Gold-catalyzed oxidative aminoesterification of unactivated alkenes

Article abstract of DOI:10.1007/s00706-018-2144-8

Abstract: This paper describes an efficient aminoesterification of unactivated alkenes through Au(I)/Au(III) redox catalytic cycles using Selectfluor or hypervalent iodine(III) reagents. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-018-2144-8

Monatsh Chem
https://doi.org/10.1007/s00706-018-2144-8
ORIGINAL PAPER
Gold-catalyzed oxidative aminoesterification of unactivated
alkenes
Pascal Feige1 Teresa de Haro1 Giulia Rusconi1 Estibaliz Merino1
Cristina Nevado1
•
•
•
•
Received: 12 December 2017 / Accepted: 1 January 2018
Ó Springer-Verlag GmbH Austria, part of Springer Nature 2018
Abstract This paper describes an efficient aminoesterifi-
cation of unactivated alkenes through Au(I)/Au(III) redox
catalytic cycles using Selectfluor or hypervalent iodine(III)
reagents.
transformations [34–43]. In addition, metal-free method-
ologies have also been developed [44–47]. A combination
of carbophilic gold complexes and Au(I)/Au(III) redox
catalytic cycles was employed in the past years by several
groups to design new transformations along these lines
[48–55]. In this context, our group reported a gold-cat-
alyzed difunctionalization of alkenes to yield
aminoalcohols, aminoesters, aminoethers, and diamines in
a highly flexible manner (Scheme 1) [56–58].
Graphical abstract
[Au]
[Au]
R1
R1
R1
R1
R1
R1
Selectfluor
Hypervalent iodine(III)
NaHCO3
NTs
NaHCO3
NTs
NHTs
DMF
Nu
Nu
To further expand the scope of these transformations, we
envisaged the combination of Selectfluor as oxidant and
DMF as solvent to attain the synthesis of aminoformate
derivatives. Furthermore, we considered that the use of
different hypervalent iodine(III) reagents could enable the
introduction of other nucleophiles, thus expanding the
scope of this reaction towards the synthesis of new ami-
noesters (Scheme 2).
2
=
Nu OCOH
=
Nu OCOR
Keywords Selectfluor Á Hypervalent iodine(III) reagents Á
Heterocycles Á Homogeneous catalysis Á Redox reactions
Introduction
New methodologies to access highly important motifs in
organic chemistry such as diols, diamines, and aminoal-
cohols have been developed during the past decades
[1–14]. Palladium catalysts have been employed together
with PhI(OAc)2 in the aminooxygenation and diamination
of unactivated alkenes in both an intra- [15–20] as well as
in an intermolecular fashion [21–26]. In these transfor-
mations, the oxidation of Pd(II) to Pd(IV) species is crucial
for the formation of the new carbon–heteroatom bonds
[27–33]. Copper catalysts have also been used in similar
Results and discussion
We started to investigate the formation of aminoformates
using N-tosyl-2,2-diphenyl-4-pentenylamine (1a) as sub-
strate. When ten equivalents of DMF were used in a
reaction performed in nitromethane, 5,5-diphenyl-1-to-
sylpiperidin-3-yl formate 2a could be obtained in 45%
yield (Table 1, entry 1). Reducing the equivalents of DMF
from 10 to 5, delivered the same amount of aminoaldehyde
2a together with 13% of 5,5-diphenyl-1-tosylpiperidin-3-ol
20a (Table 1, entry 2). We envisaged that a faster hydrol-
ysis of the iminium intermediate might prevent formation
of byproduct 20a. Remarkably, the addition of 2 equivalents
of water to hydrolyze the iminium ion in situ afforded 79%
of aminoaldehyde 2a and 13% of aminoalcohol 20a
(Table 1, entry 3). These conditions (Table 1, entry 3) were
& Cristina Nevado
cristina.nevado@chem.uzh.ch
1
Institute of Chemistry, University of Zurich,
Winterthurerstrasse 190, 8057 Zurich, Switzerland
123

