Catalytic asymmetric ring-opening metathesis/cross metathesis (AROM/CM) reactions. Mechanism and application to enantioselective synthesis of functionalized cyclopentanes

Article abstract of DOI:10.1021/ja010684q

Studies regarding the first examples of catalytic asymmetric ring-opening metathesis (AROM) reactions are detailed. This enantioselective cleavage of norbornyl alkenes is followed by an intermolecular cross metathesis with a terminal olefin partner; judic

Full text of DOI:10.1021/ja010684q

J. Am. Chem. Soc. 2001, 123, 7767-7778
7767
Catalytic Asymmetric Ring-Opening Metathesis/Cross Metathesis
(AROM/CM) Reactions. Mechanism and Application to
Enantioselective Synthesis of Functionalized Cyclopentanes
Daniel S. La,† Elizabeth S. Sattely,† J. Gair Ford,† Richard R. Schrock,‡ and
Amir H. Hoveyda*,†
Contribution from the Departments of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02467, and Massachusetts Institute of Technology,
Cambridge, Massachusetts 02139
ReceiVed March 14, 2001
Abstract: Studies regarding the first examples of catalytic asymmetric ring-opening metathesis (AROM)
reactions are detailed. This enantioselective cleavage of norbornyl alkenes is followed by an intermolecular
cross metathesis with a terminal olefin partner; judicious selection of olefin is required so that oligomerization
and dimerization side products are avoided. Results outlined herein suggest that the presence of suitably
positioned heteroatom substituents may be critical to reaction efficiency. Mo-catalyzed tandem AROM/CM
affords functionalized cyclopentyl dienes in >98% ee and >98% trans olefin selectivity; both secondary and
tertiary ether products can be obtained. The examples provided include the catalytic synthesis of an optically
pure cyclopentyl epoxide and dimethyl acetal. Mechanistic studies suggest that it is the more substituted
benzylidene or silylated alkylidenes that are involved in the catalytic process (vs the corresponding Mo-
methylidenes). Although electron rich benzylidenes react more efficiently, the derived electron poor Mo
complexes promote AROM/CM transformations as well; alkylidenes that bear a boron substituent are unreactive.
Introduction
effected that are unique to olefin metathesis. In the context of
asymmetric catalysis and the synthesis of optically pure materi-
als,6 a wider range of such tandem catalytic transformations
realize their full potential if efficient and functional group
tolerant chiral nonracemic metathesis catalysts are available.
Easily accessible achiral substrates can then be directly con-
verted into optically enriched and highly functionalized com-
pounds (e.g., 5 in Scheme 1). To access the products obtained
in this study by the more commonly adopted strategy, namely,
the utilization of achiral catalysts to effect metatheses of
optically enriched starting materials,7 would be less practical;
this is largely because the preparation of the requisite nonra-
cemic starting materials would require significantly longer
routes.
Metal-catalyzed ring-opening metathesis (ROM) represents
a class of C-C bond-forming transformations that has notable
potential in organic synthesis but has received less attention
than the related ring-closing metathesis (RCM).1 Since catalytic
ROM processes generate a new metal-alkylidene complex, they
can be followed by a subsequent metathesis step. A tandem
catalytic ring-opening metathesis/cross metathesis (ROM/CM)
protocol may therefore be envisioned.2-5 Such transformations
allow for synthetically useful skeletal reorganizations to be
† Boston College.
‡ Massachusetts Institute of Technology.
(1) For reviews on catalytic olefin metathesis, see: (a) Grubbs, R. H.;
Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446-452. (b) Schmalz,
H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34, 1833-1836. (c) Schuster,
M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 2036-2056. (d)
Ivin, K. J.; Mol, J. C. Olefin Metathesis and Metathesis Polymerization;
Academic Press: San Diego, 1997. (e) Furstner, A. Top. Catal. 1997, 4,
285-299. (f) Schrock, R. R. In Alkene Metathesis in Organic Synthesis;
Furstner, A., Ed.; Springer: Berlin 1998; pp 1-36. (g) Armstrong, S. K. J.
Chem. Soc., Perkin Trans. 1 1998, 371-388. (h) Grubbs, R. H.; Chang, S.
Tetrahedron 1998, 54, 4413-4450. (i) Randall, M. L.; Snapper, M. L. The
Strem Chemiker 1998, 17, 1-9. (j) Phillips, A. J.; Abell, A. D. Aldrichchim.
Acta 1999, 32, 75-89. (k) Wright, D. L. Curr. Org. Chem. 1999, 3, 211-
240. (l) Furstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012-3043.
(2) For studies on metal-catalyzed nonasymmetric tandem ROM/CM
processes, see: (a) Randall, M. L.; Tallarico, J. A.; Snapper, M. L. J. Am.
Chem. Soc. 1995, 117, 9610-9611. (b) Snapper, M. L.; Tallarico, J. A.;
Randall, M. L. J. Am. Chem. Soc. 1997, 119, 1478-1479. (c) Schneider,
M. F.; Lucas, N.; Velder, J.; Blechert, S. Angew. Chem., Int. Ed. Engl.
1997, 36, 257-259. (d) Cuny, G. D.; Cao, J.; Hauske, J. R. Tetrahedron
Lett. 1997, 38, 5237-5240. (e) Cao, J.; Cuny, G. D.; Hauske, J. R. Mol.
DiVers. 1998, 3, 173-179. (f) Michaut, M.; Parrain, J.-L.; Santelli, M. Chem.
Commun. 1998, 2567-2568. (g) Katayama, H.; Urushima, H.; Nishioka,
T.; Wada, C.; Nagao, M.; Ozawa, F. Angew. Chem., Int. Ed. 2000, 39,
4513-4515.
(3) For studies on metal-catalyzed nonasymmetric ROM/RCM reactions,
see: (a) Zuercher, W. J.; Hashimoto, M.; Grubbs, R. H. J. Am. Chem. Soc.
1996, 118, 6634-6640. (b) Harrity, J. P. A.; Visser, M. S.; Gleason, J. D.;
Hoveyda, A. H. J. Am. Chem. Soc. 1997, 119, 1488-1489. (c) Harrity, J.
P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda, A. H. J. Am. Chem.
Soc. 1998, 120, 2343-2351. (d) Burke, S. D.; Quinn, K. J.; Chen, V. J. J.
Org. Chem. 1998, 63, 8626-8627. Related application to target-oriented
synthesis: (e) Johannes, C. W.; Visser, M. S.; Weatherhead, G. S.; Hoveyda,
A. H. J. Am. Chem. Soc. 1998, 120, 8340-8347. (f) Adams, J. A.; Ford, J.
G.; Stamatos, P. J.; Hoveyda, A. H. J. Org. Chem. 1999, 64, 9690-9696.
(g) Stragies, R.; Blechert, S. J. Am. Chem. Soc. 2000, 122, 9584-9591.
(h) Voigtmann, U.; Blechert, S. Org. Lett. 2000, 2, 3971-3974.
(4) For recent examples of tandem CM/RCM and applications to target-
oriented synthesis, see: (a) Smith, A. B.; Adams, C. M.; Kozmin, S. A. J.
Am. Chem. Soc. 2001, 123, 990-991 and references therein. (b) Furstner,
A.; Thiel, O. R.; Ackermann, L. Org. Lett. 2001, 3, 449-451.
(5) For recent reviews on catalytic ring-opening/cross metathesis, see:
(a) Gibson, S. E.; Keen, S. P. In Alkene Metathesis in Organic Synthesis;
Furstner, A., Ed.; Springer: Berlin, 1998; pp 172-179. (b) Arjona, O.;
Csaky, A. G.; Plumet, J. Synthesis 2000, 6, 857-861.
(6) For a brief overview of catalytic enantioselective olefin metathesis,
see: Hoveyda, A. H.; Schrock, R. R. Chem.sEur. J. 2001, 7, 945-950.
10.1021/ja010684q CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/18/2001

