Synthesis and domino reactions of 1,1-bis(hydroxymethyl)allenes

Article abstract of DOI:10.1039/a901208g

The reaction of dilithiated 1,1-diphenylallene with aryl ketones provides a convenient access to novel 1,1-bis(hydroxymethyl)allenes, which undergo Friedel-Crafts-type domino reactions upon treatment with TsOH.

Full text of DOI:10.1039/a901208g

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Synthesis and domino reactions of 1,1-bis(hydroxymethyl)allenes
Peter Langer*
Institut für Organische Chemie der Georg-August-Universität Göttingen, Tammannstraße 2, 37077 Göttingen,
Germany. E-mail: planger@uni-goettingen.de
Received (in Cambridge, UK) 15th February 1999, Accepted 12th April 1999
The reaction of dilithiated 1,1-diphenylallene with aryl
ketones provides a convenient access to novel 1,1-bis(hy-
droxymethyl)allenes, which undergo Friedel–Crafts-type
domino reactions upon treatment with TsOH.
sterically crowded allenes 4a–e were regioselectively formed
and isolated in high yields.
Treatment of allenes 4a–e with TsOH in toluene resulted in
elimination of 2 equiv. of water and selective formation of the
orange coloured 5,10,10,11-tetraaryl-10H-benzo[b]fluorenes
5a–e in very good yields (Scheme 2, Table 1).‡ In the case of
allene 4b containing two asymmetric carbon atoms, the
cyclization proceeded regioselectively via the p-methoxyphenyl
rather than the phenyl group to give 5b in good yield.
Pentafulvenes related to 5 have been used as intermediates in
the synthesis of fullerene fragments.6 Due to their curved
structure, 10H-benzo[b]fluorenes 5a–e are chiral as demon-
strated by separation of the two atropic enantiomers of 5a by
HPLC using a chiral stationary phase.§
Domino reactions of alkynes have been used for the efficient
synthesis of carbocycles and polycyclic aromatic hydrocarbons
(PAHs).1 Hydroxymethylalkynes have been converted into the
more labile allenes and cumulenes which have then been used in
situ for the preparation of [4]radialenes, macrocycles and
1,2-dihydrocyclobutaarenes.2 However, only a few domino
reactions using allenes as starting materials have been reported
so far.3 Herein, we report a convenient synthesis of 1,1-bis(hy-
droxymethyl)allenes.4 These new difunctionalized substrates
are used as starting materials in a unimolecular cationic domino
reaction. In this context the first, to the best of our knowledge,
Nazarov–Friedel–Crafts tandem reaction of an allene is re-
ported which we believe represents a new type of domino
process.
1,1-Diphenyl-3,3-dilithioallene 2 was generated in one pot by
treatment of the TBDMS enol ether 1 with an excess of LDA in
THF, a reaction recently developed by us.5 The reaction of 2
with 2 equiv. of aryl ketones 3a–e regioselectively provided the
colourless bis(hydroxymethyl)allenes 4a–e (Scheme 1, Table
1).† Due to the steric hindrance of the allenic phenyl groups, the
The formation of 10H-benzo[b]fluorenes 5 can be explained
by a Nazarov–Friedel–Crafts domino reaction. Carbocation I is
initially generated by dehydration (Scheme 2). The central
allene carbon atom is attacked by the ortho carbon atom of one
R1
R1
R2
R2
R2
R2
5a–e
R1
R1
OTBDMS
Li
LDA (3.3 equiv.)
•
TsOH
PhMe
80 °C
CH3
THF, 0 °C
R1
Li
–2 H2O
2
R2
4a–e
1
+
O
R2
–H2O
R1
R1
(1)
R1
R2
3a–e (2.5 equiv.)
H2O (excess)
R2
R2
(2)
HO
HO
R1
III
•
.
•
R2
+
HO
R2
R1
–H2O
R2
R1
R1
I
HO
H
4a–e
R2
Scheme 1
+
Table 1 Synthesis of 4 and 5
R2
R1
Isolated yield (%)
II
4/5
R1
R2
4
5
O
+
a
b
c
d
e
H
H
H
MeO
Me
Cl
80
62
75
76
71
85
73
76
83
86
R1
MeO
MeO
Me
Cl
6
R1
R2
R1 = R2 = OMe
3c
Scheme 2
Chem. Commun., 1999, 1217–1218
1217

