Regioselective functionalization of gem-bis(trifluoromethylated) alkanols

Article abstract of DOI:10.1016/j.mencom.2018.11.030

One-pot functionalization of sp³ C–H bond in 1,1,1-trifluoro-2-(trifluoromethyl)decan-2-ol with CO and nucleophiles under the action of superelectrophilic complex CBr₄·2 AlBr₃ affords products of neo-structure and remote functionalities.

Full text of DOI:10.1016/j.mencom.2018.11.030

Mendeleev
Communications
Mendeleev Commun., 2018, 28, 651–652
Regioselective functionalization of gem-bis(trifluoromethylated) alkanols
Irena S. Akhrem,* Dzhul’etta V. Avetisyan, Lyudmila V. Afanas’eva,
Andrey A. Tyutyunov, Oleg I. Artyushin and Nikolai D. Kagramanov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. E-mail: cmoc@ineos.ac
DOI: 10.1016/j.mencom.2018.11.030
F3C CF3
CBr3+, CO, NuH
One-pot functionalization of sp3 C–H bond in 1,1,1-trifluoro-
Me
H2O
HO
2-(trifluoromethyl)decan-2-ol with CO and nucleophiles
under the action of superelectrophilic complex CBr4·2AlBr3
affords products of neo-structure and remote functionalities.
Me Me
O
F3C CF3
HO
Nu
Due to importance of alcohols in various fields,1 numerous examples
could reduce its ability of coordinating superelectrophile and
therefore facilitate the ionization of C–H bond. On the other
hand, a functional group dramatically affects the sp3 C–H bond
functionalization. In the presence of superacids, functionalization
of alkanes with CO and alcohols proceeds unselectively.11 With
CBr4·2AlBr3 as the initiator, degradative functionalization of
alkanes C6–C10 did not occur, however, two isomers with neo-
alkyl groups, such asAlk(Me)2COOR andAlk(Me)EtCOOR were
formed.12 On the contrary, the processing of functional organics,
XCnH2n+1 (X = ROCO, MeCO, MeCOO, NR2, OH; n = 6–9) with
CO and nucleophiles (NuH) occurred regioselectively, resulting
in a sole neo-isomer, XCn–3H2(n–3)C(Me)2CONu.7
In fact, at –20°C under atmospheric CO pressure and in the
presence of 100% molar excess of CBr4·2AlBr3 in dry CH2Br2,
carbonylation of polyfluoro alkanol 1 followed by in situ quenching
with nucleophilic agents led to the corresponding bifunctional
products of neo structures 2 in good or moderate yields (Scheme 1).
No products of destructive functionalization with lower number
of carbon atoms were detected.
The tentative mechanism of the process (see Scheme 1)
involves the coordination of the hydroxyl group at the super-
electrophilic complex (CBr3+Al2Br7–) to form oxonium cation A
at the first stage. The cleavage of sp3 C–H bond leads to the
secondary carbocation B with cationic centre remoted from the
oxonium group as a result of the repulsion of positive charges.
The species B would isomerize into more stable tertiary cation C.
The latter adds CO to form acylium cation D. Addition of nucleo-
phile at cation D gives rise to product 2.
of functionalization of their sp3 C–H bond by radicals,2,3 metal
5
complexes,4 H2SO4 and HF·SbF5 acids have been described. The
potent superelectrophilic complexes CX4·2AlX3 (X = Br or Cl)6
turned out to be effective for initiating sp3 C–H functionalization
of alkanes6(b) and functional organic compounds7 including
primary alcohols.7(d)
Synthesis of alcohols containing polyfluorinated groups is of
interest,8 since they possess valuable properties in comparison
with their non-fluorinated analogues such as improved chemical
and thermal stabilities, lower boiling points and increased hydro-
phobicity. Many polyfluorinated alcohols and their derivatives
are biologically active compounds.9
The examples of free radical and transition metal initiated
intermolecular functionalizations of sp3 C–H bond in fluorinated
alcohols have been reported.10 Both of them, the free radical
domino reaction10(a) and ruthenium catalyzed C–C coupling with
allenes10(b) involved α-functionalization of short fluorinated
alcohols. The superelectrophiles open the possibility of preparing
products with neo- or tertiary structures and remote functional
groups directly from linear functional organics.7
In this paper, we report on access to a new series of alcohols
with polyflouoromethyl groups on the example of one-pot func-
tionalization of 1,1,1-trifluoro-2-(trifluoromethyl)decan-2-ol 1
with CO and nucleophiles in the presence of CBr4·2AlBr3.
We could not predict a priori how two trifluoromethyl groups
would affect activity of compound 1 in this reaction. On the one
hand, the presence of two strong electron-withdrawing groups
F3C CF3
F3C
O
CF3
i
F3C CF3
Me
Me
Br3C
Me
HO
HO
1
H
A
B
Me Me
O
Me Me
O
F3C CF3
CF3
F3C
HO
Me
ii
CO
F3C
HO
CF3
Nu
HO
Me
2a Nu = OCH2CF3 (84%)
2d Nu = 2-pyrrolyl (40%)
C
D
2b Nu = OCH2(CF2)2H (74%) 2e Nu = 4-MeOC6H4 (60%)
2c Nu = 2-thiophenyl (64%)
Scheme 1 Reagents and conditions: i, CBr4·2AlBr3, CH2Br2, –20°C, CO (1 atm), 2 h; ii, NuH, CO (1 atm), –20°C, 10–20 min, heating to 0°C (30 min),
then H2O.
© 2018 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2018, 28, 651–652
This work was supported by the Russian Foundation for Basic
Research (grant no. 17-03-00022a).
Me
Me
F3C
HO
CF3
CO
CBr3
1
D
MeOC6H5
Online Supplementary Materials
C
Supplementary data associated with this article can be found
in the online version at doi: 10.1016/j.mencom.2018.11.030.
2e (60%)
MeOC6H5
Me Me
F3C CF3
HO
References
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Scheme 2
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Earlier, we observed the examples of alkylation of nucleo-
philes with cations XCnH2n (to form the alkylation products
+
similar to 3) in analogous reactions.7(c)–(e) The formation of
alkylation products in CO atmosphere shows that generation of
acylium cations can be reversible.13 Indeed, while the decarbonyla-
tion of MeCO+ is endothermic14 (by ~340 kJ mol–1), the acylium
salts, R3CCO+ (R = Me15, Ph16) are decarbonylated even at low
temperature.
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substrate 1 was not full, and HOC(CF3)2(CH2)5CMe2C(O)OEt
was produced in a mixture with nonreacted compound 1. The
structure of this ester was supported by GC-MS spectra (M+ + H =
= 353). The use of octanethiol as a nucleophile led to the target
thioester HOC(CF3)2(CH2)5CMe2C(O)SC8H17 (M+ + H = 453)
in a mixture with the dimeric dioctyl disulfide (M+ + H = 291),
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C8H17SSC8H17.
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conversion within 2 h reached 92%). The reaction probably
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addition to the oxygen atom to form oxonium ion E which in
turn eliminated proton and underwent cyclization (Scheme 3).
Based on the NMR and GC-MS spectra of the isomeric mixture,
structures 4a and 4b were assigned to the main isomers.
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F3C CF3
O
+
Me
Me
CBr3
CO
O
H
1
D
E
CF3
CF3
O
O
O
O
+
+ (isomers)
CF3
CF3
Me
Bu
Et
Pr
4a
4b
Scheme 3
Received: 28th April 2018; Com. 18/5563
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