A Bulky Disulfoxide Ligand for Pd-Catalyzed Oxidative Allylic C-H Amination with 2,2,2-Trichloroethyl Tosyl Carbamate

Article abstract of DOI:10.1021/acs.joc.6b03089

Challenging substrates and conditions in homogeneous catalysis pose stringent demands on the ligands used. A novel, bulky, 1-adamantyl-substituted disulfoxide ligand designed after a systematic evaluation of the electronic and steric properties of disulfoxide substituents permits the allylic oxidative C-N coupling reaction to proceed at lower catalyst loading while requiring a smaller excess of reagents. Additionally, this ligand improves the yields when TsNHCOOCH₂CCl₃, a novel reagent that permits deprotection of the products under both acidic and basic conditions, is used.

Full text of DOI:10.1021/acs.joc.6b03089

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Note
A bulky disulfoxide ligand for Pd-catalyzed oxidative allylic
C-H amination with 2,2,2-trichloroethyl tosyl carbamate
You-Gui Li, Li Li, Ming-Yue Yang, Gang He, and Eric Assen B. Kantchev
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 19 Apr 2017
Downloaded from http://pubs.acs.org on April 19, 2017
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The Journal of Organic Chemistry
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A bulky disulfoxide ligand for Pd-catalyzed oxidative allylic C-
H amination with 2,2,2-trichloroethyl tosyl carbamate.
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YouꢀGui Li,* Li Li, MingꢀYue Yang, Gang He, Eric Assen B. Kantchev*
School of Chemistry and Chemical Engineering, Hefei University of Technology, 193 Tunxi Road, Hefei 230009, China.
Fax: +86ꢀ551ꢀ62901450; Phone: ++86ꢀ551ꢀ62901450; Eꢀmail: liyg@ hfut.edu.cn; ekantchev@hfut.edu.cn, ekantchev@gmail.com.
ABSTRACT: Challenging substrates and conditions in homogeneous catalysis pose stringent demands on the ligands used. A novꢀ
el, bulky, 1ꢀadamantylꢀsubstituted disulfoxide ligand designed after a systematic evaluation of the electronic and steric properties of
disulfoxide substituents permits the allylic oxidative CꢀN coupling reaction to proceed at lower catalyst loading while requiring
smaller excess of reagents. Additionally, this ligand improves the yields when TsNHCOOCH2CCl3, a novel reagent that permits
deprotection of the products under both acidic and basic conditions, is used.
Carbonꢀnitrogen bonds are ubiquitous in natural and manꢀ
made bioactive organic compounds. Therefore, development
of synthetic methods for CꢀN bond formation is an enduring
theme in organic synthetic chemistry.1 In the case of amines,2
usually prior installation of an oxygenꢀcontaining functional
group or a halogen is required. Subsequent introduction of
amine requires labor intensive and wasteꢀgenerating functional
group interconversions. Hence, the direct amination of a CꢀH
bond is a prized alternative.3 Allylic CꢀH bonds are amenable
to selective activation under mild conditions due to their lower
bond dissociation energy.4 Since 2004, mild and functionalꢀ
group tolerant allylic oxidative esterification,5 intermolecular
amination,6 enolate allylation7, and related8 reactions have
Figure 1. A rationallyꢀdesigned disulfoxide ligand set (1ꢀ10) with
variable σꢀdonicity and steric bulk.
been developed mainly by M. C. White’s group by using just
two disulfoxide ligands. Sulfoxides are electronically and
structurally similar to the ubiquitous P(III) ligands. Despite
their ease of synthesis, Sꢀcenter chirality, low toxicity, and
tolerance to air, moisture and long term storage, sulfoxide
ligands are still quite underrepresented9 in transitionꢀmetal
catalyzed organic synthetic methods.10 It is conceivable that a
systematic exploration of the disulfoxide ligand diversity
space could yield ligands that lead to improvements in imꢀ
portant parameters of the synthetic protocol such as catalyst
loading or substrate scope.
Firstly, we demonstrate the effect of electronic and steric
properties of the sulfoxide substituents on the allylic oxidative
CꢀN coupling reaction. These properties can be systematically
and independently investigated with a set of disulfoxides (1ꢀ
10; Figure 1) prepared (Scheme 1) by oxidation of the correꢀ
sponding disulfides (1aꢀ10a) with H2O2 or mCPBA (for 6, 7,
Scheme 1. Disulfoxide ligand synthesis.
stoichiometic
oxidant
2,6ꢀdimethylꢀ1,4ꢀbenzoquinone
(DMBQ) using 5 mol% [(1ꢀ10)Pd(OAc)2]11 and 6 mol% Et3N
(Table 1).12 The yields of 13aa with 4ꢀtꢀBuC6H5ꢀ (2; 65%) and
cyclohexylꢀ (9; 69%) substituted disulfoxide ligands were the
highest, and the 4ꢀMeOC6H5ꢀ (1, 52%) and 4ꢀtꢀBuC6H5ꢀ (10,
50%) substituted disulfoxides were also decent performers.13
Because bulky, electronꢀrich disulfoxides exhibited superior
activity, two such secondꢀgeneration sulfoxides (14 and 15)
were also synthesized (Scheme 2). Gratifyingly, the 1ꢀ
and 9). The disulfides in turn were accessed from 1,2ꢀ
dibromoethane and the required thiols in the presence of KOH
in MeOH. The set includes the two widely used disulfoxides
developed by White's group (3 and 8).
The activity of the sulfoxide ligands 1ꢀ10 was evaluated for
the CꢀN coupling of allylbenzene (11a) with only 1.1 equiv.
each of the amination reagent TsNHCOOMe (12a) and the
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adamantylꢀsubstittued ligand 14 outperformed all first generaꢀ lished oxidative allylic amination with methyl, benzyl and tertꢀ
1
2
3
4
tion disulfoxides 1ꢀ10, giving 75% yield of 13aa; ligand 15
butyl tosylcarbamate, as well as tertꢀbutyl methanesulfonylꢀ
carbamate in good yields.14 We investigated the performance
Table 1. Evaluation of [(disulfoxide)Pd(OAc)2] catalysts for
allylic oxidative C-N bond formation.
Table 2. Oxidative C-H allylic amination at lower Pd load-
ing (2-5 mol)% with second generation ligands.
5
6
7
8
9
Ligand
1
2
3
4
5
6
7
8
9
10
10
11
12
13
14
15
16
17
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R
Pd (x mol%)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(TFA)2 (2)
[Pd(CH3CN)4] 14 6%a,c
(BF4)2 (2)
[Pd2(dba)3] (2) 14 24%a,b
L
Yield
%
13aaa 52 65 48 45 37 22 42 27 69 50
Ph (11a)
Ph
15 34% (13aa)a,b
14 75%a,b
aAveraged isolated yields. The reactions were performed in duꢀ
plicate and combined before purification. In all cases, other possiꢀ
ble products ((Z)ꢀ13aa, Nꢀalkenyl and branched) were not obꢀ
served at levels that permit quantification by 1H NMR.
Ph
14 65%a,b
14 62% (1 atm O2)a,b
14 17%a,c
Ph
X
Ph
Br AdSH (2.05 equiv.)
KOH (2.1 equiv.)
14a, 88%
X = :
S
Ad
Ad
mCPBA (2.05 equiv.)
CH2Cl2, 0°C to rt, 16 h
Ph
Br
S
X
14
, 80%
X = O
MeOH, 0°C to rt, 16 h
Ph
X
S
Ph
15a
X = :
, 72%
HS
mCPBA
(2.05 equiv.)
CH2Cl2,
14 75% (13ba)a,b
14 62%a,b
SH
4ꢀFC6H5 (11b)
4ꢀFC6H5
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Ph
S
X
Ph
cat. H2SO4
AcOH, 60°,
16 h
(2.05
equiv.)
15, 65%
X = O
0°C to rt, 16 h
4ꢀMeOC6H5 (11c) Pd(OAc)2 (2)
14 63% (13ca)a,b
14 83% (13da)a,b
14 80% (13ea)a,b
14 21% (13fa)a,c
14 7%a,c
14 30% (13ga)a,b
14 9%a,b
Scheme 2. Second generation disulfoxide ligand synthesis.
2ꢀMeC6H5 (11d)
2ꢀOAcC6H5 (11e)
nꢀC7H15 (11f)
nꢀC7H15
Pd(OAc)2 (2)
Pd(OAc)2 (2)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
Pd(OAc)2 (5)
Pd(OAc)2 (2)
was much less effective (Table 2). Lowering the loading of the
catalyst prepared from 14 to 2 mol% resulted in 65% yield.
Evaluating of a number of other Pd sources revealed that only
Pd(OAc)2 was suitable. Finally, conducting of the reaction
under O2 atmosphere or with an excess of 11a led to no further
increase in yield. A number of oꢀ and pꢀsubstituted allylbenꢀ
zenes 11bꢀe also gave 13baꢀea in good yields. However,
yields with simple alkenes 11fꢀh (deactivated substrates) were
low. A direct comparison of ligands 3 and 14 (Scheme 3) unꢀ
der previously developed conditions6b using 1,4ꢀbenzoquinone
(1.1 equiv.) revealed that ligand 3 only gave a total of 34% of
13fa and the corresponding branched (terminal double bond)
isomer 16fa (E/Z/B = 11:1:1) whereas the new ligand 14 gave
59% (E/Z/B = 15:1:1.1). The reaction was performed experiꢀ
mentally by preꢀmixing an equimolar mixture of the disulfoxꢀ
ide and Pd(OAc)2 in the reaction solvent for 15 min prior to
adding the reactants, which simplified and accelerated the
reaction procedure. However, that led to a decrease in yield for
ligand 3: for comparison, the published yield of 13fa with
White's catalyst [(3)Pd(OAc)2] was 67%.6b
Cy (11g)
Cy
PhCH2 (11h)
PhCH2
14 30% (13ha)a,b
14 9%a,b
aAveraged isolated yields. The reactions were performed in duꢀ
plicate and combined before purification. In all cases, Nꢀalkenyl
product was not observed by H NMR. ((Z)ꢀ13 and branched
isomer were not detected by H NMR. Due to low yield, deterꢀ
mination of the E/Z/branched ratio was not carried out.
1
b
1
c
The nitrogen substrate 12a represents NH3 that is
doublyꢀactivated as well as protected by methyl carbamoyl
and tosyl groups. These groups can be cleaved in the products
sequentially by treatment with K2CO3/MeOH and
Na·C10H8/DME, respectively. However, if the Ts group was
removed first, the carbamate could be cleaved only under agꢀ
gressive basic (NaOH/H2OꢀEtOH, 110 °C, giving ꢀNH2) or
reducing (LiAlH4/THF, reflux, giving ꢀNHMe) conditions.6b
Thus, methyl carbamate deprotection for baseꢀsensitive subꢀ
strates or protecting groups is expected to be very challenging
if not impossible but a different carbamate should not be a
subject to such a limitation. White et al. have reported high
yields for the amination of 11g with benzyl, tertꢀbutyl, and 9ꢀ
fluorenylmethyl carbamates using [(3)Pd(OAc)2] as the cataꢀ
lyst and BQ (2 equiv.) as the oxidating agent.6b Liu et al. pubꢀ
Scheme 3. Ligand comparison in the oxidative C-H allylic
amination of n-decene.
of ligand 14 with known (12b, c) tosylcarbamates as well as
the hitherto unknown 2,2,2ꢀtrifluoroethyl (12d) and 2,2,2ꢀ
trichloroethyl analogs (12e) (Table 3). In all but one cases,
ligand 14 outperꢀformed 3 both in terms of yields as well as
the selectivity towards the desired linear (E)ꢀlinear products
(13fbꢀfe). However, the improvement even though syntheticalꢀ
ly beneficial was not dramatic. Surprisingly, the tꢀBu carbaꢀ
mate 12b, reacted poorly despite the reported 69% yield using
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(17ee) and TBDPS phenol protecting groups (17je, le) were
White's catalyst [(3)Pd(OAc)2] with 10 mol% iꢀPr2NEt as coꢀ
catalyst in CCl4.6b
retained whereas the Bocꢀprotected phenol in 13ie gave a mixꢀ
ture of the unprotected 17qe (75%) and the Bocꢀprotected 17ie
1
2
3
4
5
6
7
8
9
O
Table 3. Oxidative C-H allylic amination of various N-tosyl
carbamates.
R
11b-p
Pd(OAc)2 (10 mol%)
14 (10 mol%)
R
N
O
CCl3
Ts
O
(E+Z)-Linear
+
+
H
13be-pe
R
BQ (2.0 equiv.),
Et3N (6 mol%),
t-BuOMe, 45 °C, 72 h
N
O
CCl3
Ts
N
O
CCl3
Branched
O
Ts
12e (1.1 equiv.)
16fe, le-ne
10
11
12
13
14
15
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11d
11e
11b
11c
MeO
Me
OAc
F
96%/32%a,b (13de)
R
Yield (E/Z/B)a
98% (13be) 93%/25%a,b (13ce)
(E)-only
83% (13ee)
(E)-only
93% (1.14 g; 10 mmol)
(E)-only
Ligand 3
Ligand 14
(E)-only
F
10% (13fb;b 12:1:0.5)
39% (13fc;b 12:1:0.8)
41% (13fd;b 12:1:1)
39% (13fe;b 15:1:0.8)
25% (9:1:0.6)
58% (17:1)c
64% (12:1:0.9)
68% (15:1:1)
F
tꢀBu (12b)
11i
OBOC
87% (13ie)
(E)-only
11j
11k
F
11g
Bn (12c)
F
OTBDMS
52%b (13ge)
(E)-only
F
CH2CF3 (12d)
CH2CCl3 (12e)
88% (13je)
(E)-only
53% (13ke) (E)-only
n-C7H15
TBDPSO
O
aAveraged isolated yields. The reactions were performed in duꢀ
plicate and combined before purification. Isomer rations were
determined by H NMR. In all cases, Nꢀalkenyl and branched
11h
11f
11l
N
58%b (13le + 16le)
E/Z/B = 10:1:1.4
3
58%b (13he)
(E)-only
13fe 16fe
E/Z/B = 15:1:1
68% (
+
)
1
11m
O
product were not observed at levels that permit quantification.
AcO
AcO
AcO
bThe major product. The branched product amount was too low
c
O
61% (13me + 16me)
E/Z/B = 15:1:1
O
for quantification by 1H NMR.
