Expanding the scope of Et3B/O2-mediated coupling reactions of O,Te-acetal

Article abstract of DOI:10.1016/j.tet.2016.04.023

Et₃B/O₂-mediated radical coupling reactions of O,Te-acetal 2 were explored using diverse electrophilic double bonds. Ethyl radical derived from Et₃B under air cleaved the C–Te bond of 2 to generate α-alkoxy bridgehead radi

Full text of DOI:10.1016/j.tet.2016.04.023

Tetrahedron xxx (2016) 1e10
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Expanding the scope of Et3B/O2-mediated coupling reactions of
O,Te-acetal
,
,
Daigo Kamimura a b, Masanori Nagatomo a, Daisuke Urabe a, Masayuki Inoue a
*
a Graduate School of Pharmaceutical Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
b Research Center, Kaken Pharmaceutical Co., Ltd, 14, Shinomiya, Minamikawara-cho, Yamashina, Kyoto 607-8042, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Et3B/O2-mediated radical coupling reactions of O,Te-acetal 2 were explored using diverse electrophilic
double bonds. Ethyl radical derived from Et3B under air cleaved the CeTe bond of 2 to generate -alkoxy
Received 10 March 2016
Received in revised form 2 April 2016
Accepted 7 April 2016
Available online xxx
a
bridgehead radical I, which reacted with cycloalkenones, cycloalkylidenemalononitriles, allyl halides,
and imines at or below ambient temperature. These intermolecular reactions from O,Te-acetal 2 were
mild and versatile, and were superior to those of O,Se-acetal 1 in terms of efficiency and substrate scope.
A total of 14 new and nine improved coupling reactions are described, all of which realized the in-
stallation of the functionalized carbon units at the sterically hindered bridgehead position of
trioxaadamantane.
Keywords:
Radical reactions
CeC bond formation
Ó 2016 Elsevier Ltd. All rights reserved.
a
-alkoxy bridgehead radical
Organotellurium compounds
Triethylborane
1. Introduction
by slow addition of n-Bu3SnH and V-40 into the refluxing toluene
solution of 1. The generated nucleophilic radical I added to the
Radical-based CeC bond formations are powerful reactions for
assembling multiple-substituted carboskeletons, and have been
employed for the total syntheses of natural products.1 Carbon
radical species are highly reactive, yet electronically neutral, so they
are suitable for installation of sterically congested tri- and tetra-
substituted carbon centers without affecting polar functional
groups. In addition, because of their complementary nature, se-
quential use of radical and ionic processes offers great potential for
streamlining the construction of structurally complex organic
molecules.
electron-deficient double bond of 3a to form the second radical
intermediate II, which was then hydrogenated by n-Bu3SnH to af-
ford 7a and the stannyl radical. The a-alkoxy bridgehead radical
strategy has been further applied to the total syntheses of complex
natural terpenoids.4
Despite its efficiency for the intermolecular formation of hin-
dered bonds, transformation of O,Se-acetal 1 to 7a has several
drawbacks. First, tedious chromatography is required to remove
excess tin residue from the products.5 Second, unwanted reactions
originating from the use of n-Bu3SnH at elevated temperatures
competes to decrease the yield of the desired product (e.g., addition
of the stannyl radical to unsaturated bonds,6 or premature re-
duction of the radical intermediates).7 To improve the synthetic
utility of the bridgehead radical couplings, milder conditions
without use of the tin reagent are highly desirable.8
Our recent efforts have been directed toward the development of
radical-based coupling strategies for the synthesis of highly oxy-
genated natural products. We have been particularly interested in
the effective utilization of
a
-alkoxy bridgehead radicals as the key
-alkoxy bridgehead
intermediates.2,3 The advantageous features of
a
radicals include enhanced reactivity, minimized steric hindrance,
and the stereochemically predestined structure of the radical-
generating carbon center. In this context, the intermolecular re-
action between O,Se-acetal 1 and cyclopentenone 3a was developed
to connect the contiguous tri- and tetrasubstituted carbon centers of
To realize mild tin-free coupling, O,Te-acetal 2 was designed as
a more reactive radical precursor,9,10 and the combination of Et3B
and O2 was selected as a more versatile set of reagents (Scheme
1A).11 In this alternative scenario, Et3B would play three key
roles: radical initiation, reaction acceleration, and radical termi-
nation. Namely, Et3B, under an O2 atmosphere, would eject an ethyl
radical, which would homolytically cleave the CeTe bond of O,Te-
oxygenated carbocycle 7a (Scheme 1A).2a The radical at the
a-alkoxy
bridgehead position of the trioxaadamantane structure was formed
acetal 2 to generate a
-alkoxy bridgehead radical I.12 The smaller
bond dissociation energy (BDE) of the CeTe bond compared to that
of the CeSe bond should help facilitate the radical exchange
* Corresponding author. E-mail address: inoue@mol.f.u-tokyo.ac.jp (M. Inoue).
http://dx.doi.org/10.1016/j.tet.2016.04.023
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.
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2
D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
Table 1
Investigation of the reactivity of 1 and 2
Entry
Radical donor
Conditions
Yield (%)
1a
2b
3a
4c
2: Y¼TePh
1: Y¼SePh
1: Y¼SePh
1: Y¼SePh
Et3B, O2, CH2Cl2, 0 ꢀC
88
77
V-40, n-Bu3SnH, toluene, 110 ꢀC
Et3B, O2, CH2Cl2, 0 ꢀC
0d
Et3B, O2, n-Bu3SnH, toluene, 0 ꢀC
12e
a
Reaction conditions: 1 or 2 (1 equiv), 3a (3 equiv), Et3B (3 equiv), CH2Cl2 (0.1 M),
0
ꢀC, 15 min.
b
Reaction conditions: 1 (1 equiv), 3a (5 equiv), V-40 (0.6 equiv), n-Bu3SnH
(6 equiv), refluxing toluene (0.02 M). V-40 (0.2 equiv) and n-Bu3SnH were added by
syringe pump over 3 h, and the reaction mixture was stirred for additional 1 h
(Ref. 2a).
c
Reaction conditions: 1 (1 equiv), 3a (5 equiv), Et3B (0.6 equiv), n-Bu3SnH
(6 equiv), toluene (0.02 M), 0 ꢀC. Et3B (0.2 equiv) and n-Bu3SnH were added by
syringe pump over 3 h, and the reaction mixture was stirred for additional 1 h.
d
1 was recovered in 97% yield.
1 was recovered in 47% yield.
e
five-membered ring at the bridgehead position of the triox-
aadamantane structure.9a Thus, generation of the
a-alkoxy
bridgehead radical intermediate I and its coupling reaction both
occurred at 0 ꢀC to furnish the adduct 7a. The yield of the adduct 7a
(88%) in entry 1 was higher than that of 7a (77%) in entry 2, where
O,Se-acetal
1 was subjected to the previous conditions [3a
(5 equiv), n-Bu3SnH (6 equiv) and V-40 (0.6 equiv) in refluxing
toluene (0.02 M)]. O,Se-acetal 1 was completely inert under tin-free
conditions at 0 ꢀC (recovery of 1, 97%, entry 3). Even when n-
Bu3SnH was introduced to a mixture of 2 and Et3B under air at 0 ꢀC
to produce the stannyl radical,15 the efficiency of the reaction im-
proved only slightly, affording 7a in 12% yield (entry 4). These data
together clarified the greater reactivity of 2 as the radical precursor,
and the benefit of milder conditions using 2, Et3B, and O2 for the
coupling efficiency.
Scheme 1. (A) Coupling reactions of a-alkoxy bridgehead radical intermediate I de-
rived from O,Se-acetal 1 or O,Te-acetal 2. (B) Radical acceptors (3e6) used for coupling
reactions of O,Te-acetal 2. V-40¼1,1ʹ-azobis(cyclohexanecarbonitrile).
reaction from ethyl radical to I.13 Et3B also would function as
a Lewis acid toward the C]O bond of 3a, thereby decreasing the
LUMO energy level of the conjugated C]C double bond.14 Ac-
cordingly, addition of I to Et3B-activated 3a would be accelerated,
2.2. Coupling reactions of O,Te-acetal 2 with cycloalkenone or
cycloalkylidenemalononitrile derivatives
The reaction outcomes of O,Te-acetal 2 and O,Se-acetal 1 were
accessed further by using the four cycloalkenones (3bee, Table 2).
In doing so, 2 and 1 were separately submitted to their optimized
conditions (Et3B and O2 in CH2Cl2 at 0 ꢀC for 2, n-Bu3SnH, and V-40
in toluene at 110 ꢀC for 1). Cyclohexenone 3b, cycloheptenone 3c,
and cyclooctenone 3d all participated in the coupling reaction with
O,Te-acetal 2 by the action of Et3B and O2, giving rise to 7b, 7c, and
7d in 80, 78, and 87% yields, respectively (entries 1e3). Irrespective
of the ring size of the radical acceptor, the products 7b, 7c, and 7d
were formed in higher yields from 2 than from 1. Remarkably, the
yield of 7c with the seven-membered ketone was tripled by
switching the radical precursor 1 with 2 (entry 2), accentuating the
advantageous feature of the mild reaction system. The Et3B/O2-
promoted intermolecular addition of O,Te-acetal 2 to chiral cyclo-
and the resulting a-carbonyl radical II would in turn be captured by
Et3B to generate the boron enolate intermediate III. As the radical
reaction would be terminated by Et3B, this reaction system does not
require excess amount of hydrogen donor, and thus direct hydro-
genation of I would be prevented. Finally, hydrolysis of III would
afford the desired adduct 7a. In this report, the scope of Et3B/O2-
mediated coupling reactions of O,Te-acetal 2 was explored in detail.
O,Te-acetal 2 was consistently superior in reactivity to O,Se-acetal 1,
and was demonstrated to serve as an excellent precursor of a-alk-
oxy bridgehead radical I for intermolecular reactions with the four
structurally distinct acceptors (3, 4, 5 and 6), even at or below
ambient temperature (Scheme 1B).
2. Results and discussion
pentenone 3e proceeded from the opposite face of the bulky a-
oriented OTBS group, providing 7e as a single isomer (72%, entry 4).
The yield of 7e from 2 was again higher than that from 1.
Next, the 5-, 6-, 7- and 8-membered malononitriles 4aed were
2.1. Comparison of reactivity of O,Te-acetal 2 and
O,Se-acetal 1
utilized as acceptors, along with 2 or 1 as the precursor of the a-
First, the applicability of O,Te-acetal 2 to the reagent system of
Et3B and O2 below ambient temperature was validated (Table 1).
