Enantioselective synthesis of fused cycloheptadienes by a tandem intramolecular cyclopropanation/cope rearrangement sequence

Article abstract of DOI:10.1021/jo990888d

The asymmetric induction in the intramolecular cyclopropanations of allyl vinyldiazoacetates catalyzed by tetrakis[N-[4-dodecylphenyl)sulfonyl]- (S)-prolinato]dirhodium [Rh₂(S-DOSP)₄] is very dependent on the allyl substitution patte

Full text of DOI:10.1021/jo990888d

J . Org. Chem. 1999, 64, 8501-8508
8501
En a n tioselective Syn th esis of F u sed Cycloh ep ta d ien es by a
Ta n d em In tr a m olecu la r Cyclop r op a n a tion /Cop e Rea r r a n gem en t
Sequ en ce
Huw M. L. Davies* and Brian D. Doan
Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260-3000
Received J une 2, 1999
The asymmetric induction in the intramolecular cyclopropanations of allyl vinyldiazoacetates
catalyzed by tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-prolinato]dirhodium [Rh2(S-DOSP)4] is very
dependent on the allyl substitution pattern. The reactions of cis-alkenes result in much higher
asymmetric induction than trans-alkenes while the highest enantioselectivity was obtained with a
disubstituted terminal alkene. The intramolecular cyclopropanation of dienylmethyl vinyldiazo-
acetates results in the synthesis of fused cycloheptadiene ring systems with full control of relative
stereochemistry and variable enantioselectivity. The synthetic utility of this process was demon-
strated by a short synthesis of 5-epi-tremulenolide in 93% ee.
The 3 + 4 annulation between vinylcarbenoids and
dienes is a very general process for the synthesis of seven-
membered rings.1,2 Both inter- and intramolecular ver-
sions of the reaction are known, and the reaction is
applicable to a vast array of cyclic and acyclic dienes,
including furans and pyrroles.1,3 The annulation occurs
by a two-step process, cyclopropanation of the diene to
form a cis-divinylcyclopropane followed by a Cope rear-
rangement. As the Cope rearrangement of divinylcyclo-
propanes proceeds through a well-defined boat transition
state, predictable stereocontrol can be achieved at up to
three stereogenic centers in the resulting cycloheptadi-
ene.4 Recently, tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-
prolinato]dirhodium (Rh2(S-DOSP)4 (1)) has been shown
to be an excellent chiral catalyst for the intermolecular
version of these transformations such that cyclohepta-
dienes can be obtained with high asymmetric induction.5
In this paper, we describe a systematic evaluation of
Rh2(S-DOSP)4 in intramolecular cyclopropanations of
rhodium-stabilized vinylcarbenoids with alkenes and
dienes (eq 1), which have culminated in a practical
asymmetric 3 + 4 annulation strategy for the construc-
tion of fused cycloheptadienes.
very high asymmetric cyclopropanation with allyl diazo-
acetates, homoallyl diazoacetates, N-allyl diazoamides,
or N-homoallyl diazoamides.6 Various C2 copper catalysts
such as Pfaltz’ copper semicorrins, Evans’ copper bisoxa-
zolines, and Nishiyama’s ruthenium pybox have also
proven to be effective for intramolecular cyclopropanation
of diazoacetate derivatives.7,8 As kinetically active dirhod-
ium tetracarboxylates are required for effective decom-
position of vinyldiazoacetates to carbenoid intermedi-
Even though no studies have been reported on the
asymmetric intramolecular reactions between vinylcar-
benoids and alkenes, several excellent chiral catalysts
have been developed for other intramolecular carbenoid
systems. The most notable are Doyle’s dirhodium car-
boxamide catalysts such as Rh2(5S-MEPY)4, Rh2(5S-
MEOX)4, and Rh2(S-MPPIM)4, which have resulted in
(6) (a) Doyle, M. P.; Austin, R. E.; Bailey, A. S.; Dwyer, M. P.;
Dyatkin, A. B.; Kalinin, A. V.; Kwan, M. M. Y.; Liras, S.; Oalmann, C.
J .; Pieters, R. J .; Protopopova, M. N.; Raab, C. E.; Roos, G. H. P.; Zhou,
Q.; Martin, S. P. J . Am. Chem. Soc. 1995, 117, 5763. (b) Doyle, M. P.;
Austin, R. E.; Bailey, A. S.; Dwyer, M. P.; Dyatkin, A. B.; Kalinin, A.
V.; Kwan, M. M. Y.; Liras, S.; Oalmann, C. J .; et al. J . Am. Chem. Soc.
1995, 117, 5763. (c) Doyle, M. P.; Peterson, C. S.; Parker, D. L., J r.
Angew. Chem., Int. Ed. Engl. 1996, 35, 1334. (d) Doyle, M. P.; Kalinin,
A. V. J . Org. Chem. 1996, 61, 2179. (e) Doyle, M. P.; Winchester, W.
R.; Protopopova, M. N.; Kazala, A. P.; Westrum, L. J . Org. Synth. 1996,
73, 13. (h) Doyle, M. P.; Peterson, C. S.; Zhou, Q.-L.; Nishiyama, H.
Chem. Commun. (Cambridge) 1997, 211. (f) Doyle, M. P.; Protopopova,
M. N.; Poulter, C. D.; Rogers, D. H. J . Am. Chem. Soc. 1995, 117, 7281.
(g) Doyle, M. P.; Zhou, Q.-L.; Dyatkin, A. B.; Ruppar, D. A. Tetrahedron
Lett. 1995, 36, 7579. (h) Doyle, M. P.; Dyatkin, A. B.; Kalinin, A. V.;
Ruppar, D. A.; Martin, S. F.; Spaller, M. R.; Liras, S. J . Am. Chem.
Soc. 1995, 117, 11021. (i) Doyle, M. P.; Eismont, M. Y.; Protopopova,
M. N.; Kwan, M. M. Y. Tetrahedron 1994, 50, 4519. (j) Doyle, M. P.;
Pieters, R. J .; Martin, S. F.; Austin, R. E.; Oalmann, C. J .; Mueller, P.
J . Am. Chem. Soc. 1991, 113, 1423.
(1) (a) Davies, H. M. L. In Advances in Cycloaddition; Harmata, M.,
Ed.; J ai Press Inc.: Greenwich, CT, 1999; Vol. 5, p 119-164. (b) Davies,
H. M. L. Curr. Org. Chem. 1998, 2, 463.
(2) (a) Davies, H. M. L.; Clark, T. J .; D., S. H. J . Org. Chem. 1991,
56, 3817. (b) Davies, H. M. L.; Clark, T. J . Tetrahedron 1994, 50, 9883.
(c) Davies, H. M. L.; Clark, T. J .; Kimmer, G. F. J . Org. Chem. 1991,
56, 6440. (d) Cantrell, W. R., J r.; Davies, H. M. L. J . Org. Chem. 1991,
56, 723.
(3) (a) Davies, H. M. L.; Matasi, J . J .; Hodges, L. M.; Huby, N. J . S.;
Thornley, C.; Kong, N.; Houser, J . H. J . Org. Chem. 1997, 62, 1095.
(b) Davies, H. M. L.; Ahmed, G.; Churchill, M. R. J . Am. Chem. Soc.
1996, 118, 10774.
(4) Piers, E. In Comprehensive Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: Oxford, U.K., 1991; Vol. 8, pp 971-998.
(5) Davies, H. M. L.; Stafford, D. G.; Doan, B. D.; Houser, J . H. J .
Am. Chem. Soc. 1998, 120, 3326.
(7) (a) Nishiyama, H.; Aoki, K.; Itoh, H.; Iwamura, T.; Sakata, N.;
Kurihara, O.; Motoyama, Y. Chem. Lett. 1996, 1071. (b) Park, S. B.;
Murata, K.; Matsumoto, H.; Nishiyama, H. Tetrahedron Asymmetry
1995, 6, 2487.
10.1021/jo990888d CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/22/1999

8502 J . Org. Chem., Vol. 64, No. 23, 1999
Davies and Doan
Ta ble 1. Rh 2(S-DOSP )4-Ca ta lyzed Decom p osition of 2
Extension of the study to dienyl vinyldiazoacetates 4
and 5 led to some interesting differences to the reactions
of allyl vinyldiazoacetates 2. The reactions of the trans-
dienyl systems 4a -c led directly to the formation of the
fused cycloheptadienes 6a -c, presumably via the inter-
mediacy of the cis-divinylcyclopropane 7 (eq 3). The
entry diazo R1
R2
R3 cyclopropane ee, % yield, %
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
H
H
H
H
H
H
Me
Et
Pr
H
H
H
H
H
H
Me
Et
Pr
H
3a
3b
3c
3d
3e
3f
25
2
54
55
75
72
56
81
81
62
53
68
47
10
72
69
66
28
74
87
45
60
H
3ga
3h
3i
Me Me
H
Me
Me Me
Me Me Me
H
H
10
11
2j
2k
3j
3k
a
Cyclopropane was prepared using Rh2(R-DOSP)4 as catalyst
at 0 °C.
enantioselectivity in these reactions (24-50% ee) were
considerably higher than those that were obtained with
the trans-allyl derivatives 2a -c (2-25% ee). As expected,
cycloheptadienes 6a -c were formed with excellent con-
trol of relative stereochemistry due to the requirements
of the boat transition state for the Cope rearrangement
of divinylcyclopropanes.4
ates,9 the current study is focused on the use of Rh2(S-
DOSP)4 as the chiral catalyst.