7768 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
La et al.
Scheme 1
Chart 1
Results and Discussion
1. Initial Mechanistic Considerations. Catalytic AROM/
CM processes involve the intermolecular reactions of two
different alkene substrates that could also react to afford a variety
of side products in addition to the desired chiral compounds.
That is, alkene substrates can (i) catalytically dimerize or self-
oligomerize and (ii) react with the transition metal catalyst to
afford various metal-alkylidenes that promote the formation of
different products (see below for details). Thus, the effectiveness
of catalytic tandem asymmetric ring-opening metathesis/cross
metathesis (AROM/CM) is directly and strongly related to
myriad mechanistic issues that must first be considered in the
context of reaction design. Conditions must be carefully selected
to minimize other competitive metathesis reactions that yield a
multitude of undesired compounds and may give rise to low
enantioselectivity. Some of these issues become more apparent
when a specific catalytic AROM/CM reaction, such as that
involving norbornene (3) and styrene (4a) to afford chiral
cyclopentyl adduct 5, is considered (eq 1). Related questions
and their implications will be briefly discussed first, since an
awareness of mechanistic principles is imperative for a better
understanding of various subtleties implied by the data disclosed
below.
The above considerations, together with the efficiency with
which chiral Mo-based complexes 18 and 29 (Chart 1) have been
used in these laboratories in catalytic asymmetric ring-closing
metathesis (ARCM), led us to establish a program toward
developing the Mo-catalyzed tandem asymmetric ring-opening
metathesis/cross metathesis (AROM/CM).10 Our studies have
led us to carry out the first examples of catalytic tandem AROM/
CM transformations with meso norbornenes in conjunction with
a range of terminal alkenes. The results of this study are detailed
herein.11
(7) For examples of enantioselective total syntheses, where a chiral
nonracemic intermediate has been subjected to catalytic metathesis (in
addition to refs 3-4), see: (a) Xu, Z.; Johannes, C. W.; Houri, A. F.; La,
D. S.; Cogan, D. A.; Hofilena, G. E.; Hoveyda, A. H. J. Am. Chem. Soc.
1997, 119, 10302-10316. (b) Meng, D.; Su, D. S.; Balog, A.; Bertinato,
P.; Sorensen, E. J.; Danishefsky, S. J.; Zheng, Y.-H.; Chou, T.-C.; He, L.;
Horwitz, S. B. J. Am. Chem. Soc. 1997, 119, 2733-2734. (c) Nicolaou, K.
C.; Winssinger, N.; Pastor, J.; Ninkovic, S.; Sarabia, F.; He, Y.; Vourloumis,
D.; Yang, Z.; Li, T.; Giannakakou, P.; Hamel, E. Nature 1997, 387, 268-
272. (d) Johannes, C. W.; Visser, M. S.; Weatherhead, G. S.; Hoveyda, A.
H. J. Am. Chem. Soc. 1998, 120, 8340-8347. (e) Delgado, M.; Martin, J.
D. J. Org. Chem. 1999, 64, 4798-4816. (f) Lee, D.; Sello, J. K.; Schreiber,
S. L. J. Am. Chem. Soc. 1999, 121, 10648-10649. (g) Furstner, A.; Thiel,
O. R. J. Org. Chem. 2000, 65, 1738-1742. (h) Limanto, J.; Snapper, M.
L. J. Am. Chem. Soc. 2000, 122, 8071-8072. (i) Smith, A. B.; Kozmin, S.
A.; Adams, C. M.; Paone, D. V. J. Am. Chem. Soc. 2000, 122, 4984-
4985. (j) Wu, Y.; Esser, L.; De Brabander, J. K. Angew. Chem., Int. Ed.
2000, 39, 4308-4310.
(8) (a) Alexander, J. B.; La, D. S.; Cefalo, D. R.; Hoveyda, A. H.;
Schrock, R. R. J. Am. Chem. Soc. 1998, 120, 4041-4042. (b) La, D. S.;
Alexander, J. B.; Cefalo, D. R.; Graf, D. D.; Hoveyda, A. H.; Schrock, R.
R. J. Am. Chem. Soc. 1998, 120, 9720-9721. (c) Weatherhead, G. S.;
Houser, J. H.; Ford, J. G.; Jamieson, J. Y.; Schrock, R. R.; Hoveyda, A. H.
Tetrahedron Lett. 2000, 41, 9553-9559. (d) Aeilts, S. L.; Cefalo, D. R.;
Bonitatebus, P. J., Jr.; Houser, J. H.; Hoveyda, A. H.; Schrock, R. R. Angew.
Chem., Int. Ed. 2001, 40, 1452-1456. For application of catalytic ARCM
in target-oriented synthesis: (e) Burke, S. D.; Muller, N.; Beudry, C. M.
Org. Lett. 1999, 1, 1827-1829.
One of the most critical issues vis-a`-vis the mechanism of
catalytic AROM/CM reactions relates to the identity of the
reacting Mo-alkylidene (Scheme 1).12 The chiral Mo-based
catalyst (the initial Mo neophylidene in Scheme 1), through
direct reaction with styrene (4a) or by initial reaction with
norbornene (6 via 3) may be transformed to benzylidene i or
methylidene ii, which are readily interconvertible. Reaction of
ii with 4a affords ethylene in addition to i, which can then react
with ethylene to regenerate ii. Importantly, as illustrated in
Scheme 1 (box), if reaction of 3 with i delivers 5 via iii, reaction
through methylidene ii with the same enantiofacial selectivity
would afford ent-5 via iW. Thus, whereas in a nonasymmetric
process either i or ii may deliVer the desired product, in a
catalytic enantioselectiVe Variant reaction through the Mo-
benzylidene or the Mo-methylidene can result in the formation
of opposite enantiomers and reduced enantioselection.
Highly reactive olefinic substrates, such as norbornene (3),
allow for two strategic advantages in the design of catalytic
(11) For related catalytic tandem AROM/RCM reactions, see: (a)
Weatherhead, G. S.; Ford, J. G.; Alexanian, E. J.; Schrock, R. R.; Hoveyda,
A. H. J. Am. Chem. Soc. 2000, 122, 1828-1829. (b) Cefalo, D. R.; Kiely,
A. F.; Wuchrer, M.; Jamieson, J. Y.; Schrock, R. R.; Hoveyda, A. H. J.
Am. Chem. Soc. 2001, 123, 3139-3140.
(12) (a) Schrock, R. R. Polyhedron 1995, 14, 3177-3195. (b) Feldman,
J.; Schrock, R. R. Prog. Inorg. Chem. 1991, 39, 1-74. (c) Reference 1f.
(9) Zhu, S.; Cefalo, D. R.; La, D. S.; Jamieson, J. Y.; Davis, W. M.;
Hoveyda, A. H.; Schrock, R. R. J. Am. Chem. Soc. 1999, 121, 8251-8259.
(10) For the initial communication regarding this work, see: La, D. S.;
Ford, J. G.; Sattely, E. S.; Bonitatebus, P. J.; Schrock, R. R.; Hoveyda, A.
H. J. Am. Chem. Soc. 1999, 121, 11603-11604.

Ring-Opening Metathesis/Cross Metathesis Reactions
J. Am. Chem. Soc., Vol. 123, No. 32, 2001 7769
Scheme 2. Representative Potential Side Reactions in
Scheme 3
Catalytic AROM/CM
AROM/CM: (1) Strained olefins more likely possess the
reactivity to ensure that catalytic AROM/CM is appropriately
efficient. Otherwise, with slower reacting disubstituted alkene
partners, longer reaction times will be required and, as shown
in Scheme 2 (a), further CM of 5 with styrene (4a) effectively
competes to contaminate the desired reaction product with meso
7. (2) ROM is likely irreversible due to the release of ring strain.
Ring cleavage (e.g., 3 f iii, box in Scheme 1) therefore becomes
the likely stereochemistry-determining step (kinetic control of
enantioselectivity), allowing various substrate-catalyst associa-
tion models to serve as reasonably reliable elements in
understanding the origins of stereochemical control. Strained
olefins should however not be too reactive, as the initial metal-
alkylidene intermediates iii or iW (cf. Scheme 1) may then react
with another molecule of the strained alkene to cause oligo-
merization (see (b), Scheme 2).
Various considerations need to be applied to the terminal
olefin partner as well: it must be sufficiently reactive not to
allow the metal-alkylidene intermediate iii or iW to initiate the
previously mentioned oligomerization. Yet, the same terminal
alkene, if too reactive, may be prematurely consumed through
homodimerization (see (c), Scheme 2) and not be available to
react with the alkylidene that results from ROM (e.g., iii,
Scheme 2).
With the above mechanistic issues in mind, we set out to
examine the possibility of Mo-catalyzed tandem AROM/CM
reactions involving various meso norbornyl substrates and
terminal alkenes. In the discussion outlined below, first the
results of the methodological studies on catalytic AROM/CM
of several norbornyl substrates and terminal olefins are pre-
sented. Subsequently, various mechanistic issues and the related
additional data are disclosed.
2. Mo-Catalyzed AROM/CM with Norbornyl Substrates.
(a) Initial Attempts with Norbornene 3. We began our
investigation by examining the reaction of norbornene 3 in the
presence of varying amounts of styrene 4a and 5 mol % of the
chiral Mo complex 1a. As illustrated in eq 2, these conditions
do little to increase the amount of the desired AROM/CM
product; even in the presence of 10 equiv of styrene, <5% of
the nonoligomeric adducts is detected (400 MHz 1H NMR
analysis of the unpurified reaction mixture). Similarly discour-
aging results were obtained with allylsilane 10 (eq 2). Slow
addition of 3 to a CH2Cl2 solution of 10 equiv of 10 leads to
<5% of the desired AROM/CM adduct (as judged by analysis
1
of the 400 MHz H NMR spectrum).
(b) Initial Investigation with 7-Norbornyl TBS Ether 11.
To address the above complications in connection to norbornene
oligomerization, we decided to reduce the reactivity of the
strained disubstituted olefin through incorporation of some steric
bulk in the vicinity of the reacting alkene, but without
jeopardizing the meso character of the substrate. Toward this
end, we prepared 7-siloxynorbornene 1113 (Scheme 3) since we
surmised that the Mo-alkylidene likely approaches the norbornyl
alkene from the exo face; this conjecture finds support in X-ray
crystal structures of various norbornyl molybdacyclobutanes
reported previously.12b,14
As illustrated in Scheme 3 (catalyst optimization section),
when 11 is subjected to 5 mol % of chiral Mo complexes 1a,
1b, or 2 in the presence of 10 equiv of styrene (4a) at 22 °C,
the desired AROM/CM product 12a is formed in appreciable
1
amounts (reaction progress was monitored by 400 MHz H
NMR). The most promising level of enantioselectivity is that
obtained from the reaction of 1a (>98% ee; chiral HPLC
analysis), although the sterically less demanding dimethylimido
complex 1b delivers the best reactivity (51% conversion in 7
h).15
Next, we turned our attention to improving the efficiency of
the catalytic process without imposing any adverse effects on
enantioselectivity. Within this context, we were surprised to find
that, contrary to our initial expectation, lowering the amount of
styrene leads to higher leVels of conVersion (see Scheme 3,
styrene optimization section). Furthermore, as the data in
Scheme 3 indicate, variations in styrene concentration result in
little or no change in the optical purity of 12a.
A plausible rationale regarding the lower rate of AROM/CM
product formation with higher equivalents of 4a may involve
nonproductive or degenerate reaction of the chiral Mo-ben-
(13) Gerteisen, T. J.; Kleinfelter, D. C. J. Org. Chem. 1971, 36, 3255-
3259.
(14) (a) Bazan, G. C.; Khosravi, E.; Schrock, R. R.; Feast, W. J.; Gibson,
V. C.; O’Reagan, M. B.; Thomas, J. K.; Davis, W. M. J. Am. Chem. Soc.
1990, 112, 8378-8387. (b) Bazan, G. C.; Oskam, J. H.; Cho, H.; Park, L.
Y.; Schrock, R. R. J. Am. Chem. Soc. 1991, 113, 6899-6907.
(15) At the time these studies were carried out, only complexes 1 and 2
were available. Additional chiral Mo complexes are now in hand (see refs
6 and 8).
(at 22 °C, CH2Cl2 or C6H6) lead to the rapid formation of
oligomeric substances (15 min). Larger equivalents of styrene

