Regioselective Cp*Ir(III)-Catalyzed Allylic C-H Sulfamidation of Allylbenzene Derivatives

Article abstract of DOI:10.1021/acs.joc.9b01816

In this study we report the development of the regioselective Cp*Ir(III)-catalyzed allylic C-H sulfamidation of allylbenzene derivatives, using azides as the nitrogen source. The reaction putatively proceeds through a Cp*Ir(III)-π-allyl intermediate and demonstrates exclusive regioselectivity for the branched position of the π-allyl. The reaction performs well on electron-rich and electron-deficient allylbenzene derivatives and is tolerant of a wide range of functional groups, including carbamates, esters, and ketones. The proposed mechanism for this reaction proceeds via C-N reductive elimination from a Cp*Ir(V) nitrenoid complex at the branched position of the π-allyl.

Full text of DOI:10.1021/acs.joc.9b01816

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Note
Regioselective Cp*Ir(III)-catalyzed Allylic C–
H Sulfamidation of Allylbenzene Derivatives
Amaan M. Kazerouni, Taylor Alexandria Farmer Nelson,
Steven W. Chen, Kimberly R Sharp, and Simon B. Blakey
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01816 • Publication Date (Web): 16 Aug 2019
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Regioselective Cp*Ir(III)-catalyzed Allylic C–H Sulfamidation of
Allylbenzene Derivatives
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Amaan M. Kazerouni,† Taylor A. F. Nelson, † Steven W. Chen, Kimberly R. Sharp, and Simon B. Blakey*
Department of Chemistry, Emory University, Atlanta Georgia, 30322, United States
email: sblakey@emory.edu
ABSTRACT: In this study we report the development of
[IrCp*Cl2]2
AgNTf2, CsOAc
Cp*
IrV
reductive
elimination
NHTs
H
the regioselective Cp*Ir(III)-catalyzed allylic C–H
sulfamidation of allylbenzene derivatives, using azides as
R
R
R
TsN3
NTs
Branch Selective
the nitrogen source. The reaction putatively proceeds through a Cp*Ir(III)-π-allyl intermediate, and demonstrates
exclusive regioselectivity for the branched position of the π-allyl. The reaction performs well on electron-rich and
electron-deficient allylbenzene derivatives, and is tolerant of a wide range of functional groups, including carbamates,
esters, and ketones. The proposed mechanism for this reaction proceeds via C–N reductive elimination from a
Cp*Ir(V) nitrenoid complex at the branched position of the π-allyl.
Transition metal-catalyzed allylic substitution reactions proceeding via metal-π-allyl intermediates, have
been established as powerful transformations, typified by their strategic use in the synthesis of an eclectic class of
natural products and biologically relevant molecules.1,2 Historically, the key π-allyl intermediates have been accessed
from substrates containing allylic leaving groups and, more recently, from other pre-oxidized substrates (dienes,
allenes, alkynes, etc.).3
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Conversely, allylic C–H functionalization has emerged as a useful and versatile variant of this reaction, in
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which the required π-allyl intermediate can be directly
Scheme 1: Intermolecular Allylic C–H
Functionalization
A) Allylic C–H Functionalization of Terminal Olefins
(White)
accessed from the olefin by activation of the allylic C–H
bond, eschewing the need for pre-oxidized substrates.4 In a
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H
[Pd], BQ
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R
Nu
R
seminal report,5 White and coworkers disclosed a palladium
catalyst which was capable of accessing the π-allyl complex
directly from the olefin to be intercepted with a wide range
of nitrogen,6–8 oxygen,9–12 and carbon12–15 nucleophiles
(Scheme 1A). While this was a significant advance to the
field, the palladium-catalyzed intermolecular allylic C–H
functionalization reactions generally require activated
nucleophiles and are limited to the functionalization of
terminal olefins. Additionally, the reaction profiles for
intermolecular reactions predominantly favor the formation
of linear products, with the exception of a single catalyst
system for carboxylate nucleophiles.5
Linear
Selective
O
R
EWG
EWG
EWG
Nu =
N
O
R
B) Allylic C–H Functionalization of Mono-, Di-, Trisubstituted
Olefins (Blakey, Glorius)
[RhCp*Cl2]2, Ag+
H
Nu
R
R
R
R
Linear
Selective
R
EWG
O
Nu =
N
O
R
Ar
O
R
C) Allylic C–H Functionalization of Terminal Olefins via
Dioxazolones (Blakey, Glorius, Rovis)
[IrCp*Cl2]2
CsOAc
AgSbF6
O
H
Branch
Selective
HN
R
O
O
R
R
R
O
N
D) This Work: Allylic C–H Sulfamidation
[IrCp*Cl2]2
CsOAc
H
NHTs
Branch
Selective
R
TsN3
R
Cossy and coworkers established the Cp*Rh(III) catalyzed intramolecular allylic C–H amination,16 which
was later demonstrated to proceed via a Cp*Rh-π-allyl intermediate.17 Building on this report, we recently disclosed
the Cp*Rh(III)-catalyzed intermolecular allylic C–H amination and etherification of mono-, di- and tri-substituted
olefins (Scheme 1B).18,19 Further showcasing the utility of this catalytic system, Glorius and coworkers reported the
use of electron-rich aromatics and arylboroxines as nucleophiles for allylic C–H arylation (Scheme 1B).20,21 Under
this first generation mechanistic manifold, exclusive linear selectivity was observed for all terminal olefins.22
More recently, we reported the use of dioxazolones for the allylic C–H amidation of unactivated mono-, di-,
and tri-substituted olefins (Scheme 1C).23 Concomitant reports were independently published by Rovis24 and
Glorius.25 Dioxazolones, originally developed by Chang and coworkers as oxidative amidating reagents in the context
of directed C(sp2)–H functionalization, are proposed to oxidize Cp*Rh(III) and Cp*Ir(III) complexes to the
corresponding M(V)-nitrenoids.26,27 In sharp contrast to our initial disclosures, these complexes deliver the amide
products with excellent selectivity for the branched position, consistent with an inner-sphere reductive elimination
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pathway. However, due to the innate decomposition pathway for dioxazolones, these reactions are limited to
amidations. Although the amide products themselves have significant value, they are far from ideal nitrogen protecting
groups, often requiring harshly acidic or basic conditions to remove. Here we report the use of tosyl azide (TsN3) as
the nitrenoid precursor to selectively deliver tosylamides at the branched position of allylbenzenes (Scheme 1D).