H
O
H
OAc
O
11o
O
O
A major synthetic benefit of using 12e is that it permits
deprotection with a mild reducing agent (Zn powder) in
AcOH15 while retains the facile deprotection under mildly
basic conditions characteristic for the methyl analog. Hence,
this reagent permits removal of the carbamate under condiꢀ
tions compatible with both acidꢀ and baseꢀsensitive protecting
groups. A range of terminal olefins (11bꢀp; Scheme 4) couꢀ
pled in moderate to excellent yields but the product isomer
distribution depended on the nature of the alkene. As exꢀ
pected, pꢀ (11b, c) and oꢀsubstituted (11d, e, i, j) allyl benꢀ
zenes gave very high yields of the (E)ꢀlinear products (13ge,
he) at 10% catalyst loading. We attempted lowering of the
catalyst loading to 2/5 mol% for Pd(OAc)2 and 14, respectiveꢀ
ly. Even with 2.0 equiv. of 12e, the yields of 13ce and 13de
plummeted to 25 and 32%, respectively. These results conꢀ
firmed that for TsNHCOOCH2CCl3, 10 mol% of catalyst are
required, underscoring the main theme of this work that deꢀ
manding substrates require specialized, often novel, catalysts.
However, the reaction scaled up well: 13ce was obtained in
93% (1.14 g) yield on a 10ꢀmmol scale. Allylpentafluorobenꢀ
zene (11k) and the alkylꢀsubstituted terminal olefins 11g, h
coupled in moderate yields (52 ꢀ 58%), similarly giving only
the (E)ꢀlinear products 13he, ge, ke. For the remaining alkylꢀ
substituted terminal olefins, a mixture of (E)ꢀ and (Z)ꢀlinear
products (13fe, leꢀpe) were always observed in E/Z ratios in
the range 10:1 ꢀ 20:1. In some cases, the linear product was
accompanied by the analogous branched isomer (16fe, leꢀne)
in slightly larger amounts than the minor (Z)ꢀ13 product (Z/B
= 1:2.4 to 1:1). For 11g, h, l, p, 2 equiv. of 12e were required
for good yields.
11p
68% (13oe)
E/Z = 14:1
O
O
68%b (13pe)
E/Z = 14:1
11n
67% (13ne + 16ne)
E/Z/B = 18:1:2
a2 mol% Pd(OAc)2, and 5 mol% 14 were used. b2.0 equiv. 12e were used.
Scheme 4. Oxidative C-H allylic amination of terminal
alkenes with 2,2,2-trichloroethyl tosylcarbamate.
Table 4. Deprotection of the 2,2,2-trichloroethylcarbonyl
(Troc) group.
N-Troc compd. Cond. Yield (product; isomer ratio)
13ee
A
A
B
A
B
A
B
A
B
A
A
A
94% (17ee)
13ie
25% (17ie) + 75% (17qe)
97% (17qe)
13ie
13je
92% (17je)
13je
99% (17qe)
13fe + 16fe
13fe + 16fe
13ge
93% (17fe; E/Z/B = 20:1:0.7)
100% (17fe; E/Z/B = 20:1:0.7)
94% (17ge)
The 2,2,2ꢀtrichloroethylcarbonyl (Troc) group in
products 13 was readily removed (Table 4) by heating with
excess of Zn in AcOH at 60 °C (conditions A) or with K2CO3
in MeOH (conditions B; identical to those employed by White
et al.6b for removal of the MeOCO group) giving γꢀsubstituted
Nꢀtosylallylamines 17. Under conditions (A), the acetate
13ge
100% (17ge)
13he
81% (17he)
13le + 16le
13oe
91% (17le; E/Z/B = >20:<0.1:1)
83% (17oe; E/Z = >20:1)
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C
16H18NaO2S2 ([M+Na]+): 329.0640; found: 329.0653 (δ 2.1 ppm).
products. Overall, the yields for deprotection under conditions
A ranged from 81 to 100% for both (3ꢀarylallyl)ꢀ or (3ꢀ
alkylallyl)tosylcarbamates. Particularly, the Troc removal in
17oe proceeded in very satisfying 83% without affecting the
four acetates attached to the glucose moiety. The Troc removal
took place in near quantitative yields under the basic condiꢀ
tions B as expected for the relatively small and electronꢀpoor
2,2,2ꢀtrichloroethyl ester. From oꢀallylphenol protected with
both Boc (13ie) and TPS (13je), only the free phenol 17qe was
isolated in contrast with conditions A. In almost all cases, the
deprotection led to increasing of the content of the (E)ꢀlinear
product 17 when mixtures of (E)+(Z)ꢀ13 and 16 were used.
1,2-bis((4-(tert-butyl)phenyl)thio)ethane (2a). From 4ꢀ(tertꢀbutyl)benzenethiol (3.5
mL, 3.4 g, 20.5 mmol) following the general procedure, 2a (2.26 g, 63%) was isolatꢀ
ed as a white solid. m. p. 107ꢀ108 °C. 1H NMR (CDCl3, 600 MHz): δ 7.33 – 7.28 (m,
4H), 7.27 – 7.23 (m, 4H), 3.06 (s, 4H), 1.32 (s, 18H). 13C NMR (CDCl3, 150 MHz): δ
149.9, 131.5, 130.2, 126.0, 34.5, 33.8, 31.3. HRꢀMS (APCI): m/z calcd. for
1
2
3
4
5
6
7
8
C
22H39NaS2 ([M+Na]+): 381.1681; found: 381.1695 (δ 3.7 ppm).
1,2-bis(phenylthio)ethane (3a). From benzenethiol (2.1 mL, 2.3 g, 20.5 mmol)
following the general procedure, 3a (2.0 g, 83%) was isolated. Spectroscopic data
were identical with the literature.5e
1,2-bis((4-chlorophenyl)thio)ethane (4a). From 4ꢀchlorobenzenethiol (2.16 mL,
2.96 g, 20.5 mmol) following the general procedure, 4a (2.7 g, 87%) was isolated as
a white solid. m. p. 94ꢀ95 °C. 1H NMR (CDCl3, 600 MHz): δ 7.27 – 7.21 (m, 8H),
3.03 (s, 4H). 13C NMR (150 MHz, CDCl3): δ 133.4, 132.8, 131.5, 129.2, 33.6. HRꢀ
MS (APCI): m/z calcd. for C14H12Cl2NaS2 ([M+Na]+): 336.9650; found: 336.9661 (δ
3.3 ppm).
9
10
11
12
13
14
15
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17
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The Nꢀtosyl group could not be deprotected in the
presence of Troc by a number of methods we tried. When
clean deprotection was possible, it led to Troc removal instead
of Ts (a representative example is shown on Scheme 5).
1,2-bis((4-(trifluoromethyl)phenyl)thio)ethane
(5a).
From
4ꢀ
(trifluoromethyl)benzenethiol (3.63 g, 20.5 mmol), following the general procedure,
5a (3.1 g, 82%) was isolated as a white solid. m. p. 83ꢀ85 °C. 1H NMR (CDCl3, 600
MHz): δ 7.52 (d, J = 8.3 Hz, 4H), 7.38 (d, J = 8.2 Hz, 4H), 4.39 (s, 8H). 13C NMR
(CDCl3, 150 MHz): δ 140.3, 128.6, 128.4 (q, 2JCꢀF = 33 Hz), 125.9 (q, 3JCꢀF = 4.5 Hz),
1
124.5 (q, JCꢀF = 270 Hz), 32.2. HRꢀMS (APCI): m/z calcd. for C16H12F6NaS2
([M+Na]+): 405.0177; found:405.0187 (δ 2.5 ppm).
1,2-bis(hexylthio)ethane (6a). From 1ꢀhexanethiol (2.9 mL, 2.42 g, 20.5 mmol)
following the general procedure, 6a (1.82 g, 80%) was isolated as a colorless liquid.
1H NMR (CDCl3, 600 MHz): δ 2.70 (s, 4H), 2.53 (t, J = 7.5 Hz, 4H), 1.57 (dt, J =
15.1, 7.5 Hz, 4H), 1.37 (dt, J = 15.0, 7.3 Hz, 4H), 1.32 – 1.20 (m, 8H), 0.87 (t, J =
7.0 Hz, 6H). 13C NMR (150 MHz, CDCl3): δ 32.2, 32.1, 31.4, 29.6, 28.5, 22.5, 14.0.
HRꢀMS (APCI): m/z calcd. for C14H30NaS2 ([M+Na]+): 285.1681; found: 285.1692
(δ 3.9 ppm).
1,2-bis(isobutylthio)ethane (7a). From isobutylthiol (2.36 mL, 1.85 g, 20.5 mmol)
following the general procedure, 7a (1.9 g, 92%) was isolated as a colorless liquid.
1H NMR (CDCl3, 600 MHz): δ 2.66 (s, 4H), 2.40 (d, J = 6.9 Hz, 4H), 1.76 (m, 2H),
0.96 (d, J = 6.7 Hz, 12H). 13C NMR (150 MHz, CDCl3): 41.4, 32.7, 28.6, 21.9. HRꢀ
MS (APCI): m/z calcd. for C10H22NaS2 ([M+Na]+): 229.1055; found: 229.1065. (δ
4.4 ppm).
Scheme 5. Attempted N-Ts deprotection.
In conclusion, a novel, electronꢀrich, bulky 1ꢀ
adamantylꢀsubstituted disulfoxide (ADS) carrying showed an
enhanced performance as a ligand in the Pdꢀcatalyzed allylic
oxidative amination reaction of terminal olefins compared to
the standard Phꢀsubstituted analog. For activated substrates
(allylbenzenes), the reaction proceeded in good yields with as
low as 2 mol% Pd (vs. 10 mol% typically used). Moreover,
this ligand allows the use of 2,2,2ꢀtrichloroethyl tosylcarabaꢀ
mate. This new amination reagent is more versatile by virtue
of deprotection of the Troc group in excellent yields in both
acidic and basic conditions. However, removal of the Ts group
in the presence of Troc was not possible.
1,2-bis(benzylthio)ethane (8a). From benzylthiol (2.34 mL, 2.55 g 20.5 mmol)
following the general procedure, 8a (0.85 g, 62%) was isolated. Spectroscopic data
were identical with the literature.16
1,2-bis(cyclohexylthio)ethane (9a) From cyclohexylthiol (2.44 mL, 2.38 g, 20.5
mmol) following the general procedure, 9a (2.3 g, 89%) was isolated. Spectroscopic
data were identical with the literature.7b
1,2-bis(tert-butylthio)ethane (10a). From tertꢀbutylthiol (1.18 mL, 1.85 g, 20.5
mmol) following the general procedure, 10a (1.78 g, 86%) was isolated. Spectroꢀ
scopic data were identical with the literature.7b
1,2-bis(adamantan-1-ylthio)ethane (14a). From 1ꢀadamanthanethiol (3.12 g, 20.5
mmol) following the general procedure, 14a (3.2 g, 88%) was isolated as a white
solid. m. p. 120ꢀ122 °C. 1H NMR (CDCl3, 600 MHz): δ 2.66 (s, 4H), 2.03 (broad s,
6H), 1.85 (s, 12H), 1.67 (q, J = 12.4 Hz, 12H). 13C NMR (CDCl3, 150 MHz): δ 43.7,
36.3, 29.7, 26.9. HRꢀMS (APCI): m/z calcd. for C22H34NaS2 ([M+Na]+): 385.1994;
found: 385.2009 (δ 3.9 ppm).
Experimental section
General. Unless otherwise noted, the allylic CꢀH oxidative amination reactions were
performed in screwꢀcap glass vials (volume 8 mL; used as received) without special
precautions to exclude air and moisture. The reaction temperature was maintained by
immersion of the vials into a silicon oil bath mounted on a commercial stirꢀhotplate
with automatic temperature control. All reagents and solvents were purchased from a
variety of commercial suppliers, used as received, and weighed on open balances in
air, unless specified otherwise. Thinꢀlayer chromatography (TLC) was performed on
silica gel 60 F254 precoated plates (0.25 mm) and visualized with UV and anisaldeꢀ
hyde stain. Flash column chromatography was performed on silica gel (60 ꢀm; TCI).
1H and 13C NMR spectra were recorded in the specified solvents on a Varian
VNMRS600 at 600MHz, and at 150 MHz, respectively, and Bruker Avance
300MHz, and at 75 MHz, respectively. Chemical shifts (ppm) were referenced
against the residual protonated solvent peaks and the multiplicities described as
follows: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, m = multiplet, br
= broad; the coupling constants are given in Hz. High resolution mass spectra were
recorded on a Waters XEVO G2 QꢀTOF mass spectrometer.
1,3-bis((2-phenylpropan-2-yl)thio)ethane (15a). (CAUTION! Stench. Use a wellꢀ
ventillated fume hood for all operations). Into a 100ꢀmL, 3ꢀnecked, roundꢀbottomed
flask equipped with a reflux condenser and a 25ꢀmL pressure equalizing addition
funnel, ethaneꢀ1,2ꢀdithiol (0.84 mL, 0.94 g, 10 mmol), AcOH (15 mL), and conc.
H2SO4 (5 drops) were added in that order under Ar. A solution of αꢀmethylstyrene
(2.8 mL, 2.42 g, 20.5 mmol) in AcOH (10 mL) was added to the addition funnel. The
reaction flask was heated to 60°C and αꢀmethylstyrene solution was added dropwise
to the reaction mixture under Ar. The reaction mixture was stirred at 60 °C overnight
under Ar over 24 h. After cooling to room temperature, Et3N was added to adjust pH
to 7.0, and the volatiles were removed under reduced pressure. The residue was
diluted with water (20 mL) and extracted with CH2Cl2 (3 × 30 mL). The combined
organic layers were dried (MgSO4,) and the volatiles were removed under reduced
pressure. Compound 15a (2.38 g, 72%) was isolated as a white solid after flash
chromatography (neat petrolium ether). m. p. 53ꢀ55 °C. 1H NMR (600 MHz, CDCl3):
δ 7.44 (dd, J = 7.6, 0.7 Hz, 4H), 7.28 (d, J = 7.3 Hz, 4H), 7.17 (td, J = 7.6, 0.6 Hz,
2H), 2.17 (broad s, 4H), 1.61 (d, J = 0.9 Hz, 12H). 13C NMR (150 MHz, CDCl3): δ
146.4, 128.0, 126.5, 126.4, 47.8, 30.2, 29.5. HRꢀMS (APCI): m/z calcd. for
C20H26NaS2 ([M+Na]+): 353.1368; found: 353.1382 (δ 4.0 ppm).
