Synthesis of N-aryl-2-allylpyrrolidines via palladium-catalyzed carboamination reactions of γ-(N-arylamino)alkenes with vinyl bromides

Article abstract of DOI:10.1002/adsc.200505172

A palladium-catalyzed carboamination reaction of γ-N-arylamino alkenes with vinyl bromides that affords N-aryl-2-allyl pyrrolidines is described. These reactions proceed with high diastereoselectivity for the formation of trans-2,3- and cis-2,5-disubstituted pyrrolidines. Conditions for a tandem N-arylation/ carboamination sequence that leads to the formation of an N-aryl-2-allyl pyrrolidine or indoline via the coupling of a primary γ-amino alkene, an aryl bromide, and a vinyl bromide are also reported. The mechanism of the carboamination reactions and the origin of unexpected products that formally derive from rearrangement of the vinyl bromide are discussed.

Full text of DOI:10.1002/adsc.200505172

FULL PAPERS
DOI: 10.1002/adsc.200505172
Synthesis of N-Aryl-2-allylpyrrolidines via Palladium-Catalyzed
Carboamination Reactions of g-(N-Arylamino)alkenes with Vinyl
Bromides
Joshua E. Ney, Michael B. Hay, Qifei Yang, John P. Wolfe*
University of Michigan, Department of Chemistry, 930 N. University Ave, Ann Arbor, Michigan 48109-1055, USA
Fax: (þ1)-734-763-2307, e-mail: jpwolfe@umich.edu
Received: April 22, 2005; Accepted: July 16, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: A palladium-catalyzed carboamination re- mide, and a vinyl bromide are also reported. The
action of g-N-arylamino alkenes with vinyl bromides mechanism of the carboamination reactions and the
that affords N-aryl-2-allyl pyrrolidines is described. origin of unexpected products that formally derive
These reactions proceed with high diastereoselectivity from rearrangement of the vinyl bromide are dis-
for the formation of trans-2,3- and cis-2,5-disubstitut- cussed.
ed pyrrolidines. Conditions for a tandem N-arylation/
carboamination sequence that leads to the formation
of an N-aryl-2-allyl pyrrolidine or indoline via the Keywords: heterocycles; homogeneous catalysis; pal-
coupling of a primary g-amino alkene, an aryl bro- ladium; pyrrolidines; tandem reactions; vinyl halides
Introduction
The pyrrolidine ring is a common motif found in a num-
ber of biologically active small molecules.[1] As a result, a
great deal of effort has been devoted to the development
of synthetic methods for the construction of this core.[2]
Some of the most interesting and useful of these meth-
ods have utilized palladium catalysis to effect ring clo-
sure of a b- or g-aminoalkene or -alkyne with concomi-
tant carbon-carbon bond formation.[3–5] For example,
Larock and Weinreb have described the synthesis of 2-
vinylpyrrolidines via the coupling and cyclization of b-
N-tosylaminoalkenes with vinyl halides.[3] Tamaru has
also described a palladium-catalyzed synthesis of pyrro- afford N-aryl-2-allylpyrrolidines. However, initial at-
lidines, which employs a Wacker-type carbonylative cy- tempts to couple 1 with b-bromostyrene using condi-
clization to afford products bearing ester substituents.[4] tions identical to those employed in the analogous reac-
We have recently reported a new method for the ster- tions of aryl bromides resulted in low yields of the de-
eoselective synthesis of N-aryl-2-benzylpyrrolidines via sired pyrrolidine 3b due to competing N-vinylation of
the carboamination of g-N-arylaminoalkenes with aryl the substrate [Eq. (2)]. We reasoned that this problem
bromides in the presence of a palladium(0) catalyst and could be circumvented by employing a palladium/phos-
a base [Eq. (1)].[6–9] These reactions proceed in good phine catalyst system that would disfavor carbon-nitro-
yieldsandareeffectivewithavarietyofarylbromidecou- gen bond-forming reductive elimination,[10] as the side
pling partners. High diastereoselectivity for the forma- product presumably results from relatively facile reduc-
tion of trans-2,3- and cis-2,5-disubstituted pyrrolidines is tive elimination of an intermediate vinylpalladium ami-
observed for most substrate combinations (dr>20:1).
