A convergent route to functional protected amines, diamines, and β-amino acids

Article abstract of DOI:10.1016/j.tet.2014.07.055

Phthalimide protected amines react with NBS under peroxide initiation to give geminal phthalimido-bromo derivatives, which are readily converted into the corresponding xanthates. These xanthates in turn undergo radical additions to numerous olefins, provi

Full text of DOI:10.1016/j.tet.2014.07.055

Tetrahedron 70 (2014) 7192e7206
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journal homepage: www.elsevier.com/locate/tet
A convergent route to functional protected amines, diamines,
and b-amino acids
Songzhe Han, Rachel A. Jones, B eꢀ atrice Quiclet-Sire, Samir Z. Zard *
Laboratoire de Synth ꢁe se Organique associ ꢀe au C. N. R. S., UMR 7652, Ecole Polytechnique, 91128 Palaiseau, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Phthalimide protected amines react with NBS under peroxide initiation to give geminal phthalimido-
bromo derivatives, which are readily converted into the corresponding xanthates. These xanthates in
turn undergo radical additions to numerous olefins, providing a convergent and modular access to
densely functionalized protected amines and diamines.
Received 12 April 2014
Received in revised form 8 July 2014
Accepted 14 July 2014
Available online 24 July 2014
Ó 2014 Elsevier Ltd. All rights reserved.
This paper is dedicated with respect to the
memory of Professor Alexander McKillop
Keywords:
Radical addition
Xanthates
Amines
Phthalimides
1. Introduction
The amino unit is one of the fundamental functional groups in
organic chemistry. The vast majority of substances in medicinal and
agrochemical use, as well as numerous natural products, such as
alkaloids and aminoacids, contain one or more nitrogen atoms.
Their synthesis therefore depends crucially on the ability to prepare
functionalized amine intermediates and, while a large number of
methods have been devised over the decades, the development of
1
new flexible routes remains an important objective. We have re-
cently exploited the stabilization of a radical by a phthalimido
group to accomplish efficient intermolecular radical chain addi-
tions of phthalimido-substituted xanthates to various alkenes and
thus access
a plethora of complex highly functionalized
2
,3
phthalimido-protected amines. The three approaches we studied
are summarized in Scheme 1. Initially, we explored the reactions of
the parent reagent 1 with various alkenes 2 to give adducts 3
0
(
PhthN¼phthalimido and FG and FG indicate the possible presence
2
a
of functional groups on the xanthate or the alkene partner). We
then established a route to more functionalized starting xanthates
4
hinging on a decarbonylative rearrangement of S-acyl xanthates
2
b
derived from various a-amino acids. The addition of xanthates 4
*
Corresponding author. Tel.: þ33 169335971; fax: þ33 169335972; e-mail ad-
Scheme 1.
dresses: tetlet@polytechnique.fr, zard@poly.polytechnique.fr (S.Z. Zard).
http://dx.doi.org/10.1016/j.tet.2014.07.055
0
040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7193
furnishes protected amines of type 5. Finally, even more elaborate
amine products 9 could be obtained by first adding functional
xanthates 6 to commercially available N-vinyl-phthalimide 7 and
There are in fact many other highly significant synthetic con-
sequences of this effect. They are summarized in Scheme 3. For
instance, the presence of an N-acetyl group increases the stability of
2
c
0
00
using adduct 8 in a second radical addition. The addition products
, 5, 8, and 9 may then be further transformed through ionic or
radical 18 via canonical structures 18 and 18 and allows the
preparation of complex -lactams such as 21 by addition of imide
3
b
4
radical-based methods. We now report what appears to be a very
useful complement to this otherwise fairly general approach.
At the origin of our work is an interesting observation: the ad-
dition of S-pyrrolidyl xanthate 10 to allyl cyanide leads mostly to
oligomers and hardly any of the adduct 11 can be isolated; in
contrast, under the same conditions, the addition of S-succinimi-
domethyl xanthate 12a or the phthalimido analogue 12b proceeds
efficiently to give the corresponding addition products 13a and 13b,
xanthate 19 to Feist ester 20. In the absence of an acetyl group, the
radical addition cannot be accomplished cleanly. Another impor-
tant extension is the replacement of one of the carbonyls of the
imide group by an aromatic ring, as shown by radical 22 and its
0
00
corresponding canonical structures 22 and 22 . The radical addi-
tions now lead to open chain and cyclic aniline derivatives, as il-
lustrated by the efficient addition of isatin derived xanthate 23 to
5
Boc-protected allylamine to furnish adduct 24 in high yield. The
2
a
respectively (Scheme 2). We ascribed this difference to an in-
creased allylic character of intermediate radicals 15a,b in compar-
ison to 14 due to the more extended conjugation in canonical
presence of a protected amine in product 24 underscores yet an-
other way to synthesize amines. Finally, S-phenyltriazolylmethyl
xanthate 26, described and studied by Katritzky and co-workers
0
00
6
structures 15 a,b and 15 a,b, leading to extra stabilization.
many years ago, is an equally good partner for the radical addi-
tion, and adducts such as 27 are readily obtained. The corre-
sponding radical 25 benefits from an analogous enhanced
stabilization due to the small allylic character visible in canonical
0
00
structures 25 and 25 . At the time, the significance of this mode of
radical stabilization was not appreciated.
Scheme 2.
As can be easily seen in the simplified mechanism for the radical
addition of xanthates pictured at the bottom of Scheme 2, it is
ꢀ
important for the initial radical R to be more stable than adduct
radical 16 in order to drive the sequence in the forward direction
(
this is to a first approximation, not taking into account possible
3
polar effects). In other words, the collapse of intermediate 17 must
preferentially give rise to radical R and not to adduct radical 16.
ꢀ
This is not the case with radicals 14, but fortunately appears to
happen with radicals 15. Even if small in magnitude, this additional
stabilization makes a large difference in practice and opens up all
the routes to the functional amines displayed in Scheme 1.
Scheme 3.

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S. Han et al. / Tetrahedron 70 (2014) 7192e7206
Since carbon radicals geminal to phthalimido groups possess
a small but nevertheless significant allylic character, we envisaged
exploiting this feature to introduce a bromine atom on a simple
phthalimide protected amine 28, by the same radical chain in-
volved in the classical WohleZiegler allylic bromination using N-
bromosuccinimide (NBS). Displacement of the bromine in 29 would
furnish the corresponding xanthate 30, which then could be in-
corporated in typical radical additions to alkenes (Scheme 4). This
would expand considerably the scope of the amine synthesis in
view of the pool of commercially available or easily accessible
primary amines.
xanthates, many different functional groups are tolerated on the
alkene partner.
Table 1
Synthesis of protected
b-aminoacids
Alkene
Radical adducts 32 and 33
3
3
2a, X¼SCSOEt
3a, X¼H, 76%
3
3
2b, X¼SCSOEt
3b, X¼H, 71%
3
3
2c, X¼SCSOEt
3c, X¼H, 66%
3
3
2d, X¼SCSOEt
3d, X¼H, 82%
3
3
2e, X¼SCSOEt
3e, X¼H, 78%
3
3
2f, X¼SCSOEt
3f, X¼H, 64%
3
3
2g, X¼SCSOEt
3g, X¼H, 81%
Scheme 4.
A search of the literature revealed just one instance where such
7
32h, X¼SCSOEt
a transformation was carried out on
b
-alanine derivative 28a. The
3
3h, X¼H, 66%
corresponding brominated derivative 29a could indeed be pro-
duced by selective bromination under standard NBS conditions.
While polar effects presumably play a role, it is nevertheless re-
markable that hydrogen abstraction takes place on the carbon
bearing the phthalimido group rather than on the carbon adjacent
to the ester, which would have led to a more thermodynamically
stable radical. Indeed, the very fact that hydrogen abstraction oc-
curs is in itself a testimony that radical 31a must benefit from some
form of stabilization arising from the presence of the phthalimido
group; and the most plausible explanation is the existence of the
3
3
2i, X¼SCSOEt
3i, X¼H, 57%
32j, X¼SCSOEt
33j, X¼H, 61%
0
extended conjugation similar to that shown in canonical forms 15
0
0
and 15 .
With an expedient access to bromo precursor 29a in hand, the
3
3
2k, X¼SCSOET
2k, X¼H, 71%
synthesis of the desired xanthate 30a was readily accomplished in
high yield by exposure of 29a to potassium O-ethyl xanthate in
acetone. Radical addition to a broad variety of alkenes proceeded
smoothly to give the corresponding adducts 32 (Table 1). In order to
simplify characterization by eliminating an asymmetric center, the
xanthate group was reductively removed by the Barton method,
8
using the triethylammonium salt of hypophosphorus acid. The
yields in Table 1 for compounds 33aek thus correspond to the
combined two steps. In line with previous radical additions of
All these reduced adducts are protected forms of the corre-
sponding b -amino acid 34 (b - indicates that the substituent is on
3
3

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7195
the carbon bearing the amino group in the
to the nomenclature introduced by Seebach).
b-amino acid, according
9
b
-Amino acids are of
major importance for the construction of metabolically stable
peptidomimetics and in the synthesis of medicinal substances,
since such motifs are found in numerous natural and unnatural
10
biologically active products. One prominent example is the clin-
ically very valuable taxol and its semi-synthetic derivatives, but
other examples are displayed in Fig. 1 (note the presence of the
arginine component in TAN-1057 A). Of particular interest in the list
in Table 1 is adduct 33h, which corresponds to methyl -lysinate
with the two amino groups protected as phthalimides. -Lysine (or
isolysine) is one of the earlier -amino acids to be found in nature,
along with -alanine and -leucine. It is present in blood platelets
b-
b
b
b
b
b
during coagulation and in tears, and acts as an antibiotic by causing
lysis of numerous Gram-positive bacteria. It was also observed as
a component of several antibiotics, such as streptolin, viomycin,
and streptothricin, mostly isolated from Streptomyces strains in the
940s and 1950s.1
1
b
-Lysine is biosynthetically derived from lysine
1
12
itself by the action of a SAM dependent lysine 2,3-aminomutase.
Scheme 5.
3
0e. The addition of the former to various alkenes gives the usual
mono-adducts 40aee and subsequently their reduction products
1aee (Scheme 6 and Table 3), whereas the latter undergoes
4
a double addition leading to structures 42aei as a complex mixture
of isomers (Scheme 6 and Table 4). Reductive elimination of the
xanthate groups simplifies considerably the mixture, since now
only meso and dl modifications of 43aei remain, in approximately
Fig. 1. Examples of important b-aminoacids.
2:1 ratio. It is worthwhile noting that the dl modification possesses
a C2v symmetry, and such 1,3-diamines, once resolved into the
enantiomers, should therefore prove useful as ligands for transition
metal catalyzed enantioselective transformations.
Other adducts of interest are 33i, which illustrates the possi-
bility of introducing fluorine substituents onto the -amino acid
side-chain, and 33j and 33k, where bicyclic azepine structures with
-amino acid sub-unit may be constructed by freeing the amino
group and allowing it to condense onto the internal cyclic ketone.
The possibility, in principle, of converting any given primary
amine into its corresponding xanthate 30 through formation of the
phthalimido derivative 28 and bromination with NBS opens up
many exciting opportunities for the synthesis of more complex
amines. For instance, phthalimides 28b,c derived from ethylamine
and 4-chlorobutylamine are readily brominated into 29b,c and
transformed into xanthates 30b,c as depicted in Scheme 5. Addition
to various alkenes and reduction of the corresponding adducts
b
Most of the compounds in Table 3, particularly diamines 43aei,
would be very tedious to prepare by traditional routes. Functional
polyamine derivatives are notoriously difficult to prepare because
a
b
13
of the extensive need for protectionedeprotection steps. An in-
triguing twist with di-xanthate 30e pictured in Scheme 7 is its
14
reaction with radical allylating agents such as vinyl epoxide. The
first additioneelimination generates allylic diethylborinate 44,
with the alkene moiety suitably placed for ring-closure with the
remaining xanthate to give protected 1,3-diaminocyclopentane
structure 45 as a mixture of diastereoisomers in good yield
where, surprisingly, the xanthate group, which normally should
have been present, has been replaced by a hydrogen atom. It ap-
pears that, once the second cyclization takes place, the resulting
radical 46 is ideally placed to abstract a hydrogen atom from one of
the ethyl radicals on the boron. This leads to a more highly stabi-
lized radical 47, because the overlap of the SOMO with the empty
orbital on boron results in a favorable one-electronetwo orbital
interaction. Radical 47 could combine with oxygen or exchange
a xanthate group with the starting material 30e. Either way, the
chain is ultimately propagated. Finally, hydrolysis upon work up
releases the observed alcohol 45.
3
5aee and 37aee with triethylammonium hypophosphite fur-
nishes the respective phthalimides 36aee and 38aee, respectively
Scheme 5 and Table 2). The simultaneous presence of a protected
(
amine and a chlorine atom four carbons away in adducts 38 can be
exploited to construct substituted pyrrolidines, as illustrated by the
smooth formation of pyrrolidine 39 from compound 38e (Scheme
5
). All, that is, needed is to unmask the amine with hydrazine in
methanol followed by treatment with 4-toluenesulfonyl chloride
and triethylamine without purification of the intermediate.
A more interesting extension of this approach is outlined in
Scheme 6; it involves treatment of di-phthalimide 28d derived
from 1,3-diaminopropane with NBS under irradiation. Both the
mono-bromo- or the di-bromo-products 29d and 29e can be ob-
tained, depending on the number of equivalents of NBS employed,
and converted cleanly into the corresponding xanthates 30d and
In conclusion, the present approach, in association with those
previously described and summarized in Scheme 1 above, consti-
tute a very powerful unified, flexible, and modular strategy for
assembling functional primary terminal or internal aliphatic
amines. They all rely on the hitherto unappreciated stabilizing

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S. Han et al. / Tetrahedron 70 (2014) 7192e7206
Table 2
Radical addition of phthalimido-substituted xanthates
Alkene
Radical adducts 35e38
3
3
5a, X¼SCSOEt
6a, X¼H, 76%
3
3
5a, X¼SCSOEt
6a, X¼H, 71%
3
3
5c, X¼SCSOEt
6c, X¼H, 66%
3
3
5d, X¼SCSOEt
6d, X¼H, 82%
3
3
5e, X¼SCSOEt
6e, X¼H, 78%
Scheme 6.
3
3
7a, X¼SCSOEt
8a, X¼H, 64%
Table 3
Synthesis of protected 1,3-diamines
3
3
7b, X¼SCSOEt
8b, X¼H, 64%
Alkene
Radical adducts 40 and 41
4
4
0a, X¼SCSOEt
1a, X¼H, 68%
3
3
7c, X¼SCSOEt
8c, X¼H, 68%
4
4
0b, X¼SCSOEt
1b, X¼H, 71%
3
3
7d, X¼SCSOEt
8d, X¼H, 61%
4
0c, X¼SCSOEt
3
3
7e, X¼SCSOEt
8e, X¼H, 67%
41c, X¼H, 71%
4
4
0d, X¼SCSOEt
1d, X¼H, 66%
4
4
0e, X¼SCSOEt
1e, X¼H, 62%
effect of an imide, and especially the phthalimido group. This
concept can be extended to other nitrogen derivatives, such as
b
-
lactams, anilines, and benzotriazoles, where analogous canonical
resonance structures provide the intermediate carbon radical with
some measure of allylic character. The possibility of bringing to-
gether an amine and various reactive electrophilic groups such as
halides, ketones, nitriles, or esters allows interesting subsequent
transformations based on traditional ionic or organometallic
chemistry. The synthesis of pyrrolidine 39 is one simple illustration
of the synthetic potential of combining the radical addition of
xanthates with an ionic substitution reaction.
2. Experimental
2.1. General conditions
Anhydrous dichloromethane was obtained by distillation from
calcium hydride under nitrogen. Anhydrous THF and diethyl ether