Disulfide synthesis, general procedure: (CAUTION! Stench. All operations must
be conducted in a wellꢀventilated fume hood.) In a flameꢀdried 100ꢀmL roundꢀ
bottom flask was charged sequentially with a stir bar, KOH (2.8 g, 50 mmol) and
MeOH (25 mL). After stirring for 20 min at room temperature, 1,2ꢀdibromoethane
(0.86 mL, 10 mmol), and the required thiol (20.5 mmol) were added to the solution.
After stirring overnight, the volatiles were removed at ~50 °C under reduced presꢀ
sure, the residue diluted with water (30 mL) and extracted with CH2Cl2 (3 × 50 mL).
The combined organic layers were dried (MgSO4), filtered and the volatiles removed
under reduced pressure. The products are isolated after flash chromatography (neat
petrolium ether).
Disulfoxide synthesis, general procedure A (disulfide oxidation with H2O2). A
100ꢀmL roundꢀbottom flask was charged with a stir bar, the required amount of
disulfide, and glacial acetic acid (20 mL). The mixture was stirred at room temperaꢀ
ture until it became homogeneous. Next, it was cooled to 0°C and the required
amount of H2O2 (30 wt% solution in water) was added dropꢀwise. The reaction was
warmed up to room temperature and then stirred overnight. The acetic acid was
removed at ~60°C under reduced pressure and the disulfoxides were isolated after
flash chromatography as (R*,S*)ꢀ and (R*,R*)ꢀdiastereomeric mixtures.
1,2-bis((4-methoxyphenyl)thio)ethane (1a). From 4ꢀmethoxybenzenethiol (2.5 mL,
2.92 g, 20.5 mmol) following the general procedure, 1a (2.7 g, 88%) was isolated as
a white solid. m. p. 108ꢀ109 °C. 1H NMR (CDCl3, 600 MHz): δ 7.29 (dd, J = 9.4, 2.5
Hz, 4H), 6.82 (t, J = 5.9 Hz, 4H), 3.79 (s, 6H), 2.93 (s, 4H). 13C NMR (150 MHz,
CDCl3): δ 159.2, 133.6, 125.2, 114.6, 55.3, 35.2. HRꢀMS (APCI): m/z calcd. for
Disulfoxide synthesis, general procedure B (disulfide oxidation with mCPBA). A
100ꢀmL roundꢀbottom flask was charged with a stir bar, the required amount of
disulfide, and CH2Cl2 (20 mL). Next, the required amount of mCPBA (85 wt%)
dissolved in CH2Cl2 (30 mL) was added dropꢀwise. The mixture was stirred at 0°C
ACS Paragon Plus Environment

Page 5 of 10
The Journal of Organic Chemistry
over 30 min, then warmed up to room temperature, and the stirring continued overꢀ
tion unassigned): 1H NMR (CDCl3, 600 MHz): δ 7.47 (d, J = 7.6 Hz, 4H), 7.32 (t, J =
7.6 Hz, 4H), 7.21 (t, J = 7.3 Hz, 2H), 2.19 (broad s, 4H), 1.63 (s, 12H). 13C NMR
(150 MHz, CDCl3): δ13C NMR (151 MHz, cdcl3) δ 138.2, 128.8, 128.2, 126.5, 40.6,
24.2, 19.1.
night. Next, satd. aq. NaHCO3 solution (20 mL) and water (40 mL) were added
carefully (CAUTION! Rapid evolution of CO2), and the product extracted into
CH2Cl2 (3 × 30 mL). The organic layers were combined, dried (MgSO4), filtered and
the volatiles removed under reduced pressure. The disulfoxides were isolated after
flash chromatography as (R*,S*)ꢀ and (R*,R*)ꢀdiastereomeric mixtures.
1
2
3
4
5
6
7
8
Disulfoxide ligand evaluation (Table 1), general procedure: Catalyst preparation
was performed as described by White et al.5a Briefly, an equimolar mixture of a
disulfoxide ligand and Pd(OAc)2 was refluxed in CH2Cl2 overnight, the solvent
evaporated to dryness and after brief drying in high vacuum, the catalyst was used
immediately. Two runs were set side by side. Each vial was charged with [(1-
10)Pd(OAc)2] (12.5 ꢀmol, 5 mol%), 2,6ꢀdimethylꢀ1,4ꢀbenzoquinone (37 mg, 0.275
mmol), methyl tosylcarbamate (12a; 63 mg, 0.275 mmol), allylbenzene (11a; 33 ꢀL,
29.5 mg, 0.25 mmol) in sequence. Tertꢀbutyl methyl ether (1 mL) and Et3N (2 ꢀL,
1.5 mg, 15 ꢀmol, 6 mol%) were added via syringes. The vials were securely capped
and the reaction mixtures were stirred at 45 °C for 24 hours. Next, the vials were
cooled down to room temperature, pooled together in CH2Cl2 and concentrated under
reduced pressure. Compound 13aa was obtained as a white solid after flash chromaꢀ
tography (petroleum ether ꢀ EtOAc = 10:1). Spectroscopic data were identical with
the literature.17
Ligand 1: From [(1)Pd(OAc)2] (7.0 mg) following the general procedure, 13aa (44.9
mg, 52%) was obtained.
Ligand 2: From [(2)Pd(OAc)2] (7.7 mg) following the general procedure, 13aa (55.7
mg, 65%) was obtained.
Ligand 3: From [(3)Pd(OAc)2] (6.3 mg) following the general procedure, 13aa (41.4
mg, 48%) was obtained.
Ligand 4: From [(4)Pd(OAc)2] (7.1 mg) following the general procedure, 13aa (38.8
mg, 45%) was obtained.
1,2-bis((4-methoxyphenyl)sulfinyl)ethane (1). From 1a (2.7 g, 8.8 mmol) and H2O2
(2.1 mL, 18.5 mmol) following general procedure A, 1 (1.96 g, 66%) was isolated as
a white solid after flash chromatography (petroleum ether ꢀ EtOAc = 2:1). 1H NMR
(600 MHz, CDCl3): δ 7.28 (d, J = 8.8 Hz, 4H), 6.81 (d, J = 8.7 Hz, 4H), 3.79 (s, 6H),
2.92 (s, 4H). 13C NMR (CDCl3, 150 MHz): δ 162.2, 162.1, 133.1, 132.9, 125.8 (mulꢀ
tiple carbons), 115.0, 114.9, 55.5, 55.5, 48.1, 47.4. HRꢀMS (APCI): m/z calcd. for
C16H18NaO4S2 ([M+Na]+): 361.0539; found: 361.0552 (δ 3.6 ppm).
9
1,2-bis((4-(tert-butyl)phenyl)sulfinyl)ethane (2). From 2a (2.26 g, 6.3 mmol) and
H2O2 (1.49 mL, 13.2 mmol) following general procedure A, 2 (1.30 g, 53%) was
isolated as a white solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:2).
HRꢀMS (APCI): m/z calcd. for C22H30NaO2S2 ([M+Na]+): 413.1579; found:
413.1595 (δ 3.9 ppm). Chemical shifts for the major diastereomer (4.4:1, configuraꢀ
tion unassigned): 1H NMR (CDCl3, 600 MHz): δ 7.53 (d, J = 8.4 Hz, 4H), 7.47 (d, J
= 8.4 Hz, 4H), 3.04 (s, 4H), 1.34 (d, J = 7.0 Hz, 18H). 13C NMR (CDCl3, 150 MHz):
δ 155.0, 138.7, 126.4, 123.8, 47.0, 35.0, 31.1.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1,2-bis(phenylsulfinyl)ethane (3). From 3a (2.0 g, 8.3 mmol) and H2O2 (1.96 mL,
17.4 mmol) following general procedure A, 3 (1.75 g, 76%) was isolated after flash
chromatography (petroleum ether ꢀ EtOAc = 1:2). Spectroscopic data were identical
with the literature.5e
1,2-bis((4-chlorophenyl)sulfinyl)ethane (4). From 4a (2.74 g, 8.7 mmol) and H2O2
(2.05 mL, 18.3 mmol) following general procedure A, 4 (1.51 g, 50%) was isolated
as a white solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:2). 1H
NMR (CDCl3, 600 MHz): δ 7.54 – 7.43 (m, 8H), 3.43 – 3.37 (m), 3.04 – 3.01 (m),
2.71 – 2.65 (m, total 4H). 13C NMR (CDCl3, 150 MHz): δ 140.7, 140.5, 137.8, 137.7,
129.8, 129.7, 125.3, 125.2, 47.5, 46.7. HRꢀMS (APCI): m/z calcd. for
C14H12Cl2NaO2S2 ([M+Na]+): 368.9548; found: 368.9564 (δ 4.3 ppm).
Ligand 5: From [(5)Pd(OAc)2] (8.0 mg) following the general procedure, 13aa (31.9
mg, 37%) was obtained.
Ligand 6: From [(6)Pd(OAc)2] (6.5 mg) following the general procedure, 13aa (19.0
mg, 22%) was obtained.
Ligand 7: From [(7)Pd(OAc)2] (5.8 mg) following the general procedure, 13aa (36.3
mg, 42%) was obtained.
Ligand 8: From [(8)Pd(OAc)2] (6.6 mg) following the general procedure, 13aa (23.3
mg, 27%) was obtained.
Ligand 9: From [(9)Pd(OAc)2] (5.9 mg) following the general procedure, 13aa (59.6
mg, 69%) was obtained.
Ligand 10: From [(10)Pd(OAc)2] (5.8 mg) following the general procedure, 13aa
(43.2 mg, 50%) was obtained.
1,2-bis((4-(trifluoromethyl)phenyl)sulfinyl)ethane (5). From 5a (3.13 g, 8.2 mmol)
and H2O2 (1.94 mL, 17.2 mmol) following general procedure A, 5 (2.99 g, 88%) was
isolated as a white solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:2).
1H NMR (CDCl3, 600 MHz): δ 7.82 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 8.2 Hz, 2H),
7.70 (d, J = 8.1 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 3.59 – 3.30 (m, 1H), 3.28 – 2.96
(m, 2H), 2.96 – 2.41 (m, 1H). 13C NMR (CDCl3, 150 MHz): δ 146.7, 146.5, 133.6 (q,
2JCꢀF = 33 Hz), 133.5 (q, 2JCꢀF = 33 Hz), 126.5 (q, 3JCꢀF = 8.0 Hz), 126.5 (q, 3JCꢀF = 8.0
C-H aminations with methyl tosylcarbamate mediated by Pd(OAc)2 complexes
of ligands 14 and 15 (Table 2), general procedure. Two runs were set side by side.
Each vial was charged with Pd(OAc)2 or other Pd sources (2 mol% or 5 mol%),
ligand 14 or 15 (4.9 or 4.5 mg, respectively; 12.5 ꢀmol, 5 mol%), a stir bar, and tertꢀ
butyl methyl ether (1 mL) was added using a disposable syringe. Each vial was
capped and stirred for 15 min, Then 2,6ꢀdimethylꢀ1,4ꢀbenzoquinone (37 mg, 0.275
mmol), methyl tosylcarbamate (63 mg, 0.275 mmol), and the required alkene (0.25
mmol) were added in a sequence, Et3N (2 ꢀL, 1.5 mg, 15 ꢀmol, 6 mol%) was added
via syringe. The vials were securely capped and the reaction mixtures were stirred at
45 °C for 24 hours. Next, the vials were cooled down to room temperature, pooled
together in CH2Cl2 and concentrated under reduced pressure.
1
1
Hz), 124.5, 124.4, 123.3 (q, JCꢀF = 271 Hz), 123.3 (q, JCꢀF = 271 Hz), 47.5, 46.7.
HRꢀMS (APCI): m/z calcd. for C16H12F6NaO2S2 ([M+Na]+): 437.0075; found:
437.0091 (δ 3.7 ppm).
1,2-bis(hexylsulfinyl)ethane (6). From 6a (1.82 g, 7.0 mmol) and mCPBA (2.96 g,
14.5 mmol) following general procedure B, 6 (1.62 g, 66%) was isolated as a white
solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:1). 1H NMR (CDCl3,
600 MHz): δ 3.24 – 3.16 (m, 2H), 3.02 – 2.93 (m, 2H), 2.83 – 2.78 (m, 2H), 2.74ꢀ
2.67 (m, 2H), 1.82 – 1.71 (m, 4H), 1.51 – 1.39 (m, 4H), 1.35 – 1.29 (m, 8H), 0.91 –
0.85 (m, 6H). 13C NMR (CDCl3, 150 MHz): δ 53.3, 52.8, 44.9, 44.2, 31.3, 28.4, 22.6,
22.5, 22.3 (2 carbons), 13.9 (2 carbons). HRꢀMS (APCI): m/z calcd. for
C14H30NaO2S2 ([M+Na]+): 317.1579; found: 317.1591 (δ 3.8 ppm).
(E)-methyl (3-phenylallyl)(tosyl)carbamate (13aa). Ligands/palladium loading
variation: From Pd(OAc)2 (2.8 mg, 12.5 ꢀmol, 5 mol%), and allylbenzene (11a; 33
ꢀL, 29.5 mg, 0.25 mmol) following the general procedure, 13aa (ligand 15: 29.3 mg,
34%; ligand 14: 64.7 mg, 75%) was obtained after flash chromatography (petroleum
ether ꢀ EtOAc = 10:1). From Pd(OAc)2 (1.1 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg,
12.5 ꢀmol, 5 mol%), allylbenzene (11a; 33 ꢀL, 29.5 mg, 0.25 mmol) following the
general procedure, 13aa (56.0 mg, 65%) was obtained. From an identical run under
O2 atmosphere (rubber balloon; 1 atm), 13aa (53.5 mg, 62%) was obtained. Palladi-
um source variation: From the required Pd source (Pd(TFA)2: 1.5 mg,
[Pd(CH3CN)4](BF4)2: 2.2 mg, Pd2(dba)3: 4.6 mg; 5 ꢀmol, 2 mol% Pd), ligand 14 (4.9
mg, 12.5 ꢀmol, 5 mol%), allylbenzene (11a; 33 ꢀL, 29.5 mg, 0.25 mmol) following
the general procedure, 13aa (Pd(TFA)2: 14.7 mg, 17%; [Pd(CH3CN)4](BF4)2: 5.2 mg,
6%; Pd2(dba)3: 20.7 mg, 24%) was obtained.