Upon treatment of a mixture of 2 and cyclopentenone 3a (3 equiv)
with Et3B (3 equiv) under air in CH2Cl2 (0.1 M) at 0 ꢀC (entry 1), the
radical coupling reaction smoothly proceeded to incorporate the
alkoxy bridgehead radical (Table 3). Coupling reactions using O,Te-
acetal 2 with cycloalkylidenemalononitriles 4aed with Et3B and O2
at 0 ꢀC linked the two functionalized carbocycles, producing the
adducts 8aed in 58, 88, 87, and 33% yields, respectively (entries
1e4). Significantly, the extremely hindered bond between the
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D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
3
Table 2
Table 3
Coupling reactions between 2 and cycloalkenones 3beea
Coupling reactions between 2 and cycloalkylidenemalononitriles 4aeda
Yieldb (%)
80 (56)
Entry
1
Radical acceptor
Product
Yieldb (%)
58 (54)
Entry
1
Radical acceptor
Product
4a
3b
8a
8b
8c
7b
7c
2
78 (26)
2
88 (72)
4b
4c
3c
3
4
87 (45)
72 (65)
3
4
87 (57)
3d
3e
7d
33c (27)
4d
7e
8d
a
a
Reaction conditions: 2 (1 equiv), 3bee (3 equiv), Et3B (3 equiv), CH2Cl2 (0.1 M),
Reaction conditions: 2 (1 equiv), 4aed (3 equiv), Et3B (3 equiv), CH2Cl2 (0.1 M),
ꢀC, 15 min.
0
ꢀC, 15 min.
0
b
b
Yields in parentheses represent results of coupling of O,Se-acetal 1 (1 equiv) and
Yields in parentheses represent results of coupling of O,Se-acetal 1 (1 equiv) and
3 (5 equiv) by using V-40 (0.6 equiv) and n-Bu3SnH (6 equiv) in refluxing toluene
(0.02 M) (Ref. 2a).
4 (5 equiv) by using V-40 (0.6 equiv) and n-Bu3SnH (6 equiv) in refluxing toluene
(0.02 M) (Ref. 2a).
c
Yield was determined by 1H NMR analysis.
tetrasubstituted and quaternary carbons was formed through in-
termolecular radical addition to the electron-withdrawing tetra-
substituted olefin of 4aed. Although O,Se-acetal 1 was used as the
starting material for the preparation of 8aed by means of n-Bu3SnH
and V-40, the yields were generally lower. Consequently, single-
step construction of the two contiguous tetrasubstituted carbons
at 0 ꢀC from O,Te-acetal 2 corroborated the power of the present
radical coupling strategy.
2.3. Radical-polar crossover reaction between O,Te-acetal 2
and 3f or 3g
The Et3B/O2-mediated coupling reactions of O,Te-acetal 2 were
shown to be a robust method for introduction of carbocycles at the
sterically congested bridgehead position of the trioxaadamantane
(Tables 1e3). To further increase molecular complexity in a single
step, we planned to utilize the boron enolate intermediate III for
the intramolecular aldol reaction with the aldehyde (Scheme 1A).
Namely, cycloalkenones 3f and 3g were designed to contain the
aldehyde within the molecules (Scheme 2). The boron enolate in-
termediate generated from 3f or 3g would participate in the aldol
reaction, prior to its protonation, to produce spiro-fused ring
system.9,16
Scheme 2. Synthesis of radical acceptors 3f and 3g. 9-BBN¼9-borabicyclo[3.3.1]non-
ane,
dppf¼1,1ʹ-bis(diphenylphosphino)ferrocene,
TBAF¼tetra-n-butylammonium
fluoride, TEMPO¼2,2,6,6-tetramethylpiperidine 1-oxyl.
product 13/16. The OTBDPS group of the elongated carbon chain of
13/16 was deprotected with TBAF to afford the primary alcohol 14/
17, which was then oxidized to the corresponding aldehyde 3f/3g
by applying TEMPO as a catalyst and PhI(OAc)2 as a co-oxidant.18
Upon treatment of 3f and 3g with 2 and Et3B under air at 0 ꢀC,
O,Te-acetal 2 indeed reacted with the trisubstituted olefin of 3f and
3g to produce 7f and 7g bearing the 5/5- and 5/6-membered spiro-
Compounds 3f and 3g were synthesized in three steps from 11
and 15, respectively (Scheme 2). Hydroboration of the terminal
alkene of 11/15 was followed by SuzukieMiyaura coupling17 with
12 using catalytic PdCl2(dppf) and K3PO4 to provide the coupling
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4
D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
fused rings, respectively, as a single stereoisomer (Scheme 3A).
Compound 7f was derivatized to p-bromobenzoate 18, and the
structures of 18 and 7g were determined by X-ray crystallographic
analysis, thereby establishing their stereochemistries (Scheme 3B).19
Thus, a single operation integrated the relative stereochemistry of
the two tertiary, one quaternary, and bridgehead tetrasubstituted
carbon centers. These reaction outcomes can be explained by
a radical-polar crossover mechanism. After generation of bridgehead
radical I from 2, I adds to the tri-substituted olefin of 3f/3g, sub-
sequently transforming to boron enolate IV by reaction with Et3B.
Then, the boron atom fixes the most sterically favorable 5/6-
membered transition state V. The new CeC bond stereoselectively
forms from V through an intramolecular aldol reaction to furnish 7f/
7g.20 It is noteworthy that the aldehyde group of 3f/3g served as
acceptor for the polar addition, but not for the radical addition,21
showing the high chemoselectivity of the present reaction.
2.4. Coupling reactions of O,Te-acetal 2 with allyl halide or
imine derivatives
Because of the high reactivity and chemoselectivity of the
present reaction system, we presumed that the scope of the radical
acceptors could be expanded from the electrophilic olefins in Tables
1e3 to the allyl halide and imine derivatives in Tables 4 and 5. The
five allyl halide derivatives 5aed (Table 4) are problematic sub-
strates for the radical reactions in general, because the carbon-
halogen bonds are potentially reactive under the conditions, and
the double bonds are less polarized in comparison to the carbonyl
conjugated olefins.22 In fact, the coupling reaction between O,Se-
acetal 1 and 2,3-dichloroprop-1-ene 5a using n-Bu3SnH and V-40
at 110 ꢀC afforded 9a only in 12% yield (entry 1), presumably due to
direct hydrogenation of the allylic chloride of 5a with n-Bu3SnH. In
contrast, treatment of O,Te-acetal 2 and 5a with Et3B and O2 at 0 ꢀC
led to formation of 9a in 79% yield through an SH20 reaction (entry
2). Consequently, ethyl radical derived from Et3B chemoselectively
activated the CeTe bond of 2 without cleaving the allylic CeCl bond
of 5a or the vinylic CeCl bonds of 5a and 9a.23 While reaction be-
tween 2 and allyl chloride 5ba proceeded smoothly to give 9b in
65% yield (entry 3), 2 added to 2-bromo-3-chloroprop-1-ene 5c
(71%) with retention of the vinylic CeBr bond (entry 4). The two
allylic bromides 5bb and 5d were submitted to the Et3B/O2 condi-
tions to produce the monosubstituted olefin 9b (57%, entry 5) and
the disubstituted olefin 9d (61%, entry 6), respectively. These re-
sults indicated that even scission of the weak allylic CeBr bond was
not the major pathway. Therefore, Et3B/O2-mediated radical con-
ditions effectively distinguished the CeTe bond from the CeCl/
CeBr bond.
Table 4
Coupling reactions between 2 with allyl halides 5aeda
Entry
Radical acceptor
Product
Yield (%)
1b
2
3
5a: R3¼Cl
5a: R3¼Cl
5ba: R3¼H
5c: R3¼Br
9a: R3¼Cl
9a: R3¼Cl
9b: R3¼H
9c: R3¼Br
12
79
65
71
4
5
6
5bb: R3¼H
5d: R3¼Me
9b: R3¼H
57
61
9d: R3¼Me
a
Reaction conditions: 2 (1 equiv), 5aed (5 equiv), Et3B (5 equiv), CH2Cl2 (0.1 M),
0
ꢀC, 15 min.
b
Reaction conditions: 1 (1 equiv), 5c (5 equiv), V-40 (0.6 equiv), n-Bu3SnH
(6 equiv), refluxing toluene (0.02 M). V-40 (0.2 equiv) and n-Bu3SnH were added by
syringe pump over 3 h, and the reaction mixture was stirred for additional 1 h.
Finally, the seven imine derivatives 6aeg were used as the
radical acceptors (Table 5). Entry 1 represents the negative control
experiment, in which O,Se-acetal 1 and Boc-protected imine 6a
were treated with n-Bu3SnH and V-40 at 110 ꢀC. As a result, re-
duction of the C]N double bond of 6a occurred to give the cor-
responding Boc-protected amine without formation of 10a,
suggesting the inadequateness of the stannyl radical-promoted
Scheme 3. (A) Synthesis of the spiro-fused ring system 7f/7g from O,Te-acetal 2 via
the radical-polar crossover reaction. (B) The structure confirmation of 7f and 7g by the
X-ray crystallographic analyses of 18 and 7g. DMAP¼N,N-dimethyl-4-aminopyridine.
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D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
5
Table 5
the sterically cumbersome bridgehead position of the triox-
aadamantane. In addition, the boron enolate intermediate formed
after addition of the bridgehead radical to the cyclopentenones was
intramolecularly attacked on the aldehyde moiety to stereo-
selectively generate the spiro-fused bicycles in a single operation.
Because of the high efficiency in connecting the hindered carbon
atoms and the high tolerance of the various polar and reactive
functional groups, the present method will serve as a pivotal
transformation for simplifying schemes for total synthesis of
structurally complex natural products. Further application of the
present coupling method to natural product synthesis is currently
underway in this laboratory.
