Utilization of o-[(E)-2-trimethylsilyl-2-iodovinyl]phenylthio derivatives as carbon radical precursors by anchimeric approach

Article abstract of DOI:10.1055/s-2001-12338

o-[(E)-2-Trimethylsilyl-2-iodovinyl]phenylthio derivatives have been introduced as effective precursors for the generation of carbon centered radicals even in the presence of certain nucleophiles; this provides useful information about the structural requirement for inducing an efficient anchimeric effect under mild conditions.

Full text of DOI:10.1055/s-2001-12338

LETTER
541
Utilization of o-[(E)-2-Trimethylsilyl-2-iodovinyl]phenylthio Derivatives as
Carbon Radical Precursors by Anchimeric Approach
Takashi Ooi, Mayumi Furuya, Daiki Sakai, Yasutoshi Hokke, Keiji Maruoka*
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Department of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan
Fax +81-75-753-4041; E-mail: maruoka@kuchem.kyoto-u.ac.jp
Received 19 December 2000
ical into facilitating the subsequent homolytic cleavage of
a carbon-sulfur bond;4 this has stimulated our interest in
the structural requirement to induce such an anchimeric
effect. Here we wish to disclose that o-[(E)-2-trimethylsil-
Abstract: o-[(E)-2-Trimethylsilyl-2-iodovinyl]phenylthio deriva-
tives have been introduced as effective precursors for the generation
of carbon centered radicals even in the presence of certain nucleo-
philes; this provides useful information about the structural require-
ment for inducing an efficient anchimeric effect under mild yl-2-iodovinyl]phenylthio derivatives of type 2 exhibit
conditions.
the similar reactivity, thereby enabling rapid generation of
carbon centered radicals under mild reaction conditions
(Scheme 1).
Key words: anchimeric effect, carbon radicals, cyclizations, reduc-
tions, vinyl iodides
As already reported,3 radical reduction of simple phe-
nylthio derivative with Bu3SnH (1.2 equiv) and catalytic
amount of Et3B (5 mol%)5 in toluene at -78 °C for 30 min
resulted in almost total recovery of the starting material
(Scheme 2).6 In sharp contrast, however, treatment of 2
with Bu3SnH/cat. Et3B in toluene at -78 °C for 30 min
gave rise to the corresponding reduction product 3 in 91%
isolated yield. This eminent reactivity stems from the rap-
id intramolecular radical translocation with the preferable
formation of a five-membered heterocycle as illustrated in
Scheme 2.7,8
Along with the integration of free radical chemistry into
the general knowledge of organic reactions from the con-
ceptual as well as methodological viewpoints, radical re-
actions have become a valuable and even indispensable
tool for both the selective bond-forming and cleavage re-
actions, which play an important role in the construction
of biologically active molecules with complex struc-
tures.1,2 Although alkyl halides, especially iodides and
bromides, are generally used as precursors to generate
various carbon radicals, such reactive alkyl halides have
an inherent tendency of suffering from undesired reaction
processes represented by displacement with internal and/
or external nucleophiles. Recently, we reported our own
solution to this longstanding problem by introducing o-(o-
iodophenyl)phenylthio derivatives 1 as highly effective
carbon radical precursors with various functional group
compatibility.3 One of the key elements of our approach is
the employment of a biphenyl framework that assures the
strong participation of an initially generated biphenyl rad-
5 mol% Et3B
Bu3SnH
CH3
Ph
O
X
Ph
O
CH2Cl2
3
-78 °C, 30 min
X = SPh
~0%
(97% recovery)
S
I
91%
(2)
SiMe3
R
S
S
•
+
R
S
R
S
R •
SiMe3
SiMe3
cat. Et3B
Bu3SnH
I
[R = (CH2)5OCH2Ph]
Scheme 2
1
S
Based on the results, we synthesized several vinyl iodide
analogues 4-6 and evaluated their ability as a carbon rad-
ical precursor in the radical reduction. Sequential addition
of Bu3SnH (1.2 equiv) and catalytic Et3B (5 mol%) at
-78 °C to a solution of 4 in toluene and subsequent stirring
at -78 °C for 2 h and at -40 °C for 1 h gave only a trace
amount of the desired 3 with predominant formation of 7
as a result of simple vinyl iodide reduction. Although the
yield of 3 was improved to 36% when the reaction was
+
R
R
S
R
I
S
I
SiMe3
2 [R = (CH2)5OCH2Ph]
Scheme 1
Synlett 2001 No. 4, 541–543 ISSN 0936-5214 © Thieme Stuttgart · New York

