Organocatalytic Enantioselective Friedel-Crafts Alkylation of 1-Naphthol Derivatives and Activated Phenols with Ethyl Trifluoropyruvate

Article abstract of DOI:10.1002/adsc.201500548

An organocatalytic enantioselective Friedel-Crafts alkylation of a series of substituted 1-naphthol derivatives and activated phenols with ethyl trifluoropyruvate, catalyzed by a quinine-derived squaramide, is presented. Good yields and high to excellent enantioselectivities of the Friedel-Crafts alkylation products were obtained.

Full text of DOI:10.1002/adsc.201500548

COMMUNICATIONS
DOI: 10.1002/adsc.201500548
Organocatalytic Enantioselective Friedel–Crafts Alkylation of
-Naphthol Derivatives and Activated Phenols with Ethyl
Trifluoropyruvate
1
a
a
a
a
Marc Montesinos-Magraner, Carlos Vila, Gonzalo Blay, Isabel Fernµndez,
b
a,
M. Carmen MuÇoz, and JosØ R. Pedro *
Departament de Química Orgànica, Facultat de Química, Universitat de Val›ncia, Dr. Moliner 50, 46100 Burjassot,
a
Val›ncia, Spain
E-mail: jose.r.pedro@uv.es
b
Departament de Física Aplicada, Universitat Polit›cnica de Val›ncia, Camí de Vera s/n, 46022 Val›ncia, Spain
Received: June 5, 2015; Revised: July 20, 2015; Published online: September 25, 2015
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500548.
[
6]
Abstract: An organocatalytic enantioselective Frie-
del–Crafts alkylation of a series of substituted 1-
naphthol derivatives and activated phenols with
ethyl trifluoropyruvate, catalyzed by a quinine-de-
rived squaramide, is presented. Good yields and
high to excellent enantioselectivities of the Friedel–
Crafts alkylation products were obtained.
been recently reported, using isatins as substrates.
Nevertheless, the enantioselective alkylation of 1-
naphthol with alkyl trifluoropyruvates is not de-
scribed, to the best of our knowledge. This reaction
would provide access to chiral tertiary benzylic alco-
hols bearing a trifluoromethyl group as a substitu-
[7,8]
ent.
This particular motif has become an important
structural characteristic in several drugs such as CJ-
17493 or Efavirenz (Figure 1).
[9]
Keywords: asymmetric catalysis; Friedel–Crafts re-
action; naphthols; organocatalysis; trifluoropyru-
vates
The Friedel–Crafts (F-C) reaction is one of the most
fundamental, important and powerful CÀC bond
[
1]
forming reactions in organic chemistry. This reaction
provides an efficient synthetic pathway to prepare Figure 1. Structures of drugs containing a chiral tetrasubsti-
tuted carbon bearing a trifluoromethyl group.
functionalized aromatic compounds of great impor-
tance and widely used in academia and industry.
Moreover, the catalytic enantioselective version of
the F-C reaction leads to the formation of highly val-
uable chiral aromatic compounds.
Since the pioneering work by Jørgensen and co-
workers, who described the alkylation of different
[
2]
[10]
However, most of the examples reported in the lit- aromatic and heteroaromatic compounds with alkyl
erature with regard to this version are concerned with trifluoropyruvate, several methodologies have been
[11]
the use of heteroarenes such indoles and pyrroles as reported. However, the enantioselective alkylation
[
3]
nucleophilic partners, whilst other nucleophiles such of naphthols with ethyl trifluoropyruvate remains elu-
[12]
as naphthols have been less studied, probably due to sive (Scheme 1). As a part of our continuous inter-
[
4]
their reduced reactivity towards electrophiles. Con- est in the enantioselective synthesis of CF -cointaining
3
[13]
sequently, the extension of the asymmetric F-C alky- compounds,
herein we report an organocatalytic
lations to include naphthols is of great interest for or- enantioselective F-C alkylation of 1-naphthol deriva-
ganic synthesis. Since the first example of Erker in tives with ethyl trifluoropyruvate under mild condi-
[
5]
[14]
1
990 where the enantioselective alkylation of naph- tions using a squaramide organocatalyst
thol was described using an activated ketone such from quinine.
methyl pyruvate, only two asymmetric examples of The reaction of 1-naphthol (1a) with ethyl trifluoro-
the reaction between naphthols and ketones have pyruvate (2) was studied with different bifunctional
derived
Adv. Synth. Catal. 2015, 357, 3047 – 3051
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3047

Marc Montesinos-Magraner et al.