Coupling reactions between 2 and imines 6aega
Entry
Radical acceptor
Product
Yield (%)
4. Experimental section
4.1. General
1b
2
3
6a: R4¼Boc
6a: R4¼Boc
6b: R4¼Ts
6c: R4¼Ph
10a: R4¼Boc
10a: R4¼Boc
10b: R4¼Ts
10c: R4¼Ph
0
93
76
60
All radical reactions using Et3B were carried out under air. The
other reactions sensitive to air or moisture were carried out under
argon atmosphere in dry solvents, unless otherwise noted. CH2Cl2,
THF and toluene were purified by Glass Contour solvent dispensing
system (Nikko Hansen & Co., Ltd., Japan). All other reagents were
used as supplied. Analytical thin-layer chromatography (TLC) was
performed using E. Merck Silica gel 60 F254 pre-coated plates
(0.25 mm). Preparative thin-layer chromatography (PTLC) was
performed using Merck silica gel 60 F254 pre-coated plates
(0.5 mm). Flash column chromatography was performed using
4
5
6
7
8
6d: R5¼H
10d: R5¼H
93
70
38
89
6e: R5¼Ph
6f: R5¼i-Bu
6g: R5¼CO2Et
10e: R5¼Ph
10f: R5¼i-Bu
10g: R5¼CO2Et
a
Reaction conditions: 2 (1 equiv), 6aeg (3 equiv), Et3B (3 equiv), CH2Cl2 (0.1 M),
room temperature, 15 min.
40e50 mm Silica Gel 60N (Kanto Chemical Co., Inc., Japan). Melting
b
Reaction conditions: 1 (1 equiv), 6a (5 equiv), V-40 (0.6 equiv), n-Bu3SnH
points were measured on Yanaco MP-J3 micro melting point ap-
paratus, and are uncorrected. Infrared (IR) spectra were recorded
on JASCO FT/IR-4100 spectrometer. 1H and 13C NMR spectra were
recorded on JNM-ECX-500 or JNM-ECS-400 spectrometer. Chemical
(6 equiv), refluxing toluene (0.02 M). V-40 (0.2 equiv) and n-Bu3SnH were added by
syringe pump over 3 h, and the reaction mixture was stirred for additional 1 h. O,Se-
acetal 1 was recovered in 28% yield, and the Boc-protected benzyl amine was ob-
tained in 63% yield based on 6a.
shifts were reported in ppm on the
d
scale relative to CHCl3 (
d
¼7.26
for 1H NMR), CDCl3
(
d
¼77.0 for 13C NMR), CD3OD (
d
¼49.0 for 13C
conditions. On the other hand, when the mixture of O,Te-acetal 2
and the same imine 6a was treated with Et3B under air at room
temperature, 10a was obtained in 93% yield (entry 2). In this re-
action, coordination of BEt3 to the C]N double bond of 6a and
subsequent conversion of the unstable amidyl radical to the boron
amide by BEt3 would have favorable effects on the facile cou-
pling.24 N-Ts imine 6b and N-Ph imine 6c reacted with O,Te-acetal
2 in the presence of Et3B and O2, leading to 10b (76%, entry 3) and
10c (60%, entry 4). Benzyloxyimine 6d was transformed to 10d in
93% yield under the same conditions (entry 5).25 The three ben-
zyloxyimines 6e, 6f, and 6g also served as acceptors, and their
reactions led to formation of benzyl amine 10e (70%, entry 6),
aliphatic amine 10f (38%, entry 7), and amino acid derivative 10g
(89%, entry 8). Single-step preparation of the functionalized amine
motif demonstrated here would have further application to the
efficient synthesis of structurally related pharmaceuticals and
natural products.
NMR) as internal references. Signal patterns are indicated as s,
singlet; d, doublet; t, triplet; m, multiplet; br, broaden peak. High
resolution mass spectra were measured on JEOL JMS-T100LP in-
strument (ESI or DART).
4.2. General procedure A: synthesis of compound 7a from
O,Te-acetal 2 [CAS: 1326319-34-9]
Et3B (1.03 M in hexane, 0.37 mL, 0.38 mmol) was added to
a solution of O,Te-acetal 29a (46.1 mg, 0.128 mmol) and cyclo-
pentenone 3a (32 m
L, 0.38 mmol) in CH2Cl2 (1.3 mL) at 0 ꢀC. The
reaction mixture was stirred for 15 min at 0 ꢀC, and was then di-
rectly subjected to flash column chromatography on silica gel (10 g,
hexane/EtOAc 1/1) to afford 7a (26.9 mg, 0.113 mmol) in 88% yield.
The analytical data of 7a were identical to those reported
previously.2a
4.3. Synthesis of compound 7a from O,Se-acetal 1
3. Conclusions
Et3B (0.99 M in hexane, 43
lution of O,Se-acetal 12a (33.0 mg, 0.106 mmol) and cyclopentenone
3a (46
L, 0.53 mmol) in toluene (2.0 mL) at 0 ꢀC. Two other so-
lutions of n-Bu3SnH (176 L, 0.636 mmol) in toluene (1.0 mL) and
Et3B (0.99 M in hexane, 21 L, 0.021 mmol) in toluene (1.0 mL) were
mL, 0.042 mmol) was added to a so-
In summary, we successfully expanded the scope of the radical
acceptors for the Et3B/O2-mediated coupling reactions of O,Te-
acetal 2. Compared to the previous method using O,Se-acetal 1, n-
Bu3SnH, and V-40 at 110 ꢀC, the present tin-free reaction system
significantly improved efficiency and chemoselectivity. Key fea-
m
m
m
simultaneously added to the above mixture at 0 ꢀC via syringe
pumps over 3 h. After additional 1 h at 0 ꢀC, the reaction mixture
was concentrated. The residue was purified by flash chromatogra-
phy [a column consecutively packed with silica gel 4 g and 10% (w/
w) KF contained silica gel 1 g, hexane/EtOAc 5/1 to 3/1] to afford 7a
(3.0 mg, 0.013 mmol) and the unreacted 1 (15.5 mg, 0.498 mmol) in
12% and 47% yields, respectively.
tures include facile conversion of 2 to the
a-alkoxy bridgehead
radical below ambient temperature, and the multiple roles of Et3B
as radical initiator, Lewis acid and radical terminator. A variety of
cycloalkenones, cycloalkylidenemalononitriles, allyl halides and
imines participated in the couplings to allow efficient attachment
of carbocycles, allyl groups, and amino-substituted alkyl groups to
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6
D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
4.4. Compound 7b [CAS: 1326319-35-0]
(46.0 mg, 0.287 mmol) by using Et3B (1.03 M in hexane, 0.28 mL,
0.29 mmol) in CH2Cl2 (0.95 mL). The reaction mixture was purified
by flash column chromatography on silica gel (10 g, hexane/EtOAc
2/1). The analytical data of 8c were identical to those reported
previously.2a
According to the general procedure A, 7b (18.2 mg,
0.0721 mmol) was synthesized in 80% yield from O,Te-acetal 2
(32.4 mg, 0.0900 mmol) and cyclohexenone 3b (26 mL, 0.27 mmol)
by using Et3B (1.03 M in hexane, 0.26 mL, 0.27 mmol) in CH2Cl2
(0.90 mL). The reaction mixture was purified by flash column
chromatography on silica gel (10 g, hexane/EtOAc 1/1). The ana-
lytical data of 7b were identical to those reported previously.2a
4.11. Compound 8d [CAS: 1326319-45-2]
According to the general procedure A, 8d (16.7 mg) containing
impurity was synthesized from O,Te-acetal
2
(35.0 mg,
4.5. Compound 7c [CAS: 1326319-36-1]
0.0973 mmol) and cyclooctylidenemalononitrile 4d27 (51.0 mg,
0.293 mmol) by using Et3B (1.03 M in hexane, 0.28 mL, 0.29 mmol)
in CH2Cl2 (0.97 mL). The reaction mixture was purified by flash
column chromatography on silica gel (10 g, hexane/EtOAc 2/1).
Because of inseparable impurity, the yield was calculated to be 33%
(0.0321 mmol) based on the 1H NMR analysis using anisole as an
internal standard. The 1H NMR data of 8d was identical to those
reported previously.2a
According to the general procedure A, 7c (20.3 mg,
0.0762 mmol) was synthesized in 78% yield from O,Te-acetal 2
(35.1 mg, 0.0975 mmol) and cycloheptenone 3c (32.0 mg,
0.290 mmol) by using Et3B (1.03 M in hexane, 0.28 mL, 0.29 mmol)
in CH2Cl2 (0.98 mL). The reaction mixture was purified by flash
column chromatography on silica gel (10 g, hexane/EtOAc 2/1). The
analytical data of 7c were identical to those reported previously.2a
4.12. Aldehyde 3f
4.6. Compound 7d [CAS: 1326319-37-2]
9-BBN (0.5 M THF solution, 8.5 mL, 4.3 mmol) was added to
a solution of 4-[(tert-butyldiphenylsilyl)oxy]-1-butene 11 (1.20 g,
3.86 mmol) in THF (8.5 mL) at 0 ꢀC, and resultant mixture was
stirred at 60 ꢀC for 4 h. The above reaction mixture and 3 M aqueous
K3PO4 (3.2 mL, 9.6 mmol) were successively added to a solution of
2-iodo-2-cyclopentene-1-one 1228 (800 mg, 3.85 mmol) and
PdCl2(dppf) (281 mg, 0.344 mmol) in DMF (8.5 mL) at room tem-
perature. After being stirred at 60 ꢀC for 2 h, the reaction mixture
was cooled to room temperature. Then, H2O (20 mL) was added.
