Concave butterfly-shaped organometallic hydrocarbons?

Article abstract of DOI:10.1002/1521-3773(20010417)40:8<1460::AID-ANIE1460>3.0.CO;2-Q

A metamorphosis of the tetraethynyl precursor 1 through double Cu-catalyzed ring closure leads to the corresponding butterfly-shaped cyclobutadiene complexes 2 in high yield (94%). Single-crystal X-ray diffraction shows that the large organic ligand is distinctly nonplanar with a concave topology. Cp = cyclopentadiene.

Full text of DOI:10.1002/1521-3773(20010417)40:8<1460::AID-ANIE1460>3.0.CO;2-Q

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[4] a) C. A. Krueger, K. W. Kuntz, C. D. Dzierba, W. G. Wirschun, J. D.
Gleason, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 1999, 121,
4284 ± 4285; b) J. R. Porter, W. G. Wirschun, K. W. Kuntz, M. L.
Snapper, A. H. Hoveyda, J. Am. Chem. Soc. 2000, 122, 2657 ±
2658.
[5] J. R. Porter, J. F. Traverse, A. H. Hoveyda, M. L. Snapper, J. Am.
Chem. Soc. 2001, 123, 984 ± 985.
[6] S. J. Degrado, H. Mizutani, A. H. Hoveyda, J. Am. Chem. Soc. 2001,
123, 755 ± 756.
Hoveyda in Stimulating Topics in Organic Chemistry (Eds.: F. Vögtle,
J. F. Stoddart, M. Shibasaki), Wiley-VCH, Weinheim, 2000, pp. 145 ±
162.
[22] Reaction of di-2-methylpentylzinc (cf. 24, Scheme 2) with 20a in the
presence of 19 that has been pretreated with Et2Zn affords alkylation
products with ee levels similar to those shown in Scheme 2 (76 ±
78% ee). These data indicate that reactions with Et2Zn are not
promoted by amine ligands that are reduced in situ by various metal
hydrides (see ref. [5]).
[7] For a recent review regarding the use of some non-C2-symmetric
chiral ligands in metal-catalyzed enantioselective reactions, see:
a) A. Pfaltz in Stimulating Topics in Organic Chemistry (Eds.: M.
Shibasaki, J. F. Stoddart, F. Vögtle), VCH-Wiley, Weinheim, 2000,
pp. 89 ± 103; b) G. Helmchen, A. Pfaltz, Acc. Chem. Res. 2000, 33,
336 ± 345.
[8] For previous work from these laboratories in connection to catalytic
asymmetric allylic substitutions with hard alkylmetals and other
related studies, see: a) A. H. Hoveyda, N. M. Heron in Comprehensive
Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),
Springer, Berlin, 1999, pp. 431 ± 454. For a review concerning catalytic
asymmetric addition of soft nucleophiles to olefins, see: b) B. M. Trost,
V. L. van Vranken, Chem. Rev. 1996, 96, 395 ± 422.
Concave Butterfly-Shaped Organometallic
Hydrocarbons?**
Matthew Laskoski, Gaby Roidl, Mark D. Smith, and
Uwe H. F. Bunz*
[9] For a review of catalytic enantioselective methods for the synthesis of
quaternary carbon stereogenic centers, see: E. J. Corey, A. Guzman-
Perez, Angew. Chem. 1998, 110, 402 ± 405; Angew. Chem. Int. Ed.
1998, 37, 388 ± 401.
[10] a) C. C. Tseng, S. D. Paisley, H. L. Goering, J. Org. Chem. 1986, 51,
2884 ± 2891; b) J.-E. Backvall, M. Sellen, B. Grant, J. Am. Chem. Soc.
1990, 112, 6615 ± 6621.
[11] For Cu-catalyzed (nonasymmetric) addition of organotitanium and
organozirconium reagents to allylic phosphates, see: a) A. Masayuki,
E. Nakamura, B. H. Lipshutz, J. Org. Chem. 1991, 56, 5489 ± 5491;
b) L. M. Venanzi, R. Lehmann, R. Keil, B. H. Lipshutz, Tetrahedron
Lett. 1992, 33, 5857 ± 5860.
