Construction of trifluoromethylated quaternary stereocenters: Via p -quinone methides

Article abstract of DOI:10.1039/c9cc08936e

Development of a new synthetic method for the construction of quaternary centers with a trifluoromethyl group was realized by way of 1,6-addition of various nucleophiles including active methylene compounds to highly reactive δ-trifluoromethylated p-quinone methides generated in situ from the corresponding tertiary carbonates with a catalytic amount of an appropriate base.

Full text of DOI:10.1039/c9cc08936e

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DOI: 10.1039/C9CC08936E
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Construction of the trifluoromethylated quaternary stereocenters
via p-quinone methides
Kyu Terashima,a Tomoko Kawasaki-Takasuka,a Tomohiro Agou,b Toshio Kubota,b and Takashi
Received 00th January 20xx,
Accepted 00th January 20xx
Yamazaki*a
DOI: 10.1039/x0xx00000x
Development of a new synthetic method for construction of
quaternary centers with a trifluoromethyl group was realized by
way of 1,6-addition of various nucleophiles including active
methylene compounds a to highly reactive -trifluoromethylated p-
quinone methides generated in situ from the corresponding
tertiary carbonates with a catalytic amount of an appropriate base.
Quaternary centers containing a trifluoromethyl (CF3) group
are widely found as the intriguing partial structure of a variety of
biologically active substances.1 However, because of the
inherent steric congestion and/or electronic repulsion by this
moiety, construction of these targets is still remained as the
challenging problems in the field of organic synthesis.2 Among
recent examples for the ready bond formation of various
nucleophiles to p-quinone methides (pQMs,
1) via 1,6-
addition,3,4 construction of a new carbon-carbon framework is
undoubtedly one of the most important of all (Scheme 1).5
Among these compounds, the -CF3--substituted pQMs
1
have strongly drawn our attention as the potent as well as
convenient prototypes for construction of CF3-containing
quaternary centers while their in situ generation and reactivity
with appropriate carbon nucleophiles have been rarely
Scheme 1 C-C bond formations via p-quinonemethides
investigated thus far.6 As the precursors of
1
,
2
was considered
would
withdrawing CF3 group should give an additional tremendous
effect for the stability of 2, which led to expectation to nicely
to be potent compounds because addition of a base to
2
affect facile deprotection of a TBS group and, along with the CO2
gas evolution, allow to generate t-butoxide ion. To the best of our
knowledge, no report has been appeared until now for such a
base-catalyzed system which is apparently important from the
standpoint of the concept of atom economy.5a,5b,6,7 Moreover,
another advantageous point of our method is that we can select
three independent routes to get access to 2 by way of the addition
reactions of R, CF3, or p-TBSO-C6H4 anions to the
corresponding adequate ketones.8,9,10 Attachment of an electron-
avoid the undesired elimination process to furnish the styrene
derivative during incorporation of a Boc moiety (see Scheme S1
in ESI). In this communication, we would like to report our
successful development of
a novel synthetic route for
construction of quaternary centers with a CF3 group by way of
1,6-addition reactions of active methylene compounds to highly
reactive -CF3--substituted pQMs
1 generated in situ with a
catalytic amount of an appropriate base.
First of all, optimization of the reaction conditions was
performed for the construction of the desired compound 3aa
from 2a and acetylacetone as the representative model partners
(Table 1). As our expectation, only a catalytic amount of Bu4NF
(TBAF) in DMF was found to afford 3aa in moderate yield
initiated by deprotection of the TBS group in 2a which allowed
a.Division of Applied Chemistry, Institute of Engineering, Tokyo University of
Agriculture and Technology, 2-24-16 Nakamachi, Koganei 184-8588, Japan.
b.Department of Biomolecular Functional Engineering, Ibaraki University,
Nakanarusawa 4-12-1, Hitachi 316-8511, Japan.
to convert it to the corresponding pQM
1 along with formation
Electronic Supplementary Information (ESI) available: Physical properties for new
of the unpreferable byproduct in a small amount (entry 1).
