Synthesis of furano[2,3-c]pyran-3-one and thieno[2,3-c]pyran-3-one derivatives through the coupling of 3-alkynyl-2-heteroaromatic carboxaldehydes with fischer carbene complexes: Total synthesis of a Baccharis-derived cadinene derivative

Article abstract of DOI:10.1021/jo011136y

The coupling of Fischer carbene complexes with 3-alkynyl-2-heteroaromatic carboxaldehyde derivatives has been examined. The reaction affords pyrones fused to furans or thiophenes in a single step. The compounds are stable enough for isolation. If the carbene complex features a remote alkene substituent, a subsequent Diels-Alder reaction can occur. This reaction has been used as the key step in the synthesis of a naturally occurring cadinene derivative.

Full text of DOI:10.1021/jo011136y

J . Org. Chem. 2002, 67, 4177-4185
4177
Syn th esis of F u r a n o[2,3-c]p yr a n -3-on e a n d
Th ien o[2,3-c]p yr a n -3-on e Der iva tives th r ou gh th e Cou p lin g of
3-Alk yn yl-2-h eter oa r om a tic Ca r boxa ld eh yd es w ith F isch er
Ca r ben e Com p lexes: Tota l Syn th esis of a Ba cch a r is-Der ived
Ca d in en e Der iva tive
Yanshi Zhang and J ames W. Herndon*
Department of Chemistry & Biochemistry, New Mexico State University, MSC 3C,
Las Cruces, New Mexico 88003
jherndon@nmsu.edu
Received December 10, 2001
The coupling of Fischer carbene complexes with 3-alkynyl-2-heteroaromatic carboxaldehyde
derivatives has been examined. The reaction affords pyrones fused to furans or thiophenes in a
single step. The compounds are stable enough for isolation. If the carbene complex features a remote
alkene substituent, a subsequent Diels-Alder reaction can occur. This reaction has been used as
the key step in the synthesis of a naturally occurring cadinene derivative.
Sch em e 1
In tr od u ction
In recent publications, the generation of isobenzofuran
intermediates (e.g., 5, Y ) -CHdCH-, Scheme 1)
through the coupling of Fischer carbene complexes (e.g.,
2) with o-alkynylbenzoyl derivatives (1) has been dem-
onstrated.1 In these reactions, coupling of the carbene
complex with the alkyne initially provides intermediate
alkenylcarbene complex 3 in a regioselective and stereo-
selective manner, which is then captured to form the
carbonyl ylide derivative 4. Loss of the metal from the
carbonyl ylide leads to the isobenzofuran derivative,
which is then captured through reaction with an alkene
in a Diels-Alder reaction.2 Similar chemistry resulting
in stable furan rings from enyne-aldehyde derivatives
had previously been demonstrated.3 In these examples,
capture of the intermediate vinylcarbene complex by the
oxygen precedes any CO insertion processes. The hypo-
thetical products of CO insertion, pyrones (e.g., 7), were
not detected in any of these reactions.
In a preliminary report,4 it was noted that furan and
thiophene analogues (e.g., 1, Y ) O or S) do in fact lead
to furanopyrones (7) and not the furanofurans (5). This
represents a novel entry into this synthetically useful
ring system5 and is the first example of a chromium
carbene-derived ketene undergoing cyclization to a py-
rone system.6,7 In this paper, a full and detailed account
of this process will be presented, along with an applica-
tion of this reaction to the total synthesis of a cadinene
natural product isolated from Baccharis species.
* To whom correspondence should be addressed. Fax: (505)646-
2487.
(1) (a) J iang, D.; Herndon, J . W. Org. Lett. 2000, 2, 1267-1269. (b)
Ghorai, B. K.; Herndon, J . W.; Lam, Y. F. Org. Lett. 2001, 3, 3535-
3538.
Resu lts
(2) For
a review of isobenzofurans, see: Friedrichsen, W. Adv.
Heterocycl. Chem. 1999, 73, 1-96.
Syn th esis of Alkyn e Aldeh ydes. The requisite alkyne
aldehydes 10A-D were prepared from the corresponding
(3) Herndon, J . W.; Wang, H. J . Org. Chem. 1998, 63, 4564-4565.
(4) Zhang, Y.; Herndon, J . W. Tetrahedron Lett. 2001, 42, 777-779.
(5) This is the first example of this furanopyrone ring system. For
previous examples of the thienopyrone ring system, see: (a) J ackson,
P. M.; Moody, C. J .; Shah, P. J . Chem. Soc., Perkin Trans. 1 1990,
2909-2918. (b) J ackson, P. M.; Moody, C. J . J . Chem. Soc., Perkin
Trans. 1 1990, 681-687.
(7) Electronically similar compounds have been reported from
rearrangement of in situ-generated metal-vinylidene complexes con-
taining a carbonyl substituent. (a) Iwasawa, N.; Shido, M.; Maeyama,
K.; Kusama, H. J . Am. Chem. Soc. 2000, 122, 10226-10227. (b)
Iwasawa, N.; Shido, M.; Kusama, H. J . Am. Chem. Soc. 2001, 123,
5814-5815. (c) Ohe, K.; Miki, K.; Yokoi, T.; Nishino, F.; Uemura, S.
Organometallics 2000, 19, 5525-5528.
(6) For an iron-carbene-derived example, see: Semmelhack, M. F.;
Tamura, R.; Schnatter, W.; Springer, J . J . Am. Chem. Soc. 1986, 106,
5363-5364.
10.1021/jo011136y CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/11/2002

4178 J . Org. Chem., Vol. 67, No. 12, 2002
Zhang and Herndon
Sch em e 2
Sch em e 3
commercially available (2,3-dibromothiophene) or known8
dibromo compounds (8) according to the sequence of
reactions in Scheme 2. Selective halogen-metal exchange
followed by treatment with DMF afforded the bromo
aldehyde derivatives (9),9 which afforded the requisite
alkyne aldehydes after Sonogashira coupling.9c
Cou p lin g of Alk yn e Ald eh yd es w ith Meth ylca r -
ben e Com p lex 1. Coupling of carbene complex 1 with
furancarboxaldehyde 8A afforded a moderately stable
compound assigned as structure 11A (Scheme 3). Hy-
drolysis afforded ketone 12A, which was more stable and
used for characterization purposes. Chemical and spec-
troscopic properties are consistent only with the furan-
opyrone structure, and not the furanofuran structure
13A. The product shows mass, IR, and carbon-13 NMR
spectra that confirm the incorporation of a CO ligand and
verify the presence of a carbonyl group. As further proof
of structure, compound 12A was unreactive to dimethyl
acetylenedicarboxylate (DMAD) at room temperature;
furanofuran derivative 13A should be reactive to DMAD
at room temperature based on literature precedent.9c The
Diels-Alder reaction with DMAD required refluxing
chlorobenzene and afforded benzofuran derivative 14,
which presumably arises through Diels-Alder reaction
followed by expulsion of CO2. Although this ring system
is unknown,10 sulfur5 and nitrogen11 analogues of 6A are
known and undergo the Diels-Alder reaction with DMAD
under comparable conditions, affording the aromatic
rings after thermal elimination of carbon dioxide.12 The
optimal conditions for the synthesis of pyrone derivative
12A are refluxing a 1:1:1 mixture of carbene complex,
alkyne, and triphenylphosphine in dioxane, which led to
12A in 72% yield.
