Flexible synthesis of metacycloprodigiosin and functional derivatives thereof

Article abstract of DOI:10.1021/jo991022a

A conceptually new approach to m-pyrrolophane derivatives is outlined providing ready access to compound 23 which can be elaborated into the immunosuppressive alkaloid metacycloprodigiosin 2 according to literature procedures. The key steps of this sequence involve a palladium-catalyzed macrocyclization reaction of vinyl epoxide 10, the conversion of the α- pyrone derivative 14 into the pyrrole targets, and the attachment of the side chain via a Wittig (or Peterson) olefination followed by hydrogenation of the alkene formed over Crabtree's catalyst. The flexibility of this route is demonstrated by the synthesis of several analogues of the parent compound 23 which may help to assess the structure/activity profile of the prodigiosin family of natural products in more detail. The unusual pyrone structure 14 used to encode the meta-bridged pyrrolophane units was characterized by X-ray crystallography.

Full text of DOI:10.1021/jo991022a

J . Org. Chem. 1999, 64, 8281-8286
8281
F lexible Syn th esis of Meta cyclop r od igiosin a n d F u n ction a l
Der iva tives Th er eof
Alois Fu¨rstner* and Helga Krause
Max-Planck-Institut fu¨r Kohlenforschung, D-45470 Mu¨lheim/ Ruhr, Germany
Received J une 25, 1999
A conceptually new approach to m-pyrrolophane derivatives is outlined providing ready access to
compound 23 which can be elaborated into the immunosuppressive alkaloid metacycloprodigiosin
2 according to literature procedures. The key steps of this sequence involve a palladium-catalyzed
macrocyclization reaction of vinyl epoxide 10, the conversion of the R-pyrone derivative 14 into the
pyrrole targets, and the attachment of the side chain via a Wittig (or Peterson) olefination followed
by hydrogenation of the alkene formed over Crabtree’s catalyst. The flexibility of this route is
demonstrated by the synthesis of several analogues of the parent compound 23 which may help to
assess the structure/activity profile of the prodigiosin family of natural products in more detail.
The unusual pyrone structure 14 used to encode the meta-bridged pyrrolophane units was
characterized by X-ray crystallography.
In tr od u ction
Recent reports on the pronounced immunosuppressive
activity of prodigiosin alkaloids have led to strongly
renewed interest in this well-known class of natural
products, particularly because their biochemical mech-
anism of action is distinctly different from that of
cyclosporin A and FK 506.1,2 Most studies are dealing
with undecylprodigiosin (prodigiosin 25-C) 1 as the most
accessible member of this family,3,4 although preliminary
data indicate that its cyclic analogues metacycloprodigi-
osin 2 and streptorubin B 3 show similar potency.5
Intrigued by this pharmacological perspective, we have
embarked in a detailed study of compounds of this type.
As part of this program, the first total synthesis of the
macrocyclic derivative nonylprodigiosin 4 via an intrinsi-
cally modular metathesis approach was reported,6 as well
as a convenient approach to compounds 2 and 3 based
(1) (a) Lin, J . Immunol. Today 1993, 14, 290. (b) Nakamura, A.;
Nagai, K.; Ando, K.; Tamura, G. J . Antibiot. 1986, 39, 1155. (c) Tsuji,
R. F.; Yamamoto, M.; Nakamura, A.; Kataoka, T.; Magae, J .; Nagai,
on a conceptually new, PtCl2-catalyzed pyrrole synthe-
sis.7,8 Although the latter method is highly optimized,
delivering the natural products in excellent overall yield
in a few steps only, it is less adequate for the formation
of functionalized analogues thereof. We now describe a
complementary approach to metacycloprodigisin 2 which
forms its core 5 by a palladium-catalyzed macrocylization
reaction and encodes the pyrrole ring in a keto-pyrone
entity. This unusual strategy can be used for a synthesis-
driven mapping of the structure/activity relationship of
2 because it provides access to various metacycloprodi-
giosin analogues bearing polar substituents on the mac-
rocyclic part and allows systematic variations of the side
chain.
K.; Yamasaki, M. J . Antibiot. 1990, 43, 1293. (d) Kataoka, T.; Magae,
J .; Nariuchi, H.; Yamasaki, M.; Nagai, K. J . Antibiot. 1992, 45, 1303.
(e) Tsuji, R. F.; Magae, J .; Yamashita, M.; Nagai, K.; Yamasaki, M. J .
Antibiot. 1992, 45, 1295. (f) Kataoka, T.; Magae, J .; Kasamo, K.;
Yamanishi, H.; Endo, A.; Yamasaki, M.; Nagai, K. J . Antibiot. 1992,
45, 1618. (g) Kataoka, T.; Muroi, M.; Ohkuma, S.; Waritani, T.; Magae,
J .; Takatsuki, A.; Kondo, S.; Yamasaki, M.; Nagai, K. FEBS Lett. 1995,
359, 53. (h) Lee, M.-H.; Yamashita, M.; Tsuji, R. F.; Yamasaki, M.;
Kataoka, T.; Magae, J .; Nagai, K. J . Antibiot. 1998, 51, 92. (i) Han, S.
B.; Kim, H. M.; Kim, Y. H.; Lee, C. W.; J ang, E.-S.; Son, K. H.; Kim,
S. U.; Kim, Y. K. Int. J . Immunopharmacol. 1998, 20, 1. (j) Sato, T.;
Konno, H.; Tanaka, Y.; Kataoka, T.; Nagai, K.; Wasserman, H. H.;
Ohkuma, S. J . Biol. Chem. 1998, 273, 21455. (k) Nakamura, A.; Magae,
J .; Tsuji, R. F., Yamasaki, M.; Nagai, K. Transplantation 1989, 47,
1013.
(2) Songia, S.; Mortellaro, A.; Taverna, S.; Fornasiero, C.; Schreiber,
E. A.; Erba, E.; Colotta, F.; Mantovani, A.; Isetta, A.-M.; Golay, J . J .
Immunol. 1997, 158, 3987.
(3) Compound 1 is available e. g. by fermentation of Streptomyces
hiroshimensis, cf. Harashima, K.; Tsuchida, N.; Tanaka, T.; Nagatsu,
J . Agric. Biol. Chem. 1967, 31, 481.
Resu lts a n d Discu ssion
(4) Undecylprodigiosin 1 has been shown to inhibit T cell activation
in the mid to late G1 phase, mostly downstream from the interaction
of IL-2 with its receptor, cf. ref 2.