4
compounds, crystallographic analysis data for 3gf (CCDC 1958059) and
8 (CCDC
1958059). For ESI and the CIF file for 3gf and , see. See DOI: 10.1039/x0xx00000x
8
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Table 1 Optimization of the reaction conditions
Table 2 Reactions of 2a with various NuHs
View Article Online
DOI: 10.1039/C9CC08936E
Nu
(MeCO)2CH
(PhCO)2CH
(MeCO)(EtOCO)CH
(MeCO)(tBuOCO)CH
(PhCO)(EtOCO)CH
(EtOCO)2CH
Isolated yielda,b (%)
Entry
1
2
3
4
5
6
7
8
Products
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
83 [70]
46 [50]c,d
90e [87]f
[72]g
[91]h
83 [86]
53 (68)d
45c (87)i,j
83k
NO2CH
(EtOCO)(CN)CH
(PhCO)(Ph)CH
(MeCO)(Me2NCO)CH
(MeCO)((EtO)2PO)CH
PhCOCH
19F NMR yielda,b) (%)
Entry
Base
Solv.
9
3aa
4
10
11
12
13l
14m
4
4
4
3aj
[70]
1
2c,d)
3
4
5
6
7
8
9
TBAF
TBAF
KF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
63
17
46
55
40
46
46
61
15
10
25
18
31
30
25
14
0
99 [86]
86 [90]
[72]
CN
CsF
KOAc
Bu4NOAc
KOtBu
DBU

Ph(TMSO)C=CH2
3ak
[68]
a) In the brackets were shown isolated yields conducted at 30 °C for 24 h. b) d.r.
was determined by 19F NMR. c) 19F NMR yield of the sum of TBS protected and non-
protected products before the step 2. d) Usage of 4.0 eq. of NuH. e) d.r. = 54:46. f)
d.r. = 61:39. g) d.r. = 64:36. h) d.r. = 58:42. i) Conducted at 30 °C for 72 h and usage
of 10 mol% of TBAF instead of DBU. j) d.r. = 74:26. k) d.r. = 78:22. l) In this case,
Me2C(OH)CN was employed as the Nu– precursor. m) 1.5 eq. of the corresponding
silyl enol ether was employed as the Nu– precursor in THF at 30 °C for 24 h and the
following desilylation was performed by 1.5 eq. KF in MeOH/THF = 1/2 at 30 °C for
1 h.
NEt3
0
10
11
12
13
14
15e)
16e,f)
17e,f)
18e,f,g,h,i)
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
TBAF
DBU
Toluene
THF
55
21
24
12
76
84
14
6
5
0
8
16
16
17
17
MeCN
EtOH
DMSO
DMSO
DMSO
DMSO
DMSO
84 [81]
84 [83]
66 (17) [83]
instance of entry 17 (entry 18). With the optimized reaction
DBU
conditions in hand, 1,6-addition to pQM
1 derived from 2a was
a) In the brackets were shown the isolated yields. b) In the parentheses were
shown the 19F NMR yield of the TBS protected 3aa (5aa). c) An Ac group was chosen
as the leaving group instead of Boc. d) 10 mol% of TBAF was used. e) Conducted at
50 °C for 9 h. f) Usage of 5.0 mol% of bases. g) Usage of 1.1 eq. of acetylacetone.
h) After appropriate reaction time, the TBS group of the product 5aa was
deprotected under the following conditions like addition of 1.5 eq. KF and stirring
at 30 °C for 1 h. i) Conducted at 50 °C for 9 h.
performed with various nucleophiles as summarized in Table 2.