The pyrone-forming reaction was tested for various
heteroaromatic carboxaldehyde derivatives; the results
are presented in Table 1. An efficient pyrone-forming
reaction was observed for the examples in Table 1, entries
A-C. Hydrolysis of the enol ether product of Table 1,
entry D, 11D, afforded a highly fluorescent compound
that was prone to decomposition; the low yield noted is
for the relatively unstable enol ether. Only 2-heteroaro-
matic carboxaldehydes underwent this transformation.
No pyrone-containing products were obtained from the
reaction of methylcarbene complex 2 with 2-alkynyl-3-
furancarboxaldehyde derivative 8E. A compound tenta-
tively indentified as cyclobutenone 16E (IR 1768, 1688
13
cm-1
)
was obtained from this reaction in low yield.
Coupling of methylcarbene complex 2 with methyl ketone
derivative 8F afforded an impure compound consistent
with furanopyrone structure 11F ; however, all attempts
to isolate this compound free of impurities were unsuc-
cessful.
Ta n d em P yr on e F or m a tion -Diels-Ald er Rea c-
tion . In the reaction of furan-aldehyde 8B with butenyl-
carbene complex 17A14 (Scheme 4), the initially formed
pyrone derivative 13G undergoes an intramolecular
Diels-Alder reaction to afford lactone derivative 18G as
a single diastereomer,5 accompanied by a minor amount
of alcohol derivative 19G. Compounds analogous to 19G
were obtained from intramolecular Diels-Alder reactions
(8) (a) 2,3-Dibromofuran: Gronowitz, S.; Michael, U. Ark. Kemi.
1970, 32, 283-294. (b) 2,3-dibromobenzofuran: Benincori, T.; Brenna,
E.; Sannicolo, F.; Trimarco, L.; Antognazza, P.; Cesarotti, E.; Demartin,
F.; Pilati, T. J . Org. Chem. 1996, 61, 6244-6251. (c) 2,3-Dibromoben-
zothiophene: Chippendale, K. E.; Iddon, B.; Suschitzky, H.; Taylor,
D. S. J . Chem. Soc., Perkin Trans. 1 1974, 1168-72.
(9) (a) For 3-bromo-2-furancarboxaldehyde, see: Zaluski,-M. C.;
Robba, M.; Bonhomme, M. Bull. Soc. Chim. Fr. 1970, 1838-1846. (b)
For 3-bromo-2-thiophenecarboxaldehyde, see: Chadwick, D.; Cham-
bers, J .; Hodgson, P. H. K.; Meakins, G. D.; Snowden, R. L. J . Chem.
Soc., Perkin Trans. 1 1974, 1141-1145. (c) For benzo derivatives, see:
Eberbach, W.; Laber, N.; Bussenius, J .; Fritz, H.; Rihs, G. Chem. Ber.
1993, 126, 975-995.
(10) A computer substructure search turned up a single literature
citation; however, no compound featuring this ring system is contained
in the article. Clavey, E. M.; Page, S. W.; Taylor, L. T. J . Supercrit.
Fluids 1990, 3, 115-120.
(11) (a) Hong, B. C.; J iang, Y. F.; Kumar, E. S. Bioorg. Med. Chem.
Lett. 2001, 11, 1981-1984. (b) Nag, S.; Saha, K.; Choudhuri, M. A. J .
Plant Growth Reg. 2001, 20, 182-194. (c) Haider, N.; Kaferbock, J .;
Matyus, P. Heterocycles 1999, 51, 2703. (d) Moody, C. J . Synlett 1994,
681-688.
(12) For a review of pyrone Diels-Alder reactions, see: Afarinkia,
K. A.; Vinader, V.; Nelson, T. D.; Posner, G. H. Tetrahedron 1992, 42,
9111-9171.
(13) Cyclobutenones are frequently observed in the coupling of
carbene complexes and alkynes. Wulff, W. D. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.;
Pergamon: Oxford, 1991; Vol. 5, pp 1065-1113.

Total Synthesis of a Baccharis-Derived Cadinene Derivative
J . Org. Chem., Vol. 67, No. 12, 2002 4179
Ta ble 1. Scop e a n d Lim it for P yr on e F or m a tion w ith
Meth ylca r ben e Com p lex 2
Ta ble 2. Solven t Effects on th e Distr ibu tion of 18G a n d
19Ga
entry
solvent
concn (M) total yield (%) 18G/19G
A
B
Cb
D
E
THF
DME
benzene
1,2-dichloroethane
acetonitrile
acetone
0.03
0.03
0.03
0.03
0.03
0.03
0.007
72
66
78:22
35:65
not catalyzed
51
70
77
88
63:37
86:14
81:10
66:34
F
G
THF
a
All reactions were conducted at the reflux temperature. b Only
chromium-complexed products were obtained, which could not be
efficiently converted to simple organic compounds.
Sch em e 5
Sch em e 4
this solvent was utilized for subsequent studies. The
reaction was tested for similar complexes featuring either
a monosubstituted or 1,1-disubstituted alkene append-
age; the results are depicted in Table 3. Only in one case
(Table 3, entry G) was a compound isolated that failed
to undergo the Diels-Alder reaction; however, successful
Diels-Alder reaction was observed when the reaction
was conducted at 125 °C in refluxing chlorobenzene.
The tandem pyrone formation-Diels-Alder reactions
involving simple furan derivative 8A and carbene com-
plexes 17A or 17B (Scheme 5) proceeded by a different
course and provided enone 21N as the exclusive product.
The reaction involving electron-deficient furan 8F led to
the expected Diels-Alder adduct 18O accompanied by
trace amount of compound 21O.
Com p et it ive Ben za n n u la t ion -P yr on e F or m a -
tion . Coupling of dialkyne complex 8I (Scheme 6) with
carbene complex 2 led to lactone derivative 25 as the
exclusive product of the reaction in 43% yield. In this
case, two cyclization modes are possible for intermediate
ketene 22, benzannulation to form phenol aldehyde 2316
or cyclization of the aldehyde to form pyrone 24. Lactone
25 is most likely an oxidation product of phenol aldehyde
23, thus indicating that pyrone formation is not competi-
tive with the two alkyne benzannulation process.
of isobenzofuran intermediates,1b and presumably arise
from furan 13G. The stereochemistry has been assigned
as the depicted endo isomer since the coupling between
HB and HD (8.9 Hz) is greater than HC and HD (4.8 Hz);
similar values have been reported for related com-
pounds.15 The effect of solvent on the distribution of 18G
and 19G was briefly examined (Table 2). Optimal yields
of 18G were observed using acetone as the solvent, and
Discu ssion
Mech a n ism of th e P yr on e-F or m in g Rea ction . The
mechanism for pyrone formation is depicted in Scheme
(14) Hoye, T. R.; Vyvyan, J . R. J . Org. Chem. 1995, 60, 4184-4195.
