the major product, albeit the reaction
proceeds less readily and with low monomer/dimer selectivity.
When the Ru-catalyzed rearrangement is carried out under
ethylene atomsphere, monomeric 5 is obtained in 92% yield.
A plausible mechanism for the Ru-catalyzed rearrangement
is presented (Scheme 2). Reaction of 4 with 3 delivers 7, which
is cleaved to provide 8. Subsequent intramolecular addition
affords 9, which rearranges to chromene-containing 10, reaction
of which with a second equivalent of 4 yields 5 and regenerates
1
0
8
. Additionally, as increasing amounts of 5 are produced, 10
otherwise identical conditions, large amounts of oligomeric
may react with 5 to afford 6. With ethylene present (entry 3,
Table 1), less dimer is formed, likely because the olefinic
additive competitively reacts with 10 to produce 5 and Ln-
1
1
products are isolated.
These observations imply that 11
effectively competes with allylic ether 12 for the active Ru
complex. It is tenable that chelated complex 13 sequesters the
1
2
(1) The Mn-catalyzed kinetic resolution of 2,2-disubstituted chromenes
active Ru system to inhibit oligomerization of 12.
was recently reported (Vander Velde, S. L.; Jacobsen, E. N. J. Org. Chem.
As illustrated in Table 2, styrenyl ethers derived from
-cyclohepten-2-ol and 1-cycloocten-2-ol, which are of diverse
1
995, 60, 5380-5381). One instance of resolution of a 2-substituted
1
chromene was reported; the low level of selectivity observed (krel ) 2.7)
was attributed to “competitive decomposition pathways”.
electronic properties, undergo efficient rearrangement to afford
the derived chromene system in excellent yield. The electronic
properties of the aromatic moiety do not have a significant
influence on the reactivity of the diene substrates. In all cases,
(2) Van Lommen, G.; De Bruyn, M.; Schroven, M. J. Pharm. Belg. 1990,
4
5, 355-360 and references cited therein.
(3) (a) Morken, J. P.; Didiuk, M. T.; Visser, M. S.; Hoveyda, A. H. J.
Am. Chem. Soc. 1994, 116, 3123-3124. (b) Visser, M. S.; Heron, N. M.;
Didiuk, M. T.; Sagal, J. F.; Hoveyda, A. H. J. Am. Chem. Soc. 1996, 118,
4
1
7
291-4298.
(9) If any dimeric product (e.g., 6) is formed, LnRudCH2 can reconvert
it to its corresponding monomer. Treatment of 6 with 5 mol % of 3 (ethylene
(4) Crowe, W. E.; Zhang, Z. J. J. Am. Chem. Soc. 1993, 115, 10998-
1
0999.
atmosphere, 12 h) leads to an equal mixture of 5 and 6 (400 MHz H NMR).
(5) (a) Fu, G. C.; Grubbs, R. H. J. Am. Chem. Soc. 1992, 114, 7324-
(10) (a) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117,
5162-5163. (b) Randall, M. L.; Tallarico, J. A.; Snapper, M. L. J. Am.
Chem. Soc. 1995, 117, 9610-9611. (c) Schneider, M. F.; Blechert, S.
Angew. Chem., Int. Ed. Engl. 1996, 35, 411-412. (d) Schuster, M.;
Pernerstorfer, J.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 1979-
1980.
325. (b) Zuercher, W. J.; Hashimoto, M.; Grubbs, R. H. J. Am. Chem.
Soc. 1996, 118, 6634-6640 and references cited therein. (c) Bazan, G. C.;
Schrock, R. R.; Cho, H.-N.; Gibson, V. C. Macromolecules 1991, 24, 4495-
4
502.
(
6) Unlike what is typically observed with Ru-catalyzed ring-closing
metatheses (ref 5a,b), the products of reactions reported herein are isomers
of the starting materials; the Ru-catalyzed reactions thus constitute a
rearrangement.
(11) Hillmyer, M. A.; Laredo, W. R.; Grubbs, R. H. Organometallics
1995, 28, 6311-6316.
(12) Complex 13 may suffer lower reactivity for electronic reasons as
well (Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100-110). For related observations in connection to the influence of
internal chelation on metal-carbene reactivity, see: (a) Feldman, J.;
Murdzek, J. S.; Davis, W. M.; Schrock, R. R. Organometallics 1989, 8,
2260-2265. (b) Reference 5a.
(
7) Visser, M. S.; Harrity, J. P. A.; Hoveyda, A. H. J. Am. Chem. Soc.
996, 118, 3779-3780. For a recent review, see: Hoveyda, A. H.; Morken,
J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 1262-1284.
8) Miller, S. J.; Kim, S.; Chen, Z.; Grubbs, R. H. J. Am. Chem. Soc.
995, 117, 2108-2109.
1
(
1
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