542
T. Ooi et al.
LETTER
performed at room temperature, 7 was still obtained as a
major product. Reaction of 5 with Bu3SnH/cat. Et3B, in
contrast, furnished 3 in 82% yield, though stirring for 1 h
at room temperature was required. These results revealed
that the trimethylsilyl group played a role in enhancing the
reactivity of vinyl iodide, and the conjugation with aro-
matic moiety was necessary to facilitate the participation
of initially generated vinyl radical into the subsequent ho-
molytic S-C bond cleavage process. This observation
seems consistent with the fact that attempted reaction of 6,
which possesses an additional methylene carbon between
the sulfur atom and aromatic ring, afforded unknown
compounds under similar conditions.9
Me3Si
I
S
R
SPh
Ph
N
Ph
N
R
8a : R = CH2Ph
8b : R = H
11a : R = CH2Ph
11b : R = H
110 mol% Et3B
Bu3SnH
toluene, -78 °C, 1 h
10 mol% Et3B
Bu3SnH
toluene, -78 °C, 1.5 h
cat. DMAP
Ac2O, Py
N
Ph
N
Ph
Ph
Ac
R
S
R
S
9
10
83% (E/Z = 56:44)
88% (E/Z = 56:44)
I
Scheme 3
4
7
R
I
R
S
S
H
Acknowledgement
SiMe3
I
5
6
This work was partially supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Science, Sports and Cul-
ture, Japan.
[R = (CH2)5OCH2Ph]
Synthetic utility of the o-[(E)-2-trimethylsilyl-2-iodovi-
nyl]phenylthio group was highlighted by the remarkably
facile intramolecular radical cyclization of amino deriva-
tives 8. Although simple phenylthio group is usually em-
ployed as a radical precursor in this type of reaction
mainly due to the difficulty in preparation and isolation of
the corresponding iodide, it unfortunately diminishes the
reactivity to a great extent. For instance, attempted reac-
tion of 11a with Bu3SnH/cat. Et3B in toluene at -78 °C for
1.5 h showed no evidence of the product formation and re-
sulted in 81% recovery of the starting material.10 Howev-
er, smooth cyclization of 8a was observed under the
similar reaction conditions producing the desired cyclic
amine 9 in 83% yield. Moreover, the cyclization of sec-
ondary amino derivative 8b also appeared feasible with
the present approach giving the corresponding cyclic
amide 10 in 88% yield after acetylation in the usual man-
ner, whereas none of the cyclization product was obtained
from the simple phenylthio derivative 11b (Scheme 3).
References and Notes
(1) Reviews: (a) B. Giese, Radicals in Organic Synthesis:
Formation of Carbon-Carbon Bonds; Pergamon Press: New
York, 1986. (b) G. Pattenden, Chem. Soc. Rev. 17, 361, 1988.
(c) D. P. Curran, In Comprehensive Organic Synthesis, Trost,
B. M.; Fleming, I.; Semmelhock, M. F. Eds.; Pergamon Press:
Oxford, 1991; Vol. 4, p. 715. (d) C. P. Jasperse, D. P. Curran,
and T. L. Fevig, Chem. Rev. 91, 1237, 1991. (e) W. B.
Motherwell, D. Crich, Free-Radical Reactions in Organic
Synthesis, Academic Press: London, 1992. (f) A. L. J.
Beckwith, Chem. Soc. Rev. 22, 143, 1993. (g) G. G. Melikyan,
Synthesis 833, 1993. (h) G. A. Molander, C. R. Harris, Chem.
Rev. 96, 307, 1996. (i) B. B. Snider, ibid. 96, 339, 1996. (j) S.