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7197
Table 4
Double radical additions of phthalimido-substituted di-xanthates
Alkene Radical adducts 42 and 43
4
4
2a, X¼SCSOEt
3a, X¼H, 58%
4
4
2b, X¼SCSOEt
3b, X¼H, 61%
4
4
2c, X¼SCSOEt
3c, X¼H, 67%
Scheme 7.
were obtained by distillation from sodium benzophenone ketyl
under nitrogen. Other solvents were used as supplied by com-
mercial sources. Petroleum ether refers to the fraction of light pe-
4
4
2d, X¼SCSOEt
3d, X¼H, 67%
ꢁ
troleum ether, boiling between 40 and 60 C. Purification
procedures were in accordance with the instructions in D. D. Perrin
and W. L. F. Armarego, ‘Purification of Laboratory Chemicals’, Fourth
Edition, The Bath Press, Bath, 2002. All reactions were carried out
4
4
2e, X¼SCSOEt
3e, X¼H, 53%
under dry, oxygen free nitrogen. Flash chromatography was per-
ꢂ
formed on silica gel (SDS, 60 A, 40e63
mm) as the stationary phase.
Thin Layer Chromatography (TLC) was performed on aluminum
plates pre-coated with silica gel (Merck silica gel, 60 F254), which
were visualized by the quenching of UV fluorescence when appli-
cable (
l
max¼254 nm and/or 366 nm) and/or by staining with ani-
saldehyde or vanillin in acidic ethanol followed by heating. When
compounds could not be visualized with anisaldehyde or vanillin,
a solution of phosphomolybdic acid in ethanol or a potassium
permanganate aqueous solution was used. Infrared spectra were
4
4
2f, X¼SCSOEt
3f, X¼H, 61%
3 2
recorded as solutions in CDCl using CaF cells, on a PerkineElmer
FT 1600 or FT 2000. Absorption maxima (
n
max) are reported in
ꢂ1
wavenumbers (cm ) and only selected peaks are reported. Mag-
netic resonance spectra were recorded at ambient temperature on
either a Bruker AMX 400, or a Bruker Avance DPX 400 instrument.
4
4
2g, X¼SCSOEt
3g, X¼H, 63%
1
Proton magnetic resonance spectra ( H NMR) were recorded at
4
00 MHz and coupling constants (J) are reported to ꢃ0.5 Hz. The
following abbreviations were utilized to describe peak patterns
when appropriate: br¼broad, s¼singlet, d¼doublet, t¼triplet,
q¼quartet, and m¼multiplet. Carbon magnetic resonance spectra
1
3
(
H C
C NMR) were recorded at 100 MHz. Chemical shifts (d , d ) are
4
4
2h, X¼SCSOEt
3h, X¼H, 54%
quoted in parts per million (ppm) and are referenced to the residual
solvent peak (CDCl
3
:
H
d ¼7.26 and
d
C
¼77.0). High-resolution mass
þ
spectra were recorded by positive electron impact ionization (EI )
at 70 eV on a JEOL JMS-GCmate II mass spectrometer. The quoted
masses are accurate to ꢃ5 ppm. DLP corresponds to di-lauroyl
peroxide (often sold under lauroyl peroxide or laurox).
4
4
2i, X¼SCSOEt
3i, X¼H, 71%
2.2. General procedure A for radical addition
A magnetically stirred solution of xanthate (1 equiv) and olefin
(1.5e3.0 equiv) was dissolved in ethyl acetate (1 ml/mmol of xan-
thate) was refluxed for 15 min. DLP (5 mol %) was then added and
additional DLP (5 mol %) was added every 60 min until total

7198
S. Han et al. / Tetrahedron 70 (2014) 7192e7206
consumption of xanthate. The mixture was then cooled to room
temperature and the solvent was evaporated under reduced pres-
sure. The residue was either engaged in a new reaction or purified
by flash chromatography on silica gel to yield the desired
compounds.
(m, 1H, CHHCH
2H, NCHCH ); C NMR (100 MHz, CDCl ): d
2 3 C
2
Ph), 1.82e1.73 (m, 1H, CHHCH
2
Ph), 1.64e1.57 (m,
171.3 (OCO), 168.3
(NCO), 141.7 (CqAr), 133.9 (CHPhth), 131.7 (CqPhth), 128.3, 128.2,
125.8 (Ar), 123.2 (CHPhth), 51.7 (CO CH ), 47.8 (NCH), 36.7
1
3
2
3
(CH
CCl
2
CO
2
Me), 35.2 (ArCH
2
), 31.8 (NCHCH
2
), 28.1 (ArCH
CH
2 2
);
n
max
ꢂ1
þ
(
4
)/cm : 1776, 1745, 1716, 1206, 1173; HRMS (EI ): m/z calcu-
2
.3. General procedure B for reduction
4
lated (found) for C21H21NO : 351.1471 (351.1471).
The residue was dissolved in dioxane (10 ml/mmol) then trie-
2.6. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-acetoxy-hex-
anoic acid methyl ester (33b)
thylamine (3.3 equiv) and a solution of H
3 2
PO 50% in water
(
3 equiv) were added. The solution was refluxed for 15 min and
AIBN (10 mol %) was then added. After 1 h, the solution was allowed
to cool to room temperature, water and ethyl acetate were added.
The organic layer was washed with water and brine, dried
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and allyl acetate (64 mg 0.64 mmol), and needed 20 mol % of DLP to
go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
(
2 4
Na SO ), and concentrated in vacuo. The residue was purified by
flash chromatography on silica gel to yield the desired compounds.
ethyl acetate, 10:1e4:1 v/v) afforded 99 mg 33b (yield: 71%) as
1
2
.4. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-3-ethoxythio-car-
a colorless oil. H NMR (400 MHz; CDCl
3
):
d
H
7.87e7.79 (m, 2H,
bonylsulfanyl-propionic acid methyl ester (30a)
CHPhth), 7.76e7.67 (m, 2H, CHPhth), 4.71e4.63 (1H, m, NCH), 4.04
t, 2H, J¼6.5 Hz, CH OAc), 3.60 (s, 3H, CO CH ), 3.18 (dd, 1H, J¼9.4,
16.1 Hz, CHHCO Me), 2.01
Me), 2.80 (dd, 1H, J¼5.4, 16.1 Hz, CHHCO
(s, 3H, OCOCH ), 1.87e1.76 (m, 2H, NCHCH ), 1.63e1.55 (m, 2H,
171.2 (OCO), 171
(OCO), 168.2 (NCO), 134 (CHPhth), 131.7 (CqPhth), 123.3 (CHPhth),
(
2
2
3
Phthalimide (30 g, 0.21 mol) and methyl acrylate (28.2 ml,
2
2
0
.3 mol) with DBU (15.6 ml, 0.1 mmol) were stirred in acetonitrile
3
2
1
3
(
100 ml) at room temperature for 2 h. The reaction mixture was
2 2 3 C
NCHCH CH ); C NMR (100 MHz, CDCl ): d
then concentrated under reduced pressure and poured into pe-
troleum ether to get a solid, which was washed with water to yield
pure product 28a (45.4 g, 94%). Compound 28a (2.1 g, 9.00 mmol),
63.6 (CH
28.9 (NCHCH
2
CH
2
OAc), 51.8 (CO
2
CH
3
), 47.7 (NCH), 36.7 (CH
2
CO
2
Me),
ꢂ1
2
), 25.5 (NCHCH
2
CH
2
);
nmax (CCl
4
)/cm : 1777, 1744,
þ
NBS (1.92 g, 10.08 mmol) in CCl
4
(150 ml) were heated at reflux
1717, 1237, 1173; HRMS (EI ): m/z calculated (found) for C17
H
19NO
6
:
under nitrogen for 5 h; the reaction was initiated by irradiation
with a 300 W lamp. The reaction mixture was then cooled, filtered,
and washed with sodium thiosulfate. After extracting the solution
with DCM, the organic layer was concentrated under reduced
pressure to yield 2.3 g product 29a (83%) without further purifi-
cation. Compound 29a (2.3 g, 7.5 mmol) was dissolved in acetone
333.1212 (333.1210).
2.7. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-(trimethylsilyl)-
hexanoic acid methyl ester (33c)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and allyl trimethylsilane (96 mg, 0.84 mmol), and needed 20 mol %
of DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
(
8
2 ml/mmol). Under a nitrogen atmosphere KSCSOEt (1.3 g,
mmol) was added portion wise over a period of 5 min. It was then
left to stir for a further 20 min before the acetone was evaporated
off under reduced pressure. The residue was then taken up in DCM/
H
2
O and extracted. The DCM layers were dried over Na
2
SO
4
before
ether/ethyl acetate, 5:1 v/v) afforded 96 mg 33c (yield: 66%) as
1
being filtered and evaporated under reduced pressure to yield the
crude xanthate. This was then purified by column chromatography
using petroleum ether/ethyl acetate, 25:1e10:1 v/v, to obtain 2.1 g
a colorless oil. H NMR (400 MHz; CDCl
3
):
d
H
7.87e7.78 (m, 2H,
CHPhth), 7.75e7.66 (m, 2H, CHPhth), 4.71e4.64 (1H, m, NCH), 3.59
(s, 3H, CO CH Me), 2.76 (dd,
), 3.16 (dd, 1H, J¼9.6, 16.0 Hz, CHHCO
1H, J¼5.3, 16.0 Hz, CHHCO Me), 2.17e2.08 (m, 1H, CHCHHCH ),
1.73e1.68 (m, 1H, CHCHHCH ), 1.29e1.22 (m, 2H, CH CH Si),
0.60e0.38 (m, 2H, CH Si), 0.09 (s, 9H, Si(CH ); C NMR (100 MHz,
CDCl ): 173.2 (OCO), 170 (NCO), 135.7 (CHPhth), 133.6 (CqPhth),
125 (CHPhth), 53.5 (CO CH ), 49.4 (NCH), 38.5 (CH CO Me), 37.7
(CHCH ), 26.9, 25.2 (CH SiMe ), 22.5, 17.8 (CH CH SiMe ), 0.021
)/cm : 1776, 1745, 1716, 1249, 1204; HRMS
Si: 347.1553 (347.1546).
2
3
2
1
3
0a as a pale yellow oil in 80% yield. H NMR (400 MHz; CDCl
3
):
d
H
2
2
7
.91e7.85 (m, 2H, CHPhth), 7.77e7.72 (m, 2H, CHPhth), 6.65 (dd,1H,
J¼5.5, 10.2 Hz, CHS), 4.67 (dq, 2H, J¼1.0, 7.1 Hz, eOCH CH ), 3.66 (s,
H, CO CH
), 3.49 (dd, 1H, J¼10.2, 16.5 Hz, CHSCHH), 3.16 (dd, 1H,
2
2
2
13
2
3
2
3 3
)
3
2
3
3
d
C
1
3
J¼5.5, 16.5 Hz, CHSCHH), 1.44 (t, 3H, J¼7.1 Hz, eOCH
2
CH
209.7 (C]S), 169.4 (C]O), 166.5 (C]O), 134.4
CPhth), 131.6 (CPhth), 123.7 (CPhth), 70.6 (OCH CH ), 53.2 (CHS),
): max 2963,
3
); C NMR
2
3
2
2
(
(
5
100 MHz, CDCl
3
):
d
C
2
2
3
2
2
3
ꢂ1
2
3
(SiMe
3
);
n
max (CCl
4
þ
2.2 (CO
2
CH
3
), 37.2 (CH
2
), 13.7 (OCH
2
CH
3
); IR (CCl
4
n
(EI ): m/z calculated (found) for C18
H25NO
4
þ
1780, 1726, 1555, 1377, 1226, 1051; HRMS (EI ): m/z calculated
(
found) for C15
H15NO S
5 2
: 353.0392 (353.0391).
2.8. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-cyano-hexanoic
acid methyl ester (33d)
2
.5. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-phenyl-hex-
anoic acid methyl ester (33a)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and allyl cyanide (43 mg, 0.64 mmol), and needed 20 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and allylbenzene (76 mg, 0.64 mmol), and needed 20 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
ethyl acetate, 10:1e5:1 v/v) afforded 112 mg 33a (yield: 76%) as
ethyl acetate, 4:1 v/v) afforded 103 mg 33d (yield: 82%) as a pale
1
yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
7.89e7.81 (m, 2H,
CHPhth), 7.77e7.69 (m, 2H, CHPhth), 4.71e4.63 (1H, m, NCH), 3.62
(s, 3H, CO CH Me), 2.84 (dd,
1H, J¼5.7, 16.3 Hz, CHHCO
2.30e2.20 (m, 1H, CHHCH
a colorless oil. 1H NMR (400 MHz; CDCl
CHPhth), 7.75e7.66 (m, 2H, CHPhth), 7.23 (t, 2H, J¼7.3 Hz, Ar), 7.15
t, 1H, Ar), 7.12 (d, 2H, J¼6.9 Hz, Ar), 4.74e4.66 (m, 1H, NCH), 3.6 (s,
H, CO CH Me), 2.77 (dd, 1H,
), 3.17 (dd, 1H, J¼9.5, 16.1 Hz, CHHCO
J¼5.3, 16.1 Hz, CHHCO Me), 2.66e2.58 (m, 2H, CH Ph), 2.19e2.11
):
d
7.85e7.79 (m, 2H,
), 3.18 (dd, 1H, J¼9.0, 16.3 Hz, CHHCO
3
H
2
3
2
2
Me), 2.38 (t, 2H, J¼7.2 Hz, CH
2
CN), 1.90e1.82 (m, 1H, CHHCH
2
CN),
CN),
(
2
1
3
3
2
3
2
1.68e1.58 (m, 2H, CHCH
2 3 C
); C NMR (100 MHz, CDCl ): d 170.9
2
2
(OCO), 168.1 (NCO), 134.1 (CHPhth), 131.4 (CqPhth), 123.3 (CHPhth),