do complex.[11] Herein we report the use of a Pd2(dba)3/
A significant extension of this methodology would in- tri-2-furylphosphine catalyst system to effect the dia-
volve the use of vinyl bromides as coupling partners to stereoselective synthesis of N-aryl-2-allylpyrrolidines
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Synthesis of N-Aryl-2-allylpyrrolidines
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Table 2. Palladium-catalyzed synthesis of N-phenyl-2-allyl-
via the palladium-catalyzed carboamination of g-N-aryl-
aminoalkenes with vinyl bromides.
pyrroldines.[a]
Results and Discussion
Catalyst Optimization
In our preliminary experiments we elected to optimize
the palladium-catalyzed reaction of amine 1 with vinyl
bromide 2a, which was easily prepared in isomerically
pure form [Eq. (3), Table 1]. Unfortunately, the
Pd2(dba)3/dppb catalyst system, which provided high
yields for the synthesis of 2-benzylpyrrolidines from g-
N-arylamino-olefins and aryl bromides, afforded an in-
separable mixture of the desired product 3a, regioiso-
mer 4a, and unexpected isomer 5a (Table 1, entry 1). Cu-
riously, N-vinylation was less problematic with this sub-
strate combination than in the reaction of 1 with b-bro-
mostyrene described above. After some optimization
we found that 3a was obtained in 81% isolated yield
when the reaction was conducted with tri-2-furylphos-
phine as the ligand (Table 1, entry 4). These conditions
provided good selectivity for the formation of 3a (versus
4a and 5a), and did not afford detectable amounts of N-
vinylated side products.
Scope and Diastereoselectivity
With optimized conditions in hand, we proceeded to ex-
amine the reaction of 1 with a variety of vinyl bromides.
Table 1. Catalyst optimization.[a]
[a]
Reaction conditions: amine 1 (1.0 equiv), vinyl bromide 2
(1.1–2.0 equivs.), NaO-t-Bu (1.2 equivs.), Pd2(dba)3
(1 mol %), P(2-furyl)3 (4 mol %), toluene (0.25 M), 60–
1108C.
[b]
Product ratios refer to the isolated material, as judged by
1H NMR analysis. Product ratios and yields refer to the
average of two or more experiments.
[c]
This material contained ~5% of 5a as an inseparable im-
purity.
[d]
This material contained ~10% of 5d as an inseparable im-
purity.
[a]
Reaction conditions: amine 1 (1.0 equiv.), vinyl bromide 2a
As shown in Table 2, N-aryl-2-allylpyrrolidines 3a–h
were obtained in good to excellent yields with 13:1 to
>20:1 selectivity for 3 versus regioisomer 4. Isomers
5, which derive from formal rearrangement of the vinyl
bromide, were observed in only two reactions, both of
which employed E-substituted vinyl bromides (Table 2,
entries 1 and 4). Notably, an analogous rearranged prod-
uct was not observed in the reaction of the correspond-
(1.1 equivs.), NaO-t-Bu (1.2 equivs.), Pd2(dba)3 (1 mol
%), Ligand (2 mol % of bidentate ligand or 4 mol % of
monodentate ligand), toluene (0.25 M), 608C.
Ratios determined by GC analysis of crude reaction mix-
tures.
Isolated yields refer to the total yield of an inseparable
mixture of products 3a, 4a, and 5a.
This reaction was conducted at 1108C.
[b]
[c]
[d]
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Joshua E. Ney et al.
Table 3. Stereoselective synthesis of disubstituted N-aryl-2-allylpyrroldines.[a]
FULL PAPERS
ing Z-substituted vinyl bromide 2e
(Table 2, entry 5). Side products re-
sulting from N-vinylation or Heck
vinylation of the alkene were gener-
ally not observed in reactions cata-
lyzed by Pd2(dba)3/tri-2-furylphos-
phine, even with the previously
problematic b-bromostyrene (2b).
All products were obtained as a sin-
gle olefin stereoisomer,[12] and reac-
tions of Z-substituted vinyl bro-
mides afforded the desired pyrroli-
dine products with retention of the
vinyl bromide geometry (Table 2,
entries 3 and 5). However, although
the reaction of 1 with (2-bromovi-
nyl)trimethylsilane (2 h) produced
a single pyrrolidine product (Ta-
ble 2, entry 8), the analogous reac-
tion of 1 with the isomeric (1-bro-
movinyl)trimethylsilane (2i) af-
forded an inseparable 7:4 mixture
of pyrrolidines 3i and 3h (Table 2,
entry 9).