(15) Afarinkia, K.; Posner, G. H. Tetrahedron Lett. 1992, 53, 7839-
7842.
(16) Wulff, W. D.; Kaesler, R. W.; Peterson, G. A.; Tang, P. C. J .
Am. Chem. Soc. 1985, 107, 1060-1062.

4180 J . Org. Chem., Vol. 67, No. 12, 2002
Zhang and Herndon
Ta ble 3
Sch em e 6
cesses are suppressed for electron-rich metal-carbene
species,17 CO insertion should be less likely in the
thiophene and furan systems (8) than in the less electron
rich benzene analogues (8, Y ) -CHdCH-). The sur-
prising formation of pyrones in these studies might be
attributed to the greater ring strain in derivatives such
as 13 and the greater distance between the carbonyl
oxygen and the carbene carbon in intermediate 26 when
fused to a five-membered ring vs a six-membered ring.
Thus, the furan ring-closure step in these systems (26
to 28) is less favorable than in systems where Y ) -CHd
CH-,18 and CO insertion to form ketene 27 is favored
over direct ring closure to form 28 and subsequently 13.
Failure of pyrone formation from the 3-thiophenecarbox-
aldehyde derivative 8E (Table 1, entry E) might be
attributed to the reduced nucleophilicity of the carbonyl
oxygen.19
Effect of Alk en e Ap p en d a ges on th e P yr on e-
F or m in g Rea ction : F or m a tion of th e Min or P r od -
(17) (a) Grotjahn, D. B.; Kroll, F. E. K.; Scha¨fer, T.; Harms, K.; Do¨tz,
K. H. Organometallics 1992, 11, 298-310. (b) Barluenga, J .; Lopez,
L. A.; Mart´ınez, S.; Toma´s, M. J . Org. Chem. 1998, 63, 7588-7589. (c)
For
a universal discussion of electronic effects in carbene-alkyne
couplings, see: Waters, M. A.; Brandvold, T. A.; Isaacs, L.; Wulff, W.
D.; Rheingold, A. L. Organometallics 1998, 17, 4298-4308.
(18) For other examples where a CO insertion process occurs due
to ring strain, see: (a) Barluenga, J .; Aznar, F.; Palomero, M. A.;
Barluenga, S. Org. Lett. 1999, 1, 541-543. (b) Wu, H. P.; Aumann, R.;
Fro¨hlich, R.; Wibbeling, B. Eur. J . Org. Chem. 2000, 1183-1192.
(19) Francesco, F.; Gianlorenzo, M.; Taticchi, A. J . Chem. Soc. B
1971, 2302-2303.
7. Formation of pyrone derivatives from these reactions
was not expected initially based on previous observations
using o-alkynylbenzaldehyde derivatives, which lead to
isobenzofuran intermediates. Since CO insertion pro-

Total Synthesis of a Baccharis-Derived Cadinene Derivative
J . Org. Chem., Vol. 67, No. 12, 2002 4181
Sch em e 7
Sch em e 8
u ct 19. The use of complexes having alkene appendages
led to Diels-Alder adducts of general structure 18;
however, a minor product in these processes is the alcohol
derivative 19. A likely mechanism for the formation of
alcohol 19 is via formation of furanothiophene derivative
13, followed by Diels-Alder reaction and ring opening
(Scheme 8). Compounds analogous to 19 were formed in
the reaction of γ,δ-unsaturated carbene complexes with
2-ethynylbenzaldehyde; this reaction proceeds through
isobenzofuran intermediates.1b Since none of the furan-
othiophene compound 13B was observed in the reaction
of thiophenecarboxaldehyde derivative 8B with methyl-
carbene complex 2, this implies that the alkene is to a
small extent directing the reaction toward formation of
the furanothiophene. A likely role for the alkene group
is depicted in Scheme 9, where to some extent intermedi-
ate complex 32 is formed by displacement of a carbonyl
ligand from intermediate complex 31. Carbonyl insertion
in complex 32 would be less likely than in complex 31
due to the greater electron density at chromium.
Effect of Solven t of th e Distr ibu tion of 18G/19G.
As noted in Table 2, solvent and concentration play an
important role in the distribution of products between
Diels-Alder adducts 18G and 19G. The amount of 19G
is maximized in DME, a solvent whose ligand properties
can best be described as chelating and strongly electron-
donating. Similar distributions of 18G and 19G were
observed in THF, acetonitrile, and acetone, which are all
strongly ligating but not chelating. Acetonitrile and
acetone also have back-bonding capability. If these spe-
cies complex to chromium, the electron density at chro-
mium would be less relative to analogous DME or THF
complexes, and thus, the CO insertion process would be
more favorable. In one case, entry G of Table 3, it was
noted that the amount of non CO-inserted product was
considerably higher in dilute solution. This is consistent
with the allelochemical effect previously described by
Wulff and co-workers,20 in that CO-insertion is sup-
pressed in dilute solution since coordination of a second
alkyne ligand is crucial for the CO insertion event.
F or m a tion of Com p ou n d 18 fr om Bu ten ylca r ben e
Com p lexes 17. As anticipated, the major products from
the coupling of butenylcarbene complex 17 and 3-alkynyl-
2-heteroaromaticcarboxaldehydes are adducts of general
structure 18. Surprisingly, the Diels-Alder step is ap-
parently very facile at 56 °C, which is unexpected based
on other studies of the intramolecular Diels-Alder reac-
tion in similar system.5 Although the authors did not
report a study of the reaction at different temperatures,
they employed a very unconventional solvent system,
refluxing bromobenzene (bp 156 °C), to effect the Diels-
Alder step. The Diels-Alder step occurs with complete
control of stereochemistry, resulting in the endo isomer.
The unusually low temperatures coupled with the high
degree of stereochemical control might indicate the
involvement of chromium in the Diels-Alder step.21 In
two cases, entries E and F of Table 3, efficient formation
of Diels-Alder adducts 18K and 18L was noted, even
though the pyrone synthesis using aldehyde 8D was
inefficient.
In one of the examples (entry G of Table 3 and Scheme
10) a pyrone derivative, 11M, which fails to undergo the
Diels-Alder reaction, could be isolated in low yield.
However, the reaction in refluxing chlorobenzene afforded
(20) Bos, M. E.; Wulff, W. D.; Miller, R. A.; Chamberlin, S.;
Brandvold, T. A. J . Am. Chem. Soc. 1991, 113, 9293-9319.
(21) Rigby, J . H. Tetrahedron 1999, 55, 4521-4538.