The resultant mixture was extracted with EtOAc (20 mL x3), and the
combined organic layers were washed with H2O (30 mL) and brine
(30 mL), dried over Na2SO4, filtered, and concentrated. The residue
was purified by flash column chromatography on silica gel (40 g,
hexane/EtOAc 4/1) to afford enone 13 (961 mg, 2.45 mmol) in 64%
yield: colorless oil; IR (film) 3069, 3048, 2931, 2859, 1704, 1631,
1589, 1468, 1428, 1388, 1361, 1301, 1254, 1192, 1108, 1002 cmꢁ1; 1H
According to the general procedure A, 7d (26.4 mg,
0.0942 mmol) was synthesized in 87% yield from O,Te-acetal 2
(38.8 mg, 0.108 mmol) and cyclooctenone 3d (40.0 mg,
0.322 mmol) by using Et3B (1.03 M in hexane, 0.31 mL, 0.32 mmol)
in CH2Cl2 (1.1 mL). The reaction mixture was purified by flash col-
umn chromatography on silica gel (10 g, hexane/EtOAc 2/1). The
analytical data of 7d were identical to those reported previously.2a
4.7. Compound 7e [CAS: 1326319-38-3]
According to the general procedure A, 7e (26.2 mg,
0.0711 mmol) was synthesized in 72% yield from O,Te-acetal 2
(35.5 mg, 0.0986 mmol) and 4-(tert-butyldimethylsilyloxy)-2-
cyclopentenone 3e26 (63.0 mg, 0.297 mmol) by using Et3B
(1.03 M in hexane, 0.29 mL, 0.30 mmol) in CH2Cl2 (0.99 mL). The
reaction mixture was purified by flash column chromatography on
silica gel (10 g, hexane/EtOAc 3/1). The analytical data of 7e were
identical to those reported previously.2a
NMR (500 MHz, CDCl3)
d 1.05 (9H, s, t-Bu), 1.53e1.62 (4H, m,
CH2CH2CH2OTBDPS), 2.16 (2H, m, C(¼O)CCH2), 2.39 (2H, m, C(¼O)
CH2), 2.55 (2H, ddd, J¼9.2, 4.6, 1.7 Hz, C(¼O)CH2CH2), 3.67 (2H, t,
J¼6.3 Hz, CH2OTBDPS), 7.27 (1H, m, C(¼O)CCH), 7.35e7.44 (6H, m,
aromatic), 7.66 (4H, dd, J¼8.0,1.8 Hz, aromatic); 13C NMR (125 MHz,
4.8. Compound 8a [CAS: 1326319-42-9]
CDCl3)
d 19.2, 23.9, 24.5, 26.4, 26.8 (3C), 32.2, 34.6, 63.6, 127.6 (4C),
According to the general procedure A, 8a (16.6 mg, 0.0576 mmol)
129.5 (2C), 134.0 (2C), 135.5 (4C), 146.3, 157.3, 210.0; HRMS (ESI)
was synthesized in 58% yield from O,Te-acetal
2 (35.7 mg,
calcd for C25H32NaO2Si [MþNa]þ 415.2064, found 415.2072.
0.0992 mmol) and cyclopentylidenemalononitrile 4a (39.0 mg,
0.295 mmol) by using Et3B (1.03 M in hexane, 0.29 mL, 0.30 mmol)
in CH2Cl2 (0.99 mL). The reaction mixture was purified by flash
column chromatography on silica gel (10 g, hexane/EtOAc 2/1). The
analytical data of 8a were identical to those reported previously.2a
TBAF (1 M in THF, 1.1 mL, 1.1 mmol) was added to a solution of
enone 13 (144 mg, 0.367 mmol) and AcOH (0.11 mL, 1.8 mmol) in
THF (1.8 mL) at room temperature. The reaction mixture was stirred
at room temperature for 22 h, and then saturated aqueous NH4Cl
(10 mL) was added. The resultant mixture was extracted with CHCl3
(10 mL x2), and the combined organic layers were washed with
brine (10 mL), dried over Na2SO4, filtered, and concentrated. The
residue was purified by flash column chromatography on silica gel
(10 g, hexane/EtOAc 1/4) to afford alcohol 14 (50.9 mg, 0.330 mmol)
in 90% yield: colorless oil; IR (film) 3413, 2933, 2865, 1688, 1629,
1441, 1355, 1254, 1204, 1056, 1004 cmꢁ1; 1H NMR (500 MHz, CDCl3)
4.9. Compound 8b [CAS: 1326319-43-0]
According to the general procedure A, 8b (26.0 mg, 0.0860 mmol)
was synthesized in 88% yield from O,Te-acetal
2 (35.1 mg,
0.0975 mmol) and cyclohexylidenemalononitrile 4b (43.0 mg,
0.294 mmol) by using Et3B (1.03 M in hexane, 0.28 mL, 0.29 mmol)
in CH2Cl2 (0.98 mL). The reaction mixture was purified by flash
column chromatography on silica gel (10 g, hexane/EtOAc 2/1). The
analytical data of 8b were identical to those reported previously.2a
d
1.47e1.58 (4H, m, CH2CH2CH2OH), 2.15 (2H, m, C(¼O)CCH2), 2.35
(2H, m, C(¼O)CH2), 2.42e2.58 (3H, m, C(¼O)CH2CH2, OH), 3.60 (2H,
t, J¼6.3 Hz, CH2OH), 7.30 (1H, m, C(¼O)CCH); 13C NMR (125 MHz,
CDCl3)
d 23.9, 24.3, 26.4, 32.2, 34.5, 62.2, 146.0, 157.9, 210.3; HRMS
(ESI) calcd for C9H14NaO2 [MþNa]þ 177.0886, found 177.0879.
PhI(OAc)2 (467 mg, 1.45 mmol) and TEMPO (19.0 mg,
0.122 mmol) were successively added to a solution of alcohol 14
(187 mg, 1.21 mmol) in CH2Cl2 (2.4 mL) at room temperature. The
reaction mixture was stirred at room temperature for 18 h, and was
then concentrated. The residue was purified by flash column
4.10. Compound 8c [CAS: 1326319-44-1]
According to the general procedure A, 8c (26.0 mg,
0.0822 mmol) was synthesized in 87% yield from O,Te-acetal 2
(34.2 mg, 0.0950 mmol) and cycloheptylidenemalononitrile 4c27
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D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
7
chromatography on silica gel (15 g, hexane/EtOAc 1/1) to afford
aldehyde 3f (147 mg, 0.966 mmol) in 80% yield: colorless oil; IR
(film) 2926, 2846, 2727, 1696, 1631, 1442, 1403, 1357, 1297, 1254,
purified by flash column chromatography on silica gel (10 g, hex-
ane/EtOAc 1/3): colorless oil; IR (film) 3449, 3003, 2952, 2872,
2360, 2340, 1728, 1447, 1395, 1324, 1298, 1226, 1150, 1129,
1202, 1169, 1088, 1051, 1002 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.79
1073 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 1.41 (3H, s, CCH3), 1.52 (1H,
(2H, dt, J¼15.1, 7.8 Hz, CH2CH2CHO), 2.17 (2H, m, C(¼O)CCH2), 2.37
(2H, m, C(¼O)CH2), 2.43 (2H, td, J¼7.3, 1.8 Hz, CH2CHO), 2.55 (2H,
ddd, J¼9.2, 4.6, 2.3 Hz, C(¼O)CH2CH2), 7.33 (1H, m, C(¼O)CCH), 9.73
dd, J¼12.8, 1.4 Hz, COCHaxHeqCHO), 1.60 (1H, dt, J¼12.8, 1.8 Hz,
CHOCHaxHeqCHO), 1.64e1.95 (6H, m, COCHaxHeqCHO, C(¼O)
CH2CHAHB, CH(OH)CHAHB, CH(OH)CH2CH2, CH(OH)CH2CH2CHAHB),
1.99e2.26 (3H, m, C(¼O)CHAHB, C(¼O)CH2CHAHB, CH(OH)CHAHB),
2.26e2.40 (4H, m, C(¼O)CHAHB, C(¼O)CCH, CH(OH)CH2CH2CHAHB,
(1H, t, J¼1.4 Hz, CHO); 13C NMR (100 MHz, CDCl3)
d 20.2, 24.1, 26.4,
34.4, 43.3, 145.3, 158.1, 202.0, 209.7; HRMS (ESI) calcd for
C9H12NaO2 [MþNa]þ 175.0730, found 175.0723.
COCHaxHeqCHO), 2.42e2.57 (2H, m, COCHaxHeqCHO, CHOCHaxHeq
-
CHO), 4.28 (1H, t, J¼7.3 Hz, CH(OH)), 4.38e4.46 (2H, m, CH2CHOCH2
4.13. Aldehyde 3g
x2); 13C NMR (100 MHz, CDCl3)
d 19.8, 21.4, 26.1, 28.9, 32.5, 33.9,
34.6, 37.4, 37.5, 51.2, 62.6, 68.0, 68.2, 74.6, 81.0, 110.0, 222.2; HRMS
According to the synthetic protocol of 13, enone 16 (635 mg,
1.56 mmol) was synthesized from 12 (800 mg, 3.85 mmol) and 5-
[(tert-butyldiphenylsilyl)oxy]-1-penten 1529 (1.25 g, 3.85 mmol) in
41% yield by using 9-BBN (8.5 mL of a 0.5 M solution in THF,
4.3 mmol), THF (8.5 mL), PdCl2(dppf) (281 mg, 0.344 mmol) and
DMF (8.5 mL). The residue was purified by flash column chroma-
tography on silica gel (30 g, hexane/EtOAc 10/1): colorless oil; IR
(film) 3065, 3048, 2931, 2859, 2361, 1703, 1631, 1466, 1432, 1386,
1355, 1297, 1251, 1193, 1106, 1002 cmꢁ1; 1H NMR (500 MHz, CDCl3)
(ESI) calcd for C17H24NaO5 [MþNa]þ 331.1516, found 331.1517.
4.15. Compound 7g
According to the general procedure A, 7g (30.1 mg, 0.0934 mmol)
was synthesized in 93% yield from O,Te-acetal
2 (36.0 mg,
0.100 mmol) and 3g (33.0 mg, 0.199 mmol) by using Et3B (1.03 M
hexane solution, 0.29 mL, 0.30 mmol) in CH2Cl2 (1.0 mL). The reaction
mixture was purified by flash column chromatography on silica gel
(10 g, hexane/EtOAc 1/3): colorless prism; mp 173e174 ꢀC; IR (film)
3449, 2948, 2863, 1727, 1448, 1394, 1394, 1324, 1298, 1154, 1129,
d
1.05 (9H, s, t-Bu), 1.34e1.52 (4H, m, CH2CH2CH2CH2OTBDPS), 1.58
(2H, dt, J¼14.6, 6.9 Hz, CH2CH2OTBDPS), 2.17 (2H, m, C(¼O)CCH2),
2.39 (2H, m, C(¼O)CH2), 2.54 (2H, ddd, J¼9.2, 4.6, 2.3 Hz, C(¼O)
CH2CH2), 3.66 (2H, t, J¼6.4 Hz, CH2OTBDPS), 7.27 (1H, m, C(¼O)
CCH), 7.35e7.45 (6H, m, aromatic), 7.67 (4H, dd, J¼8.2, 1.8 Hz, aro-
1041 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.26 (1H, m, CH(OH)
CH2CHAHB),1.40e1.52 (2H, m, CH(OH)CH2CH2CH2),1.43 (3H, s, CCH3),
1.54e1.64 (2H, m, COCHaxHeqCHO x2), 1.69 (1H, m, CH(OH)
CH2CH2CH2CHAHB), 1.73e1.86 (3H, m, CHOCHaxHeqCHO, CH(OH)
CHAHB, CH(OH)CH2CHAHB),1.86e2.02 (3H, m, C(¼O)CH2CH2, CH(OH)
CH2CH2CH2CHAHB), 2.02e2.24 (2H, m, C(¼O)CHAHB, CH(OH)CHAHB),
2.37 (1H, m, C(¼O)CHAHB), 2.45e2.62 (3H, m, COCHaxHeqCHO x2,
CHOCHaxHeqCHO), 2.67 (1H, dd, J¼11.0, 8.2 Hz, C(¼O)CH2CH2CH),
3.99 (1H, dd, J¼11.4, 5.5 Hz, CH(OH)), 4.41 (2H, m, CH2CHOCH2 x2);
matic); 13C NMR (100 MHz, CDCl3)
d 19.2, 24.7, 25.6, 26.4, 26.8 (3C),
27.4, 32.3, 34.6, 63.8, 127.5 (4C), 129.5 (2C), 134.1 (2C), 135.5 (4C),
146.3, 157.3, 210.0; HRMS (ESI) calcd for C26H34NaO2Si [MþNa]þ
429.2220, found 429.2222.