To evaluate the effect of alkene and diene structure
on the asymmetric induction in intramolecular vinylcar-
benoid cyclopropanations, a series of allyl vinyldiazo-
acetates and 2,4-pentadienyl vinyldiazoacetates were
prepared as summarized in eq 2. Acid chloride (method
The reaction of the cis-dienylmethyl systems 5a -c
resulted in the formation of isolable trans-divinyl cyclo-
propanes 8a -c in 41-62% ee.13 Considerable improve-
ment in the enantioselectivity was possible if the reaction
was carried out at low temperature, but this also resulted
in a severe decrease in the yield. For example, the
reaction of 5a at -78 °C resulted in the formation of 8a
in 85% ee and 29% yield. As the trans-divinylcyclopro-
A) or DCC (method B) coupling of 4-phenyl-3-butenoic
acid with allyl or dienyl alcohols provided the requisite
esters. Conversion to the vinyldiazoacetates was readily
achieved by a diazo transfer reaction using p-acetamido-
benzenesulfonyl azide (p-ABSA) and DBU as base.10
The intramolecular cyclopropanation of the series of
allyl vinyldiazoacetates 2 was examined under the stan-
dard reaction conditions of Rh2(S-DOSP)4 in hexane at
-78 °C. The level of asymmetric induction was found to
be very dependent on the substituents around the allyl
group as summarized in Table 1. With the trans-
substituted allyl systems 2a -c, the enantioselectivity in
formation of 3a -c was very low (2-25% ee), but with
the cis-substituted allyl systems 2d -f, much higher
enantioselectivity was observed (66-73% ee).11 Moder-
ately low enantioselectivity was observed for the unsub-
stituted allyl 2g (25% ee)12 and the 3,3-disubstituted allyl
2h (47% ee),12 while the highest enantioselectivity was
observed for the methallyl system 2i (87% ee). Moderate
enantioselectivity was obtained for the more highly
substituted systems 2j (45% ee) and 2k (60% ee).
(11) Relative stereochemistry was assigned based on nOe spectral
analysis of cyclopropanes 3a ,d as shown in structures
i and ii,
respectively. Cyclopropanes 3b,c,e,f,h were assigned by analogy on
the basis of 1H NMR resonances of the lactone methylene. See the
Supporting Information for full details.
(12) The absolute stereochemistry for cyclopropane 3g was deter-
mined by conversion to iii and comparison to published results. The
absolute stereochemistry of cyclopropane 3h was determined by
conversion to isopropyl butyrolactone iv and comparison to published
results. See the Supporting Information for full details.
(8) (a) Pfaltz, A. Acta Chem. Scand. 1996, 50, 189. (b) Tokunoh, R.;
Tomiyama, H.; Sodeoka, M.; Shibasaki, M. Tetrahedron Lett. 1996,
37, 2449. (c) Sato, H. Kim, Y. S.; Shibasaki, M. Tetrahedron Lett. 1999,
40, 2973. (d) Koskinen, A. M. P. Hassila, H. Acta Chem. Scand. 1996,
50, 323. (e) Pique, C.; Fahndrich, B.; Pfaltz, A. Synlett 1995, 491. (f)
Koskinen, A. M. P.; Hassila, H. J . Org. Chem. 1993, 58, 4479.
(9) Davies, H. M. L.; Huby, N. J . S.; Cantreel, W. C., J r.; Olive, J .
L. J . Org. Chem. 1993, 58, 9468.
(10) Baum, J . S.; Shook, D. A.; Davies, H. M. L.; Smith, H. D. Synth.
Commun. 1987, 17, 1709.

Enantioselective Synthesis of Fused Cycloheptadienes
J . Org. Chem., Vol. 64, No. 23, 1999 8503
panes 8a -c do not contain functionality that would allow
a competing 1,5-homodienyl rearrangement to occur,
heating 8a -c at 140 °C leads to the smooth conversion
to the fused cycloheptadienes 6a -c, the same products
that were derived from the trans-dienyl systems 4a -c.
Presumably, this transformation occurs with the inter-
mediacy of cyclopropane 7. No change in the enantiomeric
excess occurs on conversion of trans-divinyl cyclopropanes
8a -c to fused cycloheptadienes 6a -c (eq 4).
metric induction has been found in the intramolecular
cyclopropanations of substituted allyl diazoacetates.14
To test the asymmetric influence of the catalyst, a
competition study was carried out between inter- and
intramolecular reactions by decomposition of 5c in the
presence of 10 equiv of styrene (eq 5). The intramolecular
product 8c was isolated as a minor component (8% yield)
while the intermolecular cyclopropanation product 12
was obtained in 44% yield. Conversion to the known
methyl ester 1315 and analysis revealed that the 1S,5S
isomer was the major component and the asymmetric
induction in the formation of 12 was very high (93% ee).
An example of the synthetic potential of the asym-
metric intramolecular cyclopropanation was demon-
strated by an asymmetric synthesis of 5-epi-tremuleno-
lide 14.16 It was envisioned that the three stereocenters
in 14 could be readily controlled by the tandem cyclo-
propanation/Cope rearrangement of dienyl vinyldiazo-
acetates 15a (2-trans) or 15b (2-cis) (eq 6).
The sense of asymmetric induction in these reactions
was found to be dependent on the dienyl substitution
pattern. Rh2(S-DOSP)4-catalyzed decomposition of 9,
which contains an internally substituted diene, resulted
in the formation of the fused cycloheptadiene 10 in 52%
ee (Scheme 1). The asymmetric induction in the forma-
Sch em e 1
The vinyldiazoacetates 15a ,b were prepared as out-
lined in Scheme 2. Hydrolysis of the methyl cyclopentenyl
Sch em e 2
tion of 10 was opposite to that obtained in the formation
of 6b derived from either the trans-dienylmethyl vinyl-
diazoacetate 4b or the cis-dienyl system 5b. The absolute
stereochemistry was determined by conversion of 10 and
6b to phenylsuccinic acid. The oxidative cleavage of 10
generated the S-phenylsuccinic acid ((+)-S-11) while the
oxidative cleavage of the fused cycloheptadiene 6b de-
rived from either 4b or 5b generated R-phenylsuccinic
acid ((-)-R-11). Similar change in the sense of asym-
(13) Relative stereochemistry of cyclopropanes 8a ,b was assigned
by nOe spectral analysis. Similarities in enhancement between the
two cyclopropyl protons and the styrenyl proton suggest the spacial
distances are equal and therefore the protons are oriented cis on the
cyclopropanes. The relative stereochemistry of 8c has been previously
determined (see ref 26).
acetate 16 using lithium hydroxide provided the acid 17
in 90-96% yield. Coupling of 17 with either (2E,4E) or
(2Z,4E) hexadienols (18a or 18b) provided the requisite
(14) Fox, M. E.; Li, C.; Marino, J . P.; Overman, L. E. J . Am. Chem.
Soc. 1999, 121, 5467-5480.
(15) Davies, H. M. L.; Bruzinski, P. R.; Lake, D. H.; Kong, N.; Fall,
M. J . J . Am. Chem. Soc. 1996, 118, 6897.
(16) For a preliminary report, see: Davies, H. M. L.; Doan, B. D.
Tetrahedron Lett. 1996, 37, 3967.

8504 J . Org. Chem., Vol. 64, No. 23, 1999
Davies and Doan
esters 19a or 19b, respectively, in 80-85% yields.
Conversion of 19a or 19b to the vinyldiazoacetates 15a
and 15b was accomplished in 45-55% yield using p-
ABSA and an excess of DBU at 45 °C.