1,2-bis(isobutylsulfinyl)ethane (7). From 7a (1.83 g, 8.9 mmol) and mCPBA (3.8 g,
18.6 mmol) following general procedure B, 7 (1.1 g, 52%) was isolated as a white
solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:1). 1H NMR (CDCl3,
600 MHz): δ 2.67 (m, 4H), 2.42 – 2.39 (m, 4H), 1.80 – 1.72 (m, 2H), 0.97 – 0.95 (m,
12H). 13C NMR (CDCl3, 150 MHz): 62.5, 62.0, 45.2, 44.7, 24.0, 22.7, 21.7, 21.6.
HRꢀMS (APCI): m/z calcd. for C10H22NaO2S2 ([M+Na]+): 261.0953; found:
261.0963 (δ 3.8 ppm).
1,2-bis(benzylsulfinyl)ethane (8). From 8a (0.85 g, 3.1 mmol) and H2O2 (0.72 mL,
6.5 mmol) following general procedure A, 8 (0.77 g, 82%) was isolated as a white
solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:2). Spectroscopic data
were identical with the literature.7c
(E)-methyl (3-(4-fluorophenyl)allyl)(tosyl)carbamate (13ba). From Pd(OAc)2 (2.8
mg, 12.5 ꢀmol, 5 mol% or 1.12 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol,
5 mol%), 1ꢀallylꢀ4ꢀfluorobenzene (11b; 35 ꢀL, 34.0 mg, 0.25 mmol), following the
general procedure, 13ba (5 mol% Pd: 68.1 mg, 75%; 2 mol% Pd: 56.3 mg, 62%) was
obtained as a white solid after flash chromatography (petroleum ether ꢀ EtOAc =
12:1). m. p. 72ꢀ74 °C. 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 8.1 Hz, 2H), 7.34
(dd, J = 8.3, 5.6 Hz, 2H), 7.27 (d, J = 8.1 Hz, 2H), 7.01 (t, J = 8.6 Hz, 2H), 6.64 (d, J
= 15.8 Hz, 1H), 6.16 (dt, J = 15.7, 6.4 Hz, 1H), 4.60 (d, J = 6.5 Hz, 2H), 3.71 (s, 3H),
2.41 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 162.4 (d, 1JCꢀF = 246 Hz), 152.6, 144.6,
1,2-bis(cyclohexylsulfinyl)ethane (9). From 9a (0.87 g, 3.3 mmol) and mCPBA
(1.41 g, 6.9 mmol) following general procedure B, 9 (0.7 g, 72%) was isolated after
flash chromatography (petroleum ether ꢀ EtOAc = 1:1). Spectroscopic data were
identical with the literature.7b
1,2-bis(tert-butylsulfinyl)ethane (10). From 10a (1.42 g, 6.9 mmol) and H2O2 (1.6
mL, 14.5 mmol) following general procedure A, 10 (1.24 g, 76%) was isolated as a
white solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:2). Spectroꢀ
scopic data were identical with the literature.7b
3
2
136.3, 132.8, 132.4, 129.3, 128.4, 128.1 (d, JCꢀF = 7.5 Hz), 123.5, 115.5 (d, JCꢀF
=
1,2-bis(adamantan-1-ylsulfinyl)ethane (14). From 14a (2.54 g, 7.0 mmol) and
mCPBA (2.98 g, 14.7 mmol) following general procedure B, 14 (2.21 g, 80%) was
isolated as a white solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:1).
1H NMR (600 MHz, CDCl3) δ 3.06 – 2.85 (m, 4H), 2.18 (broad s, 6H), 1.95 – 1.81
(m, 12H), 1.81 – 1.66 (m, 12H). 13C NMR (CDCl3, 150 MHz): 36.2, 36.2, 35.0, 35.0,
28.6, 28.6. HRꢀMS (APCI): m/z calcd. for C22H34NaO2S2 ([M+Na]+): 417.1892;
found: 417.1906 (δ 3.4 ppm).
21.0 Hz), 53.9, 48.7, 21.6. HRꢀMS (ESI): m/z calcd. for C18H18FNNaO4S ([M+Na]+):
386.0833; found: 386.0846 (d 3.4 ppm).
(E)-methyl (3-(4-methoxyphenyl)allyl)(tosyl)carbamate (13ca). From Pd(OAc)2
(1.1 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol, 5 mol%), 1ꢀallylꢀ4ꢀ
methoxybenzene (11c; 38 ꢀL, 30.5 mg, 0.25 mmol) following the general procedure,
13ca (59.1 mg, 63%) was obtained after flash chromatography (petroleum ether ꢀ
EtOAc =12:1). Spectroscopic data were identical with the literature.17
1,2-bis((2-phenylpropan-2-yl)sulfinyl)ethane (15). From 15a (2.0 g, 6.0 mmol) and
H2O2 (1.4 mL, 12.6 mmol) following general procedure A, 15 (1.41 g, 65%) was
isolated as a white solid after flash chromatography (petroleum ether ꢀ EtOAc = 1:2).
HRꢀMS (APCI): m/z calcd. for C20H26NaO2S2 ([M+Na]+): 385.1266; found:
385.1281 (δ 3.9 ppm). Chemical shifts for the major diastereomer (4.3:1, configuraꢀ
(E)-methyl (3-(o-tolyl)allyl)(tosyl)carbamate (13da). From Pd(OAc)2 (1.1 mg, 5
ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol, 5 mol%), oꢀallyltoluene (11d; 37 ꢀL,
33.1 mg, 0.25 mmol) following the general procedure, 13da (74.6 mg, 83%) was
obtained as a white solid after flash chromatography (petroleum ether ꢀ EtOAc =
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15:1). m. p. 90ꢀ92 °C. 1H NMR (600 MHz, CDCl3): δ 7.85 (d, J = 8.0 Hz, 2H), 7.40
MS (ESI): m/z calcd. for C25H29OSi ((M+H)+): 373.1988; found 373.1986 (δ 0.5
(d, J = 6.8 Hz, 1H), 7.29 (d, J = 7.9 Hz, 2H), 7.17 (m, 3H), 6.92 (d, J = 15.7 Hz, 1H),
6.12(dt, J = 15.7, 6.5 Hz, 1H), 4.64 (d, J = 6.2 Hz, 2H), 3.72 (s, 3H), 2.42 (s, 3H),
2.35 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 152.7, 144.6, 136.4, 135.6, 135.4,
132.1, 130.3, 129.3, 128.5, 127.8, 126.1, 125.7, 125.0, 53.8, 48.9, 21.6, 19.7. HRꢀMS
(ESI): m/z calcd. for C19H21NNaO4S ([M+Na]+): 382.1084; found: 382.1098 (δ 3.7
ppm).
ppm).
1
2
3
4
5
6
7
8
(3aR,5R,6S,6aR)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-6-(hex-5-en-1-yloxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3]dioxole (11n). To a stirred solution of 1,2,5,6ꢀ
diisopropylideneꢀDꢀglucose (0.52 g, 2 mmol) in DMF (10 mL) were added NaH
(60% in oil) (96 mg, 4 mmol). The mixture was cooled to 0 °C and 6ꢀbromohexꢀ1ꢀ
ene (0.55 mL, 0.65 mg, 4 mmol) was added dropwise. Then the mixture was warmed
up to room temperature and stirred for 1 hours, quenched with MeOH and washed
with H2O (3 x 10 mL), and the aqueous rinses backꢀextracted with ether (3 x 20 mL).
The combined organic extracts were dried over MgSO4 and filtered, and the volatiles
removed under reduced pressure. 11n (671.8 mg, 98%) was obtained as a light
yellow oil after flash chromatography (petroleum ether ꢀ EtOAc = 16:1). 1H NMR
(600 MHz, CDCl3): δ 5.85 – 5.80 (m, 1H), 5.80 – 5.70 (m, 1H), 4.96 (ddd, J = 17.1,
3.3, 1.6 Hz, 1H), 4.92 – 4.88 (m, 1H), 4.48 (dd, J = 4.1, 2.3 Hz, 1H), 4.29 – 4.22 (m,
1H), 4.11 – 4.00 (m, 2H), 3.93 (ddd, J = 8.4, 6.0, 3.1 Hz, 1H), 3.84 – 3.77 (m, 1H),
3.62 – 3.53 (m, 1H), 3.51 – 3.44 (m, 1H), 2.02 (s, 2H), 1.58 – 1.49 (m, 2H), 1.46 –
1.44 (m, 3H), 1.43 – 1.39 (m, 2H), 1.39 – 1.37 (m, 3H), 1.31 – 1.29 (m, 3H), 1.28 –
1.26 (m, 3H). 13C NMR (150 MHz, CDCl3): δ 138.5, 114.5, 111.6, 108.8, 105.2,
82.4, 82.0, 81.1, 72.4, 70.3, 67.2, 33.3, 29.0, 26.7, 26.67, 26.1, 25.3, 25.2. HRꢀMS
(ESI): m/z calcd. for C18H30NaO6 ([M+Na]+): 365.1935; found: 365.1948 (δ 3.6
ppm).
(E)-methyl (3-(2-acetoxyphenyl)allyl)(tosyl)carbamate (13ea). From Pd(OAc)2
(1.1 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol, 5 mol%), 2ꢀallylphenyl
acetate18 (11e; 44 mg, 0.25 mmol) following the general procedure, 13ea (80.6 mg,
80%) was obtained as a yellow semi solid after flash chromatography (petroleum
1
ether ꢀ EtOAc = 12:1). H NMR (600 MHz, CDC3): δ 7.82 (d, J = 8.2 Hz, 2H), 7.49
(d, J = 7.7 Hz, 1H), 7.30 – 7.25 (m, 3H), 7.20 (t, J = 7.5 Hz, 1H), 7.05 (d, J = 8.0 Hz,
1H), 6.73 (d, J = 15.9 Hz, 1H), 6.23 (dt, J = 15.8, 6.3 Hz, 1H), 4.61 (d, J = 6.2 Hz,
2H), 3.69 (s, 3H), 2.39 (s, 3H), 2.30 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.4,
152.6, 148.1, 144.6, 136.2, 129.3, 128.8, 128.5, 127.6, 126.9, 126.2, 126.2, 122.6,
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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56
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58
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60
114.9, 53.9, 48.7, 21.6, 20.8. HRꢀMS (ESI): m/z calcd. for
C20H21NNaO6S
([M+Na]+): 426.0982; found: 426.0996 (δ 3.3 ppm).
(E)-methyl dec-2-en-1-yl(tosyl)carbamate (13fa). From Pd(OAc)2 (2.8 mg, 12.5
ꢀmol, 5 mol% or 1.1 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol, 5 mol%),
1ꢀdecene (11f; 50 ꢀL, 35.1 mg, 0.25 mmol) following the general procedure, 13fa (5
mol% Pd: 19.3 mg, 21%; 2 mol% Pd: 6.4 mg, 7%) was obtained after flash chromaꢀ
tography (petroleum ether ꢀ EtOAc = 20:1). Spectroscopic data for the product
matched that which was reported previously.7h
2,2,2- trifluoroethyl tosylcarbamate (12d). Following the procedure for 12e, from
2,2,2ꢀtrifluoroethanol (1.1 mL, 1.5 g, 15 mmol), tosyl isocyanate (1.5 mL, 2.0 g, 10
mmol), 12d (2.22 g, 75%) was obtained as a white solid after flash chromatography
(petroleum ether ꢀ EtOAc = 2:1). m. p. 126ꢀ128 °C. 1H NMR (300 MHz, CDCl3): δ
7.93 (d, J = 8.3 Hz, 2H), 7.80 (s, 1H), 7.37 (d, J = 8.1 Hz, 2H), 4.43 (q, J = 8.2 Hz,
2H), 2.46 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 148.9, 145.7, 134.7, 129.8, 128.4,
121.2 (q, 1JCꢀF = 276 Hz), 61.9 (q, 2JCꢀF = 36.0 Hz), 21.7. HRꢀMS (ESI): m/z calcd.
for C10H10F3NNaO4S ([M+Na]+): 320.0175; found: 320.0188 (δ 4.1 ppm).
(E)-methyl (3-cyclohexylallyl)(tosyl)carbamate (13ga). From Pd(OAc)2 (2.8 mg,
12.5 ꢀmol, 5 mol% or 1.1 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol, 5
mol%), allylcyclohexane (11g; 40 ꢀL, 31.0 mg, 0.25 mmol) following the general
procedure, 13ga (5 mol% Pd: 26.3 mg, 30%; 2 mol% Pd: 7.9 mg, 9%) was obtained
after flash chromatography (petroleum ether ꢀ EtOAc = 12:1). Spectroscopic data
were identical with the literature.7h
2,2,2-trichloroethyl tosylcarbamate (12e). To
a stirred solution of 2,2,2ꢀ
trichloroethanol (1.4 mL, 2.24 g, 15 mmol) in CH2Cl2 (20 mL). The mixture was
cooled to 0°C and tosyl isocyanate (1.5 mL, 2.0 g, 10 mmol) was added dropwise.
Then the mixture was warmed up to room temperature and stirred for 3 hours, diluted
with CH2Cl2, washed with water and brine, dried (MgSO4) and filtered, and the
volatiles removed under reduced pressure; 12e (1.47 g, 85%) was obtained as a white
solid after flash chromatography (petroleum ether ꢀ EtOAc = 2:1). m. p. 95ꢀ97 °C. 1H
NMR (600 MHz, CDCl3): δ 8.19 (s, 1H), 7.95 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.0
Hz, 2H), 4.69 (s, 2H), 2.45 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 149.1, 145.5,
134.9, 129.7, 128.5, 126.4, 93.9, 75.2, 21.7. HRꢀMS (ESI): m/z calcd. for
(E)-methyl (4-phenylbut-2-en-1-yl)(tosyl)carbamate (13ha). From (2.8 mg, 12.5
ꢀmol, 5 mol% or 1.1 mg, 5 ꢀmol, 2 mol%), ligand 14 (4.9 mg, 12.5 ꢀmol, 5 mol%),
3ꢀbutenylbenzene (11h; 38 ꢀL, 33.1 mg, 0.25 mmol) following the general proceꢀ
dure, 13ha (5 mol%: 9.9 mg, 11%; 2 mol%: 5.4 mg, 6%) was obtained as a white
semi solid after flash chromatography (petroleum ether ꢀ EtOAc = 16:1). 1H NMR
(600 MHz, CDCl3): δ 7.78 (d, J = 8.2 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.26 – 7.21
(m, 3H), 7.18 (d, J = 7.4 Hz, 2H), 5.98 – 5.91 (m, 1H), 5.65 – 5.57 (m, 1H), 4.45 (d,
J = 6.3 Hz, 2H), 3.68 (s, 3H), 3.39 (d, J = 6.8 Hz, 2H), 2.42 (s, 3H). 13C NMR (150
MHz, CDCl3): δ 152.7, 144.5, 139.6, 136.4, 134.1, 129.2, 128.5, 128.5, 128.5, 126.2,
125.7, 53.7, 48.4, 38.6, 21.6. HRꢀMS (ESI): m/z calcd. for C19H21NNaO4S
([M+Na]+): 382.1084; found: 382.1097 (δ 3.4 ppm).