According to the synthetic protocol of 14, alcohol 17 (242 mg,
1.44 mmol) was synthesized from enone 16 (635 mg, 1.56 mmol) in
92% yield by using TBAF (1 M in THF, 4.7 mL, 4.7 mmol) in AcOH
(0.45 mL, 7.8 mmol) and THF (7.8 mL). The residue was purified by
flash column chromatography on silica gel (30 g, hexane/EtOAc 1/4):
colorless oil; IR (film) 3402, 2930, 2861, 1691, 1630, 1441, 1407, 1350,
1301, 1249, 1203, 1148, 1053, 1004 cmꢁ1; 1H NMR (400 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
d 18.5, 20.3, 24.3, 26.1, 27.0, 31.3, 32.5, 35.2,
37.6, 37.9, 48.6, 57.5, 68.2, 68.3, 72.7, 74.9, 110.1, 220.8; HRMS (ESI)
calcd for C18H26NaO5 [MþNa]þ 345.1672, found 345.1664.
4.16. p-Bromobenzoyl ester 18
d
1.29 (2H, m, CH2CH2CH2OH),1.38e1.56 (4H, m, CH2CH2CH2CH2OH),
2.11 (2H, m, C(¼O)CCH2), 2.26e2.36 (3H, m, C(¼O)CH2, OH), 2.50 (2H,
p-Bromobenzoyl chloride (p-Br-BzCl, 22.0 mg, 0.100 mmol) was
added to a solution of alcohol 7f (27.5 mg, 0.0892 mmol) and DMAP
(13.0 mg, 0.106 mmol) in CH2Cl2 (0.89 mL) at room temperature.
The reaction mixture was stirred at room temperature for 12 h, and
then was directly subjected to flash column chromatography on
silica gel (10 g, hexane/EtOAc 1/1) to afford p-bromobenzoyl ester
18 (35.7 mg, 0.0727 mmol) in 82% yield: colorless prism; mp
158.0e159.0 ꢀC; IR (film) 2952, 2360, 2341, 1732, 1716, 1590, 1395,
ddd, J¼9.2, 4.6, 2.3 Hz, C(¼O)CH2CH2), 3.55 (2H, t, J¼6.9 Hz, CH2OH),
7.26 (1H, m, C(¼O)CCH); 13C NMR (100 MHz, CDCl3)
d 24.6, 25.4, 26.3,
27.4, 32.3, 34.5, 62.4, 146.1, 157.7, 210.2; HRMS (ESI) calcd for
C
10H16NaO2 [MþNa]þ 191.1043, found 191.1033.
According to the synthetic protocol of 3f, aldehyde 3g (188 mg,
1.13 mmol) was synthesized from alcohol 17 (203 mg, 1.21 mmol) in
93% yield by using PhI(OAc)2 (467 mg,1.45 mmol), TEMPO (19.0 mg,
0.122 mmol) in CH2Cl2 (6.1 mL). The residue was purified by flash
column chromatography on silica gel (15 g, hexane/EtOAc 1/1):
colorless oil; IR (film) 2929, 2862, 2725, 1721, 1697, 1631, 1442, 1407,
1390, 1351, 1298, 1252, 1200, 1160, 1092, 1045, 1003 cmꢁ1; 1H NMR
1272, 1128, 1011 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.43 (3H, s,
CCH3), 1.49 (1H, dd, J¼12.8, 1.4 Hz, COCHaxHeqCHO), 1.60 (1H, m,
CHOCHaxHeqCHO), 1.80e2.11 (7H, m), 2.17e2.36 (5H, m), 2.37e2.48
(2H, m), 2.53 (1H, m, CHOCHaxHeqCHO), 4.38e4.46 (2H, m,
CH2CHOCH2 x2), 5.45 (1H, dd, J¼6.4, 6.0 Hz, CHOC(¼O)Ar), 7.56 (2H,
m, aromatic), 7.79 (2H, m, aromatic); 13C NMR (100 MHz, CDCl3)
(400 MHz, CDCl3)
d 1.50 (2H, m, CH2CH2CH2CHO), 1.62 (2H, dt,
J¼15.6, 7.8 Hz, CH2CH2CHO), 2.18 (2H, m, C(¼O)CCH2), 2.37 (2H, m,
C(¼O)CH2), 2.44 (2H, td, J¼7.3, 1.8 Hz, CH2CHO), 2.54 (2H, ddd,
J¼9.2, 4.6, 1.8 Hz, C(¼O)CH2CH2), 7.30 (1H, m, C(¼O)CCH), 9.74 (1H,
d
19.7, 21.5, 26.0, 28.6, 30.0, 32.5, 34.3, 37.0, 37.6, 51.4, 61.1, 67.9,
68.2, 74.6, 83.0, 110.0, 128.2, 129.0, 131.0, 131.8, 165.5, 218.3; HRMS
t, J¼1.8 Hz, CHO); 13C NMR (100 MHz, CDCl3)
d
21.6, 24.4, 26.3, 27.1,
(ESI) calcd for C24H27BrNaO6 [MþNa]þ 513.0883, found 513.0891.
34.4, 43.4, 145.6, 157.6, 202.3, 209.8; HRMS (ESI) calcd for
C
10H14NaO2 [MþNa]þ 189.0886, found 189.0885.
4.17. Synthesis of olefin 9a from O,Se-acetal 1 and 5a
4.14. Compound 7f
A solution of O,Se-acetal
1 (33.0 mg, 0.106 mmol), 2,3-
dichloroprop-1-ene 5a (50 L, 0.53 mmol) and V-40 (10.4 mg,
m
According to the general procedure A, 7f (16.1 mg, 0.0522 mmol)
was synthesized in 100% yield from O,Te-acetal 2 (18.8 mg,
0.0522 mmol) and 4-(5-oxocyclopent-1-en-1-yl)butanal 3f
(16.0 mg, 0.105 mmol) by using Et3B (1.03 M hexane solution,
0.15 mL, 0.16 mmol) in CH2Cl2 (0.52 mL). The reaction mixture was
0.0424 mmol) in toluene (2.0 mL) was degassed by freeze-thaw
procedure (ꢂ3). The mixture was heated to 110 ꢀC. Then, another
degassed solution of n-Bu3SnH (176
mL, 0.636 mmol) and V-40
(5.2 mg, 0.021 mmol) in toluene (2.0 mL) by freeze-thaw procedure
(ꢂ3) was added via a syringe pump over 3 h. After additional 1 h at
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8
D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
110 ꢀC, the reaction mixture was cooled to room temperature and
concentrated. The residue was purified by flash chromatography [a
column consecutively packed with silica gel 4 g and 10% (w/w) KF
contained silica gel 1 g, hexane/EtOAc 20/1 to 10/1] to give the
crude 9a (15.0 mg). The crude was further purified by PTLC (hex-
ane/EtOAc 5/1ꢂ2) to afford 9a (3.0 mg, 0.013 mmol) in 12% yield.
4.21. Synthesis of olefin 9b from O,Te-acetal 2 and 5bb
According to the general procedure A, 9b (10.5 mg,
0.0535 mmol) was synthesized in 57% yield from O,Te-acetal 2
(34.0 mg, 0.0945 mmol) and allyl bromide 5bb (41 mL, 0.47 mmol)
by using Et3B (1.03 M hexane solution, 0.46 mL, 0.47 mmol) in
CH2Cl2 (0.94 mL). The reaction mixture was purified by flash col-
umn chromatography on silica gel (10 g, hexane/EtOAc 5/1).
4.18. Synthesis of olefin 9a from O,Te-acetal 2 and 5a
4.22. Olefin 9d
According to the general procedure A, 9a (18.5 mg,
0.0802 mmol) was synthesized in 79% yield from O,Te-acetal 2
According to the general procedure A, 9d (13.1 mg,
0.0623 mmol) was synthesized in 61% yield from O,Te-acetal 2
(36.7 mg, 0.102 mmol) and 3-bromo-2-methylprop-1-ene 5d
(36.6 mg, 0.102 mmol) and 2,3-dichloroprop-1-ene 5a (47
mL,
0.51 mmol) by using Et3B (1.03 M hexane solution, 0.49 mL,
0.51 mmol) in CH2Cl2 (1.0 mL). The reaction mixture was purified by
flash column chromatography on silica gel (10 g, hexane/EtOAc 5/
1): colorless oil; IR (film) 3009, 2971, 2947, 2930, 2851, 1632, 1444,
(51 mL, 0.51 mmol) by using Et3B (1.03 M hexane solution, 0.50 mL,
0.51 mmol) in CH2Cl2 (1.0 mL). The reaction mixture was purified by
flash column chromatography on silica gel (10 g, hexane/EtOAc 10/
1): colorless oil; IR (film) 3073, 3007, 2951, 2851, 1645, 1445, 1394,
1395, 1325, 1298, 1161 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 1.43 (3H,
1324, 1297, 1125 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.43 (3H, s,
s, CCH3), 1.57 (1H, dt, J¼12.8, 1.8 Hz, CHOCHaxHeqCHO), 1.80 (2H, d,
J¼13.3 Hz, COCHaxHeqCHO x2), 2.27 (2H, m, COCHaxHeqCHO x2),
2.47e2.55 (3H, m, CHOCHaxHeqCHO, CH2C(Cl)]CH2), 4.42 (2H, m,
CH2CHOCH2 x2), 5.25 (1H, s, CH2C(Cl)¼CHAHB), 5.35 (1H, d,
CCH3), 1.55 (1H, dt, J¼13.3, 1.8 Hz, CHOCHaxHeqCHO), 1.56 (2H, d,
J¼13.3 Hz, COCHaxHeqCHO x2), 1.81 (3H, s, CH2C(CH3)¼CH2), 2.18
(2H, s, CH2C(CH3)¼CH2), 2.25 (2H, m, COCHaxHeqCHO x2), 2.51 (1H,
dtt, J¼12.8, 4.6, 2.3 Hz, CHOCHaxHeqCHO), 4.40 (2H, m, CH2CHOCH2
x2), 4.70 (1H, m, CH2C(CH3)¼CHAHB), 4.89 (1H, m, CH2C(CH3)¼
J¼0.9 Hz, CH2C(Cl)¼CHAHB); 13C NMR (100 MHz, CDCl3)
d 26.1, 32.1,
36.4 (2C), 51.0, 68.1 (2C), 72.3, 110.4, 117.2, 135.8; HRMS (DART)
CHAHB); 13C NMR (125 MHz, CDCl3)
d 24.6, 26.2, 32.4, 36.6 (2C),
calcd for C11H16ClO3 [MþH]þ 231.0782, found 231.0785.