P. Feige et al.
Scheme 1
[Au]
R1
R1
R1
R1
Oxidant
NTs
NaHCO3
NHTs
Conditions
Nu
OR2 NHCOR3
,
=
Nu
OH,
Scheme 2
R1
R1
[Au]
[Au]
PhI(OCOR2)
NHTs NaHCO3
R1
R1
Selectfluor
R1
NTs
NTs
R1
NaHCO3
DMF
Nu
Nu
2
=
=
Nu OCOH
Nu OCOR
Table 1 Optimization of the gold-catalyzed synthesis of aminoaldehydes 2a, 2b
Entry
Substrate
Reaction conditionsa
Product, yield/%b
Product, yield/%b
1
2
3
4
1a
1a
1a
1b
[Au], Selectfluor, NaHCO3, DMF (10 equiv.)
[Au], Selectfluor, NaHCO3, DMF (5 equiv.)
2a, 45
2a, 45
2a, 79
2b, 67
–
20a, 13
20a, 13
–
[Au], Selectfluor, NaHCO3, DMF (10 equiv.), H2O (2 equiv.)
[Au], Selectfluor, NaHCO3
(1 equiv.), DMF (5 equiv.), H2O (2 equiv.), MeNO2, 80 °C, 2 h
aReaction conditions: [Au] = Ph3PAuSbF6 (5 mol%), Selectfluor (2 equiv.), NaHCO3 (1 equiv.), MeNO2 (0.1 M), 80 °C
bIsolated yield after column chromatography
applied also to N-(2,2-dimethylpent-4-en-1-yl)-4-methyl-
benzenesulfonamide (1b) furnishing 5,5-dimethyl-1-
Specifically, when PhI(OPiv)2 was employed as oxidant,
both 1a and 1b could be efficiently converted into the
desired products 3a and 3b in 86 and 80% yields, respec-
tively (Table 2, entries 1 and 2). Other hypervalent iodine
reagents such as PhI(OCOCF3)2 could also be successfully
used to introduce the trifluoroacetoxy moiety delivering
both products 4a and 4b in 80% yield (Table 2, entries 3
and 4). Encouraged by these results, PhI(OCO(4-NO2C6-
H4))2 was tested providing product formation in rather
tosylpiperidin-3-yl formate 2b in 67% yield (Table 1, entry
4).
The use of different hypervalent iodine(III) reagents to
introduce additional nucleophiles was studied next. The
previously optimized conditions had to be adapted. It was
found that, changing the solvent from nitromethane to 1,2-
dichloroethane, was beneficial for the reaction outcome.
123

Gold-catalyzed oxidative aminoesterification of unactivated alkenes
Table 2 Gold-catalyzed intramolecular difunctionalization of 1a and 1b
Entry
Substrate
Oxidanta
Product
Yield/%c
1
2
3
4
5
6
7
8
1a
1b
1a
1b
1a
1b
1a
1b
PhI(OPiv)2
3a, R2 = COt-Bu
3b, R2 = COt-Bu
4a, R2 = COCF3
4b, R2 = COCF3
5a, R2 = CO(4-NO2C6H4)
5b, R2 = CO(4-NO2C6H4)
6a, R2 = CO(3,5-MeOC6H3)
6b, R2 = CO(3,5-
MeOC6H3)
86
80
80
80
42
44
21
72
PhI(OPiv)2
PhI(OCOCF3)2
PhI(OCOCF3)2
PhI(OCO(4-NO2-C6H4))2
PhI(OCO(4-NO2-C6H4))2
PhI(CO2(3,5-MeO-C6H3))2b
PhI(CO2(3,5-MeO-C6H3))2b
aOxidant (2 equiv.), NaHCO3 (1 equiv.), DCE, 80 °C, 2 h
b17 h
cIsolated yield after column chromatography
moderate yields (5a and 5b, Table 2, entries 5 and 6).
