Conjugate Addition and Cyclization Reactions
COMMUNICATION
mediate C. Of course, intermediate A may also undergo in-
tramolecular Friedel–Crafts cyclization[13] to afford zinc
naphthoxide C. Subsequent hydrolysis of intermediate C
would provide the naphthol product 3 (Scheme 2).
Scheme 4. Synthetic application of 3db. a) TsCl (3 equiv), Et3N (3 equiv),
CH2Cl2, 08C to RT, 24 h; b) p-MeOC6H4B(OH)2 (2 equiv), [Pd
(5 mol%), K3PO4 (2 equiv), toluene, reflux, 3 h; c) m-MeOC6H4B(OH)2
(1.5 equiv), Pd(OAc)2 (5 mol%), SPhos (10 mol%), K3PO4 (2 equiv), tol-
uene, 1108C, 1.5 h; d) PhB(OH)2 (6 equiv), Pd(OAc)2 (5 mol%), XPhos
(12.5 mol%), K3PO4 (7.5 equiv), xylenes, reflux, 25 h. Ar1 =4-(p-meth-
oxyphenyl)phenyl; Ar2 =m-methoxyphenyl.
ACHTUNGTRENNUNG(PPh3)4]
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
3-{4’-(p-methoxyphenyl)phenyl}-7-(m-methoxyphenyl)-2-
methyl-1-phenylnaphthalene (9db) by applying the tosyla-
tion and three highly selective sequential Suzuki–Miyaura
coupling reactions (Scheme 4), indicating the potential of
this methodology.[14]
In summary, we have developed a highly efficient tandem
reaction of easily available 4-aryl-2,3-allenoates[15] with orga-
nozinc reagents[8] to afford the diversified polysubstituted a-
naphthols in moderate to excellent yields. Different substitu-
ents may be introduced to different positions of naphthols
by just installing these substituents in 2,3-allenoates and or-
ganozinc reagents. The product 3db has been successfully
applied to the synthesis of polysubstituted naphthalene 9db
utilizing sequential coupling reactions. This method will be
of high interest to synthetic, material, and medicinal chem-
ists. Further studies in this area including the mechanistic
study are being conducted in our laboratory.
Scheme 2. Rationale for this transformation.
We were quite surprised to note that under Method B,
even the reaction of ethyl 2-methyl-4-phenyl-2,3-buta-
ACHTUNGTRENNUNGdienoate 1a with diethyl zinc 2d afforded 3-alkyl-substituted
naphthol 3ad in 20% yield, along with the 5-benzylidenecy-
clohex-2-enone product, which has been generated exclu-
sively in our previous study,[5] in 6% NMR spectroscopic
yield (Scheme 3, top). Furthermore, the reaction of 1a with
Experimental Section
A typical procedure for the preparation of 3db: To a dried Schlenk flask
equipped with a Teflon-coated magnetic stirring bar were added a solu-
tion of 4-bromophenyl zinc iodide (2b; 24 mL, 0.5m in THF, 12 mmol,
3 equiv) and xylenes (30 mL) sequentially with a nitrogen atmosphere at
room temperature. The flask was then submerged in an oil bath preheat-
ed to 1408C to distill off THF with a distillation apparatus for 0.5 h with
a stream of N2. A solution of 1d (0.9485 g, 4.0 mmol) in xylenes (20 mL)
was added with a syringe dropwise quickly at 1408C. After 0.5 h, the re-
action was complete as monitored by TLC and quenched subsequently
by dropwise addition of saturated aqueous NH4Cl (5 mL) at 08C. After
warming up to room temperature and extraction with diethyl ether (3ꢁ
60 mL), the organic layer was washed sequentially with diluted HCl (5%,
aq.), a saturated aqueous solution of NaHCO3, and brine. After being
dried over anhydrous Na2SO4, filtration, evaporation, and column chro-
matography on silica gel (eluent: 30–608C petroleum ether/ethyl ace-
tate=50:1) afforded 3db (0.9710 g, 70%): Solid; m.p. 157.5–159.08C;
1H NMR (300 MHz, CDCl3): d=8.16 (d, J=1.8 Hz, 1H), 7.70 (d, J=
8.4 Hz, 1H), 7.62–7.54 (m, 2H), 7.40 (dd, J1 =8.7 Hz, J2 =1.8 Hz, 1H),
7.30 (s, 1H), 7.25–7.19 (m, 2H), 5.20 (s, 1H), 2.27 ppm (s, 3H); 13C NMR
(CDCl3, 75 MHz): d=148.5, 140.34, 140.28, 131.3, 131.0, 130.6, 129.2,
127.0, 124.1, 121.4, 120.8, 120.6, 115.7, 13.3 ppm; MS (EI): m/z (%): 350
Scheme 3.
diphenyl zinc in toluene at room tempeature[5] also afforded
naphthol 3aa in 35% NMR spectroscopic yield (Scheme 3,
bottom). Thus, the chemistry shown here is mostly due to
the nature of the zinc reagents and substrates. In addition,
the high temperature, which increase the rate of either
cyclic Friedel–Crafts reaction[13] or 6p electrocyclization[12]
of intermediate A with respect to its conjugate addition to
the second molecule of allenoate,[5] may also be partially re-
sponsible.
The reaction can be easily extended to a scale of
4.0 mmol of the substrates 1d with 3 equivalents of 2b af-
fording
(3db) in 70% yield (Scheme 4). Under different conditions,
3db may easily be converted to polysubstituted naphthalene
3-(p-bromophenyl)-7-chloro-2-methyl-1-naphthol
(24.95) [M
[M
+A(79Br35Cl)]; IR (KBr, cmÀ1): n˜ =3407, 2923, 2852, 1636, 1595, 1570,
1489, 1441, 1418, 1393, 1367, 1298, 1270, 1224, 1203, 1168, 1146, 1112,
+A(81Br37Cl)], 348 (100) [M+(79Br37Cl or 81Br35Cl)], 346 (76.80)
CHTUNGTRENNUNG
CTHUNGTRENNUNG
Chem. Eur. J. 2009, 15, 11083 – 11086
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11085