Photoinduced Kochi Decarboxylative Elimination for the Synthesis of Enamides and Enecarbamates from N-Acyl Amino Acids

Article abstract of DOI:10.1021/acs.joc.9b00167

Decarboxylative elimination of easily accessible N-acyl amino acids to provide enamide and enecarbamate building blocks has been realized through the combination of an organophotoredox catalyst and copper acetate as the terminal oxidant. This operationally simple process utilizes inexpensive and readily available reagents without preactivation of the carboxylic acid. Enamides and enecarbamates are now accessible directly from N-acyl amino acids consequently improving upon the utility of Kochi's oxidative decarboxylation of carboxylic acids.

Full text of DOI:10.1021/acs.joc.9b00167

Article
pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Photoinduced Kochi Decarboxylative Elimination for the Synthesis
of Enamides and Enecarbamates from N‑Acyl Amino Acids
Kaitie C. Cartwright, Simon B. Lang, and Jon A. Tunge*
Department of Chemistry, The University of Kansas, 2010 Malott Hall, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, United
States
S
* Supporting Information
ABSTRACT: Decarboxylative elimination of easily accessible
N-acyl amino acids to provide enamide and enecarbamate
building blocks has been realized through the combination of
an organophotoredox catalyst and copper acetate as the
terminal oxidant. This operationally simple process utilizes
inexpensive and readily available reagents without preactiva-
tion of the carboxylic acid. Enamides and enecarbamates are
now accessible directly from N-acyl amino acids consequently improving upon the utility of Kochi’s oxidative decarboxylation of
carboxylic acids.
Scheme 1. Strategies for Decarboxylative Elimination
INTRODUCTION
■
The plethora of nitrogen-containing, biologically active natural
products has led to significant interest in the development of
methods toward the incorporation of nitrogen moieties. One
strategy involves the use of enamides and enecarbamates which
have proven to be valuable nucleophilic building blocks with
versatile applications in the synthesis of complex molecules.1
As such, many efforts in the development of methods toward
enamide synthesis have been reported. Classical methods
include condensation reactions of amines with aldehydes,2 the
Curtius rearrangement of acyl azides,3 Wittig reactions of
amides,4 and the addition of Grignard reagents to isocyanates
or N,N-dialkyl formamides.5 Modern routes toward enamide
and enecarbamate synthesis include transition metal-catalyzed
cross coupling reactions,6 isomerization of allylamines,7
hydrogenation of ynamides,8 and hydroamination of al-
kynes.910 Despite the vast attention enamide synthesis has
received, the methods reported do not meet all ideal
requirements, such as operational simplicity, easily accessible
starting materials, configurational selectivity, mild and environ-
mentally benign reaction conditions, as well as being
economical.
Amino acids are readily available, inexpensive, and possess a
variety of side chain functionalities. Thus, operationally simple
methods offering direct conversion of these substrates into
synthetically useful enamines would be advantageous. Con-
sequently, several reports of methods following this design
have emerged including decarbonylation reactions of amino-
thioesters with Pd and Ni catalysts.11
Likewise, decarboxylation reactions of this manifold inspired
by Kochi’s decarboxylative elimination have been reported for
the synthesis of alkenes.12 Kochi’s pioneering work employed
lead tetraacetate as the oxidant to achieve decarboxylation
along with catalytic copper(II) acetate for further oxidation to
the alkene (Scheme 1A).13
Modern advancements of this method include Liu’s use of
stoichiometric hypervalent iodide under microwave condi-
tions14 as well as Glorius who employed the use of redox active
esters to achieve the decarboxylation under milder conditions
in a dual catalytic system.15 However, these methods were not
shown to be applicable to amino acids.
Recently, our group and the Ritter group simultaneously
reported a direct decarboxylative elimination that utilizes the
combination of photoredox catalysis and cobaloxime to
provide alkenes without the need for preactivation of the
carboxylic acid moiety or a stoichiometric oxidant.16 Although
highly efficient and elegant in their design, some drawbacks to
these methods include the complex reagent mixtures and the
production of hydrogen gas, which can be problematic upon
scale-up.
We sought to develop a complementary direct decarbox-
ylative elimination method that is mild, operationally simple,
and economical. In addition, we wanted to forge a method that
would be compatible with N-acyl amino acids of interest for
enamide synthesis.12e Herein, a new alternative protocol that
makes use of an acridinium photocatalyst, Cu(OAc)2, and blue
Received: January 17, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b00167
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The Journal of Organic Chemistry
Article
light to efficiently generate enamides from unactivated amino
acids is described (Scheme 1B).
RESULTS AND DISSCUSSION
■
Initial efforts toward developing a photoinduced decarbox-
ylative elimination of N-acyl amino acids were conducted with
an aspartic acid derivative and Cu(OAc)2 as the inexpensive
and readily available terminal oxidant (Table 1). The
Table 1. Optimization of Reaction Conditions
Figure 1. Acridinium photocatalyst.
absence of base, indicating additional base is not needed under
these conditions to generate the carboxylate (Table 1, entry 4).
A solvent screen revealed that the highest yields were
achieved with acetonitrile, toluene, and diethyl ether, but the
E/Z-isomer ratio was variable (Table 1, entries 5−10).
Specifically, acetonitrile and diethyl ether, provided greater
Z-selectivity than toluene. Along these lines, it is interesting to
note that, although poor yields were observed when the
reaction was performed in DME, only the Z-isomer was
observed (Table 1, entry 7).
Ultimately, the Cu(OAc)2 and photocatalyst loadings could
be decreased to 1.5 equiv and 2.5 mol %, respectively, without
any loss in yield (Table 1, entry 15). Since 2 equiv of
Cu(OAc)2 should be necessary as the terminal oxidant, the
high yield at lower loading suggests that either (A) CuOAc
may also be performing the oxidation to ultimately produce
Cu(0) or (B) CuOAc could be reoxidized to Cu(OAc)2 by the
photocatalyst. Further decreases in the Cu(OAc)2 and
photocatalyst resulted in lower yield (Table 1, entry 16). A
catalytic loading of Cu(OAc)2 (33 mol %) was able to effect
decarboxylative elimination through cycling the Cu(I) back to
Cu(II) under O2.20 However, the reaction with stoichiometric
Cu(II) is more operationally simple and is thus preferable.
With optimized conditions established, several control
experiments were conducted (Table 1). It was found that no
product was produced in the absence of Cu(OAc)2, and only
8% yield was achieved in the absence of photocatalyst (Table
1, entries 17 and 18). Additionally, the reaction could be
readily performed under aerobic conditions (Table 1, entry
19).
In addition to Cu(OAc)2, a variety of copper sources were
screened in the model reaction (Table 2). Surprisingly, it was
found that the E/Z-selectivity varied depending on the copper
salt. Of the copper salts examined, Cu(OAc)2, Cu(acac)2, and
Cu(thiophene-2-carboxylate)2 gave excellent yields. However,
Cu(acac)2 displayed inverse E/Z-selectivity to that seen with
Cu(OAc)2 and Cu(thiophene-2-carboxylate)2. Conversely, the
copper halide salts did not perform well, suggesting that a
counterion dependence exists for this transformation. Despite
the success of Cu(thiophene-2-carboxylate)2, Cu(OAc)2 was
chosen for further exploration of this reaction due to its lower
expense.