The reaction of 2a with 1,3-diphenylpropane-1,3-dione afforded
the desired compound 3ab only in moderate yield even by the
addition of an excess amount (4.0 eq.) of this 1,3-diketone
possibly because of its lower nucleophilicity (entry 2). On the
other hand, -ketoesters and malonate showed a reasonably high
reactivity to provide the desired products 3 in high yields (entries
Usage of an Ac group as a leaving group instead of a Boc moiety
was not suitable for this reaction (entry 2). Although most of
bases checked were not as effective as TBAF, DBU was the
exception to give a similar level of result to TBAF (Table 1,
entries 1 vs 3-9). It was also clarified that a highly polar solvent
such as DMSO was preferred and the less polar toluene, THF,
and MeCN, as well as the protic EtOH were found not to be
suitable (entries 10-14). The yield of 3aa was slightly improved
by raising the temperature to 50 °C, and reduction of the
equivalent of a base to 5 mol% did not affect the chemical yield
at all (entries 15 and 16). Because substitution of TBAF for DBU
recorded a same level of the chemical yield of 3aa, we selected
the latter as the optimized base by considering its easy handling
and lower cost (entry 17). Reduction of the equivalent of
acetylacetone lowered the yield of 3aa with increased formation
of 5aa, the TBS-protected 3aa. In this case, addition of KF at the
end of this transformation led to efficient conversion of 5aa to
3aa and the good total yield was eventually attained like the
3-6). A slightly lower efficiency was noticed by incorporation of
a bulkier tBu group at the ester alcohol part, while the
substituents attached to the ketone carbonyl group was found to
affect only slightly (entries 3-5). It is worth to be mentioned that
the same products were alternatively obtained under such milder
conditions as 24 h stirring at 30 °C (entries 1, 2, 3 and 6). In
addition to 1,3-dicarbonyl compounds, reagents shown in entries
7-9 also behaved in an appropriate manner to furnish the desired
1,6-addition products
3 in high to excellent yields. TBAF was
found to be more suitable for ethyl 2-cyanoacetate (entry 8). As
the acidity of the active methylene protons11 or electronic
repulsion with the CF3 group in pQM
1 increased, formation of
the trifluoromethylated styrene became the major pathway
4
possibly due to the retardation of the desired 1,6-addition (entries
10-12). It was observed that acetone cyanohydrin and the silyl
enol ether from acetophenone as nucleophiles showed high
reactivity to 2a to nicely incorporate desired functional groups at
the carbon center with a CF3 group (entries
2 | J. Name., 2012, 00, 1-3
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t
quite reasonable for the compound 2o with a bulky Bu moiety
Table 3 Reactions of a variety of 2 with diethyl malonate
View Article Online
only to result in obtaining a complex mixDtuOrIe: 1(0e.1n0t3ry9/C194C).CO08n93th6Ee
other hand, -elimination was the preferred pathway for 2p
rather than the desired 1,6-addition because of the presence of
relatively acidic methylene protons at  to the ethoxy carbonyl
group (entry 15). For investigation of the present reaction
mechanism, we conducted some additional experiments
(Scheme S2 in ESI). When only DBU was used, 2a was
consumed to exclusively afford 4. On the other hand, because 2a
was recovered when mixing with diethyl malonate in the absence
of DBU, it is apparent that a base is necessary for the promotion
of this reaction. Moreover, when 2a analogs with the m-TBSO-
or p-MeO-C6H4 groups were subjected to the standard
conditions, only desilylation or recovery of the starting material,
respectively, were observed. Thus, these results unambiguously
proved the present process proceeding via the pQMs
Isolated yield (%)
Entry
R
Products
Ph (2b)
4-F-C6H4 (2c)
4-F3C-C6H4 (2d)
4-NC-C6H4 (2e)
4-Me-C6H4 (2f)
4-MeO-C6H4 (2g)
2-MOMO-C6H4 (2h)
2,4-(MeO)2-C6H4 (2i)
2-pyridyl (2j)
1-naphtyl (2k)
PhCC (2l)
3bf
3cf
