Stannylated allyl carbonates as versatile building blocks for the diversity oriented synthesis of allylic amines and amides

Article abstract of DOI:10.1039/c0ob00945h

Stannylated allylic carbonates are suitable substrates for Pd-catalyzed allylic aminations. In DMF and with [allylPdCl]₂ as catalyst the stannylated allyl amines formed can be directly coupled with electrophiles according to the Stille protocol, giving rise to highly functionalized buiding blocks in excellent yields.

Full text of DOI:10.1039/c0ob00945h

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PAPER
Stannylated allyl carbonates as versatile building blocks for the diversity
oriented synthesis of allylic amines and amides†
Christian Bukovec and Uli Kazmaier*
Received 27th October 2010, Accepted 10th February 2011
DOI: 10.1039/c0ob00945h
Stannylated allylic carbonates are suitable substrates for Pd-catalyzed allylic aminations. In DMF and
with [allylPdCl]2 as catalyst the stannylated allyl amines formed can be directly coupled with
electrophiles according to the Stille protocol, giving rise to highly functionalized buiding blocks in
excellent yields.
Introduction
In pharmaceutical chemistry as well as in chemical biology the
generation of libraries of small molecules is a powerful tool to find
new lead structures for the development of new drug candidates.1
In particular diversity oriented synthesis (DOS), introduced by
Schreiber et al.,2 is a concept that provides a high degree of
substitutional, stereochemical and scaffold diversity.3
A key point for a successful application of this protocol is the
proper choice of suitable building blocks, allowing a wide range
of different modifications and the generation of molecular com-
plexity. Stannylated allylic carbonates, such as 1a, are absolutely
predestined for this purpose, because they combine the structural
features of two very important cross coupling reactions, the allylic
alkylation4 and the Stille coupling.5 The stannylated carbonates
can easily be obtained by a molybdenum-catalyzed hydrostan-
nation of the corresponding propargyl carbonate in a highly
regioselective fashion (Scheme 1).6 The best results were obtained
under an atmosphere of CO, which suppressed side reactions such
as protodestannylations nearly completely.7 With these stannanes
Scheme 1 Stannylated allyl carbonates (1a) as versatile building blocks.
in hand we could show that highly reactive nucleophiles, such as
chelated enolates of a-amino esters, undergo a very clean allylic
alkylation, giving rise to stannylated amino acid derivatives.8 This
protocol can also be applied to the modification of peptides by
using peptide enolates.9 In this case, the stereochemical outcome
of the reaction can be controlled by the stereogenic centers in the
peptide chain. The stannylated amino acids and peptides obtained
can subsequently be subjected to Stille couplings, which proceed
under neutral conditions, allowing side chain modification without
epimerization of the stereogenic centers.10
trivial issue, because vinylstannanes can also react as electrophiles
in allylic alkylations, which might result in an oligo- or polymer-
ization of the allylic substrate 1. With less reactive nucleophiles
such as malonates, in general no stannylated allylation products
are obtained, because elimination of the substrate 1 towards the
corresponding allene is a faster process.11
To increase the synthetic potential of the stannylated allyl
substrates 1, we investigated a wide range of other nucleophiles
including several types of amines. Amines are more nucleophilic
compared to C-nucleophiles such as malonates, allowing al-
lylations under milder conditions without decomposition. In
principle, under optimized conditions the allylic amination and
the subsequent Stille coupling can be carried out in an one-pot
protocol.12 Herein we describe the details as well as scope and
limitations of this interesting allylic amination process.
These examples clearly indicate that with reactive nucleophiles
it is possible to selectively address the allylcarbonate subunit,
without affecting the vinylstannane functionality. This is not a
Institut fu¨r Organische Chemie, Universita¨t des Saarlandes, D-66123,
Saarbru¨cken, Germany. E-mail: u.kazmaier@mx.uni-saarland.de; Fax: +
49 681 302 2409; Tel: + 49 681 302 3409
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c0ob00945h
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Table 1 Investigation of the reaction conditions and the leaving groups
Table 2 Optimization of the catalyst for allylic aminations
Yield (%)a
Entry
Subs.
X
Reaction conditions
Yield (%)a
Entry
Catalyst
1
2
3
4
5
6
7
8
9
1b
1b
1b
1b
1b
1a
1c
1d
1e
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOMe
OCOOEt
OCOOtBu
OAc
THF, 0 ◦C, 5 h
THF, 20 ◦C, 1 h
DMF, 20 ◦C, 1 h
DMF, 0 ◦C, 2 h
DMF, -20 ◦C, 7 h
DMF, 0 ◦C, 2 h
DMF, 0 ◦C, 2 h
DMF, 0 ◦C, 2 h
DMF, 0 ◦C, 2 h
74
0
70
79
80
81
56
1
2
3
4
1 mol% [allylPdCl]2, 4.5 mol% dppf
1 mol% [allylPdCl]2, 4.5 mol% PBu3
2 mol% Pd(PPh3)4
79
n.d.b
94
2 mol% Pd(OAc)2, 4.5 mol% PPh3
94
a 1.1 equiv of piperidine were used. b Slow reaction and incomplete
conversion.
88 (impure)
71
OTHP
Table 3 Allylation of a wide range of amines
a 1.1 equiv of piperidine were used.
Results and discussion
Entry R1R2NH
Reaction conditions
Product Yield (%)
To avoid side reactions such as double allylations we started our
investigations with piperidine as the nucleophile (1.1 equiv). THF
was used as the solvent and [allylPdCl]2/PPh3 as the catalyst, as
these were the conditions which gave the best results in previous
work with the amino acid enolates.8 While a good conversion
and yield was obtained at 0 ◦C from the methyl carbonate 1b
(Table 1, entry 1), absolutely no allylation product was obtained at
room temperature (entry 2). Under these conditions, elimination
towards the allene, as also observed previously with malonates,
is much faster than the allylic substitution. Obviously THF is
a good solvent for allylic alkylations at low temperatures, but
not at room temperature. Therefore, we investigated several other
solvents. By far the best results were obtained in DMF, which
provided a clean allylation product at room temperature (entry 3).
1
2
3
morpholine
pyrrolidine
Et2NH
DMF, 0 ◦C, 2 h
DMF, 0 ◦C, 2 h
DMF, 0 ◦C, 2 h
2b
2c
2d
87
86
90
84
53
17
0
4
5
(allyl)2NH
Bn2NH
DMF, 0 ◦C to rt, 16 h 2e
DMF, 0 ◦C to rt, 16 h 2f
DMF, 0 ◦C to rt, 16 h 2g
6
7
(cHex)2NH
Ph2NH
DMF, 0 ◦C to rt, 16 h
—
8
9
10
11
12
PhNH2
DMF, 0 ◦C to rt, 16 h 2h
25
58
51a
65b
84
p-MeOC6H4NH2 DMF, 0 ◦C to rt, 16 h 2i
BnNH2
DMF, 0 ◦C to rt, 16 h 2k
DMF, 0 ◦C to rt, 16 h 2l
cHexNH2
PhCH(CH3)NH2 DMF, 0 ◦C to rt, 16 h 2m
a In addition 34% of the diallylated product 2k¢ was obtained. b In addition
19% of the diallylated product 2l¢ was obtained.
