One-pot α-ferrocenylalkylation of amines and alcohols with α-ferrocenyl substituted alcohols under acid-free conditions

Article abstract of DOI:10.1016/j.jorganchem.2018.10.021

One-pot reaction of FcCH(R)OH with equimolar quantities of BuⁿLi and EtOCOCl followed by an excess of amine produces N-(α-ferrocenylalkyl)amines in up to 98% yields. Nitrogen heteroaryl amines undergo the α-ferrocenylalkylation at the amino group. The α-ferrocenylalkylation of alcohols and phenols (R'OH) leads to a formation of ethers FcCH(R)OR′ in lower yields. The reactions proceed via an intermediate formation of α-ferrocenylalkyl carbonates FcCH(R)OCOOEt. The side reactions associated with this protocol are discussed.

Full text of DOI:10.1016/j.jorganchem.2018.10.021

Journal of Organometallic Chemistry 880 (2019) 29e38
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
One-pot
a
-ferrocenylalkylation of amines and alcohols with
a-ferrocenyl substituted alcohols under acid-free conditions
Ekaterina V. Shevaldina, Anastasia D. Shagina, Andrey B. Ponomaryov, Sergey K. Moiseev*
Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, V-334, Moscow, 119991, Russia
a r t i c l e i n f o
a b s t r a c t
One-pot reaction of FcCH(R)OH with equimolar quantities of BunLi and EtOCOCl followed by an excess of
Article history:
Received 14 September 2018
Received in revised form
12 October 2018
Accepted 25 October 2018
Available online 28 October 2018
amine produces N-(
the -ferrocenylalkylation at the amino group. The
leads to a formation of ethers FcCH(R)OR0 in lower yields. The reactions proceed via an intermediate
formation of -ferrocenylalkyl carbonates FcCH(R)OCOOEt. The side reactions associated with this pro-
tocol are discussed.
a
-ferrocenylalkyl)amines in up to 98% yields. Nitrogen heteroaryl amines undergo
a
a
-ferrocenylalkylation of alcohols and phenols (R’OH)
a
© 2018 Elsevier B.V. All rights reserved.
Keywords:
Ferrocenylalkylation
Ferrocenylalkyl amines
Ferrocenylalkyl ethers
Carbonates
Carbocations
1. Introduction
We have recently reported that
a-ferrocenylalkyl carbonates 2
readily generated in situ from the
a
-ferrocenyl substituted alcohols
In addition to their use in chemistry, ferrocene derivatives have
found the applications in medicine [1], agriculture [2], and material
sciences [3]. a-Ferrocenylalkylation is an important reaction in the
1 on the sequential action of the equimolar quantities of BunLi and
an alkyl chloroformate are ferrocenylalkylating reagents acting
under acid-free conditions (Scheme 2) [11].
chemistry of ferrocene for it provides preparations of a variety of
ferrocene derivatives [4]. Typically, either quaternary ammonium
The a-ferrocenylalkylation with carbonates 2 is based on the
spontaneous heterolytical breakdown of the CeO bond furnishing
carbocation 3 and carbonate anion 4 (Scheme 2) [11]. The last one
reversibly releases a carbon dioxide molecule yielding alkoxide
anion 5 which deprotonates a pre-nucleophile NuH thus generating
the nucleophile Nuꢀ (6) that reacts with carbocation 3 to form
ferrocenylalkylation product 7. All transformations above excepting
the last stage are reversible. As one can see from Scheme 2, both the
decay of the ferrocenyl carbonate and further transformations
occur without the addition of an external base or acid, i. e. under
acid-free conditions. This allows using the substrates NuH sensitive
to acids in the reaction.
salts derived from
substituted alcohols are used as the
(Scheme 1) [4]. With the ammonium salts, the
tion proceeds as a nucleophilic substitution at the Ca atom. The use
of
-ferrocenyl substituted alcohols FcC(OH)RR’ (Fc ¼ ferrocenyl) as
the ferrocenylalkylating agents is based on their ability to readily
generate the
-ferrocenyl carbocations FcCþRR’ on the action of an
acid, typically HBF4 (aq.) [4,5].
a
-ferrocenylalkyl amines or
-ferrocenylalkylating reagents
-ferrocenylalkyla-
a-ferrocenyl
a
a
a
a
Some other
a-ferrocenylalkylation procedures reported up to
date include the reactions of FcC(OH)RR0 in the presence of Lewis
However, what about the substrates that are nucleophiles as is?
Amines, alcohols, nitrogen heterocycles, etc. need not necessary to
be deprotonated to enter the alkylation reactions. According to
Scheme 2, when alkylating such substrates with ferrocenyl car-
bonates 2, several nucleophiles (R'Oꢀ, NuH, Nuꢀ) can
acids [6, 7], or cerium(IV) ammonium nitrate (CAN) [8], or “on
water” [7]. In addition, the
a-ferrocenylalkylation of azoles have
been carried out by the reactions of FcC(OH)RR0 with N,N-carbon-
yldiimidazole [9,10], N,N0-thionyldiimidazole [10] or N,N0-thio-
nyldibenzimidazole [10].
* Corresponding author.
E-mail address: skm@ineos.ac.ru (S.K. Moiseev).
https://doi.org/10.1016/j.jorganchem.2018.10.021
0022-328X/© 2018 Elsevier B.V. All rights reserved.

30
E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
Table 1
One-pot a-ferrocenylalkylation of aryl and heteroaryl amines with ferrocenyl alco-
hols 1a,b.
Entry
1
R
H2NR1
Product Yield (%)a
Scheme 1.
a-Ferrocenylalkylation reactions using a-ferrocenylalkylammonium salts
1
2
1a
1b
Me
Ph
9a
9b
96 (98)
87 (96)
(a) or a-ferrocenyl substituted alcohols (b) (Nu e nucleophile).
9
3
4
1a
1b
Me
Ph
10a
10b
54 (55)
80 (70)
10
11
12
5
6
1a
1b
Me
Ph
11a
11b
60 (85)
62 (65)
7
8
1a
1b
Me
Ph
12a
12b
67 (40)
67 (71)
9
10
1a
1b
Me
Ph
13a
13b
55 (42)b
47 (49)
13
11
12
1a
1b
Me
Ph
14a
14b
50 (59)
76 (34)
Scheme 2.
a-Ferrocenylalkylations with a-ferrocenylalkyl carbonates 2.
14
15
simultaneously present in the reaction mixture, which can lead to
the formation of a mixture of the products.
13
14
1a
1b
Me
Ph
15a
15b
39 (37)
65 (50)
Herein, we report the use of ferrocenyl alcohols 1 for the one-
pot
a-ferrocenylalkylation of amines and alcohols via an interme-
a
diate formation of the (
a-ferrocenylalkyl) carbonates 2 and discuss
Conditions: 2 eq. of amine, room temperature, 24 h, in THF. A yield of the
product in the presence of KHSO4 (2 eq.) is given in parentheses.
the unwanted competitive side processes accompanying the
alkylation reactions.
b
Isolated as hydrochloride 13a.HCl.