Carbon-rich organometallic materials are of special interest
because their structures display topologies, such as tetragonal
or pentagonal, unattainable by their hydrocarbon counter-
parts.[1±3] In the realm of organic structures, Haley et al. made
a series of large polycyclic hydrocarbons of hexagonal top-
ology, in which benzene rings are separated by alkyne units.[4]
We are interested in the chemistry and materials science
of tetragonal cyclobutadiene complexes,[5] and herein we
present the synthesis (4a ± c, see Scheme 1 and 2) and single-
[12] For Cu-catalyzed asymmetric alkylation of an allylic phosphate with
Grignard reagents, see: a) M. van Klaveren, E. S. M. Persson, A.
del Villar, D. M. Grove, J.-E. Backvall, G. van Koten, Tetrahedron
Lett. 1995, 36, 3059 ± 3062. For W-catalyzed asymmetric alkylation of
allylic phosphates with soft nucleophiles, see: b) G. C. Lloyd-Jones, A.
Pfaltz, Angew. Chem. 1995, 107, 534 ± 536; Angew. Chem. Int. Ed.
Engl. 1995, 34, 462 ± 464.
[13] N. S. Josephsohn, K. W. Kuntz, M. L. Snapper, A. H. Hoveyda,
unpublished results.
[14] As depicted in Scheme 1, the combination of 5 and (CuOTf)2 ´ C6H6,
provides slightly higher enantioselectivity, but is less efficient than 6
and CuCN (50% vs. >98% conversion). Further examination of the
former system is in progress.
[15] Tripeptide 8 and its derived Me ester afford similar results.
[16] When d-Val is used as AA1, the sense of enantioselection is reversed,
indicating that the stereochemical identity of AA1 is critical to the
sense of stereochemical induction and that the d,l-ligand may deliver
lower levels of enantioselectivity than the l,l isomer.
[17] The absolute configuration of 2a was determined to be S through
comparison of its [a]D value with those reported (authentic material
was also prepared). See: T. Hayashi, T. Hagihara, Y. Katsuro, M.
Kumada, Bull. Chem. Soc. Jpn. 1983, 56, 363 ± 364.
[18] The corresponding electron-rich p- and o-OMe substrates proved to
be unstable.
Scheme 1. Synthesis of the unsubstituted bow-tie complex 4a.
a) [(PPh3)2PdCl2], CuI, piperidine, 18 h, 258C; aqueous workup and
chromatography. b) K2CO3, THF, methanol, 16 h, 258C. c) Cu(OAc)2,
CH3CN (20 mL), 18 h, 808C; aqueous workup and chromatography.
[19] F. Dubner, P. Knochel, Angew. Chem. 1999, 111, 391 ± 393; Angew.
Chem. Int. Ed. 1999, 38, 379 ± 381; b) F. Dubner, P. Knochel,
Tetrahedron Lett. 2000, 41, 9233 ± 9237. Moreover, in ref. [12b], a
catalytic alkylation of 1a with nBuMgCl to afford 2a is reported to
proceed in 10% ee (92% SN2').
[*] Prof. Dr. U. H. F. Bunz, M. Laskoski, Dr. G. Roidl, Dr. M. D. Smith
Department of Chemistry and Biochemistry
The University of South Carolina
[20] Absolute configuration of 21a was determined to be S by comparison
of its [a]D with those reported. See: H. Yamamoto, A. Yanagisawa, N.
Nomura, Y. Yamada, H. Hibino, Synlett 1995, 841 ± 842.
[21] For previous enantioselective total syntheses of sporochnol, see: a) M.
Takahashi, Y. Shioura, T. Murakami, K. Ogasawara, Tetrahedron:
Asymmetry 1997, 8, 1235 ± 1242; b) T. Kambikubo, M. Shimizu, K.