◦
At 0 C the reaction was significantly faster than in THF (entry
4), and even at -20 ◦C a high yield of allylated piperidine was
obtained, although the reaction is much slower at this temperature
(entry 5). Therefore, we carried out our further investigations
concerning the influence of the leaving group at 0 ◦C. The results
with the ethylcarbonate 1a (entry 6) were comparable to those
obtained with the methyl derivative 1b, while with the sterically
more demanding t-butylcarbonate 1c a significant drop in the yield
was observed (entry 7). So far the best yield was obtained with the
acetate 1d, but in this case the allylation product was contaminated
with a not identified side product, which could not be removed by
flash chromatography. Interestingly, even the THP ether 1e gave a
satisfying yield, although THP is not a typical leaving group for
allylic alkylations (entry 9).
Under these optimized reaction conditions we next examined
the allylation of a wide range of amines to evaluate the scope
and limitations of this reaction (Table 3). Sterically unhindered
secondary amines such as morpholine, pyrrolidine, diethylamine,
diallylamine showed a reactivity comparable to piperidine and
gave a comparable yields (entries 1 to 4). With increasing
steric demand of the nucleophile the yield dropped significantly,
becoming as low as 17% in case of the dicyclohexyl derivative 2g
(entry 6). No reaction at all was observed with diphenylamine
(entry 7), but here probably also the electronic effect of the two
phenyl groups has to be considered, in addition to the steric
aspects. For example, with the sterically unhindered but not very
nucleophilic aniline also a low yield was obtained (entry 8).
Increasing the nucleophilic character of this amine by introduction
of an electron donating group, such as in anisidine, resulted in
acceptable yield of the allylation product 2i (entry 9). As expected,
primary alkylamines (entries 10 and 11) gave better yields, but in
these cases also significant amounts of diallylated products were
formed, which could be separated by flash chromatography. By
far the best results with primary amines were obtained with 1-
phenylethylamine (entry 12) which provided the monoallylated
product 2m exclusively in high yield.
Of course, one might also expect to see an influence of the
catalyst system on the outcome of the reaction. This forced us to
investigate the influence of different ligands under the optimized
reaction conditions (Table 2). No difference was observed by
switching from PPh3 to the bidentate ligand dppf, while with
electron-rich phosphine PBu3 a significant drop of the reactivity
was observed (entry 2). By far the best yield was obtained with
commercial Pd(PPh3)4 (entry 3). This catalyst is relatively sensitive
◦
and should be stored under argon at low temperature (-20 C).
Otherwise the yields vary (5–10%) depending on the quality of the
catalyst. Therefore, it is a good alternative to generate the active
catalyst in situ from Pd(OAc)2 and PPh3 (entry 4).
With these stannylated allylamines in hand we next tried to
optimize the reaction conditions for the subsequent Stille coupling
(Table 4). As standard substrate we used the allylated piperidine
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Table 4 Optimization of the Stille coupling
Table 5 One-pot allylic amination–Stille couplings
Entry RXa
Cat.b Reaction conditions
THF, 60 ◦C, 2 d
Product Yield (%)
Entry RXa
1
Reaction conditions
rt, 3 h
Product Yield (%)
1
2
3
4
5
6
7
allylBr A
3a
3b
3b
3c
97
99
98
37
97
0
3d
96b
PhI
A
A
A
THF, 60 ◦C, 3 d
THF, 60 ◦C, 3 d
THF, 60 ◦C, 3 d
PhBr
BnBr
allylBr A
allylBr A
allylBr B
2
3
4
PhI
1) 65 ◦C, 3 h; 2) 90 ◦C, 1 h 3b
1) 65 ◦C, 3 h; 2) 90 ◦C, 1 h 3e
82
80
70
THF, MW, 300 W, 100 ◦C, 1 h 3a
DMF, MW, 300 W, 100 ◦C, 1 h 3a
THF, MW, 300 W, 100 ◦C, 1 h 3a
p-NO2C6H4Br
p-BrC6H4CHO 90 ◦C, 16 h
3f
0
a 2 equiv of the electrophile RX were used. b E/Z ratio 9/91.
a 2 equiv of the electrophile RX were used. b Catalysts used: A: 2 mol%
[allylPdCl]2, 4 mol% PPh3; B: 2 mol% Pd(PPh3)4.
temperature to 90 ◦C the reaction was complete after 1 h and the
coupling product 3b was isolated in high yield (entry 2). A similar
reactivity and yield were observed for p-nitrobromobenzene (entry
3), while with p-bromobenzaldehyde the reaction mixture had to
be warmed to 90 ◦C for 16 h to get a complete consumption of the
starting material (entry 4). But under these conditions the catalyst
was not stable and precipitation of Pd(s) was observed.
derivative 2a and we investigated the coupling with allylbromide
under various reaction conditions with the aim to find conditions
which allow the combination of the two Pd-catalyzed processes to
a simple one-pot protocol.
An excellent yield of the coupling product 3a was obtained in
THF, using [allylPdCl]2 and PPh3 (ratio Pd : PPh3 1 : 1) as catalyst,
reaction conditions which have been optimized previously for the
modification of stannylated amino acids and peptides.8,9 After 2 d
at 60 ◦C an almost quantitative yield of coupling product 3a was
obtained (Table 4, entry 1). In principle, comparable results were
obtained with aryl halides (entries 2 and 3), although these sub-
strates were slightly less reactive. In contrast, with benzylbromide
the yield of Stille product dropped significantly (entry 4), probably
because of side reactions such as N-benzylation. The relatively
long reaction time under the standard conditions for the Stille
coupling could be dramatically reduced by using microwave (MW)
irradiation. Under these conditions an almost quantitative yield
was obtained after 1 h of irradiation. It is worth mentioning, that
no coupling product could be obtained in DMF or if Pd(PPh3)4
was used as a catalyst (entries 6 and 7), conditions which had been
found to be the best for the allylic aminations.