Z. Zard, Angew. Chem. Int. Ed. Engl. 36, 673, 1997.
(2) (a) B. Giese, Angew. Chem. Int. Ed. Engl. 28, 969, 1989.
(b) N. A. Porter, B. Giese, D. P. Curran, Acc. Chem. Res. 24,
296, 1991. (c) T. V. RajanBabu, ibid. 24, 139, 1991.
(d) W. Smadja, Synlett 1, 1994. (e) D. P. Curran, N. A. Porter,
and B. Giese, Stereochemistry of Radical Reactions:
Concepts, Guidelines, and Synthetic Applications; VCH:
Weinheim, 1996.
A typical experimental procedure is as follows (radical re-
duction of 2): To a solution of 2 (290 mg, 0.57 mmol) in
toluene (5.7 mL) was added Bu3SnH (183 L, 0.68 mmol)
and Et3B (28 L, 28 mol) sequentially at -78 °C under ar-
gon. The reaction was monitored by thin-layer chroma-
tography (TLC) analysis. The mixture was stirred at
-78 °C for 30 min and poured into saturated NaHCO3. Ex-
tractive workup was performed with ether and the organic
extracts were dried over Na2SO4. Evaporation of solvents
and purification of the residual oil by column chromatog-
raphy on silica gel (ether/hexane = 1:50 as eluent) fur-
nished 3 (92.3 mg, 0.52 mmol, 91% yield) as a colorless
oil.
(3) T. Ooi, M. Furuya, D. Sakai, K. Maruoka, Adv. Synth. Catal.
in press.
(4) For the pioneering work on the utilization of intramolecular
homolytic substitution at sulfur for the generation of acyl
radicals, see: (a) D. Crich, Q. Yao, J. Org. Chem. 61, 3566,
1996. (b) D. Crich, X. L. Hao, J. Org. Chem. 62, 5982 , 1997.
For other radical translocation methodologies, see: D. P.
Curran, A. C. Abraham, H. Liu, J. Org. Chem. 56, 4335, 1991;
D. P. Curran, A. C. Abraham, Tetrahedron 49, 4821, 1993.
(5) H. Nozaki, K. Oshima, K. Utimoto, J. Am. Chem. Soc. 109,
2547, 1987.
(6) Only a trace amount of the desired reduction product 3 was
obtained even when the reaction was carried out in refluxing
benzene in the presence of cat. AIBN for several hours.
Synlett 2001, No. 4, 541–543 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Utilization of o-[(E)-2-Trimethylsilyl-2-iodovinyl]phenylthio Derivatives
543
(7) Although we utilized (E)-vinyl iodide, (Z)-isomer would also
exhibit similar reactivity because configurationally isomeric
vinyl radicals with bent structure rapidly interconvert through
a linear structure shown in Scheme 2.8 See: (a) B. Giese, J. A.
Gonzalez-Gomez, S. Lachhein, J. O. Metzger, Angew. Chem.
Int. Ed. Engl. 26, 479, 1987. (b) T. Ooi, Y. Hokke, E. Tayama,
and K. Maruoka, Tetrahedron 57, 135, 2001.
(9) Abstraction of the benzylic proton by the initially generated
vinyl radical seemed to be involved.
(10) Exposure of 11a to Bu3SnH/cat. AIBN in refluxing benzene
for 2.5 h afforded a deteriorated mixture.
(8) A linear structure of the trimethylsilyl vinyl radicals has been
previously claimed. See, for example: P. C. Montevecchi, M.
L. Navacchia, P. Spagnolo, Tetrahedron 53, 7929, 1997.
Article Identifier:
1437-2096,E;2001,0,04,0541,0543,ftx,en;Y20700ST.pdf
Synlett 2001, No. 4, 541–543 ISSN 0936-5214 © Thieme Stuttgart · New York