Ogasawara, Enantiomer 1997, 2, 297 ± 301; c) A. Fadel, L. Van-
dromme, Tetrahedron: Asymmetry 1999, 10, 1153 ± 1162. For a review
on asymmetric catalysis in target-oriented synthesis, see: A. H.
Columbia, SC 29208 (USA)
Fax (‡1)803-777-9521
E-mail: bunz@mail.chem.sc.edu
[**] U.H.F.B. and M.L. thank the NSF for generous support (CAREER,
CHE 9981765, 2000 ± 2004). U.H.F.B. is Camille Dreyfus Teacher-
Scholar (2000 ± 2004).
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Scheme 2. Synthesis of the substituted bow-tie complexes 4b and 4c. a) [(PPh3)2PdCl2], CuI, piperidine, 18 h, 258C; aqueous workup and chromatography.
‡
b) K2CO3, THF, methanol, 16 h, 258C. c) Cu(OAc)2, CH3CN, 18 h, 808C; aqueous workup and chromatography. d) Me4N F , DMSO, diethyl ether 2 h,
258C; aqueous workup and chromatography. TMS ˆ trimethylsilyl.
crystal X-ray structure analysis (4b, see Figure 1) of novel,
large, concave organometallic hydrocarbons (4) with a cen-
tral tetraethynylcyclobutadiene(cyclopentadienylcobalt) core.
Topologies of type 4 are attractive because related species
featuring the tetraethynylcylobutadiene motif have been
suggested by Jarrold et al.[6] to play an important role in the
formation of fullerenes such as C60.
Vollhardt, Youngs et al.[7] have developed a powerful
method to assemble dehydrobenzo[14]annulenes,[8±10] which
is suitable for preparing the butterfly complexes 4. Starting
from 1a,[11] fourfold Pd-catalyzed coupling with 2a furnishes
3a after chromatography and removal of the trimethylsilyl
groups by K2CO3 in methanol in an overall yield of 16%
(64% per coupling step; Scheme 1). Treatment of 3a with
Cu(OAc)2 in acetonitrile/THF under conditions described by
Vögtle and Berscheid[9] and recently utilized by us[10] leads to
4a as sole product in 94% yield (Table 1). The almost
quantitative yield was surprising and is probably due to the
preorganization of the alkyne groups in 3a with respect to
each other. While 3a is well soluble in dichloromethane and
pentane, 4a is only slightly soluble in THF, but practically
insoluble in pentane or halogenated solvents, which hampered
attempts to obtain single crystals. Interest in expanding this
concept and obtaining more soluble derivatives led us to
explore a step-by-step route to 4b and 4c. Starting from 1b,
Pd-catalyzed reaction with 2b followed by deprotection, Cu-
catalyzed coupling, and removal of the triisopropylsilyl
(TIPS) groups furnishes 5b as a valuable intermediate.
Repetition of the sequence (Scheme 2) leads, via 7, to the
tetrakis-tert-butyl-substituted compound 4b (Table 1), which
is very soluble in THF, dichloromethane, and pentane.
Coupling of the intermediate 5a (Table 1) to 1-chloro-4-
trimethylsilylbuten-3-yne followed by deprotection and ring
closure of 8b furnishes the unsymmetrical 4c (Table 1), in
which one dehydroannulene and one dehydrobenzoannulene
Figure 1. Structure of the butterfly compound 4b. a) Top view. Selected
bond lengths [Š]: C1-C2, C3-C4 1.448(5), C1-C3, C2-C4 1.472(5). b) Side
view.
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Table 1. Spectroscopic data for selected compounds.
additional increase in the kink angle from 168 to 208 (PM3-
tm), qualitatively indicating that steric effects play a role.