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Table 1: Reaction development for C–H
Tosyl azide has been previously utilized as a nitrenoid
sulfamidation of allylbenzenea
NHTs
precursor in directed C(sp2)–H amination methods.28
TsN3 (2 equiv)
CsOAc (5 mol%)
[Cp*MCl2]2 (2.5 mol%)
H
Moreover, sulfonyl protecting groups can be easily cleaved
2a
+
Ag(I) salt (mol%)
Solvent (0.2 M)
80 °C, 24 h
under reductive conditions.29 With this in mind, we explored
the sulfamidation of allylbenzene with tosyl azide (Table 1).
Based on our dioxazolone study, we began our investigation
with [Cp*RhCl2]2 (2.5 mol%) as the precatalyst, AgSbF6 (10
mol%) as the halide scavenger, and CsOAc (5 mol%) as the
carboxylate base for concerted-metalation deprotonation at
the allylic position. Under these conditions, allylbenzene
was successfully sulfamidated with TsN3 (2 equiv) at 80 °C,
1a
NHTs
3a
entry
[MCp*Cl2]2 Ag(I) (mol%)
% yield (2)b % yield (3)b
Solvent
[Cp*RhCl2]2
[Cp*IrCl2]2
[Cp*RhCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
AgSbF6 (10)
AgSbF6 (10)
AgSbF6 (40)
AgSbF6 (40)
AgBF4 (10)
AgOTs (10)
AgNTf2 (10)
AgNTf2 (10)
AgNTf2 (10)
1
2
3
4
5
6
7
8
9
DCE
DCE
DCE
DCE
DCE
DCE
DCE
TFE
13
17
4
8
trace
trace
<5
0
0
trace
trace
0
<5
23
55
0
HFIP
60
0
aReactions were run using 1a (0.10 mmol), TsN3 (0.40 mmol),
CsOAc (0.005 mmol), AgNTf2 (0.0025 mmol), [Cp*IrCl2]2
(0.0025 mmol). bIsolated yields.
providing the branched and linear products in 13% and 4% yield, respectively (entry 1, Table 1) along with some
unidentified side products. [IrCp*Cl2]2 marginally improved the yields of the aminated products (entry 2, Table 1).
Using dioxazolones as the nitrenoid precursor, we had previously observed that a slight excess of the silver halide
scavenger (40 mol%) resulted in higher yields of the amidated products. However, 40 mol% AgSbF6 provided only
trace amounts of tosylamide product (entries 3 and 4, Table 1). A small screen of silver salts (entries 5-7, Table 1)
revealed that while AgNTf2 (10 mol%) slightly improved the yield of branch-selective tosylamidation to 23%, no trace
of the linear product was observed (entry 7, Table 1). We note that the nature of the counterion impacts the
regioselectivity as well as the yield of the reaction, but do not have sufficient information to rationalize the mechanistic
underpinnings of this observation. We also observed that solvent was a key factor in facilitating the tosylamidation
reaction. Fluorinated solvents like 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)
drastically improved the yield of the reaction to 55% (entry 8, Table 1) and 60% (entry 9, Table 1), respectively. Due
to evaporation of the low-boiling HFIP at the elevated reaction temperature, the reactions were performed in sealed
pressure tubes to ensure reproducibility.
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With optimal conditions for the tosylamidation of
allylbenzene in hand, we turned our attention to the
examination of the functional group compatibility of this
reaction (Scheme 2). A wide range of allylbenzenes of type
1 were tosylamidated under these conditions, providing the
branched sulfonamides 2. The reaction performs well on
electron-rich (1b, 57% yield and 1c, 61% yield) as well as
electron-deficient (1d, 52% yield and 1f, 46% yield)
allylbenzene derivatives. It is also tolerant of an aryl fluoride,
providing tosylamide 2e in 67% yield. The increased
electron-density on safrole (1g) proved to be deleterious for
this reaction, providing tosylamide 2g in 47% yield after an
increased reaction time of 48 hours. o-Allyltoluene (1h),
presumably due to the increased steric hindrance of the ortho
substituent, required 48 hours to provide tosylamide 2h in
60% yield. 4-Phenylbutene (1i) and 1-hexene (1j), which
proceed through non-conjugated π-allyl complexes, also
required extended reaction times (48 hours) to provide
tosylamides 2i and 2j (as a 4.5:1.5:1 mixture of regioisomers)
in 75% and 49% yield, respectively. When CbzN3 was used
Scheme 2: Effect of Allylbenzene Substitution
on Allylic C–H Sulfamidationa
TsN3 (2 equiv)
CsOAc (5 mol%)
H
NHTs
[Cp*IrCl2]2 (2.5 mol%)
R
AgNTf2 (10 mol%)
HFIP (0.2 M)
80 °C, 24 h
R
2
1
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NHTs
NHTs
NHTs
tBu
MeO2C
MeO
2b, 57%
2c, 61%
2d, 52%
NHTs
NHTs
NHTs
O
O
CF3
F
2e, 67%
2f, 46%
2g, 47%b
NHTs
NHTs
NHTs
Me
Me
2h, 60%b
2i, 75%b
2j, 49%b
4.5:1.5:1d,e
NHTs
NHCbz
2k, 17%c
2l, 54%
O
Me
NHTs
H
H
H
CbzHN
CO2Me
NHTs
2m, 50%
2n, 62%
1:1 d.r.e
2:1 d.r.e
b
c
aIsolated yields. Isolated yields after 48 hours. CbzN3 (0.40
mmol, 2 equiv) was used instead of TsN3. dIsolated as mixture
of regioisomers of allylic sulfonamide products at the 3-, 4-,
and 2-positions, respectively (major isomer shown)
eDetermined by integration of crude reaction 1H NMR
spectrum.
as the nitrogen source, the resulting benzyl carbamate 2k was isolated, albeit in reduced yield (17%). The reaction
proceeded smoothly on 1,2-disubstituted olefin 1l to provide tosylamide 2l in 54% yield, indicating the suitability of
this method for the sulfamidation of internal olefins. This reaction is also efficient on biologically relevant molecules
such as phenylalanine derivative 1m and estrone derivative 1n, providing the corresponding sulfonamide products 2m
and 2n in 50% and 62% yield, respectively.30 We note that the crude reaction mixtures predominantly consisted of the
branched tosylamide products and small amounts of starting material (the volatility of the starting olefins precludes
accurate quantification). In some cases, we observed the presence of TsNH2 by crude 1H NMR, which we hypothesize
could coordinate the Cp*Ir, leading to catalyst arrest and reduced yields. No additional side products were observed.