3df
3ef
3ff
91
1
2
89
3
4
5
89
intermediate 1. When the enol silyl ether from acetylacetone was
91
employed as a nucleophile, the same 3aa was also obtained albeit
in lower yield of 39% (83% by the standard conditions). It would
be possible for DBU to abstract an acidic proton in acetylacetone
and the resultant anion would be converted to the corresponding
enol silyl ether as a consequence of its attacking at the TBS
group. This consequence clearly proved that inclusion of this
pathway does not inhibit the desired process. With considering
these results, the present reaction would be mechanistically
explained as follows (Scheme 2). At first, deprotection of the
93
6
3gf
3hf
3if
92
7
8
9
88
xx
3jf
90
10
11
3kf
3lf
90
97
12
13
14
15
Pr (2m)
iPr (2n)
tBu (2o)
3mf
3nf
3of
3pfa
90
TBS group in
2 would proceed by the action of DBU to afford 1
46
complex mixture
95
by subsequent elimination of a BocO moiety. The resultant tBuO
anion after CO2 evolution would play a role as a Base. Then,
deprotonation would occur from NuH by this Base (or possibly
CH2CO2Et (2p)
a) The yield of the corresponding -unsaturated carbonyl compound as the sum
by DBU) to give Nu whose 1,6-addition to
reprotonation by H+-Base to furnish
. At the same instance, a
Base was regenerated, and the phenolic OH group in captured
with
1, followed by the
of stereoisomers. (See detail in SI).
3
3
13 and 14). At the next stage, in order to investigate further
a TBS group from TBS-X to afford the desired products
establishment of this catalytic cycle.
5
substrate scope and limitation,
2 with different substituents from
a Me group were employed for the reaction with diethyl
malonate as the representative nucleophile. For the Ph-
Finally, further experiments were conducted for clarification of
the synthetic utility of the products (Scheme 3). Condensation
of 3aa with hydroxyl amine and the following cyclization
3
possessing compound 2b
,
the expected catalytic process
smoothly proceeded under the same mild conditions as the one
determined above (Table 3, entry 1). No apparent effect was
noticed for other substrates possessing additional substituents on
the Ph moiety in 2b and both electron-rich and -poor groups
smoothly proceeded to furnish the isoxazole
(6). Nice
unanimously recorded high yields for the desired products
3
(entries 2-6).12 Moreover, 2h and 2i with the substituent at the
sterically sensitive ortho position was also found to be adequate
for this protocol (entries 7 and 8) and the structure of this product
3hf was determined by its crystallographic analysis (see ESI for
the detailed information).13 Incorporation of 2-pyridyl (2j) and
1-naphthyl (2k) were also compatible, furnishing the products
3jf and 3kf, respectively, in excellent 90% yields in both cases
(entries 9 and 10). It is interesting to note that 1,6-addition was
selectively occurred without formation of the corresponding 1,8-
product in the case of 2l containing the alkynyl group conjugated
to the pQM framework (entry 11).14 Besides these substrates
with a variety of aromatic substituents, alkyl groups at the same
position (2m and 2n) also worked nicely while the moderate
yield was noticed for the latter possibly due to its higher steric
hindrance (entries 12 and 13). In line with this result, it would be
Scheme 2 Plausible reaction mechanism
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Senda, K. Nakajima and Y. Nishibayashi, Angew. Chem. Int. Ed.,
View Article Online
2016, 55, 9728; (f) M. Holmes, K. D. Nguyen, L. A. Schwartz, T.
DOI: 10.1039/C9CC08936E
Luong and M. J. Krische, J. Am. Chem. Soc., 2017, 139, 8114; (g) W.
Wang, Y. Guo, K. Sun, S. Wang, S. Zhang, C. Liu and Q.-Y. Chen, J.
Org. Chem., 2018, 83, 14588; (h) R. Calvo, A. Comas-Vives,
A.Togni and D. Katayev, Angew. Chem. Int. Ed., 2019, 58, 1447; (i)
H. Liu, L. Ge, D.-X. Wang, N. Chen and C. Feng, Angew. Chem. Int.
Ed., 2019, 58, 3918.
3
4
For the recent review on the reactions of pQMs, see, W. Li, X. Xu, P.