Based on these encouraging results we next focused on the
development of an one-pot process for the allylic amination and
the subsequent Stille coupling. This is not a trivial issue, because
the reaction conditions are different for both reactions, although
Pd is used as the catalyst in each of these processes. While a
phosphine/Pd-ratio of >2 : 1 is perfect for allylic alkylations, the
best results in the Stille coupling are generally obtained with an
1 : 1 ratio. Therefore, we tried to find conditions which were a good
compromise for both reactions. To make sure that the first step—
the allylic amination—proceeds without problems, we first used
the optimized conditions for this reaction (Table 5). Piperidine was
reacted with stannylated allylcarbonate 1a at 0 ◦C and the reaction
mixture was warmed to room temperature overnight. As a reactive
electrophile (Z)-iodoacrylate was added in excess (2 equiv.) and
the reaction mixture was stirred at room temperature. After 3 h
a complete conversion was observed and the coupling product 3d
was obtained in excellent yield (entry 1). Interestingly, around 10%
of the isomerized (E)-coupling product was obtained. Under the
same conditions no reaction was observed with iodobenzene (entry
2). After heating to 65 ◦C for 3 h product formation was observed,
but the reaction was not complete, but after increasing the
Therefore, we decided to use this reaction to optimize our
catalyst system for the one-pot process (Table 6). A comparable
◦
yield was obtained if the reaction mixture was warmed to 65 C
for 48 h, although already after 1 h Pd(s) started to precipitate
(entry 1). To reduce the Pd : P ratio into a range which should be
more suitable for Stille couplings, we added [allylPdCl]2 together
with the elctrophile after the allylic amination step. And indeed, if
the two Pd-catalysts were used in equimolar amounts (Pd/P 1 : 2),
the yield could be increased to 82% (entry 2), but also here a slow
precipitation of Pd(s) was observed. A further reduction of the
Pd/P-ratio definitely was counterproductive (entry 3). Pd(s) was
formed immediately, no complete conversion was observed, and
the yield dropped dramatically. Because [allylPdCl]2 in general is
also a good catalyst for allylic alkylations, we decided to use this Pd
source solely and to vary the Pd/P-ratio simply by adding different
amounts of PPh3. Interestingly, the catalytic species generated by
this protocol seems to be more reactive and at the same time
more stable, giving better yields in a shorter time. Although a slow
precipitation of Pd(s) was observed at a Pd/P-ratio of 1 : 2, the
reaction was complete after 7 h (entry 4). Increasing the amount
of phosphine resulted in the formation of a stable catalyst and at
a 1 : 4 ratio nearly a quantitative yield of the coupling product 3f
was obtained (entry 5).
Under these optimized conditions we investigated a wide range
of further one-pot reactions, using different electrophiles and
amines (Table 7). For example, the yield of the reaction with piperi-
dine and PhI could be increased to 96% (entry 1), and a comparable
result was obtained with the corresponding triflate (entry 2). Aryl
bromides are less reactive, requiring higher reaction temperatures
(entries 3–7). For example, with p-methoxybromobenzene a slow
◦
reaction was observed at 65 C, while the reaction was complete
after 6 h at 100 ◦C (entry 5). Replacing the methoxy group
by an electron-withdrawing nitro group allowed the reduction
of the temperature (entry 6) and the coupling of aryl chlorides
(entry 8). b-Bromostryrene showed a reactivity comparable to the
aryl iodides and triflates (entry 9). Replacing piperidine by other
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Table 6 Optimization of the catalyst system for one-pot reactions
Entry
Catalyst
Ratio Pd : P
t (h)
Yield (%)
Comment
1
2
2 mol% Pd(PPh3)4
1) 2 mol% Pd(PPh3)4
2) 1 mol% [allylPdCl]2
1) 2 mol% Pd(PPh3)4
1 : 4
1 : 2
48
48
70a
82a
Pd(s) after 1 h
Pd(s) after 1 h
3
1 : 1
48
39a
Pd(s) immediately, no compl. conv.
2) 3 mol% [allylPdCl]2
1 mol% [allylPdCl]2, 4 mol% PPh3
1 mol% [allylPdCl]2, 8 mol% PPh3
4
5
1 : 2
1 : 4
7
16
86a
95b
Pd(s) formed slowly, compl. conversion.
compl. conversion.
a 2 equiv of electrophile were used. b 1.2 equiv of electrophile were used.
Table 7 Optimized one-pot allylic amination–Stille couplings
Entry
R1R2NH
RX
React. cond.
Product
Yield (%)
1
2
3
4
5
6
7
8
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
piperidine
morpholine
pyrrolidine
Et2NH
PhI
PhOTf
PhBr
2-bromo-naphthalin
65 ◦C, 16 h
65 ◦C, 16 h
100 ◦C, 6 h
90 ◦C, 16 h
90 ◦C, 16 h
100 ◦C, 6 h
65 ◦C, 16 h
90 ◦C, 16 h
65 ◦C, 16 h
65 ◦C, 16 h
65 ◦C, 16 h
65 ◦C, 16 h
65 ◦C, 16 h
65 ◦C, 16 h
65 ◦C, 16 h
3b
3b
3b
3g
3h
3i
3e
3e
3k
4a
5a
6a
7a
8a
9a
96
94
64
62
97
69
80
67
95
96
91
74
66
89
73
5-bromo-pyrimidine
p-MeOC6H4Br
p-NO2C6H4Br
p-NO2C6H4Cl
9
b-bromostyrene
10
11
12
13
14
15
PhI
PhI
PhI
PhI
PhI
PhI
(allyl)2NH
tBuNH2
secondary and sterically hindered primary amines provided the
coupling products 4–9 in comparable yields (entries 10–15).
The difference in reactivity between aryl iodides and aryl
bromides could be used to selectively react p-bromoiodobenzene
at lower temperature at the iodo position without touching the
bromo substituent (Scheme 2). The corresponding product 3l
was obtained in excellent yield. This intermediate could then be
further modified in a second Stille coupling at higher temperature
with tributyl(2-furyl)stannane. This reaction sequence yielded
product 3m in a four component one pot procedure in very good
yield.
Interestingly, no coupling products were obtained with acyl
halides such as benzoyl chloride, probably because of an acylation
of the amine functionality. But this problem could easily be solved
by combining the Stille coupling with a CO-insertion, giving
rise to a,b-unsaturated ketone 3o. Reactions with alkyl and allyl
halides, such as allyl or cinnamyl bromide, also failed (alkylation
of the tertiary amine) but the stannylated amine intermediate
could successfully be coupled via allylic alkylation. For example,
cinnamyl carbonate provided diene 3n in excellent yield and very
high regioselectivity (> 97% of the linear product). Probably
for steric reasons, the reaction with o-iodobenzoate was rather
sluggish. No reaction was observed at 65 ◦C, but at 100 ◦C
a complete conversion was obtained after 5 h, providing 3p in
acceptable yield.
o-Iodobenzoate is an interesting candidate for the synthesis of
more complex products because of its two electrophilic centres.
For example, if primary amines are used in the allylic alkylation
step, the Stille coupling product can undergo a subsequent
cyclization providing lactam 9b with an exocyclic methylene group.
