Palladium/Light induced radical alkenylation and allylation of alkyl iodides using alkenyl and allylic sulfones

Article abstract of DOI:10.1021/acs.orglett.7b04050

Alkenylation and allylation of alkyl iodides with alkenyl and allyl sulfones, respectively, took place under Pd/photoirradiation system. The initial alkyl radical, derived from a single electron transfer between Pd(0) and RI, underwent the title transformations. Pd(0) was regenerated through a reductive elimination of PhSO₂PdI, which is formed by the combination of the sulfonyl radical and the palladium radical. The addition of water was effective, presumably by pushing the equilibrium through hydrolysis of PhSO₂I.

Full text of DOI:10.1021/acs.orglett.7b04050

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Palladium/Light Induced Radical Alkenylation and Allylation of Alkyl
Iodides Using Alkenyl and Allylic Sulfones
Shuhei Sumino,†,§ Misae Uno,† Hsin-Ju Huang,‡ Yen-Ku Wu,‡ and Ilhyong Ryu*,†,‡
†Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
‡Department of Applied Chemistry, National Chiao Tung University, Hsinchu, Taiwan
S
* Supporting Information
ABSTRACT: Alkenylation and allylation of alkyl iodides with alkenyl and allyl sulfones, respectively, took place under Pd/
photoirradiation system. The initial alkyl radical, derived from a single electron transfer between Pd(0) and RI, underwent the
title transformations. Pd(0) was regenerated through a reductive elimination of PhSO2PdI, which is formed by the combination
of the sulfonyl radical and the palladium radical. The addition of water was effective, presumably by pushing the equilibrium
through hydrolysis of PhSO2I.
eq 3).4 Thus far, a number of alkenylating reagents has been
ransition metal-catalyzed cross-coupling reactions of aryl
examined in different types of radical alkenylation reactions,
Tand alkenyl halides constitute a useful means for C−C bond
halides.1,2 A radical-based formal Mizoroki−Heck reaction of
alkyl halides involves the addition of a carbon radical to a
which include alkenyltins,5 alkenylsulfides,6 alkenyl sulfones,7,8
forming processes, and nowadays, much effort has been directed
nitroalkenes,9 alkenylindiums,10 alkenylgalliums,10b alkenyl
to expand the reaction scope by engaging sp3-hybridized alkyl
chlorides,11 and alkenyl bromides.12−14 Also, the radical allylation
reactions following a related mechanistic pathway have been
investigated (Scheme 1, eq 2).4,6,7e,15 As part of our research
heteroatom-substituted alkene followed by a β-scission pathway
program in developing Pd/light-initiated radical reactions,16,17
(Scheme 1, eq1).3 Inorder tosustain theradicalchain, theleaving
we recently reported a coupling reaction of alkyl iodides and
radical Y• has to trigger a propagation sequence, and
alkenyl bromides with Hanztsch ester as a reducing agent
(Scheme 1, eq 4).18 In this reaction system, the single electron
hexabutylditin is often used to facilitate this process (Scheme 1,
transfer (SET) reaction between alkyl iodides and Pd(0) under
Scheme1. Radical Alkenylation andAllylation ofAlkyl Halides
photoirradiation is responsible for the generation of the initial
alkyl radical, and Hanztsch ester serves an essential role in
reducing Pd(II)IBr to Pd(0) to sustain radical chain.
We envisioned that if alkenyl phenyl sulfones are employed in
lieu of alkenyl bromides, the reductive elimination of Pd(II)-
ISO2Ph would be much more facile than the case with
Pd(II)IBr,19 thus obviating the need of an additional reductant
fortheregenerationofPd(0)(Scheme1, eq6). Thesameconcept
would promisingly be extended to the allylation sequence using
allyl sulfones7e,20,21 (Scheme 1, eq 5). Herein, we report the Pd/
light-induced synthesis of alkenylated or allylated alkanes from
the corresponding sulfone precursors.