To probe the diastereoselectivity
of these reactions, several g-N-aryl-
aminoalkenes with substituents at
the 1- or 3-position were prepared
and subjected to our optimized re-
action conditions. As shown in Ta-
ble 3, reactions of amines 6–9 with
various vinyl bromides afforded
2,3- and 2,5-disubstituted pyrroli-
dines in good yields with good to ex-
cellent levels of diastereoselectivity
(dr 7:1 to>20:1). These reactions
were effective with substrates bear-
ing both electron-rich (Table 3, en-
tries 1 and 2 and 4–8) and elec-
tron-poor (Table 3, entry 3) N-aryl
substituents. The observed prefer-
ence for the formation of trans-
2,3- and cis-2,5-disubstituted pyrro-
lidines is analogous to that ob-
served in the previously described
reactions of related substrates with
[a]
Reaction conditions: amine (1.0 equiv.), vinyl bromide 2 (1.4–2.0 equivs.), NaO-t-
Bu (1.2 equivs.), Pd2(dba)3 (1 mol %), P(2-furyl)3 (4 mol %), toluene (0.25 M),
1108C.
[b]
[c]
Product ratios refer to the isolated material, as judged by 1H NMR analysis. Prod-
uct ratios and yields refer to the average of two or more experiments.
Dppe (2 mol %) used as ligand in this reaction.
PMP¼p-methoxyphenyl.
aryl bromides, and is complementary to the selectivity good yield but with somewhat lower (dr 7:1) diastereo-
for the formation of cis-2,3-disubstituted N-tosylpyrroli- selectivity (Table 3, entry 1). The reactions of 3-substi-
dines described by Larock and Weinreb.[3]
tuted amine 9 provided the highest selectivity (dr>
The size of the vinyl bromide had a notable effect on 20:1) when the relatively small b-bromostyrene (2b)
the stereoselectivity of the carboamination reactions. was employed (Table 3, entry 8). Use of a-bromostyrene
In reactions of 1-substituted amines 6–8 the highest se- (2f) or tetrasubstituted vinyl bromide 2g afforded prod-
lectivities (dr>20:1) were observed in cases where the ucts with lower (dr 10:1) diastereoselectivity (Table 3,
vinyl bromide and/or the substituent on the amine entries 6 and 7).
were small (Table 3, entries 2–5). In contrast, the reac-
tion of amine 6, which bears a 1-(p-biphenyl) substitu-
ent, with hindered vinyl bromide 2g provided 10g in
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Synthesis of N-Aryl-2-allylpyrrolidines
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TandemReactions
Mechanism
We have recently reported the development of palladi- The carboamination reactions of g-N-arylaminoalkenes
um-catalyzed tandem N-arylation/carboamination re- 1 and 6–9 with vinyl bromides likely proceed through a
actions for the synthesis of N-aryl-2-benzylpyrroli- mechanism similar to that described previously for the
dines[13] and -indolines[14] from appropriate primary analogous transformation involving aryl bromides
amine precursors [Eq. (4), R¼aryl]. These reactions en- (Scheme 1).[6] The catalytic cycle presumably commen-
able the modular assembly of heterocyclic compounds ces with oxidative addition of the vinyl bromide to palla-
from very simple precursors and could be amenable to dium(0), which affords vinylpalladium bromide inter-
library synthesis. In these reactions, the primary amine mediate I. The reaction of I with the amine substrate
substrate undergoes N-arylation in the presence of a and NaO-t-Bu yields vinylpalladium amido intermedi-
monophosphine-supported palladium(0) catalyst.[15] ate II, which undergoes intramolecular amidopallada-
After the first transformation is complete, an in situ li- tion to afford III. Carbon-carbon bond-forming reduc-
gand exchange process is effected via the addition of a tive elimination from III provides the observed pyrroli-
bisphosphine to the reaction mixture, and then a second dine 3 and regenerates the palladium(0) catalyst. The N-
vinylated side product that is observed under the non-
optimized reaction conditions presumably derives
from carbon-nitrogen bond-forming reductive elimina-
tion of intermediate II.[11] This side reaction is effectively
suppressed by the use of the relatively small tri-2-furyl-
phosphine ligand. Interestingly, the fact that N-vinyla-
tion is more problematic than N-arylation with the
Pd2(dba)3/dppb catalyst system suggests that vinyl sp2
carbon-nitrogen bond-forming reductive elimination is
a more facile transformation than aryl sp2 carbon-nitro-
gen bond-forming reductive elimination in cases where
aryl bromide is added to provide
the desired heterocycle in a one-
pot process. An extension of this
methodology to allow for the use
of vinyl bromides as the second
coupling partner would allow for
the synthesis of an even broader ar-
ray of compounds.