With the similar electrophile ethyl 2-iodobenzyl carbonate the
isoquinoline derivative 11a was obtained after allylic alkylation,
Stille coupling and benzylic amination. Interestingly in both
reactions, no isomerization of the exocyclic methylene double
bond to the endo position was observed, even under the relatively
harsh reaction conditions.
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Conclusion
In conclusion, we have shown, that stannylated allyl carbonates are
versatile synthetic building blocks for the synthesis of stannylated
allylamines, which can be further modified via Stille couplings.
Under optimized conditions both reactions can be carried out in
an one-pot protocol, giving rise to a wide range of substituted and
functionalized allylamines, including aziridines and lactams.
Experimental
General remarks
All reactions were carried out in oven-dried glassware (70 ◦C)
under an atmosphere of nitrogen. Dried solvents were distilled
before use: THF was distilled from LiAlH4, dry DMF was pur-
chased from Sigma-Aldrich. The products were purified by flash
chromatography on silica gel columns (Macherey-Nagel 60, 0.063–
0.2 mm). Mixtures of ethyl acetate and hexanes were generally
used as eluents. Analytical TLC was performed on precoated
R
silica gel plates (Macherey–Nagel, Polygramꢀ SIL G/UV254).
Visualization was accomplished with UV-light, KMnO4 solution
or Iodine. 1H and 13C NMR spectra were recorded with a Bruker
AC-400 [400 MHz (1H) and 100 MHz (13C)] spectrometer in
CDCl3. Chemical shifts are reported in ppm (d) with respect to
TMS, and CHCl3 was used as the internal standard. Mass spectra
were recorded with a Finnigan MAT 95 spectrometer using the
CI or EI technique. Elemental analyses were performed at the
Saarland University. Microwave reactions were carried out in a
CEM Discover microwave oven.
General procedure for allylic aminations
In a Schlenk flask Pd(PPh3)4 (6 mg, 5.0 mmol, 2 mol%) was
dissolved in dry DMF (2 mL) and stirred for 15 min at room
temperature under nitrogen. After addition of the amine (0.275–
0.5 mmol), the solution was cooled to 0 ◦C and ethyl 2-
(tributylstannyl)allyl carbonate 1a (105 mg, 0.25 mmol) was added
dropwise. The reaction mixture was stirred at 0 ◦C for 2 h or
was allowed to warm up to room temperature within 16 h. After
evaporation of the solvent in vacuo and flash chromatography
(hexanes/ethyl acetate/triethylamine = 99 : 0 : 1–97 : 2 : 1) the pure
product was obtained.
1-(2-(Tributylstannyl)allyl)piperidine (2a). Following the gen-
eral procedure for allylic aminations 2a was obtained from piperi-
dine (24 mg, 0.275 mmol) and 2-(tributylstannyl)allyl carbonate
1a (105 mg, 0.25 mmol) in 2 h at 0 ◦C. After evaporation of
the solvent in vacuo and flash chromatography (hexanes/ethyl
acetate/triethylamine = 99 : 0 : 1–97 : 2 : 1) the desired product
could be isolated in 94% yield (98 mg, 0.236 mmol) as a colorless
oil. 1H NMR: d 5.76 (m, JSn = 138.6 Hz, 1H), 5.17 (m, JSn = 62.8 Hz,
1H), 2.98 (m, JSn = 47.1 Hz, 2H), 2.27 (m, 4H), 1.59–1.44 (m, 10H),
1.40 (m, 2H), 1.36–1.27 (m, 6H), 0.97–0.80 (m, 15H). 13C NMR: d
155.8, 124.9, 69.8, 54.7, 29.2 (JSn = 19.4 Hz), 27.5 (JSn = 57.3 Hz),
26.1, 24.5, 13.7, 9.6 (JSn = 328.8 Hz). 119Sn NMR: d -50.1. MS (CI)
m/z 415 (5, M+), 359 (100), 125 (9), 84 (18). HRMS (CI) m/z calcd
for C20H41NSn [M]+: 415.2261. Found: 415.2273. Anal. calcd for
C20H41NSn (414.24): C 57.99; H 9.98; N 3.38. Found: C 57.89; H
10.04; N 3.27.
Scheme 2 Allylic aminations and following reactions.
The stannylated allylamine intermediate can also be subjected
to a tin-halogen exchange, giving rise e.g. to iodinated ally-
lamines such as 9c, compounds which are interesting synthetic
intermediates as well. Treatment of 9c with strong base resulted
in an intramolecular SN-reaction towards methylene aziridine
10a,13 while a Pd-catalyzed carbonylation gave direct access to
methylene-substitued b-lactams (10b).14
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General procedure for Stille couplings of stannylated amines
complete consumption of the intermediate stannylated amine (0.5
to 24 h). After the solution was cooled to room temperature, it
was diluted with diethyl ether and extracted three times with 1
N HCl. The combined aqueous layers were neutralised with sat.
NaHCO3 solution and then extracted twice with diethyl ether. The
combined organic layers were dried with anhydrous Na2SO4, and
after evaporation of the solvent in vacuo the crude product was
purified by flash chromatography.
Method 1: Thermal conditions. In a Schlenk flask [allylPdCl]2
(2.0 mg, 5 mmol, 2 mol%) and PPh3 (2.6 mg, 10 mmol, 4 mol%)
were dissolved in dry THF (1 mL) and stirred for 15 min at
room temperature under nitrogen. In a second Schlenk flask 2-
(tributylstannyl)allyl piperidine 2a (105 mg, 0.25 mmol) and the
electrophile (0.5 mmol) were dissolved in dry THF (1 mL) and
heated to 60 ◦C. Then the catalyst solution was added and the
reaction mixture was stirred at the indicated temperature until
TLC showed complete consumption of the stannylated amine (2
to 3 d). After completion of the reaction, water (5 mL) and a small
amount of KF were added and the resulting mixture was stirred
overnight. Then ethyl acetate was added and the organic layer was
separated. The aqueous phase was extracted three times with ethyl
acetate and the combined organic layers were dried over Na2SO4.
After evaporation of the solvent in vacuo the crude product was
purified by flash chromatography.
1-(2-Phenylallyl)piperidine (3b). Following the general pro-
cedure for one-pot allylic aminations/Stille couplings 3b was
obtained from piperidine (21.3 mg, 0.25 mmol), ethyl 2-
(tributylstannyl)allyl carbonate 1a (109 mg, 0.26 mmol) and
phenyliodide (102 mg, 0.5 mmol) with [allylPdCl]2 (0.9 mg,
2.5 mmol, 1 mol%) and PPh3 (5.2 mg, 20 mmol, 8 mol%) as catalyst.