(5) (a) Magae, J .; Miller, M.; Nagai, K.; Shearer, G. M. J . Antibiot.
1996, 49, 86. (b) Abe, F.; Morimoto, M.; Shibuya, K.; Yamazaki, M.;
Nishigori, T.; Saito, S.; Shimada, N. J pn. Kokai Tokkyo Koho J P
02,250,828 [90,250,828], Oct 8, 1990. Chem. Abstr. 1990, 114: 108967g.
It is well established in the literature that prodigiosin
derivatives can be conveniently formed by condensation
(6) Fu¨rstner, A.; Grabowski, J .; Lehmann, C. W. J . Org. Chem. 1999,
64, 8275.
10.1021/jo991022a CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/29/1999

8282 J . Org. Chem., Vol. 64, No. 22, 1999
Fu¨rstner and Krause
Sch em e 1
Sch em e 2
of an appropriate pyrrole segment (i.e., 5 for metacyclo-
prodigiosin) with aldehyde 6 or analogues thereof (Scheme
1).8,9 Early studies have outlined productive routes to the
latter and have described numerous modifications of the
parent pyrrolylpyrromethene chromophore by introduc-
ing different N-substituents, by replacing the pyrrole
units with other heterocycles, or by changing the sub-
stitution pattern on the individual aromatic rings.10 In
contrast, however, variations of the macrocyclic core are
scarce since a general entry into compounds of this type
is missing.
Summarized in the following is a flexible approach to
meta-pyrrolophane derivatives of type 7 bearing substit-
uents of different polarity on the macrocyclic perimeter.
The initial steps (Scheme 2) closely follow our route to
the antitumor alkaloid roseophilin outlined recently.11 In
this study, we have identified sulfonium salt 812 as a
valuable building block for heterocycle synthesis via
transition metal-catalyzed C-C-bond formations.11,13
Specifically, deprotonation of 8 with tert-BuLi followed
by trapping of the sulfur ylide14 thus formed with
8-bromooctanal affords vinylepoxide 9, which can be
alkylated at its bromine terminus with the potassium salt
of methyl (phenylsulfonyl)acetate. Exposure of the result-
ing product 10 to catalytic amounts of Pd(PPh3)4 and
dppe (dppe ) bis(diphenylphosphino)ethane) under high
dilution conditions delivers the desired 12-membered ring
11 via a π-allylpalladium intermediate formed upon
regioselective activation of the vinylepoxide group.15
Compound 11 is obtained as a mixture of diastereo-
isomers;16 however, it is not necessary to separate the
individual compounds since all of them converge into the
final meta-pyrrolophane target. Cleavage of the silyl
ether then effects a lactonization of the primary hydroxyl
group with the adjacent ester. This seemingly trivial step
turned out to be somewhat delicate and was best achieved
by using TASF () tris(dimethylamino)sulfonium difluo-
rotrimethylsilicate) in dilute THF solution. Subsequent
oxidation of the secondary OH group of 12 by means of
Dess-Martin periodinane as the preferred reagent pro-
vides ketone 13 in 74% isolated yield.17
(7) Fu¨rstner, A.; Szillat, H.; Gabor, B.; Mynott, R. J . Am. Chem.
Soc. 1998, 120, 8305.
(8) For previous synthetic studies on metacycloprodigiosin, see: (a)
Wasserman, H. H.; Rodgers, G. C.; Keith, D. D. J . Am. Chem. Soc.
1969, 91, 1263. (b) Wasserman, H. H.; Keith, D. D.; Nadelson, J . J .
Am. Chem. Soc. 1969, 91, 1264. (c) Wasserman, H. H.; Keith, D. D.;
Rodgers, G. C. Tetrahedron 1976, 32, 1855. (d) Wasserman, H. H.;
Gosselink, E.; Keith, D. D.; Nadelson, J .; Sykes, R. J . Tetrahedron 1976,
32, 1863. (e) Wasserman, H. H.; Keith, D. D.; Nadelson, J . Tetrahedron
1976, 32, 1867.
Exposure of compound 13 to DBU in refluxing THF
converts the saturated lactone into R-pyrone 14 by
elimination of the sulfone moiety and concomitant shift
of the exocyclic double bond into the ring. The outcome
(9) For previous syntheses of other prodigiosins derivatives, see inter
alia: (a) Hearn, W. R.; Elson, M. K.; Williams, R. H.; Medina-Castro,
J . J . Org. Chem. 1970, 35, 142. (b) Wasserman, H. H.; Lombardo, L.
J . Tetrahedron Lett. 1989, 1725. (c) Rapoport, H.; Holden, K. G. J . Am.
Chem. Soc. 1962, 84, 635. (d) Boger, D. L.; Patel, M. Tetrahedron Lett.
1987, 28, 2499. (e) Boger, D. L.; Patel, M. J . Org. Chem. 1988, 53,
1405.
(10) For preparation and the biological evaluation of prodigiosin
analogues, see the following for leading references: (a) Brown, D.;
Griffiths, D.; Rider, M. E.; Smith, R. C. J . Chem. Soc., Perkin Trans.
1 1986, 455. (b) Blake, A. J .; Hunter, G. A.; McNab, H. J . Chem. Soc.,
Chem. Comun. 1990, 734. (c) Berner, H.; Schulz, G.; Reinshagen, H.
Monatsh. Chem. 1977, 108, 233. (d) Berner, H.; Schulz, G.; Reinshagen,
H. Monatsh. Chem. 1978, 109, 137. (e) Berner, H.; Schulz, G.;
Reinshagen, H. Monatsh. Chem. 1977, 108, 285. (f) Berner, H.; Schulz,
G.; Fischer, G.; Reinshagen, H. Monatsh. Chem. 1978, 109, 557. (g)
Castro, A. J .; Gale, G. R.; Means, G. E.; Tertzakian, G. J . Med. Chem.
1967, 10, 29. (h) D’Auria, M.; De Luca, E.; Mauriello, G.; Racioppi, R.
Synth. Commun. 1999, 29, 35.
(11) (a) Fu¨rstner, A.; Weintritt, H. J . Am. Chem. Soc. 1997, 119,
2944. (b) Fu¨rstner, A.; Weintritt, H. J . Am. Chem. Soc. 1998, 120, 2817.
(c) Fu¨rstner, A.; Gastner, T.; Weintritt, H. J . Org. Chem. 1999, 64,
2361.
(12) A large scale preparation is described in the Supporting
Information.