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7199
1
(
1
C
19 (CH
CHCH ), 22.2 (CH
745, 1716, 1211, 1172; HRMS (EI ): m/z calculated (found) for
2
CN), 51.8 (CO
2
CH
3
), 46.7 (NCH), 36.5 (CH
2
CO
2
Me), 31.1
1.33e1.26 (m, 2H, CHCH
2
CH
2
); 13C NMR (100 MHz, CDCl
3
):
d
C
171.1
2
2
CH CN), 16.5 (CH
2
2
CN); IR (CCl ): max 2248, 1776,
4
n
(OCO), 168.1 (NCO), 133.8 (CHPhth), 131.5 (CqPhth), 123.14, 123.11
(CHPhth), 119.3 (CH CN), 51.602 (CO CH ), 47.6 (NCH), 36.6
(CH CO Me), 31.7 (CHCH ), 27.9 (CHCH CH CH ), 25.3 (CH CH CN),
5 (CH CN); IR (CCl ): max 2249, 1776, 1744, 1712,
þ
2
2
3
H
16 16
N
2
O
4
: 300.1110 (300.1100).
2
2
2
2
2
2
2
2
2
2
CH
2
CN), 16.8 (CH
2
4
n
þ
2
.9. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-phenoxy-hex-
1206, 1178; HRMS (EI ): m/z calculated (found) for C18
H
20
N
2
O
4
:
anoaic acid methyl ester (33e)
328.1423 (328.1426).
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and allyl phenyl ether (86 mg, 0.64 mmol), and needed 20 mol % of
DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
2.12. 3,6-Bis(1,3-dioxo-1,3-dihydroisoindol-2-yl)hexanoic acid
methyl ester (33h)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and 2-allylisoindoline-1,3-dione (119 mg, 0.64 mmol), and needed
20 mol % of DLP to go to completion. The reduction was done fol-
lowing the general procedure B. Flash chromatography on silica gel
ether/ethyl acetate, 10:1 v/v) afforded 120 mg 33e (yield: 78%) as
1
a pale yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
7.88e7.79 (2H, m,
CHPhth), 7.76e7.68 (m, 2H, CHPhth), 7.27e7.18 (m, 2H, Ar), 6.90 (t,
1
3
H, J¼7.3 Hz, Ar), 6.83 (d, 2H, J¼7.9 Hz, Ar), 4.76e4.66 (1H, m, NCH),
.94 (t, 2H, J¼6.1 Hz, CH OPh), 3.60 (s, 3H, CO CH ), 3.21 (dd, 1H,
Me), 2.82 (dd, 1H, J¼5.3, 16.1 Hz,
Me), 2.31e2.18 (m, 1H, CHHCH OPh), 1.98e1.90 (m, 1H,
OPh), 1.78e1.69 (m, 2H, CHCH
170.9 (C]O), 168 (C]O), 158.5 (CqeO), 133.8 (CPhth),
31.4 (CqPhth), 129.1 (Ar), 123 (CPhth), 120.3 (Ar), 114.1 (Ar), 66.5
eCH OPh), 51.5 (CO CH ), 47.5 (NCH), 36.4 (CH CO ), 28.6
NCHCH max 1777, 1746, 1721, 1245, 1201,
21NO
(petroleum ether/ethyl acetate, 4:1 v/v) afforded 116 mg 33h (yield:
1
2
2
3
66%) as a colorless oil. H NMR (400 MHz; CDCl
3
):
d
H
7.84e7.75 (m,
J¼9.5, 16.1 Hz, CHHCO
CHHCO
CHHCH
CDCl ):
1
(
(
2
4H, CHPhth), 7.75e7.64 (m, 4H, CHPhth), 4.73e4.64 (m, 1H, NCH),
3.67 (m, 2H, NCH ), 3.58 (s, 3H, CO CH
), 3.18 (dd,1H, J¼9.6,16.1 Hz,
CHHCO Me), 2.19e2.09
Me), 2.77 (dd, 1H, J¼5.3, 16.1 Hz, CHHCO
(m, 1H, NCH CHH), 1.81e1.73 (m, 1H, NCH CHH), 1.69e1.61 (m, 2H,
NCHCH CH ); C NMR (100 MHz, CDCl ): 171.1 (OCO), 168.2,
168.2 (NCO), 133.9, 133.9 (CHPhth), 132, 131.7 (CqPhth), 123.3, 123.2
(CHPhth), 51.8 (CO CH ), 47.5 (NCH), 37.3 (NCH ), 36.6 (CH CO Me),
max 1776, 1745, 1718,
2
2
2
2
3
13
2
2
); C NMR (100 MHz,
2
2
3
d
C
2
2
13
2
2
3
d
C
2
2
3
2
2
2
), 25.9 (CH
2
); IR (CCl
4
):
n
2
3
2
2
2
þ
1174, 1006; HRMS (EI ): m/z calculated (found) for C21
H
5
:
29.6 (NCHCH
2
), 25.5 (NCH
2
CH
2
); IR (CCl
4
):
n
þ
3
67.1420 (367.1421).
1206, 1173; HRMS (EI ): m/z calculated (found) for C23
20
H N
2
O
6
:
420.1321 (420.1322).
2
.10. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-(4-
bromophenoxy)-hexanoic acid methyl ester (33f)
2.13. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-8,8,8-trifluoro-7-
hydroxy-7-(trifluoromethyl)-octanoic acid methyl ester (33i)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and 1-(allyloxy)-4-bromobenzene (136 mg, 0.64 mmol), and
needed 20 mol % of DLP to go to completion. The reduction was
done following the general procedure B. Flash chromatography on
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and 1,1,1-trifluoro-2-(trifluoromethyl)-pent-4-en-2-ol (133 mg,
0.64 mmol), and needed 20 mol % of DLP to go to completion. The
reduction was done following the general procedure B. Flash
chromatography on silica gel (petroleum ether/ethyl acetate, 10:1
silica gel (petroleum ether/ethyl acetate, 2:1 v/v) afforded 119 mg
1
3
3f (yield: 64%) as a yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
1
7
.88e7.78 (m, 2H, CHPhth), 7.75e7.66 (m, 2H, CHPhth), 7.34 (d, 2H,
J¼8.9 Hz, Ar), 6.80 (d, 2H, J¼8.9 Hz, Ar), 4.75e4.68 (1H, m, NCH),
.90 (dt, 2H, J¼1.6, 6.4 Hz, CH OPhBr), 3.60 (s, 3H, CO CH ), 3.21
dd, 1H, J¼9.5, 16.1 Hz, CHHCO Me), 2.82 (dd, 1H, J¼5.3, 16.1 Hz,
CHHCO Me), 2.29e2.21 (m, 1H, NCHCH CHH), 1.97e1.89 (m, 1H,
NCHCH CHH), 1.76e1.68 (m, 2H, NCHCH
CDCl ): 171.2 (C]O), 168.3 (C]O), 158.8 (CqeO), 134.0, 133.9
CPhth), 131.7 (CqPhth), 129.3 (Ar), 123.3, 123.2 (CPhth), 120.6 (Ar),
14.4 (Ar), 66.7 (CH OPh), 51.8 (CO CH ), 47.7 (NCH), 36.7 (CH CO ),
8.9 (NCHCH ), 24.3 (CH max 1776, 1745, 1716,
v/v) afforded 106 mg 33i (yield: 57%) as a colorless oil. H NMR
(400 MHz; CDCl
CHPhth), 4.71e4.63 (1H, m, NCH), 3.71 (s, 1H, OH), 3.61 (s, 3H,
CO CH Me), 2.84 (dd, 1H,
J¼5.9, 16.4 Hz, CHHCO
2.09e2.02 (m,1H, CH CHH(CF
1.63e1.54 (m, 2H, CHCH
3 H
): d 7.87e7.78 (m, 2H, CHPhth), 7.77e7.68 (m, 2H,
3
2
2
3
(
2
2
3
), 3.17 (dd, 1H, J¼8.9, 16.4 Hz, CHHCO
Me), 2.25e2.17 (m, 1H, CH
), 1.87e1.76 (m, 2H, CH
); C NMR (100 MHz, CDCl
2
2
2
2
2
CHH (CF
3
)
)
2
),
),
13
2
2
CH
2
); C NMR (100 MHz,
2
3
)
2
2
CH
):
2
(CF
3
2
1
3
3
d
C
2
3
d
C
171.3
(
(OCO), 168.6 (NCO), 134.2 (CHPhth), 131.5 (CqPhth), 123 (q, 1H,
J¼271.1 Hz, CF ), 123.4 (CHPhth), 51.9 (CO CH ), 47 (NCH), 36.6
(CH CO Me), 32.2 (CHCH ), 29.324 (CH CH(OH)(CF ), 18.432
(CHCH CH ); IR (CCl ): max 3474, 1776, 1744, 1717, 1206, 1178;
HRMS (EI ): m/z calculated (found) for C18 NO : 441.1011
441.101).
1
2
2
3
2
2
3
2
3
2
2
2
CH
2
OPh); IR (CCl
4
):
n
2
2
2
2
3 2
)
þ
1241, 1173, 1047; HRMS (EI ): m/z calculated (found) for
2
2
4
n
þ
C
21
H
20BrNO
5
: 445.0525 (445.0534).
H F
17 6
5
(
2
.11. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-8-cyano-octanoic
acid methyl ester (33g)
2.14. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-(2-
oxocyclopentyl)-hexanoic acid methyl ester (33j)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and hex-5-enenitrile (61 mg, 0.64 mmol), and needed 20 mol % of
DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and 2-allyl-cyclopentanone (79 mg, 0.64 mmol), and needed
20 mol % of DLP to go to completion. The reduction was done fol-
lowing the general procedure B. Flash chromatography on silica gel
(petroleum ether/ethyl acetate, 4:1 v/v) afforded 91 mg 33j (yield:
ether/ethyl acetate, 3:1 v/v) afforded 112 mg 33g (yield: 81%) as
1
a pale yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
7.87e7.78 (m, 2H,
CHPhth), 7.75e7.68 (m, 2H, CHPhth), 4.71e4.62 (1H, m, NCH), 3.61
s, 3H, CO CH Me), 2.80 (dd,
H, J¼5.6, 16.1 Hz, CHHCO
.05e1.97 (m, 1H, CHHCH
), 1.51e1.43 (m, 2H, CH
61%) as a colorless oil and a mixture of two diastereoisomers in
1
(
1
2
2
3
), 3.15 (dd, 1H, J¼9.2, 16.1 Hz, CHHCO
Me), 2.29 (t, 2H, J¼7.1 Hz, CH
CN), 1.75e1.66 (m, 1H, CHHCH
CH CH
2
a ratio 1:1. H NMR (400 MHz; CDCl
3
): Mixture of diastereoisomer:
2
2
2
2
CN),
CN),
CN),
d
H
7.89e7.77 (m, 2H, CHPhth), 7.76e7.65 (m, 2H, CHPhth),
4.70e4.61 (1H, m, NCH), 3.60 (s, 3H, CO CH
), 3.17 (dd, 0.5H, J¼2.1,
9.5 Hz, CHHCO Me), 2.79
Me), 3.13 (dd, 0.5H, J¼2.1, 9.5 Hz, CHHCO
2
2
3
1
.64e1.57 (m, 2H, CHCH
2
2
2
2
2