Monitoring the model reaction over time revealed the
reaction reaches completion after 14 h of irradiation (Figure
2).21 The E-isomer was found to predominate at the onset of
the reaction, but as the reaction progressed, the Z-isomer
prevails with a maximum selectivity of 34:66 E:Z being
observed after 14 h of irradiation. Allowing the reaction to be
irradiated further did not lead to significant changes in the
yield or isomer ratio.
isomer
c
solvent
(4 mL)
ratio
b
entry Cu(OAc)2(equiv) photocatalyst
yield
(E:Z)
d
d
d
1
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
2.7
0.75
PC3
(5 mol %)
PC1
(5 mol %)
PC2
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
PC3
(5 mol %)
MeCN
MeCN
MeCN
MeCN
THF
91%
71%
65%
90%
24%
19%
18%
91%
29%
87%
66%
83%
95%
93%
94%
72%
0%
52:48
59:41
49:51
36:64
46:54
37:63
0:100
45:55
38:62
38:62
88:12
36:64
42:58
40:60
34:66
35:65
-
2
3
4
5
6
DCM
7
DME
8
toluene
DMF
9
10
11
12
13
14
15
16
17
ether
MeOH
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
PC3
(5 mol %)
18
19
1.5
1.5
MeCN
MeCN
8%
85%
50:50
42:58
e
PC3
(2.5 mol %)
a
b
c
Reactions performed on 0.2 mmol scale. Isolated yields. Isomers
isolated separately. Reactions contain Na2CO3 (0.4 mmol).
d
e
Performed under air.
Fukuzumi family of acridinium photocatalysts17 was chosen
because of their favorable oxidation potential for amino
carboxylates (>+2.0 V and ∼+0.95 V vs SCE, respectively,
Figure 1).18
A quick screen of various photocatalysts from this family
showed that, when paired with light and cupric acetate, the 9-
mesityl-2,7-dimethyl-10-phenylacridinium (Mes-2,7-Me2-Acr-
Ph+BF4 ; PC3) photocatalyst provided the highest yield of
−
decarboxylative elimination (Table 1, entry 1).19 Additionally,
the reaction was found to produce comparable yield in the
An assortment of N-protected amino acids were next
subjected to the established reaction conditions (Table 3).
B
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Table 2. Copper Salt Screen
Table 3. Reaction Scope
b
d
Cu
yield
isomer ratio (E:Z)
Cu(OAc)2
Cu(acac)2
Cu(thiophene-2-carboxylate)2
Cu(CL)2
90%
98%
98%
36:64
68:32
38:62
Cu(Sulfate)2
Cu(OAc)
Cu(2-ethylhexanoate)
Cu(l)
Cu(Br)
Cu(phthalocyanide)2
Cu(OTf)2
83%
39:61
48:52
33:67
47:53
62:38
c
69%
12%
17%
13%
c
a
b
c
Reactions performed on 0.2 mmol scale. Isolated yields. Yield
d
determined by q1HNMR. Isomers isolated separately.
These reactions were found to perform best with the addition
of 4 Å molecular sieves to prevent hydrolysis.12e,22 Aspartic
acid derivatives produced excellent yields and displayed a small
preference for the Z-isomer (2a−d). Likewise, N-Boc
asparagine provided a high yield of the corresponding
enecarbamate and generated predominately the Z-isomer
while only trace amounts of the E-isomer were observed
(2e). Phenylalanine and its derivatives reacted smoothly, but
these substrates favored the E-isomer (2f−j). Conversely,
when a pendant pyridine was present, the Z-isomer
predominated while only trace amounts of the E-isomer were
observed (2k). The variation in the isomer ratios is suspected
to be a result of the hydrogen bonding ability of the amide
proton with a nearby heteroatom, providing a thermodynamic
preference for the Z-isomer. Other aliphatic amino acids with
various functionalities (2m−s), as well as a tertiary amino acid
(2p), were able to undergo elimination. In addition to
screening various amino acids, the influences of several
nitrogen protecting groups on alkene formation were evaluated
using norleucine as the reaction platform. This revealed that
Boc, Cbz, and Ac protecting groups all provide similar yields
a
b
Reactions were performed on 0.4 mmol scale. Isomer ratios of
c
mixed products were determined by HNMR. Isomers were isolated
d
separately. Major determined by NOESY (see the Supporting
e
−
Information). Reaction on 1 mmol scale with Mes-Acr-Ph+ BF4
photocatalyst.
and selectivities (2t−v). However, when unprotected phenyl-
alanine was subjected to the elimination conditions, no alkene
product was observed. To explore the scalability of this
reaction, the elimination of 1 mmol of 1g was performed
providing 40% yield of 2g. It is also worthwhile to note that
Figure 2. Reaction time.
C
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these reactions produced the alkenes as the sole product which
are easily separated from the remaining starting material,
copper, and photocatalyst with a silica plug.
To gain further insight into the observed isomer ratios,
several additional experiments were conducted (Scheme 2).
generating an alkyl Cu(III) species (path A) or be oxidized
further to a cation by Cu(II) (path B).13a,26 If the reaction
proceeds via path A, either β-hydride elimination or an E2-type
elimination of Cu would provide the alkene product.
Dissociation of the alkyl Cu(III) intermediate in path A
could also provide the cationic intermediate in path B. Kochi
has previously shown that carbon radicals are oxidized by Cu
in a near diffusion-controlled reaction that produces an
intermediate alkyl copper species.13,27 However, α-amino
radicals are much more easily oxidized to cations than the
radicals investigated by Kochi.28
Scheme 2. Isomerization Studies
CONCLUSION
■
In conclusion, a photoinduced oxidative decarboxylation has
been developed as a mild, inexpensive, and simple method for
the generation of enamides from amino acids. The use of an
acridinium photocatalyst replaces the need for toxic lead
tetraacetate and allows the reaction to proceed using visible
light as an economical and environmentally friendly energy
input. Moreover, this process offers a potentially attractive
route toward enamide and enecarbamate synthesis.
EXPERIMENTAL SECTION
■
General Methods. Purification was accomplished with column
chromatography using silica gel (60 Å porosity, 230 × 400 mesh,
standard grade) which was purchased from Sorbent Technologies
(catalog no. 30930M-25). TLC analysis was performed (fluorescence
quenching and potassium permanganate acid stain) with silica gel HL
TLC plates with UV254 purchased from Sorbent Technologies. Celite
We previously observed that the E/Z-isomer ratios were an
artifact of a photoisomerization16b similar to one described by
Weaver23 with iridium photosensitizers. Independently sub-
jecting pure E and Z isomers of 2a to the Mes-2,7-Me2-Acr-
Ph+BF4− photocatalyst revealed that both single configurations
isomerized to the same E/Z-ratio, which also coincides with
the ratio observed in the model reaction (Scheme 2A).
Importantly, when the model reaction was charged with
additional photocatalyst after the 14 h reaction time and
irradiated, no change in the isomer ratio was observed. In order
to evaluate the thermal influence on the isomerization, both
isomers were separately irradiated as well as heated at 50 °C in
the absence of photocatalyst and no isomerization was
observed. Taken together, it was concluded that a photo-
isomerization of the enamine products is occurring in the
elimination reactions and the observed isomer ratio is a result
of an equilibrium established under the reaction conditions.
Two general reaction pathways have been envisioned for the
elimination (Scheme 3). Initially, irradiation provides the
C212-500 (545 Filter Aid) was purchased from Fisher. H and 13C
1
NMR spectra were obtained on a Bruker ADVANCE 500 DRX
equipped with a QNP cryoprobe. These spectra were referenced to
residual protio solvent signals. HRMS data was obtained on an ESI
LC-TOF Micromass LCT (Waters). HRMS data was collected using
ESI mass spectrometry. Melting points were obtained with Digimelt
MPA 160 SRS (no. 111278) and samples were loaded with
borosilicate glass Kimble tube capillaries (no. 34505−9a). All
carboxylic acid starting materials are commercially available. Photo-
catalysts Mes-Acr-Ph and Mes-2,7-Me2-Mes-Acr-Ph were purchased
from Sigma-Aldrich. Photocatalyst Mes-Acr-Me was purchased from
TCI. All copper salts used are commercially available. Anhydrous
MeCN was purchased from Acros. Final decarboxylative elimination
reactions were run in borosilicate glass Biotage microwave vials
(Biotage no. 355631), with Biotage caps (Biotage no. 352298), and
were sealed with crimper (no. 356671). Kessil H150 Blue LED grow
lights provided 450 nm light. Reactions were run in the presence of 4
Å molecular sieves (3−5 mm beads) purchased from Alfa Aesar.