4182 J . Org. Chem., Vol. 67, No. 12, 2002
Zhang and Herndon
Sch em e 9
Sch em e 11
missing the CO2 bridge (21). The mechanism for forma-
tion of this compound is depicted in Scheme 11. Forma-
tion of carbocation 36 followed by extrusion of CO2 leads
to conjugated triene 32, which is subsequently hydrolyzed
to the observed enone 21. Alternatively, direct thermal
extrusion of CO2 from 18 would lead to 37. The ionic
mechanism depicted explains why this reaction pathway
is unique to the furan ring system, which is more
electron-donating than the other systems employed.22
Placement of an electron-withdrawing group on the furan
ring (8H, Y ) COOMe) inhibits this reaction pathway
due to destabilization of carbocation 36O, and bridged
structure 18O was the major product from coupling of
this substrate with butenylcarbene complex 17A.
Sch em e 10
Tota l Syn th esis of Ba cch a r is-Der ived Ca d in en e
Na tu r a l P r od u cts. The furanodecalin ring system simi-
lar to 21 is found in a number of naturally occurring
compounds23 and has been the target of numerous
synthetic efforts.24 Closely related furanone analogues
(22) (a) Noyce, D. S.; Lipinski, C. A.; Nichols, R. W. J . Org. Chem.
1972, 37, 2615-2620. (b) Noyce, D. S.; Pavez, H. J . J . Org. Chem. 1972,
37, 2623-2625. (c) Olah, G. A.; Berrier, A. L.; Prakash, G. K. S. J .
Org. Chem. 1982, 47, 3903-3909.
(23) (a) Zdero, C.; Bohlmann, F.; King, R. M.; Robinson, H. Phy-
tochemistry 1986, 25, 2841-2855. (b) Bohlmann, F.; Singh, P.; J ak-
upovic, J .; King, R. M.; Robinson, H. Phytochemistry 1982, 21, 371-
374. (c) Bohlmann, F.; Zdero, C.; King, R. M.; Robinson, H. Phytochem-
istry 1979, 18, 1177-1179. (d) Loayza, I.; Abujder, D.; Aranda, R.;
J akupovic, J .; Collin, G.; Deslauriers, H.; J ean, F. I. Phytochemistry
1995, 38, 381-389. (e) Braga de Oliveira, A.; De Oliveira, G. G.;
Carazza, F.; Braz Filho, R.; Moreira Bacha, C. T.; Bauer, L.; Silva, G.
A. de A. B.; Siqueira, N. C. S. Tetrahedron Lett. 1978, 30, 2653-2654.
(f) Bohlmann, F.; Zdero, C. Chem. Ber. 1977, 110, 487-490. (g) De
Oliveira, A. B.; Carazza, F.; Ramos, L. S.; Maia, J . G. S. J . Essent. Oil
Res. 1990, 2, 49-50. (g) J akupovic, J .; Schuster, A.; Ganzer, U.;
Bohlmann, F.; Boldt, P. E. Phytochemistry 1990, 29, 2217-2222.
(24) (a) Demir, A. S.; Gercek, Z.; Duygu, N.; Igdir, A. C.; Reis, O.
Can. J . Chem. 1999, 77, 1336-1339. b. Chavan, S. P.; Rao, Y. T. S.;
Govande, C. A.; Zubaidha, P. K.; Dhondge, V. D. Tetrahedron Lett.
1997, 38, 7633-7634. (c) Chavan, S. P.; Dhondge, V. D.; Patil, S. S.;
Rao, Y. T. S.; Govande, C. A. Tetrahedron: Asym. 1997, 8, 2517-2518.
(d) J uo, R. R.; Herz, W. J . Org. Chem. 1985, 50, 700-703. (e) Kano,
S.; Ebata, T.; Shibuya, S. Heterocycles 1980, 14, 43-46.
the benzothiophene derivative 20 as the exclusive prod-
uct. The origin of benzothiophene 20 is unclear and might
result from exclusive formation of furanothiophene 13M
in chlorobenzene, which affords 20 after Diels-Alder
reaction and dehydration.
Ta n d em P yr on e F or m a tion -Diels-Ald er Rea c-
tion s Usin g Sim p le F u r a n a ld eh yd es. Coupling of
aldehyde 8A, which contains a simple furan ring, with
γ,δ-unsaturated carbene complexes 17 led to compounds

Total Synthesis of a Baccharis-Derived Cadinene Derivative
J . Org. Chem., Vol. 67, No. 12, 2002 4183
Sch em e 12
Con clu sion s
In summary, we have shown a new and general route
to the heteroaromatic-fused pyrone ring systems and are
further exploring the synthesis and reactivity of these
unusual pyrone derivatives. These compounds undergo
very facile and highly stereoselective intramolecular
Diels-Alder reactions to afford hydronaphthalene rings
fused to heteroaromatic rings. If the heterocyclic ring is
highly electron rich, the cycloadducts undergo a loss of
carbon dioxide to afford simple hydronaphthalene ring
systems. The tandem pyrone formation-Diels-Alder-
carbon dioxide extrusion process has been utilized as the
key step in the one-step synthesis of natural product
ketone 38.
Sch em e 13
Exp er im en ta l Section 29
Gen er a l P r oced u r e 1. Cou p lin g of Ca r ben e Com p lex
2 w ith Alk yn yl-Ald eh yd es. An 0.06 M solution of carbene
complex (1 equiv) in dioxane was added dropwise over a period
of 15 min to a refluxing 0.06 M solution of alkyne-aldehyde
(1 equiv) and PPh3 (1 equiv) in dioxane. After completion of
the addition, the mixture was allowed to reflux for 1.5 h. The
resulting red brown solution was dried in vacuo, followed by
the hydrolysis using 5 M HCl solution to afford the product
as yellow oil. Final purification was achieved by flash chro-
matography on silica gel using (2:1) hexane/ethyl acetate as
eluent. Compounds 12A and 12B decomposed during shipment
to an external mass spectrometry facility; only the more stable
benzo analogue 12C could be completely characterized.
Cou p lin g of Alk yn e Ald eh yd e 8A w ith Ca r ben e Com -
p lex 2. General procedure 1 was followed using carbene
complex 2 (150 mg, 0.600 mmol), alkyne aldehyde 8A (106 mg,
0.600 mmol), and triphenylphosphine (157 mg, 0.600 mmol).