(13) For an application of this building block to a furan synthesis,
see: Fu¨rstner, A.; Gastner, T. Synlett 1999, 29.
(14) (a) tert-BuLi was recommended as the deprotonating agent of
choice, cf.: LaRochelle, R. W.; Trost, B. M.; Krepski, L. J . Org. Chem.
1971, 36, 1126. (b) Review: Trost, B. M.; Melvin, L. S. Sulfur Ylides;
Organic Chemistry Series; Academic Press: New York, 1975; Vol. 31.
(15) For pertinent reviews on Pd(0)-catalyzed reactions of vinyl
epoxides, see: (a) Tsuji, J . Palladium Reagents and Catalysts; Wiley:
New York, 1995. (b) Trost, B. M. Angew. Chem. 1989, 101, 1199.
(16) The same is true for compounds 9-13 in Scheme 2.
(17) (a) Dess, D. B.; Martin, J . C. J . Org. Chem. 1983, 48, 4155. (b)
Meyer, S. D.; Schreiber, S. L. J . Org. Chem. 1994, 59, 7549.

Flexible Synthesis of Metacycloprodigiosin
J . Org. Chem., Vol. 64, No. 22, 1999 8283
Sch em e 4
F igu r e 1. ORTEP diagram of the molecular structure of
compound 14. Anisotropic displacement parameter ellipsoids
are drawn at 50% probability, hydrogen atoms are omitted for
clarity. Selected bond lengths (Å) and torsion angles (deg):
O3′-C3′ 1.358(1), O3′-C5′ 1.372(2), O5′-C5′ 1.212(2), C3-
C3′ 1.337(2), C3-C4 1.429(2), C4-C5 1.346(2), C5-C5′
1.448(2); C5-C6-C7-C8 -77.2(2), C6-C7-C8-C9 72.8(2),
C7-C8-C9-C10 70.1(2), C8-C9-C10-C11 -176.80(13), C9-
C10-C11-C12 68.33(18), C10-C11-C12-C1 68.57(18), C12-
C1-C2-C3 58.32(17).
delicate.20 Specifically, treatment of compound 15 with
benzylamine in the presence of HOAc in THF leads to a
mixture of pyrroles 16-18. Despite considerable experi-
mentation (solvent, temperature, acid, amine) we were
unable to change this distribution pattern to a significant
extent.
Fortunately, however, the prevailing product of this
step, i.e., compound 16 formed by concomitant 1,4-
addition of an acetate during the pyrrole condensation
reaction, lends itself very well for the purpose of this
study (Scheme 4). Cleavage of the acetoxy group with
NaOMe in MeOH delivers aldol 19 in 91% yield which
can be oxidized to the â-ketoester derivative 20 by using
tetra-n-propylammonium perruthenate.21 This smooth
transformation is in stark contrast to attempted oxida-
tions with PDC or under Swern conditions, which destroy
Sch em e 3
the rather sensitive pyrrole ring. Decarboxylation of
22
ketoester 20 according to Krapcho’s protocol
in the
presence of NaCl in hot aq DMSO forms ketone 21 in
excellent yield which serves as a convenient platform for
a systematic variation of the side chain. To demonstrate
this aspect, compound 21 was converted into alkene 22
on exposure to freshly prepared ethylidenetriphenylphos-
phorane. 22 is then reduced in the presence of Crabtree’s
catalyst23 to product 23 which can be elaborated into
metacycloprodigiosin 2 according to literature procedures
by condensation with the known aldehyde 6.8,9 The more
lipophilic analogue 24 is analogously obtained upon
reaction with undecylidenetriphenyl-phoshorane. Like-
wise, ketone 21 allows the formation of functionalized
core compounds as demonstrated by the preparation of
ester 25 via a Peterson olefination with the lithium
enolate of ethyl trimethylsilyl acetate as the reagent.24
In summary, we have outlined a conceptually novel
route to meta-pyrrolophane derivatives based on a pal-
ladium-catalyzed macrocyclization of a vinyl epoxide
precursor followed by an unprecedented transformation
of a keto-pyrone derivative into a 2,4-disubstituted pyr-
role ring. This methodology gives ready access to com-
pound 23 which constitutes a key intermediate en route
of this unusual transformation was corroborated by the
X-ray structure of the meta-bridged R-pyrone 14 depicted
in Figure 1.18 Note that this rearrangement advanta-
geously adjusts the oxidation pattern of the former
primary OH group, because 14 mimics a masked 1,4-
dicarbonyl compound encoding the targeted pyrrole ring.
The enol lactone character of 14 is reflected in the
alternating C-C-bond length of the fully planar six-
membered ring (mean deviation from least squares plane
is 0.018 Å), with the formal single bonds being somewhat
shortened via conjugation. The macrocyclic ring of 14
adopts a conformation which involves only gauche inter-
actions (except for the anti arrangement of C8-C9-C10-
C11) forcing the carbonyl group into an axial position.
Solvolysis of pyrone 14 with NaOMe in MeOH unravels
tricarbonyl compound 15, in which the residual double
bond appears in conjugation to the aldehyde group as
unequivocally deduced from its NMR spectra (Scheme
3).19 This Michael acceptor system, however, renders the
subsequent Paal-Knorr pyrrole synthesis somewhat
(20) For a timely and comprehensive review on the Paal-Knorr and
related pyrrole syntheses, see: Gossauer, A. In Houben-Weyl, Methoden
der Organischen Chemie; Kreher, R. R., Ed.; Thieme: Stuttgart, 1994;
Vol. E 6a, Part 1, pp 556-798.
(21) Ley, S. V.; Norman, J .; Griffith, W. P.; Marsden, S. P. Synthesis
1994, 639.
(18) Full information on the X-ray structure of compound 14 is given
in the Supporting Information. The complete set of data has been
deposited at the Cambridge Crystallographic Data Center, Cambridge,
UK, under the deposition number CCDC 127650.
(22) Krapcho, P. A. Synthesis 1982, 893.
(23) Crabtree, R. H.; Felkin, H.; Fellebeen-Khan, T.; Morris, G. E.
J . Organomet. Chem. 1979, 168, 183.
(24) For a review on the Peterson olefination, see: Ager, D. J . Org.
React. 1990, 38, 1.
(19) For details, see the Supporting Information.

