A palladium-catalyzed dehydrogenative diamination of terminal olefins

Article abstract of DOI:10.1002/anie.200803184

(Chemical Equation Presented) A dynamic diamination: The title transformation has been developed with diaziridine 1 as the nitrogen source (see scheme; dba=trans,trans-dibenzylidene-acetone). The reaction proceeds through an allylic amination and subsequent cyclization, and a variety of terminal olefins can be effectively diaminated with high regioselectivity.

Full text of DOI:10.1002/anie.200803184

Communications
DOI: 10.1002/anie.200803184
Palladium Catalysis
A Palladium-Catalyzed Dehydrogenative Diamination of Terminal
Olefins**
Bin Wang, Haifeng Du, and Yian Shi*
Metal-mediated and -catalyzed diamination of olefins pro-
vides an effective approach to vicinal diamines, which are very
important functional moieties contained in various biologi-
cally active compounds and are widely used as chiral-control
elements in asymmetric synthesis.[1–6] Recently, we reported
that various dienes and trienes can be regio- and stereoselec-
tively diaminated using di-tert-butyldiaziridinone (2)[7] as the
nitrogen source and palladium(0)[8] or copper(I)[9] as the
catalyst. When readily available terminal olefins were treated
with 2 and [Pd(PPh3)4], the diamination occurred regio- and
diastereoselectively at the allylic and homoallylic carbon
centers to form 3 (Scheme 1). This reaction is likely to
proceed via a diene species which is formed in situ.[10]
However, when N,N-di-tert-butylthiadiaziridine 1,1-dioxide
diamination products similar to 3 were detected. Instead
terminal diamination product 5 was formed with a 34%
conversion. The diamination process was further improved by
using 10 mol% Pd catalyst which was prepared from [Pd2-
(dba)3] and tri-2-furylphosphine at a higher reaction temper-
ature. For example, treatment of 1a with [Pd2(dba)3]
(0.05 equiv), tri-2-furylphosphine (0.3 equiv), and
4
(2.0 equiv) at 758C for 10 h gave terminal diamination
product 5a in 68% yield (Table 1, entry 1). This diamination
process can be extended to a variety of terminal olefins
(Table 1, entries 2–11; the X-ray structure of 5 f is shown in
Figure 1). In all cases, the diamination products 5 were
formed as major products along with small amounts of
unidentified isomers. One possible isomer could result from
the migration of the double bond in 5. In one case a
substantial amount of this type of isomer was observed (5d’;
Table 1, entry 4).
When a mixture of 1,3-pentadiene (6) and 1a was
subjected to the diamination reaction conditions, compounds
Scheme 1. Previous work.
(4)[11,12] is used as the nitrogen source along with the Pd
catalyst, then terminal olefins are regioselectively diaminated
at the terminal carbon position to form 5 via a different
reaction mechanism to that already reported (Scheme 2).
Herein, we report our preliminary results on this subject.
When terminal olefins such as 1-nonene (1a) were treated
with 5 mol% [Pd(PPh3)4] and 4, no allylic or homoallylic
Figure 1. The X-ray structure of compound 5 f.
7 and 5a were formed, respectively (Scheme 3). Diene 6
underwent diamination predominately at the internal double
bond,[13] whereas for terminal olefin 1a diamination occurred
at the terminal carbon position. These results indicate that the
diamination reaction is unlikely to proceed via a diene species
which is generated in situ, as is the case when 2 was used as
the nitrogen source (Scheme 1).
Scheme 2. This work.
While the elucidation of a precise reaction mechanism
[*] B. Wang, Dr. H. Du, Prof. Dr. Y. Shi
Department of Chemistry
awaits further study, a plausible catalytic cycle is shown in
0
ꢀ
Scheme 4. Firstly, Pd inserts into the N N bond of 4 to form
the four-membered-PdII species 8, which then forms complex
9 with olefin 1. Removal of an allylic hydrogen from 9 forms
the [(p-allyl)Pd] complex 10,[14,15] which gives allyl sulfamide
11 and regenerates the Pd0 catalyst after reductive elimina-
tion.[16] Subsequently, 11 complexes with 8 to form 12, which
then undergoes a palladium(II)-catalyzed cyclization to form
13.[17] Finally, 13 undergoes a b-hydride elimination and
Colorado State University
Fort Collins, CO 80523 (USA)
Fax: (+1) 970-491-1801
E-mail: yian@lamar.colostate.edu
[**] We are grateful for generous financial support from the National
Institute of General Medical Sciences, National Institutes of Health
(grant no. GM083944-01) and the Camille and Henry Dreyfus
Foundation.
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Table 1: Catalytic dehydrogenative diamination[a]
Entry Substrate (1)
Product (5)
Yield [%][b]
68
1
2
3
47
74
Scheme 3.
4
77[c]
5[d]
45
62
61
61
6
Scheme 4. A proposed catalytic cycle for the diamination process.
R=tert-butyl.
7
8
proposed mechanism. To further probe the allylic amination
process, deuterium-labeled styrene derivatives 15 and 16 were
subjected to the reaction conditions. Although these two
substrates were found to be less reactive owing to steric effect,
some allylic amination products were isolated and the
deuterium label was almost equally distributed at terminal
and allylic positions of the olefin in both cases (Scheme 5).
This result suggests that the initial allylic amination of
complex 10 is a viable process (Scheme 4).
9[e]
1i, R=H (E)
1j, R=H (Z)
1k, R=Ph
(Z/E 6:1)
42
10[f]
11[e]
40
66[g]
[a] All reactions were carried out with olefin (1.0 mmol), [Pd2(dba)3]
(0.050 mmol), tri-2-furylphosphine (0.30 mmol), and 4 (2.0 mmol) in