Amino acid N-Boc Protections. (tert-Butoxycarbonyl)leucine
(1o). was synthesized via boc-protection of leucine following literature
procedure and optained NMR specra matched previously reported
values.29 1H NMR (500 MHz, CD3CN): δ [5.51, broad s, 1H], [4.08,
q, 1H], [1.68, m, 2H], [1.53, m, 1H], [1.41, s, 9H], [0.92, d, 6H].
13C{1H} NMR (126 MHz, CD3CN): δ 51.9, 40.1, 27.5, 24.6, 22.1,
Scheme 3. Proposed Reaction Pathways
20.7.
2-((tert-Butoxycarbonyl)amino)-2-phenylbutanoic acid (1l). 2-
Amino-2-phenylbutanoic acid (900 mg, 5.02 mmol) and K2CO3 (714
mg, 5.17 mmol) were added to a 100 mL flask equipped with
magnetic stir bar. Then, H2O (18 mL) was added and the solution
stirred for 2 h. The flask was then charged with a solution of Boc2O
(1.73 mL, 7.5 mmol) in THF (20 mL), and the reaction mixture was
allowed to stir for ∼14 h. After, the reaction was refluxed for 2 days.
Post reflux, the THF was removed in vacuo. To the aqueous solution,
10% NaOH was added until pH 12. The aqueous layer was then
washed with DCM (∼10 mL, 2×) and acidified with citric acid until
pH 3. The resulting solution was extracted with EtOAc2 (∼20 mL,
3×), washed with H2O, dried with MgSO4, and condensed. The white
solid isolated was washed with hexanes and used without further
excited state photocatalyst which then oxidizes the carboxylate
by a single electron.17a,24 Facile radical decarboxylation
produces a stabilized α-amino alkyl radical.25 The photo-
catalyst can then be reoxidized by Cu(OAc)2 to return to the
ground state and complete the catalytic cycle. From this point,
the alkyl radical can either form a copper−carbon bond,
D
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purification. 1H NMR (500 MHz, CD3CN): δ [7.44, d, 2H], [7.36, t,
2H], [7.30, t, 1H], [6.18, broad s, 1H], [2.52−2.36, m, 2H], [1.37, s,
9H], [0.85, t, 3H]. 13C{1H} NMR (126 MHz, CD3CN): δ 129.2,
128.5, 127.0, 80.2, 66.3, 28.4, 28.2, 8.7.
[4.94 (d, J= 8.86 Hz, 1H)], [1.87 (m, 2H), 1.67 (m, 6H), Σ8H],
[1.47 (s, 9H)]. E isomer: δ [7.95 (s, 1H)], [7.61 (dd, J = 14.09, 11.76
Hz, 1H)], [5.30 (d, J = 14.08 Hz, 1H)], [5.13 (m, 1H)], [1.84 (m,
2H), 1.66 (m, 6H), Σ5H], [1.45 (s, 9H)]. 13C{1H} NMR (126 MHz,
CD3CN): Z isomer: δ 169.8, 152.8, 141.2, 95.1, 82.6, 77.6, 33.3, 28.2,
24.4. E isomer: δ 167.9, 153.1, 140.7, 99.3, 82.3, 77.1, 33.3, 28.2, 24.4.
IR (film): 3335, 2972, 2872, 1740, 1682, 1630, 1481, 1387, 1370,
1211, 1148, 1055, 1032, 974, 760 cm−1. HRMS (ESI-TOF) m/z:
Calc’d for C13H21NO4Na (M+Na)+ 278.1368; Found = 278.1374.
tert-Butyl (Z)-(3-amino-3-oxoprop-1-en-1-yl)carbamate (2e).
Isolated 58.6 mg of Z isomer exclusively as a white solid, mp =
General Decarboxylative Elimination Procedure for the
Synthesis of Compounds 2. A microwave vial with stir bar was
charged with amino acid (0.4 mmol, 1 equiv), Cu(OAc)2 (109 mg,
−
0.6 mmol, 1.5 equiv), and Mes-2,7-Me2-Acr-Ph+ BF4 (4.9 mg, 2.5
mol %). Anhydrous MeCN (8 mL) was added to the vial followed by
the addition of microwave oven activated 4 Å molecular sieves. The
vial was then sealed and sparged with argon for 5 min though the
septa using a 20 gage needle to bubble gas through the solvent and
another needle to vent the vial. After the flask was sparged, the cap
was wrapped with parafilm. The reaction was placed in front of a 450
nm 32 W blue LED light with no distance between the front of the
light source and the glass wall of the reaction vessel for 14 h. After
irradiation, the reaction mixture was filtered through a Celite plug
using EtOAc as the wash solvent (∼10 mL) to remove Cu salts. The
filtrate was concentrated and purified via flash column chromatog-
raphy on silica with 1:10−1:20 EtOAc:Hexanes. Note: Enamide
products were found to degrade in chloroform.
1
147−149 °C, in 79% yield. H NMR (500 MHz, CD3CN): δ [10.39
(s, 1H)], [7.06 (dd, J = 11.00, 8.76 Hz, 1H)], [6.10 (s, 1H), 5.57 (s,
1H), Σ2H], [4.99 (d, J = 8.79 Hz, 1H)], [1.45 (s, 9H)]. 13C{1H}
NMR (126 MHz, CD3CN): δ 171.8, 153.2, 138.6, 97.0, 82.0, 28.2. IR
(film): 3630, 3366, 3279, 3090, 2261, 1728, 1668, 1630, 1595, 1391,
1267, 1221, 1157, 1036, 843 cm−1. HRMS (ESI-TOF) m/z: Calc’d
for C8H14N2O3Na (M+Na)+ 209.0902; Found = 209.0898.
tert-Butyl (E/Z)-styrylcarbamate (2f). Isolated 76.2 mg as a mix of
E/Z isomers as a colorless oil in 87% yield, 89:11 E:Z. 1H NMR (500
MHz, CD3CN): δ [7.54 (s, Σ1H)], [7.38−7.11 (m, Σ5H)], [7.17
(dd, J = 15.0, 10.0 Hz, maj.) and 6.60 (dd, J = 11.38, 9.81 Hz, min.),
Σ1H], [6.01 (d, J = 14.69 Hz, maj.) and 5.55 (d, J = 9.78 Hz, min),
Σ1H], [1.46 (s, Σ9H)]. 13C{1H} NMR (126 MHz, CD3CN): Mix of
E/Z isomers δ 153.9, 138.0, 129.7, 129.5, 128.8, 127.3, 126.7, 125.9,
110.0, 80.8, 66.2, 28.4. IR (film): 3630, 3538, 3368, 3277, 3090, 2980,
2936, 2261, 2114, 1944, 1881, 1701, 1483, 1451, 1370, 1153, 1101,
1030 cm−1. HRMS (ESI-TOF) m/z: Calc’d for C13H17NO2Na (M
+Na)+ 242.1157; Found = 242.1156.
Cyclohexyl (E/Z)-3-((tert-butoxycarbonyl)amino)acrylate (2a).