The first approach was to synthesize the ring system
directly using the trans-dienyl system. Rh2(R-DOSP)4-
catalyzed decomposition of 15a in hexane at room tem-
perature resulted in the formation of the tremulane
skeleton 20 in 69% yield (eq 7). The enantioselectivity of
F igu r e 1.
the reaction, however, was low (24% ee) as expected from
the model studies. Some improvement in enantioselec-
tivity was possible by carrying out the reactions at lower
temperatures (up to 35% ee at -78 °C), but still the
overall results were not very satisfactory. Use of the cis-
dienyl system 15b, however, resulted in an improvement
of enantioselectivity. Rh2(R-DOSP)4-catalyzed decomposi-
tion of 15b in hexane at room temperature resulted in
the formation of the expected trans-divinylcyclopropane
21 in 79% yield. The trans-divinylcyclopropane 21 was
stable under ambient conditions, but on heating in
refluxing xylene, 21 underwent smooth rearrangement
to the tremulane skeleton 20 in 85% yield, presumably
though initial equilibration to a cis-divinylcyclopropane.
By this two-step process, the overall yield of 20 was
similar to that obtained from the one-step process start-
ing from the trans-diene 15a . The enantioselectivity,
however, of the two-step process from 15b was 47% ee.
Further optimization of enantioselectivity in the forma-
tion 20 was obtained by carrying out the decomposition
of 15b at progressively lower temperatures (up to 93%
ee (65% yield) at -78 °C). Completion of the synthesis of
(+)-5-epi-tremulenolide 14 was readily achieved in 76%
yield by hydrogenation of 20 using Wilkinson’s catalyst.
F igu r e 2.
tion (vide infra), the chiral influence is not as pronounced
as in the intermolecular reactions.
The sense of asymmetric induction in the intramolecu-
lar cyclopropanation reaction can be rationalized by
expanding on the model that has been developed for the
asymmetric intermolecular cyclopropanations of vinyl-
diazoacetates. In the intermolecular case, there are
several mechanistic imperatives that are believed to
account for the observed results as summarized in Figure
1.15 Rh2(S-DOSP)4 behaves as if it is D2 symmetric, and
so, only one face of the dirhodium complex needs to be
considered. The aryl sulfonyl groups (thickened vertical
lines in Figure 1) act as blocking groups. The approach
of the alkene or diene to the carbenoid occurs over the
side of the electron-withdrawing group of the carbenoid
in a side-on, nonsynchronous manner. The greater initial
bond formation on the alkene occurs at the electronically
and/or sterically more favored position. Finally, alkyl
groups on the alkene or diene will preferentially point
away from the catalyst.
When the model of Figure 1 is extended to intramo-
lecular reactions, the steric demand for formation of the
3-oxobicyclo[3.1.0]hexan-2-one must be imposed on the
transition state. This results in two different orientations
that are reasonable for approach of the alkene (or diene)
as shown in Figure 2 (for the notation Ri, Rc, and Rt, see
eq 1). Both transition states lead to the same relative
stereochemistry for the cyclopropane products. However,
cyclopropanation occurring at opposite faces of the alkene
result in the formation of either enantiomer of the
cyclopropanes, even though in both orientations the same
face of the carbenoid is exposed. The issues that govern
which transition state will be involved are dependent on
steric interference between the alkene substituents and
the catalyst and on the ability of the substituents to
Discu ssion
One notable difference between the asymmetric in-
tramolecular and intermolecular cyclopropanations of
vinyldiazoacetates is the extent of asymmetric induction.
While the intramolecular reactions occurred with moder-
ate enantioselectivity, they fall quite short of what is
typically observed in intermolecular vinylcarbenoid reac-
tions (73-99% ee). The formation of the intermolecular
cyclopropanation product 12 with high enantioselectivity
is indicative that the catalyst is effective at inducing face
selectivity in the reaction of carbenoids that contain a
dienyl ester functionality. However, due to the confor-
mational demands for the intramolecular cyclopropana-

Enantioselective Synthesis of Fused Cycloheptadienes
J . Org. Chem., Vol. 64, No. 23, 1999 8505
stabilize the partial positive charge buildup. This model
has many similarities to that proposed by Doyle to
explain the asymmetric induction for allyl diazoacetates
except the influence of charge stabilization was not
considered as an issue in the Doyle model.6,17
The absolute stereochemistry observed in the intramo-
lecular cyclopropanations of vinyldiazoacetates can be
rationalized according to Figure 2. In the case of either
the cis- or trans-allyl vinyldiazoacetates (Ri ) H), transi-
tion states A or B are equally preferred on electronic
grounds. A trans substituent does not interfere with
either transition state, and so, trans-vinyldiazoacetates
2a -c resulted in the formation of vinylcyclopropanes
3a -c with low enantioselectivity. In contrast, cis sub-
stituents would interfere in transition state B, and so cis-
vinyldiazoacetates 2d -f resulted in high asymmetric
induction in the formation of vinylcyclopropanes 3d -f.
In the case of the dienyl diazoacetates 4 and 5, transition
state A is preferred on electronic grounds for both trans-
and cis-dienyl vinyldiazoacetates. Consequently, reason-
able asymmetric induction is exhibited in the reactions
of both trans-and cis-dienyl vinyldiazoacetates 4a -c and
5a -c. The absolute stereochemistry determined for 6b
is consistent with a reaction that proceeds through
transition state A.
F igu r e 3.
with cis-olefins than with trans-olefins. Internally sub-
stituted olefins result in highly enantioselective cyclo-
propanations, but the sense of asymmetric induction is
reversed. Furthermore, use of dienes allows for the
asymmetric synthesis of fused cycloheptadiene ring
systems with excellent control of relative stereochemistry.
An internally substituted allyl vinyldiazoacetate would
strongly favor transition state B on both electronic and
steric grounds. Consequently, the reaction with 2i occurs
with very high asymmetric induction. In the case of
dienyl vinyldiazoacetate 9, structure A would direct the
internal methyl group into the catalyst, while transition
state B would accommodate the methyl substituent. The
determined absolute stereochemistry for 10 is consistent
with a reaction proceeding through transition state B.
In the case of the unubstituted allyl vinyldiazoacetate
2g, both transition state structures are viable on steric
grounds, but transition state B is better suited to stabilize
the developing positive charge. This is in agreement with
the observed absolute stereochemistry in the formation
of 3g.18 In contrast, in the reaction with dimethylallyl
derivative 2h , transition state A is better suited to
stabilize the positive charge, leading to the preferred
formation of the 1R isomer of 3h .
One final feature of these reactions is that the ther-
molysis of trans-divinylcyclopropanes to cycloheptadienes
(8a -c to 6a -c) occurs without loss of enantioselectivity.
It is generally considered that the rearrangement would
occur by homolytic ring opening of the divinylcyclopro-
pane to the diradical 22.4 Free rotation of the alkyl group
to 23 and then reclosure results in equilibration to the
cis-divinylcyclopropane 7 as illustrated in Figure 3. Even
though two stereocenters in 8 are lost in the diradical
intermediate 22, the third stereocenter is maintained by
the lactone ring and is transmitted to the newly formed
cis-divinylcyclopropane 7. Thus, the absolute stereochem-
istry in 8 is maintained through the thermolysis.
In summary, the intramolecular asymmetric cyclopro-
panation of allyl or dienylmethyl vinyldiazoacetates
catalyzed by Rh2(S-DOSP)4 occurs with higher selectivity
Exp er im en ta l Section
1H NMR spectra were run at either 200, 300, 400, or 500
MHz, and 13C NMR at either 50, 75, or 125 MHz in CDCl3
unless otherwise noted. Mass spectral determinations were
carried out at 70 eV. Melting points are uncorrected. Enanti-
oselectivities were determined either by 1H NMR using chiral
shift reagents, by GC using an Astec Chiraldex â-PH column
(20 m × 0.25 mm) or by HPLC using a Daicel OJ or OD
analytical column (25.0 × 0.46 cm, UV detection at 255 nm).
Glassware was oven-dried at >60 °C prior to use. Reactions
were carried out under an atmosphere of argon. Column
chromatography was carried out on Merck silica gel 60 (230-
400 mesh). Solvent hexanes, THF, and Et2O were distilled over
sodium with triglyme and benzophenone. Acetonitrile and
dichloromethane were distilled over calcium hydride prior to
use. Reagents were purchased from the Aldrich Chemical Co.
and used without additional purification unless noted.