The results of
a-ferrocenylalkylations of aryl and heteroaryl
2. Results and discussion
amines 9e15 substituted with both electron donating and with-
drawing groups are summarized in Table 1. According to 1H NMR
data, the alkylation of heteroaryl amines 14,15 proceeds at the
amino function. Specifically, the peaks of CH proton in FcCHCH3 and
FcCHPh moieties of heterocyclic derivatives 14a, 15a (4.54,
4.62 ppm) and 14b, 15b (5.35, 5.34 ppm) are very similar to that
ones of the aniline derivatives 9a and 9b (4.40 and 5.14 ppm,
respectively). In addition, unlike the quadruplet signal of CH in 9a,
the corresponding peaks of CH in 14a and 15a appears as
2.1.
a-Ferrocenylalkylation of alcohols and amines
2.1.1.
a-Ferrocenylalkylation of amines
a-Ferrocenylalkylation of amines is a method for preparation of
amines bearing a ferrocenyl group. Ferrocenyl substituted aromatic
amines can be prepared from ferrocenyl carbinols and aniline or
substituted anilines at elevated temperature [12] or by the re-
actions catalysed by an acid [13], [(Cp)Fe(CO)2]þ[OTf]- [14], Bi(III)
salts [15], cerium ammonium nitrate (CAN) [16] or Ca2þ-bentonite
[17].
Aliphatic a-ferrocenylalkyl amines can be obtained by a direct
aminomethylation of ferrocene [18], or by a nucleophilic substitu-
tion of either the acetoxy group in esters FcCH(R)OAc on the action
of amines [19e21] or the cyano group in FcCH(CN)NMe2 on the
action of MeMgI [22]. In addition, the reductive amination of ace-
tylferrocene with secondary amines in the presence of Ti(OPri)4 or
NaBH4 also affords aliphatic
In this paper, we report a one-pot preparation of
lalkyl amines from -ferrocenyl substituted alcohols 1 under acid-
a-ferrocenylalkyl amines [23].
a-ferroceny-
a
free conditions. The reaction proceeds at room temperature via the
intermediate formation of ethyl carbonates FcCH(R)OC(O)OEt (8).
Since the reaction proceeds in a acid-free medium, this method
avoids a protonation of the amine in a course of the reaction.
Scheme 3. The competitive target and side processes on the decomposition of FcCH(R)
OC(O)OEt (8a,b) in the presence of PhNH2 (9).

E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
31
Table 2
-Ferrocenylalkylation of PhNH2 (9).
a
Entry
1
R
Substrate
9
Amount of 9 or 9 . HCl, eq.
tꢁC
Product
Yield (%)a
1
2
3
4
5
6
7
8
1b
1b
1a
1b
1a
1b
1b
1b
Ph
Ph
Me
Ph
Me
Ph
Ph
Ph
1
1
2
2
2
2
2
2
20
20
20
20
20
20
66
66
9b
9b
9a
9b
9a
9b
9b
9b
15
19
9
9
9
9
9
9
9
. HCl
96 (98b)
87 (96b)
15
. HCl
. HCl
40
55
38
. HCl
a
In THF, 24 h.
In the presence of KHSO4 (2 eq.).
b
multiplets. Besides that, the signal of NH (5.56 ppm) in the spec-
trum of 14b appears as the dublet.
However, much more effective was found to be the use of a 2-fold
excess of amine 9 that resulted in 87% yield of 9b. The reaction of 1b
with 2 eq. of 9 in the presence of 2 eq. of KHSO4, which was sup-
posed to protonate EtOꢀ, likewise 9.HCl, lead to increasing the yield
of 9b to 96%. The reaction of 1a with 2 eq. of 9 resulted in a for-
mation of the alkylation product 9a in 98% yield.
It should be specially stressed that the almost quantitative yields
of the target amines 9a,b in the reactions of 1a,b with 9 is the
conclusive proof that the in situ generation of carbonates 8a,b from
the parent alcohols 1a,b occurs also quantitatively. This fact is
important for a correct understanding that the alcohols FcCH(R)OH
One of the synthetic problems associated with this protocol of a-
ferrocenylalkylation of amines is exemplified in Scheme 3 by the
decomposition process of carbonates 8a,b in the presence of 9. As
one can see, two nucleophiles, EtOꢀ and PhNH2, are simultaneously
present in the reaction mixture in this case. These nucleophiles are
able to compete with each other for carbocation Fc(R)CHþ. More-
over, anion EtOꢀ can very effectively compete with the neutral
PhNH2 molecule in the nucleophilic attack. This should lead to a
formation of ether FcCH(R)OEt (16) along with the target amine 9a
or 9b. And this is the case.
found out among the products of the
a-ferrocenylalkylation re-
The equimolar alkylation of 9 with 1b produces amine 9b in only
15% yield (Table 2). To avoid the side reaction, aniline hydrochloride
(9.HCl) was taken instead of the free amine. It was assumed that
EtOꢀ formed in the course of decomposition of the intermediate
carbonate 8b must first deprotonate the hydrochloride, thereby
disappearing from the reaction mixture and releasing amine 9,
which would attack the carbocation 3 to give the desired product.
However, with an equimolar ratio of the reagents, this resulted in
only a slight increase in the yield of amine 9b (19%). The use of a 2-
fold excess of 9.HCl notably increased the yield of 9b (40%).
actions are not the parent alcohols 1a,b, but arise in the course of
unwanted side reactions (see below).
The
lead in the lower yields of the products.
The -ferrocenylalkylation reactions of aliphatic amines (Et2NH,
a-ferrocenylalkylations of amines at higher temperature
a
Me2NH) with alcohols 1a,b (Table 3) furnish the corresponding
ferrocenyl amines FcCH(R)NR02 (17, 18). As one can see from Table 3,
the yields of amines 17a,b only slightly increase on going from 2-
fold excess to 20-fold excess of Et2NH. The alkylation products
18a,b were obtained in higher yields than 17a,b.
Table 3
a-Ferrocenylalkylation of aliphatic amines (Et2NH, Me2NH).
Entry
FcCH(R)OH
R
R0
FcCH(R)OH/amine molar ratio
Product
Yielda, %
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1b
Me
Me
Me
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Et
Et
Et
Et
Me
Me
Et
Et
Et
1:2
1:2
17a
17a
17a
17a
18a
18a
17b
17b
17b
17b
18b
18b
35
31b
1:20
1:20
1:20
1:20
1:2
38(67)
34(69)b
46(62)
47(73)b
43
1:2
51b
9
1:20
1:20
1:20
1:20
49
10
11
12
Et
Me
Me
55b
67(80)
Ph
70(93)b
a
Isolated yield, room temperature, 24 h, in THF. The yield calculated from the 1H NMR spectrum of the reaction mixture after the hydrolytic workup followed by an
extraction of the products is given in parentheses.
b
A yield of the product in the presence of KHSO4 (2 eq.).

32
E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
Scheme 4.
a-Ferrocenylalkylation of ArOH.
All in all, the use of 2-fold excess of the starting amine is suffi-
cient to obtain the highest achievable yield of the -ferroceny-
lalkylation product. As for KHSO4, this salt only slightly and
ambiguously affects on the yields of the alkylation products both in
the case aromatic (Tables 1 and 2) and aliphatic amines (Table 3).
This may be due to the poor solubility of KHSO4 in THF.
56% for R ¼ Me). Aryl ether 19 (Ar ¼ 2-MeOC6H4, R ¼ Ph) was iso-
lated in 29% yield. All our attempts to isolate pure products 19
(Ar ¼ 2-(allyl)C6H4, 2-naphthyl; R ¼ Me, Ph) from the reactions
a
with 2-allylphenol and b-naphthol failed.
In the reactions with ArOH (Scheme 4), the intermediate anion
EtOꢀ rapidly and irreversibly deprotonates ArOH (i. e. NuH) acting
as base 5 in Scheme 2. Thus, three nucleophiles (EtOH, ArOH, ArOꢀ)
capable to compete with each other in nucleophilic reactions are
simultaneously present in the reaction mixture. The absence of
ethers 16a,b among the reaction products indicates that EtOH can
not effectively compete as the nucleophile with ArOꢀ and ArOH.