8284 J . Org. Chem., Vol. 64, No. 22, 1999
Fu¨rstner and Krause
Sch em e 5a
eluent affords the title compound as a colorless syrup (1.57 g,
78%, mixture of diastereoisomers). 1H NMR (300 MHz,
CDCl3): δ ) 7.53-7.91 (m, 5H), 5.17-5.22 (m, 1.5H), 5.00 (m,
0.5H), 4.09-4.17 (m, 2H), 3.93 (dd, J ) 10.3, 4.7 Hz, 1H), 3.61
(s, 3H), 3.36-3.45 (m, 0.5H), 3.14 (d, J ) 2.2 Hz, 0.5H), 3.04
(m, 0.5H), 2.82-2.89 (m, 0.5H), 1.94-1.99 (m, 2H), 1.22-1.49
(m, 12H), 0.91 (s, 4.5H), 0.90 (s, 4.5H), 0.07 (s, 3H), 0.06 (s,
3H). 13C NMR (CDCl3, 75 MHz): δ ) 166.4, 144.7, 142.1, 137.0,
134.1, 130.0, 129.2, 128.9, 128.5, 111.8, 111.1, 70.8, 64.4, 62.6,
59.9, 58.6, 58.2, 56.2, 52.8, 32.1, 29.6, 29.1, 29.0, 28.9, 28.8,
26.8, 26.6, 26.5, 26.1, 26.0, 25.8, 25.7, 18.3, 18.2, -5.40, -5.44.
Anal. Calcd for C27H44O6SSi (524.78): C 61.8, H 8.5, S 6.1.
Found: C 61.66, H 8.41, S 6.01.
Ma cr ocycle 11. A solution of compound 10 (2.43 g, 4.63
mmol) in THF (150 mL) is added over a period of 2 h to a
refluxing solution of Pd(PPh3)4 (538 mg, 0.465 mmol) and dppe
(368 mg, 0.924 mmol) in THF (300 mL). Once the addition is
complete, the reaction is worked up by evaporation of the
solvents. The remaining residue is purified by flash chroma-
tography (hexane/ethyl acetate, 3/1) affording macrocycle 11
as a pale yellow syrup (1.68 g, 68%, mixture of diastereo-
isomers). Careful chromatography allows enrichment of two
individual isomers for analytical purposes. Diastereoisomer
11a : 1H NMR (400 MHz, CDCl3): δ ) 7.50-7.78 (m, 5H), 5.78
(d, J ) 8.8 Hz, 1H), 4.54 (dt, J ) 8.8, 2.7 Hz, 1H), 4.01 (AB, J
) 11.6 Hz, 2H), 3.59 (s, 3H), 2.98 and 3.16 (AB, J ) 13.9 Hz,
2H), 2.07-2.24 (m, 2H), 1.20-1.86 (m, 14H), 0.82 (s, 9H), 0.01
(s, 3H), -0.02 (s, 3H). 13C NMR (CDCl3, 100 MHz): δ ) 168.1,
140.1, 136.5, 134.5, 134.1, 134.0, 133.4, 130.0, 129.9, 128.7,
76.5, 68.1, 60.7, 52.8, 38.0, 34.4, 29.4, 27.0, 25.9, 25.8, 25.6,
23.6, 22.6, 19.9, 18.1, -5.5. Diastereoisomer 11b: 1H NMR
(400 MHz, CDCl3): δ ) 7.50-7.79 (m, 5H), 5.17 (d, J ) 8.6
Hz, 1H), 4.35 (dt, J ) 8.0, 4.5 Hz, 1H), 4.29 and 4.15 (AB, J )
11.9 Hz, 2H), 3.60 (s, 3H), 3.11 and 2.98 (dAB, J ) 16.9, 1.1
Hz, 2H), 2.14-2.25 (m, 2H), 1.92 (br. s, 1H, OH), 1.05-1.72
(m, 13H), 0.88 (s, 9H), 0.09 (s, 3H), 0.07 (s, 3H). 13C NMR
(CDCl3, 100 MHz): δ ) 169.1, 136.0, 134.8, 134.2, 134.1, 130.2,
128.7, 75.9, 69.1, 62.0, 53.0, 33.8, 33.3, 26.7, 26.2, 25.8, 24.5,
24.0, 21.9, 19.3, 18.1, -5.4, -5.5.
a
Key: (a) Ph3PdCH2, DMSO, rt, 73%; (b) H2 (1 atm),
[Ir(COD)(PCy3)(pyridine)] (10 mol %), rt, 88%; (c) Ph3PdCH(CH2)9-
CH3, DMSO, rt, 51%; (d) Me3SiCH2COOEt, LDA, THF, -78 °C f
rt, 78%.
to metacycloprodigiosin 2. Moreover, we have obtained
a panel of functional analogues thereof (i.e., compounds
16-21, 24, and 25) which allow investigation of the
biological response to structural variations within the
macrocyclic ring of this lead structure. Studies along
these lines are underway and will be described in due
course.
Exp er im en ta l Section
La cton e 12. A solution of silyl ether 11 (1.43 g, 2.72 mmol)
in THF (200 mL) is treated with TASF () tris(dimethylamino)-
sulfonium difluorotrimethylsilicate) (1.00 g, 3.65 mmol). After
stirring for 20 min at ambient temperature, the reaction
mixture is partitioned between ethyl acetate and brine, the
organic layer is dried over Na2SO4, the solvent is evaporated,
and the crude product is purified by flash chromatography
(hexanes/ethyl acetate, 2/1), affording lactone 12 as a colorless
foam (562 mg, 55%, mixture of diastereoisomers). mp ) 70-
72 °C. 1H NMR (300 MHz, CDCl3): δ ) 7.51-7.90 (m, 5H),
5.62 (d, J ) 10.4 Hz, 1H), 5.09 (dd, J ) 12.5, 2.7 Hz, 0.5H);
4.83 (dt, J ) 12.5, 1.2 Hz, 0.5H), 4.51-4.65 (m, 0.5H), 4.31-
4.41 (m, 0.5H), 3.73 (s), 3.72 (s), 3.71 (s), 3.70 (s) [0.5H], 3.54
(ddd, J ) 14.8, 2.1, 1.1 Hz, 0.5H), 3.40 (ddd, J ) 16.0, 2.5, 1.1
Hz, 0.5H), 3.15 (dd, J ) 16.0, 2.9 Hz, 0.5H), 2.77 (dd, J ) 14.9,
2.8 Hz, 0.5H), 2.01-2.10 (m, 1.5H), 0.80-1.70 (m, 14H). 13C
NMR (CDCl3, 75 MHz): δ ) 167.0, 134.6, 134.5, 134.4, 133.5,
133.0, 131.4, 131.2, 129.9, 128.6, 128.5, 128.3, 74.6, 72.6, 71.9,
68.6, 68.1, 65.8, 36.2, 35.9, 35.4, 34.9, 34.5, 27.5, 26.4, 26.3,
25.6, 24.5, 23.5, 23.1, 22.7, 21.9, 20.5. Anal. Calcd for C20H26O5S
(378.48): C 63.5, H 6.9, S 8.5. Found: C 63.52, H 7.04, S 8.32.