C
10H10Cl3NNaO4S ([M+Na]+): 367.9288; found: 367.9301 (δ 3.5 ppm).
C-H amination of various tosyl carbamates. (Table 3), general procedure. Two
runs were set side by side. Each vial was charged with Pd(OAc)2 (5.6 mg, 25 ꢀmol,
10 mol%), ligand 3 (6.3 mg, 25 ꢀmol, 10 mol%) or 14 (9.8 mg, 25 ꢀmol, 10 mol%),
a stir bar, and tertꢀbutyl methyl ether (1 mL) was added using a disposable syringe.
Each vial was capped and stirred for 15 min, then 1,4ꢀbenzoquinone (54 mg, 0.5
mmol), the required tosyl carbamate (0.275 mmol), and 1ꢀdecene (50 ꢀL, 35.1 mg,
0.25 mmol) were added in a sequence. Finally, Et3N (2 ꢀL, 1.5 mg, 15 ꢀmol, 6
mol%) was added via syringe. The vials were securely capped and the reaction
mixtures were stirred at 45 °C for 72 hours. Next, the vials were cooled down to
room temperature, pooled together in CH2Cl2 and washed sequentially with saturated
aqueous NaHSO3 and brine. The organic layer was dried (MgSO4), filtered and
concentrated under reduced pressure.
C-H amination of n-decene with methyl tosylcarbamate (Scheme 3). (E)- and
(Z)-methyl dec-2-en-1-yl(tosyl)carbamate (13fa) and methyl 2-tosyl-3-
vinyldecanoate (16fa). Two runs were set side by side. Each vial was charged with
Pd(OAc)2 (5.6 mg, 25 ꢀmol, 10 mol%), ligand 3 (6.3 mg, 25 ꢀmol, 10 mol%) or 14
(9.8 mg, 25 ꢀmol, 10 mol%), a stir bar, and tertꢀbutyl methyl ether (1 mL) was added
using a disposable syringe. Each vial was capped and stirred for 15 min, Then 1,4ꢀ
benzoquinone (27 mg, 0.25 mmol), methyl tosylcarbamate (63 mg, 0.275 mmol), and
1ꢀdecene (50 ꢀL, 35.1 mg, 0.25 mmol) were added in a sequence. Finally, Et3N (2
ꢀL, 1.5 mg, 15 ꢀmol, 6 mol%) was added via syringe. The vials were securely
capped and the reaction mixtures were stirred at 45 °C for 72 hours. Next, the vials
were cooled down to room temperature, pooled together in CH2Cl2 and washed
sequentially with saturated aqueous NaHSO3 and brine. The organic layer was dried
(MgSO4), filtered and concentrated under reduced pressure. A mixture of (E)ꢀ and
(Z)ꢀ13fa, and 16fa (ligand 3: 31.2 mg, 34%, E/Z/B = 11:1:1, ligand 14: 54.1 mg,
59%, E/Z/B = 15:1:1) was isolated as a light yellow oil after flash chromatography
(petroleum ether ꢀ EtOAc = 20:1).
(E)- and (Z)-tert-butyl dec-2-en-1-yl(tosyl)carbamate (13fb) and tert-butyl dec-
1-en-3-yl(tosyl)carbamate (16fb). From tertꢀbutyl tosylcarbamate (74.2 mg, 0.275
mmol) following the general procedure, a mixture of (E)ꢀ and (Z)ꢀ13fb and 16fb
(ligand 3: 10.3 mg, 10%, E/Z/B = 12:1:0.5; ligand 14: 25.7 mg, 25%, E/Z/B =
9:1:0.6) was isolated after flash chromatography (petroleum ether ꢀ EtOAc = 20:1).
Spectroscopic data were identical with the literature.19
2-allylphenyl tert-butyl carbonate (11i). To a stirred solution of 2ꢀallylphenol (0.65
mL, 0.67 g, 5 mmol) in CH2Cl2 (20 mL) was added DMAP (0.61 g, 5 mmol). The
mixture was cooled to 0°C and (Boc)2O (2.4 g, 11 mmol) was added. Next, the
mixture was warmed up to room temperature and stirred for 20 min. The solution
was then diluted with CH2Cl2, washed with water and brine, dried (MgSO4), and the
volatiles were removed under reduced pressure. 11i (1.16 g, 98%) was obtained as a
colorless oil after flash chromatography (petroleum ether ꢀ EtOAc = 20:1). 1H NMR
(600 MHz, CDCl3): δ 7.24 (ddd, J = 7.1, 4.1, 2.2 Hz, 2H), 7.20 – 7.15 (m, 1H), 7.13
– 7.09 (m, 1H), 5.92 (ddt, J = 16.8, 10.1, 6.7 Hz, 1H), 5.17 – 5.01 (m, 2H), 3.36 (d, J
= 6.6 Hz, 2H), 1.55 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 151.8, 149.2, 135.8,
132.0, 130.3, 127.3, 126.1, 122.2, 116.2, 83.2, 34.3, 27.6. HRꢀMS (ESI): m/z calcd.
for C14H18NaO3 ((M+Na)+): 257.1148; found: 257.1152 (δ 1.6 ppm).
(E)- and (Z)-benzyl dec-2-en-1-yl(tosyl)carbamate (13fc) and benzyl dec-1-en-3-
yl(tosyl)carbamate (16fc). From benzyl tosylcarbamate (83.9 mg, 0.275 mmol)
following the general procedure, a mixture of (E)ꢀ and (Z)ꢀ13fc and 16fc (ligand 3:
43.3 mg, 39%, E/Z/B = 12:1:0.8; ligand 14: 64.3 mg, 58%, E/Z/B = 17:1:0) was
isolated as a yellow semi solid after flash chromatography (petroleum ether ꢀ EtOAc
= 20:1). HRꢀMS (ESI): m/z calcd. for C25H33NNaO4S ([M+Na]+): 466.2023; found:
466.2038 (δ 3.2 ppm). The peaks for the major isomer (13fc) are as follows:1H NMR
(600 MHz, CDCl3): δ 7.75 (d, J = 8.2 Hz, 2H), 7.36 – 7.30 (m, 3H), 7.24 – 7.18 (m,
4H), 5.80 – 5.76 (m, 1H), 5.58 – 5.53 (m, 1H), 5.10 (s, 2H), 4.45 (d, J = 6.4 Hz, 2H),
2.42 (s, 3H), 2.05 (q, J = 7.1 Hz, 2H), 1.39 – 1.33 (m, 2H), 1.33 – 1.29 (m, 8H), 0.91
(t, J = 7.0 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 152.1, 144.2, 136.6, 136.1,
134.6, 129.1, 128.4, 128.4, 128.4, 128.7, 124.1, 68.8, 48.7, 32.2, 31.8, 29.1, 29.1,
28.9, 22.6, 21.6, 14.1.
(2-allylphenoxy)(tert-butyl)diphenylsilane (11j). To
a stirred solution of 2ꢀ
allylphenol (2.0 mL, 2.01 g, 15 mmol) in CH2Cl2 (20 mL) was added imidazole (2.0
g, 30 mmol). The solution was cooled at 0 °C and TBDPSCl (3.9 mL, 4.12 g, 15
mmol) was added. Then the mixture was warmed up to room temperature and stirred
for 20 min, diluted with CH2Cl2, washed with water and brine, dried (MgSO4), and
the volatiles were removed under reduced pressure. 11j (4.74 g, 85%) was obtained
as a colorless oil after flash chromatography (petroleum ether ꢀ EtOAc = 20:1). 1H
NMR (600 MHz, CDCl3): δ 7.91 – 7.77 (m, 4H), 7.50 (t, J = 7.4, 2H), 7.45 (t, J =
7.1, 4H), 7.26 (dd, J = 7.8, 2.0, 1H), 6.91 (t, J = 7.7, 1H), 6.86 (td, J = 7.7, 1.8, 1H),
6.60 – 6.51 (m, 1H), 6.23 (ddt, J = 15.7, 10.7, 6.5, 1H), 5.29 – 5.09 (m, 2H), 3.71 (d,
J = 6.4, 2H), 1.23 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 153.1, 137.1, 135.4,
132.7, 130.1, 130.0, 129.9, 127.8, 126.8, 121.0, 118.8, 115.5, 34.7, 26.6, 19.5. HRꢀ
(E)- and (Z)-2,2,2-trifluoroethyl dec-2-en-1-yl(tosyl)carbamate (13fd) and 2,2,2-
trifluoroethyl dec-1-en-3-yl(tosyl)carbamate (16fd). From 2,2,2ꢀtrifluoroethyl
tosylcarbamate (81.7 mg, 0.275 mmol) following the general procedure, a mixture of
(E)ꢀ and (Z)ꢀ13fd and 16fd (ligand 3: 44.6 mg, 41%, E/Z/B = 12:1:1; ligand 14: 69.7
mg, 64%, E/Z/B = 12:1:0.9) was isolated as a yellow semi solid after flash chromaꢀ
tography (petroleum ether
C
ꢀ EtOAc = 20:1). HRꢀMS (ESI): m/z calcd. for
20H28F3NNaO4S ([M+Na]+): 458.1583; found: 458.1601 (δ 3.9 ppm). The peaks for
the major isomer (13fd) are as follows: 1H NMR (600 MHz, CDCl3): δ 7.82 (d, J =
8.3 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 5.81 – 5.77 (m, 1H), 5.53 – 5.49 (m, 1H), 4.44
– 4.40 (m, 4H), 2.42 (s, 3H), 2.03 (q, J = 7.0 Hz, 2H), 1.38 – 1.33 (m, 2H), 1.30 –
1.26 (m, 8H), 0.87 (t, J = 6.9 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.9,
136.8, 135.9, 129.3, 128.5, 123.4, 122.4 (q, JCꢀF = 276 Hz), 62.1 (q, 2JCꢀF = 37.5 Hz),
1
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The Journal of Organic Chemistry
49.1, 32.1, 31.7, 29.1, 29.1, 28.8, 22.6, 21.6, 14.0.
102 °C. 1H NMR (600 MHz, CDCl3): δ 7.89 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 7.7 Hz,
1H), 7.31 – 7.27 (m, 3H), 7.21 (t, J = 7.5 Hz, 1H), 7.15 (d, J = 8.1 Hz, 1H), 6.88 (d, J
= 15.9 Hz, 1H), 6.33 (dt, J = 15.7, 6.7 Hz, 1H), 4.72 (s, 2H), 4.71 (d, J = 6.8 Hz, 2H),
2.40 (s, 3H), 1.55 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 151.7, 150.7, 148.4,
145.0, 135.5, 129.4, 129.0, 128.7, 128.7, 128.4, 126.9, 126.1, 125.5, 122.5, 94.0,
83.8, 75.7, 49.2, 27.6, 21.6. HRꢀMS (ESI): m/z calcd. for C24H26Cl3NNaO7S
([M+Na]+): 600.0388; found: 600.0413 (δ 4.2 ppm).
(E)- and (Z)-2,2,2-trichloroethyl dec-2-en-1-yl(tosyl)carbamate (13fe) and 2,2,2-
trichloroethyl dec-1-en-3-yl(tosyl)carbamate (16fe). From 2,2,2ꢀtrichloroethyl
tosylcarbamate (95 mg, 0.275 mmol) following the general procedure, a mixture of
(E)ꢀ and (Z)ꢀ13fe and 16fe (ligand 3: 47.9 mg, 39%, E/Z/B = 15:1:0.8; ligand 14:
82.4 mg, 68%, E/Z/B = 15:1:1) was isolated as a white solid after flash chromatogꢀ
1
2
3
4
5
6
7
8
raphy (petroleum ether
C
ꢀ EtOAc = 20:1). HRꢀMS (ESI): m/z calcd. for
20H28Cl3NNaO4S ([M+Na]+): 506.0702; found: 506.0712. The peaks for the major
(E)-2,2,2-trichloroethyl (3-(2-((tert-butyldiphenylsilyl)oxy)phenyl)allyl)(tosyl)-
carbamate (13je). From (2ꢀallylphenoxy)(tertꢀbutyl)diphenylsilane (11j; 93 mg,
0.25 mmol) following the general procedure, 13je (157.3 mg, 88%) was isolated as a
white solid after flash chromatography (petroleum ether ꢀ EtOAc = 16:1). m. p. 118ꢀ
120 °C. 1H NMR (600 MHz, CDCl3): δ 7.92 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 7.0 Hz,
4H), 7.45ꢀ7.41 (m, 4H), 7.39 (t, J = 7.3 Hz,4H), 7.27 (d, J = 8.1 Hz, 2H), 6.84 (m,
2H), 6.46 (m, 1H), 6.32 (dt, J = 15.9, 6.7 Hz, 1H), 4.78 (d, J = 6.7 Hz, 2H), 4.74 (s,
2H), 2.41 (s, 3H), 1.12 (s, 9H). 13C NMR (150 MHz, CDCl3): δ 152.9, 150.9, 144.8,
135.9, 135.4, 132.5, 130.1, 129.9, 129.4, 128.7, 128.7, 127.8, 126.9, 126.5, 123.2,
121.1, 119.5, 94.1, 75.7, 49.6, 26.6, 21.6, 19.6. HRꢀMS (ESI): m/z calcd. for
C35H36Cl3NNaO5SSi ([M+Na]+): 738.1041; found: 738.1072 (δ 4.2 ppm).
isomer (13fe) are as follows: The peaks for the major isomer (13fe) are as follows:
1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H),
5.88 – 5.81 (m, 1H), 5.62 – 5.54 (m, 1H), 4.69 (s, 2H), 4.48 (d, J = 6.5 Hz, 2H), 2.43
(s, 3H), 2.04 (q, J = 7.1 Hz, 2H), 1.38 – 1.33 (m, 2H), 1.32 – 1.24 (m, 8H), 0.88 (t, J
= 7.0 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 150.9, 144.8, 136.8, 136.0, 129.3,
128.6, 123.7, 94.1, 75.7, 49.1, 32.2, 31.8, 29.1, 29.1, 28.9, 22.6, 21.6, 14.1.