Unlike the reactions with ArOH, there is the next equilibrium in
the reactions of 1a,b with alkyl alcohols AlkOH:
2.1.2.
a-Ferrocenylalkylation of alcohols
a-Ferrocenylalkylation of alcohols R’OH produces the corre-
sponding ethers FcCH(R)OR’. To date, several methods for the
preparation of such ethers have been reported.
The reactions of (N,N-dimethylaminomethyl)ferrocene iodo-
methylate with alcohols and phenols or alcoholates thereof at 90 ꢁC
produce the corresponding ethers in 40e80% yields [24,25].
Another reported method is the reaction of 1b with a neat aliphatic
alcohol in the presence of AcOH [13] or CAN [16]. However, in both
cases, the reactions with branched alcohols (PriOH, ButOH) pro-
duced the symmetric ether, FcCH(Ph)OCH(Ph)Fc, solely. The au-
thors explained this result by steric hindrances caused by bulky
nucleophiles [16]. In addition, the ferrocenyl substituted ethers can
be obtained by the reactions of ferrocenylcarbinols with alcohols
and phenols catalysed by [(Cp)Fe(CO)2]þ[OTf]- [26], Yb(OTf)3 [27] or
InBr3 [6] along with the reaction of FcCH2OH with ArOH and diethyl
azodicarboxylate in the presence of PPh3 (Mitsunobu reaction) [28].
Ethers FcCH(R)OR’ and (FcCH(R))2O have been reported to form in
the reactions of FcCH2OCH ¼ CH2 with alcohols and phenols in the
presence of CF3COOH [29] and, as the by-products, in the synthesis
of ferrocenyl esters FcCH(R)OCH(R0)COOMe (R ¼ H, Me, Ph) [30].
We studied the one-pot synthesis of FcCH(R)OR0 from 1a,b and
R’OH (R’ ¼ alkyl, aryl) in THF (20 ꢁC, 24 h). Reactions of 1a,b with
ArOH (Scheme 4) produced aryl ethers FcCH(R)OAr (19) along with
alcohols FcCH(R)OH and the traces of ethers FcCH(R)OCH(R)Fc
(20a,b) as the by-products (1H NMR data).
EtOꢀ þ %EtOH þ AlkOꢀ
with the balance depending on the relative basicity of EtOꢀ and
AlkOꢀ. As a result, four nucleophiles (EtO-, AlkO-, AlkOH and EtOH)
that can compete with each other for the carbocation 3 (Scheme 2)
are simultaneously present in the reaction mixture. Therefore, it is
imperative for the a-ferrocenylalkylation of AlkOH to use a large
excess of AlkOH to increase the selectivity of the reaction and
obtain higher yields of the target ethers FcCH(R)OAlk.
Therefore, 25-fold excess of PriOH was used in its reaction with
1a,b to obtain ethers FcCH(R)OPri (21a,b) in good yields (Scheme 5).
The result shows an applicability of this protocol for a preparation
of ferrocenyl ethers from AlkOH including the alcohols with
branched alkyl groups. In the reaction of 1a,b with PriOH, anion
EtOꢀ generated in situ from the intermediate carbonates 8a,b does
not significantly compete with PriOH for carbocation 3, apparently,
because of the low concentration of EtOꢀ in the reaction mixture
compared to that one of PriOH.
We also tried to synthesise tert-butyl ethers FcCH(R)OBut (22)
that have not been reported up to date. However, the reaction of 1b
with ButOH (Scheme 6) furnished the mixture of 16b and FcCH(Ph)
OH instead of 22b. Ether 16b is formed from the intermediate
carbonate 8b as a result of the side process depicted in Scheme 3; as
for FcCH(Ph)OH, see below section 2.1.3.
Aryl ethers 19 were found to undergo a partial decomposition
during the column chromatography on Al2O3 (for a decomposition
of ethers FcCH(R)OR’ during a chromatography on silica gel see
also: [16]). This may be due to the heterolytic breakdown of the
CeO bond in these molecules resulting in a formation of relatively
stable Fc(R)CHþ and ArOꢀ ions. As a result, only 4-tolyl ethers 19
(Ar ¼ 4-MeC6H4) were isolated in moderate yields (47% for R ¼ Ph;
So, an attempt was made to prepare ethers 22 by a decompo-
sition of tert-butyl carbonates 23a,b (Scheme 6) in the absence of
Scheme 5.
a
-Ferrocenylalkylation of PriOH.

E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
33
Scheme 6. The unsuccessful attempts to prepare FcCH(R)OBut (22).
FcCH(R)Oꢀ (27) that produces FcCH(R)OH on the subsequent
hydrolytic work-up of the reaction mixture (see also path e).
As one can see, product FcCH(R)OH is identical to starting
alcohol 1 taken for the in situ generation of reagent 24. Thus,
this process explains the presence of FcCH(R)OH among the
reaction products after a hydrolysis of the reaction mixture
despite the quantitative formation of carbonyl reagents 24
(see above);
an external nucleophile. It was expected that the interaction of
alkoxide anion 5 (R' ¼ But) with carbocation 3 (Scheme 2) should
lead to a formation of ethers 22 similar to a formation of ethers 16
on the decomposition of carbonates 2 (R' ¼ Et) in the absence of
NuH [11]. However, the decomposition of carbonates 23 generated
in situ from FcCH(R)OLi and Boc2O furnished the mixture of ethers
20 and FcCH(R)OH (Scheme 6). The mechanism of their formation
is discussed in section 2.1.3.
(c) reacting the anion Xꢀ (or XH) with carbocation 3 resulting in
the formation of product 26 (i. e. ether or amine, if reactant
24 is a carbonate or carbamate);
Unlike aryl ethers 19, alkyl ethers FcCH(R)OAlk do not decom-
pose on chromatography and can be easily separated from the other
reaction products by chromatography on Al2O3.
(d) reacting of alcoholate anion 27 with carbocation 3 resulting
in the formation of bisferrocenyl ether 20;
(e) in addition, anion 27 can deprotonate the pre-nucleophile
NuH to form nucleophile Nuꢀ and alcohol FcCH(R)OH iden-
tical to the product of path b.
2.1.3. Ferrocenylalkylation and competitive side reactions
Thus, ferrocenylalkylations via the intermediate formation of a-
ferrocenylalkyl carbonates result in the target products along with
some by-products. This is because of the transformations depicted
in Scheme 2 can be accompanied by a spectrum of side processes.
These side reactions are of particular significance in the case of such
substrates NuH as alcohols, amines, etc., which exhibit nucleophilic
properties without preliminary deprotonation and can react with
carbocations 3 as is. In these cases, two nucleophiles, NuH and
alcoholate ion 5, are simultaneously present in the reaction mixture
Both a composition and ratio of the products in the a-ferroce-
nylalkylation reactions can be easily monitored by 1H NMR spectra
of the reaction mixtures after hydrolysis, extraction of the products,
and evaporation of the solvent. In various experiments, we actually
identified the products of all side reactions mentioned above.
