Formal [(2+2)+2] and [(2+2)+(2+2)] nonconjugated dienediyne cascade cycloadditions

Article abstract of DOI:10.1021/ol0514799

(Chemical Equation Presented) Fluoranthene 2 and heptacycle 3 are easily accessible from the reaction of diyne 1 and norbornadiene (NBD) in the presence of the rhodium catalyst. The unusual [(2+2)+(2+2)] adduct 3 was confirmed by the X-ray crystal structu

Full text of DOI:10.1021/ol0514799

ORGANIC
LETTERS
2005
Vol. 7, No. 20
4353-4355
Formal [(2+2)+2] and [(2+2)+(2+2)]
Nonconjugated Dienediyne Cascade
Cycloadditions
Yao-Ting Wu, Anthony Linden, and Jay S. Siegel*
Institute of Organic Chemistry, UniVersity of Zurich, Winterthurerstrasse 190,
CH-8057 Zurich, Switzerland
jss@oci.unizh.ch
Received June 24, 2005
ABSTRACT
Fluoranthene 2 and heptacycle 3 are easily accessible from the reaction of diyne 1 and norbornadiene (NBD) in the presence of the rhodium
catalyst. The unusual [(2 2) (2 2)] adduct 3 was confirmed by the X-ray crystal structure analysis.
+
+ +
Through-space interaction between proximal olefins, as in
norbornadiene (NBD), leads to reactivity analogous with
conjugated dienes.1 NBD reacts directly with tetracyano-
ethylene to give a homo-Diels-Alder [(2+2)+2] adduct.2
In the presence of transition-metal catalysts, NBD and
acetylenes generate homo-Diels-Alder products among other
coupling products, depending on the catalyst.3 Similar
perturbations of reactivity could be anticipated for functional
groups in the peri (i.e., 1,8)-positions of naphthalene.
Therefore, reactivity of 1,8-dialkynylnaphthalenes should be
a good test of this hypothesis. We report a general variant
of the reaction in which 1,8-dialkynylnaphthalenes and NBD
undergo metal-catalyzed [(2+2)+2] and [(2+2)+(2+2)]
cycloadditions. In the latter case, four new bonds form in a
one-pot transformation, and three-, five-, and seven-
membered rings are formed at once.
Several complexes are known to effect transformations
A-D (Scheme 1). Pauson-Khand conditions, formally a
Scheme 1. Reaction Types of NBD with Alkynes
[2+2+1] cycloaddition of NBD, an alkyne and CO, generate
cyclopentenones A.4 Reaction of NBD and 1 equiv of alkyne
(1) (a) Bischof, P.; Hashmall, J. A.; Heilbronner, E.; Hornung, V. HelV.
Chim. Acta 1969, 52, 1745-9. (b) Hoffmann, R. Acc. Chem. Res. 1971, 4,
1-9. (c) Fickes, G. N.; Metz, T. E. J. Org. Chem. 1978, 43, 4057-61.
(2) Blomquist, A. T.; Meinwald, Y. C. J. Am. Chem. Soc. 1959, 81, 667-
72.
(3) Review of reactions of NBD and alkynes: (a) Lautens, M.; Tam W.
In AdVances in Metal-Organic Chemistry; Liebeskind, L. S., Ed.; JAI
Press: London, 1998; Vol. 6, pp 49-101. (b) Lautens, M.; Klute, W.; Tam,
W. Chem. ReV. 1996, 96, 49-92.
(4) Selected examples: (a) Marchueta, I.; Montenegro, E.; Panov, D.;
Poch, M.; Verdaguer, X.; Moyano, A.; Pericas, M. A.; Riera, A. J. Org.
Chem. 2001, 66, 6400-9. (b) Lee, B. Y.; Moon, H.; Chung, Y. K.; Jeong,
N. J. Am. Chem. Soc. 1994, 116, 2163. (c) Verdaguer, X.; Moyano, A.;
Pericas, M. A.; Riera, A.; Bernardes, V.; Greene, A. E.; Alvarez-Larena,
A.; Piniella, J. F. J. Am. Chem. Soc. 1994, 116, 2153.
