Annulations Using Phosphonium Salts and Enolate Anions - A Direct Route to Naphthalenes

Article abstract of DOI:10.1055/s-2003-44994

Ketone enolates react with an aldehyde phosphonium salt to produce naphthalenes in a one-pot reaction.

Full text of DOI:10.1055/s-2003-44994

LETTER
97
Annulations Using Phosphonium Salts and Enolate Anions – A Direct Route to
Naphthalenes
A
Direct Route to
e
N
aphthalen
o
es rge A. Kraus,* Prabir K. Choudhury
Department of Chemistry, Iowa State University, Ames, IA 50011, USA
E-mail: gakraus@iastate.edu
Received 19 August 2003
The reaction of the lithium enolate of acetophenone
(LDA, THF, –78 °C) with phosphonate aldehyde 1 gave
the aldol dimer of acetophenone in low yield.12
Abstract: Ketone enolates react with an aldehyde phosphonium
salt to produce naphthalenes in a one-pot reaction
Key words: annulations, phosphonium salts, ketone enolates
Fortunately, the reaction of the enolate of acetophenone
with aldehyde 2 afforded a bicyclic alcohol, which could
be readily dehydrated with PTSA in methylene chloride to
provide 2-phenylnaphthalene in 58% yield from 2. Both
the proton NMR and the melting point matched that of a
sample previously prepared by Ila.13 Interestingly, alcohol
4 is stable to storage at 0 °C. It is possible that the diver-
gent reactivity of 1 versus 2 is the result of the greater
acidity of the benzylic protons in phosphonium salt 2,
leading to efficient deprotonation by the internal alkoxide.
Annulations that create new aromatic rings are often
termed benzannulations. The most common substrates for
benzannulations are alkynes1 and ketones. Notable exam-
ples of benzannulations onto ketones include the strate-
gies developed by Corey,2 Boger,3 Ila,4 Rao,5 Krohn,6 and
Takaki.7 Annulations appending a naphthalene ring are
much less common and frequently involve linear multi-
step sequences.8 As part of a synthetic approach to naph-
thoquinone anticancer agents9 we required an efficient
transformation of the type illustrated below (Scheme 1).
OH
LDA,
O
2
PTSA
Ph
O
R
Ph
Ph
R'
R
5
4
R'
Scheme 3
Scheme 1
With the facile production of naphthalene 5 (Scheme 3),
we evaluated several representative ketones. We subse-
quently found that we could simplify the procedure to a
one-pot reaction by adding concentrated HCl to the solu-
We recently described an annulation reaction of a ketone
with aliphatic aldehyde phosphonates.10 As an extension
of that earlier work, we synthesized and evaluated alde-
hydes 1 and 2 (Scheme 2). Both compounds were pre-
pared from the known bromo diester 3 that had been
prepared in two steps from o-tolualdehyde.11 Aldehyde 1
was generated by treatment of 3 with triethylphosphite
(70 °C, 24 h) followed by acidic hydrolysis of the geminal
diacetate (HCl, MeOH, r.t.). Compound 2 was produced
by treatment of 3 with triphenylphosphine (toluene,
110 °C, 12 h) followed by acidic hydrolysis (HCl, MeOH,
r.t.).
Table 1 Reactions of Enolates with Phosphonium Salt 2
OH
LDA,
O
R'
R
R'
2
PTSA
R'
R
R
R
R¢
Yield (%) Lit. ref.
13
Ph
H
65
OAc
15
Ph
Me
H
61
CHO
OAc
CH2Br
16
C3H5
Am
67
CH2X
17
H
51
1: X = PO(OEt)2
2: X = PPh3+ Br-
3
6-Methyl-5-hepten-2-one
Et
50
18
Me
57
Scheme 2
13
Cyclopentanone
Cyclohexanone
Mesityl oxide
70
SYNLETT 2004, No. 1, pp 0097–0098
0
5.
0
1.
2
0
0
4
13
73
Advanced online publication: 17.12.2003
DOI: 10.1055/s-2003-44994; Art ID: S05903ST.pdf
© Georg Thieme Verlag Stuttgart · New York
19
54