For example, the reactions of 1a,b with 2 eq. of Et2NH pro-
ceeding through the intermediate formation of carbonates 8a,b
produced the mixture of 17a,b and FcCH(R)OH in 1: 0.58 (for 17a)
and 1: 0.16 (for 17b) ratios along with the traces of 16a,b (a: R ¼ Me;
b: R ¼ Ph) and FcCH ¼ CH2 (in the case of 1a), the product of an
elimination of the proton from the intermediate carbocation
Fc(CH3)CHþ.
and compete with each other both for
and for participation in side processes.
a-ferrocenylcarbocation 3
An overview of the
a-ferrocenylalkylations using reagents of
general formulae FcCH(R)OC(O)X (24) including
a
-ferrocenylalkyl
carbonates and relative compounds prone to the heterolytic decay
producing cation 3 and anion XC(O)Oꢀ (25) along with the
competitive side reactions are shown in Scheme 7. It is required of X
that it would ensure that CO2 to be released from 25 furnishing
anion Xꢀ possessing strong both basic and nucleophilic properties
(ROꢀ, R2Nꢀ, etc.). Then, the possible side reactions (paths a-e)
In the reaction of 1a with Et2NH, the use of 20 eq. of the amine
increased the FcCH(Me)NEt2: FcCH(Me)OH ratio up to 1: 0.49.
Further increase took place in the presence of 2 eq. of KHSO4 (1:
0.37). The similar results were obtained with Me2NH. Thus, an
excess of the amine increases the efficiency of the target alkylation,
and the presence of KHSO4, a proton donor, hinders the competitive
reaction of anion EtOꢀ (Scheme 3, path b). The results are consistent
with what is expected.
accompanying the
a-ferrocenylalkylation process and the corre-
sponding products are as follows:
(a) the nucleophilic attack of anion Xꢀ on the Ca carbon atom in
carbonyl compound 24 resulting in product 26. This process
is more likely to occur at the earlier stages of the ferroce-
nylalkylation reaction when the concentration of compound
24 in the reaction mixture is still high;
It is obviously that a composition of the products of the a-fer-
rocenylalkylation process must depend on the ratio of the rates of
the target and side reactions, as well as on the ratio of the rates of
the forward and reverse reactions in the reversible stages. Specif-
ically, the composition of the reaction products must be affected by
(b) the nucleophilic attack of Xꢀ on the carbonyl carbon in
compound 24 resulting in the release of alcoholate anion

34
E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
Scheme 7.
a-Ferrocenylalkylation of NuH with FcCH(R)OC(O)X and competitive side reactions.
the nucleophilicity of Xꢀ, the base formed on the decomposition of
the intermediate carbonyl compound 24, because of its nucleo-
philicity should influence the decay rates of both the carbonyl
compound 24 and anion 25. In addition, the basicity and nucleo-
philicity of Xꢀ should affect the NuH deprotonation rate and the
equilibrium position in the reversible stages, as well as the effi-
ciency of the side reactions involving Xꢀ.
formation of the nucleophilic anion. Thus, the nature of the base
should not affect the deprotonation stage, but it have to affect some
stages of both the target
a-ferrocenylalkylation (for example, a
decay of anion XC(O)Oꢀ into Xꢀ and CO2) and side processes
(Scheme 7). As show the data from Table 4, the nature of anion Xꢀ
has a pronounced effect on the yield of the ferrocenylalkylation
products. The highest yields of the target products were achieved in
the case of ethyl carbonates 8a,b. Excepting methyl carbonate
28a,b, the higher the nucleophilicity of Xꢀ, the lower the yields of
To demonstrate the influence of the nature of base Xꢀ on the
side reactions and, hence, the composition of the products, methyl
carbonates 28a,b, ethyl carbonates 8a,b, tert-butyl carbonates
23a,b, and carbamates 29a,b generated in situ by an addition to a
solution of 1a,b in THF of the equimolar quantities of BunLi followed
by MeOC(O)Cl, EtOC(O)Cl, Boc2O or Me2NC(O)Cl, respectively, were
entered the reaction with acetylacetone that was chosen as the pre-
nucleophile NuH (Table 4).
the
a-ferrocenylalkylation products regardless of the group R,
which is due to the occurrence of the side reactions. Obviously, the
higher nucleophilicity of ButOꢀ and Me2Nꢀ hinders the decay of the
corresponding carbonate and carbamate anions 25 but facilitates
the nucleophilic attacks of these anions on the carbonyl group of
compounds 24 (Scheme 7, path b) leading to a formation of anion
27 that can not participate in a formation of target product 7.
As for the methyl carbonates 28a,b, anion MeOꢀ is a weaker
nucleophile than EtOꢀ. Therefore, anion MeOCOOꢀ formed as a
Any of the bases Xꢀ (MeOꢀ, EtOꢀ, ButOꢀ, Me2Nꢀ) appearing in
the reaction mixture during the decomposition of the intermediate
carbonyl compounds can easily deprotonate acetylacetone with a
Table 4
a-Ferrocenylalkylation of acetylacetone with carbonyl compounds 8a,b, 23a,b, 28a,b, 29a.b.
Entry
FcCH(R)OH
R
X
Y
Сarbonyl interme-diate
Product
Yielda, %
1
2
3
4
5
6
7
8
1a
1b
1a
1b
1a
1b
1a
1b
Me
Ph
Me
Ph
Me
Ph
Me
Ph
OEt
OEt
Cl
Cl
Cl
Cl
8a
8b
30a
30b
30a
30b
30a
30b
30a
30b
70
76
43
46
14
18
traces
traces
OMe
OMe
OBut
OBut
NMe2
NMe2
28a
28b
23a
23b
29a
29b
OC(O)OBut
OC(O)OBut
Cl
Cl
a
Conditions: 3 eq. of acetylacetone, room temperature, 24 h, in THF.

E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
35
Scheme 8. Decomposition of carbamate 30b in the absence of an external nucleophile.
result of the heterolylic decay of 28a,b (see Scheme 7) dissociates to
CO2 and MeOꢀ faster than does anion EtOCOOꢀ in the case of ethyl
carbonates 8a,b. In addition, the equilibrium in a reversible pro-
cess: R'OCOOꢀ 4 R'Oꢀ þ CO2 is shifted more right for R’ ¼ Me than
for R’ ¼ Et. So, MeOꢀ appears in the reaction mixture at the earlier
stage of the reaction than EtOꢀ (i. e. at higher concentration of the
undissociated parent carbonate 28 in the reaction mixture) and, in
addition, its concentration is higher than that one of EtOꢀ. All of
these make the side nucleophilic attack of MeOꢀ on the carbonyl
group in the parent carbonate 23 more effective than in the case of
EtOꢀ, thus leading to a higher yield of the “starting” alcohol
Carlo-Erba CE-1106 elemental analyzer; the contents of Fe were
determined by an X-ray fluorescence (XRF) method using a VRA-30
XRF-spectrometer. Melting points were determined with an Elec-
trorthermal 1002 MEL-TEMP® capillary melting point apparatus
and are uncorrected. TLC was performed on Silufol UV-254 plates;
the spots were visualized in camera with iodine. Column chroma-
tography was performed using aluminum oxide (Brockmann Ac-
tivity III).
All reactions were carried out in an argon atmosphere. All sol-
vents were purified (dried and distilled) before use according to
literature methods. EtOCOCl, MeOCOCl, Boc2O, Me2NCOCl, HNEt2,
PriOH, 2-methoxyphenol, 2-naphthol, 2-allylphenol and com-
pounds 9e15 are commercially available (Aldrich). Alcohols 1a,b
were prepared by a reduction of the corresponding carbonyl
compounds with LiAlH4 in Et2O [31,32].
FcCH(R)OH and, hence, to a lower yield of the a-ferrocenylalkyla-
tion product 30.