Keton e 13. Dess-Martin periodinane (1.575 g, 3.71 mmol)
is added to a solution of alcohol 12 (562 mg, 1.48 mmol) in
CH2Cl2 (125 mL), and the resulting mixture is stirred for 3 h.
For workup, the reaction is diluted with ethyl acetate and
successively extracted with aq sat. NaHCO3 and aq sat.
Na2S2O3, the organic layer is dried over Na2SO4, the solvent
is evaporated, and the residue is purified by flash chromatog-
raphy (hexanes/ethyl acetate, 3/1), affording ketone 13 as a
colorless foam (414 mg, 74%, mixture of diastereoisomers). mp
Gen er a l. The setup of the reactions and the purification of
chemicals was carried out as described in the preceding paper
of this issue. For the instrumentation used and the spectral
formats see the Supporting Information.
{2-[(7-Br om oh ep t yl)oxir a n -3-yl]p r op en yl-1-oxy}-ter t-
bu tyld im eth ylsila n e (9). A solution of tert-BuLi (1.5 M in
pentane, 21 mL, 31 mmol) is slowly added to a solution of the
sulfonium salt 8 (10.8 g, 30.0 mmol) in THF (350 mL) at -78
°C under Ar. After stirring for 30 min at that temperature, a
solution of 8-bromooctanal (5.4 g, 26.0 mmol) in THF (20 mL)
is added, and the mixture is stirred for another 30 min at -78
°C and then slowly warmed to ambient temperature. Standard
extractive workup with EtOAc and water followed by flash
chromatography of the crude product (hexane/ethyl acetate,
50/1) provides compound 9 as a colorless syrup (6.86 g, 67%,
mixture of diastereoisomers). Experiments on a smaller scale
(2.51 g of the sulfonium salt) lead to slighly better yields of 9
(1.71 g, 73% yield). 1H NMR (300 MHz, CDCl3): δ ) 5.15-
5.10 (m, 1.5H), 4.93 (m, 0.5H), 4.10 (s, 1H), 4.02-4.04 (m, 1H),
3.37 (m, 0.5H), 3.30 (t, 1.5H), 2.80-3.09 (m, 2H), 1.75-1.80
(m, 2H), 1.26-1.35 (m, 10H), 0.84 (s, 4.5H), 0.83 (s, 4.5H),
0.019 (s, 3H), 0.010 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ )
144.8, 142.2, 111.9, 111.1, 64.4, 62.7, 60.0, 58.6, 58.3, 56.2, 33.8,
32.7, 32.2, 29.2, 29.1, 28.6, 28.3, 26.5, 26.1, 25.8, 18.3, 18.2,
-4.5, -4.6. Anal. Calcd for C18H35BrO2Si (391.46): C 55.2, H
9.0, Br 20.4. Found: C 55.34, H 9.12, Br 20.16.
2-(Be n ze n e su lfon yl)-9-{3-[1-(((t er t -b u t yld im e t h yl-
silan yl)oxy)m eth yl)vin yl]oxir an -2-yl}n on an oic Acid Meth -
yl Ester (10). KH (197 mg, 4.92 mmol) is added to a solution
of methyl (phenylsulfonyl)acetate (922 mg, 4.29 mmol) in DMF
(50 mL). After stirring for 15 min at ambient temperature, a
solution of bromide 9 (1.50 g, 3.83 mmol) in DMF (15 mL) is
added, and the resulting mixture is stirred at ambient tem-
perature for 24 h. Standard extractive workup followed by
flash chromatography with hexane/ethyl acetate (6/1) as the
1
) 71-73 °C. H NMR (300 MHz, CDCl3): δ ) 7.50-8.03 (m,
5H), 6.40-6.51 (m, 1H), 5.09 (d, J ) 12 Hz, 0.5H), 4.52 (dd, H
) 12.2, 2.8 Hz, 0.5H), 3.76 (dd, J ) 16.4, 2.8 Hz, 0.5H), 3.39
(ddd, J ) 16.5, 2.8, 1.2 Hz, 0.5H), 3.16 (d, J ) 12.5 Hz, 1H),
2.75-3.06 (m, 1.5H), 2.63-2.70 (m, 0.5H), 2.15-2.27 (m, 1H),
0.90-2.05 (m, 12H). 13C NMR (CDCl3, 75 MHz): δ ) 206.4,

Flexible Synthesis of Metacycloprodigiosin
J . Org. Chem., Vol. 64, No. 22, 1999 8285
202.6, 166.0, 163.8, 141.6, 138.2, 136.0, 134.5, 134.3, 131.6,
131.3, 129.2, 129.0, 128.7, 128.6, 110.9, 73.5, 73.1, 68.9, 46.2,
43.5, 36.7, 35.1, 30.2, 27.9, 26.1, 26.0, 25.9, 25.1, 23.6, 23.3,
23.2, 22.3, 21.9, 21.0, 20.1, 19.5. HRMS (C20H24O5S): calcd
376.134445; found 376.134468.
at ambient temperature for 1.5 h. The solvent is evaporated
and the residue purified by flash chromatography (hexanes/
ethyl acetate, gradient: 6/1 f 4/1 f 1/1), providing product
19 as a colorless syrup (67 mg, 91%). 1H NMR (300 MHz, CD2-
Cl2): δ ) 7.01-7.25 (m, 5H), 6.52 (d, J ) 1.9 Hz, 1H), 6.05 (d,
J ) 1.9 Hz, 1H), 4.90 (AB, J ) 16 Hz, 2H), 4.47 (d, J ) 10.3
Hz, 1H), 3.61 (s, 3H), 2.55 (dt, J ) 14.8, 4.2 Hz, 1H), 2.30-
2.47 (m, 3H), 0.79-1.62 (m, 10H), 0.58 (m, 1H), -0.32 (m, 1H).