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Based on the regiochemical outcome, we hypothesize
that this reaction mimics the mechanism of the dioxazolone
allylic amidation. Thus, the likely mechanism is outlined in
Scheme 3. Cp*Ir(III) complex I is the active catalyst in this
reaction, produced from [Cp*IrCl2]2, AgNTf2, and CsOAc.
Following olefin coordination (complex II), a concerted-
metalation-deprotonation of the allylic C–H bond produces
Cp*Ir(III)-π-allyl complex III. At this stage, TsN3 decomposition
can release nitrogen gas and form the Cp*Ir(V) nitrenoid IV,
which can undergo reductive elimination to form the C–N bond
at the more electron-rich position of the π-allyl.
Protodemetalation of the tosylamide complex V then produces the
branched sulfonamide 2 and regenerates the Cp*Ir(III) catalyst.
Scheme 3: Proposed Catalytic Cycle
[IrCp*Cl2]2
AgNTf2
2 AgCl
-OAc
Me
Me
+
Me
Me
NHTs
Me
H
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Ph
IrIII
Ph
2
OAc
L
1
I
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
TsN
IrIII
IrIII
Ph
Ph
OAc
V
II
Reductive
Elimination
C–H
Activation
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Nitrene
Formation
IrIII
IrV
Ph
Ph
NTs
III
IV
N2
TsN3
The synthetic utility of this reaction was further
Scheme 4: Diversification of tosylamidation
products
explored in the diversification of the sulfamidation products
(Scheme 4). Tosylamide 2c was successfully allylated, and the
resulting diene 4 was subjected to ring-closing metathesis
NHTs
K2CO3 (2 equiv)
TsN
allyl bromide (1.1 equiv)
DMF, r.t., 16 h
70%
tBu
2c
tBu
4
Ts
N
Grubbs II (5 mol%)
(RCM) to provide dihydropyrrole
5 in 61% yield.
DCM, 40 °C, 16 h
61%
5
tBu
Additionally, tosylamide 6, the product of sulfamidation of 6-
Ts
bromohexene, was subjected to base-promoted cyclization to
K2CO3 (7 equiv)
Br
N
MeCN, 80 °C, 6 h
NHTs
96%
6
provide 2-vinylpyrrolidine
7
in 96% yield. These
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transformations display the applicability of allylic tosylamides as precursors in the synthesis of pharmaceutically
relevant nitrogen-containing heterocycles.
SUMMARY
We have developed conditions for the sulfamidation of allylbenzene derivatives using tosyl azide as an
oxidative aminating reagent. This reaction is regioselective for the branched position of the π-allyl complex, and
displays good functional group tolerance. The reaction likely proceeds via inner-sphere C–N reductive elimination of
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a Cp*Ir*(V)-π-allyl nitrenoid complex. Investigations to elucidate the mechanisms of allylic C–H functionalizations
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via reductive elimination of Cp*M(V) nitrenoid complexes are currently ongoing in our laboratory.
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EXPERIMENTAL SECTION
General Information
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All reactions were carried out under nitrogen atmospheres with anhydrous solvents in oven- or flame-dried glassware
using standard Schlenk technique, unless otherwise stated. Anhydrous dichloromethane (DCM), diethyl ether (Et2O),
tetrahydrofuran (THF), and toluene were obtained by passage through activated alumina using a Glass Contours
solvent purification system. 1,2-dichloroethane (DCE), 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-
hexafluoroisopropanol (HFIP) were distilled over CaH2 and stored over activated molecular sieves. Solvents for
workup, extraction, and column chromatography were used as received from commercial suppliers without further
purification. Pd(PPh3)4, LiCl, AgSbF6, AgBF4, AgOTs, AgNTf2, CsOAc, [Cp*IrCl2]2, and [Cp*RhCl2]2 were stored
and weighed in a nitrogen-filled glovebox. Tosyl azide (TsN3),31 [Cp*IrCl2]2, and [Cp*RhCl2]2 were synthesized
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according to previously reported methods. All other chemicals were purchased from Sigma-Aldrich, Strem Chcmicals,
Oakwood Chemicals, Alfa Aesar, or Combi-Blocks, and used as received without further purification.
1H and 13C nuclear magnetic resonance (NMR) spectra were recorded on a Varian Inova 600 spectrometer (600 MHz
1H, 151 MHz 13C), a Bruker 600 spectrometer (600 MHz 1H, 151 MHz 13C), a Varian Inova 500 spectrometer (500
MHz 1H, 126 MHz 13C), and a Varian Inova 400 spectrometer (400 MHz 1H, 100 MHz 13C) at room temperature in
CDCl3 (neutralized and dried over anhydrous K2CO3) with internal CHCl3 as the reference (7.26 ppm for 1H, 77.16
ppm for 13C), unless otherwise stated. Chemical shifts (δ values) were reported in parts per million (ppm) and coupling
constants (J values) in Hz. Multiplicity was indicated using the following abbreviations: s = singlet, d = doublet, t =
triplet, q = quartet, qn = quintet, m = mutiplet, br = broad. Infrared (IR) spectra were recorded using a Thermo Electron
Corporation Nicolet 380 FT-IR spectrometer. High resolution mass spectra (HRMS) were obtained using a Thermo
Electron Corporation Finigan LTQFTMS (at the Mass Spectrometry Facility, Emory University). Analytical thin layer
chromatography (TLC) was performed on precoated glass backed Silicycle SiliaPure® 0.25 mm silica gel 60 plates
and visualized with UV light, ethanolic p-anisaldehyde, or aqueous potassium permanganate (KMnO4). Flash column
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chromatography was performed using Silicycle SiliaFlash® F60 silica gel (40-63 µm) on a Biotage Isolera One
system. Preparatory TLC was performed on precoated glass backed Silicycle SiliaPure® 1.0 mm silica gel 60 plates.
We acknowledge the use of shared instrumentation provided by grants from the NIH and the NSF.
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Preparation of Olefin Coupling Partners
1a, 1b, 1e, 1f, 1g, and 1h were purchased from commercial sources and used as received without further purification.
1c,30 1d,33 1l,8 and 1m34 were prepared according to previously reported procedures, Pd(PPh3)4 was used as the
palladium precatalyst in all cases.