We first studied the coupling reaction of iodocyclohexane 1a
and phenyl styryl sulfone 2a (Table 1). When a benzene solution
of 1a and 2a was irradiated by a xenon lamp in the presence of
PdCl2, LiCl, t-BuNC, and Et3N, the desired product 3aa was
obtained in 39% yield (Table 1, entry 1). Interestingly, the
Received: December 29, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b04050
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of Reaction Conditions
Table 2. Radical Alkenylation of Alkyl Iodides 1 with Alkenyl
Sulfones 2
a
b
entry
2a (equiv)
Et3N (equiv)
solvent (mL)
yield (%)
1
2
3
4
5
6
1.5
1.5
2.0
1.5
1.5
1.5
1.5
1.5
1.5
2
2
2
2
3
0
2
2
2
C6H6 (2)
− (39)
65 (73)
C6H6/H2O (2/1)
C6H6/H2O (2/1)
C6H6/H2O (2/2)
C6H6/H2O (2/1)
C6H6/H2O (2/1)
C6H6/H2O (2/1)
C6H6/H2O (2/1)
C6H6/H2O (2/1)
60 (74)
64
69
0
c
7
− (56)
0
d
8
e
9
0
a
Reaction conditions: alkyl iodide 1a (0.5 mmol), alkenyl sulfone 2a
(0.75 mmol), PdCl2 (5 mol %), t-BuNC (20 mol %), LiCl (20 mol %),
Et3N (1 mmol), C6H6 (2 mL), H2O (1 mL), 16 h, hν (SolarBox (Xe,
b
800 W/m2), Pyrex). Isolated yield; number in parentheses refers to
c
d
NMR yield. With Hantzsch ester (0.75 mmol). Without PdCl2, LiCl,
e
or t-BuNC. Under dark conditions.
addition of H2O increased the yield to 65% (Table 1, entry 2).
There was no further improvement of the yield by increasing the
amount of 2a, water, or Et3N (Table 1, entries 3−5). Et3N was
necessary for the reaction to proceed (Table 1, entry 6). The
additionofHantzschesterdidnotimprovetheyield, incontrastto
our previous report on the alkenylation with alkenyl bromides18
(Table 1, entry 7). In the absence of PdCl2, LiCl, and t-BuNC, no
alkenylation reaction took place (Table 1, entry 8). The reaction
didnotproceedunderdarkconditions(Table1, entry9). Inorder
to confirm the involvement of a radical chain process, the reaction
of 1a with 2a was carried out in the presence of TEMPO. As our
expectation, cyclohexyl-TEMPO was formed in 9% yield, and no
alkenylation reaction took place.
With the optimized conditions in hand, we set out to examine
the scope of the radical alkenylation reaction (Table 2). The
reactions of primary, secondary, and tertiary alkyl iodides 1a−f
with 2a gave the corresponding alkenylated alkanes 3aa−3fa in
good to moderate yields (Table 2, entries 1−6). Although the
reaction of nitro-substituted sulfone 2b failed to deliver the
product (Table 2, entry 7), we were delighted to find that a wide
range of substituted 2-aryl alkenyl sulfones 2c−2i are compatible
with the alkenylation reaction (Table 2, entries 8−14). It is
noteworthy that chloro and bromo substituents on the arene
moieties remain intact and therefore could be further function-
alized after the radical alkenylation event (Table 2, entries 11−
14). The reaction of 1a with trans-1,2-bis(phenylsulfonyl)ethene
2j provided the conjugated sulfone 3aj albeit in moderate yield
(Table 2, entry 15). The reaction of 1a with ethyl (E)-3-
(phenylsulfonyl)acrylate 2k furnished conjugated ester 3ak in
low yield; presumably, 3ak serves as a good radical trap for
undesired addition reactions thus giving rise to numerous side
products (Table 2, entry 16).
a
Reaction conditions: alkyl iodide 1 (0.5 mmol), alkenyl sulfone 2
(0.75 mmol), PdCl2 (5 mol %), t-BuNC (20 mol %), LiCl (20 mol %),
Et3N (1.5 mmol), C6H6 (2 mL), H2O (1 mL), 16 h, hν (SolarBox (Xe,
b
800 W/m2), Pyrex). NMR yield in crude mixture.
transformations isclearly displayed inthesynthesis of 5ga−5ja. 2-
Phenyl-substituted ally sulfone 4b was also applicable resulting in
the formation of 5ab and 5bb in good yields.