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14
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16
17
18
19
20
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22
23
24
25
26
27
28
29
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31
32
33
34
35
36
37
38
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41
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44
45
46
47
48
49
50
51
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53
54
55
56
57
58
59
60
C-H amination with 2,2,2-trichloroethyl tosylcarbamate (Scheme 4), general
procedure. Two runs were set side by side. Each vial was charged with Pd(OAc)2
(5.6 mg, 25 ꢀmol, 10 mol%), ligand 14 (9.8 mg, 25 ꢀmol, 10 mol%), a stir bar, and
tertꢀbutyl methyl ether (1 mL) was added using a disposable syringe. Each vial was
capped and stirred for 15 min, then 1,4ꢀbenzoquinone (54 mg, 0.05 mmol), 2,2,2ꢀ
trichloroethyl tosylcarbamate (95 mg, 0.275 mmol), and the required alkene (0.25
mmol) were added in a sequence. Finally, Et3N (2 ꢀL, 1.5 mg, 15 ꢀmol, 6 mol%)
was added via syringe. The vials were securely capped and the reaction mixtures
were stirred at 45 °C for 72 hours. Next, the vials were cooled down to room temperꢀ
ature, pooled together in CH2Cl2 and washed sequentially with saturated aqueous
NaHSO3 and brine. The organic layer was dried (MgSO4), filtered and concentrated
under reduced pressure.
(E)-2,2,2-trichloroethyl (3-(perfluorophenyl)allyl)(tosyl)carbamate (13ke). From
1ꢀallylꢀ2,3,4,5,6ꢀpentafluorobenzene (11k, 39 ꢀL, 52.0 mg, 0.25 mmol) following
the general procedure, 13ke (73.2 mg, 53%) was isolated as a white solid after flash
1
chromatography (petroleum ether ꢀ EtOAc = 20:1). m. p. 106ꢀ108 °C. H NMR (600
MHz, CDCl3): δ 7.90 (d, J = 7.9 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 6.68 – 6.60 (m,
2H), 4.73 (broad s, 4H), 2.44 (s, 3H). 13C NMR (150 MHz, CDCl3): δ (C6F5 carbon
signals are hidden in the noise) 150.6, 145.4, 135.5, 132.7, 129.5, 128.6, 118.4, 93.9,
75.8, 49.4, 21.7. HRꢀMS (ESI): m/z calcd. for C19H13Cl3F5NNaO4S ([M+Na]+):
573.9443; found: 573.9467 (δ 4.2 ppm).
(E)-2,2,2-trichloroethyl (3-(4-fluorophenyl)allyl)(tosyl)carbamate (13be). From
1ꢀallylꢀ4ꢀfluorobenzene (11b; 35 ꢀL, 34.0 mg, 0.25 mmol) following the general
procedure, 13be (117.8 mg, 98%) was isolated as a white solid after flash chromaꢀ
tography (petroleum ether ꢀ EtOAc = 16:1). m. p. 107ꢀ108 °C. 1H NMR (600 MHz,
CDCl3): δ 7.88 (d, J = 8.2 Hz, 2H), 7.34 (dd, J = 8.4, 5.5 Hz, 2H), 7.29 (d, J = 8.1
Hz, 2H), 7.02 (t, J = 8.6 Hz, 2H), 6.69 (d, J = 15.8 Hz, 1H), 6.22 (dt, J = 15.7, 6.6
Hz, 1H), 4.73 (s, 2H), 4.68 (d, J = 6.6 Hz, 2H), 2.42 (s, 3H). 13C NMR (150 MHz,
(E)-2,2,2-trichloroethyl (3-cyclohexylallyl)(tosyl)carbamate (13ge). From allylcyꢀ
clohexane (11g; 40 ꢀL, 31.0 mg, 0.25 mmol) and 2,2,2ꢀtrichloroethyl tosylcarbamate
(173 mg, 0.50 mmol), following the general procedure, 13ge (60.8 mg, 52%) was
isolated as a white solid after flash chromatography (petroleum ether ꢀ EtOAc =
16:1). m. p. 119ꢀ121 °C. 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.2 Hz, 2H),
7.30 (d, J = 8.1 Hz, 2H), 5.80 (dd, J = 15.5, 6.6 Hz, 1H), 5.54 (dt, J = 15.5, 6.5 Hz,
1H), 4.69 (s, 2H), 4.48 (d, J = 6.5 Hz, 2H), 2.43 (s, 3H), 1.98 (m, 1H), 1.72 (m, 4H),
1.66 (d, J = 12.6 Hz, 1H), 1.31 – 1.22 (m, 2H), 1.20 – 1.13 (m, 1H), 1.11 – 1.03 (m,
2H). 13C NMR (150 MHz, CDCl3): δ 150.9, 144.8, 142.3, 135.9, 129.3, 128.7, 121.3,
94.1, 75.7, 49.2, 40.3, 32.6, 26.1, 25.9, 21.6. HRꢀMS (ESI): m/z calcd. for
C19H24Cl3NNaO4S ([M+Na]+): 490.0384; found: 490.0402 (δ 3.7 ppm).
1
CDCl3): δ 162.6 (d, JCꢀF = 246 Hz), 150.8, 145.1, 135.7, 133.6, 132.2, 132.2, 129.4,
3
2
128.6, 128.2 (d, JCꢀF = 7.5 Hz), 122.9, 122.9, 115.6 (d, JCꢀF = 21 Hz), 94.1, 75.8,
49.7, 21.6. HRꢀMS (ESI): m/z calcd. for C19H17Cl3FNNaO4S ([M+Na]+): 501.9826;
found: 501.9837 (δ 2.2 ppm).
(E)-2,2,2-trichloroethyl (3-(4-methoxyphenyl)allyl)(tosyl)carbamate (13ce). From
1ꢀallylꢀ4ꢀmethoxybenzene (11c; 38 ꢀL, 30.5 mg, 0.25 mmol) following the general
procedure, 13ce (114.6 mg, 93%) was isolated as a white solid after flash chromatogꢀ
raphy (petroleum ether ꢀ EtOAc = 16:1). m. p. 157ꢀ159 °C. 1H NMR (600 MHz,
CDCl3): δ 7.89 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 8.7 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H),
6.87 (d, J = 8.6 Hz, 2H), 6.68 (d, J = 15.8 Hz, 1H), 6.16 (dt, J = 15.7, 6.7 Hz, 1H),
4.73 (s, 2H), 4.68 (d, J = 6.7 Hz, 2H), 3.82 (s, 3H), 2.41 (s, 3H). 13C NMR (150
MHz, CDCl3): δ 159.6, 150.9, 145.0, 135.8, 134.5, 129.4, 128.8, 128.7, 127.8, 120.8,
114.0, 94.1, 75.7, 55.3, 49.4, 21.6. HRꢀMS (ESI): m/z calcd. for C20H20Cl3NNaO5S
([M+Na]+): 514.0020; found: 514.0040 (δ 3.9 ppm). Low catalyst loading run:
From 1ꢀallylꢀ4ꢀmethoxybenzene (11c; 38 ꢀL, 30.5 mg, 0.25 mmol), Pd(OAc)2 (1.1
mg, 5 ꢀmol, 2 mol%), 14 (4.9 mg, 12.5 ꢀmol, 5 mol%), and 12e (172.5 mg, 0.5
mmol) following the general procedure, 13ce (30.7 mg, 25%) was isolated as above.
Larger scale run: From 1ꢀallylꢀ4ꢀmethoxybenzene (11c; 380 ꢀL, 305 mg, 2.5
mmol), Pd(OAc)2 (56 mg, 0.25 mmol, 10 mol%), 14 (98 mg, 0.25 mmol, 10 mol%),
Et3N (20 ꢀL, 15 mg, 0.15 mmol, 6 mol%) and 12e (950 mg, 2.75 mmol) following
the general procedure, 13ce (1.14 g, 93%) was isolated as above.
(E)-2,2,2-trichloroethyl (4-phenylbut-2-en-1-yl)(tosyl)carbamate (13he). From 3ꢀ
butenylbenzene (11h; 38 ꢀL, 33.1 mg, 0.25 mmol) and 2,2,2ꢀtrichloroethyl tosylcarꢀ
bamate (173 mg, 0.50 mmol) following the general procedure, 13he (68.9 mg, 58%)
was isolated as a white solid after flash chromatography (petroleum ether ꢀ EtOAc =
16:1). m. p. 103ꢀ105 °C. 1H NMR (600 MHz, CDCl3): δ 7.83 (d, J = 8.3 Hz, 2H),
7.30 (t, J = 7.5 Hz, 2H), 7.27 – 7.21 (m, 3H), 7.17 (d, J = 7.5 Hz, 2H), 6.02 (m, 1H),
5.65 (m, 1H), 4.67 (s, 2H), 4.52 (d, J = 6.4 Hz, 2H), 3.40 (d, J = 6.7 Hz, 2H), 2.43 (s,
3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.9, 139.4, 135.7, 135.0, 129.3, 128.6,
128.6, 128.5, 126.2, 125.1, 94.0, 75.6, 48.7, 38.6, 21.7. HRꢀMS (ESI): m/z calcd. for
C20H20Cl3NNaO4S ([M+Na]+): 498.0071; found: 498.0087 (δ 3.2 ppm).
(E)- and (Z)-2,2,2-trichloroethyl (5-((tert-butyldiphenylsilyl)oxy)pent-2-en-1-
yl)(tosyl)carbamate (13le) and 2,2,2-trichloroethyl (5-((tert-butyldiphenyl-
silyl)oxy)pent-1-en-3-yl)(tosyl)carbamate (16le). From 5ꢀ((tertꢀbutyldipehylsilyl)ꢀ
oxy)pentꢀ1ꢀene (11l; 81 mg, 0.25 mmol) and 2,2,2ꢀtrichloroethyl tosylcarbamate
(173 mg, 0.50 mmol) following the general procedure, a mixture of (E)ꢀ and (Z)ꢀ13le
and 16le (98.6 mg, 58%, E/Z/B = 10:1:1.4) was isolated as a yellow oil after flash
chromatography (petroleum ether ꢀ EtOAc = 20:1). HRꢀMS (ESI): m/z calcd. for
C31H36Cl3NNaO5SSi ([M+Na]+): 690.1041; found: 690.1066 (δ 3.6 ppm). The peaks
for the major isomer (13le) are as follows: 1H NMR (600 MHz, CDCl3): δ 7.89 (d, J
= 7.4 Hz, 2H), 7.70 (d, J = 6.8 Hz, 4H), 7.46 – 7.40 (m, 6H), 7.26 (d, J = 8.0 Hz,
2H), 5.89 (m, 1H), 5.68 (m, 1H), 4.70 (s, 2H), 4.51 (d, J = 6.0 Hz, 2H), 3.75 (t, J =
6.6 Hz, 2H), 2.41 (s, 3H), 2.36 (m, 2H), 1.09 (d, J = 1.7 Hz, 9H). 13C NMR (150
MHz, CDCl3): δ 150.8, 144.8, 135.5, 135.5, 133.8, 132.8, 129.6, 129.3, 128.6, 127.6,
125.8, 94.1, 75.6, 63.2, 49.0, 35.6, 26.8, 21.6, 19.2.
(E)-2,2,2-trichloroethyl (3-(o-tolyl)allyl)(tosyl)carbamate (13de). From 1ꢀallylꢀ2ꢀ
methylbenzene (11d; 37 ꢀL, 33.1 mg, 0.25 mmol) following the general procedure,
13de (114.4 mg, 96%) was isolated as a white solid after flash chromatography
(petroleum ether ꢀ EtOAc = 16:1). m. p. 110ꢀ112 °C. 1H NMR (600 MHz, CDCl3): δ
7.90 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 6.5 Hz, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.22 –
7.15 (m, 3H), 6.97 (d, J = 15.7 Hz, 1H), 6.19 (dt, J = 15.6, 6.5 Hz, 1H), 4.74 (s, 2H),
4.73 (d, J = 7.3 Hz, 2H), 2.42 (s, 3H), 2.35 (s, 3H). 13C NMR (150 MHz, CDCl3): δ
150.8, 145.0, 135.7, 135.2, 132.7, 130.3, 129.4, 128.6, 127.9, 126.4, 126.1, 125.7,
124.4, 94.1, 75.7, 49.4, 21.6, 19.7. HRꢀMS (ESI): m/z calcd. for C20H20Cl3NNaO4S
([M+Na]+): 498.0071; found: 498.0086 (δ 3.0 ppm). Low catalyst loading run:
From 1ꢀallylꢀ2ꢀmethylbenzene (11d; 37 ꢀL, 33.1 mg, 0.25 mmol), Pd(OAc)2 (1.1
mg, 5 ꢀmol, 2 mol%), 14 (4.9 mg, 12.5 ꢀmol, 5 mol%), and 12e (172.5 mg, 0.5
mmol) following the general procedure, 13de (38.2 mg, 32%) was isolated as above.
(E)- and (Z)-2,2,2-trichloroethyl (6-(1,3-dioxoisoindolin-2-yl)hex-2-en-1-
yl)(tosyl)carbamate (13me) and 2,2,2-trichloroethyl (6-(1,3-dioxoisoindolin-2-
yl)hex-1-en-3-yl)(tosyl)carbamate (16me). From 2ꢀ(hexꢀ5ꢀenꢀ1ꢀyl)isoindolineꢀ1,3ꢀ
dione (11m; 57.3 mg, 0.25 mmol) following the general procedure, a mixture of (E)ꢀ
and (Z)ꢀ13me and 16me (85.8 mg, 60%, E/Z/B = 11:1:2.4) was isolated as a white
solid after flash chromatography (petroleum ether ꢀ EtOAc = 5:1). HRꢀMS (ESI): m/z
calcd. for C24H23Cl3N2NaO6S ([M+Na]+): 595.0235; found: 595.0258 (δ 3.9 ppm).