7770 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
La et al.
Table 1. Tandem Mo-Catalyzed AROM/CM Reactions with Norbornyl Secondary Ethers and Various Styrenesa
b
1
c
a Conditions: 5 mol % 1a, 2 equiv 4, Ar atm 22 °C, C6H6. Percent product determined by 400 MHz H NMR analysis. Determined by 400
1
d
MHz H NMR analysis. Determined by chiral HPLC (Chiralcel OD for entries 1,2, 4-7 and AD chiralpak for entries 8-9), in comparison with
authentic racemic materials. Analysis of products in entries 1, 4, 6, and 7 was performed on the derived acetates. e Isolated yield of purified products
by silica gel chromatography.
Scheme 4
complex i (see below for discussions related to evidence favoring
the intermediacy of Mo-benzylidene i).
(c) Catalytic AROM/CM Reaction of Secondary Nor-
bornyl Ethers. With the first successful example of a catalytic
AROM/CM in hand, we next set out to examine in detail the
following critical issues: (i) The influence of the size and nature
of the norbornyl alkoxy substituent. (ii) The effect of the
electronic attributes of the styrenes. (iii) The identity and extent
of side products that may be formed as a function of various
pathways, some of which are mentioned earlier. As illustrated
at the heading of Table 1, in addition to the expected catalytic
AROM/CM product represented by I, potential side products
include meso diene II, homometathesis adduct III, and meso
terminal diene IV.
The results in entries 1 and 2 of Table 1 indicate that with
the sterically demanding TBS ether reaction with the electron
rich p-OMe-styrene 4b is more efficient in delivering the derived
AROM/CM product (12) than styrene 4a. In contrast, when the
electron deficient p-CF3-styrene 4c is used, <10% reaction is
observed after 10 h (see below for discussion of rate difference).
Although the transformation with 4a (96% ee) is somewhat more
enantioselective than that with 4b (91% ee), both processes
generate exclusively trans products (>98%) and nearly equal
amounts of side products corresponding to meso dienes II and
IV; <2% homometathesis product (i.e., III) is detected in both
instances (analysis of 400 MHz 1H NMR spectrum of the
unpurified reaction mixture).
zylidene (i) or methylidene (ii) with excess styrene.16 Thus, as
illustrated in Scheme 4, reaction of benzylidene i with 4a may
lead to the formation of metallacyclobutanes 13 or 14. Inter-
mediate 13 can only decompose to re-deliver styrene and
benzylidene i, whereas molybdacycle 14 could lead to the
formation of stilbene (9). Analysis of the unpurified reaction
mixtures does not indicate a substantial amount of stilbene
generation (<5% 9 with 10 equiv of 4a). Formation of
metallacycle 13 may be favored due to the following: (i)
Accumulation of electron density at both carbons of the two
C-Mo bonds is stabilized by an adjacent phenyl group (cf.
Scheme 4). (ii) Metallacyclobutane 14 might suffer from more
severe steric interactions than the alternative 13 (steric interac-
tion between Ph and MoLn is offset by the longer C-Mo bond).
Excess styrene can thus preoccupy the active chiral catalyst and
cause diminution of reaction rates through formation of the more
favored and relatively stable 13. Similar arguments may be put
forth involving the Mo-methylidene complex ii; the metallacy-
clobutane from addition of styrene to ii can undergo fragmenta-
tion to regenerate ii and styrene or ethylene and benzylidene
With TMS ether 15 as the substrate (Table 1, entries 4-6),
catalytic AROM/CM reactions occur smoothly, affording the
desired products 16a-c in >98% ee and >98% trans selectivity.
Catalytic metathesis of 4a or 4b with the more reactive TMS
ether (vs 11) generates lower amounts of byproducts (compare
entries 4-5 with entries 1-2), indicating that with a faster
reacting substrate (1 h for 15 vs 7 h for 11), the desired pathway
can more effectively compete with unwanted side reactions (see
(16) For a study of degenerate exchanges in a catalytic cross metathesis
reaction, see: McGinnis, J.; Katz, T. J.; Hurwitz, S. J. Am. Chem. Soc.
1976, 98, 605-606.

Ring-Opening Metathesis/Cross Metathesis Reactions
J. Am. Chem. Soc., Vol. 123, No. 32, 2001 7771
Table 2. Tandem Mo-Catalyzed AROM/CM Reactions with
Functionalized Norbornyl Secondary Ethers, Secondary Esters and
Styrenea
Figure 2.
selectivity. The trend in relative rates of various styrenes (4b
> 4a > 4c), similar to that observed with 11 (entries 1-3) and
15 (entries 4-6), is recorded here. With this sterically less
demanding substrate (vs 11 and 15), reactions proceed to >98%
conversion in less than an hour even with the least reactive 4c;
but compounds from further functionalization of the initial
AROM/CM product are also formed before all the substrate is
consumed. In the case of the reaction of 17 with 4a (entry 7),
4% of the meso adduct corresponding to II and 1% product
represented by III are observed; nearly an identical mixture is
obtained from the reaction of 17 with 4b (entry 8). Longer
reaction times lead to an increase in the amount of II-IV.
Additional data in connection to Mo-catalyzed AROM/CM
reactions of secondary norbornyl ethers are illustrated in Table
2. All transformations were carried out with styrene (4a) as the
terminal alkene partner. The enantioselective metathesis of the
sterically demanding t-Bu ether 1917 proceeds to deliver 20
within 1 h in the optically pure form with <2% byproduct
formation (see II-IV, Table 1), >98% trans selectivity, and in
92% yield after silica gel chromatography. The highly func-
tionalized chiral cyclopentyl adducts 2218 (entry 2, Table 2) and
24 (entry 3) are generated catalytically with similarly high levels
of selectivity and efficiency. The relative rates with which
substrates 19 (fastest, 1 h), 21, and 23 (slowest, 5 h) undergo
reaction is likely, at least in part, due to the reduced Lewis
basicity of the reactive alkene caused by the interaction of the
C-C π electrons with the properly aligned low-lying σ* orbitals
at C5 and C6 (Figure 2). Thus, the rate of AROM/CM is slowest
with the more electron withdrawing (lowest energy C-O σ*)
acetate substituents.19 The absence of byproducts (corresponding
to II and III, Table 1) derived from further reaction of the
terminal alkene in 20, 22, and 24 likely arises from the steric
bulk of the O-t-Bu group which renders reaction at the olefinic
site sterically prohibitive.
a Conditions: 5 mol % of 1a, 2 equiv of 4a, Ar atm, 22 °C, C6H6.
b Percent product determined by 400 MHz 1H NMR analysis. c Deter-
1
mined by 400 MHz H NMR analysis. d Determined by chiral HPLC
(OJ Chiralpak for entry 1, AD Chiralpak for entry 2, and Chiralcel
OD for entries 3-4), in comparison with authentic racemic materials.
e Isolated yield of purified products by silica gel chromatography.
Similar to substrates in Table 1 and the alkyl ethers 19, 21,
and 23 in Table 2, aryl ether 2520 undergoes catalytic AROM/
CM readily to afford 26 in >98% ee and >98% trans selectivity
(Table 2, entry 4). The reaction mixture is however contaminated
with previously mentioned byproducts (>98% conversion, 77%
conversion to 26). As illustrated in entry 5 (Table 2), the derived
electron rich and electron deficient esters 27a and 27b afford
<2% reaction product even after several hours (>95% recovery
Figure 1. Chem 3D rendition of the crystal structure of the camphor
sulfonate derivative obtained from 16b.
below for further details). It is important to note that when the
less sterically demanding TMS ether 15 is used (vs TBS ether
11), catalytic reactions proceed to completion with all three
styrene substrates (4a-4c). Thus, the less reactive p-CF3 styrene
undergoes efficient metathesis with 15, albeit at a rate slower
than 4a and 4b, to afford 16c in 48% isolated yield and >98%
ee (>98% trans). Another noteworthy difference between
reaction of 15 with 4a,b and that with the less reactive 4c is
that in the latter case similar to transformations with the
sterically more encumbered norbornyl alkene in 11, significant
amounts of byproducts corresponding to II and IV are generated.
The stereochemical identity of the reaction products in Table
1 is based on the X-ray crystal structure of the camphor sulfonate
derivative (Figure 1) obtained from AROM/CM product 16b
(Table 1, entry 5). Deprotection of 12b and 18b affords the
same parent alcohol enantiomer as that obtained from desily-
lation of 16b. The remainder of the stereochemical assignments,
including results in Tables 2 and 3 are by inference.
(17) Micheli, R. A.; Hajos, Z. G.; Cohen, N.; Parrish, D. R.; Portland,
L. A.; Sciamanna, W.; Scott, M. A.; Wehrli, P. A. J. Org. Chem. 1975, 40,
675-681.
(18) Cheikh, A. B.; Craine, L. E.; Recher, S. G.; Zemlicka, J. J. Org.
Chem. 1988, 53, 928-936. (b) Story, P. R.; Hahrenholtz, S. R. Organic
Syntheses; Wiley: New York, 1973; Collect. Vol. 5, pp 151-154.
(19) For examples of studies relating to the effect of stereoelectronics
on the reactivity and selectivity of reactions with rigid polycyclic substrates,
see: (a) Winstein, S.; Shatavsky, M. J. Am. Chem. Soc. 1955, 78, 592-
597. (b) Lambert, J. B.; Holcomb, A. G. J. Am. Chem. Soc. 1971, 93, 2994-
3001. (c) Cristol, S. J.; Beimborn, D. A. J. Am. Chem. Soc. 1973, 95, 3651-
3654. (d) Goering, H. L.; Chang, C.-H. J. Am. Chem. Soc. 1977, 99, 1547-
1550. (e) Srivastava, S.; le Noble, W. J. J. Am. Chem. Soc. 1987, 109,
5874-5875. (f) Lin, M.-H.; Cheung, C. K.; le Noble, W. J. J. Am. Chem.
Soc. 1988, 110, 6562-6563. (g) Hahn, J. M.; le Noble, W. J. J. Am. Chem.
Soc. 1992, 114, 1916-1917. (h) Mehta, G.; Khan, F. A. Tetrahedron Lett.
1992, 33, 3065-3068. (i) Pudzianowski, A. T.; Barrish, J. C.; Spergel, S.
H. Tetrahedron Lett. 1992, 33, 293-296.
The catalytic AROM/CM reactions of the MOM ether 17
are illustrated in entries 7-9 of Table 1. As before, all reactions
afford the expected Mo-catalyzed AROM/CM products 18a-c
in >98% ee and >80% isolated yield with >98% trans olefin
(20) Substrate 25 was prepared by treatment of the corresponding C7-
potassium alkoxide (KH at 0 °C) with 1-iodo-4-trifluoromethylbenzene (1
equiv).