49.7, 68.2 (2C), 72.8, 110.2, 115.0, 140.9; HRMS (DART) calcd for
C
12H19O3 [MþH]þ 211.1329, found 211.1338.
4.19. Synthesis of olefin 9b from O,Te-acetal 2 and 5ba
4.23. The reaction of O,Se-acetal 1 and 6a
According to the general procedure A, 9b (12.0 mg,
0.0611 mmol) was synthesized in 65% yield from O,Te-acetal 2
(33.7 mg, 0.0936 mmol) and allyl chloride 5ba (38 mL, 0.47 mmol)
A solution of O,Se-acetal 1 (33.0 mg, 0.106 mmol), tert-butyl(-
phenylmethylene)carbamate 6a (109 mg, 0.530 mmol) and V-40
(10.4 mg, 0.0424 mmol) in toluene (2.0 mL) was degassed by
freeze-thaw procedure (ꢂ3). The mixture was heated to 110 ꢀC.
by using Et3B (1.03 M hexane solution, 0.45 mL, 0.47 mmol) in
CH2Cl2 (0.94 mL). The reaction mixture was purified by flash col-
umn chromatography on silica gel (10 g, hexane/EtOAc 5/1): col-
orless oil; IR (film) 3077, 3008, 2953, 2929, 2850, 1445, 1395, 1325,
Then another degassed solution of n-Bu3SnH (176 mL, 0.636 mmol)
and V-40 (5.2 mg, 0.021 mmol) in toluene (2.0 mL) by freeze-thaw
procedure (ꢂ3) was added via a syringe pump over 3 h. After ad-
ditional 1 h at 110 ꢀC, the reaction mixture was cooled to room
temperature and concentrated. The residue was purified by flash
chromatography [a column consecutively packed with silica gel 4 g
and 10% (w/w) KF contained silica gel 1 g, hexane/EtOAc 20/1 to 5/
1] to afford the unreacted O,Se-acetal 1 (9.3 mg, 0.030 mmol) in 28%
yield and tert-butyl benzylcarbamate (69.0 mg, 0.336 mmol) in 63%
yield based on 6a.
1297, 1160, 1127 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 1.44 (3H, s,
CCH3), 1.54 (1H, d, J¼13.3 Hz, CHOCHaxHeqCHO), 1.59 (2H, d,
J¼13.3 Hz, COCHaxHeqCHO x2), 2.16e2.25 (4H, m, COCHaxHeqCHO
x2, CH2CH]CH2), 2.51 (1H, m, CHOCHaxHeqCHO), 4.40 (2H, br s,
CH2CHOCH2 x2), 5.07e5.16 (2H, m, CH2CH]CH2), 5.81 (1H, ddt,
J¼17.8, 10.5, 7.3 Hz, CH2CH]CH2); 13C NMR (100 MHz, CDCl3)
d
26.2, 32.3, 36.4 (2C), 46.3, 68.1 (2C), 72.5, 110.3, 118.8, 131.8; HRMS
(DART) calcd for C11H17O3 [MþH]þ 197.1172, found 197.1180.
4.24. General procedure B: carbamate 10a
4.20. Olefin 9c
Et3B (1.03 M hexane solution, 0.31 mL, 0.32 mmol) was added to
a solution of O,Te-acetal 2 (38.3 mg, 0.106 mmol) and tert-butyl(-
phenylmethylene)carbamate 6a (65.0 mg, 0.317 mmol) in CH2Cl2
(1.0 mL) at room temperature. The reaction mixture was stirring for
15 min, and then saturated aqueous NaHCO3 (10 mL) was added.
The resultant solution was extracted with EtOAc (5 mL x2), and the
combined organic layers were washed with brine (10 mL), dried
over Na2SO4, filtered, and concentrated. The residue was purified by
flash column chromatography on silica gel (10 g, hexane/EtOAc 3/1)
to afford 10a (35.5 mg, 0.0982 mmol) in 93% yield: colorless oil; IR
(film) 3451, 3354, 2969, 1710, 1495, 1394, 1367, 1324, 1297, 1246,
According to the general procedure A, 9c (20.0 mg,
0.0727 mmol) was synthesized in 71% yield from O,Te-acetal 2
(37.1 mg, 0.103 mmol) and 2-bromo-3-chloroprop-1-ene 5c (49 mL,
0.52 mmol) by using Et3B (1.03 M hexane solution, 0.50 mL,
0.52 mmol) in CH2Cl2 (1.0 mL). The reaction mixture was purified
by flash column chromatography on silica gel (10 g, hexane/EtOAc
10/1): colorless oil; IR (film) 3007, 2953, 2929, 2846, 2359, 1626,
1394, 1324, 1298, 1160, 1147, 1126 cmꢁ1
CDCl3)
;
1H NMR (400 MHz,
d
1.43 (3H, s, CCH3), 1.57 (1H, dt, J¼13.3, 1.8 Hz,
CHOCHaxHeqCHO), 1.81 (2H, d, J¼12.8 Hz, COCHaxHeqCHO x2),
2.28 (2H, dt, J¼13.3, 2.3 Hz, COCHaxHeqCHO x2), 2.52 (1H, dtt,
J¼13.3, 4.6, 2.3 Hz, CHOCHaxHeqCHO), 2.67 (2H, s, CH2C(Br)]CH2),
4.42 (2H, m, CH2CHOCH2 x2), 5.62 (1H, d, J¼1.4 Hz, CH2C(Br)¼
CHAHB), 5.71 (1H, d, J¼0.9 Hz, CH2C(Br)¼CHAHB); 13C NMR
1167, 1129 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 1.34e1.48 (13H, m, t-
Bu, CCH3, COCHaxHeqCHO), 1.50e1.65 (2H, m, COCHaxHeqCHO,
CHOCHaxHeqCHO), 1.85 (1H, d, J¼12.4 Hz, COCHaxHeqCHO), 2.48
(1H, dtt, J¼13.3, 3.6, 1.8 Hz, CHOCHaxHeqCHO), 2.60 (1H, dtt, J¼13.3,
2.3, 2.3 Hz, COCHaxHeqCHO), 4.27 (1H, m, CH2CHOCH2), 4.34e4.49
(2H, m, CH2CHOCH2, PhCH), 5.53 (1H, br d, J¼5.9 Hz, NH), 7.24e7.34
(100 MHz, CDCl3)
d 26.1, 32.1, 36.4 (2C), 52.8, 68.1 (2C), 72.5,
110.4, 122.0, 125.5; HRMS (DART) calcd for C11H16BrO3 [MþH]þ
(5H, m, aromatic); 13C NMR (100 MHz, CDCl3, 40 ꢀC)
d 26.0, 28.2,
275.0277, 277.0257, found 275.0286, 277.0267.
28.3 (3C), 32.3, 34.1, 34.7, 67.7, 68.1, 74.3, 79.6, 110.6, 127.5, 128.1
Please cite this article in press as: Kamimura, D.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.04.023

D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
9
(2C), 128.5 (2C), 138.4, 155.7; HRMS (ESI) calcd for C20H27NNaO5
4.28. O-Benzylhydroxylamine 10e
[MþNa]þ 384.1781, found 384.1783.
According to the general procedure B, 10e (25.5 mg,
0.0694 mmol) was synthesized in 70% yield from O,Te-acetal 2
(35.7 mg, 0.0991 mmol) and benzaldehyde O-benzyloxime 6e32
(63.0 mg, 0.298 mmol) by using Et3B (1.03 M hexane solution,
0.29 mL, 0.30 mmol) in CH2Cl2 (1.0 mL). The residue was purified by
flash column chromatography on silica gel (10 g, hexane/EtOAc 4/1):
colorless oil; IR (film) 3267, 3061, 3029, 2952, 2864,1453,1395,1323,
4.25. Sulfonamide 10b
According to the general procedure B, 10b (32.5 mg,
0.0782 mmol) was synthesized in 76% yield from O,Te-acetal 2
(37.0 mg, 0.103 mmol) and N-benzylidene-p-toluenesulfonamide
6b (80.0 mg, 0.308 mmol) by using Et3B (1.03 M hexane solution,
0.30 mL, 0.31 mmol) in CH2Cl2 (1.0 mL). The residue was purified by
flash column chromatography on silica gel (10 g, hexane/EtOAc 5/1
to 2/1): colorless solid; mp 177e179 ꢀC; IR (film) 3279, 2954, 1451,
1298, 1145, 1127 cmꢁ1 1H NMR (500 MHz, CDCl3)
; d 1.26 (1H, dd,
J¼13.2, 1.8 Hz, COCHaxHeqCHO), 1.37 (1H, dt, J¼13.2, 1.7 Hz, CHO-
CHaxHeqCHO), 1.457 (1H, m, COCHaxHeqCHO), 1.459 (3H, s, CCH3),
2.24 (1H, m, COCHaxHeqCHO), 2.41 (1H, dtt, J¼13.2, 3.6, 1.8 Hz,
CHOCHaxHeqCHO), 2.47 (1H, m, COCHaxHeqCHO), 4.03 (1H, s, PhCH),
4.28e4.35 (2H, m, CH2CHOCH2 x2), 4.54 (1H, d, J¼11.5 Hz, PhCHAHB),
4.58 (1H, d, J¼11.5 Hz, PhCHAHB), 6.48 (1H, s, NH), 7.13e7.18 (2H, m,
aromatic), 7.22e7.29 (3H, m, aromatic), 7.30e7.38 (3H, m, aromatic),
1397, 1324, 1299, 1160, 1128, 1091, 1059 cmꢁ1
;
1H NMR (400 MHz,
CDCl3)
d
1.35 (1H, dd, J¼13.3, 1.8 Hz, COCHaxHeqCHO), 1.41 (3H, s,
CCH3), 1.42e1.48 (2H, m, COCHaxHeqCHO, CHOCHaxHeqCHO), 1.93
(1H, dtt, J¼12.8, 1.8, 1.8 Hz, COCHaxHeqCHO), 2.32 (3H, s, ArCH3),
2.44 (1H, dtt, J¼13.3, 3.6, 1.8 Hz, CHOCHaxHeqCHO), 2.58 (1H, dtt,
J¼13.3, 2.3, 2.3 Hz, COCHaxHeqCHO), 4.06 (1H, d, J¼6.9 Hz, PhCH),
4.27 (1H, m, CH2CHOCH2), 4.39 (1H, m, CH2CHOCH2), 5.53 (1H, d,
J¼6.4 Hz, NH), 7.00e7.06 (4H, m, aromatic), 7.08e7.19 (3H, m, ar-
omatic), 7.39e7.44 (2H, m, aromatic); 13C NMR (100 MHz, CDCl3)
7.42e7.47 (2H, m, aromatic); 13C NMR (125 MHz, CDCl3)
d 26.1, 31.2,
32.3, 35.5, 67.97, 68.0, 72.7, 74.4, 76.7, 110.4, 127.6, 127.8, 127.9 (2C),
128.2 (2C), 128.5 (2C), 129.1 (2C), 137.1, 137.7; HRMS (ESI) calcd for
C
22H25NNaO4 [MþNa]þ 390.1676, found 390.1681.