Thus, it is most preferable to use ethyl carbonates in the
rocenylalkylation reactions.
a-fer-
“Hard” amide ion Me2Nꢀ is the strongest nucleophile among the
discussed Xꢀ. This increases the efficiency of its attack on the
carbonyl group (Scheme 7, path b). As a result, alcohol FcCH(R)OH is
the major reaction product, amine FcCH(R)NMe2 is the minor one,
and the target ferrocenylalkylation product 30 is formed in traces.
Meanwhile, spontaneous decomposition (20 ꢁC, 24 h) of carbamate
29b in the absence of an external nucleophile (Scheme 8) leads to a
formation of amine 18 (18%) along with alcohol FcCH(R)OH and
traces of ether 20 (R ¼ Ph).
4.2.
a
-Ferrocenylalkylation of amines with 1a,b
4.2.1.
a
-Ferrocenylalkylation of Et2NH
A hexane solution of BunLi (1 eq.) was added to a solution of 1a,b
(150 mg) in THF (15 ml) and the mixture was stirred for 5 min. Ethyl
chloroformate (1 eq.) was added to the mixture in one portion
followed by 5 min stirring and, if specified, addition of KHSO4.
Diethyl amine (2 eq.) was added after 5 min stirring and the
mixture was stirred for additional 24 h at room temperature. The
reaction mixture was quenched with 5% aqueous solution of HCl
(15 ml) and diethyl ether (10 ml) was added. The organic layer was
separated and washed with 5% aqueous solution of HCl (3 ꢂ 15 ml).
The combined acidic solutions were extracted with diethyl ether
(20 ml), alkalized with aqueous ammonia to pH ¼ 10 and extracted
with diethyl ether (3 ꢂ 15 ml). The ether extracts were combined,
dried over Na2SO4 and the solvent was evaporated to afford pure
product.
Path d (Scheme 7) leading to a formation of bisferrocenyl ethers
20a,b is illustrated by a decomposition of tert-butyl carbonates
23a,b in the absence of an external nucleophile (Scheme 6).
3. Conclusion
Thus, one-pot reactions of
BunLi, EtOCOCl and an excess of amine, phenol or alcohol result in a
formation of the corresponding N-( -ferrocenylalkyl) amines or
ethers in moderate to 98% yields. The reactions proceed via the
intermediate formation of -ferrocenylalkyl carbonates 8a,b under
acid-free conditions at the -ferrocenylalkylation step. Nitrogen
heteroaryl amines undergo the selective -ferrocenylalkylation at
a-ferrocenylalkyl alcohols 1a,b with
a
a
4.2.1.1. Diethyl(1-ferrocenylethyl)amine (17a) [23]. Product 17a was
obtained from the reaction without KHSO4 (65 mg, 35%) or in the
presence of KHSO4 (55 mg, 31%) as brown oil. The same reaction
with 20 eq. of Et2NH afforded 71 mg (38%) of 17a in the absence of
KHSO4 and 63 mg (34%) of 17a in the presence of KHSO4. 1H NMR:
0.98 (t, 6H, 3J ¼ 7.1, CH3eCH2eN); 1.40 (d, 3H, 3J ¼ 6.8, CH3eCH);
2.14e2.22 (m, 2H, CH3eCH2eN); 2.37e2.46 (m, 2H, CH3eCH2eN);
3.86 (q, 1H, 3J ¼ 6.8, CH3eCH); 4.09 (s, 5H, Fc); 4.09e4.18 (m, 4H,
Fc). 13C NMR: 14.21, 16.47, 43.68, 53.65, 66.98, 67.02, 67.34, 68.31,
68.59, 68.96. MS spectrum: 285(Mþ), 213 (Fc(CH3)CHþ).
a
a
the amino group. The competitive side reactions associated with
this protocol were discussed and their occurrence was proved by
the identification of the predicted side products in the reaction
mixtures.
4. Experimental section
4.1. General
4.2.1.2. Diethyl(a-ferrocenylbenzyl)amine (17b). Product 17b was
1H and 13C NMR spectra were recorded on a Bruker Avance™400
spectrometer (400.13 MHz for 1H). Chemical shifts are reported in
ppm from tetramethylsilane with the solvent resonance as the in-
obtained from the reaction without KHSO4 (76 mg, 43%) or in the
presence of KHSO4 (90 mg, 51%) as brown oil. The same reaction
with 20 eq. of Et2NH afforded 88 mg (49%) of 17b in the absence of
KHSO4 and 98 mg (55%) of 17b in the presence of KHSO4. 1H NMR:
0.93 (t, 6H, 3J ¼ 6.9, CH3eCH2eN); 2.35e2.40 (m, 2H, CH3eCH2eN);
2.50e2.57 (m, 2H, CH3eCH2eN); 4.12e4.32 (m, 4H, Fc); 4.25 (s, 5H,
Fc); 4.55 (s, 1H, CH-Ph); 7.31e7.50 (m, 5H, Ph). 13C NMR: 11.70,
43.29, 66.57, 68.11, 68.21, 68.55, 68.80, 70.03, 126.86, 127.85, 128.26,
128.94. MS spectrum: 347(Mþ), 275 (Fc(Ph)CHþ).
ternal standard (deuterochloroform:
d
7.28 ppm for 1H and
),
77.0 ppm for 13C). Data are reported as follows: chemical shifts (
d
multiplicity (s ¼ singlet, d ¼ doublet, t ¼ triplet, q ¼ quartet,
br ¼ broad, m ¼ multiplet), coupling constants (J, Hz). Mass spectra
were recorded on a Finnigan Polaris Q instrument (EI, 70 eV, ion
trap). Elemental analyses (excepting Fe) were performed using a

36
E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
4.2.2.
a
-Ferrocenylalkylation of Me2NH
eq.). The amine (2 eq.) was added after 5 min stirring and the
mixture was stirred for additional 24 h at room temperature.
Aluminum oxide (3 g, for chromatography, Brockmann Activity III)
was added to the reaction mixture ant the solvent was rotatory
evaporated to dryness. The residue was placed on the top of the
chromatography column (Al2O3, 2 ꢂ 15 cm) and the products were
separated by elution with petroleum ether (to remove ethers 26)
followed by the mixture petroleum ether e ethyl acetate.
A hexane solution of BunLi (1 eq.) was added to a solution of 1a,b
(150 mg) in THF (15 ml) and the mixture was stirred for 5 min. Ethyl
chloroformate (1 eq.) was added to the mixture in one portion
followed by 5 min stirring and, if specified, addition of KHSO4. The
mixture was added by the pressure of argon at e5ꢁС to the bulb
charged with dimethyl amine 5 ml (20 eq.), the mixture was stirred
for 24 h at room temperature. The reaction mixture was quenched
with water (20 ml) and extracted with diethyl ether (2 ꢂ 20 ml).
The combined extracts were washed with water (20 ml) and dried
over Na2SO4. Evaporation of the solvent afforded oily residue which
was dissolved in diethyl ether (10 ml) the solution was washed with
5% aqueous HCl (2 ꢂ 15 ml). The acidic solutions were combined,
washed with diethyl ether (20 ml) and alkalized with aqueous
ammonia to pH ¼ 10 and extracted with diethyl ether (3 ꢂ 15 ml).
The ether extracts were combined, dried over Na2SO4 and the
solvent was evaporated to afford pure product.
4.2.4.1. N-(1-ferrocenylethyl)-4-methoxyaniline
(10a)
[13,16].