When PhI(CO2(3,5-MeOC6H3))2 was used, the desired
products 6a and 6b could be isolated in 21 and 72% yields,
respectively (Table 2, entries 7 and 8).
procedure [60]. Ph3PAuSbF6 was prepared from Ph3PAuCl
(1 equiv.) and AgSbF6 (1 equiv.) in DCE (0.05 M). Except
acetonitrile, solvents were purchased in HPLC quality,
degassed by purging thoroughly with nitrogen and dried
over activated molecular sieves of appropriate size. Alter-
natively, they were purged with argon and passed through
alumina columns in a solvent purification system (Inno-
vative Technology). Unless otherwise stated, reactions
were not run under inert atmosphere. Conversion was
monitored by thin-layer chromatography (TLC) using
Merck TLC silica gel 60 F 254. Flash column chro-
matography was performed over silica gel (230–400 mesh).
Infrared spectra were recorded on a JASCO FT/IR-4100
spectrometer. Absorbance frequencies are reported in
reciprocal centimeters (cm-1). High-resolution electro-
spray ionization mass spectra were measured on a Bruker
ESQUIRE-LC quadrupole ion trap instrument (Bruker
Daltonik GmbH, Bremen, Germany) with accurate mass
acquisition below 2 ppm.
Conclusion
A new protocol for the efficient aminoesterification of unac-
tivated alkenes is reported here. Taking advantage of Au(I)/
Au(III) redox catalytic cycles in the presence of either
Selectfluor or hypervalent iodine(III) reagents, aminoformate
and aminoester derivatives have been respectively formed
from 5-N-tosyl-4-pentenylamine substrates. The reactions are
operationally simple and offer a flexible entry to previously
unreported piperidine derivatives.
Experimental
Unless otherwise stated, starting materials were purchased
from Aldrich and/or Fluka. All reagents were used as
received. Substrates 1a and 1b were prepared according to
General protocol A
A mixture of aminopent-4-ene (1, 1 equiv.), Selectfluor (2
equiv.), NaHCO3 (1 equiv.), and DMF (5 equiv.) was
dissolved in MeNO2 (0.1 M) followed by addition of
Ph3PAuSbF6 (0.05 equiv.). The reaction was stirred for 2 h
at 80 °C and was monitored by TLC. Upon consumption of
the starting material, the mixture was diluted with 5 cm3
1
previously reported procedures [34, 59]. IR and H NMR
spectra of the products 2b [57] and 4b [47] were found to
be identical with the ones described. PhI(OPiv)2,
PhI(OCO(4-NO2-C6H4))2, and PhI(OCO(3,5-MeO-C6H3))2
were synthesized in analogy to a previously reported
123

P. Feige et al.
DCM and 2 cm3 water was added. The mixture was
extracted with DCM (3 9 5 cm3) and the combined
organic phases were dried over MgSO4. The solvent was
evaporated under reduced pressure and the residue was
purified through silica gel flash column chromatography
(hexane/EtOAc = 6/1) to yield the desired aminoaldehy-
des 2.
