Radico-catalysis: Possible involvement of a cobalt(II) complex in the free radical reactions of sulfur functions

Article abstract of DOI:10.1002/hc.1033

A cobalt(II) complex is paramagnetic and can be coordinated with sulfur functions; the coordination complex delocalizes an unpaired electron from cobalt(II) to the sulfur functions such as thioester and vinyl sulfide. Thus, the generation of partial unpaired electron density on the sulfur functions induces or modifies the reactions of the organo free radical containing the sulfur function.

Full text of DOI:10.1002/hc.1033

Heteroatom Chemistry
Volume 12, Number 4, 2001
Radico-Catalysis: Possible Involvement of a
Cobalt(II) Complex in the Free Radical
Reactions of Sulfur Functions
Masaru Tada
Department of Chemistry, Advanced Institute for Science and Engineering, Waseda University,
Shinjuku, Tokyo 169-8555, Japan
Received 27 July 2000; revised 25 September 2000
Acid or base catalysis generates a partial elec-
tron-pair hole (Equation 1) or a partial electron-pair
pool (Equation 2), respectively. In accord with this
concept, radico-catalysis can be defined as the gen-
eration of a partial density of an unpaired electron
in the substrate molecule (Equation 3). We have pre-
viously shown the coordination interaction between
a paramagnetic cobalt(II) complex and sulfur func-
ABSTRACT: A cobalt(II) complex is paramagnetic
and can be coordinated with sulfur functions; the co-
ordination complex delocalizes an unpaired electron
from cobalt(II) to the sulfur functions such as thioes-
ter and vinyl sulfide. Thus, the generation of partial
unpaired electron density on the sulfur functions in-
duces or modifies the reactions of the organo free rad-
ical containing the sulfur function. ᭧ 2001 John Wi-
tions such as sulfide and thioester as depicted in
ley & Sons, Inc. Heteroatom Chem 12:204–208, 2001
Scheme 2 [1].
dם
dמ
dם
d•
Acid catalysis:RXםAcid→R –X–Acid
(1)
(2)
(3)
dמ
Base catalysis:RXםBase→R –X–Base
INTRODUCTION
d•
Radico-catalysis:RXםRadical→R –X–Rad
We have reported on the radical reactions of sulfur-
containing functions in which a cobalt complex, an
organo(pyridine)dimethylglyoximatocobalt [a coba-
loxime, hereafter; e.g., methylcobaloxime 1 (RЈ ס
Me)] (Scheme 1), coexists in the reaction system.
Discussions have been focused on the effect of the
interaction between the free radical intermediate
and the paramagnetic cobalt(II) complex. In this ac-
count, I plan to summarize these reactions by the
concept of radico-catalysis.
This article is dedicated to Professor Emeritus Naoki Inamoto
of the University of Tokyo on the occasion of his 72nd birthday.
Contract Grant Sponsor: Project Research B, Advanced Re-
search Institute for Science and Engineering of Waseda Univer-
sity.
Contract Grant Sponsor: Annual Project Waseda University.
Contract Grant Sponsor: Grant-in-Aid for Scientific Research,
Ministry of Education, Culture, and Sports of Japan.
᭧ 2001 John Wiley & Sons, Inc.
SCHEME 1
204