7772 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
La et al.
Table 3. Tandem Mo-Catalyzed AROM/CM Reactions with
ee) diene 29 (85% yield of the derived alcohol after silica gel
chromatography). Olefin stereocontrol is complete (>98% trans
isomer) and there are <2% byproducts detected in the 400 MHz
1H NMR spectrum of the unpurified reaction mixture (cf. II-
IV, Table 1). Whereas catalytic AROM/CM of 28 is complete
in less than 1 h, when diastereomeric MOM ether 30 (entry 2)
is subjected to the same reaction conditions, eVen after 12 h
there is no detectable product formation (<2% by 400 MHz
1H NMR). Tertiary ether 31 reacts with 4a to deliver optically
pure 32 in 14 h (entry 3, Table 3). The conclusion may thus be
drawn that the heteroatom substituent must be disposed such
that it is proximal to the reacting olefin (see below for
discussions on mechanism). Nonetheless, the high reactivity of
the epoxide diastereomer 33,23 shown in entry 4 of Table 3,
suggests that with less hindered C7 alkyl substituents catalytic
AROM/CM may proceed efficiently. The cyclic nature of the
epoxide ring is expected to impose less steric hindrance toward
the approaching Mo complex (vs an n-Bu group). (See below
for further discussion of the influence of resident heteroatoms
on reactivity.)
Norbonyl Tertiary Ethers and Styrenea
Mechanistic implications notwithstanding, the epoxycyclo-
pentane 34, a compound that should readily serve as a versatile
optically pure synthon, is obtained in >98% ee, >98% trans
selectivity, and in 84% yield after silica gel chromatography.
Entry 5 of Table 3 depicts a related example that involves the
efficient catalytic enantioselective preparation of optically pure
acetal 36.24
a Conditions: 5 mol % of 1a, 2 equiv of 4a, Ar atm, 22 °C, C6H6.
b Percent product determined by 400 MHz 1H NMR analysis. c Deter-
1
mined by 400 MHz H NMR analysis. d Determined by chiral HPLC
(AD Chiralpak for entries 1 (on the deprotected alcohol) and 4 and
Chiralcel OD for entries 3 and 5), in comparison with authentic racemic
materials. e Isolated yield of purified products by silica gel chroma-
tography. f Overall yield of deprotected alcohol.
(e) Range of Terminal Olefin Partners. The experiments
outlined above involve various styrene substrates. This class of
terminal alkenes includes attractive reaction partners that may
be used in Mo-catalyzed AROM/CM reactions, since the related
homodimerization process is relatively slow (<2% stilbene and
related derivatives observed in all experiments). As depicted in
Scheme 5, the suitability of other terminal olefin systems for
effective participation in the catalytic AROM/CM processes was
examined as well.25 When (vinyl)trimethylsilane is used with
norbornyl MOM ether 17, functionalized cyclopentyl ether 37
is obtained in >98% ee and 62% isolated yield (Scheme 5).
(Vinyl)trimethoxysilane can also be used effectively with the
added advantage that the derived product can be directly
subjected to Pd-catalyzed cross-coupling26 to afford other
optically pure cyclopentyl dienes (e.g., 38). It must be noted
that catalytic transformations with (vinyl)trimethylsilanes and
(vinyl)trimethoxysilane are significantly slower than those of
styrenes 4. This difference in reactivity is likely partly attribut-
able to the steric bulk of the silyl moiety. Hyperconjugative
effects of the silylated anti Mo-alkylidenes A and B and
chelation in B,27 shown in Scheme 4, could not only lead to
diminished transition metal Lewis acidity and result in lower
reaction rates but also cause reduced availability of the syn
alkylidene isomer. Slower catalytic metatheses would therefore
of unreacted starting material). Addition of diallyl ether to the
reaction mixture leads to rapid and complete RCM to afford
2,5-dihydrofuran. Therefore, the lack of reactivity is not due to
irreversible binding of the catalyst to the Lewis basic ester
moiety, leading to its sequestration and inactivation. It is possible
however that association of the ester carbonyl with the Lewis
acidic Mo center preempts reaction with the strained olefin. The
observed catalyst inhibition may be due to the following: (i)
The Mo center becomes significantly less Lewis acidic due to
chelation with the ester group and thus does not bind to an olefin
unless it is dissociated from the substrate (reassociation with
alkene may rapidly lead to re-coordination with the ester). (ii)
Geometric contraints do not allow Mo-olefin association once
the transition metal is bound to the ester unit (either intramo-
lecular Mo transfer from ester to alkene or two-point binding
of Mo with alkene and ester is inhibited).
(d) Catalytic AROM/CM Reaction of Tertiary Norbornyl
Ethers. The catalytic transformations illustrated above provide
a unique, efficient, and highly enantioselective entry to the
preparation of functionalized cyclopentanes that bear a second-
ary C-O bond and easily differentiable olefin moieties. Next,
we extended this strategy to the catalytic asymmetric preparation
of adducts that bear tertiary ether units. Considering the scarcity
of effective methods for enantioselective alkylation of ketones,21
we judged that, if successful, the Mo-catalyzed AROM/CM
protocol would provide a valuable tool that can be used in
enantioselective synthesis. The results of our study regarding
catalytic metatheses of tertiary norbornyl ethers are summarized
in Table 3.
(22) For synthesis of the ketone used to prepare substrates 28, 30, and
31 in Table 3, see: Gassman, P. G.; Pape, P. G. J. Org. Chem. 1964, 29,
160-163.
(23) For preparation of substrate 33, see: Bly, R. K.; Bly, R. S. J. Org.
Chem. 1963, 28, 3165-3172.
(24) The 1H NMR spectrum of the unpurified reaction mixture for
catalytic AROM/CM of 35 indicates the presence of the desired 36 only
with <2% byproduct formation. The low isolated yield is due to the
instability of the acetal product to silica gel.
(25) For Mo-catalyzed cross metatheses reactions involving allylsilanes,
see: Crowe, W. E.; Goldberg, D. R.; Zhang, Z. J. Tetrahedron Lett. 1996,
37, 2117-2120.
(26) Tamao, K.; Kobayashi, K.; Ito, Y. Tetrahedron Lett. 1989, 30,
6051-6054.
(27) For a previous report, where Mo-O coordination is proposed to
lead to the stabilization of the anti Mo-alkylidene isomer, see: Schrock, R.
R.; Crowe, W. E.; Guillermo, C.; DiMare, M.; O’Regan, M. B.; Schofield,
M. H. Organometallics 1991, 10, 1832-1843.
As illustrated in entry 1 of Table 3, treatment of tertiary MOM
ether 2822 with 5 mol % of 1a in the presence of 2 equiv of
styrene (4a) leads to the rapid formation of optically pure (>98%
(21) (a) Dosa, P. I.; Fu, G. C. J. Am. Chem. Soc. 1998, 120, 445-446.
(b) Casolari, S.; D’Addario, D.; Tagliavini, E. Org. Lett. 1999, 1, 1061-
1063.

Ring-Opening Metathesis/Cross Metathesis Reactions
J. Am. Chem. Soc., Vol. 123, No. 32, 2001 7773
Scheme 5. Mo-Catalyzed AROM/CM with Non-Styrenyl Alkenes
a Isolated yield after deprotection of the TMS and t-Bu group (overall for two steps); 41% conversion for 39, 59% conversion for 42. b Percent
1
conversion based on analysis of the 400 MHz H NMR spectrum of the unpurified reaction mixture.
1
be observed regardless of whether it is the syn or the anti
alkylidene isomer that is the active complex. There is spectro-
scopic evidence in support of the hyperconjugation illustrated
by H NMR analysis). If these transformations were allowed
to proceed further, larger amounts of the disubstituted meso
products 40 and 43 would be isolated. In support of the above
contention, unlike styrenes, which are relatively resistant toward
homometathesis, when vinylcyclohexane is treated with 5 mol
% of 1a (22 °C, C6D6), 30% of the corresponding homomet-
athesis product is formed within 90 min. Additional studies are
required for the identification of catalysts and conditions that
allow catalytic AROM/CM reactions with aliphatic terminal
alkenes to deliver outcomes competitive with that of styrenyl
substrates.
1
in A (Scheme 5): the H NMR spectrum of silylated Mo-
alkylidene generated from reaction of 1a and vinyltrimethylsi-
lane exhibits an equal mixture of syn and anti isomers, whereas
that of styrene (1a) shows a 3:1 ratio.28
Three additional issues regarding the proposed intermediacy
of substituted Mo-alkylidenes represented by A and B merit
mention: (i) If the above catalytic AROM/CM reactions
involved the intermediacy of the Mo-methylidene ii (vs alky-
lidenes represented by A and B), little rate difference would be
expected between reactions with styrenes and vinylsilanes (more
on the identity of the active Mo-alkylidene, below).29 (ii) The
lower reactivity of the silylated alkylidenes may be partially
tied to delocalization of the electron density at the carbon atom
of the ModC moiety into the available empty d orbitals of the
adjacent Si atom (see below for further discussion). (iii) Another
rationale for the lower reactivity of vinylsilanes is that the
derived metal alkylidene (A) may be converted to an R,R′-
disubstituted metallacycle that can undergo a â-hydride rear-
rangement to deliver a reduced and inactive Mo(IV) complex.30
As illustrated in Scheme 6, a number of other terminal alkenes
were examined as partners in Mo-catalyzed AROM/CM pro-
cesses. Catalytic transformations of norbornyl TMS ether 15
with allylsilane 10 affords a complex mixture of products
including homometathesis adduct of 10 and meso dienes
represented by II and IV in Table 1. When the reaction is
stopped before complete consumption of the starting material,
(29) It may be suggested that the Mo-alkylidene (ii) is the active
catalyst (vs alkylidenes A or B) and the slower rate of reactions of
vinylsilanes is due to conversion of the corresponding AROM intermediate,
shown below, with a sterically more bulky terminal alkene (vs styrene).
As will be discussed later, the alkylidene intermediate W would likely afford
meso diene 57 (via metallacyclobutene Wi) instead of chiral diene 37.
Moreover, as will be described later it is unlikely that 57 is converted to
chiral nonracemic 37 through a subsequent asymmetric CM (cf. eq 3 and
Scheme 8).
The catalytic transformation of TMS ether 15 with aliphatic
vinylcyclohexane (f 39, Scheme 5) is hampered by substantial
formation of homometathesis products from the terminal olefin
substrate in addition to dienes 40 and 41 (Scheme 4). Diene 40
is the result of further CM of the initial AROM/CM product
39. The deprotected alcohol corresponding to chiral nonracemic
cyclopentane 39 is obtained in 31% isolated yield and 82% ee
(>98% trans); the unpurified mixture contains ∼40% 40 and
41. The reaction of tert-butoxy ether 19 proceeds to deliver 42
with similar levels of enantioselectivity (85% ee vs 82% ee with
15). Under identical conditions, AROM/CM product 42 is
generated more efficiently than 39 (59% vs 41% conversion
(28) Alexander, J. B.; Schrock, R. R.; Davis, W. M.; Hultzsch, K. C.;
Hoveyda, A. H.; Houser, J. H. Organometallics 2000, 19, 3700-3715.