COMMUNICATIONS
[
a]
Table 1. Optimization of the reaction conditions.
Scheme 1. Enantioselective Friedel–Crafts alkylation with
ethyl trifluoropyruvate.
organocatalysts under various reaction conditions
(
Table 1). We initially examined quinine (A) in tolu-
ene at room temperature (entry 1, Table 1). To our
delight, the corresponding tertiary alcohol 3a was ob-
tained smoothly in 70% yield and 43% ee. 9-O-(p-
MeC H CH )-cupreine B, where the 9-OH group was
6
4
2
protected and the 6’-OH was free, showed an inver-
sion of the enantioselectivity (48% ee), with a moder-
ate yield (Table 1, entry 2). Although cupreine cata-
lysts C and D, with different groups such as aryl ether
or benzoyl group at the 9-OH position, afforded the
product 3a with higher enantioselectivity, (78% ee, en-
tries 3 and 4) the reactions were slower. When qui-
nine-derived thiourea E was used (Table 1, entry 5),
the reaction proceed faster, furnishing the product in
Entry Catalyst
mol%)
Solvent t
T
Yield
ee
[%]
[
b]
[c]
(
[h] [8C] [%]
[
d]
1
2
3
4
5
6
7
8
9
1
1
A (5%)
B (5%)
C (5%)
D (5%)
E (5%)
F (5%)
G (5%)
F (5%)
F (5%)
F (5%)
F (5%)
toluene 2
toluene 3
toluene 7
toluene 6
toluene 1.5 r.t.
toluene 1.5 r.t.
r.t.
r.t.
r.t.
r.t.
70
54
64
66
86
89
86
91
92
88
94
43
48
78
78
46
78[
46
80
91
87
87
86% yield, although with a decrease in the enantio-
meric excess (46%). Quinine-derived squaramide F
proved to be the most efficient catalyst (entry 6,
Table 1) in terms of yield (89%) and enantioselectivi-
ty (78% ee). Other thiourea organocatalysts bearing
a tertiary amine moiety, such as Takemotoꢁs catalyst
G (entry 7, Table 1), showed good yield (86% yield),
d]
toluene 2
r.t.
r.t.
r.t.
r.t.
r.t.
CH Cl
1
2
2
2
2
2
Et O
2
0
1
EtOAc
(i-
Pr) O
2
although with decreased selectivity (46% ee). We de- 12
cided to study the effect of different solvents (en- 13
tries 8–12) with catalyst F in the Friedel–Crafts alkyla- 14
F (5%)
F (5%)
F (2%)
F (1%)
MTBE 24 r.t.
30
90
80
35
91
97
98
96
Et
Et
O
O
2
24
24
0
0
0
2
2
15
Et O
tion. To our delight, when ether was used as a solvent,
excellent results were obtained (92% yield, 91% ee,
entry 9). The enantiomeric excess of tertiary alcohol
2
[a]
Reaction conditions: 0.100 mmol 1a, 0.125 mmol 2, and
catalyst in solvent (1.0 mL).
Isolated yield after column chromatography.
Enantiomeric excess determined by chiral HPLC.
The major product is the (S)-enantiomer.
[
[
[
b]
c]
d]
3
a could reach 97% (entry 13) when the reaction was
carried out at 08C. Finally, the catalyst loading was
decreased to 2 and then 1 mol% (entries 14 and 15,
respectively), with similar results in terms of enantio-
selectivity, although the reactivity was much lower.