Radico-Catalysis: Possible Involvement of a Cobalt(II) Complex in the Free Radical Reactions of Sulfur Functions 205
This sulfur-coordinated complex is a 19-electron
with the thioester 4 (Scheme 4) [3]. This reaction is
considered to be a radical substitution by the methyl
radical on the sulfur that has become more radico-
philic by the cobalt coordination (see Scheme 3a and
A in Scheme 4). The use of methyl-tetraphenylcob-
aloxime 2 [4] or methyl-BF2-cobaloxime 3 [5] instead
of methylcobaloxime 1 gave the methylsulfide 5 only
in a small or trace amount, respectively, under the
same conditions as those of to the reactions of cob-
aloxime 1.
Photolyses of methyl-tetraphenylcobaloxime 2
and methyl-BF2-cobaloxime 3, however, generate a
methyl radical more efficiently, judging from the for-
mation of methyl-TEMPO in the presence of TEMPO
[3c]. Four phenyl groups in the tetraphenylcobalox-
ime 2 orient perpendicularly to the planar dimethyl-
glyoximato ligand [4] and shield the coordination
site of cobalt for the sulfur. The BF2 groups in BF2-
cobaloxime 3 are more electronegative [6] than the
hydrogens in cobaloxime 1 and reduce the back do-
nation from the central cobalt(II) to the sulfur of the
thioester group. As described earlier, cobalt-sulfur
bonding is mostly attributable to the back donation
[1], and hence the BF2 groups diminish the coordi-
native interaction between the sulfur and cobalt(II)
complex (Figure 2).
complex, and the axial bond of (S–Co–N) consists of
a three-centered five-electron bond, which is rein-
forced by the back donation from cobalt(II) to vacant
d-orbitals of sulfur [1]. The unpaired electron on the
SOMO orbital of the three-center bond delocalizes
to the sulfur as depicted in Figure 1a.
The unpaired electron density thus formed on
sulfur delocalizes further to the r* orbital of the al-
kyl-carbonyl bond of a thioester (Figure 1b) or to the
p* orbital of a vinyl sulfide (Figure 1c) by r-hyper-
conjugation or p-conjugation, respectively. Thus, the
interaction between sulfur and a cobalt(II) complex
may alter the free radical reactivity of thioesters and
vinyl sulfides. This phenomenon may be defined as
radico-catalysis.
Herein, I will present (1) a free radical substitu-
tion on sulfur (Scheme 3a), (2) a thioester rearrange-
ment (Scheme 3b), and (3) an ortho-addition of an
alkyl radical to vinyl sulfides (Scheme 3c) by the con-
cept of radico-catalysis.
RESULTS AND DISCUSSIONS
Photolysis of methylcobaloxime 1 generates a pair of
methyl and cobaloxime(II) radicals [2], and the for-
mer radical gives the methyl sulfide 5 by the reaction
FIGURE 1 SOMO(S–Co–N) and its conjugation with r*/p*
orbitals of thioester and vinyl sulfide.
SCHEME 2
SCHEME 3

206 Tada
Methylcobaloximes 1 having para-substituted
35/51). The photolysis of a cobaloxime derivative 6
(Xס[Co]L; Lס4-t-BuPy) (entry 4) gave a similar re-
sult as shown in entry 3 (7/8/9/10 ס 0.0/16/26/58). In
the latter two reactions, the intermediate radical B
(Scheme 5) coexists with cobaloxime(II), and both
the radical substitution to give 10 and rearrange-
ment with migration of the thioester group to give 9
are stimulated by the cobaloxime(II), (see 10/8 and
9/8 in Scheme 5) [8], because the rate of rearrange-
ment involving phenyl migration to give 8 is consid-
ered to be unaffected by the cobaloxime(II) and can
be used as an internal clock. These behaviors are ex-
plained by the induced free radical substitution on
sulfur (Scheme 3a), and the activation of the alkyl-
acyl bond for the thioester rearrangement as de-
picted in Scheme 3b.
pyridines as axial ligands react in a similar manner,
and the complex having the less basic ligand showed
greater reactivity (Scheme 4) [3c]. The trans-effect of
a pyridine derivative of weaker basicity induces
more donative and hence less back-donative inter-
action to the cobalt-sulfur bond [7] (Figure 2). The
increased coordination interaction makes the sulfur
more radicophilic and induces more free radical
substitution.
Next, we discuss radical rearrangements involv-
ing phenyl and thioester group migrations shown in
Scheme 5 [8] and Table 1. Stannyl radicals, gener-
ated as shown in Table 1, abstract the bromine atom
from bromide 6 to produce the radical B (entry 1 and
2). In entry 1, the radical B is reduced by the stan-
nane to give product 7 or undergoes rearrangement
with migration of the phenyl group to give product
8 (YסH, CH3) in a comparable ratio. However, the
thioester migration from B to give 9 is only a minor
process (7/8/9 ס 40/53/7). The use of a distannane
(entry 2) instead of the stannane gave similar results
(7/8/9 ס 37/53/10) although the reaction is sluggish
and a considerable amount of the starting material
was recovered intact.
Lastly, an intramolecular ipso/ortho addition of
a free radical to vinyl sulfides is discussed. A ben-
zothiophene derivative 11 was treated with triphen-
ylstannane or triphenylstannylcobaloxime to give
the results depicted in Scheme 6 and Table 2.
The products from the sulfanyl radical E
The reaction with triphenylstannylcobaloxime
(entry 3) is again sluggish, but evidently the ratio of
thioester/phenyl migration increased and the direct
alkyl substitution on the sulfur to give 10 became a
major process (7/8(YסCH2)/9(YסCH2)/10 ס 2.0/12/
SCHEME 4 The reaction was stopped before completion to
estimate the relative reactivity of methylcobaloximes (1), and
the starting material 4 was recovered under the reaction con-
ditions.
FIGURE 2 Coordinative interaction between Co(II) and sul-
fur.
TABLE 1 Radical Rearrangement of Phenyl vs. Thioester
Group
Entry
X
Conditions
Total Yield (%) 9/8 10/8
1
2
3
4
Br
Br
Br
Bu3SnH-AIBN
(Ph3Sn)2/hm
Ph3Sn[Co]L/hm
79
0.13 0.0
0.18 0.0
26a
25a
45a
2.9
1.7
4.3
3.6
[Co]L hm
aThe starting materials were recovered considerably.
SCHEME 5