Isolated 60.6 mg of Z isomer (major) as a white solid, mp = 58−
60 °C, and 39.8 mg of E isomer (minor) as a white solid, mp = 110−
1
112 °C, in 93% combined yield, 40:60 E:Z. H NMR (500 MHz,
CD3CN): Z isomer (major): δ [9.58 (s, 1H)], [7.22 (dd, J = 11.71,
8.86 Hz, 1H)], [4.96 (d J = 8.96, 1H)], [4.76 (m, 1H)], [1.84 (m,
2H), 1.71 (m, 2H), 1.53 (m, 1H), 1.38 (m, 4H), 1.26 (m, 1H) Σ10],
[1.47 (s, 9H)]. E Isomer (minor): δ [7.95 (s, 1H)], [7.64 (dd, J =
14.07, 11.78 Hz, 1H)], [5.31 (d, J = 14.05 Hz, 1H)], [4.72 (m, 1H),
1.83 (m, 2H) 1.69 (m, 2H), 1.53 (m, 1H), 1.36 (m, 4H), 1.27 (m,
1H), Σ10], [1.44 (s, 9H)]. 13C{1H} NMR (126 MHz, CD3CN): Z
isomer: δ 169.4, 152.8, 141.2, 95.1, 82.6, 73.1, 32.2, 28.2, 26.0, 24.4. E
isomer: δ 167.6, 153.3, 140.8, 99.3, 82.3, 72.6, 32.4, 28.2, 26.1, 24.5.
IR (film): 3335, 2978, 2936, 2861, 1740, 1680, 1632, 1483, 1454,
1389, 1368, 1207, 1148, 1038, 1017, 970, 860 cm−1. HRMS (ESI-
TOF) m/z: Calc’d for C14H23NO4Na (M+Na)+ 292.1525; Found =
292.1536.
tert-Butyl (E/Z)-(2-(naphthalen-2-yl)vinyl)carbamate (2g). Iso-
lated 85.2 mg of E isomer (major) as a tan solid, mp = 158−160 °C,
and 10.2 mg of Z isomer (minor) as a yellow oil in 88% combined
1
yield, 89:11 E:Z. H NMR (500 MHz, CD3CN): E isomer: δ [7.79
(m, 3H), 7.67 (m, 1H), 7.57 (dd, 1H), 7.42 (dddd, 2H), Σ7H], [7.33
(dd, J = 14.65, 10.68 Hz, 1H)], [6.17 (d, J = 14.70 Hz, 1H)], [1.48 (s,
9H)]. Z isomer: δ [7.85 (ddd, 3H), 7.80 (m, 1H), 7.49 (m, 2H), 7.42
(dd, 1H), Σ7H], [6.70 (dd, J = 11.39, 9.77 Hz, 1H)], [5.69 (d, J =
9.85, 1H)], [1.47 (s, 9H)]. 13C{1H} NMR (126 MHz, CD3CN): E
isomer: δ 135.7, 134.8, 133.0, 129.4, 129.0, 128.4, 127.2, 126.1, 124.6,
124.6, 124.0, 110.1, 28.4. Z isomer: δ 129.9, 129.1, 128.6, 128.4,
127.6, 127.2, 127.0, 126.7, 28.3. IR (film): 3630, 3538, 3368, 3279,
3090, 2980, 2261, 2114, 1709, 1695, 1655, 1628, 1508, 1370, 1157,
1030, 858, 847 cm−1. HRMS (ESI-TOF) m/z: Calc’d for
C17H19NO2Na (M+Na)+ 292.1313; Found 292.1300.
tert-Butyl (E/Z)-3-((tert-butoxycarbonyl)amino)acrylate (2b).
Isolated 55.4 mg of Z isomer (major) as a colorless oil and 34.6
mg of E isomer (minor) as a white solid, mp = 100−102 °C, in 93%
combined yield, 39:61 E:Z. 1H NMR (500 MHz, CD3CN): Z isomer:
δ [9.61 (s, 1H)], [7.17 (dd, J = 11.65, 8.87 Hz, 1H)], [4.89 (d, J =
8.87, 1H)], [1.47 (s, 9H)], [1.45 (s, 9H)]. E isomer (minor): δ [7.89
(s, 1H)], [7.56 (dd, J = 14.09, 11.75 Hz, 1H)], [5.25 (d, J = 14.05,
1H)], [1.45 (s, 9H)], [1.44 (s, 9H)]. 13C{1H} NMR (126 MHz,
CD3CN): Z isomer: δ 169.8, 152.9, 140.7, 96.3, 82.5, 81.2, 28.4, 28.2.
E isomer: δ 167.6, 153.1, 140.2, 100.6, 82.2, 80.0, 28.4, 28.2. IR
(film): 3337, 2978, 1740, 1678, 1632, 1481, 1381, 1368, 1238, 1219,
1146, 1055, 951, 872 cm−1. HRMS (ESI-TOF) m/z: Calc’d for
C12H21NO4Na (M+Na)+ 266.1368; Found = 266.1368.
Benzyl (E/Z)-3-((tert-butoxycarbonyl)amino)acrylate (2c). Iso-
lated 60.0 mg of Z isomer (major) as a colorless oil and 47.3 mg of E
isomer (minor) as a colorless oil in 97% combined yield, 44:56 E:Z.
1H NMR (500 MHz, CD3CN): Z isomer: δ [9.54 (s, 1H)], [7.38 (d,
4H), 7.34 (m, 1H), Σ5H], [7.28 (dd, J = 11.81, 8.84 Hz, 1H)], [5.15
(s, 2H)], [5.05 (d, J = 8.88 Hz, 1H)], [1.48 (s, 9H)]. E isomer: δ
[8.02 (s, 1H)], [7.70 (dd, J = 14.02, 11.87 Hz, 1H)], [7.37 (d, 4H),
7.33 (m, 1H), Σ5H], [5.40 (d, J = 14.05, 1H)], [5.13 (s, 2H)], [1.45
(s, 9H)]. 13C{1H} NMR (126 MHz, CD3CN): Z isomer: δ 169.7,
152.7, 142.0, 137.4, 129.5, 129.1, 94.1, 82.8, 66.4, 28.2. E isomer: δ
168.0, 153.0, 141.5, 137.9, 129.4, 128.9, 98.3, 82.4, 66.2, 28.2. IR
(film): 3341, 2980, 2936, 1740, 1686, 1632, 1485, 1456, 1391, 1368,
1196, 1148, 1057, 976, 860 cm−1. HRMS (ESI-TOF) m/z: Calc’d for
C15H19NO4Na (M+Na)+ 300.1212; Found = 300.1223.
tert-Butyl (E/Z)-(4-chlorostyryl)carbamate (2h). Isolated 73.7 mg
as a mix of E/Z isomers as an amorphous white solid in 73% yield,
89:11 E:Z. 1H NMR (500 MHz, CD3CN): δ [7.58 (m Σ1H)], [7.37−
7.23 (m, Σ4H)], [7.18 (dd, J = 14.71, 10.65 Hz, maj.) and 6.62 (dd, J
= 11.40, 9.83 Hz, min.) Σ1H], [5.98 (d, J = 14.70 Hz, maj.) and 5.51
(d, J = 9.83, min.), Σ1H], [1.45 (s, -Σ9H)]. 13C{1H} NMR (126
MHz, CD3CN): Mix of E/Z isomers δ 153.8, 137.0, 131.47, 129.4,
127.4, 126.6, 108.7, 81.0, 28.3. IR (film): 3621, 3538, 3368, 3090,
2359, 2340, 2261, 2116, 1944, 1883, 1719, 1701, 1657, 1508, 1489,
1370, 1192, 1159, 1091, 1030, 843 cm−1. HRMS (ESI-TOF) m/z:
Calc’d for C14H16N2O2Na (M+Na)+ 267.1109; Found 267.1123.
tert-Butyl (E/Z)-(2-chlorostyryl)carbamate (2i). Isolated 86.3 mg
as a mix of E/Z isomers as a white solid, mp = 109−111 °C, in 85%
1
yield, 90:10 E:Z. H NMR (500 MHz, CD3CN): δ [7.70 (s, Σ1H)],
[7.56 (d) and 7.47 (ddd) and 7.38 (dd) and 7.34 (dd) and 7.20 (m)
and 7.16 (td), Σ4H], [7.21 (m, maj.) and 6.77 (dd, J = 11.52, 9.67
Hz, min.), Σ1H], [6.40 (d, J = 14.65 Hz, maj.) and 5.64 (d, J = 9.69
Hz, min.), Σ1H], [1.49 (s, Σ9H)]. 13C{1H} NMR (126 MHz,
CD3CN): Mix of E/Z isomers δ 153.8, 135.8, 132.1, 130.8, 130.5,
130.4, 129.1, 128.1, 128.0, 126.3, 105.8, 81.1, 28.3.IR (film): 3304,
2978, 1701, 1653, 1508, 1466, 1368, 1316, 1273, 1246, 1155, 1055,
1034, 716 cm−1. HRMS (ESI-TOF) m/z: Calc’d for C13H16ClNO2Na
(M+Na)+ 276.0767; Found 276.0778.