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(1.6 M solution in hexane) to a THF solution (30 ml) of Pri2NH (3.3 equiv.)
at 0 °C. The solution was stirred at 20 °C for 6 h during which time the
colour of the solution became deep red. A THF solution (10 ml) of
benzophenone (1.34 g, 7.38 mmol) was added at 278 °C by syringe. The
temperature was allowed to rise to 20 °C within 12 h to give a deep blue
solution. The mixture was poured into water (50 ml) and was extracted with
Et2O. The combined yellow coloured organic layers were dried (MgSO4),
filtered and the solvent removed in vacuo. Purification by column
chromatography (Et2O–light petroleum 1: 5 ? 1:1) afforded the allene 4a
(1.31 g, 80%) as a colourless solid, mp 110 °C (decomp.); dH(CDCl3, 200
MHz): 3.82 (s, 2 H, OH), 6.32 (m, 4 H, Ph), 7.10–7.40 (m, 26 H, Ph);
dC(CDCl3, 50 MHz): 82.90 (C, COH), 114.85, 116.11 (C, CNCNC), 126.79,
127.91, 128.04 (CH, Ph), 127.18, 127.29, 127.83 (CH, Ph), 136.56, 146.56
(C, Ph), 205.26 (C, CNCNC); nmax(KBr)/cm21 3385 (w), 3057 (w), 1949 (m,
CNCNC), 1598 (w), 1493 (m), 1447 (m), 1348 (w), 1177 (w), 1031 (m), 698
(s). m/z (CI, H2O): 539 (M++1 2 H2O), 521 (M++1 2 2H2O), 357 (100%,
Ph2CNCNCNCPh2 + 1). (Calc. for C41H32O2: C, 88.46; H, 5.79. Found: C,
88.23; H, 5.75%.) All new compounds gave correct spectroscopical data
and elemental analyses and/or high resolution mass data.
‡ Preparation of 5a: Allene 4a (200 mg, 0.36 mmol) and TsOH (60 mg)
were heated in toluene (30 ml) at 80 °C for 2 h. The colour of the solution
changed from light yellow to deep orange. The crude mixture was purified
by column chromatography (Et2O–light petroleum = 1:5 ? 1:1) to give
5a (159 mg, 85%) as orange coloured crystals, mp 176 °C (decomp.);
dH(CDCl3, 200 MHz) 6.20 (d, J 7, 1 H, Ar), 6.56 (m, 2 H, Ar), 6.71 (d, J 7,
1 H, Ar), 6.11 (dd, J 7, J 1.5, 1 H, Ar), 6.41 (m, 2 H, Ar), 6.58 (m, 3 H, Ar),
6.85–7.25 (m, 18 H, Ar); dC(CDCl3, 50 MHz): 57.42 (C, CPh2), 119.89,
123.25, 124.70, 126.05, 126.23, 127.33, 127.34, 127.81, 127.99, 128.08,
128.20, 128.77, 128.99, 129.28, 130.14, 130.15, 130.37 (CH, Ar), 133.57,
133.81, 134.32, 135.51, 137.78, 139.80, 140.13, 142.24, 145.54, 145.82,
147.23 (C, Ar); nmax(KBr)/cm21 3056 (m), 3024 (m), 2924 (m), 1600 (m),
1492 (m), 1448 (m), 1368 (w), 1076 (w), 1032 (w), 760 (s), 744 (s), 724 (s),
700 (s); m/z (FAB) 521 (100%, M+ + 1). (Calc. for C41H28: C, 94.58; H,
5.42. Found: C, 94.27; H, 5.50%.)
of the aryl groups with formation of a five-membered ring to
give intermediate II. Aromatization and dehydration subse-
quently lead to formation of the cationic intermediate III. The
ortho carbon of the allene-derived phenyl group is attacked by
the carbocation neighboring the ketone derived aryl groups.
Aromatization finally leads to the products 5a–e. The mecha-
nism suggested is supported by the following observation:
starting with the p-methoxyphenyl-substituted allene 4c, the
benzofulvene 6 is obtained as a minor product in 10% yield.
Formation of 6 can be explained by formation of the
benzofulvene moiety and subsequent elimination of bis(p-
methoxyphenyl) ketone or, alternatively, by initial elimination
of the ketone, formation of a cumulene (vide infra) and
subsequent isomerization of the latter.
It is noteworthy that in the domino reaction leading to 5a–e
the allenic phenyl group became sterically accessible for the
cationic p-cyclization only after the previous cyclization
involving the rigid allene moiety had occurred. The reaction
cascade thus represents a combination of cyclizations as
observed for mono(hydroxymethyl)allenes7a and for aryl-
substituted bis(hydroxymethyl)alkenes Ar2CNC[C(OH)Ar2]2.
The latter have been used as precursors for the generation of
(hexaaryltrimethylene)methane dications.7b