5,5-Diphenyl-1-tosylpiperidin-3-yl pivalate
(3a, C29H33NO4S)
Following the general protocol B, compound 3a was
isolated in 86% yield. 1H NMR (500 MHz, CDCl3):
d = 7.63 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 7.5 Hz, 2H),
7.36–7.29 (m, 4H), 7.26–7.15 (m, 6H), 4.80 (tt, J = 9.4,
4.5 Hz, 1H), 4.30 (d, J = 12.2 Hz, 1H), 3.69 (dd,
J = 10.5, 4.3 Hz, 1H), 2.90 (dt, J = 12.7, 1.8 Hz, 1H),
2.82 (d, J = 12.2 Hz, 1H), 2.49 (t, J = 9.9 Hz, 1H), 2.42
(s, 3H), 2.05 (dd, J = 12.8, 10.2 Hz, 1H), 1.10 (s, 9H)
ppm; 13C NMR (125 MHz, CDCl3): d = 178.1, 146.5,
144.5, 144.0, 133.4, 130.5, 129.4, 129.2, 128.5, 128.3,
127.3, 127.2, 127.2, 54.8, 49.9, 46.9, 40.3, 39.3, 27.8, 27.7,
5,5-Diphenyl-1-tosylpiperidin-3-yl formate
(2a, C25H25NO4S)
Following the general protocol A, compound 2a was
isolated in 79% yield. 1H NMR (500 MHz, CDCl3):
d = 7.91 (s, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.49 (d,
J = 7.7 Hz, 2H), 7.38–7.14 (m, 10H), 4.92 (tt, J = 9.8,
4.1 Hz, 1H), 4.46 (d, J = 12.5 Hz, 1H), 3.91–3.86 (m, 1H),
2.93 (dt, J = 12.6, 1.7 Hz, 1H), 2.63 (d, J = 12.5 Hz, 1H),
2.43 (s, 3H), 2.40 (d, J = 7.1 Hz, 1H), 2.18–2.10 (m, 1H)
ppm; 13C NMR (125 MHz, CDCl3): d = 160.3, 146.2,
144.7, 143.6, 133.1, 130.5, 129.4, 129.2, 128.4, 128.3,
127.4, 127.3, 127.1, 67.6, 54.6, 49.8, 47.0, 40.4, 22.2 ppm;
ꢀ
27.7, 22.2 ppm; IR (film): m = 2971, 1728, 1598, 1496,
1479, 1447, 1346, 1282, 1161, 1090, 1038, 1020, 991, 910,
804, 783, 732, 699, 663, 570, 549 cm-1; HRMS (ESI): m/z
calcd for C29H33NNaO4S 514.20225, found 514.20233.
5,5-Dimethyl-1-tosylpiperidin-3-yl pivalate
(3b, C19H29NO4S)
ꢀ
Following the general procedure for the gold-catalyzed
difunctionalization of alkenes, compound 2b was isolated
IR (film): m = 2925, 2366, 1723, 1598, 1496, 1447, 1345,
1162, 1090, 1011, 908, 779, 730, 699, 661, 578, 562,
550 cm-1; HRMS (ESI): m/z calcd for C25H25NNaO4S
458.13965, found 458.13970.
1
in 80% yield. H NMR (500 MHz, CDCl3): d = 7.64 (d,
J = 8.0 Hz, 2H), 7.32 (d, J = 7.9 Hz, 2H), 5.02–4.91 (m,
1H), 3.40 (dd, J = 11.4, 3.9 Hz, 1H), 2.90 (d,
J = 11.4 Hz, 1H), 2.62 (dd, J = 11.3, 7.8 Hz, 1H), 2.50
(d, J = 11.4 Hz, 1H), 2.43 (s, 3H), 1.64 (dd, J = 13.3,
4.3 Hz, 1H), 1.23 (dd, J = 13.4, 8.2 Hz, 1H), 1.18 (s, 9H),
1.04 (s, 6H) ppm; 13C NMR (125 MHz, CDCl3):
d = 177.7, 143.6, 134.0, 129.8, 127.7, 66.7, 57.0, 49.2,
41.8, 38.8, 31.7, 27.9, 27.2, 26.2, 21.7 ppm; IR (film):
5,5-Dimethyl-1-tosylpiperidin-3-yl formate
(2b, C15H21NO4S)
Following the general protocol A, compound 2b was
isolated in 67% yield. 1H NMR (500 MHz, CDCl3):
d = 7.99 (s, 1H), 7.63 (d, J = 8.4 Hz, 2H), 7.33 (d,
J = 8.0 Hz, 2H), 5.14 (tt, J = 8.8, 4.5 Hz, 1H), 3.65 (dd,
J = 11.2, 4.4 Hz, 1H), 3.07 (d, J = 11.5 Hz, 1H), 2.48–
2.44 (m, 1H), 2.43 (s, 3H), 2.31 (d, J = 11.5 Hz, 1H), 1.73
(dd, J = 13.2, 4.5 Hz, 1H), 1.22 (dd, J = 13.2, 9.5 Hz,
1H), 1.07 (s, 3H), 1.00 (s, 3H) ppm; 13C NMR (125 MHz,
CDCl3): d = 160.6, 144.4, 134.2, 130.4, 128.2, 67.5, 57.5,
ꢀ
m = 2969, 1736, 1455, 1366, 1348, 1307, 1282, 1228,
1216, 1206, 1161, 1092, 1036, 992, 916, 813, 767, 752,
685, 660, 549 cm-1; HRMS (ESI): m/z calcd for C19H29-
NNaO4S 390.1715, found 390.17130.