Phenylalanine-derived allylbenzene (1k): In a nitrogen-filled glovebox, Pd(PPh3)4 (0.0553 g, 0.048 mmol, 0.031
equiv) and LiCl (0.3022 g, 7.13 mmol, 4.75 equiv) were added to an oven dried 15 mL vial equipped with a magnetic
stir-bar and teflon-septum screw cap. The vial was capped and brought out of the glovebox. A solution of N-Cbz-(p-
OTf)-Phe-OMe (0.7003 g, 1.50 mmol, 1 equiv) in DMF (6.30 mL) was added, followed by neat allyltributylstannane
(0.600 mL, 1.67 mmol, 1.1 equiv). The vial was placed in an aluminum heating block pre-heated to 100 °C, and stirred
for 12.5 hours. The reaction was removed from heat, allowed to cool to room temperature, and quenched with aqueous
NH4OH (1N, 7.0 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (3 x 10.0 mL).
The combined organic extracts were washed with brine (2 x 15.0 mL), dried over anhydrous Na2SO4, filtered, and
concentrated under reduced pressure. Purification by flash chromatography on silica gel (0-100% EtOAc in Hexanes)
provided 1k (0.297 g, 55% yield). 1H NMR (CDCl3, 600 MHz) δ 7.43 – 7.31 (m, 5H), 7.14 – 7.08 (m, 2H), 7.06 –
7.00 (m, 2H), 5.95 (ddt, J = 17.5, 9.5, 6.7 Hz 1H), 5.21 (d, J = 8.3 Hz, 1H) 5.15 – 4.92 (m, 4H), 4.66 (dt, J = 8.3, 5.8
Hz, 1H), 3.73 (s, 3H), 3.36 (dd, J = 6.8, 1.6 Hz, 2H), 3.10 (dd, J = 14.9, 5.8 Hz, 2H) ppm; 13C{1H} NMR (CDCl3, 151
MHz) 172.1, 155.7, 139.0, 137.4, 136.4, 133.4, 129.4, 129.0, 128.6, 128.6, 128.30, 128.2, 116.0, 67.1, 54.9, 52.4,
39.9, 37.9 ppm; HRMS (+ NSI) calculated for C21H24O4N [M+H]+ 354.1705, found 354.1706.
General Procedure A: Optimization of Allylic C–H Sulfamidation Reaction
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In a nitrogen-filled glovebox, CsOAc (0.0009 g, 0.005 mmol, 0.05 equiv), the Ag halide scavenger (0.010-0.040
mmol, 0.10-0.40 equiv, as indicated), and [Cp*MCl2]2 (0.0025 mmol, 0.025 equiv) were added to an oven-dried 4 mL
vial equipped with a magnetic stir-bar and a teflon-septum screw cap. The vial was capped and brought out of the
glovebox. The indicated solvent (0.50 mL), allylbenzene (1a) (0.013 mL, 0.10 mmol, 1 equiv, with a microsyringe),
and TsN3 (0.030 mL, 0.20 mmol, 2 equiv., with a microsyringe) were added. The vial was sealed with teflon tape and
parafilm and placed in an aluminum heating block pre-heated to 80 °C, and stirred for 24 hours. The vial was removed
from heat and allowed to cool to room temperature. The reaction was filtered through a pipette containing celite with
EtOAc (10 mL) and the filtrate was concentrated under reduced pressure. Purification by flash chromatography on
silica gel (10-30% EtOAc in Hexanes) provided branched tosylamide 2a and linear tosylamide 3a. Spectral data
matches those previously reported in the literature.19,35
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4-methyl-N-(1-phenylallyl)benzenesulfonamide (2a): 1H NMR (CDCl3, 500 MHz) δ 7.63 (d, J = 8.3 Hz, 2H), 7.24 –
7.18 (m, 5H), 7.12 – 7.07 (m, 2H), 5.86 (ddd, J = 16.9, 10.5, 5.7 Hz, 1H), 5.16 – 5.08 (m, 2H), 4.97 – 4.86 (m, 2H),
2.39 (s, 1H) ppm.
N-cinnamyl-4-methylbenzenesulfonamide (3a): 1H NMR (CDCl3, 400 MHz) δ 7.78 (d, J = 8.3 Hz, 2H), 7.42 – 7.10
(m, 7H), 6.44 (d, J = 15.9 Hz, 1H), 6.02 (dt, J = 15.8, 6.4 Hz, 1H), 4.46 (t, J = 6.2 Hz, 1H), 3.76 (td, J = 6.3, 1.5 Hz,
2H), 2.42 (s, 3H) ppm.
General procedure B: Allylic C–H Sulfamidation of Allylbenzene Derivatives
In a nitrogen-filled glovebox, CsOAc (0.0019 g, 0.010 mmol, 0.05 equiv.), the AgNTf2 (0.0078 g, 0.020 mmol, 0.10
equiv., as indicated), and [Cp*IrCl2]2 (0.0040 g, 0.005 mmol, 0.025 equiv.) were added to an oven-dried 7 mL pressure
tube equipped with a magnetic stir-bar and a screw cap. The tube was sealed and brought out of the glovebox. HFIP
(0.5 mL) and TsN3 (0.40 mmol, 2 equiv) were added through the side-arm of the tube. For allylbenzene derivatives
with known densities, a microsyringe was used for addition through the side-arm of the pressure tube (0.20 mmol, 1
equiv), followed by HFIP (0.5 mL) to wash the sides of the tube. All other allylbenzene derivatives (0.20 mmol, 1
equiv) were added as stock solutions in HFIP (0.5 mL). The tube was sealed and placed in an aluminum heating block
pre-heated to 80 °C, and stirred for 24-48 hours, as indicated. The tube was removed from heat and allowed to cool to
room temperature. The tube was opened to the side-arm and the septum was carefully removed to release pressure.
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The reaction was filtered through a pipette containing celite with EtOAc (15 mL) and the filtrate was concentrated
under reduced pressure. Purification by flash chromatography on silica gel (10-30% EtOAc in Hexanes) provided the
tosylamide products.
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Characterization of Allylic C–H Sulfamidation Products
N-(1-(4-methoxyphenyl)allyl)-4-methylbenzenesulfonamide (2b): Prepared according to General Procedure B, using
4-allylanisole (1b) (0.031 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040 g,
0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv)
in HFIP (1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (10-30% EtOAc in Hexanes)
to provide 2b (0.0365 g, 57% yield). Spectral data matches those previously reported in the literature.36 1H NMR
(CDCl3, 500 MHz) δ 7.63 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.6 Hz, 2H), 7.01 (d, J = 8.7 Hz, 2H), 6.74 (d, J = 8.9 Hz,
2H), 5.85 (ddd, J = 17.2, 10.1, 5.7 Hz, 1H), 5.14 – 5.08 (m, 2H), 4.95 (d, J = 7.5 Hz, 1H), 4.90 – 4.85 (m, 1H), 3.75
(s, 3H), 2.39 (s, 3H) ppm.