These results are in interesting contrast to Vollhardtꢁs
[N]phenylenes, in which bending of the aromatic core is
likewise observed, but which is attributed solely to crystal
packing effects.[14b]
4a: Yield: 94%; dark red crystalline solid; m.p. >2008C (decomp); IR
1
(neat): nÄ ˆ 2924, 2361, 2342, 1458 cm 1; H NMR (400 MHz, CDCl3): d ˆ
3
4
3
7.73 (dd, JH,H ˆ 7.32 Hz, JH,H ˆ 1.7 Hz, 4H), 7.52 (dd, JH,H ˆ 7.32 Hz,
4JH,H ˆ 1.7 Hz, 4H), 7.42 (quint. d, 3JH,H ˆ 7.32 Hz, 4JH,H ˆ 1.7 Hz, 8H), 5.01
(s, 5H); 13C NMR (100 MHz, CDCl3): d ˆ 131.81, 131.17, 129.99, 129.90,
128.57, 124.33 (12C), 84.61 (5C), 93.48, 90.21, 80.00, 68.21 (12C), 62.83
(4C)
The cyclobutadiene ring in 4b is not square but rectangular,
according to X-ray diffraction data, suggesting some degree of
bond fixation induced by the annulation of the aromatic
[14]dehydroannulenes;[14, 15] the C1 C2 and C3 C4
(1.448(5) Š) bonds are shorter than the C1 C3 and C2 C4
(1.472(5) Š) bonds. While the bond fixation is not dramatic, it
supports the annulation of two Hückel-aromatic dehydroan-
nulenes onto the metal-complexed cyclobutadiene ring.
Aromaticity effects thus induce subtle changes in the geom-
etry of the normally square CpCo-stabilized cyclobutadiene.
This trend is clearly supported by the comparison of the
1H NMR data of 4c and its open precursor 8b. While in 8b the
signals of the vinyl protons appear at d ˆ 5.92 and 6.06, the
same protons resonate at d ˆ 6.34 and 6.72 in 4c, suggesting
that the newly formed dehydro[14]annulene is aromatic and
thus reduces the delocalization of the cyclobutadiene com-
plex.
In conclusion we have synthesized the organometallic
butterfly complexes 4a ± c by a combination of Pd- and Cu-
catalyzed coupling reactions and determined the molecular
structure of 4b as the first example of a structurally
characterized molecular topology that resembles that in
Jarroldꢁs perethynylated cyclobutadienes, which are fascinat-
ing intermediates en route to C60.[16] The extension of this
concept towards larger systems of higher unsaturation may
lead to the formation of fullerenes from cyclobutadiene-
containing precursors under appropriate matrix-assisted laser
desorption ionization time-of-flight (MALDI-TOF) condi-
tions, similar to the coalescence of suitable cyclophynes
elegantly demonstrated independently by Rubin et al.[16] and
Tobe et al.[17]
4b: Yield: 55%; dark red crystalline solid; m.p. >2208C (decomp); IR
1
(neat): nÄ ˆ 2943, 2855, 2333, 2144, 1667, 1461, 1244 cm
;
1H NMR
3
(400 MHz, CDCl3): d ˆ 7.65 (d, JH,H ˆ 8.3 Hz, 4H), 7.53 (s, 4H), 7.43 (d,
3JH,H ˆ 8.3 Hz, 4H), 4.97 (s, 5H), 1.34 (s, 36H); 13C NMR (100 MHz,
CDCl3): d ˆ 151.18, 130.96, 127.45, 126.83, 126.52, 123.68 (24C), 92.98,
89.25, 84.52, 79.23 (16C), 83.91 (5C), 62.31 (4C), 35.17, 31.26 (16C); UV/
Vis (CHCl3): lmax (e) ˆ 296 (27530), 323 nm (22787)
4c: Yield: 88%; orange-red crystalline solid; m.p. >1908C (decomp); IR
1
(neat): nÄ ˆ 2956, 2333, 2167, 1644, 1584, 1450, 1400, 1100, 1017 cm