ꢀ
5,5-Diphenyl-1-tosylpiperidin-3-yl 2,2,2-trifluoroacetate
(4a, C16H20F3NO4S)
49.7, 42.6, 32.5, 28.7, 26.1, 22.2 ppm; IR (film): m = 2958,
1721, 1598, 1469, 1343, 1307, 1158, 1092, 993, 966, 916,
815, 660, 583, 551 cm-1; HRMS (ESI): m/z calcd for
C15H21NNaO4S 334.10835, found 334.10830.
Following the general protocol B, compound 4a was
isolated in 80% yield. 1H NMR (500 MHz, CDCl3):
d = 7.83 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 7.6 Hz, 2H),
7.56–7.49 (m, 4H), 7.46–7.30 (m, 6H), 5.14 (tt, J = 9.9,
4.3 Hz, 1H), 4.65 (d, J = 12.5 Hz, 1H), 4.12 (dd,
J = 10.5, 4.8 Hz, 1H), 3.16 (dt, J = 12.6, 1.8 Hz, 1H),
2.81 (d, J = 12.5 Hz, 1H), 2.64 (t, J = 10.2 Hz, 1H), 2.61
(s, 3H), 2.40 (dd, J = 12.5, 10.8 Hz, 1H) ppm; 13C NMR
(125 MHz, CDCl3): d = 157.0 (q, J = 42.7 Hz), 145.7,
144.9, 143.1, 133.0, 130.7, 129.6, 129.4, 128.5, 128.3,
127.8, 127.5, 127.0, 114.9 (q, J = 285.8 Hz), 72.2, 54.6,
General protocol B
A mixture of aminopent-4-ene (1, 1 equiv.), oxidant
(2 equiv.), and NaHCO3 (1 equiv.) was dissolved in 1,2-
dichloroethane (0.1 M) followed by addition of Ph3-
PAuSbF6 (0.05 equiv.). The reaction was stirred for 2 h
at 80 °C and was monitored by TLC. Upon consumption
of the starting material, the mixture was diluted with
5 cm3 DCM and filtered over celite. The solvent was
evaporated under reduced pressure and the residue was
purified through silica gel flash column chromatography
(hexane/EtOAc = 10/1) to yield the desired aminoesters
3–6.
ꢀ
49.3, 47.1, 40.0, 22.2 ppm; IR (film): m = 2852, 1784,
1598, 1496, 1448, 1347, 1221, 1158, 1091, 1009, 908, 864,
816, 803, 781, 733, 698, 662, 578, 550 cm-1; HRMS
(ESI): m/z calcd for C26H24F3NNaO4S 526.12703, found
526.12763.
123

Gold-catalyzed oxidative aminoesterification of unactivated alkenes
5,5-Dimethyl-1-tosylpiperidin-3-yl 4-nitrobenzoate
(5b, C21H24N2O6S)
551 cm-1; HRMS (ESI): m/z calcd for C23H29NNaO6S
470.16078, found 470.16067.