N-(1-(4-(tert-butyl)phenyl)allyl)-4-methylbenzenesulfonamide (2c): Prepared according to General Procedure B, using
1-allyl-4-(tert-butyl)benzene (1c) (0.0350 g, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2
(0.0040 g, 0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol.
0.05 equiv) in HFIP (1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (10-30% EtOAc
in Hexanes) to provide 2c (0.0422 g, 61% yield). 1H NMR (CDCl3, 600 MHz) δ 7.61 (d, J = 8.3 Hz, 2H), 7.21 (d, J =
8.4 Hz, 2H), 7.16 (d, J = 7.8 Hz, 2H), 7.01 (d, J = 8.1 Hz, 2H), 5.87 (ddd, J = 17.1, 10.3, 5.9 Hz, 1H), 5.20 – 5.05 (m,
2H), 5.01 (d, J = 7.3 Hz, 1H), 4.95 – 4.91 (m, 1H), 2.37 (s, 3H), 1.27 (s, 9H) ppm; 13C{1H} NMR (CDCl3, 151 MHz)
δ 150.8, 143.1, 137.9, 137.4, 136.4, 129.4, 127.4, 126.9, 125.6, 116.7, 59.8, 34.6, 31.4, 21.6 ppm; HRMS (+ APCI)
calculated for C20H29N2O2S [M+NH4]+ 361.1950, found 361.1940.
Methyl-4-(1-((4-methylphenyl)sulfonamido)allyl)benzoate (2d): Prepared according to General Procedure B, using 4-
methylallylbenzoate (1d) (0.0350 g, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040
g, 0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05
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equiv) in HFIP (1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (10-30% EtOAc in
Hexanes) to provide 2d (0.0361 g, 52% yield). 1H NMR (CDCl3, 600 MHz) δ 7.85 (d, J = 8.3 Hz, 2H), 7.61 (d, J =
8.3 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 5.83 (ddd, J = 16.7, 10.3, 6.0 Hz, 1H), 5.37 (d, J = 7.7
Hz, 1H), 5.16 – 5.03 (m, 2H), 5.01 – 4.95 (m, 1H), 3.89 (s, 3H), 2.37 (s, 3H) ppm; 13C{1H} NMR (CDCl3, 151 MHz)
δ 166.8, 144.5, 143.6, 137.6, 136.5, 130.0, 129.8, 129.6, 127.3, 126.5, 117.7, 59.7, 52.3, 21.6 ppm; HRMS (+ APCI)
calculated for C18H23N2O4S [M+NH4]+ 363.1379, found 363.1376.
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N-(1-(4-fluorophenyl)allyl)-4-methylbenzenesulfonamide (2e): Prepared according to General Procedure B, using 1-
allyl-4-fluorobenzene (1e) (0.027 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040
g, 0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05
equiv) in HFIP (1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (10-30% EtOAc in
Hexanes) to provide 2e (0.0422 g, 67% yield). 1H NMR (CDCl3, 600 MHz) δ 7.61 (d, J = 8.3 Hz, 2H), 7.19 (dd, J =
8.6, 0.8 Hz, 2H), 7.11 – 7.05 (m, 2H), 6.89 (t, J = 8.7 Hz, 2H), 5.83 (ddd, J = 17.0, 10.3, 5.8 Hz, 1H), 5.13 (d, J = 10.3
Hz, 1H), 5.10 – 5.06 (m, 2H), 4.96 – 4.90 (m, 1H), 2.39 (s, 3H) ppm; 13C{1H} NMR (CDCl3, 151 MHz) δ 162.2 (d,
JC=F = 246.3 Hz), 143.5, 137.6, 136.9, 135.3 (d, JC=F = 3.2 Hz), 129.5, 129.0 (d, JC=F = 8.2 Hz), 127.3, 117.1, 115.5
(d, JC=F = 21.5 Hz), 59.3, 21.6 ppm; HRMS (+ APCI) calculated for C16H17FNO2S [M+H]+ 306.0964, found 306.0954.
4-methyl-N-(1-(4-(trifluoromethyl)phenyl)allyl)benzenesulfonamide (2f): Prepared according to General Procedure B,
using 4-allyltriflourotoluene (1f) (0.033 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2
(0.0040 g, 0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol.
0.05 equiv) in HFIP (1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (10-30% EtOAc
in Hexanes) to provide 2f (0.033 g, 46% yield). Spectral data matches those previously reported in the literature.24 1
H
NMR (CDCl3, 500 MHz) δ 7.56 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.5 Hz, 2H), 7.13 (d, J =
8.0 Hz, 2H), 5.84 (ddd, J = 16.3, 10.3, 5.9 Hz, 1H), 5.37 (d, J = 7.4 Hz, 1H), 5.16 (d, J = 10.3 Hz, 1H), 5.11 – 4.97
(m, 2H), 2.36 (s, 3H) ppm; 13C{1H} NMR (CDCl3, 126 MHz) δ 143.7, 143.27, 143.25, 137.4, 136.4, 130.1 (q, JC-F
=
32.5 Hz), 129.6, 129.5, 127.7, 127.3, 125.5 (q, JC-F = 3.8 Hz), 117.9, 59.6, 21.5 ppm; HRMS (+ APCI) calculated for
C17H20F3N2O2S [M+NH4]+ 373.1198, found 373.1192.
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N-(1-(benzo[d][1,3]dioxol-5-yl)allyl)-4-methylbenzenesulfonamide (2g): Prepared according to General Procedure B,
using safrole (1g) (0.029 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040 g,
0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv)
in HFIP (1.0 mL) at 80 °C for 48 hours. Purified by flash chromatography on silica gel (10-30% EtOAc in Hexanes)
to provide 2g (0.0311 g, 47% yield). 1H NMR (CDCl3, 500 MHz) δ 7.63 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.5 Hz 1H),
6.64 (d, J = 8.0 Hz, 1H), 6.57 (dd, J = 8.0, 1.8 Hz, 1H), 6.53 (d, J = 1.8 Hz, 1H), 5.90 (d, J = 1.5 Hz, 1H), 5.89 (d, J
= 1.4 Hz, 1H), 5.82 (ddd, J = 17.2, 10.1, 5.4 Hz, 1H), 5.16 – 5.08 (m, 2H), 4.88 – 4.81 (m, 2H), 2.40 (s, 3H) ppm;
13C{1H} NMR (CDCl3, 151 MHz) δ 147.9, 147.3, 143.4, 137.8, 137.2, 133.4, 129.5, 127.4, 120.8, 116.9, 108.3, 107.7,
101.26, 77.2, 59.8, 21.6 ppm; HRMS (+ APCI) calculated for C17H18NO4S [M+H]+ 332.0957, found 332.0943.