13C NMR (CD2Cl2, 75 MHz): δ ) 177.2, 138.9, 134.4, 128.9,
127.7, 127.0, 123.8, 121.0, 107.2, 70.2, 51.8, 51.7, 50.4, 28.5,
27.4, 26.9, 26.4, 26.2, 26.1, 25.4. HRMS (C22H29NO3): calcd
355.214744; found 355.214716.
P yr on e 14.18 A solution of ketone 13 (410 mg, 1.08 mmol)
and DBU (186 mg, 1.22 mmol) in THF (50 mL) is refluxed for
17 h. Standard extractive workup followed by flash chroma-
tography of the crude product with hexanes/ethyl acetate (3/
1) as the eluent affords R-pyrone 14 as colorless crystals (200
1
mg, 79%). mp ) 74-75 °C. H NMR (600 MHz, CDCl3): δ )
7.34 (d, J ) 2.5 Hz, 1H), 7.05 (d, J ) 2.5 Hz, 1H), 3.27 (s, 2H),
2.55 (t, J ) 6.0 Hz, 2H), 2.35 (t, J ) 7.0 Hz, 2H), 1.66 (m, 2H),
1.55 (m, 2H), 1.33 (m, 2H), 1.22 (m, 2H), 1.03 (quint, J ) 7.4,
2H). 13C NMR (CDCl3, 150 MHz): δ ) 208.6, 162.1, 147.2,
139.3, 130.4, 113.6, 45.4, 36.5, 30.3, 28.0, 26.0, 24.8, 22.8, 22.3.
Anal. Calcd for C14H18O3 (234.29): C 71.8, H 7.7. Found: C
71.91, H 7.76.
Ketoester 20. To a slurry of compound 19 (67 mg, 0.188
mmol) and powdered molecular sieves (4 Å) in CH2Cl2 (10 mL)
is added tetra-n-propylammonium perruthenate (79.3 mg,
0.225 mmol), and the resulting mixture is stirred for 1.5 h at
ambient temperature. Insoluble residues are filtered off, and
the crude product is purified by flash chromatography (hex-
anes/ethyl acetate, 5/1), providing ketoester 20 as a colorless
Ma cr ocycle 15. NaOH (ca. 20 mg) is dissolved in MeOH
(1 mL), pyrone 14 (70 mg, 0.298 mmol) is added, and the
resulting mixture is stirred for 2.5 h at ambient temperature.
For workup, aq sat. NH4Cl is added until the mixture reaches
a pH of 4-5, the aqueous phase is extracted with tert-
butylmethyl ether, and the organic layer is dried over Na2-
SO4. Evaporation of the solvent followed by flash chromatog-
raphy (hexanes/ethyl acetate, 10/1) provides product 15 as a
1
syrup (42 mg, 63%). H NMR (300 MHz, CD2Cl2): δ ) 7.33-
7.36 (m, 3H), 7.23 (d, J ) 2.0 Hz, 1H), 7.14-7.16 (m, 2H), 6.56
(d, J ) 2.0 Hz, 1H), 5.06 (s, 2H), 4.07 (dd, J ) 9.3, 4.7 Hz,
1H), 3.72 (s, 3H), 2.59 (A part of dddAB, J ) 15.1, 7.0, 4.3, 0.9
Hz, 1H), 2.44 (B part of ddAB, J ) 15.1, 9.1, 3.8 Hz, 1H), 1.87-
1.97 (m, 1H), 1.60-1.77 (m, 2H), 1.43-1.49 (m, 2H), 0.96-
1.25 (m, 6H), 0.56-0.58 (m, 1H). 13C NMR (CD2Cl2, 75 MHz):
δ ) 193.9, 171.9, 137.2, 135.9, 129.1, 128.2, 127.3, 124.8, 124.4,
111.7, 54.1, 52.1, 51.3, 29.2, 27.4, 27.1, 26.0, 25.5, 24.9. HRMS
(C22H27NO3): calcd 353.199093; found 353.199114.
1
colorless syrup (62 mg, 78%). H NMR (600 MHz, CDCl3): δ
) 9.52 (s, 1H), 6.67 (d, J ) 10.8, 1H), 3.70 (s, 3H), 3.53 (s,
2H), 3.52 (ddd, J ) 10.7, 8.4, 5.6 Hz, 1H), 2.62 (ddd, J ) 14.7,
8.4, 2.9 Hz, 1H), 2.32 (ddd, J ) 14.6, 10.2, 3.2 Hz, 1H), 1.69-
1.88 (m, 4H), 1.23-1.44 (m, 6H), 1.07-1.19 (m, 2H). 13C NMR
(CDCl3, 150 MHz): δ ) 206.6, 193.4, 172.9, 150.7, 138.9, 52.4,
43.4, 42.7, 37.5, 31.2, 26.1, 25.9, 25.0, 24.3, 22.2. HRMS
(C15H22O4): calcd 266.151809; found 266.151928.
Ketop yr r ole 21. A solution of compound 20 (30.9 mg, 0.087
mmol) and NaCl (10 mg) in DMSO (3 mL) and water (50 µL)
is kept at 180-190 °C for 1.5 h. The reaction mixture is then
adsorbed on silica and purified by flash chromatography
(hexanes/ethyl acetate, 4/1), thus leading to product 21 as a
colorless solid (23.4 mg, 91%). 1H NMR (300 MHz, CD2Cl2): δ
) 7.32-7.35 (m, 3H), 7.14-7.17 (m, 3H), 6.58 (d, J ) 1.8 Hz,
1H), 5.04 (s, 2H), 2.63 (t, J ) 6.3 Hz, 2H), 2.49 (t, J ) 6.2 Hz,
2H), 1.57-1.65 (m, 4H), 1.30-1.39 (m, 2H), 0.90-1.10 (m, 6H).
13C NMR (CD2Cl2, 75 MHz): δ ) 199.2, 137.5, 135.0, 129.1,
128.1, 127.3, 126.1, 123.4, 112.3, 51.2, 39.1, 27.9, 27.3, 26.9,
25.8, 25.3, 25.0, 24.7. HRMS (C20H25NO): calcd 295.193614;
found 295.193599.
P a a l-Kn or r P yr r ole F or m a tion . A solution of benzyl-
amine (102 mg, 0.95 mmol) and HOAc (158 mg, 2.63 mmol) in
THF (4 mL) is added via a syringe pump over a period of 1 h
to a solution of substrate 15 (115 mg, 0.43 mmol) in THF (5
mL) at 65 °C. After the addition is complete, the solvent is
removed in vacuo and residual HOAc is coevaporated with
toluene. Flash chromatography (hexanes/ethyl acetate, 10/1)
of the remaining residue provides pyrroles 16 (78 mg, 46%),
17 (28 mg, 19%), and 18 (22 mg, 12%) each as a colorless syrup.