The peaks for the major isomer (13me) are as follows: 1H NMR (600 MHz, CDCl3):
δ 7.87 – 7.81 (m, 4H), 7.73 – 7.69 (m, 2H), 7.30 (d, J = 7.8 Hz, 2H), 5.83 (m, 1H),
5.63 (m, 1H), 4.70 (d, J = 0.9 Hz, 2H), 4.45 (d, J = 6.2 Hz, 2H), 3.68 (t, J = 6.6 Hz,
2H), 2.41 (s, 3H), 2.12 (q, J = 7.0 Hz, 2H), 1.77 (p, J = 7.0 Hz, 2H). 13C NMR (150
MHz, CDCl3): δ 168.3, 150.8, 144.9, 135.8, 134.7, 133.9, 132.1, 129.4, 128.6, 124.8,
123.2, 94.1, 75.7, 48.9, 37.5, 29.4, 27.7, 21.6.
(E)-2-(3-(4-methyl-N-((2,2,2-trichloroethoxy)carbonyl)phenylsulfonamido)prop-
1-en-1-yl)phenyl acetate (13ee). From 2ꢀallylphenyl acetate18 (11e; 44 mg, 0.25
mmol) following the general procedure, 13ee (104.8 mg, 83%) was isolated as a
white solid after flash chromatography (petroleum ether ꢀ EtOAc = 12:1). m. p. 92ꢀ
94 °C. 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 7.7 Hz,
1H), 7.32 – 7.29 (m, 3H), 7.22 (t, J = 7.5 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 6.81 (d, J
= 15.9 Hz, 1H), 6.30 (dt, J = 15.8, 6.4 Hz, 1H), 4.72 (s, 2H), 4.70 (d, J = 6.4 Hz, 2H),
2.41 (s, 3H), 2.32 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.3, 150.7, 148.1,
145.0, 135.6, 129.5, 129.0, 128.8, 128.7, 128.2, 126.8, 126.2, 125.6, 122.7, 94.1,
75.7, 49.1, 21.6, 20.8. HRꢀMS (ESI): m/z calcd. for C21H20Cl3NNaO6S ([M+Na]+):
541.9969; found: 541.9986.
(E)- and (Z)-2,2,2-trichloroethyl (6-(((3aR,5R,6S,6aR)-5-((S)-2,2-dimethyl-1,3-
dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl)oxy)hex-2-en-
1-yl)(tosyl)carbamate (13ne) and 2,2,2-trichloroethyl (6-(((3aR,5R,6S,6aR)-5-
((S)-2,2-dimethyl-1,3-dioxolan-4-yl)-2,2-dimethyltetrahydrofuro[2,3-
d][1,3]dioxol-6-yl)oxy)hex-1-en-3-yl)(tosyl)carbamate (16ne). From 11n (85.5 mg,
0.25 mmol) following the general procedure, a mixture of 13ne and 16ne (115.1 mg,
67%, E/Z/B = 18:1:2) was isolated as a yellow oil after flash chromatography (petroꢀ
(E)-2,2,2-trichloroethyl
(3-(2-((tert-butoxycarbonyl)oxy)phenyl)allyl)(tosyl)-
carbamate (13ie). From 2ꢀallylphenyl tertꢀbutyl carbonate (11i; 58.5 mg, 0.25
mmol) following the general procedure, 13ie (125.7 mg, 87%) was isolated as a
white solid after flash chromatography (petroleum ether ꢀ EtOAc = 12:1). m. p. 100ꢀ
leum ether ꢀ EtOAc = 8:1). HRꢀMS (ESI): m/z calcd. for C28H38Cl3NNaO10
S
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 10
1H), 3.80 (t, J = 6.3 Hz, 2H), 2.42 (s, 3H), 1.12 (s, 9H). 13C NMR (150 MHz,
CDCl3): δ 152.6, 143.5, 137.2, 135.4, 132.5, 130.0, 129.7, 128.6, 128.5, 127.8, 127.2,
126.9, 126.3, 124.0, 121.2, 119.6, 46.0, 26.6, 21.5, 19.6. HRꢀMS (ESI): m/z calcd.
for C32H35NNaO3SSi ([M+Na]+): 564.1999; found: 564.2018 (δ 3.4 ppm).
([M+Na]+): 708.1174; found: 708.1199 (δ 3.5 ppm). The peaks for the major isomer
(13ne) are as follows: 1H NMR (600 MHz, CDCl3): δ 7.85 (d, J = 8.2 Hz, 2H), 7.30
(d, J = 8.1 Hz, 2H), 5.86 (d, J = 3.6 Hz, 1H), 5.82 (m, 1H), 5.61 (m, 1H), 4.69 (s,
2H), 4.52 (d, J = 3.7 Hz, 1H), 4.47 (d, J = 6.3 Hz, 2H), 4.29 (dd, J = 13.5, 6.1 Hz,
1H), 4.09 (ddd, J = 14.8, 8.0, 4.5 Hz, 2H), 3.97 (dd, J = 8.5, 5.9 Hz, 1H), 3.84 (d, J =
2.9 Hz, 1H), 3.63 – 3.59 (m, 1H), 3.50 (dt, J = 9.4, 6.2 Hz, 1H), 2.42 (s, 3H), 2.15 (s,
1H), 2.13 (q, J = 7.1 Hz, 1H), 1.70 – 1.64 (m, 2H), 1.48 (s, 3H), 1.41 (s, 3H), 1.34 (s,
3H), 1.30 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 150.8, 144.9, 135.4, 135.4, 129.4,
128.5, 124.5, 111.7, 108.9, 105.2, 94.1, 82.4, 82.1, 81.1, 75.6, 72.4, 69.5, 67.2, 49.0,
28.9, 28.6, 26.8, 26.7, 26.2, 25.4, 21.6.
1
2
3
4
5
6
(E)-N-(3-(2-hydroxyphenyl)allyl)tosylamide (17qe). From 13je (28.6 mg, 0.04
mmol), MeOH (1 mL), and K2CO3 (10.5 mg, 0.076 mmol) following the general
procedure B, 17qe (12.0 mg, 99%) was isolated after flash chromatography (petroleꢀ
um ether ꢀ EtOAc = 2:1).
Or, from 13ie (57.9 mg, 0.1mmol), MeOH (1 mL), and K2CO3 (26 mg, 0.19 mmol)
following the general procedure B, 17qe (29.4 mg, 97%) was isolated after flash
chromatography (petroleum ether ꢀ EtOAc = 2:1).
7
8
9
(E)-
and
(Z)-(2R,3R,4R,5S,6R)-2-(acetoxymethyl)-6--3-(4-methyl-N-
((trichloromethoxy)carbonyl)phenylsulfonamido)prop-1-en-1-yl)tetrahydro-2H-
pyran-3,4,5-triyl (13oe) triacetate. From 11o20 (93.1 mg, 0.25 mmol) following the
general procedure, 13oe (121.6 mg, 68%, E/Z = 14:1) was isolated as a white solid
after flash chromatography (petroleum ether ꢀ EtOAc = 6:1). HRꢀMS (ESI): m/z
calcd. for C27H32Cl3NNaO13S ([M+Na]+): 738.0552; found: 738.0579 (δ 3.7 ppm).
The peaks for the major isomer (13oe) are as follows: 1H NMR (600 MHz, CDCl3): δ
7.87 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H), 6.05 – 6.01 (m, 2H), 5.26 (t, J =
9.6 Hz, 1H), 5.08 (dd, J = 10.0, 6.3 Hz, 1H), 5.03 (t, J = 9.5 Hz, 1H), 4.79 (m, 1H),
4.73 (s, 2H), 4.59 (d, J = 3.5 Hz, 2H), 4.20 (dd, J = 12.3, 4.9 Hz, 1H), 4.07 (dd, J =
10.6, 1.5 Hz, 1H), 3.96 (m, 1H), 2.44 (s, 3H), 2.08 (s, 3H), 2.03 (s, 3H), 2.02 (s, 3H),
2.01 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 170.7, 170.0, 169.7, 169.5, 150.7,
145.3, 135.6, 131.3, 129.6, 128.6, 126.6, 94.0, 77.2, 77.0, 76.8, 75.7, 69.5, 68.9, 62.3,
48.5, 21.7, 20.7, 20.7, 20.7, 20.6.
(E)- and (Z)-N-(dec-2-en-1-yl)-tosylamide (17fe). From the mixture of (E)ꢀ and
(Z)ꢀ 13fe and 16fe (48.3 mg, 0.1 mmol), AcOH (1 mL), and Zn (65 mg, 1 mmol)
following the general procedure A, a mixture of (E)ꢀ and (Z)ꢀ17fe (28.6 mg, 93%)
was isolated as a light yellow oil as the major product after flash chromatography
(petroleum ether ꢀ EtOAc = 10:1).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Or, from the same mixture (48.3 mg, 0.1 mmol), MeOH (1 mL), and K2CO3 (26.2
mg, 0.19 mmol) following the general procedure B, a mixture of (E)ꢀ and (Z)ꢀ17fe
(30.9 mg, 100%) was isolated as a pale yellow semi solid as the major product after
flash chromatography (petroleum ether ꢀ EtOAc = 10:1). HRꢀMS (ESI): m/z calcd.
for C17H27NNaO2S ([M+Na]+): 332.1655; found: 332.1667 (δ 3.6 ppm). The E/Z/B
ratio changed from 15:1:1 to 20:1:0.7 after both procedures. The peaks for the major
isomer (17fe) are as follows: 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.1 Hz, 2H),
7.30 (d, J = 8.0 Hz, 2H), 5.53 (m, 1H), 5.29 (m, 1H), 4.49 (m, 1H), 3.51 (t, J = 6.2
Hz, 2H), 2.42 (s, 3H), 1.91 (dd, J = 13.6, 6.7 Hz, 2H), 1.32 – 1.1 (m, 10H), 0.87 (t, J
= 7.0 Hz, 3H). 13C NMR (150 MHz, CDCl3): δ 143.3, 137.1, 135.1, 129.6, 127.1,
124.3, 45.3, 32.0, 31.7, 29.1, 29.0, 28.9, 22.6, 21.5, 14.0.
(E)- and (Z)-2,2,2-trichloroethyl (4-(oxiran-2-yl)but-2-en-1-yl)(tosyl)carbamate
(13pe). From 2ꢀ(butꢀ3ꢀenꢀ1ꢀyl)oxirane (11p; 28 ꢀL, 24.5 mg, 0.25 mmol) and 2,2,2ꢀ
trichloroethyl tosylcarbamate (173 mg, 0.50 mmol) following the general procedure,
13pe (75.3 mg, 68%, E/Z = 14:1) was isolated as a yellow oil after flash chromatogꢀ
raphy (petroleum ether
C
ꢀ EtOAc = 10:1). HRꢀMS (ESI): m/z calcd. for
(E)-N-(3-cyclohexylallyl)tosylamide (17ge). From 13ge (46.9 mg, 0.1 mmol),
AcOH (1 mL), and Zn (65 mg, 1 mmol) following the general procedure A, 17ge
(27.6 mg, 94%) was isolated as a white solid after flash chromatography (petroleum
ether ꢀ EtOAc = 8:1). Or, from 13ge (46.9 mg, 0.1 mmol), MeOH (1 mL), and
K2CO3 (27.4 mg, 0.19 mmol) following the general procedure B, 17ge (29.3 mg,
100%) was isolated as a white solid after flash chromatography (petroleum ether ꢀ
EtOAc = 8:1). m. p. 82ꢀ84 °C. 1H NMR (600 MHz, CDCl3): δ 7.74 (d, J = 8.1 Hz,
2H), 7.29 (d, J = 8.1 Hz, 2H), 5.46 (dd, J = 15.5, 6.6 Hz, 1H), 5.23 (dt, J = 15.5, 5.6
Hz, 1H), 4.57 (broad s, 1H), 3.50 (t, J = 5.1 Hz, 2H), 2.42 (s, 3H), 1.83 (m, 1H), 1.68
– 1.63 (m, 2H), 1.63 – 1.55 (m, 3H), 1.26 – 1.15 (m, 2H), 1.09 (ddt, J = 16.0, 12.6,
6.1 Hz, 1H), 0.92 (qd, J = 12.5, 3.3 Hz, 2H). 13C NMR (150 MHz, CDCl3): δ 143.3,
140.6, 137.1, 129.6, 127.1, 121.8, 45.5, 40.1, 32.5, 26.0, 25.8, 21.5. HRꢀMS (ESI):
m/z calcd. for C16H23NNaO2S ([M+Na]+): 316.1342; found: 316.1353 (δ 3.5 ppm).
16H18Cl3NNaO5S ([M+Na]+): 463.9864; found: 463.9883 (δ 4.1 ppm). The peaks
for the major isomer (13pe) are as follows: 1H NMR (600 MHz, CDCl3): δ 7.87 (d, J
= 7.8 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 5.86 (m, 1H), 5.74 (dt, J = 15.2, 6.0 Hz, 1H),
4.69 (broad s, 2H), 4.50 (d, J = 6.2 Hz, 2H), 2.99 (m, 1H), 2.76 (t, J = 4.3 Hz, 1H),
2.51 (dd, J = 4.2, 2.8 Hz, 1H), 2.42 (s, 3H), 2.38 – 2.28 (m, 2H). 13C NMR (150
MHz, CDCl3): δ 150.7, 145.0, 135.7, 130.4, 129.4, 128.5, 127.0, 94.0, 75.7, 50.9,
48.8, 46.5, 34.9, 21.6.
Troc removal (Table 4), general procedure
A (reductive cleavage with
Zn/AcOH). The required amount of CꢀN coupling product (13be-pe) was added to a
25ꢀmL flameꢀdried roundꢀbottomed flask charged with a stir bar, AcOH (1~2 mL)
and Zn (10 equiv.) were added, and the reaction mixture was stirred at 60 °C over 4
h. The solution was then cooled down to room temperature and filtered over a short
pad of Celite. The volatiles were removed under reduced pressure.
Troc removal (Table 4), general procedure B.6b The required amount of CꢀN
coupling product (13be-pe) was added to a 10ꢀmL flameꢀdried roundꢀbottomed flask
charged with a stir bar, MeOH (1~2 mL) and K2CO3 (1.9 equiv.) were added, and the
reaction was vigorously stirred for 3 hours at 25 °C. The volatiles were removed
under reduced pressure.