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4-methyl-N-(1-(o-tolyl)allyl)benzenesulfonamide (2h): Prepared according to General Procedure B using 1-allyl-2-
methylbenzene (1h) (0.029 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040 g,
0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv)
in HFIP (1.0 mL) at 80 °C for 48 hours. Purified by flash chromatography on silica gel (10-30% EtOAc in Hexanes)
to provide 2h (0.0359 g, 60% yield). 1H NMR (CDCl3, 600 MHz) δ 7.60 (d, J = 8.2 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H),
7.07 – 7.01 (m, 3H), 5.85 (ddd, J = 17.1, 10.3, 5.5 Hz, 1H), 5.21-5.15 (m, 1H), 5.10 (dd, J = 10.3, 1.3 Hz, 1H), 5.06 –
4.96 (m, 1H), 4.85 (d, J = 7.2 Hz, 1H), 2.37 (s, 3H), 2.21 (s, 3H) ppm; 13C{1H} NMR (CDCl3, 126 MHz) δ 143.3,
137.8, 137.4, 137.1, 135.6, 130.8, 129.5, 127.8, 127.2, 126.9, 126.4, 116.9, 56.5, 21.6, 19.3 ppm; HRMS (+ APCI)
calculated for C17H20NO2S [M+H]+ 302.1215, found 302.1204.
4-methyl-N-(1-phenylbut-3-en-2-yl)benzenesulfonamide (2i): Prepared according to General Procedure B, using 4-
phenylbutene (1i) (0.030 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040 g,
0.005 mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv)
in HFIP (1.0 mL) at 80 °C for 48 hours. Purified by flash chromatography on silica gel (10-40% EtOAc in Hexanes)
to provide 2i (0.045 g, 75% yield). Spectral data matches those previously reported in the literature.37 1H NMR
(CDCl3, 400 MHz): δ 7.60 (d, J = 8.3 Hz, 2H), 7.27 – 7.16 (m, 5H), 7.05 – 7.00 (m. 2H), 5.68 (ddd, J = 16.8, 10.4,
6.1 Hz, 1H), 5.10 – 4.96 (m, 2H), 4.49 (d, J = 7.3 Hz, 1H), 4.07 – 3.95 (m, 1H), 3.08 – 2.61 (m, 2H), 2.41 (3H, s) ppm.
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N-(hex-1-en-3-yl)-4-methylbenzenesulfonamide (2j): Prepared following General Procedure B using 1-hexene (0.025
mL, 0.20 mmol, 1 equiv). Purified by flash chromatography on silica gel (0-100% Et2O in Hexanes) to provide XX
(0.025 g, 49% yield) as an inseparable mixture of regioisomers (4.5:1.5:1 r.r.). Spectral data matches those previously
reported in the literature.38,39 1H NMR (CDCl3, 399 MHz) δ 7.73 (m, 28H), 7.28 (m, 28H), 5.53 (ddd, J = 17.0, 10.3,
6.6 Hz, 9H), 5.45 (dt, J = 15.4, 6.3 Hz, 2H), 5.41 – 5.28 (m, 3H), 5.14 (dd, J = 15.4, 6.6 Hz, 2H), 5.05 (ddd, J = 15.3,
7.4, 1.7 Hz, 3H), 5.00 – 4.93 (m, 18 H), 4.58 (d, J = 7.9 Hz, 9H), 4.50 (d, J = 7.6 Hz, 5H), 3.97 – 3.82 (m, 2H), 3.76
(quint, J = 6.8 Hz, 9H), 3.61 (quint, J = 7.2 Hz, 3H), 2.42 (s, 42H), 1.95 – 1.80 (m, 5H), 1.56 – 1.16 (m, 33H), 0.83
(t, J = 7.3 Hz, 42H) ppm.
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Benzyl (1-phenylallyl)carbamate (2k): Prepared according to General Procedure B using allylbenzene (1a) (0.026 mL,
0.20 mmol, 1 equiv), CbzN3 (0.071 g, 0.40 mmol, 2 equiv), [Cp*IrCl2]2 (0.0040 g, 0.005 mmol, 0.0025 equiv), AgNTf2
(0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv) in HFIP (1.0 mL) at 80 °C for 24
hours. Purified by flash chromatography on silica gel (10-30% EtOAc in Hexanes) to provide 2j (0.0091 g, 17% yield).
Spectral data matches those previously reported in the literature.40 1H NMR (CDCl3, 500 MHz) δ 7.40 – 7.27 (m,
10H), 6.01 (ddd, J = 16.3, 10.6, 5.3 Hz, 1H), 5.37 (br s, 1H), 5.26 (br s, 1H), 5.24 – 5.20 (m, 2H), 5.16 – 5.09 (m, 2H)
ppm.
(E)-N-(1,3-diphenylallyl)-4-methylbenzenesulfonamide (2l): Prepared following General Procedure B using 1,3-
trans-diphenylpropene (0.038 mL, 0.20 mmol, 1 equiv). Purified by flash chromatography on silica gel (10-30%
EtOAc in Hexanes) to provide 2m (0.0393 g, 54% yield). Spectral data matches those previously reported in the
literature.19 1H NMR (CDCl3, 500 MHz) δ 7.65 (d, J = 8.3 Hz, 2H), 7.28 – 7.10 (m, 12H), 6.33 (dd, J = 15.8, 1.2 Hz,
1H), 6.07 (dd, J = 15.8, 6.8 Hz, 1H), 5.22 (d, J = 7.3 Hz, 1H), 5.11 (td, J = 7.1, 1.3 Hz, 1H), 2.31 (s, 3H) ppm.