After final purification, a yellow oil identified as pyrone 12A
was obtained (106 mg, 72% yield): 1H NMR (CDCl3) δ 7.83 (s,
1 H), 7.53 (d, 1 H, J ) 2.4 Hz), 6.49 (d, 1 H, J ) 2.4 Hz), 4.04
(t, 1 H, J ) 6.8 Hz), 2.09 (s, 3 H), 1.97 (m, 1 H), 1.65 (m, 1 H),
1.21 (m, 4 H), 0.78 (t, 3 H, J ) 6.9 Hz); 13C NMR (CDCl3) δ
206.8, 162.6, 156.7, 146.4, 143.3, 133.5, 111.3, 104.9, 51.2, 29.5,
29.4, 28.9, 22.4, 13.7; IR (neat) 1696 (s), 1663 (s), 1582 (m)
display biological activity as fish toxicants.25 As a dem-
onstration of the utility of this transformation, total
synthesis of compound 38,23a isolated from aerial parts
of Baccharis ulcina, was undertaken. There is only
minimal structural difference between compound 21N
and 38, and thus the retrosynthetic analysis involves the
simple coupling of furan 39 with carbene complex 17C
(Scheme 12). Carbene complex 17C was synthesized from
acid chloride 4226 according to the procedure of Hegedus27
(Scheme 13). Furan 39 was synthesized from com-
mercially available 3-methyl-2-furancarboxylic acid.28
Coupling of carbene complex 17C with furan 39 afforded
the natural product 38 in 49% yield as a single diaste-
reomer. The spectral data for compound 38 synthesized
in this way is identical to that reported for the natural
product.23a
cm-1
.
Cou p lin g of Alk yn e Ald eh yd e 8B w ith Ca r ben e Com -
p lex 2. General procedure 1 was followed using carbene
complex 2 (150 mg, 0.600 mmol), alkyne aldehyde 8B (115 mg,
0.600 mmol), and triphenylphosphine (157 mg, 0.600 mmol).
After final purification, a yellow oil identified as pyrone 12B
was obtained (119 mg, 75% yield): 1H NMR (CDCl3) δ 7.92 (s,
1 H), 7.57 (d, 1 H, J ) 5.6 Hz), 6.83 (d, 1 H, J ) 5.6 Hz), 4.00
(dd, 1 H, J ) 8.4, 6.1 Hz), 2.03 (s, 3 H), 2.00 (m, 1 H), 1.65 (m,
1 H), 1.15 (m, 4 H), 0.73 (t, 3 H, J ) 6.9 Hz); 13C NMR (CDCl3)
δ 206.6, 162.3, 153.5, 144.7, 142.5, 122.0, 120.0, 115.1, 51.9,
29.5, 28.8, 28.6, 22.4, 13.6; IR (neat) 1697 (s), 1668 (s) cm-1
.
Cou p lin g of Alk yn e Ald eh yd e 8C w ith Ca r ben e Com -
p lex 2. General procedure 1 was followed using carbene
complex 2 (125 mg, 0.500 mmol), alkyne aldehyde 8C (113 mg,
0.500 mmol), and triphenylphosphine (131 mg, 0.500 mmol).
After final purification, a yellow oil identified as pyrone 12C
was obtained (104 mg, 70% yield): 1H NMR (CDCl3) δ 7.89
(d, 1 H, J ) 8.0 Hz), 7.85 (s, 1 H), 7.59 (t, 1 H, J ) 8.0 Hz),
7.34 (d, 1 H, J ) 8.0 Hz), 7.27 (t, 1 H, J ) 8.0 Hz), 4.17 (dd, 1
H, J ) 9.2, 5.0 Hz), 2.27 (m, 1 H), 2.14 (s, 3 H), 1.89 (m, 1 H),
1.23 (m, 4 H), 0.75 (t, 3 H, J ) 7.1 Hz); 13C NMR (CDCl3) δ
206.0, 162.4, 161.3, 143.2, 142.7, 133.5, 132.1, 126.6, 123.7,
120.2, 117.0, 112.1, 52.5, 29.8, 28.3, 27.3, 22.5, 13.7; IR (neat)
1698 (s), 1670 (s), 1609 (m), 1590 (m) cm-1; MS (FAB) 299 (M
+ 1, 89), 298 (M, 100), 255 (35), 229 (24), 136 (21); HRMS calcd
for C18H19O4 299.1283, found 299.1255.
(25) (a) Miles, D. H.; Lho, D. S.; De la Cruz, A. A.; Gomez, Edgardo
D.; Weeks, J . A.; Atwood, J . L. J . Org. Chem. 1987, 52, 2930-2932.
(b) Miles, D. H.; Ly, A. M.; Chittawong, V.; De la Cruz, A. A.; Gomez,
E. D. J . Nat. Prod. 1989, 52, 896-898.
(26) Lin, J . M.; Koch, K.; Fowler, F. W. J . Org. Chem. 1986, 51, 167-
174.
(27) (a) Schwindt, M. A.; Lejon, T.; Hegedus, L. S. Organometallics
1990, 9, 2814-2819. (b) Semmelhack, M. F.; Lee, G. R. Organometallics
1987, 6, 1839-1844. (c) For specific use of this reaction for the
synthesis of γ,δ-unsaturated carbene complexes, see: Moser, W. H.
Hegedus, L. S. J . Am. Chem. Soc. 1996, 118, 7873-7880.
(28) This compound is quite expensive but easily produced on large
scale. Burness, D. M. In Organic Syntheses; Collective; Rabjohn, N.,
Ed.; J ohn Wiley and Sons: New York, 1963; Collect. Vol. IV, pp 649-
652 and 628-630.
(29) For a general experimental procedure, see: Herndon, J . W.;
Zhu, J .; Sampedro, D. Tetrahedron 2000, 56, 4985-4993.

4184 J . Org. Chem., Vol. 67, No. 12, 2002
Zhang and Herndon
Gen er a l P r oced u r e 2. Cou p lin g of Alk yn e Ald eh yd es
w ith Alk en ylca r ben e Com p lexes 17A-C. A 0.03 M solution
of carbene complex 17 (1 equiv) in acetone was added dropwise
to a refluxing 0.036 M solution of alkyne aldehyde (1 equiv)
in acetone and kept at reflux for 18 h. The resulting reaction
mixture was concentrated in vacuo. The residue was purified
by flash chromatography on silica gel using (6:1) hexane/ethyl
acetate as the eluent.
3 H), 0.83 (t, 3 H, J ) 7.0 Hz); 13C NMR (CDCl3) δ 171.5, 155.9,
155.5, 150.3, 126.2, 124.0, 123.4, 119.4, 118.5, 114.1, 112.0,
71.0, 56.4, 55.3, 44.4, 35.9, 32.7, 31.1, 29.6, 24.0, 23.5, 22.0,
13.9; IR (neat) 1762 (s), 1666 (m) cm-1; MS (FAB) 367 (M + 1,
100), 323 (33), 266 (28); HRMS calcd for C23H27O4 367.1910,
found 367.1898.