;
1H NMR (400 MHz, CDCl3): d ˆ 7.65 (d, JH,H ˆ 8.2 Hz, 2H), 7.52 (d,
3
4JH,H ˆ 1.9 Hz, 2H), 7.42 (dd, JH,H ˆ 8.2 Hz, JH,H ˆ 1.9 Hz, 2H), 6.72 (d,
3JH,H ˆ 9.9 Hz, 2H), 6.34 (d, 3JH,H ˆ 9.9 Hz, 2H), 4.95 (s, 5H), 1.33 (s, 18H);
13C NMR (100 MHz, CDCl3): d ˆ 151.39, 130.98, 127.47, 126.56 (12C),
123.79, 116.87 (4C), 96.46, 94.01, 93.31, 88.68, 88.19, 84.44, 84.08, 79.20
(16C), 83.68 (5C), 63.33, 62.99 (4C), 35.19, 31.80 (8C); UV/Vis (CHCl3):
lmax (e) ˆ 333 nm (313)
3
4
5a: Yield: 82%; dark red oil; IR (neat): nÄ ˆ 3106, 2943, 2852, 2338, 2143,
1
3
1462, 1246 cm
;
1H NMR (400 MHz, CDCl3): d ˆ 7.49 (d, JH,H ˆ 8.2 Hz,
3
2H), 7.44 (s, 2H), 7.38 (d, JH,H ˆ 8.2 Hz, 2H), 4.93 (s, 5H), 1.31 (s, 18H),
1.14 (s, 42H), 0.05 (s, 18H); 13C NMR (100 MHz, CDCl3): d ˆ 150.80,
130.48, 127.13, 126.64, 126.32, 123.40 (12C), 100.78, 96.97, 92.21, 88.91
(8C), 83.60 (5C), 61.96, 61.38 (4C), 34.90, 30.99 (8C), 18.70, 11.11 (18C),
‡
1.01 (6C); HRMS (EI): m/z: calcd for [M ] (C59H71CoSi2) 894.4426; found
894.4401
are fused to the tetraethynylcyclobutadiene core. The latter
demonstrates the versatility of the double annulation process.
All of the polycycles 4 are surprisingly stable and can be
stored under ambient conditions for extended periods of time
without polymerization or decomposition. If the cycles are
heated to temperatures above 1908C shiny-black, insoluble,
but amorphous materials form.
Attempts to obtain mass spectra of 4a ± c under electron
impact conditions failed due to their immedaite decomposi-
tion, but gratifyingly, the tert-butyl substituents increase the
propensity of 4b to develop high-quality single crystals. The
X-ray crystal structure of 4b is shown in Figure 1.[12] The bond
lengths and bond angles are in excellent agreement with
earlier values published for 6 (see Scheme 2),[10] but an
interesting aspect of the structure of 4b is its considerable
deviation from planarity in the solid state (Figure 1b). Two
planes, which are each defined by the central cyclobutadiene
ring and two of the four alkyne groups, are tilted by 138,
leading to a (net) kink of 268 of the two dehydroannulenes
with respect to each other. This tilt is considerably larger than
that in alkynylated and butadiynylated cyclobutadiene(tricar-
bonyl)iron complexes.[13] To establish whether the bending of
the large hydrocarbon ligand is a crystal packing effect or
ªrealº, we performed a semiempirical (PM3-tm, SPARTAN
PRO) calculation of 4a. In the computationally optimized
structure the tilting is even stronger, and the plane of the
cyclobutadiene complex is kinked away by 168 from the
dehydroannulene. Increasing the steric bulk of the cyclo-
pentadienyl ring through pentamethyl substitution leads to an
Experimental Section
4b: A round-bottom flask was charged[11] with 5a (0.098 g, 0.11 mmol),
tetramethylammonium fluoride (0.300 g, 10.9 mmol), DMSO (5 mL), and
diethyl ether (10 mL). The resulting mixture was stirred at 258C for 2 h.