(E)-4-Phenyl-3-butenoic acid,14 p-ABSA,10 Rh2(S-DOSP)4
(1),14 (E)-2-methyl-2-butenol,19 (Z)-2-butenol,20 ethyl 2,3-di-
methyl-2-butenoate,21 2,3-dimethyl-2-butenol,22 E-2,4-penta-
dien-1-ol,23 ethyl (Z)-3-iodoacrylate,24 methyl (E)-4-methyl-2,4-
pentadienoate,25 (E)-4-methyl-2,4-pentadien-1-ol,26 ethyl (Z)-
4-methyl-2,4-pentadienoate,26 (Z)-4-methyl-2,4-pentadien-1-
ol,26 ethyl (E)-2-methyl-2,4-pentadienoate,27 (E)-2-methyl-2,4-
pentadien-1-ol,27
(2E,4E)-2,4-hexadienyl
(E)-4-phenyl-3-
butenoate,26 (E)-2,4-pentadienyl (E)-4-phenyl-3-butenoate,26
(E)-4-methyl-2,4-pentadienyl (E)-4-phenyl-3-butenoate,26 (Z)-
4-methyl-2,4-pentadienyl (E)-4-phenyl-3-butenoate,26 (2E,4E)-
2,4-hexadienyl (E)-2-diazo-4-phenyl-3-butenoate (4a ),26 (E)-2,4-
pentadienyl (E)-2-diazo-4-phenyl-3-butenoate (4b),26 (E)-4-
(19) Masaki, Y.; Hashimoto, K.; Kaji, K. Tetrahedron 1984, 40, 3481.
(20) Gore, W. E.; Pearce, G. T.; Silverstein, R. M. J . Org. Chem.
1975, 40, 1705.
(21) Ceccherelli, P.; Curini, M.; Marcotullio, M. C.; Rosati, O. Synth.
Commun. 1991, 17.
(22) Dang, H.; Davies, A. G.; Davidson, I. G. E.; Schiesser, C. H. J .
Org. Chem. 1990, 55, 1432.
(23) Hudlicky, T.; Reddy, D. B.; Govindan, S. V. J . J . Org. Chem.
1983, 48, 3422.
(24) Marek, I.; Meyer, C.; Normant, J . Org. Synth. 1996, 74, 914.
(25) Rodriguez, J .; Waegel, B. Synthesis 1988, 534.
(26) Davies, H. M. L.; McAfee, M. J .; Oldenburg, C. E. M. J . Org.
Chem. 1989, 54, 930.
(17) (a) Doyle, M. P.; Forbes, D. C. Chem. Rev. 1998, 98, 911. (b)
Doyle, M. P.; McKervey, M. A.; Ye, T. In Modern Catalytic Methods
for Organic Synthesis with Diazo Compounds; Wiley-Interscience: New
York, 1998; pp 238-279.
(18) Because cyclopropane 3g was formed using the enantiomer of
1 (Rh2(R-DOSP)4), the absolute stereochemistry depicted for iii, is
opposite to that predicted using transition state B of Figure 2.
(27) Piers, E.; J ung, G. L.; Ruediger, E. H. Can. J . Chem. 1987, 65,
670.

8506 J . Org. Chem., Vol. 64, No. 23, 1999
Davies and Doan
methyl-2,4-pentadienyl (E)-2-diazo-4-phenyl-3-butenoate (4c),26
(Z)-4-methyl-2,4-pentadienyl (E)-4-phenyl-3-butenoate (5c),26
and methyl 4,4-dimethyl-1-cyclopentyl acetate (15)28 were
prepared according to literature procedures. (Z)-3-iodo-2-
propen-1-ol29 was prepared by reduction of the corresponding
ester, and (Z)-2,4-pentadien-1-ol30 was prepared by Stille
coupling.31
diazo-4-phenyl-3-butenoate as a red oil: IR (neat) 3023, 2098,
1
1700 cm-1; H NMR (500 MHz) δ 7.36-7.27 (m, 4 H), 7.21-
7.16 (m, 1 H), 6.47 (d, 1 H, J ) 16.0 Hz), 6.19 (d, 1 H, J ) 16.0
Hz), 5.95 (ddt, 1 H, 17.5, 10.5, 6.0 Hz), 5.34 (dd, 1 H, J ) 17.5,
2.0 Hz), 5.26 (dd, 1 H, J ) 10.5, 2.0 Hz), 4.74 (d, 2 H, 6.0 Hz).
The spectral data were consistent with published results.32 The
vinyldiazoacetates are generally not of sufficient stability to
obtain elemental analysis.
Ester Syn th esis, Gen er a l P r oced u r e: 2-P r op en yl (E)-
4-P h en yl-3-bu ten oa te. Meth od A. Oxalyl chloride (4.83 mL,
54.8 mmol) was added neat to a mixture of (E)-4-phenyl-3-
butenoic acid (8.12 g, 50.1 mmol) in CH2Cl2 (50 mL) at 0 °C
that was vented through a drying tube (CaSO4). The mixture
was stirred 6 h, and then the solvent and excess oxalyl chloride
were removed by distillation under reduced pressure. The
resulting solid acid chloride was dried in vacuo and then
dissolved in CH2Cl2 (30 mL). This acid chloride solution was
added by cannula to a mixture of allyl alcohol (3.6 g, 53 mmol),
pyridine (4.5 mL, 55 mmol), and DMAP (2.45 g, 20.1 mmol) in
CH2Cl2 (50 mL) at 0 °C. The resulting mixture was stirred
overnight, and then saturated NaHCO3 was added. The
organics were extracted using Et2O, and the organic layer was
rinsed with saturated NaHCO3 (2×) and then with saturated
NaCl. The organic layer was concentrated under reduced
pressure to give a yellow oil. Purification by silica gel column
chromatography (petroleum ether/Et2O, 4:1, Rf ) 0.47) gave
7.75 g (76%) of 2-propenyl (E)-4-phenyl-3-butenoate as a
slightly yellow oil: 1H NMR (300 MHz) δ 7.40-7.20 (m, 5 H),
6.52 (d, 1 H, J ) 15.9 Hz), 6.32 (dt, 1 H, 15.9, 7.2 Hz), 5.94
(ddt, 1 H, J ) 17.2, 10.3, 5.9 Hz), 5.35 (dd, 1 H, J ) 17.2, 1.5
Hz), 5.25 (dd, 1 H, J ) 10.3, 1.5 Hz), 4.62, (d, 1 H, J ) 5.9
Hz), 3.29 (d, 1 H, J ) 7.2 Hz); consistent with published
results.32
3-Meth yl-2-bu ten yl (E)-4-P h en yl-3-bu ten oa te. Meth od
B. A solution of DCC in CH2Cl2 (1.0 M, 2.6 mL, 2.6 mmol)
was added to a mixture of 3-methyl-2-butenol (0.20 g, 2.5
mmol), (E)-4-phenyl-3-butenoic acid (0.40 g, 2.5 mmol), and
DMAP (30 mg, 0.24 mmol) in CH2Cl2 (5 mL) at 0 °C. The
mixture was stirred 8 h, and then saturated NaHCO3 and Et2O
were added. The mixture was filtered (paper, vacuum), and
the filtrate was extracted using Et2O. The organic layer was
concentrated under reduced pressure to give a yellow oil.
Purification by silica gel column chromatography (petroleum
ether/Et2O, 10:1, Rf ) 0.34) gave 0.57 g (88%) of 3-methyl-2-
butenyl (E)-4-phenyl-3-butenoate as a clear, colorless oil: IR
(neat) 3022, 2981, 2939, 1739, 1496 cm-1; 1H NMR (500 MHz)
δ 7.35 (d, 2 H, J ) 7.0 Hz), 7.29 (dd, 2 H, J ) 8.1, 7.6 Hz),
7.23-7.18 (m, 1 H), 6.47 (d, 1 H, J ) 16.2 Hz), 6.29 (dt, 1 H,
J ) 16.2, 7.1 Hz), 5.34 (m, 1 H), 4.60 (d, 2 H, J ) 7.6 Hz), 3.23
(d, 2 H, J ) 7.1 Hz), 1.75 (s, 3 H), 1.70 (s, 3 H); 13C NMR (75
MHz DEPT) δ 171.4 (4°), 139.0 (4°), 136.7 (4°), 133.2 (3°), 128.4
(3°), 127.4 (3°), 126.1 (3°), 121.7 (3°), 118.4 (3°), 61.5 (2°), 38.2
(2°), 25.6 (1°), 17.8 (1°). Anal. Calcd for C15H18O2: C, 78.23;
H, 7.88. Found: C, 78.16; H, 7.83.
(1â,5r,6â)-6-Meth yl-1-(2-p h en yleth en yl)-3-oxa bicyclo-
[3.1.0]h exa n -2-on e (3a ). Gen er a l P r oced u r e. A solution of
2a (212.3 mg, 0.8762 mmol) in hexane (15 mL) was added via
cannula to a solution of 1 (25 mg, 1.3 × 10-2 mmol) in hexane
(15 mL) at -78 °C. The mixture was stirred cold 24 h then
slowly warmed to RT (room temperature). The mixture was
concentrated under reduced pressure. Purification by silica gel
column chromatography (petroleum ether/Et2O, 1:1, Rf ) 0.30)
gave 101.0 mg (54%) of 3a as a white solid (mp 66-71 °C),
25% ee (determined by HPLC: OD column, 10% i-Pr-OH in
hexanes, 1.0 mL/min; tR ) 13.5 min (major), 16.8 min (minor)).