was studied with 1-naphthol substituted at the 5-posi-
Under the optimized conditions shown in entry 13, tion, with good yields and excellent enantiomeric ex-
the substrate scope was investigated (Scheme 2). Dif- cesses. Remarkably, 1,5-dihydroxynaphthalene react-
[
15]
ferent 1-naphthols
substituted with electron-with- ed smoothly affording the corresponding chiral terti-
[17]
drawing and electron-donating groups were reacted ary alcohol 3g with 70% yield and 97% ee. Finally,
with ethyl trifluoropyruvate (2). The presence of an our reaction protocol also allowed us to use electron-
electron-donating group such MeO at the position 4 rich phenols as nucleophiles. Sesamol (4a), 3,4-di-
decreased the yield, without compromising the enan- methoxyphenol (4b) and even phenols with only one
tiomeric excess (96%), however, groups such as Cl, electron-donating group (4c–4f) gave the correspond-
Br and OAc at this position gave good yields and ex- ing chiral tertiary alcohols (5a–5f), although a de-
cellent enantioselelectivities. Moreover, the reaction crease in the enantioselectivity was observed. Un-
[
16]
[18]
[19]
3
048
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3047 – 3051

COMMUNICATIONS
Organocatalytic Enantioselective Friedel–Crafts Alkylation
[
20]
Figure 2. X-ray crystal structure of 3c.
Treatment of product 3a with p-TsOH in toluene at
[21]
7
08C afforded chiral lactone
preserving the enantiomeric purity of the compound
Scheme 3).
6 in 80% yield and
(
Scheme 3. Lactonization of 3a.
In summary, we have developed a highly enantiose-
lective addition of 1-naphthol derivatives to ethyl tri-
fluoropyruvate employing a squaramide organocata-
lyst derived from quinine. The corresponding chiral
tertiary alcohols bearing a trifluoromethyl group were
obtained with good yields and excellent enantioselec-
tivities. Furthermore, the methodology was extended
to the use of activated phenols, with good yields and
enantiomeric excesses.
Experimental Section
Scheme 2. Substrate scope for the enantioselective Friedel–
Crafts alkylation. Reaction conditions: 0.100 mmol 1,
General Friedel–Crafts Procedure
0
.125 mmol 2, and F (5 mol%) in Et O (1.0 mL) at 08C. Iso-
2
lated yield after column chromatography. Enantiomeric
excess determined by chiral HPLC.
Naphthol
1
(0.100 mmol), ethyl trifluoropyruvate
2
(0.125 mmol) and squaramide F (2.4 mg, 0.050 mmol) were
dissolved in 1.0 mL of ether and the mixture stirred at 08C
until the reaction was complete (TLC). Finally, the reaction
mixture was directly applied to column chromatograpy,
fortunately, simple phenol is unreactive in our reac- using hexane:Et
tion conditions.
O (95:5) as eluent to afford product 3.
2
The absolute configuration of product 3c was as-
Synthesis of (R)-3-Hydroxy-3-(trifluoromethyl)-
naphtho[1,2-b]furan-2(3H)-one (6)
signed as (R) on the basis of an X-ray crystal struc-
[
20]
ture analysis (Figure 2). The configurations of the
rest of products were assigned on the assumption of A solution of 3a (30 mg, 0.095 mmol) and p-TsOH (4 mg,
a uniform mechanistic pathway.
0.019 mmol) in toluene (0.4 mL) was stirred for 6 h at 708C.
Adv. Synth. Catal. 2015, 357, 3047 – 3051
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3049

Marc Montesinos-Magraner et al.
COMMUNICATIONS
The corresponding reaction mixture was purified directly by
flash chromatography on silica gel affording compound 6;
yield: 19.8 mg (78%).
2015, 127, 6418; Angew. Chem. Int. Ed. 2015, 54, 6320;
p) Y. Sohtome, B. Shin, N. Horitsugi, K. Noguchi, K.
Nagasawa, Chem. Asian J. 2011, 6, 2463; q) C. Jarava-
Barrera, F. Estaban, C. Navarro-Ranninger, A. Parra, J.
Alemµn, Chem. Commun. 2013, 49, 2001.
[
[
[
5] G. Erker, A. A. H. van der Zeijden, Angew. Chem.
Acknowledgements
1990, 102, 543; Angew. Chem. Int. Ed. Engl. 1990, 29,
512.