Product 10a was eluted with petroleum ether e ethyl acetate
(50:1); orange oil. The yields are 118 mg (54%) from the reaction
without KHSO4 or 119 mg (55%) in the presence of KHSO4. 1H NMR:
1.55 (d, 3H, 3J ¼ 6.2, CH3eCH); 3.82 (s, 3H, OCH3); 4.19e4.29 (m, 4H,
Fc); 4.25 (s, 5H, Fc); 4.29e4.32 (m, 1H, CHeCH3); 6.70 þ 6.87 (d þ d,
2Hþ2H, 3J ¼ 8.9, C6H4). 13C NMR: 21.28, 48.42, 55.88, 66.27, 67.20,
67.61, 67.85, 68.56, 93.83, 115.06, 141.94, 152.12. IR (KBr pellet,
cmꢀ1): 3394 (NH). Anal. Calc. for C19H21NOFe: С, 67.86; H, 6.25; N,
4.17; Fe, 16.96. Found: C, 67.89; H, 6.32; N, 4.14; Fe, 16.50%.
4.2.2.1. (1-Ferrocenylethyl)dimethylamine (18a) [18]. Product 18a
was obtained from the reaction without KHSO4 (78 mg, 46%) or in
the presence of KHSO4 (79 mg, 47%) as brown oil. 1H NMR: 1.46 (d,
3H, 3J ¼ 6.8, CH3eCH); 2.09 (s, 6H, CH3); 3.61 (q, 1H, 3J ¼ 6.8,
CHeCH3); 4.13e4.15 (m, Fc). 13C NMR: 69.38, 68.59, 67.37, 67.23,
66.89, 58.62, 40.69, 16.13. MS spectrum: 257 (Mþ), 213 (FcCHPhþ).
4.2.4.2. N-(a-ferrocenylbenzyl)-4-methoxyaniline
(10b)
[13].
Product 10b was eluted with petroleum ether e ethyl acetate
(50:1); orange oil. The yields are 163 mg (80%) from the reaction
without KHSO4 or 143 mg (70%) in the presence of KHSO4. 1H NMR:
3.77 (s, 3H, OCH3); 4.15e4.23 (m, 4H, Fc); 4.27 (s, 5H, Fc); 4.62 (sbr,
1H, NH); 5.06 (s, 1H, CH); 6.61 þ 6.80 (d þ d, 2Hþ2H, 3J ¼ 8.9, C6H4);
7.29e7.54 (m, 5H, Ph). 13C NMR: 55.85, 66.57, 58.50, 67.55, 67.85,
68.09, 68.79, 69.87, 94.50, 114.68, 114.98, 126.87, 127.18, 128.61,
142.02, 143.59. IR (KBr pellet, cmꢀ1): 3394 (NH). Anal. Calc. for
4.2.2.2. (a-Ferrocenylbenzyl)dimethylamine (18b) [20]. Product 18b
was obtained from the reaction without KHSO4 (109 mg, 67%) or in
the presence of KHSO4 (115 mg, 70%) as orange crystalline solid, m.
p. 60-61ꢁС. 1H NMR: 2.11 (s, 6H, CH3); 3.75 (s, 5H, Fc);
3.80 þ 4.13þ4.18 (s þ s þ s, H þ H þ H, Fc); 4.25 (s, 2H, Fc þ CH);
7.33e7.54 (m, 5H, Ph). 13C NMR: 44.57, 66.48, 67.27, 68.61, 68.74,
70.55, 72.41, 90.37, 127.11, 128.04, 128.51, 143.47. MS spectrum: 319
(Mþ), 275 (FcCHPhþ).
C24H23NOFe: С, 72.52; H, 5.79; N, 3.53; О, 4.03; Fe, 14.10. Found: C,
72.58; H, 5.83; N, 3.53; Fe, 14.10%.
4.2.4.3. N-(1-ferrocenylethyl)-4-nitroaniline
(11a)
[13,16].
Product 11a was eluted with petroleum ether e ethyl acetate (8:1)
and recrystallized from hexane to afford orange crystalline solid, m.
p. 115e116 ꢁC. The yields are 142 mg (62%) from the reaction
without KHSO4 or 194 mg (85%) in the presence of KHSO4. 1H NMR:
1.58 (d, 3H, 3J ¼ 6.5, CH3eCH); 4.20e4.24 (m, 4H, Fc); 4.24 (s, 5H,
Fc); 4.44e4.48 (m, 1H, CHeCH3); 4.96 (sbr, 1H, NH); 6.58 þ 8.11
(d þ d, 2Hþ2H, 3J ¼ 9.2, Ph). 13C NMR: 20.40, 47.02, 66.02, 67.24,
68.07, 68.33, 68.64, 91.61, 111.27, 126.59, 152.32. IR (KBr pellet,
cmꢀ1): 3395 (NH), 1307 (NO).
4.2.3.
a-Ferrocenylalkylation of PhNH2
A hexane solution of BunLi (1 eq.) was added to a solution of 1a,b
(150 mg) in THF (15 ml) and the mixture was stirred for 5 min. Ethyl
chloroformate (1 eq.) was added to the mixture in one portion
followed by 5 min stirring and, if specified, addition of KHSO4 (2
eq.). Aniline or aniline hydrochloride (the quantities are shown in
Table 2) was added after 5 min stirring and the mixture was stirred
for additional 24 h at the temperature indicated in Table 2. The
reaction mixture was passed through a layer of SiO2 (4 cm; eluent:
ethyl acetate). An evaporation of the solvent produced brown oily
residue, which was kept at 120 ꢁC/1 mm Hg for 30 min to afford
pure amine 9. The yields are shown in Table 2.
4.2.4.4. N-(a-ferrocenylbenzyl)-4-nitroaniline
(11b)
[13].
Product 11b was eluted with petroleum ether e ethyl acetate (8:1);
orange crystalline solid, m. p. 99e100 ꢁC. The yields are 132 mg
(62%) from the reaction without KHSO4 or 137 mg (65%) in the
presence of KHSO4. 1H NMR: 4.05e4.26 (m, 4H, Fc); 4.23 (s, 5H, Fc);
5.25 (d, 1H, 3J ¼ 4.9, CHeNH); 5.64 (sbr, 1H, NH); 6.54 þ 8.05 (d þ d,
2Hþ2H, 3J ¼ 9.2, C6H4); 7.31e7.46 (m, 5H, Ph). 13C NMR: 56.96,
67.38, 68.41, 68.54, 68.71, 68.96, 92.20,112.11,126.46,126.83,127.81,
128.84, 138.13, 141.09, 152.16. IR (KBr pellet, cmꢀ1): 3394 (NH), 1310
(NO).
4.2.3.1. N-(1-ferrocenylethyl)aniline (9a) [13,16]. Brown oil. 1H
NMR: 1,56 (d, 3H, 3J ¼ 6.2, CH3eCH); 3.97 (sbr, 1H, NH); 4.15e4.26
(m, 4H, Fc); 4,25 (s, 5H, Fc); 4.36 (q, 1H, 3J ¼ 6.2, CHeCH3); 4.59 (s,
1H, CH-Ph); 6.69e7.28 (m, 5H, Ph). 13C NMR: 21.10, 47.18, 66.38,
67.24, 67.74, 67.98, 68.51, 68.62, 93.69, 113.35, 117.30, 129.56.
4.2.3.2. N-(a
-ferrocenylbenzyl)aniline (9b) [13]. Brown oil. 1H NMR:
4.11e4.24 (m, 4H, Fc); 4,28 (s, 5H, Fc); 4.85 (sbr, 1H, NH); 5.14 (s, 1H,
CH-Ph); 6.94e7.55 (m, 10H, Ph þ Ph). 13C NMR: 57.59, 66.84, 67.54,
67.95, 68.16, 68.84, 113.55, 117.68, 126.88, 127.25, 128.64, 129.41,
143.18, 147.62.