Phenylalanine-derived allylbenzene tosylamide (2m): Prepared according to General Procedure B using Cbz-(p-allyl)-
Phe-OMe (1k) (0.071 g, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040 g, 0.005
mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv) in
HFIP (1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (30-50% EtOAc in Hexanes) to
provide the desired product with TsNH2 impurities. Additional purification by preparatory TLC (30% EtOAc in
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Hexanes, 2 sweeps) provided 2k (0.0495 g, 50% yield) as an inseparable mixture of diastereomers (1:1 d.r.). 1H NMR
(CDCl3, 600 MHz) δ 7.64 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H), 7.40 – 7.30 (m, 10H), 7.21 (d, J = 8.3 Hz, 2H),
7.21 (d, J = 7.9 Hz, 2H), 7.03 (d, J = 8.1 Hz, 4H), 6.96 (d, J = 8.2 Hz, 2H), 6.95 (d, J = 8.1 Hz, 2H), 5.82 (ddd, J =
16.1, 10.3, 6.0 Hz, 1H), 5.82, (ddd, J = 17.0, 10.3, 6.0 Hz, 1H), 5.19 – 5.05 (m, 10H), 4.90 (q, J = 5.7 Hz, 2H), 4.73
(d, J = 7.3 Hz, 1H), 4.73 (d, J = 7.3 Hz, 1H), 4.62 (q, J = 6.0 Hz, 2H), 3.72 (s, 3H), 3.71 (s, 3H), 3.09 (dd, J = 13.9,
5.7 Hz, 1H), 3.08 (dd, J = 14.0, 5.7 Hz, 1H), 3.03 (dd, J = 14.2, 6.2 Hz, 2H), 2.39 (s, 3H), 2.39 (s, 3H) ppm; 13C{1H}
NMR (CDCl3, 151 MHz) δ 171.9, 155.7, 143.5, 138.5, 137.8, 137.07, 137.05, 136.3, 135.1, 129.73, 129.71, 129.6,
129.5, 128.7, 128.4, 128.3, 127.5, 127.4, 117.2, 117.1, 67.2, 59.6, 54.8, 52.5, 37.9, 37.9, 21.6 ppm; HRMS ( – APCI)
calculated for C28H29N2O6S [M–H]– 521.1746, found 521.1748.
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Estrone-derived allylbenzene tosylamide (2n): Prepared following General Procedure B using estrone allylbenzene
(1l) (0.0503 g, 0.171mmol, 1 equiv), TsN3 (0.0524 mL,0.342 mmol, 2 equiv), [Cp*IrCl2]2 (0.0034 g, 0.0043 mmol,
0.0025 equiv), AgNTf2 (0.0063 g, 0.0171 mmol, 0.10 equiv) and CsOAc (0.0016 g, 0.0085 mmol, 0.05 equiv) in HFIP
(1.0 mL) at 80 °C for 24 hours. Purified by flash chromatography on silica gel (30-50% EtOAc in Hexanes) to provide
2l (0.0494 g, 62% yield) as an inseparable mixture of diastereomers (2:1 d.r.). 1H NMR (CDCl3, 500 MHz) 7.81 (d, J
= 8.3 Hz, 2H), 7.63 (d, J = 8.4, 4H), 7.30 (d, J = 8.3 Hz, 2H), 7.19 (d, 8.6 Hz, 4H), 7.14 (dd, J = 8.0, 2.9 Hz, 3H), 6.89
(ddd, J = 7.9, 5.6, 2.0 Hz, 3H), 6.78 (dd, J = 3.5, 2.0 Hz, 3H), 5.84 (ddd, J = 15.4, 10.3, 6.0 Hz, 1H), 5.84 (ddd, J =
16.3, 10.3 Hz, 6.0 Hz, 2H), 5.17 - 5.08 (m, 3H), 4.99 (d, J = 7.0 Hz, 3H), 4.85 (q, J = 5.9 Hz, 3H), 2.85 - 2.69 (m,
5H), 2.50 (dd, J = 19.1, 8.8 Hz, 3H), 2.42 (s, 3H), 2.40 (s, 6H), 2.40 - 2.33 (m, 3H), 2.26 - 2.19 (m, 3H), 2.14 (dt, J =
19.0, 8.9 Hz, 3H), 2.08 - 2.02 (m, 3H), 2.01 - 1.91 (m, 6H), 1.69 - 1.56 (m, 4H), 1.56 - 1.44 (m, 12H), 1.44 - 1.32 (m,
3H), 0.90 (s, 3H), 0.90 (s, 6H) ppm; 13C{1H} NMR (CDCl3, 126 MHz) δ 220.8, 143.6, 143.2, 139.53, 139.51, 139.4,
137.95, 137.92, 137.27, 137.26, 137.01, 136.98, 136.90, 129.8, 129.44, 129.42, 127.80, 127.78, 127.4, 126.6, 125.8,
124.6, 124.7, 116.71, 116.68, 59.80, 59.79, 50.6, 48.1, 44.4, 38.23, 38.22, 36.0, 31.7, 29.4, 26.5, 25.83, 25.82, 21.70,
21.66, 21.65, 21.63, 14.0 ppm; HRMS (+ APCI) calculated for C28H34NO3S [M+H]+ 464.2259, found 464.2264.
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Synthesis of dihydropyrrole 5
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N-allyl-N-(1-(4-(tert-butyl)phenyl)allyl)-4-methylbenzenesulfonamide (4): Allyl bromide (0.011 mL, 0.126 mmol, 1.1
equiv) and K2CO3 0.0316 g, 0.229 mmol, 2 equiv) were added to a solution of N-(1-(4-(tert-butyl)phenyl)allyl)-4-
methylbenzenesulfonamide (2c) (0.0393 g, 0.114 mmol, 1 equiv) in DMF (0.50 mL), and the resulting mixture was
stirred at room temperature. After 16 hours, the reaction was diluted with water (5.0 mL) and EtOAc (5.0 mL). The
layers were separated and the aqueous layer was extracted with EtOAc (3 x 5.0 mL). The combined organic extracts
were washed with brine (2 x 15.0 mL), dried over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. Purification by flash chromatography on silica gel (5-20% EtOAc in Hexanes) to provide 4 (0.0305 g, 70%
yield). 1H NMR (CDCl3, 500 MHz) δ 7.69 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 8.6 Hz, 2H), 7.14
(d, J = 8.9 Hz, 2H), 6.05 (ddd, J = 17.2, 10.3, 7.0 Hz, 1H), 5.62 (d, J = 7.0 Hz, 1H), 5.50 (ddt, J = 16.2, 10.2, 6.3 Hz,
1H), 5.26 (d, J = 10.3 Hz, 1H), 5.14 (d, J = 17.1 Hz, 1H), 4.97 – 4.84 (m, 2H), 3.83 (dd, J = 16.3, 6.1 Hz, 1H), 3.71
(dd, J = 16.2, 6.6 Hz, 1H), 2.42 (s, 3H), 1.30 (s, 9H) ppm; 13C{1H} NMR (CDCl3, 126 MHz) δ 151.0, 143.0, 138.4,
135.5, 135.4, 135.1, 129.5, 128.2, 127.7, 125.4, 119.0, 117.2, 63.4, 48.1, 34.6, 31.5, 21.7 ppm. HRMS (+ APCI)
calculated for C23H30NO2S [M+H]+ 384.1997, found 384.1987.