Aqueous workup (diethyl ether) followed by removal of the solvent in
vacuo yielded 5b as a dark red oil. This was coupled immediately to 4-iodo-
3-(trimethylsilylethynyl)-1-tert-butylbenzene[18] (2b) (90 mg, 0.250 mmol)
under addition of [(PPh3)2PdCl2] (1.5 mg, 0.002 mmol), CuI (1.0 mg,
0.007 mmol), and piperidine (10 mL). The reaction mixture was purged
with N2 and stirred for 18 h at ambient temperature. Aqueous workup and
subsequent chromatography on silica gel with CH2Cl2/hexanes (1:1) yielded
pure 7a (R ˆ SiMe3; 34 mg, 30%) as a red oil. A round-bottom flask was
charged with 7a (34 mg, 0.033 mmol), K2CO3 (0.100 g, 0.72 mmol), THF
(3 mL), and methanol (10 mL). The resulting mixture was stirred at 258C
for 4 h. Aqueous workup with diethyl ether followed by removal of the
solvent in vacuo yielded 7b as a dark red oil (29 mg, 98%). Cu(OAc)2
(0.200 g, 1.10 mmol) and CH3CN (20 mL) were added to the oil 7b and the
reaction mixture was heated to 808C for 18 h. Aqueous workup and
chromatography on silica gel with CH2Cl2/hexanes (1:1) yielded pure 4b
(16 mg, 55%) as a dark red crystalline solid.
Received: December 28, 2000 [Z16341]
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COMMUNICATIONS
[1] F. Diederich, Y. Rubin, Angew. Chem. 1992, 104, 1123; Angew. Chem.
Int. Ed. Engl. 1992, 31, 1101; F. Diederich, Nature 1993, 369, 199; R. R.
Tykwinski, F. Diederich, Liebigs Ann. 1997, 649; F. Diederich, L.
Gobbi, Top. Curr. Chem. 1999, 201, 43.
[2] M. M. Haley, J. J. Pak, S. C. Brand, Top. Curr. Chem. 1999, 201, 81;
M. M. Haley, Synlett 1998, 557.
[3] T. Bartik, B. Bartik, M. Brady, R. Dembinski, J. A. Gladysz, Angew.
Chem. 1996, 108, 467; Angew. Chem. Int. Ed. Engl. 1996, 35, 414;
U. H. F. Bunz, Angew. Chem. 1994, 106, 1127; Angew. Chem. Int. Ed.
Engl. 1994, 33, 1073.
[4] W. B. Wan, S. C. Brand, J. J. Pak, M. M. Haley, Chem. Eur. J. 2000, 6,
2044.
Total Synthesis of ( )-Tetrazomine and
Determination of Its Stereochemistry**
Jack D. Scott and Robert M. Williams*
Dedicated to Professor K. Barry Sharpless
on the occasion of his 60th birthday
The antitumor antibiotic tetrazomine 1 was isolated from
Saccharothrix mutabilis at the Yamonouchi Pharmaceutical
company by Suzuki et al.[1] Tetrazomine is a member of the
tetrahydroisoquinoline family of antitumor antibiotics that
[5] U. H. F. Bunz, Y. Rubin, Y. Tobe, Chem. Soc. Rev. 1999, 28, 107;
U. H. F. Bunz, Top. Curr. Chem. 1999, 201, 131.
[6] J. M. Hunter, J. L. Fye, E. J. Roskamp, M. F. Jarrold, J. Phys. Chem.
1994, 98, 1810.
[7] K. P. Baldwin, A. J. Matzger, D. A. Scheiman, C. A. Tessier, K. P. C.
Vollhardt, W. J. Youngs, Synlett 1995, 1215.
[8] M. Laskoski, W. Steffen, M. D. Smith, U. H. F. Bunz, Chem. Com-
mun., submitted; M. Altmann, G. Roidl, V. Enkelmann, U. H. F.
Bunz, Angew. Chem. 1997, 109, 1133; Angew. Chem. Int. Ed. Engl.
1997, 36, 1107.
[9] F. Vögtle, R. Berscheid, Synthesis 1992, 58.
[10] U. H. F. Bunz, G. Roidl, R. D. Adams, J. Organomet. Chem. 2000, 600,
56.
[11] U. H. F. Bunz, G. Roidl, M. Altmann, V. Enkelmann, K. D. Shimizu, J.
Am. Chem. Soc. 1999, 121, 10719.