The reaction of dilithioallene 2 with 2 equiv. of fluorenone
and xanthone gave the colourless allenes 4f and 4g in 72 and
68% yields, respectively. As minor products, the yellow
coloured cumulenes 7a and 7b were isolated in 10 and 14%
O
HO
HO
§ Conditions (a) stationary phase: tris(phenylcarbamoyl)cellulose/SiO2;
eluent: EtOH; UV detection: l = 320 nm; polarimetric detection: l = 436
nm; c = 1 mg ml21 (injection of 50 ml); P = 63 bar; T = 25 °C; flow: 0.5
•
•
HO
HO
ml min21; t1
= 9 min; k1A = 0.44. The results were independently
O
confirmed by the use of different conditions: (b) stationary phase:
triacetylcellulose/SiO2; eluent: MeOH; UV detection: l
= 278 nm;
4f
4g
polarimetric detection: l = 405 nm; c = 1 mg ml21 (injection of 150 ml);
P = 68 bar; T = 25 °C; flow: 1.0 ml min21; t1 = 12.6 min; k1A = 0.60.
1 For reviews of domino reactions, see: L. F. Tietze and U. Beifuss,
Angew. Chem., Int. Ed. Engl., 1993, 32, 131; A. de Meijere and F. E.
Meyer, Angew. Chem., Int. Ed. Engl., 1994, 33, 2379.
•
•
•
•
O
2 H. Hopf and G. Maas, Angew. Chem., Int. Ed. Engl., 1992, 31, 931; F.
Toda, K. Tanaka, I. Sano and T. Isozaki, Angew. Chem., Int. Ed. Engl.,
1994, 33, 1757; H. Hopf, P. G. Jones, P. Bubenitschek and C. Werner,
Angew. Chem., Int. Ed. Engl., 1995, 34, 2367.
7a
7b
3 S. Blechert, R. Knier, H. Schroers and T. Wirth, Synthesis 1995, 592; R.
Grigg, V. Loganathan, V. Sridharan, P. Stevenson, S. Sukirthalingam
and T. Worakun, Tetrahedron, 1996, 52, 11 479; M. Schmittel, M.
Strittmatter and S. Kiau, Angew. Chem., Int. Ed. Engl., 1996, 35, 1843;
T. Doi, A. Yanagisawa, S. Nakanishi, K. Yamamoto and T. Takahashi,
J. Org. Chem., 1996, 61, 2602; H. Nemoto, M. Yoshida and K.
Fukumoto, J. Org. Chem., 1997, 62, 6450.
4 A 1,1-bis(hydroxymethyl)allene has been previously prepared by a
different route in 17% yield: H. Mori, K. Ikoma and S. Katsumura,
Chem. Commun., 1997, 2243.
5 P. Langer, M. Döring and D. Seyferth, Chem. Commun., 1998, 1927.
6 S. Hagen, M. S. Bratcher, M. S. Erickson, G. Zimmermann and L. T.
Scott, Angew. Chem., Int. Ed. Engl., 1997, 36, 406.
7 (a) F. Toda, N. Ooi and K. Akagi, Bull. Chem. Soc. Jpn., 1971, 44, 1050;
(b) N. J. Head, G. A. Olah and G. K. S. Prakash, J. Am. Chem. Soc.,
1995, 117, 11 205.
yields. Treatment of the allenes 4f and 4g with TsOH resulted in
elimination of fluorenone or xanthone and formation of the
cumulenes 7a and 7b in 85 and 70% yields, respectively, rather
than in cyclization. Previously, formation of cumulenes has
only been observed for a-unsubstituted (hydroxymethyl)-
allenes.8 In the case of 4f, the striking difference between the
course of the dehydration reactions of the allenes 4a–e and 4f–g
can be explained by the fact that cyclization would lead to a
strained unsaturated 5,5,6-ring system.9 In addition, the anti-
aromatic character of the fluoren-9-yl cation in the ground state
and the rigid character of the ketone-derived subunits of 4f and
4g presumably direct the course of the reaction.10
P. L. thanks Professor A. de Meijere and Professor D.
Seyferth for their support and Professor A. Mannschreck for his
help with the separation of the enantiomers of 5a. Financial
support from the Fonds der Chemischen Industrie (Liebig-
scholarship and funds for P. L.) is gratefully acknowledged.
8 F. W. Nader and C.-D. Wacker, Angew. Chem., Int. Ed. Engl., 1985, 24,
851.
9 For comparison, see: G. Dyker, F. Nerenz, P. Siemsen, P. Bubenitschek
and P. G. Jones, Chem. Ber., 1996, 129, 1265.
10 M. Hoang, T. Gadosy, H. Ghazi, D.-F. Hou, A. C. Hopkinson, L. J.
Johnston and E. Lee-Ruff, J. Org. Chem., 1998, 63, 7168.
Notes and references
† Preparation of 4a. A THF solution (10 ml) of 1 (950 mg, 2.95 mmol) was
added to a THF solution of LDA which was prepared by addition of BuLi
Communication 9/01208G
1218
Chem. Commun., 1999, 1217–1218