Table 4. Synthesis of 2-allylpyrrolidines and -indolines via tandem reactions of pri-
mary amines.[a]
As shown in Table 4, the condi-
tions reported previously[13,14] for
the synthesis of N-aryl-2-benzyl-
pyrrolidines and -indolines via this
tandem reaction were also effective
for the synthesis of N-aryl-2-allyl-
pyrrolidines
[Eq. (4), R¼vinyl]. Use of 2-(di-
tert-butylphosphino)biphenyl as
and
-indolines
the ligand for the first stepof the se-
quence was optimal with both the
aliphatic and the aromatic amine
substrates. In the second step, how-
ever, the ligand dppe provided the
best results for the pyrrolidine-
forming reactions (Table 4, entries
1 and 2), whereas DPEphos was op-
timal in the reactions that afforded
indoline products (Table 4, entries
3 and 4).
[a]
Conditions: amine (1.0 equiv.), aryl bromide (1.0 equiv.), NaO-t-Bu (2.4 equivs.),
Pd2(dba)3 (1 mol %), 2-di-t-butylphosphinobiphenyl (2 mol %), toluene
(0.25 M), 60–808C, then dppe or DPEphos (2 mol %) and vinyl bromide (1.2
equivs.), 105–1108C.
[b]
1
Product ratios refer to the isolated material, as judged by H NMR analysis. Pro-
duct ratios and yields refer to the average of two or more experiments.
This reaction was conducted with dppe as the second ligand.
This reaction was conducted with DPEphos as the second ligand.
This material contained ~3–10% of an inseparable regioisomer analogous to 4a.
This material contained ~7–10% of an inseparable isomer analogous to 5a.
[c]
[d]
[e]
[f]
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Joshua E. Ney et al.
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Scheme 3. Proposed mechanism for formation of 5.
nism has previously been invoked to explain the origin
of similar rearranged products observed in cross-cou-
pling reactions of (1-bromovinyl)trimethylsilane
(2i).[17a, b,d] The fact that side products 5 were observed
in reactions of amine 1 with E-substituted vinyl bro-
mides 2a and 2d but not in reactions with Z-substituted
vinyl bromide 2e (Table 2, entries 1, 4, and 5) also sup-
ports the mechanism shown in Scheme 3, as b-hydride
elimination reactions of alkylpalladium complexes re-
quire a syn relationshipbetween palladium and the in-
volved b-hydrogen atom.[20] The relatively large amount
of rearranged product 3h observed in the reaction of
amine 1 with vinyl bromide 2i may be due to a b-silyl ef-
fect, which would stabilize the developing positive
charge on the b-carbon atom in the transition state be-
tween I and VII.[21]
Scheme 1. Proposed mechanism of carboamination reaction.
Scheme 2. Proposed mechanism for formation of regioisomer 4.
Conclusion
the aryl and vinyl bromides have similar electronic prop-
erties (e.g., b-bromostyrene and 2-bromonaphtha-
lene).[16]
In conclusion, we have developed conditions for the syn-
thesis of N-aryl-2-allylpyrrolidines via the palladium-
catalyzed carboamination of g-N-arylaminoalkenes
with vinyl bromides. These reactions display broad
scope with respect to vinyl halide structure and afford
trans-2,3- and cis-2,5-disubstituted pyrrolidines with
good to excellent levels of diastereoselectivity. Addi-
tionally, we have shown that tandem N-arylation/car-
boamination reactions of unsaturated primary amines
are effective for the synthesis of N-aryl-2-allylpyrroli-
dines and -indolines. Efforts to apply this methodology
to the total synthesis of structurally interesting and bio-
logically active targets are currently underway.