10.1021/ol0514799 CCC: $30.25
© 2005 American Chemical Society
Published on Web 08/30/2005

was used instead of inconvenient acetylene gas.10 As
expected, fluoranthene 2 was generated from the correspond-
ing diyne 1 and NBD (Table 1 with legend),11 but besides
the desired product 2, the byproduct 3 was also observed.
The heptacycle 3a was confirmed by an X-ray crystal
structure analysis (Figure 1).12 To our knowledge, this
Table 1. Preparation of Fluoranthenes 2 and [(2+2)+(2+2)]
Adducts 3 from Diynes 1 and NBD
diyne
catalysta
T (°C)
2b
3b
yieldc (%)
1a
1a
1a
1b
1b
1c
1d
1e
1e
A
B
C
A
B
A
A
A
B
130
80
80
130
90
110
130
80
77
100
100
81
100
98
51
63
100
23
0
0
19
0
2
49
37
0
99
96
96
95
92
78d
83
93
99
Figure 1. The molecular structure of 3a in the crystal.
90
a A ) 5 mol % of RhCl(PPh3)3, B ) 2.5 mol % of [RhCl(COD)2]2,
C ) 2.5 mol % of Rh2(OAc)4‚2H2O. b The ratio was according to the
1H NMR spectrum of the crude product. c Isolated yields. d Thermolytic
cyclization (ca. 2%) of 1c was also observed.
unusual heptacycle 3 is the first example of [(2+2)+(2+2)]
cycloaddition of alkynes and NBD.13 It also explains that
this [(2+2)+(2+2)] cycloadduct 3 and the [(2+2)+2+2]
product D (cf. Scheme 1) can be formed only at the short
distance between two alkyne moieties.14
affords a homo-Diels-Alder product B5 or a formal [2+2]
adduct C,6 depending on the catalysts and alkynes used.
In the special case of a nickel catalyst, NBD, and acetylene
gas, a trace of the unusual tetracycle D formed;7 however,
with internal alkynes, even this system produced B and C.
The reaction to form D represents a formal [(2+2)+2+2]
cycloaddition of NBD and two acetylene moieties. NBD’s
role as a “proalkyne” raises the question of whether the
[(2+2)+2+2] product is from NBD and two molecules of
acetylene or from oligo-adducts of NBD with thermal
eliminations of cyclopentadiene.8
This protocol indicates that intermolecular reactions of 1a
and NBD are much faster than the intramolecular cyclization
of 1a alone.15 On the other hand, this reaction is performed
under neutral conditions with some functional group toler-
ance (cf. Table 1). Though the full scope of the reaction
remains to be investigated, there are advantages over the
traditional Knoevenagel condensation, which is well-used to
prepare cyclopentadienones, important precursors of fluor-
In our parallel study, 7,8,9,10-substituted fluoranthenes
are easily accessible from 1,8-bis(arylethynyl)naphthalene
and alkynes in the presence of the Wilkinson catalyst
(5 mol %) with good to excellent yields.9 To prepare 7,
10-disubstituted fluoranthene 2 in the same manner, NBD
(10) It was also observed that NBD as a “proalkyne” participates in the
[2+2+2] cycloaddition with two alkynes to generate 1,3-disubstituted
benzenes as byproducts; see ref 6c.
(11) Only the reaction products from 1 are isolated and characterized.
Yields are based on 1 as the limiting reagent. Dimers coming from NBD
were also formed but neglected.
(12) Crystal data for 3a: crystals from CH2Cl2/MeOH, Nonius Kappa-
CCD diffractometer, C33H24, M ) 420.55, monoclinic, a ) 15.6716(7),
b ) 9.0731(4), c ) 16.7091(7) Å, â ) 113.433(3)°, V ) 2179.9(2) Å3,
T ) 160(1) K, space group P21/n, Z ) 4, µ(Mo KR) ) 0.072 mm-1, 33 181
reflections measured, 3834 unique reflections (Rint ) 0.077), which were
used in all calculations (SHELXL-97), 2860 reflections with I > 2σ(I),
R(F) ) 0.0554 (I > 2σ(I) data), wR(F2) ) 0.1344 (all data). The “polycyclic
alkane” part of the molecule is disordered over two conformations (0.7:0.3
occupation ratio), which are inverted images of one another.