Analytical data of pyrrole 16: 1H NMR (300 MHz, CD2Cl2):
δ ) 7.04-7.28 (m, 5H), 6.69 (d, J ) 1.9 Hz, 1H), 6.06 (d, J )
1.9 Hz, 1H), 5.64 (d, J ) 11.0 Hz, 1H), 4.97 (s, 2H), 3.66 (s,
3H), 2.73 (ddd, J ) 11.0, 7.0, 1.5 Hz, 1H), 2.62 (dt, J ) 14.7,
3.8 Hz, 1H), 2.49 (ddd, J ) 14.9, 10.6, 4.3 Hz, 1H), 1.94 (s,
3H), 1.60-1.66 (m, 1H), 1.40-1.48 (m, 2H), 1.13-1.29 (m, 6H),
0.97-1.01 (m, 1H), 0.59-0.71 (m, 1H), -0.20 (m, 1H). 13C NMR
(CD2Cl2, 75 MHz): δ ) 175.6, 170.0, 138.5, 134.4, 129.0, 127.9,
127.4, 122.2, 120.1, 107.6, 71.7, 51.9, 51.8, 50.6, 49.3, 28.5, 27.3,
26.8, 26.1, 26.0, 25.9, 25.4, 21.3. HRMS (C24H31NO4): calcd
397.225308; found 397.225501.
P yr r ole 22. [Ph3PCH2CH3]+ I- (56 mg, 0.135 mmol) dis-
solved in DMSO (1.5 mL) is deprotonated with KH (5.4 mg,
0.135 mmol), and a solution of ketone 21 (25 mg, 0.08 mmol)
in DMSO (1.1 mL) is then introduced into the ylide thus
formed. After stirring the mixture for 20 min at ambient
temperature, the reaction is quenched with water (5 mL), the
aqueous layer is extracted with CH2Cl2 (20 mL in several
portions), the organic phase is dried over Na2SO4, the solvent
is evaporated, and the residue is purified by flash chromatog-
raphy (hexanes/ethyl acetate, 6/1) affording alkene 22 as a pale
yellow oil (18 mg, 73%, (E,Z)-mixture, ratio of isomers ≈ 3:1).
1H NMR (300 MHz, CD2Cl2) [minor isomer in brackets, where
resolved]: δ ) 7.03-7.25 (m, 5H), 6.42 (d, J ) 1.9 Hz) [6.41,
(d, J ) 1.9 Hz)] [1H], [5.96 (d, J ) 1.9 Hz)], 5.94 (d, J ) 1.9
Hz) [1H], [5.40 (q, J ) 6.8)], 5.25 (q, J ) 6.7) [1H], 4.92 (s),
[4.87 (s)] [2H], 2.38-2.47 (m, 2H), [2.24 (t, J ) 6.3 Hz)], 2.14
(t, J ) 6.3) [2H], 1.65 (d, J ) 6.7), [1.58 (d, J ) 6.8)] [3H],
1.32-1.39 (m, 2H), 0.95-1.26 (m, 8H), 0.48 (m, 2H). 13C NMR
(CD2Cl2, 75 MHz) [minor isomer in brackets, where resolved]:
δ ) 139.3, [139.2], 137.9, [137.6], 132.8, 128.9, 127.6, 127.4,
127.2, 127.1, 127.0, [121.6], 120.7, [118.3], 117.1, [115.9], 110.2,
[109.4], 50.4, [50.3], 36.5, 27.5, 27.3, 27.1, 26.9, 26.8, 26.7, 26.5,
26.4, 26.0, 25.9, 15.0, [13.4]. HRMS (C22H29N): calcd 307.230000;
found 307.232011.
Analytical data of compound 17: 1H NMR (600 MHz, CD2-
Cl2): δ ) 7.58 (s, 1H), 7.32 (t, J ) 6.2 Hz, 2H), 7.27 (t, J ) 7.3
Hz, 1H), 7.11 (d, J ) 7.3 Hz, 1H), 6.65 (d, J ) 1.5 Hz, 1H),
6.28 (d, J ) 1.5 Hz, 1H), 4.99 (s, 2H), 3.71 (s, 3H), 2.56 (t, J )
6.5 Hz, 2H), 2.52 (m, 2H), 1.60 (m, 2H), 1.25-1.28 (m, 4H),
1.12 (m, 2H), 1.02 (m, 2H). 13C NMR (CD2Cl2, 150 MHz): δ )
169.6, 138.6, 134.9, 133.8, 130.7, 129.1, 127.9, 127.1, 122.3,
119.5, 112.1, 51.8, 50.8, 30.0, 27.5, 26.2, 25.9, 25.8, 25.5, 24.5,
23.8. HRMS (C22H27NO2): calcd 337.204179; found 337.204202.
Analytical data of compound 18: 1H NMR (300 MHz, CD2-
Cl2): δ ) 7.11-7.36 (m, 10H), 6.52 (d, J ) 1.9 Hz, 1H), 6.01
(d, J ) 1.9 Hz, 1H), 5.00 (AB, J ) 16 Hz, 2H), 3.82 and 3.61
(AB, J ) 13.3 Hz, 1H), 3.67 (s, 3H), 3.50 (d, J ) 10.8 Hz, 1H),
2.66 (dt, J ) 14.7, 4.3 Hz, 1H), 2.39-2.51 (m, 2H), 0.88-1.66
(m, 11H), 0.64 (m, 1H), -0.19 (m, 1H). 13C NMR (CD2Cl2, 75
MHz): δ ) 177.4, 141.6, 139.3, 134.2, 128.9, 128.5, 128.4,
127.7, 127.0, 126.8, 123.1, 122.3, 107.0, 58.0, 51.6, 50.4, 30.0,
28.8, 27.6, 27.0, 26.8, 26.3, 25.5. HRMS (C29H36N2O2): calcd
444.277678; found 444.277692.