4.2.4.5. 4-Cyano-N-(1-ferrocenylethyl)aniline (12a). Product 12a
was eluted with petroleum ether e ethyl acetate (8:1) and recrys-
tallized from petroleum ether to afford orange crystalline solid, m.
p. 76e77 ꢁC. The yields are 145 mg (67%) from the reaction without
KHSO4 or 85 mg (40%) in the presence of KHSO4. 1H NMR: 1.53 (d,
3H, 3J ¼ 6.5, CH3eCH); 4.18e4.23 (m, 4H, Fc); 4,22 (s, 5H, Fc);
4.36e4.42 (m, 1H, CHeCH3); 4.58 (sbr, 1H, NH); 6.61 þ 7.45 (d þ d,
2Hþ2H, 3J ¼ 8.4, C6H4). 13C NMR: 20.53, 46.66, 66.09, 67.15, 67.90,
68.18, 68.60, 92.08, 98.05, 112.44, 120.72, 133.86, 150.43. IR (KBr
pellet, cmꢀ1): 3394 (NH), 2201 (СN). Anal. Calc. for C19H18N2Fe: С,
69.09; H, 5.46; N, 8.49; Fe, 16.97. Found: C, 69.01; H, 5.49; N, 8.50;
4.2.4. General procedure for a-ferrocenylalkylation of aryl or
heteroaryl amines with 1a,b
A hexane solution of BunLi (1 eq.) was added to a solution of 1a,b
(150 mg) in THF (15 ml) and the mixture was stirred for 5 min. Ethyl
chloroformate (1 eq.) was added to the mixture in one portion
followed by 5 min stirring and, if specified, addition of KHSO4 (2

E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
37
Fe, 17.20%.
(m, 3H, C6H4); 7.48e7.53 (m, 3H, C6H4); 7.66e7.69 (t, 1H, 3J ¼ 7.1,
C6H4); 7.92e8.00 (m, 2H, C6H4). 13C NMR: 25.72, 56.24, 67.01, 67.30,
68.33, 68.73, 93.02, 100.89, 117.47, 118.82, 124.30, 126.60, 127.62,
128.65, 129.15, 129.36, 140.87, 148.18, 159.53. IR (KBr pellet, cmꢀ1):
3445 (NH). Anal. Calc. for C27H24N2Fe: С, 75.00; H, 5.56; N, 6.48; Fe,
12.96. Found: С, 74.98; H, 5.55; N, 6.51; Fe, 12.94%.
4.2.4.6. 4-Cyano-N-(a-ferrocenylbenzyl)aniline (12b). Product 12b
was eluted with petroleum ether e ethyl acetate (8:1) as orange oil,
which was washed with hot hexane to afford orange solid, m. p.
163 ꢁC. The yields are 136 mg (67%) from the reaction without
KHSO4 or 144 mg (71%) in the presence of KHSO4. 1H NMR:
4.04e4.26 (m, 4H, Fc); 4.27 (s, 5H, Fc); 5.18 (s, 1H, CH); 5.35 (sbr, 1H,
NH); 6.57e7.48 (m, 10H; C6H4 þ Ph). 13C NMR: 56.74, 67.17, 67.20,
68.18, 68.28, 68.74, 92.74, 113.03, 126.65, 127.62, 128.68, 133.69,
141.21, 150.06. IR (KBr pellet, cmꢀ1): 3369 (NH), 2206 (СN). Anal.
Calc. for C24H20N2Fe: С, 73.47; H, 5.10; N, 7.14; Fe, 14.29. Found: C,
73.45; H, 5.43; N, 6.97; Fe, 14.30%.
4.2.4.11. 2-[(1-Ferrocenylethyl)amino]-5-methylpyridine
(15a).
Product 15a was eluted with petroleum ether e ethyl acetate
(50:1); yellow oil. The yields are 82 mg (39%) from the reaction
without KHSO4 or 78 mg (37%) in the presence of KHSO4. 1H NMR:
1.54 (d, 3H, 3J ¼ 6.2, CH3eCH); 2.21 (s, 3H, CH3); 4.13e4.23 (m, 4H,
Fc); 4.23 (s, 5H, Fc); 4.61e4.70 (m, 1Hþ1H, CHeCH3þNH);
6.37 þ 7.28 (d þ d, 1Hþ1H, 3J ¼ 8.4, C5H3N); 7.97 (s, 1H, C5H3N). 13
C
4.2.4.7. 4-Benzoyl-N-(1-ferrocenylethyl)aniline
hydrochloride
NMR: 17.44, 21.23, 45.62, 66.04, 66.98, 67.52, 67.78, 68.48, 106.97,
121.42, 138.48, 147.76, 156.28. IR (KBr pellet, cmꢀ1): 3255 (NH).
Anal. Calc. for C27H24N2Fe: С, 67.50; H, 6.25; N, 8.75; Fe, 17.50.
Found: С, 67.52; H, 6.26; N, 8.77; Fe, 17.54%.
(13a.HCl). Product 13a eluted from the column with petroleum
ether e ethyl acetate (50:1) contained the impurity of 1a. The
mixture was obtained after an evaporation of the solvent as orange
oil, which was dissolved in diethyl ether and acidified with HCl
(aq.). The precipitate was washed with diethyl ether and dried in
vacuo to afford orange solid 13a.HCl, m. p. 120 ꢁC. The yields are
151 mg (55%) from the reaction without KHSO4 or 112 mg (42%) in
the presence of KHSO4. 1H NMR: 1.57 (d, 3H, 3J ¼ 6.5, CH3eCH);
4.19e4.24 (m, 4H, Fc); 4.24 (s, 5H, Fc); 4.43e4.49 (m, 1H, CHeCH3);
4.58 (sbr, 1H, NH); 6.65 þ 7.81 (d þ d, 2Hþ2H, 3J ¼ 8.4, C6H4);
7.47e7.78 (m, 5H, Ph-C]O). 13C NMR: 17.70, 41.77, 67.22, 68.91,
69.98, 76.77, 77.09, 77.40, 128.22, 128.41, 129.71, 129.96, 131.16,
132.52, 132.68, 137.16, 195.30. IR (KBr pellet, cmꢀ1): 2449e2919
(NH2), 1659 (СO). Anal. Calc. for C25H24NOFeCl: С, 67.29; H, 5.38; N,
3.14; О, 3.59; Fe, 12.56; Сl, 7.96. Found: С, 67.21; H, 5.32; N, 3.13; Fe,
12.55; Сl, 7.89%.
4.2.4.12. 2-[(
a-Ferrocenylbenzyl))amino]-5-methylpyridine
(15b).
Product 15b was eluted with petroleum ether e ethyl acetate (8:1);
yellow oil. The yields are 134 mg (65%) from the reaction without
KHSO4 or 105 mg (50%) in the presence of KHSO4. 1H NMR: 2.23 (s,
3H, CH3); 4.21e4.32 (m, 4H, Fc); 4.32 (s, 5H, Fc); 5.36 (d. 1H, 3J ¼ 5.4,
CH); 5.55 (dbr. 1H, 3J ¼ 5.1, NH); 6.20 (d, 1H, C5H3N); 7.19e7.50 (m,
6H, C5H3N þ Ph); 8.00 (s, 1H, C5H3N). 13C NMR: 17.46, 55.73, 66.80,
67.07, 67.88, 67.94, 68.77, 69.89, 93.16,106.33,122.08,126.79,127.13,
128.39, 138.57, 142.81, 147.99, 156.19. IR (KBr pellet, cmꢀ1): 3412
(NH). Anal. Calc. for C23H22N2Fe: С, 72.23; H, 5.76; N, 7.33; Fe, 14.65.