For the Stille coupling the reaction mixture was heated up to 65 ◦C
for 16 h. After work-up and flash chromatography (hexanes/ethyl
acetate = 9 : 1–1 : 1) the product could be isolated in 96% yield
1
(48 mg, 0.240 mmol) as a colorless oil. H NMR: d 7.54–7.51
Method 2: Microwave conditions. In a microwave reaction
vessel [allylPdCl]2 (2.0 mg, 5 mmol, 2 mol%) and PPh3 (2.6 mg,
10 mmol, 4 mol%) were dissolved in dry THF (2 mL) and stirred
for 15 min at room temperature under nitrogen. After addition
of 2-(tributylstannyl)allyl piperidine 2a (105 mg, 0.25 mmol) and
the electrophile (0.5 mmol) the reaction mixture was heated in a
microwave oven for 1 h to 100 ◦C (300 W). After completion of the
reaction, water (5 mL) and a small amount of KF were added and
the resulting mixture was stirred overnight. Then ethyl acetate was
added and the organic layer was separated. The aqueous phase was
extracted three times with ethyl acetate and the combined organic
layers were dried over Na2SO4. After evaporation of the solvent in
vacuo the crude product was purified by flash chromatography.
(m, 2H), 7.34–7.29 (m, 2H), 7.27–7.24 (m, 1H), 5.45 (s, 1H), 5.24
(s, 1H), 3.29 (s, 2H), 2.41 (m, 4H), 1.58–1.52 (m, 4H), 1.44–1.38
(m, 2H). 13C NMR: d 144.6, 140.8, 128.1, 127.3, 126.3, 114.8,
63.7, 54.6, 26.0, 24.5. MS (CI) m/z 201 (20, M+), 115 (4), 98
(100). HRMS (CI) m/z calcd for C14H19N [M]+: 201.1517. Found:
201.1482.
1-(2-(4-Bromophenyl)allyl)piperidine (3l). Following the gen-
eral procedure for one-pot allylic aminations/Stille couplings 3l
was obtained from piperidine (21.3 mg, 0.25 mmol), ethyl 2-
(tributylstannyl)allyl carbonate 1a (109 mg, 0.26 mmol) and p-
bromophenyliodide (74 mg, 0.26 mmol) with [allylPdCl]2 (0.9 mg,
2.5 mmol, 1 mol%) and PPh3 (5.2 mg, 20 mmol, 8 mol%) as catalyst.
For the Stille coupling the reaction mixture was heated up to 65 ◦C
for 16 h. After work-up and flash chromatography (hexanes/ethyl
acetate = 9 : 1–1 : 1) the product could be isolated in 96% yield
(67 mg, 0.240 mmol) as a colorless oil. 1H NMR: d 7.42 (m, 4H),
5.44 (m, 1H), 5.23 (m, 1H), 3.24 (s, 2H), 2.37 (m, 4H), 1.53 (m, 4H),
1.42 (m, 2H). 13C NMR: d 143.6, 139.5, 131.1, 128.1, 121.3, 115.5,
63.7, 54.5, 26.0, 24.4. MS (CI) m/z 280 (31, M+), 202 (10), 116 (1),
98 (100). HRMS (CI) m/z calcd for C14H18NBr [M]+: 279.0623.
Found: 279.0581.
1-(2-Methylenepent-4-enyl)piperidine (3a). Following the gen-
eral procedure for Stille couplings of stannylated amines under Mi-
crowave conditions, 3a was obtained from 2-(tributylstannyl)allyl
piperidine 2a (105 mg, 0.25 mmol) and allyl bromide (61 mg,
0.5 mmol, 2 equiv). After work-up and flash chromatography
(hexanes/ethyl acetate = 95 : 5–8 : 2) the product could be isolated
in 97% yield (40 mg, 0.243 mmol) as a colorless oil. 1H NMR: d
5.85 (ddt, J = 17.1, 10.1, 7.0 Hz, 1H), 5.09–5.01 (m, 2H), 4.93 (m,
1H), 4.85 (m, 1H), 2.83 (s, 2H), 2.81 (d, J = 7.0 Hz, 2H), 2.37–2.25
(m, 4H), 1.58–1.52 (m, 4H), 1.44–1.40 (m, 2H). 13C NMR: d 145.7,
136.5, 115.9, 112.3, 64.7, 54.6, 38.7, 26.1 24.5. MS (CI) m/z 165
(40, M+), 98 (100), 84 (40). HRMS (CI) m/z calcd for C11H19N
[M]+: 165.1517. Found: 165.1528.
1-(2-Phenylallyl)piperidine (3m). Following the general pro-
cedure for one-pot allylic aminations/Stille couplings 3m was
obtained from piperidine (21.3 mg, 0.25 mmol), ethyl 2-
(tributylstannyl)allyl carbonate 1a (109 mg, 0.26 mmol) p-
bromophenyliodide (74 mg, 0.26 mmol) with [allylPdCl]2 (0.9 mg,
2.5 mmol, 1 mol%) and PPh3 (5.2 mg, 20 mmol, 8 mol%) as catalyst.
For the first Stille coupling the reaction mixture was heated
up to 65 ◦C for 16 h. Then tributyl(2-furyl)stannane (179 mg,
0.50 mmol) and LiCl (32 mg, 0.75 mmol) were added and the
mixture was heated up to 130 ◦C for 16 h. After work-up and flash
chromatography (hexanes/ethyl acetate = 9 : 1–1 : 1) the product
could be isolated in 77% yield (53 mg, 0.192 mmol) as a colorless
General procedure for one-pot allylic aminations/Stille couplings
Pd(PPh3)4 (6 mg, 5.0 mmol, 2 mol%) or [allylPdCl]2 (0.9 mg,
2.5 mmol, 1 mol%) and PPh3 (5.2 mg, 20 mmol, 8 mol%) were
dissolved in dry DMF (2 mL) in a Schlenk flask under nitrogen
and stirred for 15 min at room temperature after which a yellow
solution was obtained. After addition of the amine (0.25 mmol)
the solution was cooled to 0 ◦C before ethyl 2-(tributylstannyl)
allyl carbonate 1a (109 mg, 0.26 mmol) was added dropwise.
The reaction mixture was allowed to warm slowly to room
temperature overnight. Subsequently, 1.2 to 2.0 equiv of the
electrophile were added and the mixture was stirred at the indicated
temperature (room temperature to 120 ◦C) until TLC showed
1
oil. H NMR: d 7.62 (m, 2H), 7.56 (m, 2H), 7.47 (m, 1H), 6.65
(m, 1H), 6.47 (m, 1H), 5.49 (s, 1H), 5.24 (s, 1H), 3.30 (s, 2H), 2.41
(m, 4H), 1.54 (m, 4H), 1.42 (m, 2H). 13C NMR: d 154.0, 144.0,
142.0, 139.6, 128.1, 126.6, 123.5, 114.9, 111.7, 104.9, 63.7, 54.6,
26.0, 24.5. MS (CI) m/z 268 (27, M+ + 1), 184 (58), 149 (56),
2748 | Org. Biomol. Chem., 2011, 9, 2743–2750
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98 (100). HRMS (CI) m/z calcd for C18H21NO [M]+: 267.1623.