7200
S. Han et al. / Tetrahedron 70 (2014) 7192e7206
þ
(
dd, 0.5H, J¼1.1, 5.3 Hz, CHHCO
CHHCO Me), 2.30e2.21 (m, 1H, CHCOCH
COCHHCH COCH CHH, COCH CH CHH), 2.01e1.92 (m, 2H,
COCHH, COCH CHH), 1.77e1.69 (m, 3H, COCH CH CHH, NCHCH ),
.48e1.41 (m, 1H, COCHCHH), 1.34e1.21 (m, 3H, COCHCHH,
2
Me), 2.75 (dd, 0.5H, J¼1.0, 5.3 Hz,
1223, 1044; HRMS (EI ): m/z calculated (found) for C13
H
13NO
3
S
2
:
ꢁ
2
2
), 2.16e2.07 (m, 3H,
295.0337 (295.0346); mp: 103e104 C.
2
,
2
2
2
2
2
2
2
2.17. 2-(5-Phenylpentan-2-yl)isoindoline-1,3-dione (36a)
1
13
NCHCH
astereoisomer:
23.3 (CHPhth), 51.8 (CO
8.1 (CH CO Me), 36.8, 36.7 (COCH
2
CH
2
);
C
NMR (100 MHz, CDCl
171.4, 168.3 (NCO), 134 (CHPhth), 131.8 (CqPhth),
CH ), 48.9, 48.9 (NCH), 48, 47.9 (CHCO),
), 32.4, 32.3, 29.6, 29.6, 29.2,
): max 1776, 1743, 1716, 1206,
23NO : 357.1576
3
): Mixture of di-
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30b (100 mg, 0.34 mmol)
and allylbenzene (60 mg, 0.51 mmol), and needed 20 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
d
C
1
3
2
2
3
2
2
2
9.1, 24.5, 24.4, 20.7 (CH
173; HRMS (EI ): m/z calculated (found) for C20
2
); IR (CCl
4
n
þ
1
H
5
ethyl acetate, 10:1 v/v) afforded 75 mg 36a (yield: 76%) as a color-
less oil. H NMR (400 MHz; CDCl
1
(
357.1575).
3
):
d
H
7.86e7.77 (m, 2H, CHPhth),
7
.74e7.66 (m, 2H, CHPhth), 7.29e7.21 (m, 2H, Ar), 7.16 (t, 1H,
J¼6.7 Hz, Ar), 7.15 (d, 2H, J¼7.8 Hz, Ar), 4.43e4.37 (m, 1H, NCH),
2.69e2.56 (m, 2H, CH Ph), 2.17e2.12 (m, 1H, CHHCH Ph), 1.82e1.75
Ph), 1.64e1.55 (m, 2H), 1.52 (d, 3H, J¼6.9 Hz,
); C NMR (100 MHz, CDCl ): 168.4 (C]O), 133.7
2
.15. 3-(1,3-Dioxo-1,3-dihydroisoindol-2-yl)-6-(2-
oxocyclohexyl)-hexanoic acid methyl ester (33k)
2
2
(m, 1H, CHHCH
2
13
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30a (150 mg, 0.42 mmol)
and 2-allylcyclohexanone (88 mg, 0.64 mmol), and needed
NCHCH
3
3
d
c
(CPhth), 131.9 (CqPhth), 141.961, 128.288, 128.207, 125.686 (Ar), 123
(CPhth), 47.1 (NCH), 35.4 (CH Ph), 33.2 (NCHCH ), 28.6
max 2937, 1713, 1775,
1468, 1378, 1141, 1037; HRMS (EI ): m/z calculated (found) for
19 2
C H19NO : 293.1416 (293.1416).
2
2
2
0 mol % of DLP to go to completion. The reduction was done fol-
lowing the general procedure B. Flash chromatography on silica gel
petroleum ether/ethyl acetate, 5:1 v/v) afforded 110 mg 33k (yield:
1%) as a colorless oil and a mixture of two diastereoisomers in
(NCHCH
2
CH
2
), 18.649 (NCHCH
3
); IR (CCl
4
):
n
þ
(
7
1
a ratio 1:1. H NMR (400 MHz; CDCl
3
): Mixture of diastereoisomer:
7.85e7.76 (m, 2H, CHPhth), 7.76e7.68 (m, 2H, CHPhth),
.69e4.61 (1H, m, NCH), 3.60 (s, 3H, CO CH ), 3.21e3.13 (m, 1H,
Me), 2.81e2.72 (m, 1H, J¼5.0, 16.0 Hz,
Me), 2.36e2.28 (m, 1H, CHCOCH ), 2.26e2.17 (m, 2H,
CH ), 2.09e1.95 (m, 3H, COCH CHH, COCH CH CHH,
CHCHH), 1.71e1.67 (m, 3H, COCH CHH, COCH CH CHH, CHCHH),
CH ), 1.39e1.28 (m, 3H,
); C NMR (100 MHz, CDCl ): Mixture of
212.9 (CHCO), 171.4, 171.3 (OCO), 168.3 (NCO),
33.9 (CHPhth), 131.8 (CqPhth), 123.2 (CHPhth), 51.7 (CO CH ), 50.5
NCH), 47.97, 47.92 (CHCO), 41.9 (COCH ), 36.7 (CH CO Me), 34, 33.8
), 28.9, 28.8 (COCH CH ), 27.9
CH ), 23.9 (CHCH CH CH CH); IR
2.18. 4-(1,3-Dioxoisoindolin-2-yl)pentyl acetate (36b)
d
H
4
2
3
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30b (100 mg, 0.34 mmol)
and allyl acetate (51 mg, 0.51 mmol), and needed 20 mol % of DLP to
go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
J¼9.5, 16.1 Hz, CHHCO
CHHCO
COCH
2
2
2
2
2
2
2
2
2
2
2
1.66e1.56 (m, 3H, COCHCHH, CHCH
2
2
ethyl acetate, 10:1 v/v) afforded 66 mg 36b (yield: 71%) as a color-
13
1
COCHCHH, CHCH
diastereoisomer:
2
CH
2
3
less oil. H NMR (400 MHz; CDCl
3
):
d
H
7.82e7.72 (m, 2H, CHPhth),
d
C
7.72e7.63 (m, 2H, CHPhth), 4.48e4.41 (m, 1H, NCH), 4.03 (t, 2H,
J¼6.5 Hz, CH OAc), 2.15e2.08 (m, 1H, CHHCH OAc), 2.00 (s, 3H,
OCOCH ), 1.84e1.76 (m, 1H, CHHCH OAc), 1.63e1.54 (m, 2H,
NCHCH
), 1.47 (d, 3H, J¼6.9 Hz, NCHCH
CDCl ): 171 (CH CO), 168.4 (C]O), 133.9 (CPhth), 131.9 (CqPhth),
123.1 (CPhth), 63.9 (CH OAc), 47.1 (NCH), 30.2 (NCHCH ), 25.9
(NCHCH CH ), 20.9 (CH CO), 18.7 (NCHCH max 2928,
1
2
3
2
2
(
(
(
(
(
2
2
2
3
2
13
COCHCH
COCHCH
2
), 32.5 (NCHCH
), 24.9 (COCH CH
2
2
2
2
3
); C NMR (100 MHz,
2
2
2
2
2
2
2
3
d
c
3
þ
CCl
4
):
n
max 1776, 1745, 1715, 1208, 1173; HRMS (EI ): m/z calculated
25NO : 371.1733 (371.1743).
2
2
found) for C21
H
5
2
2
3
3
); IR (CCl
4
):
n
þ
1
742, 1713, 1469, 1368, 1239, 1052; HRMS (EI ): m/z calculated
2
.16. Dithiocarbonic acid [1-bis-(1,3-dioxo-1,3-
4
(found) for C15H17NO : 275.1158 (275.1151).
dihydroisoindol-2-yl)-1-ethyl] ester O-ethyl ester (30b)
2.19. 2-(5-(Trimethylsilyl)pentan-2-yl)isoindoline-1,3-dione
To a solution of 28b (4 g, 23 mmol) in CCl
4
(150 ml) NBS (4.8 g,
(36c)
27 mmol) was added and then the solution was heated at reflux
under nitrogen for 2 h; the reaction was initiated by irradiation
with a 300 W lamp. The reaction mixture was then cooled, filtered,
and washed with sodium thiosulfate. After extracting the solution
with DCM, the organic layer was concentrated under reduced
pressure to obtain 4.9 g 29b (yield: 85%) without further purifica-
tion. Compound 29b (4.9 g, 20 mmol) was dissolved in acetone
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30b (100 mg, 0.34 mmol)
and allyl trimethylsilane (78 mg, 0.68 mmol), and needed 20 mol %
of DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
ether/ethyl acetate, 10:1 v/v) afforded 64 mg 36c (yield: 66%) as
1
(
2 ml/mmol). KSCSOEt (3.5 g, 22 mmol) was then added portion
a colorless oil. H NMR (400 MHz; CDCl
3
):
d
H
7.86e7.77 (m, 2H,
wise over a period of 5 min. It was then left to stir for further 20 min
before the acetone was evaporated off under reduced pressure. The
CHPhth), 7.74e7.66 (m, 2H, CHPhth), 4.42e4.33 (m, 1H, NCH),
2.11e2.03 (m, 1H, CHHCH TMS), 1.81e1.72 (m, 1H, CHHCH TMS),
1.67e1.59 (m, 2H NCHCH
), 1.45 (d, 3H, J¼6.9 Hz), 0.55e0.44 (m,
2H, CH
TMS), ꢂ0.08 (s, 9H); C NMR (100 MHz, CDCl
(C]O), 133.7 (CPhth), 132 (CqPhth), 123 (CPhth), 46.9 (NCH), 37.3
(NCHCH ), 21.1 (NCHCH CH ), 18.6 (NCHCH ), 16.1 (CH
max 2927, 1712, 1774, 1378, 1248, 1108, 1025;
2
2
residue was then taken up in DCM/H
2
O and extracted. The DCM
2
13
layers were dried over Na SO before being filtered and evaporated
2
4
2
3 c
): d 168.5
under reduced pressure to yield the crude xanthate. This was then
purified by column chromatography using petroleum ether/ethyl
acetate, 10:1e4:1 v/v, to obtain 4.8 g 30b (yield: 81%) as a pale
2
2
2
3
2
TMS), ꢂ1.8
(TMS); IR (CCl
4
):
n
þ
yellow solid, which was crystallized from ethyl acetate/petroleum
HRMS (EI ): m/z calculated (found) for C16
H
23NO
2
Si: 289.1498
1
ether. H NMR (400 MHz; CDCl
3
):
d
H
7.85e7.76 (m, 2H, CHPhth),
(289.1504).
7
.77e7.69 (m, 2H, CHPhth), 6.34 (q, 1H, J¼7.3 Hz, CHS), 4.60 (q, 2H,
13
OCH
NMR (100 MHz, CDCl
31.7 (CPhth), 123.6 (CPhth), 70.3 (OCH
CHSCH ), 13.8 (OCH CH ); IR (CCl ): max 2928, 1781, 1723, 1376,
2
CH
3
),1.82 (d, 3H, J¼7.3 Hz),1.37 (t, 3H, J¼7.1 Hz, OCH
): 211.1 (C]S), 166.6 (C]O), 134.4 (CPhth),
CH ), 53.4 (CHS), 20
2
CH
3
);
C
2.20. 5-(1,3-Dioxoisoindolin-2-yl)hexanenitrile (36d)
3
d
C
1
(
2
3
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30b (100 mg, 0.34 mmol)
3
2
3
4
n

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7201
and allyl cyanide (35 mg, 0.51 mmol), and needed 20 mol % of DLP
2.23. 8-Chloro-5-(1,3-dioxoisoindolin-2-yl)octanenitrile (38a)
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30c (100 mg, 0.28 mmol)
and allyl cyanide (40 mg, 0.33 mmol), and needed 30 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
ethyl acetate, 10:1 v/v) afforded 67 mg product 36d (yield: 82%) as
1
a pale yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
7.81e7.72 (m, 2H,
CHPhth), 7.71e7.63 (m, 2H, CHPhth), 4.37e4.29 (m, 1H, NCH), 2.33
(
(
t, 2H, J¼7.2 Hz, CH
2
CN), 2.25e2.17 (m, 1H, CHHCH
2
CN), 1.89e1.81
), 1.46 (d, 3H,
168.3 (C]O), 134
CPhth), 131.7 (CqPhth), 123.1 (CPhth), 119.162 (CN), 46.3 (NCH),
m, 1H, CHHCH CN), 1.62e1.56 (m, 2H, NCHCH
2
2
ethyl acetate, 2:1 v/v) afforded 54 mg 38a (yield: 64%) as a pale
13
1
J¼7.2 Hz, NCHCH
3
); C NMR (100 MHz, CDCl
3
):
d
c
yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
7.88e7.79 (m, 2H,
(
CHPhth), 7.79e7.70 (m, 2H, CHPhth), 4.27e4.18 (1H, m, NCH),
3.59e3.48 (m, 2H, CH CN), 2.31e2.23
Cl), 2.36 (t, 2H, J¼7.2 Hz, CH
(m, 2H, NCHCHH, NCHCHH), 1.98e1.83 (m, 2H, NCHCHH, NCHCHH),
3
2.5 (NCHCH
IR (CCl ):
m/z calculated (found) for C14
2
), 22.7 (NCHCH
max 2929, 1713, 1776, 1469, 1370, 1144, 1041; HRMS (EI ):
2
CH
2
), 18.6 (NCHCH
3
), 16.688 (CH
2
CN);
2
2
þ
4
n
13
H
14
N
2
O
2
: 242.1055 (242.1057).
1.77e1.68 (m, 2H, CH
NMR (100 MHz, CDCl
2
CH
):
CqPhth), 123.4 (CHPhth), 119.1 (CN), 50.2 (NCH), 44.1 (CH
NCHCH ), 29.5 (NCHCH ), 29.4 (CH CH Cl), 22.5 (CH CH CN), 16.7
CH CN); IR (CCl ): max; HRMS (EI ): m/z calculated (found) for
: 304.0979 (304.0985).
2
Cl), 1.67e1.57 (m, 2H, NCHCH
168.5 (NCO), 134.2 (CHPhth), 131.4
Cl), 31.3
2
CH
2
);
C
3
d
C
(
(
(
2
2
.21. 2-(5-Phenoxypentan-2-yl)isoindoline-1,3-dione (36e)
Following the general procedure A for radical addition, the re-
2
2
2
2
2
2
þ
2
4
n
C
16
2 2
H17ClN O
action was carried out with a solution of 30b (100 mg, 0.34 mmol)
and allyl phenyl ether (68 mg, 0.51 mmol), and needed 20 mol % of
DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
0
2
.24. 2,2 -(7-Chloroheptane-1,4-diyl)bis(isoindoline-1,3-
dione) (38b)
ether/ethyl acetate, 10:1 v/v) afforded 81 mg 36e (yield: 78%) as
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30c (100 mg, 0.28 mmol)
and 2-allylisoindoline-1,3-dione (104 mg, 0.56 mmol), and needed
1
a colorless solid. H NMR (400 MHz; CDCl
3
):
d
H
7.89e7.78 (m, 2H,
CHPhth), 7.74e7.63 (m, 2H, CHPhth), 7.28e7.21 (m, 2H, Ar), 6.91 (t,
1
3
H, J¼6.7 Hz, Ar), 6.86 (d, 2H, J¼7.8 Hz, Ar), 4.50e4.41 (m, 1H, NCH),
OPh), 2.31e2.20 (m, 1H,
OPh), 1.99e1.92 (m, 1H, CHHCH OPh), 1.82e1.74 (m, 2H,
), 1.52 (d, 3H, J¼6.9 Hz, NCHCH
168.4 (C]O), 158.8 (Ar), 133.8 (CPhth), 131.8 (CqPhth),
29.3 (Ar), 123 (CPhth), 120.5 (Ar), 114.3 (Ar), 67 (CH OPh), 47.1
NCH), 30.1 (NCHCH ), 26.5 (NCHCH CH ),18.7 (NCHCH
3
5 mol % of DLP to go to completion. The reduction was done fol-
lowing the general procedure B. Flash chromatography on silica gel
petroleum ether/ethyl acetate, 4:1 v/v) afforded 116 mg 38b (yield:
.95 (dt, 2H, J¼1.6, 6.4 Hz, CH
2
CHHCH
NCHCH
CDCl ): d
3 c
1
2
2
2
(
13
3
); C NMR (100 MHz,
1
64%) as a colorless oil. H NMR (400 MHz; CDCl
4H, CHPhth), 7.75e7.64 (m, 4H, CHPhth), 4.30e4.21 (1H, m, NCH),
3.71e3.62 (m, 2H, NCH Cl), 2.27e2.16 (m,
), 3.5 (t, 2H, J¼6.3 Hz, CH
2H, NCHCH ), 1.92e1.84 (m, 1H, NCHCHH), 1.77e1.65 (m, 5H,
3 H
): d 7.85e7.76 (m,
3
2
2
(
2
2
2
3
); IR (CCl
4
):
þ
2
n
max 2939, 1713, 1775, 1470, 1369, 1172, 1051; HRMS (EI ): m/z
13
NCHCHH, CH
68.5, 168.3 (NCO), 134, 133.9 (CHPhth), 132, 131.6 (CqPhth), 123.3,
23.2 (CHPhth), 50.8 (NCH), 44.2 (CH Cl), 37.3 (NCH ), 29.6
(NCHCH ), 29.5 (NCHCH ), 29.5 (CH CH
(CCl ):
calculated (found) for C23
2 2 2 2 3 C
CH Cl, NCHCH CH ); C NMR (100 MHz, CDCl ): d
ꢁ
calculated (found) for C19
H19NO
3
: 309.1365 (309.1372), mp: 97 C.
1
1
2
2
2
.22. 4-Chloro-1-(1,3-dioxoisoindolin-2-yl)butyl-O-ethyl car-
2
n
2
2
2
Cl), 25.7 (CH
2
NCH
2
); IR
þ
bonodithioate (30c)
4
max 2937, 1718, 1773, 1356, 1244, 1038; HRMS (EI ): m/z
2 4
H21ClN O : 424.1190 (424.1198).
To a solution of 28c (4.25 g, 18 mmol) in CCl
4
(150 ml), NBS
(
3.2 g, 18 mmol) was added and then the solution was heated at
2.25. 7-Chloro-4-(1,3-dioxoisoindolin-2-yl)heptyl acetate
(38c)
reflux under nitrogen for 4 h, meanwhile the reaction was initiated
by irradiation with a 300 W lamp. The reaction mixture was then
cooled, filtered, and washed with sodium thiosulfate. After
extracting the solution with DCM, the organic layer was concen-
trated under reduced pressure to obtain 5 g 29c (yield: 88%)
without further purification. Compound 29c (5 g, 15.8 mmol) was
dissolved in acetone (2 ml/mmol). KSCSOEt (2.4 g, 15 mmol) was
added portion wise over a period of 5 min. It was then left to stir
until the starting material was totally consumed by monitoring TLC.
After concentrating the resulting solution the residue was then
taken up in DCM/H
were dried over Na
reduced pressure to yield the crude xanthate. This was then puri-
fied by column chromatography using petroleum ether/ethyl ace-
tate, 10:1e4:1 v/v, to obtain 4.8 g 30c (yield: 86%) as a pale yellow
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30c (100 mg, 0.28 mmol)
and allyl acetate (56 mg 0.56 mmol), and needed 30 mol % of DLP to
go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
ethyl acetate, 10:1e4:1 v/v) afforded 94 mg 38c (yield: 68%) as
1
a colorless oil. H NMR (400 MHz; CDCl
3
):
d
H
7.86e7.77 (m, 2H,
CHPhth), 7.77e7.66 (m, 2H, CHPhth), 4.28e4.19 (1H, m, NCH), 4.04
(t, 2H, J¼6.5 Hz, CH OAc), 3.56e3.47 (m, 2H, CH Cl), 2.26e2.17 (m,
2H, NCHCH ), 2.01 (s, 3H, OAc), 1.96e1.87 (m, 1H, NCHCHH),
1.85e1.78 (m,1H, NCHCHH),1.76e1.65 (m, 2H, CH CH Cl),1.28e1.19
171 (OCOCH ),
168.6 (NCO), 134 (CHPhth), 131.5 (CqPhth), 123.3 (CHPhth), 63.8
(CH OAc), 50.9 (NCH), 44.2 (CH Cl), 29.6 (NCHCH ), 29.5 (NCHCH ),
28.9 (CH CH Cl), 25.8 (CH CH OAc), 20.1 (OCH ); IR (CCl ):
2989, 1712, 1766, 1389, 1268, 1046; HRMS (EI ): m/z calculated
(found) for C17 20ClNO : 337.1081 (337.1087).
2
O and extracted three times. The DCM layers
SO before being filtered and evaporated under
2
2
2
4
2
2
):
2
13
(m, 2H, NCHCH
2
CH
2
); C NMR (100 MHz, CDCl
3
d
C
3
sticky liquid, which was crystallized from ethyl acetate/petroleum
ether. H NMR (400 MHz; CDCl
7
2
2
OCH
2
2
2
2
1
3
):
d
H
7.88e7.79 (m, 2H, CHPhth),
2
2
2
2
3
4
n
max
þ
.79e7.69 (m, 2H, CHPhth), 6.24 (dd, 1H, J¼7.0, 9.1 Hz, CHS), 4.60 (q,
H, J¼7.1 Hz, OCH
2
CH
3
), 3.54 (t, 2H, J¼6.5 Hz, CH
2
Cl), 2.39e2.29 (m,
Cl), 1.38 (t, 3H, J¼7.1 Hz,
210.17 (C]S), 166.6 (C]
CH ), 56.8
Cl), 13.6
max 2934, 1767, 1731, 1386, 1232, 1076; HRMS
H
4
H, CHSCH ), 1.92e1.81 (m, 2H, CH
2
2
CH
):
2
13
2
CH
3
); C NMR (100 MHz, CDCl
3
d
C
2.26. 2-(1-Chloro-7-(trimethylsilyl)heptan-4-yl)isoindoline-
1,3-dione (38d)
O),134.3 (CPhth),131.3 (CPhth),123.5 (CPhth), 70.4 (OCH
2
3
(
(
(
(
CHS), 43.5 (CH
OCH
EI ): m/z calculated (found) for
357.0266); mp: 132e133 C.
2
Cl), 30.6 (CHSCH
2 2 2
), 29.3 (CH CH
2
CH
3
); IR (CCl
4
):
n
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30c (100 mg, 0.28 mmol)
and allyl trimethylsilane (96 mg, 0.84 mmol), and needed 30 mol %
þ
15 3 2
C H16ClNO S : 357.0260
ꢁ