As previously suggested,[6,7] regioisomer 4 likely orig-
inates from b-hydride elimination of III to afford p-ole-
fin complex IV (Scheme 2). Reinsertion of the olefin
ꢀ
into the Pd H bond with reversal of regiochemistry
would provide V, which can undergo a second b-hydride
elimination/reinsertion process to afford VI. Carbon-
carbon bond-forming reductive elimination would gen-
erate regioisomer 4 with concomitant regeneration of
the palladium(0) catalyst.
The formation of isomer 5 as a side product in reac-
tions involving E-substituted vinyl bromides 2a and 2d
(Table 2, entries 1 and 4) and the formation of pyrroli-
dine 3h as a side product in the reaction of 1 with 2i (Ta-
ble 2, entry 9) both appear to involve a formal rear-
rangement of the vinyl bromide coupling partner.[17,18]
One possible origin of these products involves an unusu-
al b-hydride elimination reaction of vinylpalladium bro-
mide intermediate I to afford p-alkynylpalladium hy-
dride complex VII. Reinsertion of the alkyne into the
Experimental Section
General Remarks
All reactions were carried out under an argon atmosphere in
flame-dried glassware. Tris(dibenzylidineacetone)dipalladi-
um(0) and all phosphine ligands were purchased from Strem
Chemical Co. and used without further purification. Toluene
was purified using a GlassContour solvent purification system.
ꢀ
Pd H bond with reversal of regiochemistry would af-
ford iso-I,[19] which could re-enter the catalytic cycle
shown in Scheme 1 to afford 5 (Scheme 3). This mecha- Unless otherwise noted, yields refer to isolated yields of com-
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Synthesis of N-Aryl-2-allylpyrrolidines
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pounds estimated to be x95% pure as determined by 1H NMR
and combustion analysis. The yields and product ratios report-
ed in the Experimental Section and Supporting Information
describe the result of a single experiment, whereas those re-
ported in Tables 1–4 are averages of two or more experiments.
Thus, the yields and ratios reported in the Experimental Sec-
tion and Supporting Information may differ from those shown
Tables 1–4.
(1 mL) was added, and the temperature was increased to
1108C. After 15 min of stirring at 1108C the vinyl bromide
(1.2–2.0 equivs.) was added via syringe. Heating was continued
until the intermediate arylamine had been consumed as judged
by GC analysis. The reaction mixture was then cooled to room
temperature, quenched with saturated aqueous ammonium
chloride (2 mL) and diluted with ethyl acetate (10 mL). The
layers were separated and the aqueous layer was extracted
with ethyl acetate (2ꢁ10 mL). The combined organic extracts
were dried over anhydrous sodium sulfate, filtered, and con-
centrated under vacuum. The crude product was then purified
by flash chromatography on silica gel.
General Procedure for Palladium-Catalyzed
Carboamination Reactions with Vinyl Bromides
A flame-dried Schlenk tube was charged with Pd2(dba)3 (1 mol
% complex, 2 mol % Pd), tri-2-furylphosphine (4 mol %), and
sodium tert-butoxide (1.2 equivs.). The tube was purged with
argon and toluene (4 mL/mmol amine substrate), the amine
substrate (1.0 equiv.), and the vinyl bromide (1.1–2.0 equivs.)
were added via syringe. The mixture was heated to 60–
1108C with stirring until the starting material had been con-
sumed as judged by GC or 1H NMR analysis. The reaction mix-
ture was cooled to room temperature, quenched with saturated
aqueous ammonium chloride (2 mL), and diluted with ethyl
acetate (10 mL). The layers were separated and the aqueous
layer was extracted with ethyl acetate (2ꢁ10 mL). The com-
bined organic extracts were dried over anhydrous sodium sul-
fate, filtered, and concentrated under vacuum. The crude prod-
uct was then purified by flash chromatography on silica gel.