7774 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
La et al.
Scheme 6. Ineffective Terminal Alkenes in Catalytic
AROM/CM
and vinyl boranes 46-48, may also be extended to the faster
rate of catalytic AROM/CM reactions with p-OMe styrene 4b
vs those of p-CF3 styrene 4c. With the more electron rich
terminal alkene, the corresponding Mo-alkylidene might be more
reactive, due to increased electron density at the alkylidene
carbon. In contrast, similar to complex C (cf. Scheme 6), the
electron-withdrawing CF3 group stabilizes the alkylidene and
diminishes its catalytic activity. Such rate differences are thus
more easily rationalized if the intermediacy of Mo-benzylidene
i is proposed instead of Mo-methylidene complex ii. Similar
logic was provided in relation to the lower reactivity of vinyl
silanes vs styrenes (see Scheme 5).
To gain further insight regarding the identity of the Mo-
alkylidene that is responsible for the above catalytic reactions
(see box in Scheme 1), we monitored the progress of the reaction
1
substantial amounts of undesired products can be observed in
the 400 MHz H NMR spectrum of the unpurified reaction
mixture, indicating that alternative pathways are competitive
with the formation of the desired chiral AROM/CM adduct.
of chiral Mo complex 1a with styrene by 400 MHz H NMR
1
spectroscopy. Treatment of 1a with 40 equiv of styrene 4a (to
emulate catalytic conditions) in C6D6 at 22 °C leads to
immediate release of cumyl ethylene olefin 51 (see Scheme 7)
and generation of Mo-benzylidene i (Ln ) 2,2′-di-t-Bu-4,5-
dimethylbiphen). As illustrated in Scheme 7, the dd signal at δ
5.92 corresponds to the vinylic CH of 51 and the singlet at 11.50
represents the Mo-alkylidene CH of the syn isomer of the
transition metal complex. Also illustrated in Scheme 7 is the
Mo-catalyzed reactions with acrylonitrile 45 and vinyl boranes
46 and 4731 result in <5% reaction after 12 h (5 mol % of 1a,
22 °C). A plausible rationale for this lack of reactivity may
involve the intermediacy of chiral Mo alkylidenes C and D,
where the electron density at the carbon of the ModC is
stabilized by the electron-withdrawing CN and Lewis acidic
boron-containing groups, respectively.32 Such charge delocal-
ization may thus lead to stabilization of the Mo-alkylidenes,
reducing the rate of formation of the intermediate metallacy-
clobutane. It must be noted that the above interactions do not
necessarily lead to higher Lewis acidity of the Mo center, in
turn enhancing initial catalyst-olefin association and catalytic
activity. This is because the nonbonding electrons of the N atom
of the imido ligand or diolate oxygens can donate into the Mo
d orbitals and compensate for diminished electron density at
the alkylidene carbon.33 To minimize the Lewis acidity of the
boron atoms in vinyl boranes, vinyl boronate 48 was prepared
and examined. Despite the significant occupation of the boron
p orbital by its heteroatom substituents, the terminal olefin in
48 proves to be an ineffective reaction partner as well.
1
expansion of the downfield region of the H NMR spectrum;
the minor singlet at δ 13.05 corresponds to the ModCH of the
anti isomer (3:1 syn:anti).34 We appreciate that the above
observations do not bear testimony to the identity of the more
active Mo complex. Rather, it is the indirect observations, such
as the relative reactivity of various styrenes, that are perhaps
1
more informative in that regard. The H NMR experiments
presented here simply indicate that formation of the Mo-
benzylidene complex is rapid and highly favored, providing
support for the paradigm that involves the participation of such
complexes.
Additional indirect evidence favoring the preferential involve-
ment of Mo-benzylidenes is illustrated in Scheme 8. If Mo-
methylidene ii were an active catalyst, intermediate 49 would
likely react with styrenes (e.g., 4a) to afford meso diene 41 via
molybdacyclobutane 50. The alternative mode of addition,
involving the intermediacy of metallacycle 52, would be less
favored (f AROM/CM product 16a). In the 2,4-disubstituted
molybdacyclobutane 50, the longer Mo-C bonds give rise to
less steric repulsion between the aryl and alkyl groups;
furthermore, the charge density at C of the C-Mo bond is better
stabilized by the phenyl substituent. Thus, whereas addition by
the Mo-benzylidenes and the related substituted alkylidenes
affords the catalytic AROM/CM products shown in Tables 1-3,
the meso diene byproducts IV (e.g., 41; see also Table 1) are
likely formed as a result of competitive reaction by Mo-
methylidene ii.
(f) The Identity of the Reacting Mo-alkylidene: Ben-
zylidene vs Methylidene Complex. The arguments put forth
above, in relation to the lack of reactivity of acrylonitrile 45
(30) (a) Robbins, J.; Bazan, G. C.; Murdzek, J. S.; O’Regan, M. B.;
Schrock, R. R. Organometallics 1991, 10, 2902-2907. (b) Schrock, R. R.;
Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare, M.; O’Regan, M. J.
Am. Chem. Soc. 1990, 112, 3875-3886.
It may be argued that Mo-methylidene (ii) might be an active
catalyst and meso dienes such as 41 may well be intermediates
(33) Consistent with this rationale, positioning of electron-withdrawing
groups (e.g., CF3 or halogens) at the C2 and/or C6 positions of the imido
ligand leads to enhanced catalytic activity. This is because reduction of
electron density at the Mo-centered LUMO is concomitant with lowering
of imido N Lewis basicity; Jamieson, J. Y.; Kiely, A.; Hoveyda, A. H.;
Schrock, R. R. Unpublished results. See also: Weatherhead, G. S.; Houser,
J. H.; Ford, J. G.; Jamieson, J. Y.; Schrock, R. R.; Hoveyda, A. H.
Tetrahedron Lett. 2000, 41, 9553-9559.
(34) The assignment for syn and anti Mo-alkylidene protons is based on
values previously reported for biaryl-Mo systems (vs bis(alkoxides)Mo
complexes). See: (a) Totland, K. M.; Boyd, T. J.; Lavoie, G. G.; Davis,
W. M.; Schrock, R. R. Macromolecules 1996, 29, 6114-6125. (b) O’Dell,
R.; McConville, D. H.; Hofneister, G. E.; Schrock, R. R. J. Am. Chem.
Soc. 1994, 116, 3414-3423.
(31) Vinylboranes 46-48 were prepared according to published proce-
dures: Matteson, D. S. J. Am. Chem. Soc. 1960, 82, 4228-4233.
(32) For Ru-catalyzed olefin metathesis reactions involving vinylboranes,
see: Renaud, J.; Ouellet, S. G. J. Am. Chem. Soc. 1998, 120, 7995-7996.

Ring-Opening Metathesis/Cross Metathesis Reactions
J. Am. Chem. Soc., Vol. 123, No. 32, 2001 7775
Scheme 7
Scheme 8
in the AROM/CM catalytic cycle. This paradigm would then
involve, as illustrated in eq 3, catalytic intermolecular desym-
3), we prepared benzyl ethers 54a-c shown in Scheme 9. We
reasoned that the above-mentioned reactivity difference may
involve, in part, simultaneous association of the transition metal
with the Lewis basic heteroatom and the norbornyl olefin.35 If
such a scenario is operative, subtle electronic variations, such
as those that exist in 54a-c, would manifest themselves in terms
of differential reaction rates.
As illustrated in Scheme 9, when all three benzyl ethers are
allowed to undergo asymmetric metathesis in the same vessel,
AROM/CM products are obtained in >98% ee and 71-86%
yield (>98% trans). Importantly, however, p-CF3-benzyl ether
54c reacts noticeably slower than p-OMe-benzyl ether 54a (22
°C). The rate differences obserVed are notable, particularly in
light of the fact that the aryl groups of the benzyl ethers are
separated from the C7 oxygen by a methylene unit.36
metrization of such meso dienes through an asymmetric cross-
metathesis (ACM) transformation. To address this possibility,
authentic diene 53 was prepared and treated with 5 mol % of
1a in the presence of 2 equiv of p-OMe styrene 4b to deliver
the expected AROM/CM product in the racemic form (<5%
ee). Thus, the catalytic enantioselective transformation shown
above involves an AROM rather than an asymmetric cross
metathesis.
(35) For a review of heteroatom-directed chemical reactions, see:
Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. ReV. 1993, 93, 1307-
1370.
(36) Our attempts to prepare the corresponding phenyl ethers were
successful only in the case of p-CF3-phenyl ether 25 (see entry 4, Table 2).
(g) The Effect of Substrate Lewis Basic Sites on Reactivity.
To investigate the unexpected effect of the stereochemistry of
the neighboring heteroatom on reactivity (see entry 2, Table