(E)-N-(4-phenylbut-2-en-1-yl)tosylamide (17he). From 13he (76.3 mg, 0.16
mmol), AcOH (2 mL), and Zn (104 mg, 1.6 mmol) following the general procedure
A, 17he (38.8 mg, 81%) was isolated as a light yellow oil after flash chromatography
(petroleum ether ꢀ EtOAc = 6:1). 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz,
2H), 7.30 – 7.24 (m, 4H), 7.24 – 7.17 (m, 1H), 7.09 (d, J = 7.5 Hz, 2H), 5.72 (m,
1H), 5.39 (m, 1H), 4.75 (broad s, 1H), 3.55 (broad s, 2H), 3.27 (d, J = 6.7 Hz, 2H),
2.42 (s, 3H). 13C NMR (150 MHz, CDCl3): δ 143.3, 139.4, 136.9, 133.3, 133.2,
129.6, 128.4, 128.4, 126.1, 125.8, 45.1, 38.4, 21.5. HRꢀMS (ESI): m/z calcd. for
C17H19NNaO2S ([M+Na]+): 324.1029; found: 324.1040 (δ 3.4 ppm).
(E)-2-(3-(tosylamido)prop-1-en-1-yl)phenyl acetate (17ee). From 13ee (52.8 mg,
0.1 mmol), AcOH (1 mL), and Zn (65 mg, 1 mmol) following the general procedure
A, 17ee (32.3 mg, 94%) was isolated as a white solid after flash chromatography
(petroleum ether ꢀ EtOAc = 5:1). m. p. 73ꢀ75 °C. 1H NMR (600 MHz, CDCl3): δ
7.76 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 7.5 Hz, 2H), 7.25 (dd,
J = 9.1, 6.3 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 7.01 (d, J = 8.1 Hz, 1H), 6.49 (d, J =
15.9 Hz, 1H), 6.02 (m, 1H), 4.75 (m, 1H), 3.73 (t, J = 6.2 Hz, 2H), 2.40 (s, 3H), 2.31
(s, 3H). 13C NMR (150 MHz, CDCl3): δ 169.3, 147.9, 143.5, 137.1, 129.7, 128.7,
128.7, 127.1, 126.8, 126.8, 126.2, 126.1, 122.6, 45.5, 21.4, 20.9. HRꢀMS (ESI): m/z
calcd. for C18H18NNaO4S ([M+Na]+): 368.0927; found: 368.0941 (δ 3.8 ppm).
(E)-N-(5-((tert-butyldiphenylsilyl)oxy)pent-2-en-1-yl)tosylamide (17le). From the
mixture of (E)ꢀ and (Z)ꢀ13le and 16le (133.4 mg, 0.2 mmol), AcOH (2 mL), and Zn
(130 mg, 2 mmol) following the general procedure A, 17le (89.8 mg, 91%) was
isolated as a pale yellow oil as the major product after flash chromatography (petroꢀ
leum ether ꢀ EtOAc = 6:1). The E/Z/B ratio changed from 10:1:1.4 to >20:<0.1:1.
HRꢀMS (ESI): m/z calcd. for C28H35NNaO3SSi ([M+Na]+): 516.1999; found:
516.2018 (δ 3.7 ppm). The peaks for the major isomer (17le) are as follows: 1H
NMR (600 MHz, CDCl3): δ 7.75 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 7.7 Hz, 4H), 7.43
(t, J = 7.4 Hz, 2H), 7.39 (t, J = 7.4 Hz, 4H), 7.29 (d, J = 8.0 Hz, 2H), 5.54 (m, 1H),
5.35 (m, 1H), 4.54 (broad s, 1H), 3.64 (t, J = 6.5 Hz, 2H), 3.51 (t, J = 5.5 Hz, 2H),
2.41 (d, J = 5.3 Hz, 1H), 2.40 (s, 2H), 2.20 (q, J = 6.5 Hz, 2H), 1.05 (broad s, 9H).
13C NMR (150 MHz, CDCl3): δ 143.3, 137.0, 135.5, 133.7, 131.3, 129.6, 129.6,
127.6, 127.1, 126.4, 63.1, 45.3, 35.4, 26.8, 21.4, 19.1.
(E)-tert-butyl (2-(3-(tosylamido)prop-1-en-1-yl)phenyl) carbonate (17ie) and
(E)-N-(3-(2-hydroxyphenyl)allyl)tosylamide (17 qe). From 13ie (57.9 mg,
0.1mmol), AcOH (1 mL), and Zn (65.0 mg, 1 mmol) following the general procedure
A, 17ie (10.1 mg, 25%) and 17qe (22.8 mg, 75%) were isolated sequentially after
flash chromatography (petroleum ether ꢀ EtOAc = 5:1 and 2:1, respectively). 17ie: a
light yellow oil. 1H NMR (600 MHz, CDCl3): δ 7.77 (d, J = 8.1 Hz, 2H), 7.33 (d, J =
7.7 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.25 (t, J = 7.5 Hz, 1H), 7.16 (t, J = 7.5 Hz,
1H), 7.10 (d, J = 8.1 Hz, 1H), 6.56 (d, J = 15.9 Hz, 1H), 6.04 (dt, J = 15.7, 6.4 Hz,
1H), 4.54 (m, 1H), 3.75 (t, J = 6.2 Hz, 2H), 2.41 (s, 3H), 1.54 (s, 9H). 13C NMR (150
MHz, CDCl3): δ 151.6, 148.2, 143.6, 137.0, 129.8, 128.8, 128.7, 127.2, 126.8, 126.6,
126.5, 126.1, 122.4, 83.8, 45.7, 27.7, 21.5. HRꢀMS (ESI): m/z calcd. for
C21H25NNaO5S ([M+Na]+): 426.1346; found: 426.1361 (δ 3.5 ppm). 17qe: a white
solid. m. p. 130ꢀ132 °C. 1H NMR (600 MHz, acetoneꢀd6): δ 7.78 (d, J = 8.1 Hz, 2H),
7.39 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 7.7 Hz, 1H), 7.05 (t, J = 7.7 Hz, 1H), 6.85 (d, J
= 8.1 Hz, 1H), 6.79 – 6.74 (m, 2H), 6.11 (dt, J = 15.9, 6.4 Hz, 1H), 3.69 (d, J = 6.5
Hz, 2H), 2.40 (s, 3H). 13C NMR (150 MHz, acetoneꢀd6): δ 157.1, 145.5, 141.0,
132.2, 131.1, 129.9, 129.7, 129.7, 129.5, 127.4, 122.2, 118.3, 48.3, 23.1. HRꢀMS
(ESI): m/z calcd. for C16H17NNaO3S ([M+Na]+): 326.0821; found: 326.0833 (δ 3.7
ppm).
(E)- and (Z)-(2R,3R,4R,5S,6R)-2-(acetoxymethyl)-6-((E)-3-(4-methylphenyl-
sulfonamido)prop-1-en-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (17oe).
From the mixture of (E)ꢀ and (Z)ꢀ13oe (50.1 mg, 0.07 mmol), MeOH (1 mL), and
K2CO3 (18.4 mg, 0.13 mmol) following the general procedure B, 17oe (31.5 mg,
83%) was isolated as a white semi solid after flash chromatography (petroleum ether
ꢀ EtOAc = 1:1). The E/Z ratio changed from 14:1 to >20:1. HRꢀMS (ESI): m/z calcd.
for C24H31NNaO11S ([M+Na]+): 564.1510; found: 564.1530 (δ 3.5 ppm). The peaks
for the major isomer (17oe) are as follows: 1H NMR (600 MHz, CDCl3): δ 7.75 (d, J
= 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 5.81 (dd, J = 6.1, 4.2 Hz, 2H), 5.21 (t, J =
9.6 Hz, 1H), 5.06 – 4.96 (m, 2H), 4.87 (broad s, 1H), 4.65 (t, J = 5.5 Hz, 1H), 4.17
(dd, J = 12.3, 4.6 Hz, 1H), 4.01 (dd, J = 12.3, 1.7 Hz, 1H), 3.90 – 3.84 (m, 1H), 3.67
– 3.59 (m, 2H), 2.43 (s, 3H), 2.07 (s, 3H), 2.01 (s, 6H). 2.00 (s, 3H). 13C NMR (150
MHz, CDCl3): δ 170.7, 170.1, 169.6, 169.5, 143.7, 136.6, 132.4, 129.8, 127.1, 125.0,
72.1, 70.5, 70.1, 69.3, 68.8, 62.2, 44.8, 21.5, 20.7, 20.7, 20.6, 20.6.
(E)-N-(3-(2-((tert-butyldiphenylsilyl)oxy)phenyl)allyl)tosylamide (17je). From
13je (50.2 mg, 0.07mmol), AcOH (1 mL), and Zn (45.5 mg, 0.7mmol) following the
general procedure A, 17je (35.4 mg, 92%) was isolated as a pale yellow semi solid
after flash chromatography (petroleum ether ꢀ EtOAc = 8:1). 1H NMR (600 MHz,
CDCl3): δ 7.84 (d, J = 8.2 Hz, 2H), 7.71 (d, J = 7.8 Hz, 4H), 7.44 (t, J = 7.4 Hz, 2H),
7.38 (t, J = 7.4 Hz, 4H), 7.33 – 7.28 (m, 3H), 7.08 (d, J = 16.0 Hz, 1H), 6.82 (tt, J =
13.0, 6.4 Hz, 2H), 6.47 (d, J = 7.9 Hz, 1H), 6.02 (dt, J = 15.8, 6.5 Hz, 1H), 4.76 (m,
Troc removal during attempted Ts deprotection (Scheme 5): (E)-N-(3-(4-
metoxyphenyl)allyl)tosylamide (17ce). The sodiumꢀnaphthalene reagent was preꢀ
pared in dry DME as described.6d A flameꢀdried, 10ꢀmL pearꢀshape flask was
charged with a stirbar, 13ce (59.2 mg, 0.12 mmol), and dry, oxygenꢀfree DME (1
mL). The reaction mixture was cooled to –78°C and sodiumꢀnaphthalene reagent
(1.1 mL, ~0.9 mmol, ~8 equiv) was added dropwise over ~5 min. After an additional
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10 min at ꢀ78°C, the solution was diluted with saturated NH4Cl solution (4 mL),
Bigi, M. A.; White, M. C., J. Am. Chem. Soc. 2013, 135, 7831ꢀ7834;
(d) Stang, E. M.; White, M. C., J. Am. Chem. Soc. 2011, 133, 14892ꢀ
14895 and refs. cited therein.
allowed to warm to room temperature, and extracted with EtOAc (10 mL). The
layers were separated, and the aqueous layer extracted with EtOAc (2 × 10 mL). The
combined organic fractions were dried (MgSO4), and the volatis removed at reduced
pressure. 17ce (22.9 mg, 60%) was isolated as a light yellow oil after flash chromaꢀ
tography (petroleum ether ꢀ EtOAc = 10:1). Spectroscopic data were identical with
the literature.21
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Sipos, G.; Drinkel, E.; Dorta, R., Chem. Soc. Rev. 2015, 44,
3834ꢀ3860.
10.
(a) Trost, B. M.; Rao, M., Angew. Chem., Int. Ed. 2015, 54,
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5026ꢀ5043; (b) Mellah, M.; Voituriez, A.; Schulz, E., Chem. Rev.
2007, 107, 5133–5209.
ASSOCIATED CONTENT
1
Supporting Information. Plots of H and 13C NMR spectra for
11.
The catalyst was prepared by complexation of equimolar
amounts of the required sulfoxide and Pd(OAc)2 in refluxing CH2Cl2
over 24 h as described by White et al.,5a and used immediately to
ensure consistent results.
all new compounds.
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AUTHOR INFORMATION
Corresponding Author
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Engelin, C.; Jensen, T.; S. RodriguezꢀRodriguez; Fristrup,
P., ACS Catal. 2013, 3, 294ꢀ302.
13.
All disulfoxides were tested as an equimolar mixture of
*Fax: +86ꢀ551ꢀ62901450; Phone: ++86ꢀ551ꢀ62901450; Eꢀmail:
liyg@ hfut.edu.cn; ekantchev@hfut.edu.cn, ekantꢀ
chev@gmail.com.
mesoꢀ and dlꢀdiastereomers. However, for three of them (2, 3, and 5)
the diastereomers proved relatively easy to separate, hence we also
evaluated their activity separately. The sulfoxide stereochemistry had
little effect on reaction yields.
Author Contributions
14.
Yin, G.; Wu, Y.; Liu, G., J. Am. Chem. Soc. 2010, 132 ,
The manuscript was written through contributions of all authors.
All authors have given approval to the final version of the manuꢀ
script.
11978ꢀ11987.
15.
Montzka, T. A.; Matiskella, J. D.; Partyka, R. A., Tetrahe-
dron Lett. 1974, 15, 1325ꢀ1327.
16.
Li, J. R.; Bu, X. H.; Jiao, J.; Du, W. P.; Xu, X. H.; Zhang,
R. H. Dalton Trans. 2005, 34, 464ꢀ474.
ACKNOWLEDGMENT
The authors thank Hefei University of Technology (China) for
financial support.
17.
Liu, G.; Yin, G.; Wu, L. Angew. Chem., Int. Ed. 2008, 47,
4733ꢀ4736.
18.
Gresser, M. J.; Wales, S. M.; Keller, P. A. Tetrahedron
2010, 66, 6965ꢀ6976.
ABBREVIATIONS
mCPBA, mꢀchloroperbenzoic acid; 2,6ꢀDMBQ, 2,6ꢀdimethylꢀ
1,4ꢀbenzoquinone; Ad, 1ꢀadamantyl; BQ, 1,4ꢀbenzoquinone;
Troc = ((2,2,2ꢀtrichloroethyl)oxy)carbonyl
19.
Millán, A.; Álvarez de Cienfuegos, L.; Miguel, D.;
Campaña, A. G.; Cuerva, J. M. Org. Lett. 2012, 14, 5984ꢀ5987.
20.
McGarvey, G. J.; LeClair, C. A.; Schmidtmann, B. A. Org.
Lett. 2008, 10, 4727ꢀ4730.
.
21.
Prediger, P.; Barbosa, L. F.; Génisson, Y.; Correia, C. R. D.
J. Org. Chem. 2011, 76, 7737ꢀ7749.
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Chem. Soc. 2016, 138, 1265ꢀ1272; ꢀ (b) Reed, S. A.; Mazzotti, A. R.;
White, M. C., J. Am. Chem. Soc. 2009, 131, 11701–11706; (c) Reed,
S. A.; White, M. C., J. Am. Chem. Soc. 2008, 130, 3316ꢀ3318; (d)
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Major contributions: (a) Braun, M.ꢀG.; Doyle, A. G., J. Am.
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P. E.; White, M. C., J. Am. Chem. Soc. 2013, 135, 8460ꢀ8463; (c)
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