We then sought to integrate the radical alkenylation and
allylation methods into three-component coupling reactions
(Scheme 3). In the event, we showed the reaction engaging ethyl
iodoacetate 1k, 1-octene 6a, and sulfone 2a gave the coupling
product 7a in a yield of 59% (Scheme 3, eq 7). As for the
chemoselectivity ofthis reaction, initiallyformed α-acetate radical
is considered to be electrophilic and therefore preferentially adds
to 1-octene 6a rather than to alkenyl sulfone 2a; the resulting
We next explored the radical allylation of alkyl iodides with allyl
sulfones under the Pd-catalyzed photoirradiation system
(Scheme 2). With either a xenon lamp (800 W/m2) (condition
A) or a black light bulb (15 W, wave peak: 365 nm) (condition B)
asthelightsource, thecouplingreactionofalkyliodides1andallyl
sulfone 4a gave the corresponding allylation products 5aa−5ja in
good yields. The wide functional group compatibility of these
B
DOI: 10.1021/acs.orglett.7b04050
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
The mechanism of the radical alkenylation with alkyl iodides 1
and alkenyl sulfones 2 is illustrated in Scheme 4. First, SET
Scheme 2. Radical Allylation of Alkyl Iodides 1 with Allyl
Sulfones 4
a
Scheme4. ProposedMechanismfortheAlkenylationReaction
proceeds from photoexcited Pd(0) to the alkyl iodide to generate
an alkyl radical (R•)and a PdIradical. Thealkyl radical adds tothe
alkene of sulfone 2, and then subsequent β-scission takes place to
give concomitantly the allylated product 3 and sulfonyl radical
(PhO2S•). The combination of sulfonyl radical and Pd(I)
generates sulfonyl palladium iodide A. We assume that Pd(I)
must be persistent, which would allow selective coupling between
Pd(I) and PhSO2 radical. Reductive elimination of A resulted in
the formation of PhSO2I24 and Pd(0). To facilitate the catalytic
process, the addition of water and Et3N assists hydrolysis of
PhSO2I, preventing the reversible reaction toward the inter-
mediate A.
a
Reaction conditions: condition A, alkyl iodide 1 (0.5 mmol), allyl
sulfone 4 (0.75 mmol), PdCl2 (5 mol %), t-BuNC (20 mol %), LiCl
(20 mol %), Et3N (1.5 mmol), C6H6 (2 mL), H2O (1 mL), 16 h, hν
(SolarBox (Xe, 800 W/m2), Pyrex); condition B, alkyl iodide 1 (0.5
mmol), allyl sulfone 4 (0.75 mmol), PdCl2 (6 mol %), t-BuNC (20
mol %), LiCl (20 mol %), Et3N (1.5 mmol), MeCN (1 mL), H2O (1
mL), 6 or 12 h, hν (black light, 15 W, Pyrex). Alkyl iodide 1a (1.1
equiv), hν (black light, 15 W × 2, Pyrex). Allyl sulfone 4b (1.0 equiv),
b
c
hν (black light, 15 W × 2, Pyrex).
In summary, we have demonstrated a new protocol for the
radical alkenylation and allylation of alkyl iodides with phenyl
sulfone compounds under a Pd/photoirradiation system in which
radical intermediate and palladium species work cooperatively.
This reaction system is also applicable to the three-component
coupling reactions including the radical carbonylative trans-
formation. Facile reductive elimination of arylsulfonyl iodide
from the Pd center obviates the use of reducing agent to
regenerate Pd(0). Further research to explore transition metal/
radical cooperative systems is currently underway in this
laboratory.
Scheme 3. Three-Component Coupling Reactions
ASSOCIATED CONTENT
* Supporting Information
■
S
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.7b04050.
Typical experimental procedure and full characterization
data for 3aa−3aj, 5, and 7−9 (PDF)
radical is nucleophilic and adds to electron-deficient 2a to give
7a.22 Analogously, the three-component reaction of perfluor-
oalkyl iodide 1l, cyclooctene 6b, and 2c gave 7b in 63% yield
(Scheme 3, eq 8). Nucleophilic 2-indanyl radical derived from 1c
first underwent the addition to methyl acrylate 6c, and then the
resultingelectrophilicradicalreactedwithallylsulfone4ctogive8
in 55% yield (Scheme 3, eq 9). A three-component radical
carbonylative−alkenylation16,23 reaction of an alkyl halide was
realized giving enone 9 in 41% yield (Scheme 3, eq 10).16b
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ryu@c.s.osakafu-u.ac.jp.
ORCID
Shuhei Sumino: 0000-0002-7109-8995
Yen-Ku Wu: 0000-0002-9269-7444
Ilhyong Ryu: 0000-0001-7715-4727
C
DOI: 10.1021/acs.orglett.7b04050
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Present Address
§Osaka Research Institute of Industrial Science and Technology,
1-6-50, Morinomiya, Osaka, Japan.
Letter
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
ThisworkwassupportedbyaGrant-in-AidforScientificResearch
(A) (no. 26248031) from the JSPS and Scientific Research on
Innovative Areas 2707 Middle molecular strategy (no.
15H05850) from the MEXT.
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DOI: 10.1021/acs.orglett.7b04050
Org. Lett. XXXX, XXX, XXX−XXX