P yr r ole 24. Prepared as described above using [Ph3P(CH2)10-
CH3]+ Br- (56 mg, 0.11 mmol), KH (4.4 mg, 0.11 mmol), and
ketone 21 (20 mg, 0.067 mmol). Alkene 24 was obtained as a
pale yellow syrup (14.7 mg, 51%, (E,Z)-mixture, ratio of
1
isomers ≈ 1.5:1). H NMR (300 MHz, CD2Cl2) [minor isomer
in brackets, where resolved]: δ ) 7.14-7.36 (m, 5H), [6.52 (d,
J ) 1.9 Hz)], 6.50 (d, J ) 1.9 Hz), [6.36 (d, J ) 1.9 Hz)], [6.07
(d, J ) 1.9 Hz)], 6.03 (d, J ) 1.9 Hz), 5.83 (d, J ) 1.9 Hz), 5.45
(t, J ) 7.6 Hz), 5.28 (t, J ) 7.6 Hz), 4.98-5.03 (m, 2H), 2.49-
P yr r ole 19. A solution of acetate 16 (82.5 mg, 0.207 mmol)
and NaOMe (179 mg, 3.32 mmol) in MeOH (8 mL) is stirred

8286 J . Org. Chem., Vol. 64, No. 22, 1999
Fu¨rstner and Krause
2.60 (m, 2H), 1.83-2.35 (m, 6H), 1.05-1.49 (m, 23H), 0.89 (t,
J ) 6.8 Hz, 3H), 0.54-0.63 (m, 2H), 0.33 (m, 1H). 13C NMR
(CD2Cl2, 75 MHz): δ ) 139.6, 139.4, 139.3, 136.8, 136.7, 132.9,
132.8, 131.4, 128.9, 127.7, 127.6, 127.5, 127.2, 127.1, 127.0,
126.8, 123.9, 122.6, 122.0, 120.6, 118.7, 118.4, 112.6, 110.6,
110.3, 109.4, 50.4, 50.3, 39.3, 36.6, 32.3, 30.8, 30.6, 30.0, 29.9
(2×), 29.8 (2×), 29.7, 29.6, 28.2, 27.7, 27.6, 27.5, 27.1, 27.0,
26.9, 26.8, 26.5, 26.4, 26.2, 26.0 (2×), 23.0, 14.2. HRMS
(C31H47N): calcd 433.370850; found 433.370644.
P yr r ole 25. Ethyl trimethylsilyl acetate (18.5 mg, 0.115
mmol) is added to a solution of LDA (12.4 mg, 0.115 mmol) in
THF at -78 °C. After stirring for 10 min, a solution of ketone
21 (18.0 mg, 0.061 mmol) in THF (1 mL) is introduced and
the mixture is stirred for another 10 min at -78 °C and then
allowed to warm to ambient temperature. A standard extrac-
tive workup followed by flash chromatography of the crude
product (hexanes/ethyl acetate, 4/1) provides ester 25 as a pale
yellow syrup (17.5 mg, 78%) (E:Z mixture, ratio of isomers ≈
1.2:1). 1H NMR (300 MHz, CD2Cl2) [minor isomer in brackets,
where resolved]: δ ) 7.14-7.37 (m, 6H), 6.79 (d, J ) 1.9), [6.31
(d, J ) 1.9 Hz)], 6.20 (d, J ) 1.9 Hz), [5.90 (s)], 5.60 (s), 5.04
(s), [5.02 (s)], [4.13 (q, J ) 7.1 Hz)], 4.06 (q, J ) 7.1 Hz, 2H),
[2.99 (t, J ) 6.3 Hz)], 2.41 (t, J ) 6.3 Hz), 2.51 (dd, J ) 5.8,
6.0 Hz, 2H), 1.06-1.58 (m, 10 H), [1.27 (t, J ) 7.1 Hz)], 1.20
(t, J ) 7.1 Hz), 0.66-0.76 (m, 2H). 13C NMR (CD2Cl2, 75
MHz): δ ) 167.2, 166.9, 158.3, 155.7, 138.7, 138.3, 134.6,
132.9, 129.0, 128.9, 127.8, 127.7, 127.2, 127.0, 126.2, 124.3,
119.9, 119.6, 111.8, 110.4, 109.8, 109.7, 59.5, 59.4, 50.8, 50.7,
38.0, 28.5, 27.7, 27.5, 27.4, 27.2, 27.1, 26.7, 26.5 (2x), 26.4, 26.2,
26.1, 25.6, 25.5, 14.5, 14.4. HRMS (C24H31NO2): calcd
365.235479; found 365.235483.
Cl2 (3.5 mL) is stirred under an atmosphere of H2 (1 atm) for
10 min. The solvent is evaporated and the residue purified by
flash chromatography (hexanes/ethyl acetate, 6/1), affording
product 23 as a pale yellow oil (15 mg, 88%). 1H NMR (300
MHz, CD2Cl2): δ ) 7.11-7.32 (m, 5H), 6.39 (d, J ) 1.9 Hz,
1H), 5.90 (d, J ) 1.9 Hz, 1H), 4.98 (s, 2H), 2.58 (A part of ddAB,
J ) 14.6, 6.1, 4.0 Hz, 1H), 2.47 (B part of ddAB, J ) 14.6, 9.4,
4.0 Hz, 1H), 2.22 (m, 1H), 1.48-1.58 (m, 4H), 1.10-1.39 (m,
10H), 0.91 (t, J ) 7.3 Hz, 3H), 0.47-0.52 (m, 1H), 0.07-0.11
(m, 1H). 13C NMR (CD2Cl2, 75 MHz): δ ) 139.7, 133.1, 128.8,
127.4, 127.2, 127.0, 120.2, 110.6, 107.7, 50.2, 40.8, 33.2, 29.0,
28.7, 27.5, 27.2, 27.1, 26.2, 25.6, 21.6, 12.8. HRMS (C22H31N):
calcd 309.245650; found 309.245737.
Ack n ow led gm en t. Generous financial support by
the Max-Planck-Gesellschaft, the Deutsche Forschungs-
gemeinschaft (Leibniz Program), and the Fonds der
Chemischen Industrie is gratefully acknowledged. We
thank Mrs. B. Gabor for her help with some of the NMR
spectra and Dr. C. W. Lehmann for the X-ray analysis
of R-pyrone 14.
Su p p or tin g In for m a tion Ava ila ble: Details concerning
the X-ray structure of compound 14, complete listing of the
MS (EI) and IR data, copies of the NMR spectra of all new
compounds, full assignment of the NMR data of compounds
14, 15, and 17, procedure for the large scale preparation of
sulfonium salt 8. This material is available free of charge via
the Internet at http://pubs.acs.org.
P yr r ole 23. A solution of alkene 22 (17 mg, 0.055 mmol)
and [Ir(COD)(Cy3P)pyridine] PF6 (4.4 mg, 10 mol %)23 in CH2-
J O991022A