Radico-Catalysis: Possible Involvement of a Cobalt(II) Complex in the Free Radical Reactions of Sulfur Functions 207
(Scheme 7) formed by the Smiles rearrangement
(ipso-addition) [9] are major ones in both cases, but
the formation of product 13 by direct ortho-addition
becomes feasible only with the coexistence of caba-
loxime(II) [10].
The reaction of the uracil derivative 17 (n ס 1)
with triphenylstannane (entry 1) gives a direct ad-
dition product 19 and products 21 and 22 after ipso-
addition in comparable amounts, 19/(21 ם 22) ס 42/
58 (Scheme 8 and Table 3) [10].
The reaction with triphenylstannylcobaloxime
(entry 2) [10], in which cobaloxime(II) coexists with
the intermediate radical F (Scheme 9), gave 20 as a
sole product. In the case of the uracil derivative 17
(n ס 2) (entry 3), only a direct reduction product (18,
n ס 2) was isolated from the reaction with the tri-
phenylstannane, but only the ortho-addition to give
20, besides hydrogen abstraction to give 18, takes
place with the triphenylstannylcobaloxime (entry 4)
[10]. Thus it is evident that the coexisting cobalox-
SCHEME 7
TABLE 2 Ortho vs. Ipso Free Radical Addition on Benzo-
thiophene
TABLE 3 Ortho vs. Ipso Free Radical Addition on Uracil
Product Composition (%)
Total
Yield (%) 12 13 14 15 16
Composition (%)
Total
Yield
18 19 20 21 22 (%)
Conditions
Entry n Conditions
Ph3SnH-AIBN/80ꢀC
Ph3Sn[Co]L/130ꢀC
96
87
11
—
—
20
74
—
—
80
15
—
1
2
3
4
1 Ph3SnH-AIBN/ 80ꢀC
1 Ph3Sn[Co]L/hm
2 Ph3SnH-AIBN/ 130ꢀC 100 —
—
—
42
— 49 9.0 91
— 100 —
—
—
—
73
82
75
—
—
2 Ph3Sn[Co]L/hm 37 — 63 —
SCHEME 6
SCHEME 8

208 Tada
ime(II) increases the radicophilicity of the vinyl moi-
ety of benzothiophene and uracil derivatives as de-
picted by Scheme 3c.
All the experimental findings described here sug-
gest the involvement of the cobalt(II) complex in the
free radical reactions of sulfur functions such as
thioester and sulfide. These effects are considered to
be the consequence of the coordination interaction
between sulfur and cobalt(II), which induces a par-
tial density of unpaired electron on the sulfur, and
also its hyperconjugation with an alkyl-acyl r-bond
as well as the p-conjugation with a vinyl group. This
is a new concept of radico-catalysis as discussed at
the beginning of this article and may be a guiding
principle in designing new radical reactions.
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SCHEME 9