Found: 267.1601.
7.1 Hz, 3H). 13C NMR: d 163.3, 140.2, 137.1, 135.7, 131.9, 128.8,
128.8, 128.5, 128.2, 127.4, 127.3, 123.0, 112.0, 50.3, 46.6, 15.7.
MS (CI) m/z 274 (98, M+ + 1), 218 (100), 172 (48), 130 (15), 115
(10). HRMS (CI) m/z calcd for C16H19N [M]+: 273.1365. Found:
273.1336.
(E)-1-(2-Methylene-5-phenylpent-4-enyl)piperidine (3n). Fol-
lowing the general procedure for one-pot allylic aminations/Stille
couplings 3n was obtained from piperidine (21.3 mg, 0.25 mmol),
ethyl 2-(tributylstannyl)allyl carbonate 1a (109 mg, 0.26 mmol)
and cinnamyl ethyl carbonate (103 mg, 0.50 mmol) with
[allylPdCl]2 (0.9 mg, 2.5 mmol, 1 mol%) and PPh3 (5.2 mg,
20 mmol, 8 mol%) as catalyst. For the Stille coupling the reaction
mixture was heated up to 90 ◦C for 16h. After work-up and flash
chromatography (hexanes/ethyl acetate = 9 : 1–1 : 1) the product
could be isolated in 92% yield (55 mg, 0.230 mmol) as a colorless
oil with 97% (E)-double bond geometry. 1H NMR: d 7.36 (m, 2H),
7.29 (m, 2H), 7.20 (m, 1H), 6.44 (d, J = 15.8 Hz, 1H), 6.26 (dt,
J = 15.8, 7.1 Hz, 1H), 4.97 (m, 1H), 4.92 (m, 1H), 2.98 (m, 2H),
2.89 (s, 2H), 2.33 (m, 4H), 1.58 (m, 4H), 1.43 (m, 2H); (Z)-isomer
(selected signals): d 6.55 (d, J = 11.5 Hz, 1H), 5.76 (dt, J = 11.6,
7.8 Hz, 1H), 3.06 (d, J = 7.7 Hz, 2H). 13C NMR: d 145.8; 137.7,
131.2, 128.4, 126.8, 126.0, 117.7, 112.6, 64.7, 54.6; 37.8, 26.0, 24.5.
MS (CI) m/z 241 (100, M+), 136 (52), 98 (62). HRMS (CI) m/z
calcd for C17H23N [M]+: 241.1830. Found: 241.1831.
2-Iodo-N-(1-phenylethyl)prop-2-en-1-amine (9c). In a Schlenk
flask Pd(PPh3)4 (32 mg, 28.0 mmol,
5 mol%) and 1-
phenylethylamine (667 mg, 5.5 mmol) were dissolved in dry DMF
(10 mL) under nitrogen. The solution was cooled to 0 ◦C and
ethyl 2-(tributylstannyl)allyl carbonate 1a (2.10 g, 5.0 mmol) was
added dropwise. The reaction mixture was allowed to warm up
to room temperature within 16 h and was diluted with diethyl
ether (10 mL). I2 (1.52 g, 6.0 mmol) was slowly added and the
mixture was stirred for 30 min at room temperature. The solution
was diluted with diethyl ether and washed with a mixture of
sat. NaHCO3 and sat. Na2S2O3 solution. The organic layer was
extracted three times with 1 N HCl. The combined aqueous layers
were neutralised with sat. NaHCO3 solution and then extracted
twice with diethyl ether. The combined organic layers were dried
with anhydrous Na2SO4. After evaporation of the solvent in vacuo
and flash chromatography (hexanes/ethyl acetate = 90 : 10) the
desired product could be isolated in 76% yield (1.06 g, 3.69 mmol)
as a yellow oil. 1H NMR: d 7.37–7.30 (m, 4H), 7.25 (m, 1H), 6.13
(m, 1H), 5.85 (m, 1H), 3.78 (q, J = 6.6 Hz, 1H), 3.31 (m, 1H),
3.13 (m, 1H), 1.85 (bs, 1H), 1.37 (d, J = 6.6 Hz, 3H). 13C NMR: d
144.8, 128.4, 127.1, 126.9, 126.2, 113.7, 58.5, 55.3, 24.2. MS (CI)
m/z 288 (16, M+ + 1), 272 (100), 210 ((3), 144 (8), 105 (25), 77
(5). HRMS (CI) m/z calcd for C11H14IN [M]+: 287.0171. Found:
287.0170. Anal. calcd for C11H14IN (287.14): C 46.01; H 4.91; N
4.88. Found: C 46.07; H 4.71; N 5.37.
1-Phenyl-2-(piperidin-1-ylmethyl)prop-2-en-1-one (3o). Follo-
wing a modified procedure for one-pot allylic aminations/Stille
couplings 3o was obtained from piperidine (21.3 mg, 0.25 mmol),
ethyl 2-(tributylstannyl)allyl carbonate 1a (109 mg, 0.26 mmol),
CO and phenyliodide (102 mg, 0.50 mmol) with [allylPdCl]2
(0.9 mg, 2.5 mmol, 1 mol%) and PPh3 (5.2 mg, 20 mmol, 8 mol%) as
catalyst. After completion of the allylic amination, the atmosphere
above the reaction mixture was changed to a CO atmosphere, and
the reaction mixture was stirred for 15 min before the phenyliodide
was added. The mixture was then heated to 65 ◦C for 16 h. After
work-up and flash chromatography (hexanes/ethyl acetate = 9 : 1–
1 : 1) the product could be isolated in 88% (50 mg, 0.220 mmol)
yield as a colorless oil. 1H NMR: d 7.79 (m, 2H), 7.54 (m, 1H), 7.44
(m, 2H), 6.02 (m, 1H), 5.73 (m, 1H), 3.38 (s, 2H), 2.46 (m, 4H),
1.57 (m, 4H), 1.42 (m, 2H). 13C NMR: d 192.7, 144.9, 137.5, 132.2,
131.7, 129.5, 128.2, 54.5, 25.9, 24.2. MS (CI) m/z 230 (34, M+ +
1), 212 (42), 98 (100). HRMS (CI) m/z calcd for C15H19NO [M]+:
229.1467. Found: 229.1448.
2-Methylene-1-(1-phenylethyl)aziridine (10a). Under nitrogen
NaNH2 (146 mg, 3.75 m◦mol) was added to a Schlenk flask. The
flask was cooled to -78 C and NH3 (1 mL) was condensed. 9c
(72 mg, 0.25 mmol) was added and the resulting suspension was
stirred for 30 min at -78 ◦C. Dry THF (2 mL) was added dropwise
and the solution was stirred for 30 min at -78 ◦C after which TLC
showed completion of the reaction. Diethyl ether (5 mL) and water
(5 mL) were slowly added and the mixture was allowed to warm
up to room temperature. The ether layer was separated and the
aqueous phase was extracted three times with diethyl ether. The
combined organic layers were washed with 1 M NaOH solution
and then dried over Na2SO4. After evaporation of the solvent in
vacuo and flash chromatography (pentane/ether 95 : 5) the desired
product could be isolated in 75% yield (30 mg, 0.188 mmol) as a
colorless oil. 1H NMR: d 7.31–7.24 (m, 4H), 7.19 (m, 1H), 4.58–
4.56 (m, 2H), 2.85 (q, J = 6.6 Hz, 1H), 2.03 (s, 1H), 1.93 (s, 1H),
1.44 (d, J = 6.6 Hz, 3H). 13C NMR: d 143.9, 137.1, 128.4, 127.2,
126.7, 83.1, 68.5, 29.9, 23.5. MS (CI) m/z 160 (100, M+ + 1), 105
(8), 56 (1). HRMS (CI) m/z calcd for C11H13N [M]+: 159.1048.
Found: 159.1040.
4-Methylene-2-(1-phenylethyl)-3,4-dihydroisoquinolin-1(2H)-
one (9b). Following the general procedure for one-pot allylic am-
inations/Stille couplings 9b was obtained from phenylethylamine
(30.3 mg, 0.25 mmol), ethyl 2-(tributylstannyl)-allyl carbonate
1a (109 mg, 0.26 mmol) and ethyl 2-iodobenzoate (138 mg,
0.50 mmol) with [allylPdCl]2 (0.9 mg, 2.5 mmol, 1 mol%) and PPh3
(5.2 mg, 20 mmol, 8 mol%) as catalyst. For the Stille coupling the
reaction mixture was heated up to 90 ◦C for 16 h and then to
120 ◦C for 6 h. After cooling to room temperature the reaction
mixture was diluted with diethyl ether and washed with 1 N
HCl, sat. NaHCO3 solution and conc. KF solution. The organic
layer was dried with anhydrous Na2SO4. After evaporation of
the solvent in vacuo and flash chromatography (hexanes/ethyl
acetate = 90 : 10) the desired product could be isolated in 62%
yield (41 mg, 0.155 mmol) as a colorless oil. 1H NMR: d 8.22 (m,
1H), 7.53–7.43 (m, 3H), 7.39–7.33 (m, 4H), 7.28 (m, 1H), 6.29 (q,
J = 7.1 Hz, 1H), 5.49 (m, 1H), 5.06 (m, 1H), 4.02 (ddd, J = 14.2,
1.6, 1.6 Hz, 1H), 3.71 (ddd, J = 14.2, 1.3, 1.3 Hz, 1H), 1.62 (d, J =
3-Methylene-1-(1-phenylethyl)azetidin-2-one
(10b). In
a
Schlenk flask [allylPdCl]2 (2.0 mg, 5 mmol, 2 mol%) and PPh3
(2.6 mg, 10 mmol, 4 mol%) were dissolved in dry DMF (2 mL)
and stirred for 10 min at room temperature under nitrogen. The
nitrogen atmosphere was removed and the Schlenk flask was
connected via a syringe to a balloon filled with CO. The catalyst
solution was stirred for 10 min under CO. Triethylamine (51 mg,
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0.5 mmol) and 9c (72 mg, 0.25 mmol) were then added and the
resulting mixture was stirred for 16 h at 65 ◦C, during which
the color of the solution turned from yellow to red. After the
reaction mixture was cooled to room temperature, it was diluted
with diethyl ether and washed with 1 N HCl and sat. NaHCO3
solution. The organic layer was dried with anhydrous Na2SO4 and
the solvent was removed in vacuo. After flash chromatography
(hexanes/ethyl acetate = 1 : 1) the desired product could be
Chem., 2003, 1, 3867–3870; (d) S. L. Schreiber, Chem. Eng. News, 2003,
81, 51–61; (e) A. Nefzi, J. M. Ostresh, J. Yu and R. A. Houghten,
J. Org. Chem., 2004, 69, 3603–3609; (f) M A. Koch, L. O. Wittenberg,
S. Basu, D. A. Jeyaraj, E. Gourzoulidou, K. Reinecke, A. Odermatt
and H. Waldmann, Proc. Natl. Acad. Sci. U. S. A., 2004, 101, 16721–
16726; (g) M. A. Koch, A. Schuffenhauer, M. Scheck, S. Wetzel, M.
Casaulta, A. Odermatt, P. Ertl and H. Waldmann, Proc. Natl. Acad.
Sci. U. S. A., 2005, 102, 17272–17277; (h) P. Arya, R. Joseph, Z. Gan
and B. Rakic, Chem. Biol., 2005, 12, 163–180; (i) K. Kumar and H.
Waldmann, Angew. Chem., 2009, 121, 3272–3290, (Angew. Chem., Int.
Ed., 2009, 48, 3224).
2 (a) D. S. Tan, M. A. Foley, M. D. Shair and S. L. Schreiber, J. Am.
Chem. Soc., 1998, 120, 8565–8566; (b) S. L. Schreiber, Science, 2000,
287, 1964–1969; (c) M. D. Burke, E. M. Berger and S. L. Schreiber,
Science, 2003, 302, 613–618; (d) M. D. Burke, E. M. Berger and S. L.
Schreiber, J. Am. Chem. Soc., 2004, 126, 14095–14104.
3 For recent reviews see: (a) D. Tejedor and F. Garcia-Tellado, Chem.
Soc. Rev., 2007, 36, 484–491; (b) T. E. Nielsen and S. L. Schreiber,
Angew. Chem., 2008, 120, 52–61, (Angew. Chem., Int. Ed., 2008, 47,
48); (c) R. J. Spandl, A. Bender and D. R. Spring, Org. Biomol. Chem.,
2008, 6, 1149–1158 and references cited therein.
4 (a) J. Tsuji in Handbook of Organopalladium Chemistry for Organic
Synthesis, Vol. 2, ed. E.-I. Negishi and A. de Meijere, John Wiley, New
York, 2002, pp. 1669–1688; (b) L. Acemoglu and J. M. J. Williams, in
Handbook of Organopalladium Chemistry for Organic Synthesis, Vol.
