Highly efficient catalytic dehydrative S-allylation of thiols and thioic S-acids

Article abstract of DOI:10.1039/c0cc00096e

A SH-selective allylation method using [CpRu(2-quinolinecarboxylato) (η₃-C₃H₅)]PF₆ has been realized in various solvents including aqueous media to give allyl sulfides and allyl S-thioates, demonstrating the potential applicability to lipopeptide chemistry.

Full text of DOI:10.1039/c0cc00096e

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Highly efficient catalytic dehydrative S-allylation of thiols and
thioic S-acidsw
Shinji Tanaka, Prasun Kanti Pradhan, Yusuke Maegawa and Masato Kitamura*
Received 24th February 2010, Accepted 13th April 2010
First published as an Advance Article on the web 5th May 2010
DOI: 10.1039/c0cc00096e
A SH-selective allylation method using [CpRu(2-quinoline-
carboxylato)(g3-C3H5)]PF6 has been realized in various solvents
including aqueous media to give allyl sulfides and allyl
S-thioates, demonstrating the potential applicability to lipo-
peptide chemistry.
The results are shown in Table 1. The CpRu complex 4
itself slowly catalyzed the reaction to give 3 (R1 = R2 = R3
= R4 = H) in 17% yield after 1 h, but the reaction nearly
stopped at ca. 20% conversion (entry 1). A combination
of 4 with QAH considerably increased catalysis (84%, 1 h),
and the reaction was almost completed in 3 h (entry 2). The
p-allyl complex 5 gave a similar level of reactivity to
4/QAH-combined system (vide infra). Introduction of a methyl
group at C(8) of QAH abolished the acceleration effect
(entry 3). A similar result was observed with 2-pyridine-
carboxylic acid (PAH) and 6-t-C4H9–PAH (55% vs. 16%, 3 h)
(entries 4 and 5). [Cp*Ru(II)(CH3CN)3]PF6 (6) itself displayed
little reactivity (entry 1). PAH promoted the allylation more
efficiently than QAH (72% vs. 97%, 12 h), unlike CpRu
(entries 2 and 4). No reaction occurred with both 8-CH3–QAH
and 6-t-C4H9–PAH (entries 3 and 5). A combination of either
4 or 6 with simple Brønsted acids such as C6H5COOH,
4-CH3C6H4SO3H, CF3SO3H, and HCl also showed less reactivity
(entries 6–9).12 A series of experiments indicate that the
coordination of sp2N atom to the central Ru metal plays a key
role in achieving high levels of reactivity and robustness. Complex
formation is retarded by increased steric repulsion between the
ligands on Ru, resulting in Cp*Ru/PAH > Cp*Ru/QAH. The
lower LUMO level of QAH in comparison to PAH would
explain CpRu/QAH > CpRu/PAH.11c
Allyl sulfides and their a-oxo derivatives, S-allyl thioates, play
an important role in bioorganic chemistry1 and serve as useful
synthetic elements for organic synthesis.2 The allylic CQC
double bond, allylic proton, and sulfur group expand the type
of reactions that can be achieved, facilitating useful trans-
formations of organic molecules. The preparation is based
mainly on base-/acid-promoted3 or transition-metal-catalyzed4,5
coupling between thiols and activated allyl electrophiles
among many other methods. Catalytic dehydrative allylation
of thiols and thioic S-acids 1 with allyl alcohols 2 to give 3 is
apparently the most straightforward and ideal in terms of
atom economy, E factor, safety and operational simplicity.6
Several such trials have been reported in the literature.5,7–9
Among these examples, Cp*Ru(II)Cl(cod) by Kondo et al.5
and Pd(0)(P(C6H4(SO3Na))3)3 by Komiya et al.8 are the
most promising catalyst systems. Indeed, the Ru chemistry
has been significantly improved by Pregosin to give an
excellent [Cp*Ru(II)(CH3CN)3]PF6/TsOH combined system.9a
We have independently developed a new catalytic system
enabling the activation of an allyloxy C–O bond on the basis
of a ‘‘redox-involved donor–acceptor bifunctional catalyst
(RDACat) concept.’’10 The system, consisting of
[CpRu(II)(CH3CN)3]PF6 (4) and 2-quinolinecarboxylic acid
(QAH) or the p-allyl complex [CpRu(IV)(Z3-C3H5)QA]PF6
(5), efficiently catalyzes the dehydrative allylation of alcohols
with high versatility to give allyl ethers.11 We reasoned
that utilizing these complexes would facilitate the necessary
juxtaposition of S-allylation with O-allylation.
Table 2 shows the solvent effect and the applicability
to other allyl alcohols by use of phenylmethanethiol and 5
(for further details see ESIw). CH2Cl2, DMF, DMA, THF,
and CH3OH (entries 1, 4, 5, 7 and 9) were the solvents of
choice. The same results were obtained using C2H5OH,
i-C3H7OH, and t-C4H9OH, but the rate of reaction was slower
in CH3CN or toluene (entries 6 and 8). Even in water-containing
CH3OH, dehydrative allyl sulfide formation proceeded
quantitatively (entry 10). No solvent afforded 3 (R1 = R2 =
R3 = R4 = H) in 98% isolated yield (10 mmol scale).