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2-(4-(tert-butyl)phenyl)-1-tosyl-2,5-dihydro-1H-pyrrole (5): Grubbs II (0.0034 g, 0.00398 mmol, 0.05 equiv) was
added to a solution of N-allyl-N-(1-(4-(tert-butyl)phenyl)allyl)-4-methylbenzenesulfonamide 4 (0.0305 g, 0.0795
mmol, 1 equiv) in DCM (1.50 mL) and the resulting mixture was stirred in an aluminum heating block pre-heated to
40 °C. After 16 hours, the reaction was quenched with saturated aqueous NaHCO3 (3.0 mL) and diluted with DCM
(3.0 mL). The layers were separated, and the aqueous layer was extracted with DCM (3 x 3.0 mL). The combined
organic extracts were washed with brine (8.0 mL), dried over anhydrous Na2SO4, filtered, and concentrated under
reduced pressure. Purification by flash chromatography (10-30% EtOAc in Hexanes) provided 5 (0.0171 g, 61%
yield). 1H NMR (CDCl3, 600 MHz) δ 7.46 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4Hz, 2H), 7.14
(d, J = 8.5 Hz, 2H), 5.79 (dq, J = 6.1, 2.0 Hz, 1H), 5.66 (dq, J = 6.5, 2.2 Hz, 1H), 5.51 (dq, J = 6.3, 2.2 Hz, 1H), 4.37
(dq, J = 14.5, 2.3 Hz, 1H), 4.25 (ddt, J = 14.5, 5.7, 2.1 Hz, 1H), 2.36 (s, 3H), 1.30 (s, 9H) ppm; 13C{1H} NMR (CDCl3,
126 MHz) δ 150.9, 143.0, 137.3, 136.1, 130.8, 129.4, 127.3, 127.2, 125.4, 124.5, 70.0, 55.4, 34.6, 31.5, 21.6 ppm;
HRMS (+ APCI) calculated for C21H26NO2S [M+H]+ 356.1684, found 356.1670.
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Synthesis of 2-vinylpyrrolidine 7
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N-(6-bromohex-1-en-3-yl)-4-methylbenzenesulfonamide (6): Prepared according to General Procedure B, using 6-
bromohexene (0.025 mL, 0.20 mmol, 1 equiv), TsN3 (0.061 mL, 0.40 mmol, 1 equiv), [Cp*IrCl2]2 (0.0040 g, 0.005
mmol, 0.0025 equiv), AgNTf2 (0.0078 g, 0.02 mmol, 0.10 equiv), and CsOAc (0.0019 g, 0.01 mmol. 0.05 equiv) in
HFIP (1.0 mL) at 80 °C for 40 hours. Purified by flash chromatography on silica gel (0-100% EtOAc in Hexanes) to
provide 6 (0.0045 mg, 9% yield). 1H NMR (CDCl3, 400 MHz) δ 7.72 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H),
5.81 (ddd, J = 16.8, 10.3, 6.0 Hz, 1H), 5.28 (d, J = 17.0 Hz, 1H), 5.12 (d, J = 10.2 Hz, 1H), 4.13 (q, J = 6.9, 6.3 Hz,
1H), 3.45 (ddd, J = 9.8, 7.2, 4.1 Hz, 1H), 3.23 (dt, J = 10.0, 7.5 Hz, 1H), 2.43 (s, 3H), 2.08 – 1.57 (m, 4H) ppm;
13C{1H} NMR (CDCl3, 151 MHz) δ 143.4, 138.8, 135.4, 129.7, 127.7, 115.5, 62.1, 48.9, 32.4, 23.9, 21.7 ppm; HRMS
(+ NSI) calculated for C13H18NO2S [M–Br]+ 252.1058, found 252.1050.
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1-tosyl-2-vinylpyrrolidine (7): K2CO3 (0.0123 g, 0.0890 mmol, 7 equiv) was added to a solution of tosylamide 6
(0.0044 g, 0.013 mmol, 1 equiv) in CH3CN (0.40 mL). The vial was placed in a sand bath pre-heated to 80 °C and
stirred for 6 hours. The vial was removed heat and allowed to cool to room temperature. The reaction was filtered
through a celite plug with EtOAc (10.0 mL) and the filtrate was concentrated under reduced pressure to provide 7
(0.0032 g, 96% yield). Spectral data matches those previously reported in the literature.16 1H NMR (CDCl3, 400
MHz) δ 7.73 (d, J = 8.0 Hz, 2H), 7.34 – 7.29 (m, 2H), 5.81 (ddd, J = 17.1, 10.2, 6.0 Hz, 1H), 5.13 (dt, J = 10.3, 1.3
Hz, 1H), 3.46 (ddd, J = 11.2, 7.2, 4.1 Hz, 1H), 3.28 – 3.09 (m, 1H), 2.43 (s, 3H), 1.86 – 1.57 (m, 4H) ppm.
ASSOCIATED CONTENT
The Supporting Information is available free of charge on the ACS Publications website at DOI:
Optimization for the linear tosylamidation of allylbenzene; NMR spectra of all new compounds.
AUTHOR INFORMATION
Corresponding Author
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Simon B. Blakey: sblakey@emory.edu
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Author Contributions
†These authors contributed equally to this work.
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ORCID
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Simon B. Blakey: 0000-0002-4100-8610
Amaan M. Kazerouni: 0000-0002-4121-2603
Taylor A. F. Nelson: 0000-0002-4685-1455
ACKNOWLEDGEMENTS
This research was supported by the National Science Foundation (NSF) under the CCI Center for Selective C–H
Functionalization (CHE-1700982). NMR studies for this research were performed on instrumentation funded by NSF
(CHE-1531620).
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