7776 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
La et al.
Scheme 9a
a Yields of reactions run individually (not as mixture of 54a-c). b >98% trans in all cases.
Scheme 10
Scheme 11
The above data do not preclude other factors that lead to the
rate difference observed and may be less relevant in the case
of sterically congested C7 silyl ethers. For example, it is tenable
that anti norbornyl ethers such as 30 (see Table 3) may be
rendered unreactiVe by a specific electronic factor (vs activation
of syn norbornenyl diastereomer by chelation). As illustrated
in Scheme 10, one such scenario could involve diminution of
olefin Lewis basicity as a result of donation of π electrons to
σ* C-O at C7.37 Efficient catalytic metathesis of epoxide 33
and acetal 35 (entries 4-5, Table 3) and the lack reactivity of
5638 (Scheme 10) suggest, however, that the latter issues may
not be significant and it may well be the positioning of the
heteroatom vis-a`-vis the reacting olefin that is the critical factor
to reactivity. The unfavorable hyperconjugative effects shown
in Scheme 10 can reduce reactivity, but they are likely not the
predominant reason as to why most anti tertiary ether nor-
bornenes are completely resistant to catalytic AROM/CM.
Scheme 12
Regardless of the exact origin of the rate variations depicted in
Scheme 11, these data illustrate that the steric bulk of substit-
uents that are seemingly remote from the reactive alkene site
may have a notable influence on the facility of the catalytic
AROM/CM reaction.
Examination of the data presented in Tables 1-3 reveals
reactivity trends that may shed further light on factors related
to substrate-catalyst interaction. As the results in Scheme 11
illustrate, whereas secondary ether 17 is completely consumed
in 8 min to afford optically pure 18a, catalytic AROM/CM with
tertiary ether 28 requires 50 min to proceed to completion (f
optically pure 29) and that of tertiary ether 31 proceeds to 94%
conversion after 14 h (f optically pure 32). One plausible
explanation for the observed rate differences may involve
requisite Mo-oxygen association, as shown in E and F (Scheme
11). It may be argued, however, that approach of the sterically
demanding Mo complex from the exo face of the norbornyl
alkene would cause steric strain due to enforced propinquity
between the OMOM and the C7 alkyl groups (F, Scheme 11).
(h) The Origin of Stereochemical Induction in Mo-
Catalyzed AROM/CM. A transition state model, consistent
with the stereochemical outcome of the above catalytic trans-
formations, is proposed in Scheme 12 (complex I). The approach
of the alkene occurs from the face of the transition metal
complex so that the olefin can attain maximum overlap with
the Mo-based LUMO,39 and the addition of the syn Mo complex
takes place from the exo face of norbornyl ethers. The alternative
mode of addition (II), with the anti isomer of the Mo-
benzylidene complex, would suffer from unfavorable steric
strain between the substrate and the i-Pr units at the C2 and C6
position of the imido ligand. Thus, the lower sense of enanti-
oselectivity observed in the reaction of TBS ether 11 and styrene
with the corresponding dimethyl catalyst 1b is consistent with
(37) Winstein, S.; Shatavsky, M.; Norton, C.; Woodward, R. B. J. Am.
Chem. Soc. 1955, 77, 4183-4184.
(38) Substrate 56 was prepared according to a previously reported
procedure. See: Corey, E. J.; Ravindranathan, T.; Terashima, S. J. Am.
Chem. Soc. 1971, 93, 4326-4327.

Ring-Opening Metathesis/Cross Metathesis Reactions
J. Am. Chem. Soc., Vol. 123, No. 32, 2001 7777
by chiral HPLC analysis (Chiral Technologies Chiralcel OD, Chiralpak
OJ, and Chiralpak AD (0.46 cm × 25 cm) in comparison with authentic
racemic materials. Microanalyses were performed by Robertson Microlit
Laboratories (Madison, NJ). High-resolution mass spectrometry was
performed at the University of Illinois Mass Spectrometry Laboratories
(Urbana-Champaign, IL).
All reactions were conducted in oven- (135 °C) and flame-dried
glassware under an inert atmosphere of dry argon. All metathesis
substrates were vigorously dried by repeated (3 times) azeotropic
distillation of water (benzene) under high vacuum. Handling of Mo
catalyst was done in a drybox. Benzene was distilled from sodium metal/
benzophenone ketal. CH2Cl2 was distilled from CaH2 under an
atmosphere of Ar. Mo(NAr)(CHCMe2Ph)(OTf)2‚DME,30b Mo(N-2,6-
(i-Pr)2C6H3)(CHCMe2Ph)((S)-(-)-tert-Bu2Me4(biphen)),8a and (R)-(+)-
Mo(N-2,6-(i-Pr)2C6H3)(CHMe2Ph)(3,3′-bis(2,4,6-triisopropylphenyl)-
2,2′-dihydroxy-1,1′-dinaphthyl)‚THF9 were synthesized based on
previously reported procedures.
the suggested paradigm (79% ee vs 98% ee with catalyst 1a).
The steric repulsion between the Ar group of the alkylidene
and the imido ligand substituents is minimized by the large Mod
C-C angle caused by agostic interaction between the alkylidene
C-H and Mo-N σ* orbital (Mo-C has significant triple bond
character). The latter hyperconjugative association implies
reduced Lewis acidity of the Mo center. The driving force
behind the preference for I over the more Lewis acidic II may
thus be largely steric in nature. Approach of the alkene toward
the Mo complex is consistent with the orientation of the
complex’s LUMO (front approach is blocked by the protruding
t-Bu group). The approach of the norbornene substrate, as shown
in I, allows interaction of the C7 heteroatom with the Mo-N
σ*, an antibonding orbital that is believed to be the next ranking
LUMO.40 Such an association accounts for the observed rate
differences in reactions of various benzyl ethers (Scheme 9)
and the substantial rate differences shown in entries 1-2 of
Table 3.
Representative Procedure for Mo-Catalyzed Asymmetric Ring-
Opening Metathesis/Cross Metathesis. In a drybox, substrate 15 (163
mg, 0.891 mmol) was dissolved in benzene (4.46 mL). A 1.0 M solution
of 4b in benzene (1.78 mL) was then added to the vessel followed by
the addition of optically pure catalyst 1a (6.77 mg, 9.00 × 10-3 mmol)
in one portion. A Teflon cap was secured to the vessel and the reaction
was allowed to stir at 22 °C. After 5 h, the reaction was exposed to air