2, ed. E.-I. Negishi and A. de Meijere, John Wiley, New York, 2002,
pp. 1689–1705; (c) B. M. Trost and M. L. Crawley, Chem. Rev., 2003,
103, 2921–2944; (d) U. Kazmaier and M. Pohlman, in Metal Catalyzed
C-C and C-N Coupling Reactions, ed. A. de Meijere and F. Diederich,
Wiley-VCH, Weinheim, 2004, pp. 531–583. and references cited therein.
5 J. K. Stille, Angew. Chem., 1986, 98, 504–519, (Angew. Chem., Int. Ed.
Engl., 1986, 25, 508).
1
isolated in 71% yield (33 mg, 0.178 mmol) as a colorless oil. H
NMR: d 7.38–7.26 (m, 5H), 5.70 (m, 1H), 5.13 (m, 1H), 5.04 (q,
J = 7.0 Hz, 1H), 3.71 (dt, J = 7.5, 1.4 Hz, 1H), 3.52 (dt, J = 7.5,
1.4 Hz, 1H), 1.64 (d, J = 7.0 Hz, 3H). 13C NMR: d 163.0, 144.5,
140.3, 128.8, 127.7, 126.7, 109.3, 51.6, 45.9, 18.5. MS (CI) m/z
188 (13, M+ + 1), 172 (100), 132 (15), 105 (35), 91 (8), 69 (13).
HRMS (CI) m/z calcd for C12H13NO [M]+: 187.0997. Found:
187.1014. Anal. calcd for C12H13NO (187.24): C 76.98; H 7.00; N
7.48. Found: C 76.49; H 7.01; N 7.43.
tert-Butyl 2-(4-methylene-3,4-dihydroisoquinolin-2(1H)-yl)ace-
tate (11a). Following the general procedure for one-pot allylic
aminations/Stille couplings 11a was obtained from H2N-Gly-
OtBu (33 mg, 0.25 mmol), ethyl 2-(tributylstannyl)-allyl carbonate
1a (109 mg, 0.26 mmol) and ethyl 2-iodobenzyl carbonate (92 mg,
0.30 mmol) with [allylPdCl]2 (0.9 mg, 2.5 mmol, 1 mol%) and PPh3
(5.2 mg, 20 mmol, 8 mol%) as catalyst. For the Stille coupling the
reaction mixture was heated up to 90 ◦C for 16 h and then to 130 ◦C
for 2 h. After work-up and flash chromatography (hexanes/ethyl
acetate = 9 : 1–1 : 1) the product could be isolated in 69% (45 mg,
6 (a) U. Kazmaier, D. Schauß and M. Pohlman, Org. Lett., 1999, 1,
1017–1019; (b) U. Kazmaier, M. Pohlman and D. Schauß, Eur. J. Org.
Chem., 2000, 2761–2766; (c) S. Braune and U. Kazmaier, J. Organomet.
Chem., 2002, 641, 26–29; (d) S. Braune, M. Pohlman and U. Kazmaier,
J. Org. Chem., 2004, 69, 468–474; (e) U. Kazmaier and M. Klein,
Chem. Commun., 2005, 501–503; (f) U. Kazmaier and A. Wesquet,
Synlett, 2005, 1271–1274; (g) A. O. Wesquet, S. Do¨rrenba¨cher and U.
Kazmaier, Synlett, 2006, 1105–1109; (h) U. Kazmaier, S. Do¨rrenba¨cher,
A. Wesquet, S. Lucas and M. Kummeter, Synthesis, 2007, 320–326;
(i) N. Jena and U. Kazmaier, Eur. J. Org. Chem., 2008, 3852–3858.
7 A. O. Wesquet and U. Kazmaier, Adv. Synth. Catal., 2009, 351, 1395–
1404.
1
0.173 mmol) yield as a colorless oil. H NMR: d 7.66 (m, 1H),
7.22–7.05 (m, 2H), 7.06 (m, 1H), 5.62 (s, 1H), 5.02 (s, 1H), 3.95 (s,
2H), 3.31 (s, 2H), 1.48 (s, 9H). 13C NMR: d 169.6, 138.5, 134.0,
132.0, 127.9, 126.9, 126.6, 123.4, 108.3, 81.2, 57.7, 57.6, 55.7, 28.2.
MS (CI) m/z 259 (41, M+ + 1), 232 (50), 204 (30), 158 (50), 144
(100), 115 (13), 57 (82). HRMS (CI) m/z calcd for C11H12N [M-
tBu-CO2]+: 158.0970. Found: 158.0931.
8 (a) U. Kazmaier, D. Schauß, M. Pohlman and S. Raddatz, Synthesis,
2000, 914–916; (b) U. Kazmaier, D. Schauß, S. Raddatz and M.
Pohlman, Chem.–Eur. J., 2001, 7, 456–464; (c) H. Lin and U. Kazmaier,
Eur. J. Org. Chem., 2007, 2839–2843.
Acknowledgements
9 (a) J. Deska and U. Kazmaier, Angew. Chem., 2007, 119, 4654–4657,
(Angew. Chem., Int. Ed., 2007, 46, 4570); (b) J. Deska and U. Kazmaier,
Chem.–Eur. J., 2007, 13, 6204–6211; (c) S. Datta and U. Kazmaier, Org.
Biomol. Chem., 2011, 9, 872.
Financial support from the Deutsche Forschungsgemeinschaft
(Ka 880/8) as well as the Fonds der Chemischen Industrie is
gratefully acknowledged.
10 (a) S. Do¨rrenba¨cher, U. Kazmaier and S. Ruf, Synlett, 2006, 547–550;
(b) J. Deska and U. Kazmaier, Curr. Org. Chem., 2008, 12, 355–385.
11 A. O. Wesquet and U. Kazmaier, Angew. Chem., 2008, 120, 3093–3096,
(Angew. Chem., Int. Ed., 2008, 47, 3050).
12 C. Bukovec and U. Kazmaier, Org. Lett., 2009, 11, 3518–3521.
13 J. Ince, T. M. Ross, M. Shipman and A. M. Z. Slawin, Tetrahedron,
1996, 52, 7037–7044.
References
1 (a) R. Breinbauer, I. R. Vetter and H. Waldmann, Angew. Chem., 2002,
114, 3002–3015, (Angew. Chem., Int. Ed., 2002, 41, 2878); (b) T.-C.
Chou, H. Dong, A. Rivkin, F. Yoshimura, A. E. Gabarda, Y. S. Cho,
W. P. Tong and S. J. Danishefsky, Angew. Chem., 2003, 115, 4910–4915,
(Angew. Chem., Int. Ed., 2003, 42, 4762); (c) D. R. Spring, Org. Biomol.
14 M. Mow, K. Cwu, M. Outa, I. Kayo and Y. Ban, Tetrahedron, 1985,
41, 375–385.
2750 | Org. Biomol. Chem., 2011, 9, 2743–2750
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