An intramolecular, Pd-mediated α-arylation route to 4-aryl-2-naphthols

Article abstract of DOI:10.1016/j.tetlet.2015.06.081

1-Aryl-1-(2-bromophenyl)but-2-yn-1-ols, obtained from the addition of prop-1-yn-1-yllithium to 2-bromobenzophenones, readily rearrange to 4-aryl-4-(2-bromophenyl)but-3-en-2-ones upon treatment with TFA. Subsequent intramolecular Pd-mediated α-arylation of

Full text of DOI:10.1016/j.tetlet.2015.06.081

Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An intramolecular, Pd-mediated
naphthols
a-arylation route to 4-aryl-2-
⇑
Stuart Aiken, Ben Armitage, Christopher D. Gabbutt, B. Mark Heron
Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
1-Aryl-1-(2-bromophenyl)but-2-yn-1-ols, obtained from the addition of prop-1-yn-1-yllithium to 2-bro-
mobenzophenones, readily rearrange to 4-aryl-4-(2-bromophenyl)but-3-en-2-ones upon treatment with
Received 11 May 2015
Revised 24 June 2015
Accepted 25 June 2015
Available online xxxx
TFA. Subsequent intramolecular Pd-mediated
thols which were smoothly transformed into photochromic naphthopyrans.
Ó 2015 Elsevier Ltd. All rights reserved.
a-arylation of these but-3-en-2-ones gave 4-aryl-2-naph-
Keywords:
But-2-yn-1-ols
Meyer–Schuster rearrangement
Intramolecular
-Aryl-2-naphthol
Naphthopyran
Photochromism
a-arylation
4
Substituted 2-naphthols are extremely valuable substrates for
the preparation of biologically active molecules and pharmaceuti-
range of arylboronic acids to give 4-aryl-2-naphthols in good yields
1
4
after demethylation (Scheme 1d). 4-Phenyl-2-naphthol has been
obtained by the Friedel–Crafts acylation of phenylacetylene with
1
2
3,4
cals, BINOL ligands, azo-dyes and pigment lakes, photochromic
naphthopyrans, electroluminescent materials,6 organometallic
macrocycles and molecular machines.8 Given the versatility of
these compounds it is somewhat surprising that versatile strate-
gies to prepare 3- and or 4- substituted 2-naphthols are relatively
5
15
phenylacetyl chloride and by the gold-catalysed carbocyclization
7
16
of 2-(prop-2-yn-1-yl)benzophenone. Given the general lack of a
relatively inexpensive and simple regiospecific approach to prepar-
ing such naphthols from either commercial or readily available
starting materials, combined with our interest in photochromic
9
few in number. Recent approaches to give 3,4-disubstituted
1
7
2
-naphthols include an effective, base free, 6-endo-dig electrophilic
cyclisation of 1-phenyl-3-alkyn-2-ones to afford 3-iodo-4-phenyl-
-naphthol (Scheme 1a).10 Base-free reaction conditions were also
used in the Pd(CF CO (dppe) mediated annulation of methyl
o-(BPin)phenyl acetates to 1,2-bis(4-methoxyphenyl)ethyne
naphthopyrans which are derived from the acid-catalysed con-
densation between 1,1-diarylprop-2-yn-1-ols and substituted 2-
18
2
naphthols, we were interested in exploring new 2-naphthol con-
3
2
)
2
structs. On this theme, the Pd-mediated ring closure employed to
obtain the key tricycle (Scheme 1e), in an alternative synthesis of
duocarmycins involving the coupling between a silyl enol ether
1
1
resulting in 3,4-di(4-methoxyphenyl)-2-naphthol (Scheme 1b).
-Aryl-2-naphthols, devoid of additional substituents, have
1
9
4
and a triflate, attracted our attention.
Considering the above reaction leading to an O-protected
‘heterocyclic naphthol’ to be the forerunner of an -arylation
protocol it was postulated that suitably functionalized 4,4-diaryl-
but-3-en-2-ones could be subjected to an intramolecular -aryla-
recently been reported by strategies employing C–C bond insertion
of benzyne into aroylacetones with subsequent intramolecular
aldol condensation and dehydration, typically affording isomeric
a
2
0
mixtures
of
3-aryl-1-naphthols
Moreover a Pd(OAc)
and
4-aryl-2-naphthols
a
2
a,12
(Scheme 1c).
2
-catalysed meta-selective
tion reaction to afford 4-arylnaphthalen-2(1H)-ones which would
direct arylation protocol has been employed to synthesise
readily tautomerise to the required 2-naphthols.
2
-carbamoyloxy-4-arylnaphthalenes.13
2-Methoxy-4-trifloxy-
Thus, addition of prop-1-yn-1-yllithium, efficiently generated
21
naphthalene, derived from relatively expensive 1,3-dihydroxy-
naphthalene, has been subjected to Suzuki couplings with a
from the reaction of excess LDA to 1,2-dibromopropane, to read-
2
2
ily available 2-bromobenzophenones 1a,b gave butynols 2a,b in
excellent yield (Scheme 2). Subsequent Meyer–Schuster rearrange-
2
3