Cou p lin g of Alk yn e Ald eh yd e 8D w ith Ca r ben e Com -
p lex 17A. General procedure 2 was followed using carbene
complex 17A (136 mg, 0.47 mmol) and alkyne aldehyde 8D
(114 mg, 0.47 mmol). After final purification, a white solid
identified as ester 18K was obtained (116 mg, 67% yield): 1H
NMR (CDCl3) δ 7.81 (m, 2 H), 7.34 (m, 2 H), 5.65 (d, 1 H, J )
4.4 Hz), 3.66 (s, 3 H), 2.77 (ddd, 1 H, J ) 13.2, 8.9, 4.4 Hz)
2.55-1.23 (m, 11 H), 1.17 (dd, 1 H, J ) 13.2, 4.4 Hz), 0.90 (t,
3 H, J ) 7.3 Hz); 13C NMR (CDCl3) δ 172.8, 152.2, 140.7, 137.2,
136.7, 134.0, 124.7, 124.2, 123.0, 122.5, 114.3, 72.5, 55.2, 55.0,
35.6, 35.1, 31.5, 31.3, 26.7, 24.9, 23.6, 13.9; IR (neat) 1758 (s),
1662 (s) cm-1; LCMS (EI) 368 (M, 45), 324 (71), 235 (100), 197
(85). Anal. Calcd for C22H24OsS: C, 71.74; H, 6.57. Found: C,
71.34; H, 6.57.
Cou p lin g of Alk yn e Ald eh yd e 8D w ith Ca r ben e Com -
p lex 17B. General procedure 2 was followed using carbene
complex 17B (57 mg, 0.185 mmol) and alkyne aldehyde 8D
(45 mg, 0.185 mmol). After final purification, a white solid
identified as ester 18L was obtained (47 mg, 66% yield): 1H
NMR (CDCl3) δ 7.79 (m, 2 H), 7.35 (td, 1 H, J ) 7.1, 1.5 Hz),
7.27 (td, 1 H, J ) 7.1, 1.4 Hz), 5.58 (dd, 1 H, J ) 5.0, 1.1 Hz),
3.65 (s, 3 H), 2.85-2.15 (m, 2 H) overlapping with 2.38 (dd, 1
H, J ) 13.0, 5.0 Hz), 2.10-1.80 (m, 2 H), 1.75-0.85 (m, 6 H)
overlapping with 1.41 (dd, 1 H, J ) 13.0, 1.1 Hz) and 1.29 (s,
3 H) and 0.90 (t, 3 H, J ) 7.0 Hz); 13C NMR (CDCl3) δ 171.4,
150.4, 140.6, 137.2, 137.0, 135.5, 124.8, 124.1, 123.0, 122.7,
113.7, 72.4, 59.1, 54.9, 43.9, 35.7, 32.6, 31.2, 30.8, 24.2, 23.5,
21.9, 13.9; IR (neat) 1761 (s), 1662 (m) cm-1; MS (FAB) 383
(M + 1, 61), 339 (24), 307 (23), 282 (28), 235 (38), 211 (64);
HRMS calcd for C23H27O3S 383.1681, found 383.1693.
Diels-Ald er Rea ction of 12A a n d Dim eth yl Acetylen e-
d ica r boxyla te. A solution of pyrone ketone 12A (82 mg, 0.330
mmol) and dimethyl acetylenedicarboxylate (106 mg, 0.745
mmol) in chlorobenzene (5 mL) was heated to reflux for a 24
h period. The solvent was removed on a rotary evaporator, and
the residue was purified by flash chromatography on silica gel
using (2:3) hexane/ethyl acetate as eluent to afford a white
solid identified as diester 14 (82 mg, 72% yield): 1H NMR
(CDCl3) δ 8.07 (d, 1 H, J ) 0.9 Hz), 7.72 (d, 1 H, J ) 2.3 Hz),
6.82 (dd, 1 H, J ) 2.3, 0.9 Hz), 3.94 (s, 3 H), 3.88 (s, 3 H), 3.79
(dd,, 1 H, J ) 8.3, 6.1 Hz), 2.14 (m, 1 H), 1.98 (s, 3 H), 1.70 (m,
1 H), 1.17 (m, 4 H), 0.74 (t, 3 H, J ) 6.7 Hz); 13C NMR (CDCl3)
δ 206.8, 169.7, 165.9, 154.1, 148.4, 130.9, 130.0, 129.5, 124.4,
112.8, 106.4, 55.7, 52.5, 52.4, 29.4, 29.3, 29.0, 22.3, 13.6; IR
(neat) 1718 (s), 1529 (m) cm-1; LCMS 346 (M, 2), 315 (16),
272 (100), 230 (40), 213 (23); HRMS calcd for C19H22O6
346.1417, found 346.1414.
Cou p lin g of Alk yn e Ald eh yd e 8B w ith Ca r ben e Com -
p lex 17A. General procedure 2 was followed using carbene
complex 17A (146 mg, 0.500 mmol) and alkyne aldehyde 8B
(96 mg, 0.500 mmol). After final purification, a white solid
identified as ester 18G (99 mg, 62% yield) and a liquid
identified as alcohol 19G (21 mg, 15% yield) were obtained.
18G: 1H NMR (CDCl3) δ 7.15 (d, 1 H, J ) 4.6 Hz), 6.86 (d, 1
H, J ) 4.8 Hz), 5.62 (d, 1 H, J ) 4.4 Hz), 3.57 (s, 3 H), 2.72
(ddd, 1 H, J ) 13.2, 8.9, 4.6 Hz), 2.50-1.10 (m, 9 H), 1.29
(sextet, 2 H, J ) 7.0 Hz), 1.12 (dd, 1 H, J ) 13.2, 4.8 Hz), 0.88
(t, 3 H, J ) 7.0 Hz); 13C NMR (CDCl3) δ 173.1, 152.4, 141.4,
134.5, 125.9, 124.5, 114.7, 72.7, 55.0, 54.6, 35.6, 34.2, 31.0, 29.8,
26.3, 24.9, 23.5, 13.8; IR (neat) 1756 (s), 1666 (m) cm -1; LCMS
(EI) 318 (M, 10), 274 (100), 185 (54), 148 (75), 98 (28). Anal.
Calcd for C18H22O3S: C, 67.89; H, 6.96; S, 10.07. Found: C,
68.04; H, 7.22; S, 10.02. 19G: 1H NMR (CDCl3 with D2O) δ
7.31 (d, 1 H, J ) 5.4 Hz), 7.24 (d, 1 H, J ) 5.4 Hz), 5.07 (dd,
1 H, J ) 10.6, 5.5 Hz), 2.85-2.22 (m, 5 H), 2.08 (m, 1 H), 1.85
(m, 1 H), 1.80 (q, 1 H, J ) 10.6 Hz), 1.60-1.15 (m, 5 H), 0.93
(t, 3 H, J ) 7.2 Hz); 13C NMR(CDCl3) δ 199.4, 149.7, 146.9,
134.9, 133.7, 127.4, 124.8, 67.5, 43.4, 37.9, 36.9, 30.6, 28.4, 26.9,
22.9, 13.8; IR(neat) 3381 (s, br), 1646 (s), 1574 (m) cm-1; MS
(EI) 276 (M, 56), 258 (14), 247 (100), 243 (81); HRMS calcd for
C
16H20O2S 276.1184, found 276.1192.