(E)-4-{2-[Undec-2-enyl]pyrrolidin-1-yl}benzonitrile (17)
Reaction of amine 14 (21 mg, 0.25 mmol) with 4-bromobenzo-
nitrile (46 mg, 0.25 mmol), sodium tert-butoxide (58 mg,
0.6 mmol) and vinyl bromide 2a (110 mg, 0.5 mmol,>20:1
E/Z) following the general procedure afforded the title com-
pound 17 as a pale yellow oil; yield: 55 mg (68%,>20:1
E/Z). This material was obtained as a 30:1 mixture of insepa-
rable regioisomers and contained ~7% 4-[2-(2-methylenede-
cyl)pyrrolidin-1-yl]benzonitrile as judged by 1H NMR analysis;
data are for the major isomer. 1H NMR (400 MHz, CDCl3): d¼
7.44 (d, J¼9.2 Hz, 2H), 6.52 (d, J¼8.4 Hz, 2H), 5.56–5.47 (m,
1H), 5.40–5.31 (m, 1H), 3.80–3.73 (m, 1H), 3.45–3.39 (m, 1H),
3.25–3.17 (m, 1H), 2.39–2.31 (m, 1H), 2.12–1.91 (m, 7H),
1.40–1.22 (m, 12H), 0.88 (t, J¼7.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d¼149.6, 134.3, 133.7, 125.9, 121.2, 112.0,
96.8, 58.7, 48.3, 35.6, 32.9, 32.1, 29.7, 29.7, 29.6, 29.5, 29.4,
23.2, 22.9, 14.3; IR (film): n¼2213, 1607, 1520 cmꢀ1; anal.
calcd. for C22H32N2: C 81.43, H 9.94, N 8.63; found: C 81.51, H
10.00, N 8.72.
(E)-1-Phenyl-2-[undec-2-enyl]pyrrolidine (3a)
Reaction of amine 1 (40 mg, 0.25 mmol) with vinyl bromide 2a
(60 mg, 0.275 mmol,>20:1 E/Z) and sodium tert-butoxide
(29 mg, 0.3 mmol) at 608C following the general procedure af-
forded the title compound 3a as a colorless oil; yield: 66 mg
(88%,>20:1 E/Z). This material was obtained as a 14:1 mix-
ture of inseparable regioisomers and contained ~6% 5a, as
Acknowledgements
1
The authors thankthe University of Michigan and the National
Institutes of Health – National Institute of General Medical Sci-
ence (GM-071650) for financial support of this work. JPW
thanks the Camille and Henry Dreyfus Foundation for a new
faculty award and Research Corporation for an innovation
award. JEN acknowledges the University of Michigan for a Re-
gents Fellowship and Pfizer for a Graduate Research Fellow-
ship. Additional unrestricted support was provided by Amgen,
Eli Lilly, and 3M.
judged by H NMR analysis; data are for the major isomer.
1H NMR (400 MHz, CDCl3): d¼7.28–7.22 (m, 2H), 6.67 (t,
J¼7.4 Hz, 1H), 6.6 (d, J¼7.6 Hz, 2H), 5.57–5.48 (m, 1H),
5.47–5.38 (m, 1H), 3.75–3.69 (m, 1H), 3.47–3.40 (m, 1H),
3.22–3.14 (m, 1H), 2.48–2.41 (m, 1H), 2.07–1.87 (m, 7H),
1.44–1.25 (m, 12H), 0.91 (t, J¼6.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d¼147.4, 133.4, 129.4, 126.9, 115.4, 112.0,
58.7, 48.5, 36.3, 33.0, 32.1, 29.9, 29.7, 29.5, 29.4, 23.5, 22.9, 14.3
(two aliphatic signals are incidentally equivalent); IR (film):
n¼1598, 1505 cmꢀ1; anal. calcd. for C21H33N: C 84.22, H
11.11, N 4.68; found: C 84.47, H 11.29, N 4.70.
References and Notes
General Procedure for Palladium-Catalyzed Tandem
N-Arylation/Carboamination Reactions
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A flame-dried Schlenk tube was charged with Pd2(dba)3 (1 mol
% complex, 2 mol % Pd), 2-(di-tert-butylphosphino)biphenyl
(2 mol %) and sodium tert-butoxide (2.4 equivs.). The tube
was purged with argon and toluene (1 mL), the amine substrate
(1.0 equiv.) and the aryl bromide (1.0 equiv.) were added via sy-
ringe. The mixture was placed in a pre-heated oil bath at 608C
with stirring until the starting materials had been consumed as
judged by GC analysis. A solution of dppe (2 mol %) in toluene
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halides under catalytic amination conditions. However,
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than that of aryl halides. Thus, the competition experi-
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were present in excess, and (E)-vinyl bromides have
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