Cyclopentyl (E/Z)-3-((tert-butoxycarbonyl)amino)acrylate (2d).
Isolated 52.4 mg of Z isomer (major) as a colorless oil and 35.6 mg of
E isomer (minor) as a white solid, mp = 109−112 °C, in 86%
combined yield, 41:59 E:Z. 1H NMR (500 MHz, CD3CN): Z isomer:
δ [9.58 (s, 1H)], [7.21 (dd, J = 11.68, 8.84 Hz, 1H)], [5.15 (m, 1H)],
tert-Butyl (E/Z)-(4-cyanostyryl)carbamate (2j). Isolated 58.6 mg
of E isomer (major) as an amorphous white solid and the 12.9 mg of
Z isomer (minor) as a colorless oil in 73% combined yield, 82:18 E:Z.
E
DOI: 10.1021/acs.joc.9b00167
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1H NMR (500 MHz, CD3CN): E isomer: δ [7.57 (d, 2H)], [7.46 (d,
116.7, 81.2, 30.3, 28.4, 23.9. IR (film): 3105, 2959, 2930, 2862, 2358,
2278, 2138, 2083, 1701, 1654, 1388, 1367, 1326, 1150 cm−1. HRMS
(ESI-TOF) m/z: Calc’d for C11H22NO2Na (M+Na)+ 223.1548;
Found = 223.1560.
2H)], [7.36 (dd, J = 14.65, 10.88 Hz, 1H)], [6.02 (d, J = 14.61 Hz,
1H)], [1.46 (s, 9H)]. Z isomer: δ [7.67 (d, 2H)], [7.44 (d, 2H)],
[6.73 (dd, J = 11.56, 9.85 Hz, 1H)], [5.55 (d, J = 9.83, 1H)], [1.46 (s,
9H). 13C{1H} NMR (126 MHz, CD3CN): E isomer: δ 153.6, 143.3,
133.3, 129.3, 126.3, 120.0, 109.1, 108.3, 81.3, 28.3. Z isomer: δ 153.9,
142.0, 133.4, 129.4, 127.1, 119.8, 109.9, 106.1, 81.5, 28.2. IR (film):
3323, 2978, 2226, 1728, 1715, 1653, 1603, 1479, 1395, 1368, 1260,
1236, 1155, 1055, 1024, 764, 750 cm−1. HRMS (ESI-TOF) m/z:
Calc’d for C14H16N2O2Na (M+Na)+ 267.1109; Found 267.1123.
tert-Butyl (Z)-(2-(pyridin-2-yl)vinyl)carbamate (2k). Isolated 37.6
mg of Z isomer exclusively as a yellow oil in 47% yield. 1H NMR (500
MHz, CD3CN): δ [11.1 (s, 1H)], [8.50 (ddd, 1H), 7.68 (td, 1H),
7.15 (d, 1H), 7.10 (ddd, 1H), Σ4H], [6.95 (t, J = 9.95 Hz, 1H)],
[5.53 (d, J = 9.14 Hz, 1H)], [1.49 (s, 9H)]. 13C{1H} NMR (126
MHz, CD3CN): δ 158.7, 153.8, 148.9, 137.8, 130.4, 123.9, 121.1,
104.1, 81.4, 28.4. IR (film): 2979, 1724, 1648, 1592, 1557, 1472,
1392, 1368, 1272, 1224, 1148, 1050, 1024, 863 cm−1. HRMS (ESI-
TOF) m/z: Calc’d for C12H16N2O2Na (M+Na)+ 243.1109; Found =
243.1113.
tert-Butyl (E/Z)-(2-methylbut-1-en-1-yl)carbamate (2q). Isolated
59.1 mg as a mix of E/Z isomers as a colorless oil in 80% yield, 65:37
1
E:Z. H NMR (500 MHz, CD3CN): δ [6.68 (s, Σ1H)], [6.15 (d,
maj.) and 6.10 (d, min.), Σ1H], [1.97 (m, Σ2H)], [1.63 (d, maj.) and
1.55 (d, min.), Σ3H], [1.43 (s, Σ9H)], [0.97 (t, maj.) and 0.94 (t,
min.), CH3CH2−, Σ3H] (confirmed E/Z assignments by NOESY, see
the Supporting Information for 2D spectra). 13C{1H} NMR (126
MHz, CD3CN): Mix of E/Z isomers δ 154.3, 79.9, 30.1, 28.4, 24.0,
19.7, 14.6, 13.3, 12.3. IR (film): 2978, 2937, 1701, 1497, 1368, 1153,
1051, 809 cm−1. HRMS (ESI-TOF) m/z: Calc’d for C10H19NO2Na
(M+Na)+ 208.1313; Found = 208.1340.
Benzyl (E/Z)-prop-1-en-1-ylcarbamate (2r). Isolated 48.9 mg as a
mix of E/Z isomers as a yellow oil in 64% yield, 53:47 E:Z. 1H NMR
(500 MHz, CD3CN): δ [7.47−7.26 (m, Σ5H), [6.40 (m, Σ1H)],
[5.11 (m, Σ2H)], [5.11 (m, maj.) and 4.67 (p, min.), Σ1H], [1.62
(dd, Σ3H)]. 13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z
isomers δ 155.0, 154.6, 137.9, 129.4, 128.9, 128.7, 125.4, 124.1, 106.2,
104.5, 167.3, 167.1, 14.9, 11.1. IR (film): 3312, 3065, 3032, 2857,
1703, 1682, 1518, 1454, 1294, 1234, 1116, 1028, 947 cm−1. HRMS
(ESI-TOF) m/z: Calc’d for C11H13NO2Na (M+Na)+ 214.0844;
Found = 214.0854.
tert-Butyl 3,4-dihydropyridine-1(2H)-carboxylate (2s). Isolated
39.9 mg as a colorless oil in 54% yield. 1H NMR (500 MHz,
CD3CN): δ [6.74 (dd, 1H)], [4.84 (d, 1H)], [3.50 (s, 2H)], [1.99
(m, 2H)], [1.77 (m, 2H)], [1.44 (s, 9H)]. 13C{1H} NMR (126 MHz,
CD3CN): δ 153.4, 152.9, 126.4, 125.9, 106.6, 106.0, 80.9, 43.3, 42.2,
28.4, 22.5. IR (film): 3458, 2976, 2934, 1697, 1651, 1406, 1368, 1302,
1254, 1234, 1167, 1115, 1072, 1053, 993, 878 cm−1. HRMS (ESI-
TOF) m/z: Calc’d for C10H16NO2 (M-H) 182.1181; Found =
182.1184.