Zhang and P. Li, Chem. Asian J., 2018, 13, 2350.
Previous reports about the reactivity of pQMs with amines: (a) H. D.
Becker and K. Gustafsson, J. Org. Chem., 1976, 41, 214; (b) M.
Adamczyk and J. Grote, Tetrahedron Lett., 2000, 41, 807; alcohols
(c) A. Nishinaga, H. Iwasaki, T. Shimizu, Y. Toyoda and T.
:
Matsuura, J. Org. Chem., 1986, 51, 2257; (d) M. Niwa, T. Hirayama,
K. Okuda and H. Nagasawa, Org. Biomol. Chem., 2014, 12, 6590;
thiols: (e) N. Dong, Z.-P. Zhang, X.-S. Xue, X. Li and J.-P. Cheng,
Angew. Chem. Int. Ed., 2016, 55, 1460; (f) Q.-Y. Wu, G.-Z. Ao and
F. Liu, Org. Chem. Front., 2018, 5, 2061; phosphonates: (g) N.
Molleti and J. Y. Kang, Org. Lett., 2017, 19, 958; (h) B. Yang, W.
Yao, X.-F. Xia and D. Wang, Org. Biomol. Chem., 2018, 16, 4547 ;
carbon nucleophiles: (i) L. Roiser and M. Waser, Org. Lett., 2017,
19, 2338; (j) S. Santra, A. Porey, B. Jana and J. Guin, Chem. Sci.,
2018, 9, 6446; (k) F.-R. Yuan, F. Jiang, K.-W. Chen, G.-J. Mei and
W. Qiong, Org. Biomol. Chem., 2019, 17, 2361; other nucleophiles
(l) A. Lopez, A. Parra, C. Jarava-Barrera and M. Tortosa, Chem.
:
Commun., 2015, 51, 17684; (m) Y. Lou, P. Cao, T. Jia, Y. Zhang, M.
Wang and J. Liao, Angew. Chem. Int. Ed., 2015, 54, 12134.
(a) Y.-F. Gong and K. Kato, Synlett, 2002, 431; (b) Y.-F. Gong and
K. Kato, J. Fluorine Chem., 2003, 121, 141; (c) Z. Wang, F.-Y.
Wong and J. Sun, Angew. Chem. Int. Ed., 2015, 54, 13711.
(a) W. A. Sheppard, J. Org. Chem.,1968, 33, 3297; (b) T. Umemoto,
S. Furukawa, O. Miyano and S. Nakayama, Nippon Kagaku Kaishi,
1985, 11, 2146.
Formation of o-quinone methides (oQM) by desilylation of the
phenolic OH group under basic conditions has also reported. For the
recent generation of oQM in situ, see, A. A. Jaworski and K. A.
Scheidt, J. Org. Chem., 2016, 81, 10145. Very recently, generation of
pQMs in situ in basic condition were reported by use of an equimolar
amount of base. See, (a) Y.-J. Fan, L. Zhoua and S. Li, Org. Chem.
Scheme 3 Synthetic applications of
3
5
6
7
participation of the phenolic OH group in 3aa was proved for
deacetylative Suzuki-Miyaura cross-coupling with
phenylboronic acid after its conversion to the corresponding
triflate. Transformation of the phenol ring in 3ac was performed
to give the spirocyclic
8 which furnished a nice crystal for
crystallographic analysis to confirm its spiro structure possessing
a CF3-containing quaternary carbon atom (see ESI for the
detailed information).15 In conclusion, we have succeeded for
the first time in construction of quaternary carbon centers
containing a CF3 group via pQMs
starting from readily available substrates
1
under mild conditions
, which was realized
Front., 2018, 5, 1820; (b) X.-Y. Guan, L.-D. Zhang, P.-S. You, S.-S. Liu
2
and Z.-Q. Liu, Tetrahedron Lett., 2019, 60, 244; (c) M. F. McLaughlin, E.