[R]25 ) 71° (c 4.24, CHCl3). Reaction at RT, 18% ee. IR
D
(KBr): 3058, 2991, 2960, 1760 cm-1. H NMR (500 MHz): δ
1
7.39 (d, 2 H, J ) 7.5 Hz), 7.13 (dd, 2 H, J ) 7.5, 7.5 Hz), 7.25-
7.22 (m, 1 H), 6.60 (d, 1 H, J ) 16.5 Hz), 6.39 (d, 1 H, J ) 16.5
Hz), 4.31 (dd, 1 H, J ) 9.0, 4.5 Hz), 4.26 (d, 1 H, J ) 9.0 Hz),
2.19 (dd, 1 H, J ) 4.5, 4.5 Hz), 1.49 (dq, 1 H, J ) 6.0, 4.5 Hz),
1.16 (d, 3 H, J ) 6.0 Hz). 13C NMR (75 MHz DEPT): δ 176.2
(4°), 136.4 (4°), 133.4 (3°), 128.6 (3°), 127.7 (3°), 126.2 (3°), 119.1
(3°), 68.0 (2°), 34.1 (4°), 29.5 (3°), 27.6 (3°), 12.0 (1°). MS [m/z
(relative intensity)]: 214 (82), 157 (63), 155 (49), 141 (84), 129
(98), 115 (100), 91 (51), 77 (47), 63 (29), 51 (37). HRMS calcd
for C14H14O2, 214.0994, found 214.0998.
(2Z,4E)-2,4-Hexa d ien yl (E)-4-P h en yl-3-bu ten oa te. Gen -
er a l P r oced u r e. A solution of DCC in CH2Cl2 (1.0 M, 5.4 mL,
5.4 mmol) was added dropwise via syringe to a mixture of
(2Z,4E)-2,4-hexadien-1-ol (0.50 g, 0.0051 mol), (E)-4-phenyl-
3-butenoic acid (0.86 g, 0.0053 mol), and DMAP (60 mg, 0.49
mmol) in CH2Cl2 (6 mL) at 0 °C. The mixture was stirred 8 h,
and then saturated NaHCO3 and Et2O were added. The
mixture was filtered (paper, vacuum), and the filtrate was
extracted using Et2O. The organic layer was concentrated
under reduced pressure to give a yellow oil. Purification by
silica gel column chromatography (petroleum ether/Et2O, 10:
1, Rf ) 0.33) gave 1.02 g (83%) of (2Z,4E)-2,4-hexadienyl (E)-
4-phenyl-3-butenoate as a clear, yellow-tinted oil: IR (neat)
3029, 2912, 1731, 1655 cm-1; 1H NMR (300 MHz) δ 7.45-7.27
(m, 4 H), 7.25-7.19 (m, 1 H), 6.49 (d, 1 H, J ) 16.2 Hz), 6.34-
6.27 (m, 2 H), 6.17 (dd, 1 H, J ) 11.1, 10.5 Hz), 5.82 (dq, 1 H,
J ) 14.6, 6.9 Hz), 5.44 (dt, 1 H, J ) 10.5, 7.2), 4.79 (d, 2 H, J
) 6.9 Hz), 3.26 (d, 2 H, J ) 7.2 Hz), 1.80 (d, 3 H, J ) 6.9 Hz);
13C NMR (75 MHz DEPT) δ 171.3 (4°), 136.7 (4°), 133.3 (3°),
133.2 (3°), 132.8 (3°), 128.4 (3°), 127.4 (3°), 126.1 (3°), 125.9
(3°), 121.5 (3°), 121.2 (3°), 60.6 (2°), 38.2 (2°), 18.7 (1°). Anal.
Calcd for C16H18O2: C, 79.31; H, 7.49. Found: C, 79.21; H,
7.54.
2-P r open yl (E)-2-Diazo-4-ph en yl-3-bu ten oate (2g). Gen -
er a l P r oced u r e. A solution of DBU (2.25 g, 14.8 mmol) in
CH3CN (10 mL) was added via cannula to a mixture of
2-propenyl (E)-4-phenyl-3-butenoate (2.5 g, 12 mmol) and
p-ABSA (3.11 g, 12.9 mmol) in CH3CN (40 mL) at 0 °C. The
resulting red mixture was stirred 4 h, and then saturated
NH4Cl was added. The organics were extracted using Et2O and
then concentrated under reduced pressure. The resulting solid
was triturated (petroleum ether/Et2O, 1:1) and the solid
removed by filtration (Celite, vacuum). The resulting filtrate
was concentrated under reduced pressure to give a red oil.
Purification by silica gel column chromatography (pentane/
Et2O, 1:1, Rf ) 0.55) gave 2.15 g (76%) of 2-propenyl (E)-2-
(2Z,4E )-2,4-H e x a d ie n y l
(E )-2-D ia zo -4-p h e n y l-3-
bu ten oa te (5a ). Gen er a l P r oced u r e. A solution of DBU
(0.77 g, 0.0051 mol) in CH3CN (20 mL) was added via syringe
to a mixture of (2Z,4E)-2,4-hexadienyl (E)-4-phenyl-3-butenoate
(1.02 g, 0.00421 mol) and p-ABSA (1.06 g, 0.00442 mol) in
CH3CN (40 mL) at 0 °C. The resulting orange mixture was
stirred 12 h, and then saturated NH4Cl was added. The
organics were extracted using Et2O, and then the organics
were concentrated under reduced pressure to give an orange
oil. This gum was triturated (petroleum ether/Et2O, 1:1) and
filtered (Celite, vacuum). The filtrate was concentrated under
reduced pressure to give an orange oil. Purification by silica
gel column chromatography (petroleum ether/Et2O, 10:1, Rf
) 0.29) gave 0.742 g (66%) of 5a as a viscous, orange oil: IR
(neat) 3023, 2962, 2077, 1701, 1630 cm-1; 1H NMR (400 MHz)
δ 7.36-7.27 (m, 4 H), 7.21-7.15 (1 H), 6.47 (d, 1 H, J ) 16.0
Hz), 6.38 (dd, 1 H, J ) 14.8, 11.1 Hz), 6.17 (d, 1 H, J ) 16.0
Hz), 6.16 (dd, 1 H, J ) 11.1, 10.8 Hz), 5.81 (dq, 1 H, J ) 14.8,
6.8 Hz), 5.41 (dt, 1 H, J ) 10.8, 7.6 Hz), 4.88 (d, 2 H, J ) 7.6
Hz), 1.80 (d, 1 H, J ) 6.8 Hz); 13C NMR (75 MHz DEPT) δ
165.1 (4°), 136.8 (4°), 133.5 (3°), 133.2 (3°), 128.6 (3°), 127.0
(28) Davies, H. M. L.; Doan, B. D. J . Org. Chem. 1998, 63, 657.
(29) J ung, M. E.; Light, L. A. Tetrahedron Lett. 1982, 23, 3851.
(30) Margot, C.; Rizzolio, M.; Schlosser, M. Tetrahedron 1990, 46,
2411.
(31) Stille, J . K.; Groh, B. L. J . Am. Chem. Soc. 1987, 109, 813.
(32) Hutcheson, D. K. M.S. Thesis, Wake Forest University, 1993.
(33) Pirrung, M. C.; Dunlap, S. E.; Trinks, U. P. Helv. Chim. Acta
1989, 72, 1301.
(34) Koch, S. S. C.; Chamberlin, A. R. J . Org. Chem. 1993, 58, 2725.

Enantioselective Synthesis of Fused Cycloheptadienes
J . Org. Chem., Vol. 64, No. 23, 1999 8507
(3°), 125.9 (3°), 125.8 (3°), 122.9 (3°), 121.0 (3°), 111.3 (3°), 61.1
(2°), 18.3 1°).
(4°), 22.8 (1°), 18.5 (2°). HRMS calcd for C18H15O2 (M - C6H9),
263.1072, found 263.1080. HRMS calcd for C6H9 (M - C18H15O2),
81.0704, found 81.0710.
(1â,5r,6r)-6-((E )-P r o p e n y l)-1-(2-p h e n y le t h e n y l)-3-
oxa bicyclo[3.1.0]h exa n -2-on e (8a ). Gen er a l P r oced u r e.
A solution of 5a (151 mg, 0.562 mmol) in hexane (50 mL) was
added over 1 h via cannula to a mixture of 1 (13.0 mg, 0.69 ×
10-2 mmol) in hexane (50 mL) at RT. The mixture was stirred
1 h, and then toluene (ca. 2 mL) was added and the mixture
concentrated to ca. 2 mL volume under reduced pressure.