tert-Butyl (E)-(1-phenylprop-1-en-1-yl)carbamate (2l). Isolated
35.5 mg as a mix of E/Z isomers as a colorless oil in 76% yield, 57:43
E:Z. 1H NMR (500 MHz, CD3CN): δ [7.41−7.24 (m, Σ5H)], [6.70
(broad d), Σ1H], [5.76 (broad s), Σ1H], [1.69 (dd, Σ3H)], [1.37
(broad d, Σ9H)]. 13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z
isomers δ 154.6, 129.6, 129.2, 129.0, 128.5, 128.2, 126.3, 79.8, 28.4,
13.8, 13.6. IR (film): 2978, 2931, 2262, 1698, 1654, 1492, 1446, 1366,
1242, 1164, 1164, 1089, 1043, 1031 cm−1. HRMS (ESI-TOF) m/z:
Calc’d for C14H19NO2Na (M+Na)+ 256.1313; Found = 256.1321.
tert-butyl (E/Z)-4-((tert-butoxycarbonyl)amino)but-3-enoate
(2m). Isolated 76.1 mg as a mix of E/Z isomer. Isolated as a colorless
1
oil in 74% yield, 63:37 E:Z. H NMR (500 MHz, CD3CN): δ [7.24
(s, Σ1H)], [6.43 (dd, J = 14.40, 10.51 Hz, Σ1H), [5.04 (dt, J = 14.08,
7.12 Hz, maj.) and 4.65 (q, J = 7.86 Hz, min.), Σ1H], [2.91 (dd) and
2.87 (dd), Σ2H], [1.43 (s) and 1.42 (s), Σ18H]. 13C{1H} NMR (126
MHz, CD3CN): Mix of E/Z isomers δ 172.3, 171.7, 153.9, 127.5,
126.0, 102.7, 100.6, 81.3, 80.9, 80.7, 80.4, 36.9, 33.4, 28.4, 28.2. IR
(film): 3337, 2978, 2934, 2359, 2261, 1726, 1713, 1608, 1508, 1456,
1393, 1368, 1290, 1244, 1147, 1069, 1045, 1018, 951, 866, 843 cm−1.
HRMS (ESI-TOF) m/z: Calc’d for C13H23NO4Na (M+Na)+
280.1525; Found = 280.1535.
tert-Butyl (E/Z)-pent-1-en-1-ylcarbamate (2t). Isolated 48.3 mg as
1
a mix of E/Z isomers as a colorless oil in 65% yield, 70:30 E:Z. H
NMR (500 MHz, CD3CN): δ [7.08 (s, maj.) and 6.96 (s, min.),
Σ1H], [6.34 (m, Σ1H)], [5.00 (dt, J = 14.34, 7.20 Hz, maj.) and 5.12
(q, J = 7.99 Hz, min.), Σ1H], [1.94 (m, Σ2H), *overlaps with
CH3CN*], [1.43 (s) and 1.41 (s), Σ9H], [1.35 (m, Σ2H)], [0.90 (t)
and 0.87 (t), Σ3H]. 13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z
isomers δ 154.0, 124.9, 123.2, 110.3, 109.1, 80.0, 32.5, 28.4, 24.0,
23.4, 13.8. IR (film): 3327, 2961, 2930, 2872, 1701, 1676, 1508, 1452,
1368, 1242, 1165, 1047, 1022, 951 cm−1. HRMS (ESI-TOF) m/z:
Calc’d for C10H19NO2Na (M+Na)+ 208.1313; Found = 208.1311.
(E/Z)-N-(Pent-1-en-1-yl)acetamide (2u). Isolated 31.7 mg as a mix
tert-Butyl (E/Z)-(3-phenylprop-1-en-1-yl)carbamate (2n). Iso-
lated 54.2 mg as a mix of E/Z isomers as a colorless oil in 58%
1
yield, 66:34 E:Z. H NMR (500 MHz, CD3CN): δ [7.33−7.14 (m,
Σ5H)], [6.43 (dd, J = 14.01, 10.93 Hz, Σ1H], [5.16 (dt, J = 14.51,
7.25 Hz, maj.) and 4.70 (q, J = 8.16 Hz, min.), Σ1H], [3.34 (d) and
3.29 (d), Σ2H], [1.45 (s) and 1.42 (s), Σ9H]. 13C{1H} NMR (126
MHz, CD3CN): Mix of E/Z isomers δ 153.9, 142.4, 141.9, 129.4,
129.3, 129.2, 129.0, 126.8, 125.9, 123.9, 109.4, 107.6, 80.2, 36.5, 32.2,
28.4. IR (film): 3621, 3530, 3366, 3090, 2261, 1944, 1881, 1719,
1676, 1495, 1452, 1368, 1236, 1163, 1042 cm−1. HRMS (ESI-TOF)
m/z: Calc’d for C14H19NO2Na (M+Na)+ 256.1313; Found =
256.1303.
1
of E/Z isomers as a colorless oil in 62% yield, 76:24 E:Z. H NMR
(500 MHz, CD3CN): δ [8.07 (s) and 7.89 (s), Σ1H], [6.62 (m, maj.)
and 6.58 (m, min.), Σ1H], [5.15 (dt, J = 14.43, 7.23 Hz, maj.) and
4.64 (dt, J = 9.15, 7.64 Hz, min), Σ1H], [2.05−1.96 (m, Σ2H)], [1.96
(s) and 1.88 (s), Σ3H], [1.37 (m, Σ2H)], [0.92 (t) and 0.87 (t),
Σ3H]. 13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z isomers δ
168.5, 167.9, 123.9, 122.0, 112.4, 111.2, 32.5, 28.4, 23.8, 23.4, 22.9,
13.8. IR (film): 3279, 3200, 3063, 2959, 2928, 2872, 1657, 1528,
1460, 1437, 1371, 1302, 1282, 1172, 1038, 955 cm−1. HRMS (ESI-
TOF) m/z: Calc’d for C7H13NONa (M+Na)+ 150.0895; Found =
150.0888.
tert-Butyl (E/Z)-(3-methylbut-1-en-1-yl)carbamate (2o). Isolated
48.4 mg as a mix of E/Z isomers as a white solid, mp = 76−78 °C, in
1
65% yield, 75:25 E:Z. H NMR (500 MHz, CD3CN): δ [7.00 (s,
Σ1H)], [6.32 (dd, J = 14.09, 10.68 Hz, maj.) and 6.21 (t, J = 10.05
Hz, min.), Σ1H], [5.00 (dd, J = 14.32, 7.09 Hz, maj.) and 4.38 (t, J =
9.34 Hz, min.), Σ1H], [2.49 (m, min.) and 2.25 (m, maj.), Σ1H],
[1.44 (s) and 1.42 (s), Σ9H], [0.96 (d, maj.) and 0.93 (d, min.),
Σ6H]. 13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z isomers δ
154.1, 122.8, 117.8, 80.1, 29.7, 28.5, 23.4. IR (film): 3621, 3530, 3366,
3279, 3090, 2261, 1944, 1881, 1719, 1676, 1494, 1452, 1368, 1236,
1163, 1042 cm−1. HRMS (ESI-TOF) m/z: Calc’d for C10H19NO2Na
(M+Na)+ 208.1313; Found = 208.1323.