Following the general protocol B, compound 5b was
isolated in 44% yield. 1H NMR (500 MHz, CDCl3):
d = 8.28 (d, J = 12.0 Hz, 2H), 8.16 (d, J = 9.0 Hz, 2H),
7.65 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.1 Hz, 2H), 5.28
(dt, J = 7.8, 4.0 Hz, 1H), 3.57 (dd, J = 11.4, 3.7 Hz, 1H),
2.97 (d, J = 11.5 Hz, 1H), 2.84 (dd, J = 11.3, 7.7 Hz,
1H), 2.60 (d, J = 11.5 Hz, 1H), 2.43 (s, 3H), 1.78 (dd,
J = 13.5, 4.2 Hz, 1H), 1.46 (dd, J = 13.6, 8.3 Hz, 1H),
1.10 (s, 6H) ppm; 13C NMR (125 MHz, CDCl3):
d = 164.4, 151.5, 144.4, 136.0, 134.5, 131.5, 130.5,
128.2, 124.3, 69.4, 57.5, 49.8, 42.4, 32.4, 28.4, 26.9,
Acknowledgements We thank the European Research Council (ERC
Starting Grant 307948) and the Forschungskredit of the University of
Zurich for the financial support.
References
1. Kolb HC, VanNieuwenhze MS, Sharpless KB (1994) Chem Rev
94:2483
2. Li G, Chang HT, Sharpless KB (1996) Angew Chem Int Ed
35:451
3. Muniz K (2004) Chem Soc Rev 33:166
4. Donohoe TJ, Callens CKA, Thompson AL (2009) Org Lett
11:2305
ꢀ
22.2 ppm; IR (film): m = 2958, 1724, 1600, 1526, 1468,
1346, 1309, 1274, 1162, 1117, 1092, 993, 912, 813, 720,
661, 593, 572, 550 cm-1; HRMS (ESI): m/z calcd for
C21H24N2NaO6S 455.12473, found 455.12468.
5. Cardona F, Goti A (2009) Nat Chem 1:269
6. Bataille CJR, Donohoe TJ (2011) Chem Soc Rev 40:114
7. Mun˜iz K (2011) Dihydroxylation, aminohydroxylation, diami-
nation, and dibromination of carbon–carbon double bonds. In: De
Vries JG (ed) Science of synthesis, stereoselective synthesis, vol
1: stereoselective reactions of carbon–carbon double bonds.
Thieme, Germany, p 5
5,5-Diphenyl-1-tosylpiperidin-3-yl 3,5-dimethoxybenzoate
(6a, C33H33N2O6S)
Following the general protocol B, compound 6a was
isolated in 21% yield. 1H NMR (500 MHz, CDCl3):
d = 7.65 (d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H),
7.36 (t, J = 7.8 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 7.27–
7.08 (m, 6H), 7.03 (d, J = 2.4 Hz, 2H), 6.63 (t,
J = 2.3 Hz, 1H), 5.04 (tt, J = 9.1, 4.6 Hz, 1H), 4.37 (d,
J = 12.3 Hz, 1H), 3.87 (dd, J = 10.4, 3.6 Hz, 1H), 3.81 (s,
6H), 3.01 (d, J = 12.5 Hz, 1H), 2.83 (d, J = 12.3 Hz, 1H),
2.58 (t, J = 9.9 Hz, 1H), 2.42 (s, 3H), 2.27 (dd, J = 12.7,
10.3 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3):
d = 165.8, 161.3, 146.3, 144.6, 144.0, 133.3, 132.2,
130.5, 129.4, 129.2, 128.5, 128.3, 127.3, 127.3, 127.1,
108.0, 106.4, 68.4, 56.3, 54.7, 50.0, 46.9, 40.3, 22.2 ppm;
8. Karjalainen OK, Koskinen AMP (2012) Org Biomol Chem
10:4311
9. Rawling MJ, Tomkinson NCO (2013) Org Biomol Chem 11:1434
10. Chemler SR, Copeland DA (2013) Top Heterocycl Chem 32:39
11. Mun˜iz K (2014) Addition reactions with formation of carbon–