and the volatiles were removed in vacuo. The dark brown residue was
purified by silica gel chromatography (60:1 hexanes:Et2O). Organic
solvents were removed to afford 16b as a colorless oil (259 mg, 92%).
(1S,2S,5R)-1-tert-Butoxy-2-styryl-5-vinylcyclopentane (20). IR
(NaCl): 3074 (w), 2968 (s), 1634 (w), 1369 (m), 1193 (m), 1092 (m)
cm-1. 1H NMR (500 MHz, CDCl3): δ 7.38 (d, J ) 7.5 Hz, 2H), 7.32
(t (br), J ) 7.5 Hz, 2H), 7.20 (t, J ) 7.0 Hz, 1H), 6.37 (dd, J ) 16.5,
7.5 Hz, 1H), 6.33 (d, J ) 16.0 Hz, 1H), 5.97 (ddd, J ) 17.5, 10.5, 9.0
Hz, 1H), 5.03-4.96 (m, 2H), 4.01 (t, J ) 4.0 Hz, 1H), 2.69 (ddd, J )
13.5, 5.0, 5.0 Hz, 1H), 2.57 (ddd, J ) 13.5, 4.0, 4.0 Hz, 1H), 1.85-
1.75 (m, 4H), 1.17 (s, 9H). 13C NMR (125 MHz, CDCl3): δ 141.4,
138.3, 133.7, 128.9, 128.7, 126.9, 126.2, 113.8, 79.1, 73.5, 50.7, 49.9,
29.9, 29.6, 29.3. HRMS calcd for C19H26O: 270.1984. Found: 270.1993.
Anal. Calcd for C19H26O: C, 84.39; H, 9.69. Found: C, 84.18; H, 9.48.
(1S,2R,3R,4S,5S)-4-tert-Butoxy-1,2-O-isopropylidene-3-styryl-5-
vinylcyclopentane (22). IR (NaCl): 3069 (w), 2980 (s), 2936 (m),
Conclusions
We have disclosed the details of our studies regarding the
first examples of catalytic asymmetric ring-opening metathesis
(AROM) reactions. The catalytic enantioselective C-C bond
cleavage (ring-opening) is followed by a C-C bond-forming
cross metathesis reaction to afford efficiently a wide range of
functionalized cyclopentanes in the optically pure form (>98%
ee) with complete control of olefin stereochemistry (>98%
trans). Products may bear either a secondary or a tertiary ether
stereogenic center, in addition to a terminal and a trans
disubstituted alkene. Considering the paucity of methods avail-
able for enantioselective synthesis of tertiary ethers and because
olefinic moieties can be further functionalized in a variety of
manners, the present protocol offers a unique catalytic approach
to optically pure materials that should serve as building blocks
for enantioselective complex molecule synthesis.
Future work includes the development of efficient catalytic
AROM/CM reactions involving other alkene substrates (instead
of norbornenes), catalytic processes that allow utilization of vinyl
boranes, and applications to complex molecule total synthesis.
1
1646 (w), 1401 (m), 1212 (s), 1086 (s) cm-1. H NMR (400 MHz,
CDCl3): δ 7.36 (d, J ) 7.2 Hz, 2H), 7.30 (t (br), J ) 7.2, 2H), 7.20
(t (br), J ) 7.2 Hz, 1H), 6.48 (d, J ) 16.0 Hz, 1H), 6.33 (dd, J ) 16.0,
8.8 Hz, 1 H), 5.97 (ddd, J ) 17.2, 10.0, 8.8 Hz, 1H), 5.17 (dd, J )
17.6, 0.4 Hz, 1H), 5.13 (ddd, J ) 10.4, 2.0, 0.8 Hz, 1H), 4.67-4.60
(m, 2H), 4.27 (t, J ) 4.6 Hz, 1H), 2.81 (ddd, J ) 9.2, 4.8, 4.8 Hz,
1H), 2.68 (ddd, J ) 9.2, 4.8, 4.8 Hz, 1H), 1.53 (s, 3H), 1.33 (s, 3H),
1.11 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 138.0, 137.7, 129.8,
129.0, 127.6, 126.6, 116.9, 113.0, 84.9, 84.5, 81.1, 74.7, 56.5, 55.7,
29.6, 28.1, 25.5. HRMS calcd for C22H30O3: 342.2195. Found:
342.2200. Anal. Calcd for C22H30O3: C, 77.16; H, 8.83. Found: C,
76.88; H, 8.58.
(1S,2R,3R,4S,5S)-4-tert-Butoxy-1,2-diacetoxy-3-styryl-5-vinylcy-
clopentane (24). IR (NaCl): 2980 (m), 1759 (s), 1388 (m), 1250 (s),
1086 (m) cm-1. 1H NMR (400 MHz, CDCl3): δ 7.36 (dd, J ) 7.6, 1.2
Hz, 2H), 7.31 (dd, J ) 7.2, 7.2 Hz, 2H), 7.21 (ddd, J ) 8.0, 8.0, 1.2
Hz, 1H), 6.41 (d, J ) 16.0 Hz, 1H), 6.27 (dd, J ) 16.0, 9.2 Hz, 1H),
5.92 (ddd, J ) 17.6, 9.2, 9.2 Hz, 1H), 5.36-5.32 (m, 2H), 5.13-5.09
(m, 2H), 4.16 (t, J ) 5.6 Hz, 1H), 2.92-2.74 (m, 2H), 2.04 (s, 3H),
2.02 (s, 3H), 1.09 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 170.9,
138.2, 137.3, 132.8, 129.6, 129.2, 128.3, 127.2, 118.1, 76.2, 75.9, 75.5,
55.0, 54.1, 30.0, 22.0. HRMS calcd for C23H30O5: 386.2093. Found:
386.2091. Anal. Calcd for C23H30O5: C, 71.48; H, 7.82. Found: C,
71.55; H, 7.57.
Experimental Section41
General. Infrared (IR) spectra were recorded on a Perkin-Elmer 781
spectrophotometer, νmax in cm-1. Bands are characterized as broad (br),
strong (s), medium (m), and weak (w). 1H NMR spectra were recorded
on Varian Gemini 2000 (400 MHz) and Varian INOVA 500 (500 MHz)
spectrometers. Chemical shifts are reported in ppm from tetramethyl-
silane with the solvent resonance as the internal standard (CDCl3: δ
7.26). Data are reported as follows: chemical shift, multiplicity (s )
singlet, d ) doublet, t ) triplet, q ) quartet, br ) broad, m ) multiplet),
coupling constants (hertz), integration. 13C NMR spectra were recorded
on Varian Gemini 2000 (100 MHz) and Varian NOVA (125 MHz)
spectrometers with complete proton decoupling. Chemical shifts are
reported in ppm from tetramethylsilane with the solvent as the internal
reference (CDCl3: δ 77.70 ppm). Enantiomer ratios were determined
(39) (a) Feldman, J.; Schrock, R. R. Prog. Inorg. Chem. 1991, 39, 1-74.
(b) Cundari, T. R.; Gordon, M. S. Organometallics 1992, 11, 55-63. (c)
Folga, E.; Ziegler, T. Organometallics 1993, 12, 325-337. (d) Fox, H. H.;
Schofield, M. H.; Schrock, R. R. Organometallics 1994, 13, 2804-2815.
(e) Schrock, R. R. Polyhedron 1995, 14, 3177-3195. (f) Wu, Y.-D.; Peng,
Z.-H. J. Am. Chem. Soc. 1997, 119, 8043-8049. (g) Schrock, R. R. Top.
Organomet. Chem. 1998, 1, 1-36. (h) Monteyne, K.; Ziegler, T. Organo-
metallics 1998, 17, 5901-5907.
(40) A crystal structure of a related W complex, obtained recently,
supports the proposed association of the Lewis basic oxygens with metal-N
σ* orbital. Hultzsch, K. C.; Hoveyda, A. H.; Schrock, R. R. Unpublished
results.
(1S,2S,5R)-1-(4-Trifluoromethylphenoxy)-2-styryl-5-vinylcyclo-
pentane (26). IR (NaCl): 3037 (w), 2968 (m), 1627 (m), 1527 (m),
1
1331 (s), 1256 (s), 1124 (s) cm-1. H NMR (400 MHz, CDCl3): δ
7.48 (d, J ) 6.8 Hz, 2H), 7.28-7.18 (m, 5H), 7.01 (d, J ) 6.8 Hz,
2H), 6.45 (d, J ) 12.8 Hz, 1H), 6.17 (dd, J ) 12.8, 6.8 Hz, 1H), 5.89
(ddd, J ) 14.0, 8.4, 6.8 Hz, 1H), 5.13 (dd, J ) 14.0, 0.8 Hz, 1H), 5.01
(dd, J ) 8.0, 1.2 Hz, 1H), 4.75 (t, J ) 2.8 Hz, 1H), 2.99-2.84 (m,
2H), 2.06-1.95 (m, 4H). 13C NMR (100 MHz, CDCl3): δ 162.7, 138.6,
(41) The spectral and analytical data for products in Table 1 and the
X-ray data for the crystal structure in Figure 1 may be found in the
Supporting Information section of ref 10.