Benzyl (E/Z)-pent-1-en-1-ylcarbamate (2v). Isolated 65.6 mg as a
1
mix of E/Z isomers as a colorless oil in 75% yield, 74:26 E:Z. H
NMR (500 MHz, CD3CN): δ [7.45−7.29 (m, Σ5H)], [6.38 (m,
Σ1H)], [5.10 (m, Σ2H)], [5.09 (m, maj.) and 4.60 (q, J = 7.99 Hz,
min), Σ1H], [1.96 (m, Σ2H)], [1.35 (m, Σ2H)], [0.89 (t) and 0.87
(t), Σ3H]. 13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z isomers
δ 155.0, 154.6, 137.9, 129.4, 128.9, 128.7, 124.8, 123.1, 111.5, 110.4,
67.1, 32.4, 28.4, 23.9, 23.4, 13.8. IR (film): 2963, 2123, 1714, 1679,
1521, 1237, 1051, 831 cm−1. HRMS (ESI-TOF) m/z: Calc’d for
C13H17NO2Na (M+Na)+ 242.1157; Found = 242.1149.
tert-Butyl (E)-methyl(3-methylbut-1-en-1-yl)carbamate (2p). Iso-
1
lated 23.6 mg as a colorless oil in 30% yield. H NMR (500 MHz,
CD3CN): δ [6.87 (broad s, Σ1H)], [4.82 (broad s, Σ1H)], [2.92 (s,
Σ3H)], [2.33 (broad s, Σ1H)], [1.46 (s, Σ9H)], [0.99 (d, Σ6H)].
13C{1H} NMR (126 MHz, CD3CN): Mix of E/Z isomers δ 127.3,
F
DOI: 10.1021/acs.joc.9b00167
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Secondary and Tertiary Amides to Amines. Adv. Synth. Catal. 2013,
355, 47−52.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.9b00167.
■
S
(8) (a) DeKorver, K. A.; Li, H.; Lohse, A. G.; Hayashi, R.; Lu, Z.;
Zhang, Y.; Hsung, P. R. Ynamides: A Modern Functional Group for
the New Millennium. Chem. Rev. 2010, 110, 5064−5106. (b) Lu, T.;
Lu, Z.; Zhang, Y.; Hsung, R. P. Allenamides: A Powerful and Versatile
Building Block in Organic Synthesis. Chem. Rev. 2013, 113, 4862.
(9) (a) Pohlki, F.; Doye, S. The Catalytic Hydroamination of
Alkynes. Chem. Soc. Rev. 2003, 32, 104−114. (b) Alonso, F.;
Beletskaya, I. P.; Yus, M. Transition-Metal-Catalyzed Addition of
Heteroatom−Hydrogen Bonds to Alkynes. Chem. Rev. 2004, 104,
3079−3160. (c) Severin, R.; Doye, S. The Catalytic Hydroamination
of Alkynes. Chem. Soc. Rev. 2007, 36, 1407−1420. (d) Muller, T. E.;
Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Hydroamination:
Direct Addition of Amines to Alkenes and Alkynes. Chem. Rev. 2008,
108, 3795−3892.
1H, 13C, and NOESY NMR spectra and photo of
decarboxylative elimination reaction setup (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: tunge@ku.edu.
ORCID
Jon A. Tunge: 0000-0002-5849-0888
Notes
The authors declare no competing financial interest.
■
(10) (a) Evano, G.; Gaumont, A. C.; Alayrac, C.; Wrona, I. E.;
Giguere, J. R.; Delacroix, O.; Bayle, A.; Jouvin, K.; Theunissen, C.;
Gatignol, J.; Silvanus, A. C. Metal-Catalyzed Synthesis of Hetero-
Substituted Alkenes and Alkynes. Tetrahedron 2014, 70, 1529−1616.
(b) Matsubara, R.; Kobayashi, S. Enamides and Enecarbamates as
Nucleophiles in Stereoselective C−C and C−N Bond-Forming
Reactions. Acc. Chem. Res. 2008, 41, 292−301.
ACKNOWLEDGMENTS
■
This work was supported by the National Science Foundation
(CHE-1800147) and the Kansas Bioscience Authority Rising
Star program. Support for the NMR instrumentation was
provided by NSF Academic Research Infrastructure Grant No.
9512331, NIH Shared Instrumentation Grant No.
S10RR024664, and NSF Major Research Instrumentation
Grant No. 0320648.
(11) (a) Garcia-Reynaga, P.; Carrillo, A. K.; VanNieuwenhze, M. S.
Decarbonylative Approach to the Synthesis of Enamides from Amino
Acids: Stereoselective Synthesis of the (Z)-Aminovinyl-d-Cysteine
Unit of Mersacidin. Org. Lett. 2012, 14, 1030−1033. (b) Min, K. G.;
́
Hernandez, D.; Lindhardt, A. T.; Skrydstrup, T. Enamides Accessed
from Aminothioesters via a Pd(0)-Catalyzed Decarbonylative/β-
Hydride Elimination Sequence. Org. Lett. 2010, 12, 4716−4719.
(12) (a) Sheldon, R. A.; Kochi, J. K. Oxidative Decarboxylation of
Acid by Lead Tetraacetate. Org. React. 1972, 19, 279. (b) Bacha, J. D.;
Kochi, J. K. Alkenes from Acids by Oxidative Decarboxylation.
Tetrahedron 1968, 24, 2215−2226. (c) Krompiec, S.; Krompiec, M.;
Penczek, R.; Ignasiak, H. Double Bond Migration in N-Allylic Systems
Catalyzed by Transition Metal Complexes. Coord. Chem. Rev. 2008,
252, 1819−1841. (d) Larsen, C. R.; Grotjahn, B. Stereoselective
Alkene Isomerization over One Position. J. Am. Chem. Soc. 2012, 134,
10357−10360. (e) Compatability issues with N-acyl amino acids:
Needles, H. L.; Ivanetich, K. Decarboxylation of N-Acetylamino-Acids
with Lead Tetra-Acetate in N’Ndimethylformamide. Chem. Ind. 1967,
581.
REFERENCES
■
(1) (a) Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J.
Late Transition Metal-Catalyzed Hydroamination and Hydroamida-
tion. Chem. Rev. 2015, 115, 2596−2697. (b) Carbery, D. R.
Enamides: Valuable Organic Substrates. Org. Biomol. Chem. 2008, 6,
3455−3460.
(2) Layer, W. R. The Chemistry of Imines. Chem. Rev. 1963, 63,
489−510.
(3) (a) Brettle, R.; Mosedale, A. J. Synthesis of Enamides. J. Chem.
Soc., Perkin Trans. 1 1988, 2185. (b) Kuramochi, K.; Watanabe, H.;
Kitahara, T. Synthetic Study on Oximidines: A Concise Synthesis of
(Z)-Enamides. Synlett. 2000, 397.
(4) (a) Flitsch, W.; Schindler, S. R. Alkenylation of Imides and
Activated Amides. Synthesis 1975, 1975, 685. (b) Murphy, J. P.
Brennan The Wittig olefination reaction with carbonyl compounds
other than aldehydes and ketones. Chem. Soc. Rev. 1988, 17, 1.
(5) Hansson, C.; Wickberg, B. Preparation of enamines by addition
of Grignard reagents to N,N-dialkylformamides. J. Org. Chem. 1973,
38, 3074−3076.
(6) (a) Venkat, C. R.; Urgaonkar, S.; Verkade, J. G. A Highly
Effective Catalyst System for the Pd-Catalyzed Amination of Vinyl
Bromides and Chlorides. Org. Lett. 2005, 7, 4427. (b) Pan, X.; Cai,
Q.; Ma, D. CuI/N,N-Dimethylglycine-Catalyzed Coupling of Vinyl
Halides with Amides or Carbamates. Org. Lett. 2004, 6, 1809.
(7) (a) Krompiec, S.; Krompiec, M.; Penczek, R.; Ignasiak, H.
Double Bond Migration in N-Allylic Systems Catalyzed by Transition
Metal Complexes. Coord. Chem. Rev. 2008, 252, 1819−1841.
(b) Larsen, C. R.; Grotjahn, D. B. Stereoselective Alkene Isomer-
ization over One Position. J. Am. Chem. Soc. 2012, 134, 10357−
10360. (c) Trost, B. M.; Cregg, J.; Quach, N. Isomerization of N-Allyl
Amides To Form Geometrically Defined Di-, Tri-, and Tetrasub-
stituted Enamides. J. Am. Chem. Soc. 2017, 139, 5133−5139.