d
21.4, 25.9, 32.1, 33.0, 34.6, 64.9, 67.6, 67.9, 74.4, 110.6, 127.0 (2C),
127.7, 127.9 (2C), 128.6 (2C), 129.1 (2C), 135.4, 137.1, 142.9; HRMS
(ESI) calcd for C22H25NNaO5S [MþNa]þ 438.1346, found 438.1330.
4.29. O-Benzylhydroxylamine 10f
According to the general procedure B, 10f (12.8 mg,
0.0363 mmol) was synthesized in 38% yield from O,Te-acetal 2
(34.3 mg, 0.0953 mmol) and 3-methylbutanal O-benzyloxime 6f33
(55.0 mg, 0.288 mmol) by using Et3B (1.03 M hexane solution,
0.28 mL, 0.29 mmol) in CH2Cl2 (0.95 mL). The residue was purified
by flash column chromatography on silica gel (10 g, hexane/EtOAc
5/1): colorless oil; IR (film) 2952, 2867,1453,1394,1365,1323,1298,
4.26. Aniline 10c
According tothe generalprocedure B,10c (21.0mg, 0.0622 mmol)
was synthesized in 60% yield from O,Te-acetal
2 (37.4 mg,
0.104 mmol) and N-benzylideneaniline 6c30 (94.0 mg, 0.519 mmol)
by using Et3B (1.03 M hexane solution, 0.51 mL, 0.52 mmol) in CH2Cl2
(1.0 mL). The residue was purified by flash column chromatography
on silica gel (10 g, hexane/EtOAc 5/1): colorless oil; IR (film) 3390,
3053, 3008, 2956, 2931, 2850, 1602, 1503, 1395, 1320, 1298, 1146,
1129 cmꢁ1
;
1H NMR (500 MHz, CDCl3)
d
0.91 (3H, d, J¼6.9 Hz,
CHCH3), 0.95 (3H, d, J¼6.9 Hz, CHCH3), 1.21 (1H, ddd, J¼16.6, 9.8,
2.9 Hz, NHCHCHAHB), 1.42 (3H, s, CCH3), 1.44 (1H, m, NHCHCHAHB),
1.56 (1H, dt, J¼13.2, 1.7 Hz, CHOCHaxHeqCHO), 1.66e1.73 (2H, m,
1127 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.39 (1H, dd, J¼13.3, 1.4 Hz,
COCHaxHeqCHO), 1.46 (1H, d, J¼13.3 Hz, CHOCHaxHeqCHO), 1.51 (3H,
s, CCH3), 1.55 (1H, dd, J¼12.8, 1.4 Hz, COCHaxHeqCHO), 2.36 (1H, m,
COCHaxHeqCHO x2), 1.84 (1H, m, (CH3)2CH), 2.17 (1H, m, COCHax
-
HeqCHO), 2.43 (1H, m, COCHaxHeqCHO), 2.45 (1H, m, CHOCHaxHeq
-
COCHaxHeqCHO), 2.43e2.57 (2H, m, COCHaxHeqCHO, CHOCHaxHeq
-
CHO), 2.74 (1H, dd, J¼9.7, 2.3 Hz, NHCH), 4.35e4.43 (2H, m,
CH2CHOCH2 x2), 4.66 (1H, d, J¼11.5 Hz, PhCHAHB), 4.70 (1H, d,
J¼11.5 Hz, PhCHAHB), 6.06 (1H, br s, NH), 7.27e7.37 (5H, m, aro-
CHO), 4.13 (1H, s, PhCH), 4.37 (1H, m, CH2CHOCH2), 4.42 (1H, m,
CH2CHOCH2), 6.53 (2H, d, J¼7.8 Hz, aromatic), 6.66 (1H, t, J¼7.3 Hz,
aromatic), 7.06 (2H, t, J¼7.3 Hz, aromatic), 7.24e7.44 (5H, m, aro-
matic); 13C NMR (100 MHz, CD3OD)
d 22.1, 24.3, 26.46, 26.52, 33.4,
matic); 13C NMR (100 MHz, CDCl3)
d 26.1, 32.36, 32.39, 35.4, 66.2,
35.1, 35.3, 36.2, 66.9, 69.8, 69.9, 76.2, 77.0, 111.6, 128.8, 129.3 (2C),
129.5 (2C), 139.3; HRMS (ESI) calcd for C20H29NNaO4 [MþNa]þ
370.1989, found 370.1999.
68.0, 68.1, 74.7, 110.7, 114.2 (2C), 117.8, 127.7, 128.3 (2C), 128.6 (2C),
128.9 (2C),138.0,147.6; HRMS (ESI) calcd for C21H23NNaO3 [MþNa]þ
360.1570, found 360.1562.
4.27. O-Benzylhydroxylamine 10d
4.30. O-Benzylhydroxylamine 10g
According to the general procedure B, 10d (25.7 mg,
0.0882 mmol) was synthesized in 93% yield from O,Te-acetal 2
(34.0 mg, 0.0944 mmol) and formaldehyde O-benzyloxime 6d31
(38.0 mg, 0.281 mmol) by using Et3B (1.03 M hexane solution,
0.28 mL, 0.28 mmol) in CH2Cl2 (0.94 mL). The residue was purified
by flash column chromatography on silica gel (10 g, hexane/EtOAc
2/1): colorless oil; IR (film) 3276, 2950, 2929, 2854, 1395, 1323,
According to the general procedure B, 10g (34.3 mg,
0.0944 mmol) was synthesized in 89% yield from O,Te-acetal 2
(38.3 mg, 0.106 mmol) and O-benzyl-protected ethyl glyoxylate
oxime 6g34 (66.0 mg, 0.318 mmol) by using Et3B (1.03 M hexane
solution, 0.31 mL, 0.32 mmol) in CH2Cl2 (1.1 mL). The residue was
purified by flash column chromatography on silica gel (10 g, hexane/
EtOAc 3/1): colorless solid; mp 79e81 ꢀC; IR (film) 3266, 2955,1731,
1298,1165,1149,1127 cmꢁ1; 1H NMR (500 MHz, CDCl3)
d
1.42 (3H, s,
1453, 1396, 1325, 1299, 1230, 1201, 1191, 1164, 1128 cmꢁ1
(400 MHz, CDCl3)
;
1H NMR
CCH3), 1.57 (1H, dt, J¼13.2, 1.8 Hz, CHOCHaxHeqCHO), 1.61 (2H, d,
J¼13.2 Hz, COCHaxHeqCHO x2), 2.35 (2H, m, COCHaxHeqCHO x2),
2.51 (1H, dtt, J¼13.2, 4.6, 2.3 Hz, CHOCHaxHeqCHO), 2.92 (2H, s,
NHCH2), 4.39 (2H, br s, CH2CHOCH2 x2), 4.69 (2H, s, PhCH2),
d
1.30 (3H, t, J¼6.9 Hz, CO2CH2CH3), 1.38 (3H, s,
CCH3), 1.41 (1H, dd, J¼12.8, 0.9 Hz, COCHaxHeqCHO), 1.53 (1H, d,
J¼12.8 Hz, CHOCHaxHeqCHO), 1.75 (1H, dd, J¼13.3, 0.9 Hz, COCHax
-
HeqCHO), 2.23 (1H, m, CHOCHaxHeqCHO), 2.48 (2H, m, COCHaxHeq
-
7.27e7.37 (5H, m, aromatic); 13C NMR (125 MHz, CDCl3)
d
26.1, 32.4,
CHO x2), 3.49 (1H, s, NHCH), 4.27 (2H, m, CO2CH2CH3), 4.33e4.38
(2H, m, CH2CHOCH2 x2), 4.66 (1H, d, J¼11.9 Hz, PhCHAHB), 4.69 (1H,
d, J¼11.9 Hz, PhCHAHB), 7.26e7.37 (5H, m); 13C NMR (100 MHz,
35.5 (2C), 60.8, 68.0 (2C), 72.4, 75.9, 110.3, 127.8, 128.3 (2C), 128.4
(2C), 137.8; HRMS (ESI) calcd for C16H21NNaO4 [MþNa]þ 314.1363,
found 314.1359.
CDCl3)
d 14.3, 25.9, 32.2, 33.4, 34.8, 61.1, 67.8, 68.0, 70.8, 72.8, 76.1,
Please cite this article in press as: Kamimura, D.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.04.023

10
D. Kamimura et al. / Tetrahedron xxx (2016) 1e10
Angew. Chem., Int. Ed. 2015, 54, 1537; (c) Nagatomo, M.; Kamimura, D.; Matsui,
Y.; Masuda, K.; Inoue, M. Chem. Sci. 2015, 6, 2765.