Purification by silica gel column chromatography (petroleum
ether/Et2O, 3:1, Rf ) 0.23) gave 105.3 mg (78%) of 8a as a clear
gum, 62% ee (determined by HPLC: OD column, 10% i-Pr-
OH in hexanes, 1 mL/min; tR ) 14.0 min (major), 16.2 min
(minor)). Enantioselectivites at other temperatures: 0 °C, 73%
(1S,2S)-Met h yl 2â-P h en yl-1â-((E)-2-p h en ylet h en yl)-
cyclop r op a n e-1r-ca r boxyla te (13).9,14 A solution of 12 (55.3
mg, 0.161 mmol) in anhydrous methanol (1.0 mL) was added
to a mixture of sodium methoxide (69.4 mg, 1.28 mmol) in
anhydrous methanol (1.0 mL) at 0 °C. The mixture was stirred
4 h, and then saturated NH4Cl was added. The organics were
extracted using Et2O, and the organic layer was concentrated
under reduced pressure to give a wet oil. Purification by silica
gel column chromatography (petroleum ether/Et2O, 10:1, Rf
) 0.23) gave 40.2 mg (90%) of 139,14 as a white solid (mp 72-
76 °C), 93% ee (determined by HPLC: OJ column, 1.5% i-Pr-
OH in hexanes, 1.0 mL/min; tR ) 18.1 min (major), 24.8 min
(minor)).
ee (52% yield) [R]25 ) 15° (c 3.75, CHCl3); -40 °C, 78% ee
D
(39% yield); -78 °C, 85% ee (29% yield). IR (neat): 3027, 2965,
1
2903, 1755 cm-1. H NMR (500 MHz): δ 7.34 (d, 2 H, J ) 7.5
(-)-(R)-P h en ylsu ccin ic Acid (R-11).35 A mixture of 6b
(391.1 mg, 1.728 mmol, ca. 56% ee) in anhydrous methanol
(30 mL) was purged with ozone for 20 min. The resulting deep-
blue mixture was purged with oxygen until the color had
dissipated. The mixture was warmed to RT and then was
concentrated under reduced pressure. Formic acid (3.0 mL)
was added and the mixture cooled. Hydrogen peroxide solution
(1.5 mL, 26 mmol, 30% solution in water) was added and the
mixture stirred 2 h at RT. The mixture was heated to reflux
for 1 h. Additional formic acid (2 mL) was added and the
mixture heated to reflux until a peroxide test (water/AcOH/
NaI) was negative. The mixture was cooled to RT, and water
(4 mL) was added. The organics were extracted using EtOAc
and then were concentrated under reduced pressure. The
resulting oil was dried in vacuo to give a gum. This gum was
triturated using CHCl3 and pentane to give a white solid.
Solvent was removed by pipet and the solid dried in vacuo to
give 10.9 mg (10%) of (-)-R-11 as a white solid (mp 153-157
°C). [R]25D ) -112° ( 1 (c 0.545, acetone) (lit. value, S isomer:
Hz), 7.29 (dd, 2 H, J ) 8.0, 7.5 Hz), 7.31-7.19 (m, 1 H), 6.53
(d, 1 H, J ) 16.5 Hz), 6.43 (d, 1 H, J ) 16.5 Hz), 5.88 (dq, 1 H,
J ) 15.0, 6.5 Hz), 5.19 (ddq, 1 H, J ) 15.0, 8.5, 1.5 Hz), 4.45
(dd, 1 H, J ) 10.0, 5.5 Hz), 4.25 (d, 1 H, J ) 10.0 Hz), 2.66
(dd, 1 H, J ) 8.0, 5.0 Hz), 2.28 (dd, 1 H, J ) 8.5, 8.0 Hz), 1.72
(dd, 3 H, J ) 6.5, 1.5 Hz). 13C NMR (75 MHz DEPT): δ 173.8
(4°), 136.4 (4°), 132.7 (3°), 130.0 (3°), 128.6 (3°), 127.7 (3°), 126.2
(3°), 123.2 (3°), 121.1 (3°), 65.12 (2°), 36.03 (4°), 35.7 (3°), 31.0
(3°), 18.3 (1°). HRMS calcd for C16H16O2, 240.1150, found
240.1152.
(3a r,6r,7r)]-3,3a ,6,7-Tet r a h yd r o-6-m et h yl-7-p h en yl-
1H-cycloh ep ta [c]-fu r a n -1-on e (6a ). Gen er a l P r oced u r e.
Th er m olysis. A solution of 8a (58.8 mg, 0.240 mmol (73% ee))
in o-xylene (2 mL) was heated to 140 °C for 20 min. The
mixture was cooled to RT, and then charcoal and pentane (2
mL) were added. The mixture was stirred 10 min and then
filtered (florisil, Celite). The filtrate was concentrated under
reduced pressure and then dried in vacuo to give 54.3 mg (92%)
of 6a as a white solid (mp 85-94 °C), 73% ee (determined by
HPLC: OD column, 10% i-Pr-OH in hexanes, 1.0 mL/min; tR
) 13.4 min (major), 19.4 min (minor)): [R]25D ) -110° (c 2.50,
CHCl3); 1H NMR (500 MHz) δ 7.29-7.23 (m, 3 H), 7.16 (dd, 2
H, J ) 7.5, 1.5 Hz), 6.92 (dd, 1 H, J ) 4.5, 3.5 Hz), 5.68 (br d,
1 H, J ) 9.5 Hz), 5.36 (ddd, 1 H, J ) 9.5, 6.0, 2.5 Hz), 4.66
(dd, 1 H, J ) 9.5, 9.0 Hz), 4.22 (m, 1 H), 4.09 (dd, 1 H, J ) 9.0,
9.0 Hz), 3.68 (m, 1 H), 3.16 (m, 1 H), 0.99 (d, 3 H, J ) 7.0 Hz);
consistent with published results.26
Dir ect Syn th esis. A solution of 4a (258.0 mg, 0.9616 mmol)
in hexane (25 mL) was added dropwise over 20 min to a
mixture of 1 (27.2 mg, 1.44 × 10-2 mmol) in hexane (25 mL)
at RT. Toluene (ca. 1 mL) and CH2Cl2 (ca. 5 mL) were added,
and the mixture was concentrated to ca. 3 mL volume under
reduced pressure. Purification by silica gel column chroma-
tography (petroleum ether/Et2O, 1:1, Rf ) 0.15) gave 170.4 mg
(74%) of 6a as a white solid, 24% ee (determined by HPLC:
OD column, 10% i-Pr-OH in hexanes, 1.0 mL/min; tR ) 13.7
min (major), 18.6 min (minor)).
[R]25 ) +171.4° ( 1 (c 1.0, acetone)).35
D
(+)-(S)-P h en ylsu ccin ic a cid ((+)-S-11).35 Using the above
procedure and 10 (279 mg, 1.16 mmol, ca. 50% ee), 46.1 mg
(21%) of (+)-S-11 was obtained as a tan solid (mp 138-140
°C). [R]25 ) 58° ( 1 (c 1.45, acetone) (lit. value, S isomer:
D
[R]25 ) +171.4° ( 1 (c 1.0, acetone)).35
D
4,4-Dim eth yl-1-cyclop en tyla cetic a cid (17). A mixture
of 16 (4.28 g, 0.0254 mol) in a methanol/water solution (3:1,
11 mL) was added to a mixture of anhydrous LiOH‚H2O (2.13
g, 0.0509 mol) in a methanol/water solution (3:1, 31 mL) cooled
to 0 °C. The mixture was stirred 14 h and then was diluted
with water (60 mL). The mixture was rinsed with CH2Cl2 (20
mL), and the organic layer was discarded. The aqueous
solution was acidified to pH 2 using HCl solution (1.0 M, 54
mL). The organics were extracted using Et2O and then were
dried (Na2SO4). The organic layer was concentrated under
reduced pressure then dried in vacuo to give 3.78 g (96%) of
1
17 as an amber oil: IR (neat) 3142 (br), 1708 cm-1; H NMR
(300 MHz) δ 10.45-10.10 (br s, 1H), 5.40 (s, 1 H), 3.06 (s, 2
H), 2.12 (br s, 4 H), 1.05 (s, 6 H); 13C NMR (75 MHz) δ 178.6,
135.2, 128.0, 50.4, 48.0, 39.1, 37.5, 30.1, 28.5. Anal. Calcd for
C9H14O2: C, 70.10; H, 9.15. Found: C, 70.16; H, 9.20.