(d) Krompiec, S.; Pigulla, M.; Kuznik, N.; Krompiec, M.;
Marciniec, B.; Chadyniak, D.; Kasperczyk, J. J. Highly Selective
Isomerization of N-Allylamides Catalyzed by Ruthenium and
Rhodium Complexes. J. Mol. Catal. A: Chem. 2005, 225, 91−101.
(e) Stille, J. K.; Becker, Y. Isomerization of N-Allylamides and -Imides
to Aliphatic Enamides by Iron, Rhodium, and Ruthenium Complexes.
J. Org. Chem. 1980, 45, 2139−2145. (f) Reeves, J. T.; Tan, Z.;
Marsini, M. A.; Han, S. Z.; Xu, Y.; Reeves, D. C.; Lee, H.; Lu, B. Z.;
Senanayake, C. H. A Practical Procedure for Reduction of Primary,
(13) (a) Kochi, J. K. Mechanism of Organic Oxidation and
Reduction by Metal Complexes. Science 1967, 155, 415−424.
(b) Kochi, J. K.; Bemis, A.; Jenkins, C. L. Mechanism of electron
transfer oxidation of alkyl radicals by copper(II) complexes. J. Am.
Chem. Soc. 1968, 90, 4616−4625.
(14) Wu, S.-W.; Lui, J.-L.; Liu, F. Metal-Free Microwave-Assisted
Decarboxylative Elimination for the Synthesis of Olefins. Org. Lett.
2016, 18, 1−3.
(15) Tlahuext-Aca, A.; Candish, L.; Garza-Sanchez, R. A.; Glorius, F.
Decarboxylative Olefination of Activated Aliphatic Acids Enabled by
Dual Organophotoredox/Copper Catalysis. ACS Catal. 2018, 8,
1715−17191719.
(16) Direct decarboxylative elimination methods: (a) Sun, X.; Chen,
J.; Ritter, T. Catalytic dehydrogenative decarboxyolefination of
carboxylic acids. Nat. Chem. 2018, 10, 1229−1233. (b) Cartwright,
K. C.; Tunge, J. A. Decarboxylative Elimination of N-Acyl Amino
Acids via Photoredox/Cobalt Dual Catalysis. ACS Catal. 2018, 8,
11801−11806.
(17) (a) Fukuzumi, S.; Kotani, H.; Ohkubo, K.; Ogo, S.; Tkachenko,
N. V.; Lemmetyinen, H. Electron-Transfer State of 9-Mesityl-10-
methylacridinium Ion with a Much Longer Lifetime and Higher
Energy Than That of the Natural Photosynthetic Reaction Center. J.
Am. Chem. Soc. 2004, 126, 1600−1601. For a review on
organophotocatalysts: (b) Romero, N. A.; Nicewicz, D. A. Organic
Photoredox Catalysis. Chem. Rev. 2016, 116, 10075−10166.
Potentials reported for the acridinium photocatalyst are versus SCE
in acetonitrile: (c) Romero, N. A.; Margrey, K. A.; Tay, N. E.;
G
DOI: 10.1021/acs.joc.9b00167
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Nicewicz, D. A. Site-selective arene C-H amination via photoredox
catalysis. Science 2015, 349, 1326−1330.
(18) Boc-proline-carboxylate oxidation potential: Zuo, Z.;
MacMillian, D. W. C. Decarboxylative Arylation of α-Amino Acids
via Photoredox Catalysis: A One-Step Conversion of Biomass to Drug
Pharmacophore. J. Am. Chem. Soc. 2014, 136, 5257−5260.
(19) First reported in anti-Markovnikov hydrofluorination of
styrenes: Wilger, D. J.; Grandjean, J. W.; Lammert, T. R.; Nicewicz,
D. A. The direct anti-Markovnikov addition of mineral acids to
styrenes. Nat. Chem. 2014, 6, 720.
(20) Experiment with 1a (0.2 mmol), Cu(OAc)2 (0.33 equiv),
−
Mes-27-Me2-Acr-Me+ BF2 (2.5 mol%) in MeCN. Reaction was
irradiated for 1−2 h and then sparged with O2 for 30 min. The
irradiation and regeneration was repeated 3 times giving 2a in 71%
yield, 69:31 E:Z.
(21) Reactions were performed on 0.2 mmol scale with Cu(OAc)2
−
(1.5 equiv.) and Mes-2,7-Me2-Acr-Me+ BF4 (2.5 mol%) in MeCN.
(22) Kobayashi, S.; Gustafsson, T.; Shimizu, Y.; Kiyohara, H.;
Matsubara, R. Enecarbamates as Imine Surrogates: Nucleophilic
Addition of 1,3-Dicarbonyl Compounds to Enecarbamates. Org. Lett.
2006, 8, 4923−4925.
(23) (a) Singh, K.; Staig, S. J.; Weaver, J. D. Facile Synthesis of Z-
Alkenes via Uphill Catalysis. J. Am. Chem. Soc. 2014, 136, 5275−5278.
(b) Singh, A.; Fennell, C. J.; Weaver, J. D. Photocatalyst Size Controls
Electron and Energy Transfer: Selectable E/Z Isomer Synthesis via
C−F Alkenylation. Chem. Sci. 2016, 7, 6796−6802. (c) Metternich, J.
D.; Gilmour, R. Photocatalytic E → Z Isomerization of Alkenes.
Synlett 2016, 27, 2541−2552.
(24) (a) Ohkubo, K.; Mizushime, K.; Iwata, R.; Souma, K.; Suzuki,
S.; Fukuzumi, S. Simultaneous Production of p-Tolualdehyde and
Hydrogen Peroxide in Photocatalytic Oxygenation of p-Xylene and
Reduction of Oxygen with 9-mesityl-10-methylacridinium Ion
Derivatives. Chem. Commun. 2010, 46, 601−603. (b) Nguyen, T.
M.; Manohar, N.; Nicewicz, D. A. anti-Markovnikov Hydroamination
of Alkenes Catalyzed by a Two-Component Organic Photoredox
System: Direct Access to Phenethylamine Derivatives. Angew. Chem.,
Int. Ed. 2014, 53, 6198−6201. (c) Review on visible-light induced
decarboxylation: Xuan, J.; Zhang, Z.-G.; Xiao, W.-J. Merging
Photoredox and Nickel Catalysis: The Direct Synthesis of Ketones
by the Decarboxylative Arylation of α-Oxo Acids. Angew. Chem., Int.
Ed. 2015, 54, 7929−7933.
(25) Zuo, Z.-W.; MacMillan, D. W. C. Decarboxylative Arylation of
α-Amino Acids via Photoredox Catalysis: A One-Step Conversion of
Biomass to Drug Pharmacophore. J. Am. Chem. Soc. 2014, 136, 5257−
5260.
(26) Kochi, J. K.; Subramanian, R. Kinetics of Electron-Transfer
Oxidation of Alkyl Radicals by Copper(II) Complexes. J. Am. Chem.
Soc. 1965, 87, 4855−4866.
(27) De La Mare, H. E.; Kochi, J. K.; Rust, F. F. On a Transannular
Photodesmotic Transition. J. Am. Chem. Soc. 1961, 83, 2013−2015.
(28) Wayner, D. D. W.; McPhee, D. J.; Griller, D. Oxidation and
reduction potentials of transient free radicals. J. Am. Chem. Soc. 1988,
110, 132−137.
(29) Li, G.; Qu, J. Enantioselective Friedel−Crafts Reactions
between Phenols and N-Tosylaldimines Catalyzed by a Leucine-
Derived Bifunctional Catalyst. Chem. Commun. 2012, 48, 5518−5520.
H
DOI: 10.1021/acs.joc.9b00167
J. Org. Chem. XXXX, XXX, XXX−XXX