Massolo, T. A. Cope and J. S. Johnson, Org. Lett., 2019, 21, 6504.
G. K. Surya Prakash, R. Krishnamurti and G. A. Olah, J. Am. Chem.
Soc., 1989, 111, 393.
only by a catalytic amount of a base. Utility of the present
reaction was clearly demonstrated by its wide substrate scope,
and another advantage was clarified by the fact that the products
8
9
3
were convertible to different structures with retaining the
(a) S. Mizuta, N. Shibata, S. Akiti, H. Fujimoto, S. Nakamura and T.
Toru, Org. Lett., 2007, 9, 3707; (b) G. Mloston, E. Obijalska, A.
Tafelska-Kaczmarek and M. Zaidlewicz, J. Fluorine Chem., 2010,
131, 1289.
quaternary carbon centers with a CF3 group, which apparently
indicated their high potency as convenient building blocks.
Further applications of this reaction as well as the obtained
products are ongoing in our group.
10 (a) D. Bonnet-Delpon; C. Cambillau, M. Charpentier-Morize, R.
Jacquot, D. Mesureur and M. Ourevitch, J. Org. Chem., 1988, 53
,
754; (b) M. J. Andres, R. Pedrosa and A. Perez-Encabo, Eur. J. Org.
Chem., 2004, , 1558; (c) H. Yoshida,Y. Ito, Y. Yoshikawa, J.
7
Ohshita and K. Takaki, Chem. Commun., 2011, 47, 8664.
11 pKa values of these activated methylene protons in DMSO were
reported as follows; 14.2 for ethyl acetoacetate,a 16.4 for diethyl
malonate, a 17.2 for nitromethane,a 17.7 for benzyl phenylketone,a
18.2 for N,N-dimethylacetoacetamide,b and 24.7 for acetophenone.a
See, (a) F. G. Bordwell, Acc. Chem. Res., 1988, 21, 456; (b) F. G.
Bordwell and H. E. Fried, J. Org. Chem., 1991, 56, 4218.
Notes and references
1
(a) R. O. Iakovenko, A. N. Kazakova, V. M. Muzalevskiy, A. Yu.
Ivanov, I. A. Boyarskaya, A. Chicca, V. Petrucci, J. Gertsch, M.
Krasavin, G. L. Starova, A. A. Zolotarev, M. S. Avdontceva, V. G.
Nenajdenko and A. V. Vasilyev, Org. Biomol. Chem., 2015, 13
8827; (b) H. Wakabayashi and Y. Shishido, CA972193468; (c) EL Q.
Myriem, C. Jérôme Yves and K. Benedikt WO2014029639.
,
12 During the preparation of
2 with a 4-(dimethylamino)phenyl group as
2
For the selected previous construction of CF3-containing quaternary
centers examples, see, (a) M. Kimura, T. Yamazaki, T. Kitazume and
R, the compound was decomposed at the stage of the Boc installation.
13 CCDC1958059 contains the supplementary crystallographic data for
T. Kubota, Org. Lett., 2004, 6, 4651; (b) K. Sato, Y. Takiguchi, Y.
the compound 3hf
.
Yoshizawa, K. Iwase, Y. Simizu, A. Tarui, M. Omote, I. Kumadaki
and A. Ando, Chem. Pharm. Bull., 2007, 55, 1593; (c) H. Kawai, S.
Okusu, E. Tokunaga, E.; H. Sato, M. Shiro and N. Shibata, Angew.
Chem. Int. Ed., 2012, 51, 4959; (d) Q. Lou, Y. Ding, D. Xu, G. Liu
and J. Zhao, Adv. Synth. Catal., 2017, 15, 2557; (e) K. Tsuchida, Y.
14 P. Zhang, Q. Huang, Y. Cheng, R. Li, P. Li and W. Li, Org. Lett.,
2019, 21, 503.
15 CCDC1958058 contains the supplementary crystallographic data for
the compound 8.
4 | J. Name., 2012, 00, 1-3
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