ment of 2a,b to afford 4-aryl-4-(2-bromophenyl)but-3-en-2-ones
a,b was accomplished in high yield using TFA in toluene at room
⇑
Corresponding author. Tel.: +44 (0)1484 471728.
E-mail address: m.heron@hud.ac.uk (B.M. Heron).
3
http://dx.doi.org/10.1016/j.tetlet.2015.06.081
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0
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2
S. Aiken et al. / Tetrahedron Letters xxx (2015) xxx–xxx
O
OH
I
ICl, MeCN
1a
Ph
8 %
Ph
9
An
An
OH
An
BPin
CO
3 2 2
Pd(CF CO ) (dppe) 5 mol%
+
1b
2
Me
MeOH, 80 °C
An
An = 4-MeOC
6
H
4
-
83 %
OH
OH
SiMe
3
O
O
CsF, MeCN, reflux
+
+
1c
An
OTf
An
An
22 %
35 %
B(OH)
2
OMe
(i) Pd(PPh
3 4
) 2 mol%,
Na
2
CO , PhMe, EtOH, reflux
3
+
OH 1d
(
ii) BBr , CH Cl , N , rt
3
2
2
2
OTf
N
HO
OMe
O
76 %
OCOt-Bu
N
(
i) t-BuMe
2
SiOTf, Et
, 0 °C;
3
N,
CH Cl
2
2
1e
NH
NH
OTf
(ii) PdCl
LiCl, argon, xylene, 160 °C;
iii) t-BuCOCl, pyridine
2 3 2 3
(Ph P) 3 mol%, Bu SnF,
CO
2
Me
2
CO Me
(
89 %
Scheme 1.
O
O
R
(i)
OH
R
(ii)
R
Br
Br
Br
3a R = Ph (73 %)
3b R = 4-MeOC6H - (90 %)
1
a R = Ph
b R = 4-MeOC H -
2a R = Ph (71 %)
1
2b R = 4-MeOC 6H - (98 %)
6
4
4
4
An
An
An
An
OH
(iii)
(iv)
O
UV
O
dark
R
R
R
4
a R = Ph (27 %)
b R = 4-MeOC H - (43 %)
5a R = Ph (76 %)
5b R = 4-MeOC H - (89 %)
6a R = Ph
4
6b R = 4-MeOC H -
6
4
6
4
6
4
5c R = H
6c R = H
Scheme 2. Reagents and conditions: (i) n-BuLi, diisopropylamine, anhyd. THF, N
2
, À70 °C to rt then 1,2-dibromopropane, À60 °C to rt; (ii) CF
CH, PPTS, 1,2-DCE, reflux.
3 2 2 3
CO H, PhMe, rt; (iii) Pd (dba)
(
5 mol %), (t-Bu) PHBF , KOt-Bu, anhyd PhMe; (iv) 1,1-bis(4-methoxyphenyl)prop-2-yn-1-ol, (MeO)
3
4
3
temperature. The geometry of 3b was established as the Z-isomer
through NOE interactions between the alkene proton which res-
onated at d 6.73 and the protons meta- to the methoxy group in
the anisole ring which appeared at d 7.28. No other NOE interac-
tions were observed between the alkene proton and any other aro-
matic protons (see ESI). It is of interest to note that 3b has been
previously obtained in two steps, in 20% overall yield, through
the addition of isopropenylmagnesium bromide to 1b followed
by a Pd-catalysed oxidative rearrangement of the 1,1-diaryl-2-
combinations on the yield of this useful transformation. Evidence
for the formation of the desired naphthols was accrued from
NMR spectroscopy which exhibited key signals for the protons of
the hydroxyl-substituted naphthalene ring, for example, 4a d 5.4
2
(1H, s, OH (D O exchangeable), d 7.04 (1H, d, J = 2.0 Hz, 3-H),
d 7.14 (1H, d, J = 2.0 Hz, 1-H) and mass spectrometry which gave
good agreement between the found and required molecular ions
(see ESI). The usefulness of compounds such as 4 was demon-
strated by their facile transformation into novel naphthopyrans
5a,b in excellent yields using pyridinium p-toluenesulfonate
2
4
methylprop-2-en-1-ol. The present two step transformation of
b into 3b was accomplished more efficiently (88% over two steps).
Widely used conditions (Pd (dba) (t-Bu) PHBF KOt-Bu,
PhMe, reflux) for routine intermolecular -arylation chemistry
were adopted for a preliminary investigation into the ring closure
of 3a,b to the naphthols 4a,b. The -arylation step currently repre-
1
3
(PPTS) in conjunction with an alkynol and (MeO) CH as a dehy-
2
5
2
3
,
3
4
,
drating agent. The naphthopyrans exhibited characteristic sig-
nals for 2-H in their NMR spectra at d 6.2 (J = 10 Hz) and at d
82.2 for 3-C; both of which were indicative of the pyran unit.26
2
0
a
a
UV
irradiation
(365 nm,
8 W)
of
toluene
solutions
À6
À3
sents the weak link in this three step transformation offering only
poor to moderate yields (4a 27%; 4b 43%) and there remains much
scope to explore the impact of various ligands, catalysts and base
(ca. 1 Â 10 mol dm ) of 5a,b together with the established
naphthopyran 5c for comparative purposes resulted in the genera-
tion of orange–red coloured photomerocyanines 6a–c with
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S. Aiken et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
absorption maxima at ca. 470 nm (see ESI) in accord with their
substitution pattern.
In summary, we have developed a short route to 4-aryl-2-naph-
thols which relies upon the efficient generation and Meyer–
Schuster rearrangement of a 1,1-diarylbutynol. The C-1–C-8a bond
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substituents are ongoing.
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