(13) Similar [4+(2+2)] cycloadducts come from 1,3-butadienes and
NBD. See: (a) Lautens, M.; Tam, W.; Sood, C. J. Org. Chem. 1993, 58,
4513-15. (b) Chen, Y.; Snyder, J. K. J. Org. Chem. 1998, 63, 2060.
(14) A mixture of 1,2-diphenylethyne, NBD, and Wilkinson catalyst was
employed at 130 °C as a blank experiment. According to the HPLC and
GC analyses, only the starting materials were obtained. Thus, the key
intermediate of this reaction, the 1-rhodacyclopentadiene derivative 6, is
confirmed. The same reason can also explain how D is formed only in
high-pressure conditions.
(5) Selected examples: (a) Hilt, G.; Smolko, K. I. Synthesis 2002, 686.
(b) Hilt, G.; du Mesnil, F.-X. Tetrahedron Lett. 2000, 41, 6757. (c) Lautens,
M.; Tam, W.; Lautens, J. C.; Edwards, L. G.; Crudden, C. M.; Smith, A.
C. J. Am. Chem. Soc. 1995, 117, 6863-79. (d) Lautens, M.; Tam, W.;
Edwards, L. G. J. Org. Chem. 1992, 57, 8-9.
(6) (a) Villeneuve, K.; Jordan, R. W.; Tam, W. Synlett 2003, 2123.
(b) Jordan, R. W.; Tam, William. Org. Lett. 2001, 3, 2367. (c) Mitsudo,
T.; Naruse, H.; Kondo, T.; Ozaki, Y.; Watanabe, Y. Angew. Chem., Int.
Ed. Engl. 1994, 33, 580.
(7) From over 37 g of NBD and an excess of acetylene gas, 2.5-2.8 g
of D was isolated. See: Schrauzer, G. N.; Glockner, P. Chem. Ber. 1964,
97, 2451.
(8) Neat NBD was used as the solvent in the presence of various rhodium
complexes to generate different dimers and trimers of NBD. See: Acton,
N.; Roth, R. J.; Katz, T. J.; Frank, J. K.; Maier, C. A.; Paul, I. C. J. Am.
Chem. Soc. 1972, 94, 5446.
(9) This method has been also applied to prepare indenocorannulenes.
See: Wu, Y.-T.; Hayama, T.; Baldridge, K. K.; Linden, A.; Siegel, J. S.
Submitted to J. Am. Chem. Soc. 2005.
(15) Intramolecular cyclizations of 1a at 100 °C to form 7-phenylbenzo-
[k]fluoranthene. See: Bossenbroek, B.; Sanders, D. C.; Curry, H. M.;
Shechter, H. J. Am. Chem. Soc. 1969, 91, 371.
4354
Org. Lett., Vol. 7, No. 20, 2005

anthenes. Additionally, fluoranthene 2c has been applied to
prepare dibenzo[a,g]corannulene.16
Scheme 2. Mechanism Based on Analogy for the Reaction of
1 and NBD3a
To understand the factors controlling the distribution of
products, a limited systematic study was undertaken. The
choice of catalyst had a demonstrable effect. Wilkinson
catalyst provided a ratio of ca. 77:23 between 2a and 3a in
this reaction. [RhCl(COD)]2 and Rh2(OAc)4 led exclusively
to the formation of fluoranthene 2a (cf. Table 1). It was found
that not only the catalyst utilized but also the substituents
(R1 and R2) of diyne 1 play important roles in the chemo-
selectivity between 2 and 3. Electron-donating and/or bulky
groups (R1 and R2) on diyne 1 enhanced the formation of 2
(cf. Table 1). However, an electron-withdrawing moiety on
the diyne 1 slightly increased the ratio of 3 (cf. Table 1).
Reaction temperature does not appear to have a serious
influence on product ratios.
A working mechanism for the formation of 2 and 3 can
be formulated by analogy with literature processes (Scheme
2).3a Initially, 1-rhodacyclopentadiene 6 is formed and
subsequent coordination of NBD partitions between an
η4-complex 5 or an η2-complex 8. Complex 5 can easily
rearrange to the deltacyclane derivative 4. Heptacycle 3 is
produced from the intermediate 4 after a reductive elimina-
tion of the Rh complex. In contrast, complex 8 inserts NBD
from its ligand sphere to afford σ-complex 7. A reductive
elimination of the Rh catalyst gives a transient dihydrofluor-
anthene that thermally eliminates cyclopentadiene to produce
fluoranthene 2.