heteroatom bonds: (III) asymmetric methods of dihydroxylation,
aminohydroxylation, and diamination. In: Knochel P, Molander
GA (eds) Comprehensive organic synthesis II, 2nd edn, vol 7:
oxidation. Elsevier, Amsterdam, p 411
12. Dauban P, Darses B, Jarvis A (2014) Addition reactions with
formation of carbon–nitrogen bonds. In: Knochel P, Molander
GA (eds) Comprehensive organic synthesis II, 2nd edn, vol 7:
oxidation. Elsevier, Amsterdam, p 538
13. Zhu Y, Cornwall RG, Du H, Zhao B, Shi Y (2014) Acc Chem Res
47:3665
14. Heravi MM, Zadsirjan V, Esfandyari M, Lashaki TB (2017)
Tetrahedron Asymmetry 28:987
15. Alexanian EJ, Lee C, Sorensen EJ (2005) J Am Chem Soc
127:7690
ꢀ
IR (film): m = 2958, 1718, 1596, 1458, 1347, 1231, 1205,
1158, 1091, 1048, 767, 699, 665, 576, 549 cm-1; HRMS
(ESI): m/z calcd for C33H33NNaO6S 594.19208, found
594.19180.
¨
16. Streuff J, Hovelmann CH, Nieger M, Muniz K (2005) J Am
˜
Chem Soc 127:14586
17. Bar GLJ, Lloyd-Jones GC, Booker-Milburn KI (2005) J Am
Chem Soc 127:7308
18. Sibbald PA, Michael FE (2009) Org Lett 11:1147
19. Liskin DV, Sibbald PA, Rosewall CF, Michael FE (2010) J Org
Chem 75:6294
20. Yin G, Mu X, Liu G (2016) Acc Chem Res 49:2413
21. Liu G, Stahl SS (2006) J Am Chem Soc 128:7179
22. Desai LV, Sanford MS (2007) Angew Chem Int Ed 46:5737
23. Iglesias A, Perez EG, Mun˜iz K (2010) Angew Chem Int Ed
49:8109
24. Mun˜iz K, Kirsch J, Chavez P (2011) Adv Synth Catal 353:689
25. Martinez C, Wu Y, Weinstein AB, Stahl SS, Liu G, Mun˜iz K
(2013) J Org Chem 78:6309
26. Broggini G, Beccalli EM, Borelli T, Brusa F, Gazzola S, Mazza
A (2015) Eur J Org Chem 2015:4261
27. Beccalli EM, Broggini G, Martinelli M, Sottocornola S (2007)
Chem Rev 107:5318
28. Whitfield SR, Sanford MS (2007) J Am Chem Soc 129:15142
29. Mun˜iz K (2009) Angew Chem Int Ed 48:9412
5,5-Dimethyl-1-tosylpiperidin-3-yl 3,5-dimethoxybenzoate
(6b, C23H29N2O6S)
Following the general protocol B, compound 6b was
isolated in 72% yield. 1H NMR (500 MHz, CDCl3):
d = 7.65 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H),
7.14 (d, J = 2.4 Hz, 2H), 6.64 (t, J = 2.3 Hz, 1H), 5.22 (tt,
J = 8.4, 4.3 Hz, 1H), 3.82 (s, 6H), 3.63 (dd, J = 11.3,
4.1 Hz, 1H), 3.03 (d, J = 11.5 Hz, 1H), 2.71 (dd,
J = 11.2, 8.2 Hz, 1H), 2.50 (d, J = 11.5 Hz, 1H), 2.42
(m, 3H), 1.78 (dd, J = 13.3, 4.3 Hz, 1H), 1.39 (dd,
J = 13.3, 8.7 Hz, 1H), 1.10 (s, 3H), 1.07 (s, 3H) ppm;
13C NMR (125 MHz, CDCl3): d = 166.0, 161.3, 144.2,
134.6, 132.5, 130.4, 128.2, 108.0, 106.4, 68.4, 57.5, 56.3,
49.9, 42.6, 32.4, 28.6, 26.6, 22.2 ppm; IR (film): mꢀ = 2958,
1716, 1596, 1461, 1428, 1345, 1303, 1233, 1205, 1158,
1092, 1049, 990, 916, 813, 767, 731, 661, 587, 571,
123