110.4, 127.8, 128.2 (2C), 128.6 (2C), 137.6, 170.8; HRMS (ESI) calcd for
C
19H25NNaO6 [MþNa]þ 386.1580, found 386.1563.
10. For reviews on radical reactions of organotellurium compounds, see: (a) Ya-
mago, S. Synlett 2004, 1875; (b) Petragnani, N.; Stefani, H. A. Tellurium in Or-
ganic Synthesis, 2nd, updated and enlarged ed.; Elsevier: New York, 2007.
11. (a) Furukawa, J.; Tsuruta, T.; Inoue, S. J. Polym. Sci. 1957, 26, 234; (b) Suzuki, A.;
Acknowledgements
ꢀ
Arase, A.; Matsumoto, H.; Itoh, M.; Brown, H. C.; Rogic, M. M.; Rathke, M. W. J.
This research was financially supported by the Funding Program
for a Grant-in-Aid for Scientific Research (A) (JSPS Grant Number
26253003) to M.I., a Grant-in-Aid for Young Scientists (B) (JSPS
Grant Number 26860009) to M.N., and a Grant-in-Aid for Scientific
Research (C) (JSPS Grant Number 2546007) to D.U. The X-ray
crystallographic analyses were supported by Nanotechnology
Platform (No.12024046) of MEXT.
Am. Chem. Soc. 1967, 89, 5708; (c) Brown, H. C.; Kabalka, G. W. J. Am. Chem. Soc.
1970, 92, 714; (d) Nozaki, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1991,
64, 403; For a review, see: (e) Ollivier, C.; Renaud, P. Chem. Rev. 2001, 101, 3415.
12. (a) Barton, D. H. R.; Ozbalik, N.; Sarma, J. C. Tetrahedron Lett. 1988, 29, 6581; (b)
Curran, D. P.; Martin-Esker, A. A.; Ko, S.-B.; Newcomb, M. J. Org. Chem. 1993, 58,
4691; (c) He, W.; Togo, H.; Waki, Y.; Yokoyama, M. J. Chem. Soc., Perkin Trans. 1
1998, 2425.
13. The BDE values of the CeSe and CeTe bonds were experimentally determined:
DH298(CH3eSeCH3)¼60.0 kcal/mol, DH298(CH3eTeCH3)¼52.6 kcal/mol. Tel’noi,
V. I.; Sheiman, M. S. Russ. Chem. Rev. 1995, 64, 309.
14. Beraud, V.; Gnanou, Y.; Walton, J. C.; Maillard, B. Tetrahedron Lett. 2000, 41, 1195.
15. Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987, 109, 2547.
16. For reviews on the radical-polar crossover reactions, see: (a) Murphy, J. A. The
radical-polar crossover reaction In. Radicals in Organic Synthesis; Renaud, P.,
Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001; Vol. 1, p 298; (b) Ryu, I. Chem. Rec.
2002, 2, 249; (c) Godineau, E.; Landais, Y. Chem.dEur. J. 2009, 15, 3044.
17. (a) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.; Suzuki, A. J. Am.
Chem. Soc. 1989, 111, 314; For reviews on Suzuki-Miyaura coupling, see: (b)
Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457; (c) Chemler, S. R.; Trauner, D.;
Danishefsky, S. J. Angew. Chem., Int. Ed. 2001, 40, 4544.
Supplementary data
Supplementary data (the NMR spectra of newly synthesized
compounds) associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2016.04.023.
References and notes
18. De Mico, A.; Margarita, R.; Parlanti, L.; Vescovi, A.; Piancatelli, G. J. Org. Chem.
1997, 62, 6974.
1. For recent reviews on radical reactions, see: (a) Rowlands, G. J. Tetrahedron
2009, 65, 8603; (b) Rowlands, G. J. Tetrahedron 2010, 66, 1593.
19. CCDC1453968 (18) and CCDC1453970 (7g) contain the supplementary crys-
tallographic data. These data are provided free of charge by The Cambridge
Crystallographic Data Centre.
2. (a) Urabe, D.; Yamaguchi, H.; Inoue, M. Org. Lett. 2011, 13, 4778; (b) Urabe, D.;
Nagatomo, M.; Hagiwara, K.; Masuda, K.; Inoue, M. Chem. Sci. 2013, 4, 1615; (c)
Murai, K.; Katoh, S.; Urabe, D.; Inoue, M. Chem. Sci. 2013, 4, 2364; (d) Nagatomo,
M.; Hagiwara, K.; Masuda, K.; Koshimizu, M.; Kawamata, T.; Matsui, Y.; Urabe,
D.; Inoue, M. Chem.dEur. J. 2016, 22, 222.
€
20. (a) Fenzl, W.; Koster, R. Liebigs Ann. Chem. 1975, 1322; (b) Inoue, T.; Mukaiyama,
T. Bull. Chem. Soc. Jpn. 1980, 53, 174; (c) Evans, D. A.; Nelson, J. V.; Vogel, E.;
Taber, T. R. J. Am. Chem. Soc. 1981, 103, 3099.
3. For representative examples on application of bridgehead radicals to synthetic
21. The aldehyde group serves as the radical acceptor under the conventional
stannyl radical mediated conditions. See for examples (a) Beckwith, A. L. J.;
Roberts, D. H. J. Am. Chem. Soc. 1986, 108, 5893; (b) Enholm, E. J.; Prasad, G. Tet-
rahedron Lett. 1989, 30, 4939; (c) Hays, D. S.; Fu, G. C. J. Org. Chem. 1998, 63, 6375.
22. Huval, C. C.; Singleton, D. A. Tetrahedron Lett. 1993, 34, 3041.
23. The BDE values of the carbonehalogen bonds of 3-chloroprop-1-ene and 3-
bromoprop-1-ene were reported: DH298(CleCH2CH¼CH2)¼71.3 kcal/mol,
DH298(BreCH2CH¼CH2)¼56.7 kcal/mol Luo, Y.-R. Comprehensive Handbook of
Chemical Bond Energies; CRC Press: FL, 2007.
24. Bertrand, M. P.; Feray, L.; Nouguier, R.; Stella, L. Synlett 1998, 780.
25. (a) Hart, D. J.; Seely, F. L. J. Am. Chem. Soc. 1988, 110, 1631; (b) Miyabe, H.; Ueda,
M.; Yoshioka, N.; Naito, T. Synlett 1999, 465; For reviews, see: (c) Friestad, G. K.
Tetrahedron 2001, 57, 5461; (d) Miyabe, H.; Ueda, M.; Naito, T. Synlett 2004,
1140.
€
€
studies on natural products, see: (a) Buchi, G.; Wuest, H. J. Org. Chem. 1979, 44,
546; (b) Kraus, G. A.; Andersh, B.; Su, Q.; Shi, J. Tetrahedron Lett. 1993, 34, 1741;
(c) Hatakeyama, S.; Kawamura, M.; Takano, S. J. Am. Chem. Soc. 1994, 116, 4081;
(d) Kim, S.; Cheong, J. H. Synlett 1997, 947; (e) Tsukano, C.; Siegel, D. R.; Dan-
ishefsky, S. J. Angew. Chem., Int. Ed. 2007, 46, 8840; (f) Smith, M. W.; Snyder, S. A.
J. Am. Chem. Soc. 2013, 135, 12964; For a review on bridgehead radicals, see: (g)
Walton, J. C. Chem. Soc. Rev. 1992, 21, 105.
4. Ryanodol: (a) Nagatomo, M.; Koshimizu, M.; Masuda, K.; Tabuchi, T.; Urabe, D.;
Inoue, M. J. Am. Chem. Soc. 2014, 136, 5916; Ryanodine: (b) Masuda, K.; Koshi-
mizu, M.; Nagatomo, M.; Inoue, M. Chem.dEur. J. 2016, 22, 230; Crotophorbo-
lone: (c) Asaba, T.; Katoh, Y.; Urabe, D.; Inoue, M. Angew. Chem., Int. Ed. 2015, 54,
14457.
5. For a review on purification of a product from tin residues, see: Grognec, E. L.;
ꢀ
Chretien, J.-M.; Zammattio, F.; Quintard, J.-P. Chem. Rev. 2015, 115, 10207.
26. Watson, T. J. N.; Curran, T. T.; Hay, D. A.; Shah, R. S.; Wenstrup, D. L.; Webster,
M. E. Org. Process Res. Dev. 1998, 2, 357.
27. Arya, V. P. Indian J. Chem. 1972, 10, 1141.
6. van der Kerk, G. J. M.; Noltes, J. G.; Luijten, J. G. A. J. Appl. Chem. 1957, 7, 356.
7. For reviews on organotin-mediated radical reactions, see: (a) Neumann, W. P.
Synthesis 1987, 665; (b) Curran, D. P. Synthesis 1988, 417.
8. For reviews on tin-free radical reactions, see: (a) Studer, A.; Amrein, S. Synthesis
2002, 835; (b) Quiclet-Sire, B.; Zard, S. Z. Chem.dEur. J. 2006, 12, 6002; (c) Kim,
S.; Kim, S. Bull. Chem. Soc. Jpn. 2007, 80, 809; (d) Akindele, T.; Yamada, K.; To-
mioka, K. Acc. Chem. Res. 2009, 42, 345.
9. Three-component coupling reactions of O,Te-acetal 2 were previously reported.
(a) Kamimura, D.; Urabe, D.; Nagatomo, M.; Inoue, M. Org. Lett. 2013, 15, 5122;
For other applications of organotellurium compounds in radical reactions in
our laboratory, see: (b) Nagatomo, M.; Nishiyama, H.; Fujino, H.; Inoue, M.
28. Pandey, G.; Balakrishnan, M. J. Org. Chem. 2008, 73, 8128.
29. Dakin, L. A.; Langille, N. F.; Panek, J. S. J. Org. Chem. 2002, 67, 6812.
ꢀ
ꢀ
30. Duran-Galvan, M.; Connell, B. T. Tetrahedron 2011, 67, 7901.
31. Ikeda, K.; Achiwa, K.; Sekiya, M. Chem. Pharm. Bull. 1989, 37, 1179.
32. Donohoe, T. J.; Fishlock, L. P.; Procopiou, P. A. Org. Lett. 2008, 10, 285.
33. MacNevin, C. J.; Moore, R. L.; Liotta, D. C. J. Org. Chem. 2008, 73, 1264.
34. Torrente, S.; Alonso, R. Org. Lett. 2001, 3, 1985.
Please cite this article in press as: Kamimura, D.; et al., Tetrahedron (2016), http://dx.doi.org/10.1016/j.tet.2016.04.023