7202
S. Han et al. / Tetrahedron 70 (2014) 7192e7206
of DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
ether/ethyl acetate, 5:1 v/v) afforded 96 mg 38d (yield: 61%) as
2.29. Dithiocarbonic acid [1,3-bis-(1,3-dioxo-1,3-
dihydroisoindol-2-yl)] ester ethyl ester (30d)
a colorless oil. 1H NMR (400 MHz; CDCl
):
CHPhth), 7.78e7.67 (m, 2H, CHPhth), 4.28e4.19 (1H, m, NCH),
.57e3.47 (m, 2H, CH Cl), 2.22e2.11 (m, 2H, NCHCH ), 1.92e1.83
m, 1H, NCHCHH), 1.77e1.69 (m, 3H, NCHCHH, CH CH Cl), 1.31e1.20
m, 2H, NCHCH CH ), 0.53e0.42 (m, 2H, CH
TMS), ꢂ0.09 (s, 9H,
): 168.7 (NCO), 134 (CHPhth),
31.7 (CqPhth), 123.1 (CHPhth), 50.9 (NCH), 44.4 (CH Cl), 36
NCHCH ), 29.7 (NCHCH ), 29.6 (CH CH Cl), 20.9 (CH CH TMS),
6.093 (CH ): max 2934,1756, 1346,1287,
TMS), ꢂ1.8 (TMS); IR (CCl
023; HRMS (EI ): m/z calculated (found) for C18 26ClNO Si:
d
7.88e7.79 (m, 2H,
3
H
4
To a solution of 28d (3 g, 9.00 mmol) in CCl (150 ml), NBS
(1.92 g, 10.08 mmol) was added, then the solution was heated at
reflux under nitrogen for 3 h; the reaction was initiated by irradi-
ation with a 300 W lamp. The reaction mixture was then cooled,
filtered, and washed with sodium thiosulfate. After extracting the
solution with DCM, the organic layer was concentrated under re-
duced pressure to yield 3.2 g 29d (86%) without further purifica-
tion. Compound 29d (3.2 g, 7.7 mmol) was dissolved in acetone
(2 ml/mmol). Under nitrogen protection KSCSOEt (1.36 g, 8.5 mmol)
was added portion wise over a period of 5 min. It was then left to
stir for further 20 min before the acetone was evaporated off under
3
2
2
(
(
2
2
2
2
2
13
TMS); C NMR (100 MHz, CDCl
3
d
C
1
2
(
2
2
2
2
2
2
1
1
2
4
n
þ
H
2
3
51.1421 (351.1416).
reduced pressure. The residue was then taken up in DCM/H
2
O and
extracted. The DCM layers were dried over Na SO before being
2
4
2
.27. 2-(1-Chloro-7-(4-methoxyphenyl)heptan-4-yl)isoindo-
filtered and evaporated under reduced pressure to yield the crude
xanthate. This was then purified by column chromatography using
petroleum ether/ethyl acetate, 10:1e2:1 v/v to obtain 2.9 g 30d
line-1,3-dione (38e)
Following the general procedure A for radical addition, the
(
83%) as a white solid, which was crystallized from ethyl acetate/
reaction was carried out with a solution of 30c (100 mg,
0
needed 40 mol % of DLP to go to completion. The reduction was
done following the general procedure B. Flash chromatography on
silica gel (petroleum ether/ethyl acetate, 10:1 v/v) afforded 72 mg
1
petroleum ether. H NMR (400 MHz; CDCl
CHPhth), 7.85e7.76 (m, 2H, CHPhth), 7.78e7.69 (m, 2H, CHPhth),
.75e7.64 (m, 2H, CHPhth), 6.31e6.22 (m, 1H, CHS), 4.61 (q, 2H,
J¼7.1 Hz, COCH CH ), 3.84e3.75 (m, 2H, NCH ), 2.77e2.68 (m, 2H,
CHSCH
), 1.36 (t, 3H, J¼7.1 Hz, COCH
CDCl ): 210.2 (C]S), 168 (C]O), 166.6 (C]O), 134.3, 134 (CPhth),
31.8, 131.5 (CqPhth), 123.6, 123.2 (CPhth), 70.4 (OCH CH ), 54.9
CHS), 35 (CHSCH ), 31.4 (NCH ), 13.6 (OCH CH ); IR (CCl
3 H
): d 7.88e7.79 (m, 2H,
.28 mmol) and allyl phenyl ether (75 mg, 0.56 mmol), and
7
2
3
2
13
2 3
CH ); C NMR (100 MHz,
1
2
3
8e (yield: 67%) as a pale yellow oil. H NMR (400 MHz; CDCl
3
):
d
H
3
d
C
7
.87e7.76 (m, 2H, CHPhth), 7.75e7.68 (m, 2H, CHPhth), 7.03 (d, 2H,
J¼8.6 Hz, Ar), 6.78 (d, 2H, J¼8.6 Hz, Ar), 4.31e4.22 (1H, m, NCH),
.76 (s, 3H, ArOCH ), 3.55e3.46 (m, 2H, CH Cl), 2.60e2.49 (m, 2H,
CH Ar), 2.22e2.13 (m, 2H, NCHCH ), 1.93e1.82 (m, 1H, NCHCHH),
CH Cl), 1.59e1.50 (m, 2H,
); C NMR (100 MHz, CDCl ): 168.7 (NCO), 157.8 (Ar),
1
(
2
2
3
2
2
2
3
4
):
n
max
3
3
2
þ
983, 1777, 1724, 1542, 1394, 1228, 1112, 1049; HRMS (EI ): m/z
2
2
calculated (found) for
(
C
19
13
H N
2
O
4
[MꢂSCSOEt]: 333.0875
1.78e1.63 (m, 3H, NCHCHH, CH
2
2
ꢁ
333.0868); mp: 143e144 C.
13
NCHCH
2
CH
2
3
1
34.03 (CHPhth), 134 (Ar), 131.7 (CqPhth), 129.3 (Ar), 123.3
CHPhth), 113.8 (Ar), 55.3 (ArOCH ), 51.2 (NCH), 44.4 (CH Cl), 34.5
), 29.7 (NCHCH ), 28.7 (CH CH Cl), 25.2
max 2946, 1778, 1723, 1343, 1223, 1067;
24ClNO : 385.1445
0
2
.30. 2,2 -(6-Phenylhexane-1,3-diyl)bis(isoindoline-1,3-dione)
(
(
(
3
2
(41a)
CH
CH
2
Ar), 31.9 (NCHCH
2
2
2
2
2
CH
2
Ar); IR (CCl
4
):
n
Following the general procedure A for radical addition, the re-
þ
HRMS (EI ): m/z calculated (found) for C22
H
3
action was carried out with a solution of 30d (100 mg, 0.22 mmol)
and allylbenzene (39 mg, 0.33 mmol), and needed 20 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
(
385.1442).
2
.28. 2-(3-(4-Methoxyphenyl)propyl)-1-tosylpyrrolidine (39)
ethyl acetate, 2:1) afforded 67 mg 41a (yield: 68%) as a colorless oil.
1
To a solution of 38e (72 mg, 0.18 mmol) in methanol (0.5 ml)
3 H
H NMR (400 MHz; CDCl ): d 7.84e7.73 (m, 4H, CHPhth), 7.74e7.65
was added 0.9 ml hydrazine in methanol (1 M). The reaction was
heated to reflux for 1 h. Then the resulting solution was filtrated
and the filtrate was concentrated under reduced pressure to get
the residue. Without further purification, the residue was dis-
solved in 0.5 ml DCM and then 4-toluenesulfonyl chloride
(m, 4H, CHPhth), 7.26e7.17 (m, 2H, CHAr), 7.15e7.08 (m, 3H, CHAr),
4.30e4.21 (1H, m, NCH), 3.75e3.59 (m, 2H, NCH ), 2.60e2.51 (m,
3H, NCH CHH, CH Ph), 2.31e2.22 (m, 1H, NCH CHH), 2.16e2.07 (m,
1H, CHHCH Ph), 1.83e1.72 (m, 1H, CHHCH Ph), 1.59e1.51 (m, 2H,
168.6, 168.1 (NCO), 141.8
(CqPh), 133.9, 133.8 (CHPhth), 132, 131.8 (CqPhth), 128.32, 128.25
(CHPh), 125.8 (CHPh), 123.2 (CHPhth), 49.1 (NCH), 35.4 (NCH ), 35.3
(CH Ph), 32.1 (NCHCH ), 30.5 (NCH CH ), 28.2 (CH CH Ph); IR
(CCl ): max 2928, 1774, 1717, 1558, 1468, 1374, 1172, 1072, 1005;
2
2
2
2
2
2
1
3
2 3 C
NCHCH ); C NMR (100 MHz, CDCl ): d
(
35 mg, 0.18 mmol) and triethylamine (18 mg, 0.18 mmol) were
added into the solution, which was stirred at room temperature
for 8 h. Finally, the solution was concentrated under reduced
pressure to obtain the residue, which was then purified by col-
umn chromatography using petroleum ether/ethyl acetate,
2
2
2
2
2
2
2
4
n
þ
24 2 4
HRMS (EI ): m/z calculated (found) for C28H N O : 452.1736
1
0:1e4:1 v/v, to afford 48 mg 39 (yield: 71%) as a pale yellow
(452.1745).
1
stick liquid. H NMR (400 MHz; CDCl
3
):
d
H
7.70 (d, 2H, J¼8.2 Hz,
Ts), 7.29 (d, 2H, J¼8.2 Hz, Ts), 7.10 (d, 2H, J¼8.1 Hz, Ar), 6.83 (d,
2.31. 4,6-Bis(1,3-dioxoisoindolin-2-yl)hexyl acetate (41b)
2
3
H, J¼8.6 Hz, Ar), 3.79 (s, 3H, ArOCH
.39e3.30 (m, 1H, NCHH), 3.24e3.16 (m, 1H, NCHH), 2.61e2.53
), 2.42 (s, 3H, ArCH ), 1.89e1.79 (m, 1H, NCH CHH),
CHH), 1.67e1.56 (m, 3H, NCHCHH,
3
), 3.69e3.58 (m, 1H, NCH),
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30d (82 mg, 0.18 mmol)
and allyl acetate (33 mg, 0.33 mmol), and needed 20 mol % of DLP to
go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
(
m, 2H, ArCH
2
3
2
1.79e1.68 (m, 1H, NCH
2
3
CHCH
2
CH
2
), 1.57e1.45 (m, 3H, NCHCHH, CHCH
): 157.7 (Ar), 143.1 (Ts), 135 (Ts), 134.5 (Ar),
29.6 (Ar), 129.2 (Ts), 127.4 (Ts), 113.7 (Ar), 60.4 (OCH ), 55.2
NCH ), 48.8 (NCH), 36.1 (CH Ar), 34.9 (CHCH ), 30.7 (CHCH ),
8.3 (CH CH Ar), 24.1 (NCH CH ), 21.5 (ArCH ); IR (CCl ):
986, 1778, 1722, 1333, 1287, 1054; HRMS (EI ): m/z calculated
S: 373.1712 (373.1717).
2 2
CH
); 1 C NMR
(
1
(
2
2
100 MHz, CDCl
3
d
C
3
ethyl acetate, 2:1) afforded 55 mg product 41b (yield: 71%) as
a colorless oil. H NMR (400 MHz; CDCl
1
2
2
2
2
3
):
d
H
7.85e7.76 (m, 4H,
2
2
2
2
3
4
n
max
CHPhth), 7.75e7.66 (m, 4H, CHPhth), 4.29e4.21 (1H, m, NCH), 4.02
(t, 2H, CH ), 2.61e2.52 (m,
OAc, J¼6.5 Hz), 3.64e3.63 (m, 2H, NCH
1H, NCH CHH), 2.33e2.25 (m, 1H, NCH CHH), 2.17e2.08 (m, 1H,
þ
2
2
(
found) for C21
H
27NO
3
2
2