Financial support from the MINECO [Gobierno de EspaÇa
and FEDER (EU)] (CTQ2013-47949-P) and from Generali-
tat Valenciana (ISIC2012/001) is gratefully acknowledged. M.
M.-M. thanks the Universitat de Val›ncia for a predoctoral
grant. C. V. thanks MINECO for JdC contract. Access to
NMR and MS facilities from the Servei central de support
a la investigació experimental (SCSIE)-UV is also acknowl-
edged.
6] a) D. Wu, X. Zhang, Y. Xu, Y. Xue, J. Li, W. Wang, J.
Zhu, Asian J. Org. Chem. 2014, 3, 480; b) J. Kaur, A.
Kumar, S. S. Chimni, Tetrahedron Lett. 2014, 55, 2138.
7] a) T. Hiyama, Organofluorine Compounds: Chemistry
and Applications, Springer, Berlin, 2000; b) J. Wang, M.
Sµnchez-Roselló, J. L. AceÇa, C. del Pozo, A. E. Soro-
chinsky, S. Fustero, V. A. Soloshonok, H. Liu, Chem.
Rev. 2014, 114, 2432; c) S. Purser, P. R. Moore, S. Swal-
low, V. Gouverneur, Chem. Soc. Rev. 2008, 37, 320;
d) M. Shimizu, T. Hiyama, Angew. Chem. 2005, 117,
2
18; Angew. Chem. Int. Ed. 2005, 44, 214.
References
[
8] a) K. Mikami, Y. Itoh, M. Yamanaka, Chem. Rev. 2004,
104, 1; b) J.-A. Ma, D. Cahard, Chem. Rev. 2004, 104,
6119; c) J. Nie, H.-C. Guo, D. Cahard, J.-A. Ma, Chem.
Rev. 2011, 111, 455.
[9] a) S. Caron, N. M. Do, J. E. Sieser, P. Arpin, E. Vaz-
quez, Org. Process Res. Dev. 2007, 11, 1015; b) N. Y.
Rakhmanina, J. N. van den Anker, Expert Opin. Drug
Metab. Toxicol. 2010, 6, 95.
[10] a) N. Gathergood, W. Zhuang, K. A. Jørgensen, J. Am.
Chem. Soc. 2000, 122, 12517; b) W. Zhuang, N. Gather-
good, R. G. Hazell, K. A. Jørgensen, J. Org. Chem.
2001, 66, 1009.
11] For the use of indoles, see: a) B. Tçrçk, M. Abid, G.
London, J. Esquibel, M. Tçrçk, S. C. Mhadgut, P. Yang,
G. K. S. Prakash, Angew. Chem. 2005, 117, 3146;
Angew. Chem. Int. Ed. 2005, 44, 3086; b) M. P. A. Lyle,
N. D. Draper, P. D. Wilson, Org. Lett. 2005, 7, 901; c) S.
Nakamura, K. Hyodo, Y. Nakamura, N. Shibata, T.
Toru, Adv. Synth. Catal. 2008, 350, 1443; d) Y. Hui, W.
Chen, W. Eang, J. Jiang, Y. Cai, L. Lin, X. Liu, X.
Feng, Adv. Synth. Catal. 2010, 352, 3174; e) C. Wolf, P.
Zhang, Adv. Synth. Catal. 2011, 353, 760; f) X.-H. Xu,
A. Kusuda, E. Tokunaga, N. Shibata, Green Chem.
[
1] a) G. A. Olah, Friedel–Crafts Chemistry, Wiley, New
York, 1973; b) R. M. Roberts, A. A. Khalaf, Friedel–
Crafts Alkylation Chemistry. A Century of Discovery,
Dekker, New York, 1984.
[2] a) M. Bandini, A. Umani-Ronchi, Catalytic Asymmetric
Friedel–Crafts Alkylations, Wiley-VCH, Weinheim,
2
2
009; b) T. B. Poulsen, K. A. Jørgensen, Chem. Rev.
008, 108, 2903; c) S.-L. You, Q. Cai, M. Zeng, Chem.
Soc. Rev. 2009, 38, 2190.