Introduction of one methyl group at the C(1), C(2), or C(3)
position of C(3)H2QC(2)HC(1)H2OH exerted little effect on
the reactivity in CH3OH (entries 11–13). The CH3 substituent
at C(2) could be replaced with n-C6H13, C6H5 and COOC2H5
groups without any deceleration (entries 14, 16 and 17).
However, secondary alkyl substitution did decrease the rate
Catalytic performance was initially investigated using a fixed set
of conditions ([C6H5CH2SH] = 1000 mM, [CH2QCHCH2OH] =
1000 mM, [Cp or Cp*Ru catalyst] = 1.0 mM, CH2Cl2, 30 1C).
Research Center for Materials Science and the Department of
Chemistry, Nagoya University, Chikusa, Nagoya 464-8602, Japan.
E-mail: kitamura@os.rcms.nagoya-u.ac.jp; Fax: +81 52-789-2261
w Electronic supplementary information (ESI) available: General
procedures for the allylation and characterization of all of the
allylation products. See DOI: 10.1039/c0cc00096e
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Table 1 Acid effect on the reactivity in the reaction of phenylmethanethiol with allyl alcohol in the presence of [CpRu(CH3CN)3]PF6 or
[Cp*Ru(CH3CN)3]PF6
a
Convn (%) using
Convn (%) using
b
b
[CpRu(CH3CN)3]PF6
[Cp*Ru(CH3CN)3]PF6
1 h
3 h
12 h
24 h
1 h
3 h
12 h
24 h
Entry
Additive
1
2
3
4
5
6
7
8
9
—
QAHc,d
17
84
15
39
11
14
12
19
6
20
95
18
55
16
18
22
22
8
24
98
24
69
23
25
53
33
14
24
>99
25
70
34
26
59
34
20
o1
15
0
26
0
o1
45
1
72
o1
97
o1
2
2
2
6
1
81
o1
>99
o1
5
4
4
11
8-CH3–QAHd,e
PAHd,f
o1
69
6-t-C4H9–PAHd,g
C6H5COOH
4-CH3C6H4SO3H
CF3SO3H
HCl
o1
o1
o1
o1
2
o1
0
o1
1
a
All reactions were carried out by successive addition of a solution of a Ru precursor, allyl alcohol, and then phenylmethanethiol under the
following conditions unless otherwise specified: 3 mmol of thiol in CH2Cl2; [C6H5CH2SH] = [2 (CH2QCHCH2OH)] = 1000 mM;
[[CpRu(CH3CN)3]PF6 or [Cp*Ru(CH3CN)3]PF6] = 1 mM; temp., 30 1C. b 1H-NMR analysis of the crude products obtained after (C2H5)3N
c
d
addition for quenching. The conversions are nearly identical with the yields of allyl phenylmethyl sulfide. 2-Quinolinecarboxylic acid. H in
e
QAH and PAH represents the carboxylic acid proton. 8-Methyl-2-quinolinecarboxylic acid. 2-Pyridinecarboxylic acid. 6-tert-Butyl-2-
f
g
pyridinecarboxylic acid.
Table
dehydrative allylation of phenylmethanethiol in the presence of
2
Solvents and allyl alcohols usable in the catalytic
Primary, secondary, and even tertiary alkyl thiols were
allylated (entries 1–3) unlike the case with the corresponding
alcohols.11a Reaction of aryl thiols with allyl alcohol also
proceeded smoothly (entries 4–6). Bifunctional 2-thioethanol
and 2-thioethylamine hydrochloride predominantly gave
S-allylated products (entries 7 and 8). Even with more acidic
thioic S-acids than aryl thiols, the S-allyl thioates were
obtained in >95% yields (entries 11–15). The present
dehydrative S-allylation of thiols and thioic S-acids can func-
tion in an aqueous system, which is a substantial advantage for
the allylation of highly polar substrates such as amino acids
and peptides. The utility of this reaction was successfully
demonstrated by use of cysteine hydrochloride (7). A 1 : 1
mixture of 7 and allyl alcohol in an aqueous solvent containing
5 gave S-allyl cysteine (8a) in >95% yield (S/C = 100, 1 h;
S/C = 1000, 24 h) (entry 9). With 2-n-C6H13-substituted
allyl alcohol 8b was obtained in 99% yield (entry 10). The
results indicate the potential applicability to lipopeptide
chemistry.1,3c,f–h
[CpRu(Z3-C3H5)(QA)]PF6 (5)a
2
R1
R2 R3
R4
Entry
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
H
H
H
H
H
H
H
H
H
H
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH2Cl2
CH2Cl2
CH2Cl2
DMF
DMA
CH3CN
THF
Toluene
CH3OH
1 : 1 CH3OH–H2O 98
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
98
97c,d
95e
97
97
60
98
90
99c
98f,g
98f,h
98
CH3
n-C6H13
c-C6H11
C6H5
98
91
97
96
COOC2H5 CH3OH
In summary, we have developed an efficient synthetic
method for allyl sulfides and a-oxo derivatives using allyl
alcohols without any need for activation. Water is the only
co-product. The generic reaction proceeds with a high level of
chemoselectivity in various aprotic and protic solvents,
including water. As well as sterically demanding thiols,
electron deficient thiols and thioic S-acids can also be utilized
as substrates. The detailed mechanism of this reaction is
unclear. Nevertheless, the evident high performance of the
reaction, even when using a large molar amount of highly-
coordinative sulfur-containing compound, can be ascribed to
the following characteristics: (i) the chelation ability of QAH
that avoids pathways leading to a dead catalyst, (ii) a rapid
and exothermic transformation from [CpRu(II)(QAH)]+/allyl
alcohol to [CpRu(IV)(Z3-C3H5)(QA)]+/H2O on the basis of
the RDACat mechanism,10,11 (iii) the high oxophilicity of the
carboxylic acid proton of ligating QAH towards the allylic
oxygen atom, (iv) no inhibition of products that are associated
with the Ru(IV) complex in the resting state, and (v)
a
All reactions were carried out under the following conditions unless
otherwise specified: 0.4–1 mmol of phenylmethanethiol; [1] = [2] =
b
c
100 mM; [5] = 1 mM; temp., 30 1C; 3–4 h. Isolated yield. 3 mmol
scale. [1] = [2] = 1000 mM; [4] = 1 mM; 24 h. 84% convn after 1 h.