7778 J. Am. Chem. Soc., Vol. 123, No. 32, 2001
La et al.
137.9, 131.2, 130.6, 129.0, 127.7, 127.3, 123.7, 123.0, 116.6, 116.4,
87.1, 50.8, 50.3, 30.2, 29.7. HRMS calcd for C22H21F3O: 358.1544.
Found: 358.1536. Anal. Calcd for C22H21F3O: C, 73.73; H, 5.91.
Found: C, 73.62; H, 5.73.
products (0.50 mmol total) obtained from reaction of 19 (84 mg, 0.50
mmol) with 5 mol % of 1a was combined with 2.5 mL of CH2Cl2 in
a 5 mL round-bottom flask. TMSI (93 µL, 0.65 mmol) was added
dropwise, and the reaction was allowed to stir for 45 min. At this time,
all starting material was consumed as indicated by TLC. The reaction
was then diluted with 2.5 mL of CH2Cl2 and subsequently quenched
by addition of 2 mL of ethanol. After addition of 3 mL of water, the
resulting aqueous layer was washed three times with 3 mL portions
CH2Cl2. Organic layers were combined and washed with 10 mL of a
saturated solution of sodium bicarbonate, then dried over MgSO4,
(1S,2S,5R)-1-Butyl-2-styryl-5-vinylcyclopentanol (Alcohol De-
rived from 29). To a solution of 29 (9.90 mg, 3.15 × 10-2 mmol in
0.222 mL CH2Cl2) was added an activated 4 Å molecular sieve and
the mixture was cooled to -30 °C in a dry ice/acetone bath (monitored
by external thermometer). TMSBr (16.6 µL) was then added dropwise
to the stirring solution over 1 min. The vessel was then transferred to
an ice bath and warmed to 0 °C. The reaction was stirred for 8 h and
then poured into 5 mL of a saturated solution of sodium bicarbonate.
This mixture was then washed three times with 10 mL of CH2Cl2. The
organic layers were combined, dried over MgSO4, filtered, and
concentrated by rotary evaporation. The crude product was purified
by silica gel chromatography (12:1 hexanes:diethyl ether). The organic
solvent was removed to provide (1S,2S,5R)-1-butyl-2-styryl-5-vinyl-
cyclopentanol as a colorless oil (8.49 mg, 99%). IR (NaCl): 3484 (m),
1
filtered, and concentrated by rotary evaporation. H NMR analysis of
the unpurified mixture revealed successful deprotection of all three
metathesis products. The desired product (1S,2S,5R)-2-(2-cyclohexy-
lvinyl)-5-vinylcyclopentanol was isolated by silica gel chromatography
(20:1 pentane:Et2O) in 47% yield (52 mg, 0.24 mmol) over two steps
from 19. IR (NaCl): 3452 (m), 3075 (w), 2924 (s), 2848 (m), 1445
1
(w), 1073 (w), 973 (w), 910 (w) cm-1. H NMR (400 MHz, CDCl3):
δ 6.03-5.49 (m, 1H), 5.50-5.49 (m, 2H), 5.13 (d, J ) 1.47 Hz, 1H),
5.10 (ddd, J ) 5.5, 1.8, 1.5 Hz, 1H), 3.94-3.92 (m, 1H), 2.64-2.54
(m, 2H), 1.99-1.92 (m, 1H), 1.83-1.02 (m, 14H). 13C NMR (125 MHz,
CDCl3): δ 139.6, 139.1, 127.0, 116.4, 78.6, 50.1, 49.2, 41.6, 33.9, 28.2,
27.8, 26.8, 26.7. HRMS calcd for C15H24O: 220.1827. Found: 220.1833.
Anal. Calcd for C15H24O: C, 81.76; H, 10.98. Found: C, 81.70; H,
10.87.
(1S,2S,5R)-1-(4-Methoxybenzyloxy)-2-styryl-5-vinylcyclopen-
tane (55a). 1H NMR (400 MHz, CDCl3): δ 7.36-7.20 (m, 7H), 6.83
(d, J ) 8.8 Hz, 2H), 6.42 (d, J ) 15.6 Hz, 1H), 6.37 (dd, J ) 16.0, 6.8
Hz, 1H), 6.05 (ddd, J ) 17.6, 10.0, 8.4 Hz, 1H), 5.10 (dd, J ) 17.2,
0.8 Hz, 1H), 4.53 (d, J ) 11.2 Hz, 1H), 4.46 (d, J ) 11.2 Hz, 1H),
3.83 (t, J ) 4.0 Hz, 1H), 3.78 (s, 3H), 2.79-2.60 (m, 2H), 1.91-1.82
(m, 4H). 13C NMR (100 MHz, CDCl3): δ 159.4, 140.0, 138.3, 132.2,
131.6, 130.2, 129.9, 129.0, 127.4, 115.3, 114.1, 87.7, 74.0, 55.9, 50.8,
50.0, 30.0, 29.6. HRMS calcd for C23H26O2: 334.1933. Found:
334.1925. Anal. Calcd for C23H26O2: C, 82.60; H, 7.84. Found: C,
82.49; H, 8.07.
1
2943 (s), 2873 (m), 1659 (m), 1470 (m) cm-1. H NMR (500 MHz,
CDCl3): δ 7.42-7.39 (m, 2H), 7.32 (ddd, J ) 8.0, 8.0, 2.0 Hz, 2H),
7.23 (tt, J ) 7.5, 1.5 Hz, 1H), 6.45 (d, J ) 16.0 Hz, 1H), 6.31 (dd, J
) 15.5, 8.0 Hz, 1H), 5.18 (ddd, J ) 10.5, 2.0, 0.5 Hz, 1H), 5.13 (ddd,
J ) 17.0, 2.0, 1.0 Hz, 1H), 2.65 (dd, J ) 18.0, 9.0 Hz, 1H), 2.55 (dd,
J ) 17.0, 9.0 Hz, 1H), 1.93-1.82 (m, 4H), 1.57-1.28 (m, 6H), 0.92
(t (br), J ) 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 138.3, 138.0,
132.1, 130.4, 129.0, 127.6, 126.7, 117.3, 84.1, 51.7, 51.5, 37.9, 29.1,
28.3, 27.1, 24.1, 14.9. HRMS calcd for C19H26O: 270.1984. Found:
270.1982. Anal. Calcd for C19H26O: C, 84.39; H, 9.69. Found: C,
84.60; H, 9.76.
(1S,2S,5R)-1-Methoxymethoxy-1-phenyl-2-styryl-5-vinylcyclopen-
tane (32). IR (NaCl): 3059 (m), 3025 (m), 2946 (s), 2905 (m), 2876
(m), 2829 (m), 2792 (w), 1652 (m), 1621 (m), 1494 (m), 1446 (m),
1
1306 (m), 1218 (m), 1159 (m), 1061 (s), 1023 (s), 929 (s) cm-1. H
NMR (400 MHz, CDCl3): δ 7.48-7.45 (m, 2H), 7.36-7.24 (m, 7H),
7.19 (tt, J ) 6.8, 1.6 Hz, 1H), 6.50 (dd, J ) 16.0, 8.4 Hz, 1H), 6.25 (d,
J ) 16.4 Hz, 1H), 6.10 (ddd, J ) 18.0, 10.8, 8.0 Hz, 1H), 5.04 (d, J
) 10.4 Hz, 1H), 4.96 (d, J ) 18.0 Hz, 1H,), 4.59 (dd, J ) 10.0, 6.4
Hz, 2H), 3.47 (s, 3H), 3.05 (dd, J ) 16.8, 8.4 Hz, 2H), 2.94 (dd, J )
7.2, 8.4 Hz, 2H), 2.14-1.99 (m, 2H). 13C NMR (125 MHz, CDCl3):
δ 141.1, 138.5, 138.3, 131.9, 130.4, 129.1, 128.6, 127.9, 127.7, 127.6,
126.8, 117.0, 94.1, 92.4, 56.2, 55.9, 55.2, 28.8, 28.4. HRMS calcd for
C23H26O2: 334.1933. Found: 334.1931. Anal. Calcd for C23H26O2: C,
82.60; H, 7.84. Found: C, 82.36; H, 7.62.
(1S,2S,5R)-1-(4-Benzyloxy)-2-styryl-5-vinylcyclopentane (55b). IR
1
(NaCl): 3609 (m), 2949 (s), 2873 (s), 1344 (m), 1099 (s) cm-1. H
NMR (400 MHz, CDCl3): δ 7.35-7.19 (m, 10H), 6.44 (d, J ) 16.0
Hz, 1H), 6.39 (dd, J ) 16.4, 6.8 Hz, 1H), 6.06 (ddd, J ) 17.2, 10.0,
8.8 Hz, 1H), 5.12 (dd, J ) 17.2, 1.2 Hz, 1H), 5.05 (d, J ) 10.4 Hz,
1H), 4.60 (d, J ) 11.6 Hz, 1H), 4.55 (d, J ) 12.0 Hz, 1H), 3.85 (t, J
) 4.4 Hz, 1H), 2.86-2.62 (m, 2H), 1.94-1.83 (m, 4H). 13C NMR
(100 MHz, CDCl3): δ 139.9, 139.1, 138.3, 132.1, 130.3, 129.0, 128.8,
128.3, 127.9, 127.4, 126.6, 115.4, 88.1, 74.4, 50.9, 50.1, 30.0, 29.7.
Anal. Calcd for C22H24O: C, 86.80; H, 7.95. Found: C, 86.76; H, 8.03.
(1S,2S,5R)-1-(4-Trifluoromethylbenzyloxy)-2-styryl-5-vinylcyclo-
pentane (55c). IR (NaCl): 2962 (w), 1331 (s), 1162 (m), 1136 (s)
cm-1. 1H NMR (500 MHz, CDCl3): δ 7.55 (d, J ) 7.5 Hz, 2H), 7.44
(d, J ) 8.5 Hz, 2H), 7.37-7.23 (m, 5H), 6.45 (d, J ) 15.5 Hz, 1H),
6.35 (dd, J ) 16.0, 8.5 Hz, 1H), 6.04 (ddd, J ) 17.0, 10.0, 7.5 Hz,
1H), 5.14 (ddd, J ) 17.0, 2.0, 1.0 Hz, 1H), 5.07 (dd, J ) 10.5, 2.0 Hz,
1H), 4.66 (d, J ) 12.0, 1H), 4.60 (d, J ) 12.5 Hz, 1H), 3.86 (t, J )
4.0 Hz, 1H), 2.48-2.67 (m, 2H), 1.96-1.85 (m, 4H). 13C NMR (125
MHz, CDCl3): δ 143.7, 139.7, 138.3, 131.8, 130.7, 129.2, 128.2, 127.7,
126.7, 125.8, 115.8, 88.7, 73.5, 50.7, 49.9, 29.8, 29.5. HRMS calcd
for C23H23F3O: 372.1701. Found: 372.1705. Anal. Calcd for
C23H23F3O: C, 74.18; H, 6.22. Found: C, 74.05; H, 6.44.
(3R,4S,7R)-4-Styryl-7-vinyl-1-oxaspiro[2.4]heptane (34). IR
(NaCl): 3075 (w), 3028 (m), 2966 (s), 2929 (s), 2872 (m), 1647 (w),
1
1459 (m), 974 (m), 928 (m) cm-1. H NMR (400 MHz, CDCl3): δ
7.34-7.28 (m, 4H), 7.21 (tt, J ) 7.3, 1.5 Hz, 1H), 6.33 (d, J ) 16.1
Hz, 1H), 6.02 (dd, J ) 15.6, 8.8 Hz, 1H), 5.72-5.65 (m, 1H), 5.03
(dt, J ) 4.9, 1.5 Hz, 1H), 5.00 (d, J ) 1.0 Hz, 1H), 2.83 (dd, J ) 15.1,
8.3 Hz, 1H), 2.75 (dd, J ) 6.8, 4.9 Hz, 2H), 2.70 (dd, J ) 14.6, 8.3
Hz, 1H), 2.18-2.08 (m, 2H), 1.80-1.70 (m, 2H). 13C NMR (125 MHz,
CDCl3): δ 138.6, 137.9, 131.6, 130.3, 129.2, 128.0, 126.8, 116.4, 70.4,
49.8, 48.4, 47.8, 30.8, 30.4.
(2S,5R)-1,1-Dimethoxy-2-styryl-5-vinylcyclopentane (36). IR
(NaCl): 3027 (m), 2937 (s), 2848 (m), 1703 (s), 1635 (s), 1596 (m),
1492 (m), 1449 (s), 1360 (s), 1287 (s), 1230 (s), 1155 (m), 1070 (s),
964 (s), 918 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ 7.37-7.36 (m,
2H), 7.30 (dd, J ) 7.8, 7.8 Hz, 2H), 7.20 (tt, J ) 6.8, 1.2 Hz, 1H),
6.38 (d, J ) 15.6, 1H), 6.34 (dd, J ) 15.6, 6.8, 1H), 6.01 (ddd, J )
17.6, 10.7, 8.3 Hz, 1H), 5.09-5.04 (m, 2H), 3.27 (s, 3H), 3.26 (s, 3H),
2.91 (ddd, J ) 7.3, 7.3, 4.4 Hz, 1H), 2.80 (ddd, J ) 8.3, 8.3, 4.9 Hz,
1H), 2.02-1.91 (m, 2H), 1.75-1.67 (m, 2H). 13C NMR (125 MHz,
CDCl3): δ 139.7, 138.5, 131.6, 130.6, 129.2, 127.7, 126.8, 115.4, 112.3,
51.4, 50.8, 50.6, 49.8, 30.2, 30.0. HRMS calcd for C17H22O2: 258.1620.
Found: 258.1616. Anal. Calcd for C17H22O2: C, 79.03; H, 8.58.
Found: C, 78.80; H, 8.48.
Acknowledgment. This research was generously supported
by the NIH (GM-59426) and the NSF (CHE-9905806). D.S.L.
was supported by a graduate fellowship in organic chemistry
by the American Chemical Society, sponsored by Boehringer-
Ingelheim (1998-99); E.S.S. is grateful for a Michael P. Walsh
graduate fellowship. We thank G. S. Weatherhead for many
helpful discussions.
Supporting Information Available: Experimental proce-
dures and spectral and analytical data for starting materials
(except for those in Table 1, which are found in the Supporting
Information of ref 10). This material is available free of charge
via the Internet at http//:www.acs.pubs.org.
(1S,2S,5R)-2-(2-Cyclohexylvinyl)-5-vinylcyclopentanol (Alcohol
Derived from 39 and 42). A modified procedure for deprotection of
is 42 based on literature precedent.42 An unpurified mixture of three
(42) Heck, M. P.; Monthiller, S.; Mioskowski, C.; Guidot, J. P.; Le Gall,
T. Tetrahedron Lett. 1994, 35, 5445-5448. (b) Jung, M. E.; Lyster, M. A.
J. Org. Chem. 1977 42, 3761-3764.
JA010684Q