98
G. A. Kraus, P. K. Choudhury
LETTER
(12) Le Roux, C.; Gaspard-Ilouhmane, H.; Dubac, J.; Jaud, J.;
Vignaux, P. J. Org. Chem. 1993, 58, 1835.
(13) Rao, C. S.; Balu, M. P.; Ila, H.; Junjappa, H. Tetrahedron
1991, 47, 3499.
(14) To a freshly prepared solution of LDA (1 mmol in 3 mL of
THF) was added the ketone (1 mmol) in 1 mL of THF
dropwise at –78 °C and the reaction was stirred at –78 °C for
1 h. The cold solution was added via a cannula to the
phosphonium salt (1 mmol) in 5 mL of THF at –78 °C. The
solution was allowed to slowly warm to 0 °C.
tion containing the alcohol. The results are collected in
Table 1. Yields are based on reactions conducted on 1–2
mmol scales.14 Unfortunately, we could not convert alco-
hol 4 into a phenol by oxidation with DDQ or Dess–Mar-
tin periodinane.
The annulation described above converts ketone enolates
into naphthalenes in a one-pot reaction. The yields are
good and a broad range of ketones undergoes this annula-
tion reaction.
One-Pot Reaction: To the solution was then added 0.5 mL
of concentrated HCl and was stirred at r.t. for 0.5–3 h (except
for the adduct from cyclopentanone which required 10 h).
The aqueous layer was extracted twice with Et2O. The
combined organic layers were dried over MgSO4, filtered,
concentrated in vacuo and purified by flash chromatography
on silica gel using EtOAc:hexane.
Two-Step Reaction: To the solution was then added glacial
acetic acid followed by water. The aqueous layer was
extracted three times with EtOAc. The combined organic
layers were dried over Na2SO4, filtered and concentrated in
vacuo. To the alcohol in 4 mL of THF was added PTSA
(0.25–0.50 equiv.) The reaction was stirred for 2–18 h. After
aqueous workup, the crude product was purified by
chromatography on silica gel using EtOAc:hexane.
Adduct from methyl hepten-2-one: 1H NMR (CDCl3): d =
1.58 (s, 3 H), 1.69 (s, 3 H), 2.34–2.42 (m, 2 H), 2.79 (t,
J = 8.1 Hz, 2 H), 5.18–5.23 (m, 1 H), 7.32–7.47 (m, 3 H),
7.62 (s, 1 H), 7.74–7.81 (m, 3 H). 13C NMR (CDCl3): d =
17.9, 25.9, 30.1, 36.5, 123.9, 125.2, 126.0, 126.5, 127.6,
127.7, 127.8, 127.9, 132.1, 132.4, 133.8, 140.1. HMRS calcd
for C16H18: 210.1408. Found: 210.1413.
References
(1) Benzannulations onto acetylenes: (a) Vorogushin, A. V.;
Wulff, W. D.; Hansen, H.-J. J. Am. Chem. Soc. 2002, 124,
6512. (b) Dudley, G. B.; Takaki, K. S.; Cha, D. D.;
Danheiser, R. L. Org. Lett. 2000, 2, 3407. (c) Ciufolini, M.
A.; Weiss, T. J. Tetrahedron Lett. 1994, 35, 1127.
(d) Gordon, D. M.; Danishefsky, S. J.; Schulte, G. K. J. Org.
Chem. 1992, 57, 7052. (e) Parker, K. A.; Coburn, C. A. J.
Org. Chem. 1991, 56, 1666.
(2) Corey, E. J.; Palani, A. Tetrahedron Lett. 1997, 38, 2397.
(3) Boger, D. L.; Mullican, M. D. J. Org. Chem. 1980, 45, 5002.
(4) Ila, H.; Junjappa, H.; Mohanta, P. K. Prog. Het. Chem. 2001,
13, 1.
(5) Rao, S. C.; Rao, G. S. K. Synthesis 1987, 231.
(6) Krohn, K.; Bernhard, S. Eur. J. Org Chem. 1999, 3099.
(7) Takaki, K.; Okada, M.; Yamada, M.; Negoro, K. J. Org.
Chem. 1982, 47, 1200.
(8) (a) Hornback, J. M.; Poundstone, M. L.; Vadlamani, B.;
Graham, S. M.; Gabay, J.; Patton, S. T. J. Org. Chem. 1988,
53, 5597. (b) Tius, M. A.; Gomez-Galeno, J. Tetrahedron
Lett. 1986, 27, 2571. (c) Ghera, E.; Ben-David, Y.
Tetrahedron Lett. 1985, 26, 6253. (d) Schmidt, J. M.;
Mercure, J.; Tremblay, G. B.; Page, M.; Kalbakji, A.; Feher,
M.; Dunn-Dufault, R.; Peter, M. G.; Redden, P. R. J. Med.
Chem. 2003, 46, 1408.
(15) Yamato, M.; Hashigaki, K.; Yoshioka, S.; Takeuchi, Y.
Heterocycles 1985, 23, 1741.
(16) Gandon, V.; Bertus, P.; Szymoniak, J. Eur. J. Org. Chem.
2000, 3713.
(17) Stille, J. K.; Foster, R. T. J. Org. Chem. 1963, 28, 2703.
(18) Mitchell, R. H.; Dingle, T. W.; Williams, R. V. J. Org.
Chem. 1983, 48, 903.
(19) Kulasegaram, S.; Kulawiec, R. J. J. Org. Chem. 1997, 62,
6547.
(9) Kraus, G. A.; Wan, Z. Synlett 2000, 363.
(10) Kraus, G. A.; Choudhury, P. K. Org. Lett. 2002, 4, 2033.
(11) Berenguer, M. J.; Castells, G. J.; Galard, R. M.; Moreno-
Manas, M. J. Tetrahedron Lett. 1971, 495.
Synlett 2004, No. 1, 97–98 © Thieme Stuttgart · New York