Cou p lin g of Alk yn e Ald eh yd e 8B w ith Ca r ben e Com -
p lex 17B. General procedure 2 was followed using carbene
complex 17B (113 mg, 0.37 mmol) and alkyne aldehyde 8B
(72 mg, 0.37 mmol). After final purification, a white solid
identified as ester 18H (75 mg, 71% yield) and a clear liquid
tentatively identified as alcohol 19H (11 mg, 10% yield) were
obtained. 18H: 1H NMR (CDCl3) δ 7.11 (d, 1 H, J ) 5.1 Hz),
6.78 (d, 1 H, J ) 5.1 Hz), 5.60 (d, 1 H, J ) 4.8 Hz), 3.58 (s, 3
H), 2.51 (br t, 1 H, J ) 8.8 Hz), 2.35 (dd, 1 H, J ) 12.9, 4.8
Hz), 2.22 (m, 1 H), 2.12-1.71 (m, 2 H), 1.70-1.15 (m, 3 H)
overlapping with 1.37 (d, 1 H, J ) 12.9 Hz) and 1.24 (s, 3 H),
1.05 (td, 1 H, J ) 16.9, 6.2 Hz), 0.89 (t, 3 H, J ) 7.0 Hz); 13C
NMR (CDCl3) δ 171.7, 150.6, 143.6, 134.9, 126.0, 124.2, 115.3,
72.6, 58.4, 55.4, 44.4, 34.9, 32.5, 31.2, 29.2, 24.1, 23.5, 22.0,
13.8; IR (CDCl3) 1758 (s), 1666 (m) cm-1. Anal. Calcd for
C
19H24O3S: C, 68.74; H, 7.29. Found: C, 68.59; H, 7.41. 19H:
1H NMR (CDCl3 with D2O) δ 7.32 (d, 1 H, J ) 5.4 Hz), 7.15 (d,
1 H, J ) 5.4 Hz), 5.05 (dd, 1 H, J ) 10.2, 6.1 Hz), 2.81-2.28
(m, 3 H), 2.17 (dd, 1 H, J ) 11.3, 6.1 Hz), 2.05-1.20 (m, 8 H),
1.20 (s, 3 H), 0.92 (t, 3 H, J ) 7.2 Hz); IR 3381 (s, br), 1646
(s), 1574 (m) cm-1
.
Cou p lin g of Alk yn e Ald eh yd e 8C w ith Ca r ben e Com -
p lex 17A. General procedure 2 was followed using carbene
complex 17A (87 mg, 0.300 mmol) and alkyne aldehyde 8C
(68 mg, 0.300 mmol). After final purification, a white solid
identified as ester 18I was obtained (66 mg, 63% yield): 1H
NMR (CDCl3) δ 7.48 (m, 2 H), 7.24 (m, 2 H), 5.62 (d, 1 H, J )
4.4 Hz), 3.62 (s, 3 H), 2.81 (ddd, 1 H, J ) 13.4, 8.9, 4.5 Hz)
2.50-1.22 (m, 12 H), 0.89 (t, 3 H, J ) 7.4 Hz); 13C NMR (CDCl3)
δ 172.8, 155.92, 154.91, 152.2, 126.1, 124.0, 123.5, 119.4, 116.8,
113.9, 112.0, 71.0, 55.1, 52.8, 35.7, 34.8, 31.0, 30.3, 26.7, 24.8,
23.6, 13.8; IR (neat) 1760 (s), 1660 (m) cm-1; LCMS (EI) 352
(M, 5), 308 (40), 265 (19), 251 (100). Anal. Calcd for C22H24O4:
C, 74.98; H, 6.86. Found: C, 74.94; H, 6.90.
Cou p lin g of Alk yn e Ald eh yd e 8G w ith Ca r ben e Com -
p lex 2. General procedure 1 was followed using carbene
complex 2 (150 mg, 0.60 mmol) and alkyne aldehyde 8G (104
mg, 0.40 mmol) and using chlorobenzene as solvent; the
reaction was conducted at reflux. After final purification, a
white solid identified as ketone 20 was obtained (55 mg, 48%
yield): 1H NMR (CDCl3) δ 7.45 (d, 1 H, J ) 5.5 Hz), 7.38 (d, 1
H, J ) 5.5 Hz), 7.09 (s, 1 H), 4.02 (t, 1 H, J ) 7.3 Hz), 3.04 (t,
4 H, J ) 6.6 Hz), 2.21 (quintet, 2 H, J ) 6.6 Hz), 2.15 (m, 1
H), 1.98 (s, 3 H), 1.78 (m, 1 H), 1,24 (m, 4 H), 0.82 (t, 3 H, J )
7.0 Hz); 13C NMR (CDCl3) δ 208.4, 140.7, 137.4, 136.6, 136.2,
132.3, 125.3, 122.1, 120.3, 57.7, 33.1, 32.1, 31.1, 29.9, 28.7, 24.9,
22.6, 13.8; IR (neat) 1713 (s) cm-1; MS (EI) 286 (M, 53), 244
(34), 243 (84), 201 (21), 187 (100); HRMS calcd for C18H22OS
286.1391, found 286.1381.
Cou p lin g of Alk yn e Ald eh yd e 8A w ith Ca r ben e Com -
p lex 17A. General procedure 2 was followed using carbene
complex 17A (139 mg, 0.48 mmol) and alkyne aldehyde 8A
(84 mg, 0.48 mmol) and using THF as solvent; the reaction
was conducted at reflux. After final purification, a white solid
identified as ketone 21N was obtained (85 mg, 73% yield): 1H
NMR (CDCl3) δ 7.33 (d, 1 H, J ) 2.0 Hz), 6.58 (d, 1 H, J ) 2.0
Cou p lin g of Alk yn e Ald eh yd e 8C w ith Ca r ben e Com -
p lex 17B. General procedure 2 was followed using carbene
complex 17B (56 mg, 0.185 mmol) and alkyne aldehyde 8C
(42 mg, 0.185 mmol). After final purification, a white solid
1
identified as ester 18J was obtained (37 mg, 54% yield): H
NMR (CDCl3) δ 7.45 (m, 2 H), 7.25 (m, 2 H), 5.59 (dd, 1 H, J
) 4.7, 1.0 Hz), 3.63 (s, 3 H), 2.73 (m, 1 H), 2.43 (dd, 1 H, J )
13.2, 4.7 Hz), 2.32 (m, 1 H), 2.0 (m, 2 H), 1.82-1.10 (m, 6 H)
overlapping with 1.48 (dd, 1 H, J ) 13.2, 1.0 Hz) and 1.29 (s,

Total Synthesis of a Baccharis-Derived Cadinene Derivative
J . Org. Chem., Vol. 67, No. 12, 2002 4185
Hz), 2.85-2.75 (m, 2 H), 2.70-2.20 (m, 5 H), 2.15-1.90 (m, 2
H), 1.85-1.55 (m, 2 H), 1.55-1.10 (m, 4 H), 0.91 (t, 3 H, J )
6.6 Hz); 13C NMR (CDCl3) δ 198.6, 157.4, 147.1, 141.7, 132.0,
117.4, 109.8, 37.5, 37.3, 31.2, 30.7, 29.2, 25.5, 23.6, 22.9, 13.8;
IR (neat) 1660 (s), 1600 (m) cm-1; MS (EI) 244 (M, 66), 229
(19), 215 (92), 201 (100), 188 (11), 174 (31); HRMS calcd for
complex 2 (150 mg, 0.60 mmol) and dialkyne aldehyde 8I (101
mg, 0.50 mmol) and using THF as the solvent; the reaction
was conducted at reflux. After final purification, a white solid
identified as lactone 25 was obtained (55 mg, 43% yield): 1H
NMR (CDCl3) δ 7.78 (d, 1 H, J ) 5.3 Hz), 7.68 (d, 1 H, J ) 5.3
Hz), 7.20 (s, 1 H), 3.27 (t, 2 H, J ) 7.4 Hz), 2.97 (t, 2 H, J )
7.4 Hz), 2.45 (s, 3 H), 2.22 (quintet, 2 H, J ) 7.4 Hz); 13C NMR
(CDCl3) 157.4, 150.0, 145.0, 140.2, 136.9, 135.6, 127.0, 125.1,
124.7, 114.1, 33.8, 32.1, 29.6, 25.0, 16.3; IR 1710 (s) cm-1; MS
(EI) 256 (M, 100), 241 (42), 227 (6), 184 (13); HRMS calcd for
C
16H20O2 244.1463, found 244.1461.