Found: С, 72.25; H, 5.79; N, 7.35; Fe, 14.70%.
4.3. General procedure for a-ferrocenylalkylation of phenols and
4.2.4.8. 4-Benzoyl-N-(
a
-ferrocenylbenzyl)aniline (13b). Product 13b
alcohols with 1a,b
was eluted with petroleum ether e ethyl acetate (8:1) and recrys-
tallized from hexane to afford yellow solid, m. p. 150 ꢁC (dec.). The
yields are 113 mg (47%) from the reaction without KHSO4 or 119 mg
(49%) in the presence of KHSO4. 1H NMR: 4.07e4.25 (m, 4H, Fc);
4.25 (s, 5H, Fc); 5.24 (s, 1H, CH); 5.40 (sbr, 1H, NH); 6.61e7.76 (m,
10H, C6H4 þ Ph). 13C NMR: 56.77, 67.11, 67.25, 68.10, 68.20, 68.73,
93.02, 112.19, 126.70, 127.47, 128.03, 128.62, 129.47, 131.25, 132.95,
139.04, 141.67, 150.82, 195.17. IR (KBr pellet, cmꢀ1): 3386 (NH), 1636
(CO). Anal. Calc. for C30H25NOFe: С, 76.27; H, 5.30; N, 2.97; О, 3.39;
Fe, 11.86. Found: С, 76.25; H, 5.31; N, 3.19; Fe, 11.85%.
A solution of n-BuLi (1 eq.) in hexane was added to a solution of
1a,b (150 mg) in THF (15 ml). The mixture was stirred for 5 min and
EtOC(O)Cl was added followed by 5 min stirring and addition of
R’OH. The mixture was stirred for 24 h at room temperature.
4.3.1.
MeOC6H4, R ¼ Ph)
a
-Ferrocenylbenzyl 2-methoxyphenyl ether 19 (Ar ¼ 2-
The reaction mixture obtained from 1b and 20 (3 eq.) was
quenched with 0.1 M aqueous solution of NaOH (20 ml) and
extracted with ether (3 ꢂ 15 ml). The combined extracts were
washed with water (3 ꢂ 15 ml) and dried over Na2SO4. Evaporation
of the solvent afforded 20b (49 mg, 29%) as yellow oil. 1H NMR: 3.89
(s, 3H, CH3); 4.0e4.17 (m, 9H, Fc); 5.82 (s, 1H, CH); 6.66e6.79 (m,
4H, C6H4); 7.20e7.29 (m, 5H, Ph). 13C NMR: 43.93, 56.00, 67.25,
67.70, 68.56, 68.75, 69.28, 91.43, 108.29, 119.03, 122.01, 127.84,
125.93, 128.81, 131.36, 144.43.
4.2.4.9. 4-[(1-Ferrocenylethyl)amino]-2-methylquinoline
(14a).
Product 14a was eluted with petroleum ether e ethyl acetate (8:1).
Yellow crystalline solid, m. p. 171 ꢁC. The yields are 121 mg (50%)
from the reaction without KHSO4 or 142 mg (59%) in the presence
of KHSO4. 1H NMR: 1.60 (d, 3H, 3J ¼ 6.4, CH3eCH); 2.66 (s, 3H, CH3);
4.19e4.26 (m, 4H, Fc); 4.26 (s, 5H, Fc); 4.50e4.57 (m, 1H, CHeCH3);
5.42 (sbr, 1H, NH); 6.44 (s, 1H, C5HN); 7.40 (t, 1H, 3J ¼ 7.6, C6H4); 7.62
(t, 1H, 3J ¼ 7.6, C6H4); 7.71 (d, 1H, 3J ¼ 8.4, C6H4); 7.97 (d, 1H, 3J ¼ 8.4,
C6H4). 13C NMR: 19.98, 25.84, 46.25, 66.11, 67.16, 68.06, 68.26, 68.34,
68.53, 92.18, 99.05, 117.36, 118.95, 124.00, 129.13, 129.23, 148.43,
159.57. IR (KBr pellet, cmꢀ1): 3426 (NH). Anal. Calc. for C22H22N2Fe:
С, 71.16; H, 5.93; N, 7.55; Fe, 15.36. Found: C, 69.89; H, 5.95; N 7.05;
Fe, 14.3%.
4.3.2. 1-Ferrocenylethyl isopropyl ether (21a) [16]
The reaction mixture obtained from 1a and PriOH (25 eq.) was
evaporated. The products were separated by column chromatogr-
apy (Al2O3, petroleum ether) to afford 24a (80 mg, 47%) as orange
oil. 1H NMR: 1.10e1.12 (d, 3H, 3J ¼ 6.2, CH3CHO); 1.15e1.17 (d, 3H,
3J ¼ 6.3, CH3eCH); 3.70e3.76 (m, 1H, CH(CH3)2; 4.13e4.23 (m, 9H,
Fc); 4.38e4.40 (m, 1H, CHeCH3). 13C NMR: 21.48, 22.52, 23.08,
65.83, 67.52, 67.81, 68.26, 68.54, 68.62, 70.49. Anal. Calc. for
4.2.4.10. 4-[(a-Ferrocenylbenzyl))amino]-2-methylquinoline (14b).
Product 14b was eluted with petroleum ether e ethyl acetate (8:1).
Yellow crystalline solid, m. p. 175 ꢁC (dec.). The yields are 240 mg
(76%) from the reaction without KHSO4 or 76 mg (34%) in the
presence of KHSO4. 1H NMR: 2.50 (s, 3H, CH3); 4.04e4.26 (m, 4H,
Fc); 4.29 (s, 5H, Fc); 4.50e4.57 (m, 1H, CHeCH3); 5.33 (d, 1H,
3J ¼ 4.7, CHeNH); 6.09 (dbr, 1H, NH); 6.16 (s, 1H, C5HN); 7.30e7.41
C
15H20OFe: С, 66.23; H, 7.36; Fe, 20.53. Found: C, 66.27; H, 7.41; Fe,
20.50%.
4.3.3.
a-Ferrocenylbenzyl isopropyl ether (21b) [13]
The reaction mixture obtained from 1b and PriOH (25 eq.) was
evaporated. The products were separated by column

38
E.V. Shevaldina et al. / Journal of Organometallic Chemistry 880 (2019) 29e38
displacement of hydroxy- and similar groups from
a
-substituted ferrocenyl-
chromatograpy (Al2O3, petroleum ether: ethyl acetate ¼ 16: 1) to
afford 24b (100 mg, 58%) as orange oil. 1H NMR: 1.10e1.12 (d, 3H,
3J ¼ 6.2, CH3CHO); 1.15e1.17 (d, 3H, 3J ¼ 6.3, CH3eCH); 3.70e3.76
(m, 1H, CH(CH3)2; 4.13e4.23 (m, 9H, Fc); 4.38e4.40 (m, 1H,
CHeCH3). 13C NMR: 21.48, 22.52, 23.08, 65.83, 67.52, 67.81, 68.26,
68.54, 68.62, 70.49. Anal. Calc. for C15H20OFe: С, 66.23; H, 7.36; Fe,
20.53. Found: C, 66.27; H, 7.41; Fe, 20.50%.
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The authors would like to thank the Russian Foundation for
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