(2E,4E)-2,4-Hexa d ien yl 4,4-Dim eth yl-1-cyclop en ten yl-
a ceta te (19a ). Meth od A. Purification by silica gel column
chromatography (petroleum ether/Et2O, 4:1, Rf ) 0.53) gave
2.97 g (82%) of 19a as a clear, colorless oil: IR (neat) 2939,
1742 cm-1; 1H NMR (300 MHz) δ 6.22 (dd, 1 H, J ) 15.2, 10.4
Hz), 6.02 (dd, 1 H, J ) 15.0, 10.4 Hz), 5.72 (dq, 1 H, J ) 14.9,
6.8 Hz), 5.59 (dt, 1 H, J ) 15.2, 6.6 Hz), 5.38 (s, 1 H) 4.55 (d,
2 H, J ) 6.8 Hz), 3.05 (s, 2 H), 2.10 (br s, 4 H), 1.72 (d, 3 H, J
) 6.6 Hz), 1.04 (s, 6 H); 13C NMR (75 MHz APT) δ 171.1 (4°),
135.2 (4°), 134.9 (3°), 131.0 (3°), 130.6 (3°), 126.9 (3°), 123.9
(3°), 64.7 (2°), 49.9 (2°), 47.5 (2°), 38.5 (4°), 37.0 (2°), 29.5 (1°),
17.7 (1°). Anal. Calcd for C15H22O2: C, 76.88; H, 9.46. Found:
C, 76.75; H, 9.43.
(1S,2S)-(Z)-4-Meth yl-2,4-p en ta d ien yl 2â-P h en yl-1â-((E)-
2-p h en ylet h en yl)cyclop r op a n e-1r-ca r b oxyla t e (12). A
cooled (0 °C) solution of 5c (130.3 mg, 0.485 mmol) in hexane
(30 mL) was added dropwise via cannula over 45 min to a
mixture of 1 (18 mg, 9.5 × 10-3 mmol) and styrene (0.56 mL,
4.8 mmol) in hexane (25 mL) at 0 °C. The mixture was warmed
to RT and then was concentrated to ca. 1 mL volume under
reduced pressure to give a green oil. Purification by silica gel
column chromatography (petroleum ether/Et2O, 10:1 (300 mL)
and then petroleum ether/Et2O, 2:1, Rf ) 0.35 (petroleum
ether/Et2O, 10:1)) gave 72.5 mg (44%) of 12 as a gum (9.1 mg
of 8c (8% yield) was also isolated from this reaction): IR (neat)
3032, 2970, 1718, 1604 cm-1; 1H NMR (300 MHz) δ 7.35-7.15
(m, 10 H), 6.39 (d, 1 H, J ) 16.2 Hz), 6.17 (d, 1 H, J ) 16.2
Hz), 6.07 (br d, 1 H, J ) 11.7 Hz), 5.61 (dt, 1 H, J ) 11.7, 6.3
Hz), 5.08 (br s, 1 H), 4.92 (m, 2 H), 4.85 (br s, 1 H), 3.04 (dd,
1 H, J ) 9.0, 7.5 Hz), 2.06 (dd, 1 H, J ) 9.0, 5.0 Hz), 1.90 (s,
3 H), 1.85 (dd, 1 H, J ) 7.5, 5.0 Hz); 13C NMR (75 MHz DEPT)
δ 173.5 (4°), 140.6 (4°), 137.1 (4°), 135.5 (4°), 134.7 (3°), 132.9
(3°), 129.1 (3°), 128.3 (3°), 128.0 (3°), 127.3 (3°), 126.8 (3°), 126.2
(3°), 124.9 (3°), 124.1 (3°), 117.1 (2°), 62.2 (2°), 35.0 (3°), 33.3
(2Z,4E)-2,4-Hexa d ien yl 4,4-Dim eth yl-1-cyclop en ten yl-
a ceta te (19b). Meth od B. Purification by silica gel column
(35) Krause, H.; Sailer, C. J . Organomet. Chem. 1992, 423, 271.

8508 J . Org. Chem., Vol. 64, No. 23, 1999
Davies and Doan
chromatography (petroleum ether/Et2O, 10:1, Rf ) 0.51) gave
550 mg (90%) of 19b as a clear, colorless oil: IR (neat) 2950,
1.07 (s, 3 H), 1.06 (s, 3 H). 13C NMR (75 MHz DEPT): δ 174.0
(4°), 135.0 (4°), 132.0 (3°), 126.9 (3°), 121.5 (3°), 65.0 (2°), 48.0
(2°), 47.7 (2°), 38.2 (4°), 35.3 (4°), 30.8 (3°), 29.7 (1°), 29.7 (3°),
29.6 (1°), 18.2 (1°). HRMS calcd for C15H20O2, 232.1463, found
232.1466.
1
1749 cm-1; H NMR (300 MHz) δ 6.3 (dd, 1 H, J ) 13.8, 11.1
Hz), 6.15 (dd, 1 H, J ) 11.1, 10.6 Hz), 5.81 (dq, 1 H, J ) 13.8,
6.6 Hz), 5.42 (s, 1 H), 5.40 (dt, 1 H, J ) 10.6, 7.1 Hz), 4.73 (d,
2 H, J ) 7.1 Hz), 3.09 (s, 2 H), 2.14 (br s, 4 H), 1.80 (d, 3 H, J
) 6.6), 1.08 (s, 6 H); 13C NMR (75 MHz APT) δ 171.6 (4°), 135.3
(4°), 133.3 (3°), 132.8 (3°), 127.1 (3°), 126.3 (3°), 121.6 (3°), 60.4
(2°), 50.0 (2°), 47.6 (2°), 38.6 (4°), 37.1 (2°), 29.6 (1°), 18.0 (1°).
Anal. Calcd for C15H22O2: C, 76.88; H, 9.46. Found: C, 76.83;
H, 9.51.
(3a r,6â,6a r)]-6,8,8-Tr im eth yl-3a ,6,6a ,7,8,9-h exa h yd r o-
a zu len o[4,5-c]fu r a n -1(3H)-on e (20). Th er m olysis. A solu-
tion of 21 (62.8 mg, 0.272 mg) in o-xylene (2 mL) was heated
to 140 °C for 45 min. The mixture was cooled to RT, and then
charcoal and pentane (2 mL) were added. The mixture was
stirred 10 min and then filtered (florisil, Celite). The filtrate
was concentrated under reduced pressure then dried in vacuo
to give a yellow gum. Purification by silica gel column
chromatography (petroleum ether/Et2O, 4:1, Rf ) 0.29) gave
46.3 mg (73%) of 20 as a white solid (mp 96-100 °C), 93% ee
(determined by HPLC: OJ column, 0.5% i-Pr-OH in hexanes,
(2E,4E)-2,4-Hexa d ien yl 4,4-Dim eth yl-1-cyclop en ten yl-
1-d ia zoa ceta te (15a ). A solution of DBU (5.8 g, 0.038 mol)
in CH3CN (20 mL) was added via cannula to a mixture of
p-ABSA (3.66 g, 0.0150 mol) and 19a (2.97 g, 0.0126 mol) in
CH3CN (30 mL). The mixture was warmed to 40 °C for 4 h,
and then the mixture was cooled to 0 °C. Saturated NH4Cl
was added, and then the organics were extracted using Et2O.
The organic layer was concentrated under reduced pressure,
and the resulting oil was triturated (petroleum ether/Et2O,
1:1), and then the solution was decanted away from the solid.
This solution was concentrated under reduced pressure to give
an orange oil. Purification by silica gel column chromatography
(petroleum ether/Et2O, 30:1, Rf ) 0.24) gave 1.8 g (55%) of 15a
1.0 mL/min; tR ) 12.7 min (minor), 13.9 min (major)): [R]25
D
) -220° (c 2.219, CHCl3); IR (neat) 2949, 2870, 1751, 1683,
1468 cm-1 1H NMR (500 MHz) δ 5.75 (ddd, 1 H, J ) 12.0,
;
7.0, 2.5 Hz), 5.21 (dd, 1 H, J ) 12.0, 2.0 Hz) Hz, 1H), 4.49 (dd,
1 H, J ) 9.5, 8.0 Hz), 3.99 (m, 1 H), 3.77 (dd, 1 H, J ) 9.5, 8.0
Hz), 3.38 (m, 1 H), 3.32 (d, 1 H, J ) 17.0 Hz), 2.30 (m, 1 H),
2.08 (ddd, 1 H, J ) 17.0, 5.0, 2.5 Hz), 1.62 (ddd, 1 H, J ) 13.0,
8.5, 2.0 Hz), 1.46 (dd, 1 H, J ) 13.0, 10.0 Hz), 1.16 (s, 3 H),
0.95 (d, 3 H, J ) 7.0 Hz), 0.87 (s, 3 H); 13C NMR (75 MHz
APT) δ 170.9 (4°), 164.9 (4°), 137.0 (3°), 124.0 (3°), 120.4 (4°),
70.6 (2°), 47.4 (2°), 47.2 (3°), 43.0 (2°), 39.8 (3°), 39.4 (4°), 34.8
(3°), 28.7 (1°), 27.8 (1°), 15.8 (1°); MS m/z (relative intensity)
232 (34), 217 (100), 131 (27), 117 (25), 91 (36). Anal. Calcd for
1
as an orange oil: IR (neat) 2955. 2076, 1709 cm-1; H NMR
(300 MHz) δ 6.22 (dd, 1 H, J ) 15.4, 10.4 Hz), 6.02 (dd, 1 H,
J ) 15.0, 10.4 Hz), 5.76 (s, 1 H), 5.73 (dq, 1 H, J ) 15.0, 6.6
Hz), 5.60 (dt, 1 H, J ) 15.4, 6.6 Hz), 4.66 (d, 2 H, J ) 6.6 Hz),
2.25 (br s, 4 H), 1.72 (d, 3 H, J ) 6.6 Hz), 1.07 (s, 6 H); 13C
NMR (75 MHz APT) δ 165.6 (4°), 135.0 (3°), 131.0 (3°), 130.6
(3°), 123.8 (3°), 123.1 (3°), 122.9 (4°), 65.0 (2°), 48.7 (2°), 48.3
(2°), 37.8 (4°), 29.4 (1°), 17.8 (1°) (CdN2 signal missing).