[
[
3] a) M. Bandini, A. Eichlolzer, Angew. Chem. 2009, 121,
9786; Angew. Chem. Int. Ed. 2009, 48, 9608; b) G. Bar-
toli, G. Bencivenni, R. Dalpozzo, Chem. Soc. Rev. 2010,
[
39, 4449; c) R. Dalpozzo, Chem. Soc. Rev. 2015, 44,
742.
4] a) S. Brandes, M. Bella, A. Kjærsgaard, K. A. Jørgen-
sen, Angew. Chem. 2006, 118, 1165; Angew. Chem. Int.
Ed. 2006, 45, 1147; b) S. Brandes, B. Niess, M. Bella, A.
Prieto, J. Overgaard, K. A. Jørgensen, Chem. Eur. J.
2
006, 12, 6039; c) T.-Y. Liu, H.-L. Cui, Q. Chai, J. Long,
B.-J. Li, Y. Wu, L.-S. Ding, Y.-C. Chen, Chem.
Commun. 2007, 2228; d) X.-S. Wang, G.-S. Yang, G.
Zhao, Tetrahedron: Asymmetry 2008, 19, 709; e) X.-S.
Wang, C.-W. Zheng, S.-L. Zhao, Z. Chai, G. ; Zhao, G.-
S. Yang, Tetrahedron: Asymmetry 2008, 19, 2699; f) L.
Hong, L. Wang, W. Sun, K. Wong, R. Wang, J. Org.
Chem. 2009, 74, 6881; g) Y. Sohtome, B. Shin, N. Hori-
tsugi, R. Takagi, K. Noguchi, K. Nagasawa, Angew.
Chem. 2010, 122, 7457; Angew. Chem. Int. Ed. 2010, 49,
2011, 13, 46; g) T. Sumiyoshi, K. Tojo, D. Urable, M.
Tobe, Tetrahedron: Asymmetry 2011, 22, 153; h) G.
Grach, A. Dinut, S. Marque, J. Marrot, R. Gil, D. Prim,
Org. Biomol. Chem. 2011, 9, 497; i) X. Han, H.-B. Liu,
C. Dong, Tetrahedron: Asymmetry 2012, 23, 1332; j) M.
Rueping, T. Bootwicha, S. Kambutong, E. Suginomo,
Chem. Asian J. 2012, 7, 1195; k) X. Han, W. Ouyang, B.
Liu, W. Wang, P. Tien, S. Wu, H.-B. Zhou, Org.
Biomol. Chem. 2013, 11, 8463; l) D. Carmona, P.
Lamata, A. Sµnchez, P. Pardo, R. Rodríguez, P. Ramír-
ez, F. J. Lahoz, P. García-OrduÇa, L. A. Oro, Organo-
metallics 2014, 33, 4016; m) D. Carmona, M. P. Lamata,
A. Sµnchez, F. Viguri, R. Rodríguez, L. A. Oro, C. Liu,
S. DiØz-Gonzµlez, F. Maseras, Dalton Trans. 2014, 43,
7299; h) X. Jiang, L. Wu, Y. Xing, L. Wang, S. Wang,
Z. Chen, R. Wang, Chem. Commun. 2012, 48, 446; i) E.
Paradisi, P. Righi, A. Mazzanti, S. Ranieri, G. Benci-
venni, Chem. Commun. 2012, 48, 11178; j) L. Yu, X.
Xie, S. Wu, R. Wang, W. He, D. Qin, Q. Liu, L. Jing,
Tetrahedron Lett. 2013, 54, 3675; k) G. Liu, S. Zhang,
H. Li, T. Zhang, W. Wang, Org. Lett. 2011, 13, 828; l) P.
Chauhan, S. S. Chimni, Eur. J. Org. Chem. 2011, 1636;
m) S. Takizawa, S. Hirata, K. Murai, H. Fujiokab, H.
Sasai, Org. Biomol. Chem. 2014, 12, 5827; n) S. Takiza-
wa, F. Arteaga-Arteaga, Y. Yoshida, J. Kodera, Y.
Nagata, H. Sasai, Dalton Trans. 2013, 42, 11787; o) M.
Montesinos-Magraner, C. Vila, R. Cantón, G. Blay, I.
Fernµndez, M. C. MuÇoz, J. R. Pedro, Angew. Chem.