P. Feige et al.
30. Lyons TW, Sanford MS (2010) Chem Rev 110:1147
31. Furuya T, Benitez D, Tkatchouk E, Strom AE, Tang P, Goddard
WA, Ritter T (2010) J Am Chem Soc 132:3793
32. Racowski JM, Sanford MS (2011) Higher oxidation state
organopalladium and platinum chemistry. In: Canty A (ed)
Topics in organometallic chemistry, vol 35. Springer, Berlin, p 1
33. Wu T, Yin G, Liu G (2009) J Am Chem Soc 131:16354
34. Fuller PH, Kim JW, Chemler SR (2008) J Am Chem Soc
130:17638
46. Wardrop DJ, Bowen EG, Forslund RE, Sussman AD,
Weerasekera SL (2010) J Am Chem Soc 132:1188
47. Lovick HM, Michael FE (2010) J Am Chem Soc 132:1249
48. Wegner HA, Ahles S, Neuburger M (2008) Chem Eur J 14:11310
49. Iglesias A, Mun˜iz K (2009) Chem Eur J 15:10563
50. Zhang G, Peng Y, Cui L, Zhang L (2009) Angew Chem Int Ed
48:3112
51. Zhang G, Cui L, Wang Y, Zhang L (2010) J Am Chem Soc
132:1474
35. Mancheno DE, Thornton AR, Stoll AH, Kong A, Blakey SB
(2010) Org Lett 12:4110
36. Sequeira FC, Turnpenny BW, Chemler SR (2010) Angew Chem
Int Ed 49:6365
37. Cornwall RG, Zhao B, Shi Y (2011) Org Lett 13:434
38. Sanjaya S, Chiba S (2012) Org Lett 14:5342
39. Karyakarte SD, Smith TP, Chemler SR (2012) J Org Chem
77:7755
52. Brenzovich WE, Benitez D, Lackner AD, Shunatona HP,
Tkatchouk E, Goddard WA, Toste FD (2010) Angew Chem Int
Ed 49:5519
53. Hopkinson MN, Ross JE, Giuffredi GT, Gee AD, Gouverneur V
(2010) Org Lett 12:4904
54. Zhang R, Xu Q, Chen K, Gu P, Shi M (2013) Eur J Org Chem
2013:7366
55. Wang Q, Jiang Y, Sun R, Tang XY, Shi M (2016) Chem Eur J
22:14739
40. Shen K, Wang Q (2015) Chem Sci 6:4279
41. Wdowik T, Chemler SR (2017) J Am Chem Soc 139:9515
42. Xie J, Wang YW, Qi LW, Zhang B (2017) Org Lett 19:1148
43. Khoder ZM, Wong CE, Chemler SR (2017) ACS Catal 7:4775
44. Mahoney JM, Smith CR, Johnston JN (2005) J Am Chem Soc
127:1354
56. de Haro T, Nevado C (2010) J Am Chem Soc 132:1512
57. de Haro T, Nevado C (2011) Angew Chem Int Ed 50:906
58. de Haro T, Nevado C (2011) Chem Commun 47:248
59. Zeng W, Chemler SR (2007) J Am Chem Soc 129:12948
60. Stang PJ, Boehshar M, Wingert H, Kitamura T (1988) J Am
Chem Soc 110:3272
´
45. Correa A, Tellitu I, Domınguez E, SanMartin R (2006) J Org
Chem 71:8316
123