Cou p lin g of Alk yn e Ald eh yd e 8H w ith Ca r ben e Com -
p lex 17A. General procedure 2 was followed using carbene
complex 17A (116 mg, 0.40 mmol) and alkyne-aldehyde 8H
(93 mg, 0.40 mmol) and using THF as the solvent; the reaction
was conducted at reflux. After final purification, a white solid
identified as ketone 18O was obtained (92 mg, 64% yield): 1H
NMR (CDCl3) δ 7.06 (s, 1 H), 5.55 (d, 1 H, J ) 4.6 Hz), 3.87 (s,
3 H), 3.56 (s, 3 H), 2.77 (ddd, 1 H, J ) 13.7, 9.0, 4.6 Hz), 2.50-
1.95 (m, 5 H), 1.90-1.0.95 (m, 4 H) overlapping with 1.26
(sextet, 2 H, J ) 7.0 Hz) and 1.18 (dd, 1 H, J ) 13.7, 4.9 Hz),
0.88 (t, 3 H, J ) 7.0 Hz); 13C NMR (CDCl3): δ 172.1, 158.8,
156.1, 152.7, 144.6, 123.9, 117.3, 113.5, 70.7, 55,2, 52.5, 51.9,
35.1, 34.6, 31.1, 28.8, 26.4, 24.9, 23.5, 13.7; IR (neat) 1762 (s),
1732 (s), 1662 (m) cm-1; MS (FAB) 361 (M + 1, 18), 316 (31),
245 (10), 189 (21); HRMS calcd for C20H25O6 361.1651, found
361.1666.
Cou p lin g of Alk yn e Ald eh yd e 8A w ith Ca r ben e Com -
p lex 17B. General procedure 2 was followed using carbene
complex 17B (128 mg, 0.44 mmol) and alkyne aldehyde 8A
(102 mg, 0.44 mmol) and using THF as the solvent; the
reaction was conducted at reflux. After final purification, a
white solid identified as ketone 21P was obtained (55 mg, 65%
yield): 1H NMR (CDCl3) δ 7.34 (d, 1 H, J ) 2.0 Hz), 6.55 (d, 1
H, J ) 2.0 Hz), 2.80-2.25 (m, 5 H) overlapping with 2.86 (ddd,
1 H, J ) 17.1, 11.4, 5.7 Hz) 2.80 (m, 2 H), 1.88 (td, 1 H, J )
13.5, 5.7 Hz), 1.72 (m, 1 H), 1.60-1.00 (m, 4 H) overlapping
with 1.12 (s, 3 H), 0.91 (t, 3 H, J ) 6.7 Hz); 13C NMR (CDCl3):
δ 198.3, 156.1, 151.0, 141.9, 131.9, 116.8, 110.5, 37.7, 36.4, 35.3,
33.8, 31.1, 25.8, 23.0, 21.0, 20.8, 14.0; IR (neat) 1661 (s), 1601
(m) cm-1; MS (EI): 258 (M, 61), 243 (23), 229 (100), 215 (91),
201 (13), 187 (19); HRMS calcd for C17H22O2 258.1620, found
258.1625.
C
15H12O2S 256.0558, found 261.0564.
Cou p lin g of Alk yn e Ald eh yd e 39 w ith Ca r ben e Com -
p lex 17C. General procedure 2 was followed using carbene
complex 17C (145 mg, 0.48 mmol) and alkyne aldehyde 39 (87
mg, 0.65 mmol) and using THF as the solvent; the reaction
was conducted at reflux. After final purification, a white solid
identified as ketone 38 was obtained (50 mg, 49% yield): 1H
NMR (400 MHz) (CDCl3) δ 7.07 (s, 1 H), 6.26 (d, 1 H, J ) 2.0
Hz), 2.81 (dd, 1 H, J ) 17.2, 4.9 Hz), 2.65-2.30 (m, 4 H), 2.11
(tdd, 1 H, J ) 11.6 (t), 3.6, 2.0 Hz), 2.13 (s, 3 H), 1.85 (m, 1 H),
1.80-1.56 (m, 2 H), 1.15 (d, 3 H, J ) 6.5 Hz); 13C NMR (CDCl3)
δ 199.2, 158.5, 155.3, 139.3, 119.5, 118.4, 117.0, 42.4, 37.2, 35.6,
32.3, 26.5, 19.4, 10.7. The spectral data were identical to those
previously reported for this compound.23a
Ack n ow led gm en t. We thank the Petroleum Re-
search Fund, administered by the American Chemical
Society, the National Science Foundation, and New
Mexico State University for financial support. We thank
Ms. Caroline Ladd of the University of Maryland for
acquisition of mass spectral data.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for formation of alkynealdehydes, γ,δ-unsatuarted
carbene complexes, and the experiments in Table 1, entries
D-F. Photocopies of 1H NMR and 13C NMR spectra for
compounds 8A-C,G-I, 11D, 12A-C, 17C, 18G,J ,L,O, 19G,
20, 21N,P , 25, and 39. This material is available free of charge
via the Internet at http://pubs.acs.org.
Cou p lin g of Dia lk yn e Ald eh yd e 8I w ith Ca r ben e
Com p lex 2. General procedure 1 was followed using carbene
J O011136Y