11260. For the use of other heterocycles, see: n) K.
Aikawa, Y. Asai, Y. Hioki, K. Mikami, Tetrahedron:
Asymmetry 2014, 25, 1104. For the use of activated
arenes, see: o) A. Corma, H. García, A. Moussaif, M. J.
Sabater, R. Zniber, A. Redouane, Chem. Commun.
3
050
asc.wiley-vch.de
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2015, 357, 3047 – 3051

COMMUNICATIONS
Organocatalytic Enantioselective Friedel–Crafts Alkylation
2
002, 1058; p) J.-L. Zhao, Y. Sui, Y.-L. Liu, D. Wang,
[17] Compounds 3a, 3b, 3f, 3g and 3h were isolated with
a minor impurity that has been identified as the corre-
sponding lactone. This lactone is formed during the
course of the reaction, but we also observed the forma-
tion of the lactone during the isolation and purification
processes of the product. This lactone has been fully
characterized for the cyclization product of compound
Y.-J. Chen, Org. Lett. 2006, 8, 6127.
[
[
12] For an organocatalytic example using simple phenols
where the alkylation occurs at the para position: J.-L.
Zhao, L. Liu, C.-L. Gu, D. Wang, Y.-J. Chen, Tetrahe-
dron Lett. 2008, 49, 1476.
13] a) G. Blay, I. Fernµndez, A. Monleón, J. R. Pedro, C.
Vila, Org. Lett. 2009, 11, 441; b) G. Blay, I. Fernµndez,
M. C. MuÇoz, J. R. Pedro, C. Vila, Chem. Eur. J. 2010,
3
a, see Scheme 3.
[
18] For enantioselective additions of electron-rich phenols
to isatines, see: a) J. Kaur, A. Kumar, S. S. Chimni,
RSC Adv. 2014, 4, 62367; b) A. Kumar, J. Kaur, P.
Chauhan, S. S. Chimni, Chem. Asian J. 2014, 9, 1605.
19] a) A. M. Beekman, R. A. Barrow, J. Org. Chem. 2014,
16, 9117; c) A. Sanz-Marco, A. García-Ortiz, G. Blay,
J. R. Pedro, Chem. Commun. 2014, 50, 2275; d) G.
Blay, I. Fernµndez, A. Marco-Aleixandre, B. Monje,
J. R. Pedro, R. Ruiz, Tetrahedron 2002, 58, 8565.
14] For a reviews of the use of squaramide catalysts, see:
a) J. Alemµn, A. Parra, H. Jiang, K. A. Jørgensen,
Chem. Eur. J. 2011, 17, 6890; b) R. I. Storer, C. Aciro,
L. H. Jones, Chem. Soc. Rev. 2011, 40, 2330; c) P. Chau-
han, S. Mahajan, U. Kaya, D. Hack, D. Enders, Adv.
Synth. Catal. 2015, 357, 253.
[
79, 1017; b) W. J. Tsai, C. C. Shen, T. H. Tsai, L. C. Lin,
[
J. Nat. Prod. 2014, 77, 125; c) P. Chauhan, S. S. Chimni,
Tetrahedron Lett. 2013, 54, 4613; d) S. Bai, Y. Liao, L.
Lin, W. Luo, X. Liu, X. Feng, J. Org. Chem. 2014, 79,
10662.
[
[
20] CCDC 1405184 (3c) contains the supplementary crys-
tallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystal-
lographic Data Centre via www.ccdc.cam.ac.uk/data_
request/cif.
21] For a racemic synthesis of lactone 6, see: V. I. Dya-
chenko, A. F. Kolomiets, A. V. Fokin, Izv. Akad. Nauk
SSSR Ser. Khim. 1987, 11, 2511.
[
[
15] 2-Naphthol was unreactive under the reaction condi-
tions, probably due to steric hindrance.
16] Methyl trifluoropyruvate was tested under the reaction
conditions, but a mixture of a-hydroxy-a-CF -ester and
lactone (1:1.2 by F NMR) was observed, see the Sup-
porting Information for further details.
3
19
Adv. Synth. Catal. 2015, 357, 3047 – 3051
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3051