[12] For 4b: A red plate of 4b (0.25 Â 0.2 Â 0.08 mm) was grown from
dichloromethane. Data were obtained on a Bruker SMART APEX
CCD diffractometer at 211 K. The structure was solved and refined by
the programs SAINT‡ and SHELXTX by using heavy atom
(Patterson) methods. Hydrogen atoms were localized and refined in
the riding mode. The crystal was fixed in a capillary. CoC65H53 ´ CH2Cl2
(Mr ˆ 977.93); MoKa radiation l ˆ 0.71073 Š, graphite monochroma-
tor; 2Vmax ˆ 22.508, tetragonal, space group I41; a ˆ 19.156(5),
includes ecteinascidin 743 (2),[2] bioxalomycin a2 (3),[3] and
quinocarcin (4).[4] Tetrazomine most closely resembles quino-
carcin, except for the amino functionality at C10', the unusual
b-hydroxy pipecolic acid moiety, and the oxidation state of
C13'. Neither the relative nor the absolute stereochemistry of
tetrazomine were determined when the structure was initially
reported.[1b] We have since determined that the absolute
stereochemistry of the pipecolic acid moiety is 2S,3R.[5]
Preliminary antitumor/antimicrobial assays of tetrazomine
revealed that this substance possesses activity against P388
leukemia in vivo and good antimicrobial activity against both
Gram-negative and Gram-positive bacteria.[1a] Tetrazomine
exerts its cytotoxic activity through oxidative damage to DNA
by the superoxides formed in the auto-redox disproportiona-
tion of the fused oxazolidine, and possibly through DNA
alkylation.[6]
b ˆ 19.156(5), c ˆ 15.842(7) Š, Vˆ 5814(3) Š3, Z ˆ 48, 1calcd
ˆ
1.117 gcm 3, m ˆ 0.424 mm 1, 12129 reflections were measured and
4807 reflections with I > 2s(I) observed, R ˆ 0.0491, Rw ˆ 0.1031.
Crystallographic data (excluding structure factors) for the structure
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-154093. Copies of the data can be obtained free of charge on
application to CCDC, 12 Union Road, Cambridge CB21EZ, UK (fax:
(‡44)1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
[13] U. H. F. Bunz, V. Enkelmann, Organometallics 1994, 13, 3823.
[14] a) D. L. Mohler, K. P. C. Vollhardt, S. Wolff, Angew. Chem. 1990, 102,
1200; Angew. Chem. Int. Ed. Engl. 1990, 29, 1151; b) for a discussion of
the crystal-packing-induced nonplanarity of the [N]phenylenes see: D.
Holmes, S. Kumaraswamy, A. J. Matzger, K. P. C. Vollhardt, Chem.
Eur. J. 1999, 5, 3399.
[15] R. H. Mitchell, Y. S. Chen, N. Khalifa, P. Z. Zhou, J. Am. Chem. Soc.
1998, 120, 1785.
[16] Y. Rubin, T. C. Parker, S. J. Pastor, S. Jalisatgi, C. Boulle, C. L. Wilkins,
Angew. Chem. 1998, 110, 1353; Angew. Chem. Int. Ed. 1998, 37, 1226.
[17] Y. Tobe, N. Nakagawa, K. Naemura, T. Wakabayashi, T. Shida, Y.
Achiba, J. Am. Chem. Soc. 1998, 120, 4544.
The total synthesis of tetrazomine has not been reported in
the literature,[7] although the synthesis of the AB-ring system
of tetrazomine has been discussed by Ponzo and Kaufman.[8]
Herein, we describe the first total synthesis of ( )-tetrazo-
[18] J. J. Pak, T. J. R. Weakley, M. M. Haley, J. Am. Chem. Soc. 1999, 121,
10719.
[*] Prof. R. M. Williams, J. D. Scott
Department of Chemistry
Colorado State University
Fort Collins, CO 80523 (USA)
Fax : (‡1)970-491-3944
E-mail: rmw@chem.colostate.edu
[**] This work was supported by the National Institutes of Health (Grant
CA85419). We are grateful to Yamanouchi Pharmaceutical Co. for
providing a generous gift of natural tetrazomine.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
Angew. Chem. Int. Ed. 2001, 40, No. 8
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