d
e
3 mmol scale. [1] = 1000 mM; [2] = 2000 mM; [4] = 0.2 mM; 48 h.
A mixture of benzyl but-3-en-2-yl sulfide, (E)- and (Z)-benzyl but-2-
f
g
enyl sulfide. 1 : 0.19 : 0.01 ratio. 1 : 0.39 : 0.09 ratio.
h
(entry 15). Moreover, no product was obtained at all in the
presence of a tertiary alkyl group at C(2). With cyclohex-2-en-
1-ol, the reaction was sluggish. A C(3)-dimethyl substituted
allyl alcohol, 3-methylbut-2-en-1-ol, showed little reactivity,
while the C(1)-dimethyl substituted molecule, 2-methylbut-
3-en-2-ol, gave a 1.7 : 1 branch/normal mixture of benzyl
2-methylbut-3-en-2-yl sulfide and benzyl 3-methylbut-2-enyl
sulfide in 97% isolated yield.
A variety of thiols can be utilized in the present catalytic
system as shown in Table 3 (for further details see ESIw).
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Table 3 [CpRu(Z3-C3H5)(QA)]PF6 (5)-catalyzed allylation of thiols
and thioic S-acidsa
This work was aided by the Grant-in-Aid for Scientific
Research (No. 25E07B212) from the Ministry of Education,
Science, Sports and Culture, Japan.
Entry
1
Product 3
Yieldb (%)
96c,d (97)c,d
Notes and references
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2
3
97 (97)
95 (98)
3 For Williamson-type reactions proceeding without the formation
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4
5
6
X = H
X = CH3O
X = Cl
99 (99)
98 (98)
95 (94)
7
8
97 (96)
98 (—)
3176–3177Reductive
allyl
selenosulfide
rearrangement:
9
10
8a: R = H
8b: R = n-C6H13
>95e (—)
99e (—)
(h) D. Crich, V. Krishnamurthy and T. K. Hutton, J. Am. Chem.
Soc., 2006, 128, 2544–25451,4-Addition of allyl thiols: (i) B. Das,
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4141–4144; (b) G. Goux, P. Lhoste and D. Sinou, Tetrahedron
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11
12
— (96)c,d
98 (97)
13
96 (98)
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activated amines, see: I. Jovel, S. Prateeptongkum, R. Jackstell,
N. Vogl, C. Weckbecker and M. Beller, Chem. Commun., 2010, 46,
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14
15
X = H
X = CH3O
99 (96)
96 (96)
a
All reactions were carried out under the following conditions unless
otherwise specified: CH3OH and/or CH2Cl2; [1] = [2] = 100 mM;
b
[5] = 1 mM; 25–30 1C; 3–4 h. Isolated yields. Values in the
parentheses are those obtained in CH2Cl2. 100 mmol scale. [1] =
c
d
e
[2] = 1000 mM; [5] = 1 mM; 30 1C; 24 h. 1 : 1 H2O–CH3OH was
used as the solvent.
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12 The [Cp*Ru(CH3CN)3]PF6/4-CH3C6H4SO3H is reported to show
a high reactivity (phenylmethanethiol (0.07 mmol), allyl alcohol
(0.07 mmol), catalyst (0.0035 mmol), CD3CN (0.5 mL): 11 min,
quant). See, ref. 9.
near-irreversibility of allyl sulfide formation, unlike allyl ether
formation. Studies aimed at determining the mechanism of the
reaction as well as its application to asymmetric synthesis are
currently underway in our laboratory.
ꢀc
This journal is The Royal Society of Chemistry 2010
3998 | Chem. Commun., 2010, 46, 3996–3998