benzene (0.25 mL) at 758C under argon for 10 h, unless otherwise
stated. dba=trans,trans-dibenzylideneacetone. [b] Yield of isolated pro-
duct. [c] 5d/5d’ 2:1; reported yield is a combined yield. [d] The reaction
was carried out at 758C for 22 h. [e] The reaction was carried out at 658C
for 6 h. [f] The reaction was carried out at 508C for 20 h. [g] 7% yield of
the 1Z,3E isomer was also isolated. Bn=benzyl, Boc=tert-butoxycar-
bonyl.
reductive elimination to form the product 5 and sulfamide 14
with regeneration of the Pd0 catalyst. For aryl-substituted 1-
butenes (Table 1, entries 5 and 6), some amounts of diene
were also formed from b-hydride elimination of [(p-allyl)Pd]
complex 10,[18,19] and this outcome is consistent with the
Scheme 5. Allylic amination of deuterium-labeled styrene derivatives.
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Communications
(0.126 g, 1.0 mmol) and 4 (0.413 g, 2.0 mmol) were added successively
and the reaction mixture stirred at 758C for 10 h. Purification of the
crude reaction mixture by flash chromatography on silica gel [eluents:
toluene (to remove the dba) then petroleum ether/EtOAc (40:1!
30:1)] gave 5a as a colorless oil (0.225 g, 68%).
A typical procedure for allylic amination of deuterated styrene
derivatives (Scheme 5): As outlined above, but using the following
reagents: [Pd2(dba)3] (0.023 g, 0.025 mmol), tri-2-furylphosphine
(0.035 g, 0.15 mmol), benzene (0.125 mL), 16 (0.060 g,
0.50 mmol), 4 (0.103 g, 0.50 mmol). Purification by flash
chromatography on silica gel [eluents: toluene then petro-
leum ether/EtOAc (30:1)] gave a mixture of 17 and 18 as a
white solid (0.052 g, 32%).
Clear identification and isolation of allyl sulfamide 11
from the crude reaction mixtures proved to be difficult.
However, in the case of 1-nonene (Table 1, entry 1), trace
amounts of 11 could be detected in the reaction mixture by
1H NMR and GC–MS analysis. Thus, allyl sulfamides 19 and
20 were prepared and subjected to the reaction conditions
(Scheme 6). These sulfamides indeed cyclized to form 5a in
A typical procedure for the cyclization of allyl sulfa-
mides (Scheme 6): As outlined above, but using the follow-
ing reagents: [Pd2(dba)3] (0.018 g, 0.020 mmol), tri-2-furyl-
phosphine (0.028 g, 0.12 mmol), benzene (0.1 mL), 20
(0.133 g, 0.40 mmol), 4 (0.083 g, 0.40 mmol). The reaction
time was 14 h. Purification by flash chromatography on silica
gel [eluents: toluene then petroleum ether/EtOAc (30:1!
20:1)] gave 5a as a colorless oil (0.116 g, 88%).
Scheme 6. Cyclization of sulfamides.
Received: July 2, 2008
Revised: August 7, 2008
Published online: September 24, 2008
good yield. However, no cyclization was observed without
using 4. These results are in agreement with the mechanism
described in Scheme 4. The exact mechanism for the palla-
dium(II)-catalyzed cyclization of 11 into 5 awaits further
study.
Keywords: amination · dehydrogenation · palladium ·
terminal olefins
.
In summary, a variety of terminal olefins have been
dehydrogenatively diaminated at the terminal carbon posi-
tions using N,N-di-tert-butylthiadiaziridine 1,1-dioxide (4) as
the nitrogen source and Pd as the catalyst, to give the
diamination products in high regioselectivity. The diamina-
tion is likely to proceed through a palladium(II)-catalyzed
allylic amination and subsequent cyclization. This diamina-
tion is mechanistically distinct from the process when di-tert-
butyldiaziridinone (2) was used as the nitrogen source, thus
resulting in different regioselectivity. Further effort will be
devoted to understanding the reaction mechanism, searching
for an even more effective catalytic process, expansion of the
substrate scope, and development of an asymmetric method-
ology.
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Experimental Section
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see: a) T. P. Zabawa, D. Kasi, S. R. Chemler, J. Am. Chem.
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Preparation of N,N-di-tert-butylthiadiaziridine 1,1-dioxide (4).[11]
Over
a period of 30 min, N,N-di-tert-butyl sulfamide (10.0 g,
48.0 mmol) was added to a suspension of sodium hydride (60%;
2.0 g, 50.0 mmol) in hexanes (400 mL). The resulting slurry was
stirred at reflux under argon for 2 h. Upon cooling to ꢀ308C, tert-
butyl hypochlorite (5.43 g, 50.0 mmol) was added dropwise to the
slurry while exposure to direct light was avoided. The reaction
mixture was stirred in the dark at ꢀ308C for 3 h and then at 08C for
1 h before cold diethyl ether (200 mL) was added. The organic layers
were washed with water (100 mL), dried over MgSO4, filtered,
concentrated, and distilled under reduced pressure (958C, 8 mmHg)
to give 4 as a colorless oil, which solidified at room temperature (8.5 g,
86%).
A typical procedure for dehydrogenative diamination (Table 1,
entry 1): A Pyrex glass tube was charged with [Pd2(dba)3] (0.046 g,
0.050 mmol) and tri-2-furylphosphine (0.070 g, 0.30 mmol), and then
filled and evacuated with argon three times before benzene (0.25 mL)
was added. The mixture was stirred at 758C for 15 min before 1a
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763; e) C. H. Hꢃvelmann, J. Streuff, L. Brelot, K. Muꢁiz, Chem.
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[18] Internal diamination products from the resulting dienes were
also observed.
[19] For leading references on the formation of dienes from [(p-
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