(16) Reisch, H. A.; Bratcher, M. S.; Scott, L. T. Org. Lett. 2000, 2, 1427.
(17) Preparative procedure: a mixture of diyne 1a (164 mg, 0.5 mmol),
NBD (1 mL, 9.22 mmol), Wilkinson catalyst (23 mg, 25.0 µmol), and
p-xylene (20 mL) in a Schlenk tube at ambient temperature was passed
through nitrogen for 5 min. The mixture was kept in an oil bath under
nitrogen at 130 °C for 41 h. After cooling to room temperature and removal
of the solvent, the residue was subjected to chromatography on SiO2. Elution
with hexane/CH2Cl2 (from 4:1 to 3:1) afforded 16 mg of pure 2a and
168 mg of a mixture of 2a and 3a. Pure 3a was obtained by further
chromatography on alumina eluting with hexane. 2a: a pale yellow crystal,
mp 167 °C. IR (KBr): ν cm-1 ) 3053, 3013, 1598, 1475, 1447, 1427,
In conclusion, NBD can act as an acetylene equivalent or
a conjugated diene mimic in this rhodium-catalyzed proto-
col.17 The former role produces fluoranthenes formally by a
[(2+2)+2] reaction with excellent chemoselectivity in very
good yield and purity. The latter role for NBD results in a
formal [(2+2)+(2+2)] reaction, wherein the diene and diyne
fragments owe their special “conjugated-like” properties to
proximal through-space orbital interactions. This reactivity
exemplifies one of very few ways that three different rings
can be formed in a single reaction sequence.
1
825, 776, 759, 701. H NMR (300 MHz, CDCl3): δ ppm ) 7.24 (d, J )
7.2 Hz, 2 H), 7.35 (d, J ) 8.1 Hz, 2 H), 7.38 (d, J ) 7.2 Hz, 2 H), 7.49-
7.62 (m, 6 H), 7.64-7.69 (m, 4 H), 7.75 (d, J ) 8.1 Hz, 2 H). 13C NMR
(75.5 MHz, CDCl3, plus DEPT): δ ppm ) 122.9, 126.6, 127.4, 127.6,
128.5, 129.0 × 2 (all +), 129.7, 132.7, 136.2, 136.7, 137.9, 140.9 (all Cquat).
MS (70 eV), m/z (%): 354 (100) [M+], 328 (40), 149 (20). Elemental
analysis calcd (%) for C28H18 (354.4): C 94.88, H 5.12; found, C 94.64, H
5.16. HRMS (EI) calcd for C28H18: 354.1409; found, 354.1410. 3a: a pale
yellow crystal, mp 327-329 °C. IR (KBr): ν cm-1 ) 3051, 1577, 1487,
778, 753, 698. 1H NMR (300 MHz, CDCl3): δ ppm ) 0.86 (t, J ) 5.4 Hz,
1 H), 1.47 (s, 2 H), 1.79 (d, J ) 5.4 Hz, 2 H), 2.59 (s, 2 H), 2.61 (s, 1 H),
5.76 (d, J ) 7.2 Hz, 2 H), 6.93 (d, J ) 7.2 Hz, 2 H), 7.16-7.50 (m, 12 H).
13C NMR (75.5 MHz, CDCl3, plus DEPT): δ ppm ) 8.4, 20.1, 33.2, 55.0
(all +), 35.3 (-), 119.9, 123.0, 127.0, 127.3, 127.8, 129.3, 129.6 (all +),
130.7, 132.9, 137.5, 139.1, 142.7, 146.5 (all Cquat). MS (70 eV), m/z (%):
420 (100) [M+]. Elemental analysis calcd (%) for C33H24 (420.5): C 94.25,
H 5.75; found, C 93.96, H 5.78. HRMS (EI) calcd for C33H24: 420.1878;
found, 420.1871.
Acknowledgment. This work was supported by the Swiss
NFP grant.
Supporting Information Available: Crystal structure
data for 3a. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0514799
Org. Lett., Vol. 7, No. 20, 2005
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