(2Z,4E)-2,4-Hexa d ien yl 4,4-Dim eth yl-1-cyclop en ten yl-
1-d ia zoa ceta te (15b). A solution of DBU (1.15 g, 7.56 mmol)
in CH3CN (2 mL) was added via cannula to a mixture of 19b
(590 mg, 2.52 mmol) and p-ABSA (730 mg, 3.04 mmol) in
CH3CN (8 mL). The mixture was warmed to 40 °C for 4 h,
and then the mixture was cooled to 0 °C. Saturated NH4Cl
was added, and then the organics were extracted using Et2O.
The mixture was concentrated under reduced pressure, the
resulting oil was triturated (petroleum ether/Et2O, 1:1), and
then the solution was decanted away from the solid. This
solution was concentrated under reduced pressure to give an
orange oil. Purification by silica gel column chromatography
(petroleum ether/Et2O, 30:1, Rf ) 0.33) gave 291.4 mg (45%)
C
15H20O2: C, 77.55; H, 8.68. Found: C, 77.46; H, 8.64.
Dir ect Syn th esis. A solution of 15a (90.8 mg, 0.349 mmol)
in hexane (6 mL) was added to a mixture of (ent)-1 (6.6 mg,
3.5 × 10-3 mmol) in hexane (10 mL) at RT. The mixture was
stirred 1 h, and then the mixture was concentrated under
reduced pressure to give a green gum. Purification by silica
gel column chromatography (petroleum ether/Et2O, 4:1, Rf )
0.29) gave 56.2 mg (69%) of 20 as a white solid, 24% ee
(determined by HPLC: OJ column, 0.5% i-Pr-OH in hexanes,
1.0 mL/min; tR ) 12.8 min (minor), 14.2 min (major)). Reac-
tions at other temperatures: -20 °C, 33% ee (50% yield); -78
°C, 35% ee.
(+)-(3ar,6â,6ar)-6,8,8-Tr im eth yl-3a,4,5,6,6a,7,8,9-octah y-
d r oa zu len o[4,5-c]fu r a n -1(3H)on e ((+)-epi-5-Tr em u len o-
lid e A) ((+)-14). A solution of 20 (111 mg, 0.476 mmol, 87%
ee) and chlorotris(triphenylphosphine)rhodium(I) (5.5 mg, 5.9
× 10-3 mmol) in EtOH (20 mL) was shaken under H2 (35 psi)
for 12 h. The mixture was then concentrated under reduced
pressure to give a yellow solid. Purification by silica gel column
chromatography (petroleum ether/Et2O, 4:1, Rf ) 0.17) gave
1
of 15b as an orange oil: IR (neat) 2955, 2080, 1699 cm-1; H
NMR (300 MHz) δ 6.32 (dd, 1 H, J ) 13.7, 11.0 Hz), 6.11 (dd,
1 H, J ) 11.0, 11.0 Hz), 5.77 (dq, 1 H, J ) 13.7, 6.6 Hz), 5.76
(s, 1 H), 5.37 (dt, 1 H, J ) 11.0, 7.2 Hz), 4.81 (d, 2 H, J ) 7.2
Hz), 2.25 (br s, 4 H), 1.76 (d, 3 H, J ) 6.6 Hz), 1.08 (s, 6 H);
13C NMR (75 MHz) δ 165.6, 133.2, 132.7, 126.2, 123.0, 122.8,
121.5, 60.4, 48.6, 48.2, 37.6, 29.3, 17.9 (CdN2 signal missing).
(1â,5r,6r)-6-((E)-P r op en yl)-1-(4,4-dim eth yl-1-p en ten yl)-
3-oxa bicyclo[3.1.0]h exa n -2-on e (21). A cold (-78 °C) solu-
tion of 15b (109.2 mg, 0.419 mmol) in hexane (5 mL, dried
over Na2SO4) was added via cannula to a solution of Rh2(R-
DOSP)4 (18.9 mg, 0.0100 mmol) in hexane (5 mL) in a Kjeldahl
flash (100 mL) at -78 °C. The mixture was stirred cold for 24
h and then slowly warmed to RT. Toluene (ca. 2 mL) was added
and the mixture concentrated to ca. 1 mL volume under
reduced pressure to give a green oil. Purification by silica gel
column chromatography (petroleum ether/Et2O, 4:1, Rf ) 0.32)
gave 63.1 mg (65%) of 21 as a clear, colorless oil, 93% ee
(determined by thermolysis to 19 and then analysis by
HPLC: OJ column, 0.5% i-Pr-OH in hexanes, 1.0 mL/min; tR
85 mg (76%) of (+)-14 as a white solid (mp 101-103 °C): [R]25
D
) 25° (c 0.63, CHCl3); IR (neat) 2950, 2870, 1751, 1683, 1468
1
cm-1; H NMR (500 MHz) δ 4.46 (dd, 1 H, J ) 9.5, 9.0 Hz),
3.80 (dd, 1 H, J ) 9.0, 7.0 Hz), 3.29 (dm, 1 H, J ) 17.0 Hz),
3.10 (m, 1 H), 2.99 (dddd, 1 H, J ) 8.0, 2.4, 2.3, 1.9 Hz), 2.06
(ddd, 1 H, J ) 17.5, 4.5, 3.0 Hz), 1.94-1.85 (m, 2 H), 1.82-
1.74 (m, 1 H), 1.62-1.52 (m, 2 H), 1.50-1.42 (m, 2 H), 1.12 (s,
3 H), 0.83 (d, 3 H, J ) 7.0 Hz), 0.82 (s, 3 H); 13C NMR (75
MHz APT) δ 171.1 (4°), 165.5 (4°), 121.8 (4°), 70.7 (2°), 50.5
(3°), 47.5 (2°), 44.1 (2°), 40.3 (3°), 38.1 (4°), 36.3 (2°), 31.4 (3°),
28.3 (1°), 26.9 (1°), 25.5 (2°), 11.9 (1°); MS m/z (relative
intensity) 234 (12), 219 (100), 105 (14), 91 (19). Anal. Calcd
for C15H22O2: C, 76.88; H, 9.46. Found: C, 76.71; H, 9.41.
Ack n ow led gm en t. This work was supported by the
National Science Foundation (CHE 9726124).
) 12.7 min (minor), 13.9 min (major)). [R]25 ) 32° (c 3.155,
D
CHCl3). Enantioselectivites at other temperatures: RT, 47%
ee (79% yield); 0 °C 59% ee; -20 °C, 63% ee; -40 °C, 77% ee.
Su p p or tin g In for m a tion Ava ila ble: Experimental and
spectral data for allyl and dienyl (E)-4-phenyl-3-butenoates,
2a -f,h -k , 3b-k , 5b, 6b, 6c, 8b, 8c, 9, 10, iii, and iv. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
IR (neat): 2950, 2836, 1768 cm-1. H NMR (500 MHz) δ 5.84
(dq, 1 H, J ) 15.0, 6.5 Hz), 5.71 (m, 1 H), 5.15 (ddq, 1 H, J )
15.0, 8.5, 1.5 Hz), 4.38 (dd, 1 H, J ) 9.5, 5.0 Hz), 4.16 (d, 1 H,
J ) 9.5 Hz), 2.39 (dd, 1 H, J ) 7.0, 5.0 Hz), 2.23 (dd, 1 H, J )
8.5, 7.0 Hz), 2.18 (dm, 1 H, J ) 15.0 Hz), 2.18-2.16 (m, 2 H),
2.05 (dm, 1 H, J ) 15.0 Hz), 1.70 (dd, 3 H, J ) 6.5, 1.5 Hz).
J O990888D