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7203
CHHCH
.61e1.52 (m, 2H, NCHCH
COCH ), 168.5 (NCO), 168.2 (NCO), 134, 133.9 (CHPhth), 132, 131.7
CqPhth), 123.229, 123.203 (CHPhth), 63.8 (CH O), 49 (NCH), 35.2
NCH ), 30.5 (NCH CH ), 29.1 (NCHCH ), 25.6 (CH CH O), 20.9
OCH ); IR (CCl ):
2
OAc), 2.0 (s, 3H, OCH
3
), 1.88e1.78 (m, 1H, CHHCH
2
OAc),
d
H
7.82e7.73 (m, 4H, CHPhth), 7.73e7.62 (m, 4H, CHPhth),
4.25e4.16 (1H, m, NCH), 3.70e3.61 (m, 2H, NCH ), 2.58e2.49 (m,
1H, NCH CHH), 2.29e2.18 (m, 4H, NCH CHH, COCH , COCH),
2.06e1.93 (m, 3H, COCH CHH, COCH CH CHH, COCHCH CHH),
1.81e1.54 (m, 6H, COCH CHH, COCH CH CHH, COCHCH CHH
NCHCH , COCHCHH), 1.26e1.13 (m, 3H, COCHCHH, CHCH CH
NMR (100 MHz, CDCl ): Mixture of diastereoisomer: 213, 212.9
(CO), 168.6, 168.1 (NCO), 133.9, 133.8 (CHPhth), 132, 131.8 (CqPhth),
23.179, 123.136 (CHPhth), 50.4, 50.3 (NCH), 49.3, 49.2 (COCH), 41.9
1
3
1
2
); C NMR (100 MHz, CDCl
3
):
d
C
171
2
(
(
(
(
3
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
);
13
3
4
n
max 2927, 1773, 1712, 1558, 1468, 1365, 1235,
2
2
2
C
þ
1
172, 1038; HRMS (EI ): m/z calculated (found) for C22
H
19
N
2
O
4
3
d
C
[MꢂOAc]: 374.1345 (374.1352).
1
2
.32. 5,7-Bis-(1,3-dioxo-1,3-dihydroisoindol-2-yl)-heptaneni-
(COCH
30.4 (NCHCH
4.9, 24.8 (COCH
2924, 1774, 1717, 1558, 1374, 1251, 1005; HRMS (EI ): m/z calculated
(found) for C28 : 472.1998 (472.1998).
2
), 35.3 (NCH
CH N), 29, 28.9 (COCH
CH CH ), 24.1, 24 (COCHCH
2
), 34, 33.8 (COCHCH
CH ), 27.97, 27.92 (COCHCH
CH ); IR (CCl ):
2
), 32.7, 32.6 (NCHCH
2
),
),
trile (41c)
2
2
2
2
2
2
2
2
2
2
2
4
n
max
þ
Following the general procedure A for radical addition, the re-
action was carried out with a solution of xanthate 30d (100 mg,
28 2 5
H N O
0
2
.22 mmol) and allyl cyanide (23 mg, 0.33 mmol), and needed
0 mol % of DLP to go to completion. The reduction was done fol-
2.35. Dithiocarbonic acid [1,3-bis-(1,3-dioxo-1,3-
dihydroisoindol-2-yl)-3-ethoxythio-carbonylsulfanyl] ester O-
ethyl ester (30e)
lowing the general procedure B. Flash chromatography on silica gel
petroleum ether/ethyl acetate, 2:1 v/v) afforded 62 mg 41c (yield:
(
1
7
1%) as a pale yellow oil. H NMR (400 MHz; CDCl
m, 2H, CHPhth), 7.82e7.73 (m, 2H, CHPhth), 7.77e7.68 (m, 2H,
CHPhth), 7.74e7.65 (m, 2H, CHPhth), 4.27e4.18 (1H, m, NCH),
.72e3.63 (m, 2H, NCH ), 2.62e2.53 (m, 1H, NCH CHH), 2.39e2.28
m, 3H, CH CN, NCH CHH), 2.28e2.19 (m, 1H, CHHCH CN),
CN), 1.66e1.57 (m, 2H, NCHCH );
168.5 (NCO), 168.2 (NCO), 134.2, 134
3 H
): d 7.85e7.76
(
Compound 28d (3 g, 9.00 mmol), NBS (3.22 g, 18.08 mmol) in
CCl (150 ml) was heated at reflux under nitrogen for 3 h; the re-
4
3
(
2
2
action was initiated by irradiation with a 300 W lamp. The reaction
mixture was then cooled, filtered, and washed with sodium thio-
sulfate. After extracting the solution with DCM, the organic layer
was concentrated under reduced pressure to yield 3.7 g 29e (yield:
85%) without further purification. Compound 29e (3.7 g, 7.7 mmol)
was dissolved in acetone (2 ml/mmol). KSCSOEt (2.6 g, 16 mmol)
was added portion wise over a period of 5 min. It was then left to
stir for further half an hour before the acetone was evaporated off
under reduced pressure. The residue was then taken up in DCM/
2
2
2
13
1.95e1.86 (m, 1H, CHHCH
2
2
C
3 C
NMR (100 MHz, CDCl ): d
(
CHPhth), 132, 131.7 (CqPhth), 123.4, 123.3 (CHPhth), 119.1 (CN),
4
8.3 (NCH), 35.2 (NCH
2
), 31.5 (NCH CH
2
2 2
), 30.6 (NCHCH ), 22.5
(CH
2
CH CN), 16.8 (CH CN); IR (CCl
2
2
4
): nmax 2927, 1776, 1718, 1544,
þ
1468, 1375, 1146, 1070; HRMS (EI ): m/z calculated (found) for
C
H
23 19
N
3
O
4
: 401.1376 (401.1380).
2 2 4
H O and extracted. The DCM layers were dried over Na SO before
0
2
.33. 2,2 -(6-Phenoxyhexane-1,3-diyl)-bis-(isoindoline-1,3-
being filtered and evaporated under reduced pressure to yield the
crude xanthate. This was then purified by column chromatography
using petroleum ether/ethyl acetate, 10:1e2:1 v/v, to obtain 2.6 g
30e (72%) and as a mixture of two diastereoisomers in a ratio 1.1:1.
One diastereoisomer as a pale yellow solid was crystallized from
dione) (41d)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30d (100 mg, 0.22 mmol)
and allyloxybenzene (44 mg, 0.33 mmol), and needed 20 mol % of
DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
ethyl acetate/petroleum ether and another one as yellow oil
1
remained in the solvent.
astereoisomer 1:
CHPhth), 6.47 (dt, 2H, J¼7.1, 8.7 Hz, CHS), 4.70e4.59 (m, 4H,
J¼7.1 Hz, COCH CH ), 3.45e3.34 (m, 1H, CHSCHHCHS), 3.21e3.10
(m, 1H, CHSCHHCHS), 1.42 (t, 6H, J¼7.1 Hz, 2COCH CH ); Di-
astereoisomer 2: 7.88e7.77 (m, 4H, CHPhth), 7.78e7.70 (m, 4H,
CHPhth), 6.28e6.19 (m, 2H, CHS), 4.70e4.59 (m, 4H, J¼7.1 Hz,
COCH CH CHS), 1.31 (t, 6H,
), 3.30 (dd, 2H, J¼8.3 Hz, CHSCH
J¼7.1 Hz, 2COCH ): Diastereoisomer
1: 209.7 (C]S), 166.3 (C]O), 134.4 (CPhth), 131.4 (CqPhth), 123.5
(CPhth), 70.7 (OCH ), 54.7 (CHS), 36.2 (CH ), 13.6 (OCH CH ); Di-
astereoisomer 2: 209.6 (C]S), 166.7 (C]O), 134.5 (CPhth), 131.6
(CqPhth), 123.7 (CPhth), 70.6 (OCH ), 54 (CHS), 36.1 (CH ), 13.5
(OCH CH ); IR (CCl ): max 2926, 1783, 1724, 1558, 1376, 1226, 1112,
1046; HRMS (EI ): m/z calculated (found) for C22
3
H NMR (400 MHz; CDCl ): Di-
H
d 7.88e7.77 (m, 4H, CHPhth), 7.78e7.70 (m, 4H,
ether/ethyl acetate, 4:1 v/v) afforded 68 mg 41d (yield: 66%) as
a pale yellow oil. H NMR (400 MHz; CDCl
1
3
):
d
H
7.87e7.78 (m, 2H,
2
3
CHPhth), 7.81e7.72 (m, 2H, CHPhth), 7.75e7.74 (m, 2H, CHPhth),
.71e7.63 (m, 2H, CHPhth), 7.22 (dt, 2H, CHAr, J¼7.5, 8.5 Hz), 6.88 (t,
H, CHAr, J¼7.3 Hz), 6.82 (d, 2H, CHAr, J¼7.9 Hz), 4.32e4.25 (1H, m,
NCH), 3.91 (t, 2H, CH ),
OPh, J¼1.3, 6.3 Hz), 3.79e3.70 (m, 2H, NCH
.62e2.51 (m, 1H, NCH CHH), 2.36e2.27 (m, 1H, NCH CHH),
.27e2.18 (m, 1H, CHHCH OPh), 1.99e1.91 (m, 1H, CHHCH OPh),
168.5,
68.1 (NCO), 158.8 (CqPh), 133.9, 133.8 (CHPhth), 132, 131.8
CqPhth), 129.3 (CHPh), 123.2, 123.1 (CHPhth), 120.5 (CHPh), 114.4
CHPh), 67 (CH OPh), 49.1 (NCH), 35.3 (NCH ), 30.6 (NCH CH ), 29.1
NCHCH ), 26.2 (CH CH O); IR (CCl ): max 2927, 1774, 1719, 1558,
374, 1244, 1172, 1078; HRMS (EI ): m/z calculated (found) for
2
3
7
1
d
H
2
2
2
3
2
13
2
2
1
2
2
2 3 3
CH ); C NMR (100 MHz, CDCl
2
2
d
C
13
.78e1.67 (m, 2H, NCHCH
2
); C NMR (100 MHz, CDCl
3
):
d
C
2
2
2
3
1
d
C
(
(
(
1
C
2
2
2
2
2
2
2
3
4
n
þ
2
2
2
4
n
17 2 5 2
H N O S
þ
[MꢂSCSOEt]: 453.0579 (453.0573). Mp: Diastereoisomer 1:
ꢁ
H N
28 24 2
O
5
: 468.1685 (468.1699).
172e173 C.
0
0
2
.34. 2,2 -(6-(2-Oxocyclohexyl)hexane-1,3-diyl)bis(isoindo-
2.36. 2,2 -(1,9-Diphenylnonane-4,6-diyl)bis(isoindoline-1,3-
line-1,3-dione) (41e)
dione) (43a)
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30d (100 mg, 0.22 mmol)
and 2-allylcyclohexanone (46 mg, 0.33 mmol), and needed
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30e (200 mg, 0.35 mmol)
and allylbenzene (124 mg, 1.05 mmol), and needed 30 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
ethyl acetate, 4:1 v/v) afforded 116 mg 43a (yield: 58%) as a color-
2
0 mol % of DLP to go to completion. The reduction was done fol-
lowing the general procedure B. Flash chromatography on silica gel
petroleum ether/ethyl acetate, 2:1 v/v) afforded 64 mg 41e (yield:
2%) as a colorless oil and a mixture of two diastereoisomers in
(
6
1
less oil and two diastereoisomers in a ratio 2.1:1. H NMR
(400 MHz; CDCl ): Diastereoisomer 1: d 7.85e7.74 (m, 4H,
3 H
1
a ratio 1:1. H NMR (400 MHz; CDCl
3
): Mixture of diastereoisomer:

7204
S. Han et al. / Tetrahedron 70 (2014) 7192e7206
CHPhth), 7.75e7.68 (m, 4H, CHPhth), 7.25e7.16 (m, 4H, Ar),
.17e7.08 (m, 2H, Ar), 7.12e7.01 (m, 4H, Ar), 4.14e4.03 (m, 2H,
168.8 (C]O), 133.8 (CPhth), 131.8 (CqPhth), 123.1 (CHPhth), 48.8
(NCH), 33.8 (CHCH CH), 32.9 (CHCH CH ), 31.7, 29.3, 29.2, 29.1,
26.4, 22.6 (CH ), 14 (CH ); Diastereoisomer 2: 168.3 (C]O),
133.7 (CPhth), 131.6 (CqPhth), 122.9 (CHPhth), 48.7 (NCH), 32.9
(CHCH CH), 32.7 (CHCH CH ), 31.6, 29.1, 29, 28.8, 26.3, 22.4
(CH ), 14 (CH max 2928, 1772, 1709, 1468, 1376, 1172,
7
2
2
2
2
2
NCH), 2.72e2.63 (m, 2H CHCH
.06e1.97 (m, 2H, 2CHHCH Ph), 1.77e1.66 (m, 2H, 2CHHCH
); Diastereoisomer 2:
H, CHPhth), 7.25e7.16 (m, 4H, Ar), 7.17e7.08 (m, 4H, Ar), 7.12e7.01
2
CH), 2.58e2.47 (m, 4H, 2CH
2
Ph),
Ph),
2
3
d
C
2
2
1.53e1.42 (m, 4H, 2NCHCH
2
d
H
7.65e7.52 (m,
2
2
):
2
8
2
3
); IR (CCl
4
n
þ
(
m, 4H, Ar), 4.48e4.39 (m, 2H, 2NCH), 2.90e2.81 (m, 1H,
CHCHHCH), 2.58e2.47 (m, 4H, 2CH Ph), 2.31e2.22 (m, 1H,
CHCHHCH), 2.16e2.07 (m, 2H, 2CHHCH Ph), 1.81e1.72 (m, 2H,
CHHCH Ph), 1.57e1.42 (m, 4H, 2NCHCH
CDCl ): Diastereoisomer 1: 168.7 (C]O), 133.9 (CPhth), 131.7
CqPhth), 141.8, 128.3, 128.2, 125.7, 123.1 (Ar), 48.3 (NCH), 35.3
CH Ph), 33.7 (CHCH CH), 32.4 (CHCH CH ), 28.2 (CH CH Ph); Di-
168.6 (C]O), 133.8 (CPhth), 131.7 (CqPhth),
28.3, 125.7, 122.9 (Ar), 48.3 (NCH), 35.3 (CH Ph), 33.6 (CHCH CH),
max 2928, 1709, 1773,
1082; HRMS (EI ): m/z calculated (found) for: C35
H
46
N
2
O
4
:
2
558.3458 (558.3449).
2
13
0
2
2
2
); C NMR (100 MHz,
2.39. 2,2 -(1,9-Bis(trimethylsilyl)nonane-4,6-diyl)bis(isoindo-
line-1,3-dione) (43d)
3
d
C
(
(
2
2
2
2
2
2
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30e (200 mg, 0.35 mmol)
and allyl trimethylsilane (160 mg, 1.4 mmol), and needed 20 mol %
of DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
ether/ethyl acetate, 5:1 v/v) afforded 131 mg 43d (yield: 67%) as
astereoisomer 2:
d
C
1
2
2
3
2.3 (CHCH
2
CH
2
), 28.1 (CH
2
CH
2
Ph); IR (CCl
4
):
n
þ
1469, 1376, 1172, 1075; HRMS (EI ): m/z calculated (found) for:
C
37 34 2 4
H N O : 570.2519 (570.2509).
1
a colorless solid and two diastereoisomers in a ratio 1.9:1. H NMR
2
.37. 5,7-Bis(1,3-dioxoisoindolin-2-yl)undecanedinitrile (43b)
(400 MHz; CDCl
.77e7.65 (m, 4H, CHPhth), 4.13e4.01 (m, 2H, 2NCH), 2.69e2.59 (m,
2H, J¼7.5, 8.8 Hz, CHCH CH), 2.06e1.94 (m, 2H, 2NCHCHH),
1.76e1.60 (m, 2H, 2NCHCHH), 1.25e1.10 (m, 4H, CH CH TMS),
0.48e0.31 (m, 4H, 2CH
TMS), ꢂ0.14 (s, 18H, 2TMS); Di-
astereoisomer 2: 7.67e7.51 (m, 8H, CHPhth), 4.33e4.18 (m, 2H,
3 H
): Diastereoisomer 1: d 7.86e7.7 (m, 4H, CHPhth),
7
Following the general procedure A for radical addition, the re-
2
action was carried out with a solution of 30e (200 mg, 0.35 mmol)
and allyl cyanide (70 mg, 1.05 mmol), and needed 25 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
ethyl acetate, 1:1 v/v) afforded 99 mg 43b (yield: 61%) as a colorless
2
2
2
d
H
2NCH), 2.91e2.77 (m, 1H, CHCHHCH), 2.24e2.11 (m, 1H,
CHCHHCH), 2.08e1.93 (m, 2H, 2NCHCHH), 1.76e1.61 (m, 2H,
1
oil and two diastereoisomers in a ratio 2:1. H NMR (400 MHz;
2NCHCHH), 1.25e1.10 (m, 4H, CH
2
CH
2
TMS), 0.57e0.41 (m, 4H,
TMS), ꢂ0.13 (s, 18H, 2TMS); C NMR (100 MHz, CDCl ): Di-
astereoisomer 1: 168.7 (C]O), 133.8 (CPhth), 131.9 (CqPhth), 123
(CHPhth), 48.3 (NCH), 36.6 (CHCH CH), 33.8 (CHCH CH ), 20.716
(CH CH TMS), 16.1 (CH CH
TMS), ꢂ1.8 (TMS); Diastereoisomer 2:
168.6 (C]O), 133.8 (CPhth), 131.7 (CqPhth), 122.8 (CHPhth), 48.2
(NCH), 36.5 (CHCH CH), 33.7 (CHCH CH ), 20.6 (CH CH TMS), 16
(CH CH ): max 2954, 1773, 1712, 1468,
1
3
CDCl
m, 4H, CHPhth), 4.09e4.00 (m, 2H, 2NCH), 2.80e2.65 (m, 2H,
CHCH CN), 2.18e2.07 (m, 2H,
CN), 1.89e1.78 (m, 2H, 2CHHCH CN), 1.60e1.50 (m, 4H,
); Diastereoisomer 2: 7.67e7.54 (m, 8H, CHPhth),
3
): Diastereoisomer 1:
d
H
7.87e7.76 (m, 4H, CHPhth), 7.79e7.70
2CH
2
3
(
d
C
2
CH), 2.28 (t, 4H, J¼7.2 Hz, 2CH
2
2
2
2
2
2
4
CHHCH
2
2
2
2
2
2
NCHCH
2
d
H
d
C
.29e4.17 (m, 2H, 2NCH), 2.99e2.88 (m, 1H, CHCHHCH), 2.32 (t, 4H,
CN), 2.32e2.20 (m, 1H, CHCHHCH), 2.28e2.17 (m,
CN), 1.91e1.82 (m, 2H, 2CHHCH CN), 1.62e1.50 (m,
): Diastereoisomer 1:
2
2
2
2
2
J¼7.2 Hz, 2CH
2
2
2
TMS), ꢂ1.8 (TMS); IR (CCl
4
n
þ
2
4
H, 2CHHCH
H, 2NCHCH
2
2
1375, 1249, 1173, 1053; HRMS (EI ): m/z calculated (found) for
13
ꢁ
2
); C NMR (100 MHz, CDCl
3
d
C
C
31
H
42
N
2
O
4
Si
2
: 562.2683 (562.2688). Mp: 122e125 C.
1
(
(
1
3
68.5 (C]O), 134.2 (CPhth), 131.6 (CqPhth), 123.4 (CHPhth), 118.9
CN), 47.5 (NCH), 33.5 (CHCH CH), 31.9 (CHCH CH ), 22.4
CH CH CN), 16.7 (CH CH CN); Diastereoisomer 2: 168.1 (C]O),
34.1 (CPhth), 131.2 (CqPhth), 123.1 (CHPhth), 119 (CN), 48.8 (NCH),
4.7 (CHCH CH), 31.3 (CHCH CH ), 22.3 (CH CH CN), 16.6
max 2927, 1773, 1715, 1466, 1377, 1170, 1089;
: 468.1798
0
2
2
2
2.40. 2,2 -(1,9-Diphenoxynonane-4,6-diyl)bis(isoindoline-1,3-
dione) (43e)
2
2
2
2
d
C
2
2
2
2
2
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30e (200 mg, 0.35 mmol)
and allyloxybenzene (140 mg, 1.05 mmol), and needed 25 mol % of
DLP to go to completion. The reduction was done following the
general procedure B. Flash chromatography on silica gel (petroleum
ether/ethyl acetate, 2:1 v/v) afforded 112 mg 43e (yield: 53%) as
(
CH
2
CH
2
CN); IR (CCl
4
):
n
þ
HRMS (EI ): m/z calculated (found) for C27
H
24
N
4
O
4
(
468.1816).
0
2
.38. 2,2 -(Nonadecane-9,11-diyl)bis(isoindoline-1,3-dione)
1
(
43c)
a colorless oil and two diastereoisomers in a ratio 2.4:1. H NMR
3 H
(400 MHz; CDCl ): Diastereoisomer 1: d 7.87e7.74 (m, 4H,
Following the general procedure A for radical addition, the
reaction was carried out with a solution of 30e (200 mg,
CHPhth), 7.78e7.65 (m, 4H, CHPhth), 7.28e7.13 (m, 4H, CHAr), 6.88
(t, 2H, J¼7.3 Hz, CHAr), 6.79 (d, 4H, J¼7.8 Hz, CHAr), 4.19e4.08 (m,
0
2
.35 mmol) and oct-1-ene (157 mg, 1.4 mmol), and needed
5 mol % of DLP to go to completion. The reduction was done
2H, 2NCH), 3.86 (t, 4H, J¼6.3 Hz, 2CH
2
OPh), 2.81e2.72 (m, 2H,
J¼7.4, 8.9 Hz, CHCH
2H, 2CHHCH OPh), 1.73e1.62 (m, 4H, 2NCHCH
2: 7.66e7.53 (m, 8H, CHPhth), 7.18e7.07 (m, 4H, CHAr), 6.84 (t,
2H, J¼7.3 Hz, CHAr), 6.71 (d, 4H, J¼7.8 Hz, CHAr), 4.31e4.21 (m, 2H,
2NCH), 3.86 (t, 4H, J¼6.3 Hz, 2CH OPh), 2.98e2.87 (m, 1H,
CHCHHCH), 2.64e2.51 (m, 1H, CHCHHCH), 2.22e2.11 (m, 2H,
2
CH), 2.19e2.11 (m, 2H, 2CHHCH
2
OPh), 1.91 (m,
following the general procedure B. Flash chromatography on
silica gel (petroleum ether/ethyl acetate, 5:1 v/v) afforded 131 mg
2
2
); Diastereoisomer
d
H
4
3c (yield: 67%) as a colorless oil and two diastereoisomers in
1
a ratio 1.7:1. H NMR (400 MHz; CDCl
.86e7.74 (m, 4H, CHPhth), 7.77e7.66 (m, 4H, CHPhth), 4.08e3.97
CH),
), 1.74e1.61 (m, 2H, 2CHCHHCH ),
);
3
): Diastereoisomer 1:
d
H
2
7
(
m, 2H, 2NCH), 2.72e2.61 (m, 2H, J¼7.5, 8.9 Hz, CHCH
2
2CHHCH
2NCHCH
2
OPh), 1.96e1.87 (m, 2H, 2CHHCH
2
OPh), 1.76e1.61 (m, 4H,
13
1
.99e1.86 (m, 2H, 2CHCHHCH
.28e1.03 (m, 24H, 2 (CH
Diastereoisomer 2:
2
2
2
); C NMR (100 MHz, CDCl
3
): Diastereoisomer 1: 168.7
d
C
1
2
)
6
), 0.81 (t, 6H, J¼6.9 Hz, 2CH
2
CH
3
(C]O), 158.8 (OCqPh), 133.9 (CPhth), 131.8 (CqPhth), 129.3 (CHPh),
123.2 (CHPhth), 120.5 (CHPh), 114.4 (CHPh), 67 (CH OPh), 48.4
(NCH), 33.9 (CHCH CH), 29.5 (CHCH CH ), 26.3 (CH CH OPh); Di-
astereoisomer 2: 168.2 (C]O), 158.6 (OCqPh), 133.7 (CPhth),
131.4 (CqPhth), 129.2 (CHPh), 122.8 (CHPhth), 120.4 (CHPh), 114.3
(CHPh), 66.8 (CH OPh), 48.3 (NCH), 33.7 (CHCH CH), 29.4
d
H
7.67e7.52 (m, 8H, CHPhth), 4.28e4.15 (m,
2
2
H, 2NCH), 2.90e2.75 (m, 1H, CHCHHCH), 2.30e2.17 (m, 1H,
CHCHHCH), 2.11e1.97 (m, 2H, 2CHCHHCH ), 1.77e1.64 (m, 2H,
), 0.82 (t, 6H, J¼6.9 Hz,
): Diastereoisomer 1:
2
2
2
2
2
2
d
C
2
2
2 2 6
CHCHHCH ), 1.28e1.03 (m, 24H, 2 (CH )
13
CH
2
CH
3
); C NMR (100 MHz, CDCl
3
d
C
2
2

S. Han et al. / Tetrahedron 70 (2014) 7192e7206
7205
0
(
2
CHCH CH
2
), 26.2 (CH
2
CH
2
OPh); IR (CCl
4
):
n
max 2927, 1774, 1713,
2.43. 2,2 -(1,1,1,13,13,13-Hexafluoro-2,12-dihydroxy-2,12-
1600, 1497, 1375, 1244, 1172, 1046; HRMS: m/z calculated (found)
bis(trifluoromethyl)tridecane-6,8-diyl)bis(isoindoline-1,3-
for C37H
34
N
2
O
6
[MꢂOC
6
H
5
]: 509.2077 (509.2066).
dione) (43h)
Following the general procedure A for radical addition, the re-
actionwas carried out with a solution of 30e (200 mg, 0.35 mmol) and
0
2
.41. 2,2 -(1,9-Bis(4-methoxyphenyl)nonane-4,6-diyl)bis(i-
soindoline-1,3-dione) (43f)
1
,1,1-trifluoro-2-(trifluoromethyl)-pent-4-en-2-ol
(218
mg,
1
.05 mmol), and add 30 mol % of DLP to go to completion. The re-
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30e (200 mg, 0.35 mmol)
and 4-allylanisole (155 mg,1.05 mmol), and needed 25 mol % of DLP
to go to completion. The reduction was done following the general
procedure B. Flash chromatography on silica gel (petroleum ether/
ethyl acetate, 4:1 v/v) afforded 135 mg 43f (yield: 61%) as a color-
duction was done following the general procedure B. Flash chroma-
tographyonsilicagel(petroleumether/ethylacetate,2:1v/v)afforded
141 mg 43h (yield: 54%) as a colorless oil and two diastereoisomers in
1
a ratio 2:1. H NMR (400 MHz; CDCl
.89e7.80 (m, 4H, CHPhth), 7.85e7.76 (m, 4H, CHPhth), 4.14e4.04 (m,
3 H
): Diastereoisomer 1: d
7
2
2
2
H, 2NCH), 3.60 (s, 2H, CF
.08e1.97 (m, 2H, 2CHHCH
CH C(CF OH), 1.86e1.75 (m, 2H, 2CHHCH
); Diastereoisomer 2: 7.61e7.51 (m, 8H, CHPhth),
.25e4.16 (m, 2H, 2NCH), 3.62 (s, 2H, CF OH), 2.90e2.81 (m, 1H,
CHCHHCH), 2.55e2.47 (m, 1H, CHCHHCH), 2.06e1.97 (m, 2H,
CHHCH C(CF OH), 1.95e1.84 (m, 4H, 2CH C(CF OH), 1.87e1.76
m, 2H, 2CHHCH C(CF OH), 1.57e1.46 (m, 4H, 2NCHCH
100 MHz, CDCl ): Diastereoisomer 1: 169.1 (C]O), 134.3 (CPhth),
31.4 (CqPhth),122.96 (q, CF
, J¼286.8 Hz),123.4 (CHPhth), 76.3, 76.2,
6.2, 76, 75.9, 75.911, 75.7, 75.6 (C(CF OH), 47.442 (NCH), 32.9
CHCH CH), 32.7(CHCH CH ), 29.2(CH CH C(CF OH),18.4 (CH CH
C(CF OH); Diastereoisomer 2: 168.9 (C]O), 134.2 (CPhth), 131.2
CqPhth),122.96 (q, CF
, J¼286.8 Hz),123.3 (CHPhth), 76.3, 76.2, 76.2,
6, 75.9, 75.911, 75.7, 75.6 (C(CF OH), 47.5 (NCH), 32.7 (CHCH CH),
max 2927,
3
OH), 2.76 (dt, 2H, J¼7.4, 8.9 Hz, CHCH
C(CF OH), 1.94e1.85 (m, 4H,
C(CF OH), 1.58e1.46
2
CH),
1
less oil and two diastereoisomers in a ratio 2.5:1. H NMR
2
3 2
)
(
3 H
400 MHz; CDCl ): Diastereoisomer 1: d 7.86e7.73 (m, 4H,
2
)
3 2
2
3 2
)
CHPhth), 7.76e7.66 (m, 4H, CHPhth), 6.96 (d, 4H, J¼8.5 Hz, Ar), 6.74
(m, 4H, 2NCHCH
2
d
H
(
d, 4H, J¼8.6 Hz, Ar), 4.10e4.01 (m, 2H, 2NCH), 3.74 (s, 6H,
4
3
2
2
2
PhOCH
PhCH ), 2.05e1.94 (m, 2H, 2CHHCH
CHHCH PhOCH ), 1.62e1.51 (m, 2H, NCHCH
); Diastereoisomer 2:
d, 4H, J¼8.6 Hz, Ar), 6.73 (d, 4H, J¼8.5 Hz, Ar), 4.29e4.18 (m, 2H,
3
2
), 2.70e2.61 (m, 2H, CHCH CH), 2.51e2.41 (m, 4H,
2
2
PhOCH
3
), 1.71e1.62 (m, 2H,
), 1.54e1.43 (m, 2H,
2
(
(
1
7
2
3
)
2
2
3 2
)
2
3
2
1
3
2
)
3 2
2
); C NMR
NCHCH
(
2
H
d 7.63e7.52 (m, 8H, CHPhth), 6.96
3
d
C
3
2
2
2
2
NCH), 3.74 (s, 6H, 2PhOCH
.52e2.41 (m, 4H, 2PhCH ), 2.30e2.21 (m, 1H, CHCHHCH),
.13e2.04 (m, 2H, 2CHHCH PhOCH ), 1.77e1.66 (m, 2H,
CHHCH PhOCH ), 1.62e1.51 (m, 2H, NCHCH ), 1.53e1.42 (m, 2H,
); C NMR (100 MHz, CDCl ): Diastereoisomer 1: 168.7
C]O), 133.9 (CPhth), 157.6, 133.8, 131.8, 113.7 (Ar), 129.2 (CqPhth),
23.1 (CHPhth), 55.2 (OCH ), 48.4 (NCH), 34.4 (CH Ph), 33.7
CHCH CH), 32.4 (CHCH CH ), 28.4 (CH CH Ph); Diastereoisomer
168.6 (C]O), 133.7 (CPhth), 157.5, 133.4,131.6, 113.6 (Ar), 129.2
), 49.2 (NCH), 34.3 (CH Ph),
), 28.4 (CH CH Ph); IR (CCl ):
929, 1774, 1717, 1513, 1375, 1247, 1176, 1042; HRMS (EI ): m/z
NO ]: 483.241
3
), 2.91e2.82 (m, 1H, CHCHHCH),
3 2
)
2
(
2
2
2
2
2
)
3 2
2
2
2
3
)
3 2
d
C
2
3
2
(
7
2
3
13
NCHCH
(
1
(
2
(
3
2
2
3
d
C
)
3 2
2
9(CH CH C(CF ) OH),18.4(CH CH
2 2 3 2 2 2
C(CF
3
)
2
OH);IR(CCl
4
):
n
3
2
þ
1774, 1717, 1543, 1468, 1376, 1288, 1212; HRMS (EI ): m/z calculated
2
2
2
2
2
(found) for C31
26 12 2 6
H F N O : 750.1599 (750.1614).
: d
C
CqPhth), 122.9 (CHPhth), 55.1 (OCH
3
2
0
00 000
2
.44. 2,2 ,2 ,2 -(Nonane-1,4,6,9-tetrayl)tetrakis(isoindoline-
3.6 (CHCH
2
CH), 32.1 (CHCH
2
CH
2
2
2
4
n
max
1,3-dione) (43i)
þ
calculated (found) for:
C
39
H
38
N
2
O
6
[MꢂC
8
H
5
2
Following the general procedure A for radical addition, the re-
action was carried out with a solution of 30e (200 mg, 0.35 mmol)
and 2-allylisoindoline-1,3-dione (196 mg, 1.05 mmol), and add
25 mol % of DLP to go to completion. The reduction was done fol-
lowing the general procedure B. Flash chromatography on silica gel
(
483.241).
0
2
.42. 2,2 -(1,7-Dicyclopentylheptane-3,5-diyl)bis(isoindoline-
1,3-dione) (43g)
(
petroleum ether/ethyl acetate, 1:1 v/v) afforded 176 mg 43i (yield:
1
Following the general procedure A for radical addition, the
reaction was carried out with a solution of 30e (200 mg,
.35 mmol) and vinylcyclopentane (134 mg, 1.4 mmol), and
needed 25 mol % of DLP to go to completion. The reduction was
done following the general procedure B. Flash chromatography
on silica gel (petroleum ether/ethyl acetate, 5:1 v/v) afforded
71%) as a colorless oil and two diastereoisomers in a ratio 2:1. H NMR
(400 MHz; CDCl ): Diastereoisomer 1: 7.87e7.76 (m, 8H, CHPhth),
7.79e7.68 (m, 8H, CHPhth), 4.14e4.03 (m, 2H, 2NCH), 3.69e3.58 (m,
4H, 2CH NthPh), 2.77e2.65 (m, 2H, CHCH CH), 2.11e2.02 (m, 2H,
2CHHCH NthPh), 1.79e1.70 (m, 2H, 2CHHCH NthPh), 1.61e1.52 (m,
4H, 2NCHCH ); Diastereoisomer 2: 7.62e7.43 (m, 16H), 4.29e4.20
(m, 2H, 2NCH), 3.91e3.80 (m, 4H, 2CH NthPh), 2.94e2.84 (m, 1H,
CHCHHCH), 2.17e2.08 (m, 1H, CHCHHCH), 2.11e2.01 (m, 2H,
2CHHCH NthPh), 1.78e1.69 (m, 2H, 2CHHCH NthPh), 1.61e1.53
(m, 4H, 2NCHCH ): Diastereoisomer 1:
168.6, 168.2 (C]O), 133.9, 133.8 (CPhth), 132, 131.7 (CqPhth), 123.2,
123.1 (CHPhth), 48.1 (NCH), 37.3 (CH NthPh), 33.5 (CHCH CH), 30.1
(CHCH CH ), 25.6 (CH CH Phth); Diastereoisomer 2: 168.5, 168.4
(C]O), 133.8, 133.7 (CPhth), 131.9, 131.6 (CqPhth), 123.1, 122.8
(CHPhth), 48 (NCH), 37.2 (CH NthPh), 33.4 (CHCH CH), 30
max 2927, 1775, 1719,
3
d
H
0
2
2
2
2
2
d
H
1
16 mg 43g (yield: 63%) as
a
colorless oil and two di-
astereoisomers in a ratio 1.9:1. H NMR (400 MHz; CDCl ): Di-
astereoisomer 1: 7.86e7.74 (m, 4H, CHPhth), 7.76e7.66 (m, 4H,
2
1
3
d
H
2
2
13
CHPhth), 4.06e3.97 (m, 2H, 2NCH), 2.71e2.62 (m, 2H, J¼7.6,
2
); C NMR (100 MHz, CDCl
3
d
C
8
3
1
.7 Hz, CHCH
.5CH ), 1.51e1.39 (m, 7H, 3.5CH
), 0.97e0.86 (m, 4H, 2CH
7.66e7.54 (m, 8H, CHPhth), 4.26e4.15 (m,
H, 2NCH), 2.88e2.77 (m, 1H, CHCHHCH), 2.29e2.18 (m, 1H,
CHCHHCH), 2.05e1.94 (m, 2H, CH ), 1.68e1.58 (m, 7H, 3.5CH ),
.49e1.39 (m, 7H, 3.5CH ), 1.31e1.19 (m, 4H, 2CH ), 1.13e1.05 (m,
H, CH ), 0.96e0.85 (m, 4H, 2CH ); C NMR (100 MHz, CDCl ):
Diastereoisomer 1: 168.8 (C]O), 133.8 (CPhth), 131.8 (CqPhth),
23.1 (CHPhth), 48.9 (NCH), 39.8 (CH), 33.9, 32.7, 32.5, 32.2, 25.2,
5.1, 25.1 (CH ); Diastereoisomer 2: 168.3 (C]O), 133.7
CPhth), 131.6 (CqPhth), 122.9 (CHPhth), 50.3 (NCH), 39.6 (CH),
2
CH), 1.99e1.90 (m, 2H, CH
), 1.31e1.19 (m, 4H, 2CH
); Di-
2
), 1.69e1.61 (m, 7H,
2
2
2
),
2
2
.13e1.05 (m, 2H, CH
2
2
2
2
2
2
d
C
astereoisomer 2:
d
H
2
2
2
2
2
(CHCH
2
CH
2
), 25.5 (CH
2
CH
2
Phth); IR (CCl
4
):
n
þ
1
2
2
2
1469, 1395, 1375, 1264, 1050; HRMS (EI ): m/z calculated (found) for
13
2
2
3
C H N O
41 32 4 8
8 4 2
[MꢂC H NO ]: 562.1973 (562.1989).
d
C
0
1
2
(
2.45. 2,2 -(4-(2-Hydroxyethyl)cyclopentane-1,3-diyl)bis(i-
soindoline-1,3-dione) (45)
2
d
C
3
3.7, 32.4, 32.3, 32.1, 25.1, 24.8, 24.6 (CH
2
); IR (CCl
4
):
n
max 2928,
Triethylborane (1.0 m solution in hexane, 0.14 mmol) was added
every 30 min over 2 h to a stirred solution of 30e (200 mg,
0.35 mmol) and vinyl epoxide (49 mg, 0.7 mmol) in DCM (0.5 ml)
þ
1773, 1712, 1468, 1375, 1172, 1085; HRMS (EI ): m/z calculated
(
38 2 4
found) for: C33H N O : 526.2832 (526.2841).

7206
S. Han et al. / Tetrahedron 70 (2014) 7192e7206
under nitrogen at room temperature. During the addition, the sy-
ringe needle was lowered into the solution. Furthermore, a small
volume of air (about a quarter of the volume of the borane solution)
was introduced by syringe following each addition of triethylbor-
ane. After stirring the reaction mixture overnight, the mixture was
diluted with DCM and then washed once with water and once with
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2014.07.055.
brine. The organic phase was dried over anhydrous MgSO
4
, filtered,
References and notes
and concentrated. The residue was purified by chromatography on
silica gel (petroleum ether/ethyl acetate/DCM, 10:4:1 v/v) to give
1
2
. Amino Group Chemistry; Ricci, A., Ed.; Wiley-VCH: Weinheim, Germany, 2008.
. (a) Quiclet-Sire, B.; Zard, S. Z. Org. Lett. 2008, 10, 3279; (b) Quiclet-Sire, B.; Revol,
G.; Zard, S. Z. Org. Lett. 2009, 11, 3554; (c) Quiclet-Sire, B.; Revol, G.; Zard, S. Z.
Tetrahedron 2010, 66, 6656.
1
19 mg 45 (yield: 84%) as a colorless oil and four diastereoisomers
1
in a ratio 5:4:1:1. H NMR (400 MHz; CDCl
3
): Major diastereoisomer
7.89e7.79 (m, 4H, CHPhth), 7.75e7.66 (m, 4H, CHPhth),
.19e5.11 (m, 1H, NCHCH), 4.86e4.77 (m, 1H, NCHCH ), 3.68e3.55
OH), 2.85e2.78 (m, 1H), 2.57e2.48 (m, 2H), 2.33e2.24
m, 1H, CHCH CH OH), 2.15e2.04 (m, 1H, NCHCHHNCH), 1.84e1.75
m, 1H, NCHCHHCH), 1.72e1.63 (m, 1H, CHHCH
H, CHHCH OH); Major diastereoisomer 2:
1
5
:
d
H
3. For reviews of the radical xanthate transfer chemistry, see: (a) Zard, S. Z. Angew.
Chem., Int. Ed. 1997, 36, 672; (b) Zard, S. Z. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, Germany, 2001; Vol. 1, p 90;
2
(
(
(
m, 2H, CH
2
(
c) Quiclet-Sire, B.; Zard, S. Z. Chem.dEur. J. 2006, 12, 6002; (d) Quiclet-Sire, B.;
Zard, S. Z. Top. Curr. Chem. 2006, 264, 201; (e) Zard, S. Z. Org. Biomol. Chem. 2007,
, 205; (f) Zard, S. Z. Aust. J. Chem. 2006, 59, 663; (g) Quiclet-Sire, B.; Zard, S. Z.
2
2
5
2
OH), 1.37e1.29 (m,
H
d 7.89e7.79 (m, 4H,
Pure Appl. Chem. 2011, 83, 519; (h) El Qacemi, M.; Petit, L.; Quiclet-Sire, B.; Zard,
S. Z. Org. Biomol. Chem. 2012, 10, 5707.
1
2
CHPhth), 7.75e7.66 (m, 4H, CHPhth), 4.91e4.80 (m, 1H, NCHCH),
.62e4.51 (m, 1H, NCHCH ), 3.67e3.56 (m, 2H, CH OH), 3.43e3.34
4. Quiclet-Sire, B.; Zard, S. Z. Heterocycles 2010, 82, 263.
5. Lebreux, F.; Quiclet-Sire, B.; Zard, S. Z. Org. Lett. 2009, 11, 2844.
4
2
2
6. Katritzky, A. R.; Button, M. A. C.; Denisenko, S. N. Heterocycles 2001, 54, 301.
(
m, 1H, NCHCHHNCH), 2.82 (dd, 1H, J¼11.4 Hz, NCHCHHCH),
7
. (a) Easton, C. J.; Hutton, C. A.; Rositano, G.; Tan, E. W. J. Org. Chem. 1991, 56, 5614
For reviews on the WohleZiegler reaction, see: (b) Djerrassi, C. Chem. Rev. 1948,
3, 271; (c) Horner, L.; Winkelman, E. M. Angew. Chem. 1959, 71, 349.
8. (a) Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. Cs. Tetrahedron Lett. 1992, 33,
709; (b) Boivin, J.; Jrad, R.; Juge, S.; Nguyen, V. T. Org. Lett. 2003, 5, 1645; (c)
2
2
1
(
1
6
(
1
.51e2.40 (m, 1H, CHCH
2
CH
2
OH), 2.28e2.17 (m, 1H, NCHCHHNCH),
OH),
C NMR
168.4, 168.2 (C]O),
34, 133.9 (CPhth), 131.98, 131.9 (CqPhth), 123.22, 123.16 (CPhth),
1.4 (CH OH), 54.5 (NCH), 47.7 (NCH), 38.9 (CH), 35.7 (CH ), 35.2
CH ), 31.9 (CH); Major diastereoisomer 2: 168.8, 168.3 (C]O),
34, 133.9 (CPhth), 131.9, 131.7 (CqPhth), 123.3, 123.1 (CPhth), 61.6
CH OH), 50.2 (NCH), 49.7 (NCH), 37.4 (CHCH CH OH), 33.9
NCHCH max 2989, 1756,
4
.13e2.05 (m, 1H, NCHCHHCH), 1.74e1.65 (m, 1H, CHHCH
2
13
2
.66e1.55 (m, 1H, CHHCH OH), 1.38 (br, 1H, OH);
5
100 MHz, CDCl ): Major diastereoisomer 1
3
d
C
McMaster, C.; Bream, R. N.; Grainger, R. S. Org. Biomol. Chem. 2012, 10, 4752.
. (a) Hintermann, T.; Seebach, D. Synlett 1997, 437; (b) Seebach, D.; Gademann,
K.; Schreiber, J. V.; Matthews, J. L.; Hintermann, T.; Jaun, B.; Oberer, L.; Hommel,
U.; Widmer, H. Helv. Chim. Acta 1997, 80, 2033.
9
2
2
2
d
C
10. (a) Liu, M.; Sibi, M. P. Tetrahedron 2002, 58, 7991; (b) Enantioselective Synthesis
of -Amino Acids; Juaristi, E., Ed.; Wiley-VCH: New York, NY, 1997; (c) Enan-
tioselective Synthesis of -Amino Acids, 2nd ed.; Juaristi, E., Soloshonok, V., Eds.;
Wiley-VCH: Hoboken, NJ, 2005.
11. Spiteller, P.; von Nussbaum, F.
selective Synthesis of -Amino Acids, 2nd ed.; Juaristi, E., Soloshonok, V., Eds.;
Wiley-VCH: Hoboken, NJ, 2005; pp 19e91.
2. Frey, P. A. Acc. Chem. Res. 2014, 47, 540.
b
b
(
(
2
2
2
2
CH), 33 (CH
2
CH
2
OH), 30.5 (CH), IR (CCl
4
):
n
b-Amino Acids in Natural Products In Enantio-
þ
1
721, 1555, 1438, 1326, 1258; HRMS (EI ): m/z calculated (found)
b
20 2 5
for: C23H N O : 404.1372 (404.1381).
1
13. For a review, see: Bender, J.; Meanwell, N. A.; Wang, T. Tetrahedron 2002, 58,
Acknowledgements
3111.
1
4. (a) Charrier, N.; Gravestock, D.; Zard, S. Z. Angew. Chem., Int. Ed. 2006, 45, 6520
For comprehensive reviews on organoboranes as sources of radicals, see: (b)
Ollivier, C.; Renaud, P. Chem. Rev. 2001, 101, 3415; (c) Darmency, V.; Renaud, P.
Top. Curr. Chem. 2006, 263, 71.
One of us (S.H.) thanks the China Scholarship Council for
a scholarship.