Practical highly enantioselective synthesis of propargylamines through a copper-catalyzed one-pot three-component condensation reaction

Article abstract of DOI:10.1002/chem.200501233

The one-pot three-component reaction of terminal alkynes, aldehydes and secondary amines in the presence of copper(1) bromide/quinap is reported. The reaction scope has been determined and a broad variety of all three components has been used, which afforded the corresponding propargylamines in good to excellent yields and moderate to very good enantioselectivities. The reaction showed a strong positive nonlinear effect. The transformation of a propargylamine intermediate into the alkaloid (S-(+)-coniine has also been described.

Full text of DOI:10.1002/chem.200501233

DOI: 10.1002/chem.200501233
Practical Highly Enantioselective Synthesis of Propargylamines through a
Copper-Catalyzed One-Pot Three-Component Condensation Reaction
Nina Gommermann and Paul Knochel*[a]
Abstract: The one-pot three-component reaction of terminal alkynes,aldehydes
and secondary amines in the presence of copper(i) bromide/quinap is reported.
Keywords: alkynes
·
asymmetric
The reaction scope has been determined and a broad variety of all three compo-
nents has been used,which afforded the corresponding propargylamines in good
to excellent yields and moderate to very good enantioselectivities. The reaction
showed a strong positive nonlinear effect. The transformation of a propargylamine
intermediate into the alkaloid (S)-(+)-coniine has also been described.
À
catalysis
multicomponent
·
C H activation
·
·
reactions
organocatalysis · propargylamine
Introduction
dehydes and secondary amines. In this paper,we disclose
detailed studies on the parameters influencing the outcome
of this asymmetric reaction. Furthermore,we demonstrate
its broad scope and synthetic utility.
One of the most challenging tasks in organic synthesis is the
efficient preparation of complex molecules starting from
easily available raw materials. Especially attractive are
multicomponent reactions which allow the formation of
À
several bonds including new carbon carbon bonds in a one-
Results and Discussion
pot procedure.[1] This type of reaction plays an important
role in modern organic chemistry,since it exhibits generally
a high atom economy[2] and selectivity,as well as a lower
level of by-products compared with classical stepwise syn-
thesis. The Strecker reaction,developed in 1850,has been
recognized as the first multicomponent reaction.[3] This
three-component coupling of an amine,a carbonyl com-
pound and hydrogen cyanide giving a-aminonitriles estab-
lishes an important route to a-amino acids. The amino
group itself is one of the fundamental structures in organic
chemistry. Amines and their derivatives are widespread
functional groups which are found in various natural prod-
ucts,pharmaceuticals and fine biologically important chemi-
cals.[4] Propargylamines are both biologically relevant and
The three-component coupling of terminal alkynes 1,alde-
hydes 2 and secondary amines 3 in the presence of copper(i)
bromide (5 mol%) and guinap[8] (5.5 mol%) as the catalytic
system was found to be a highly efficient process. The de-
sired propargylamines of type 4 are obtained in general high
yield and moderate to excellent enantioselectivities
(Scheme 1).
useful synthetic intermediates for the preparation of poly-
Scheme 1. Asymmetric three-component synthesis of propargylamines.
[6]
functional amino derivatives.[5] Recently,we
and others[7]
have developed an asymmetric multicomponent one-pot
copper-catalyzed preparation of propargylamines by the ad-
dition of alkynes to in situ generated iminium ions from al-
Variations in all three components were carried out and a
broad substrate scope was found. Thus,various mono-substi-
tuted and protected terminal alkynes 1 were investigated,as
well as various aldehydes 2. Aliphatic as well as aromatic al-
dehydes were successfully used in this reaction,but aliphatic
aldehydes were usually leading to higher enantioselectivities.
As amine component,different types of aliphatic secondary
amines 3 were successfully used in the reaction. Special at-
[a] Dr. N. Gommermann,Prof. Dr. P. Knochel
Department Chemie,Ludwig-Maximilians-Universität
Butenandtstrasse 5–13,Haus F,81377 München (Germany)
Fax : (+49)89-2180-77680
E-mail: paul.knochel@cup.uni-muenchen.de
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FULL PAPER
tention was paid to reactions using dibenzylamine (3a) and
diallylamine (3b) as amine component,since these substitu-
ents can be removed by standard protecting group method-
ologies.[9] Furthermore,the sterical demand of the benzyl
groups in dibenzylamine (3a) was found to be especially
well suited for achieving high enantioselectivities. Amines
derived from anilines as well as amides were found not to
be suited for the formation of the desired propargylamines.
A summary of the products obtained by this method is dis-
played in Table 1.
The conversion is usually completed within 12–48 h for
the racemic reaction performed without ligand and within
1–6 d for the enantioselective reaction. Different alkynes
1a–d bearing either a phenyl,an alkyl or an alkenyl group
Table 1. Enantioselective three-component one-pot synthesis of propargylamines 4.
Entry
1
Alkyne (R1) 1
1a: R1 =Ph
Aldehyde (R2) 2
2a: R2 =nBu
Amine (R3) 3
3a: R3 =Bn
Propargylamine 4
Yield [%][a]
85
ee [%][b]
83
4a
2
3
1a: R1 =Ph
2b: R2 =iBu
2b: R2 =iBu
3a: R3 =Bn
3a: R3 =Bn
4b: R=Ph
4c: R=nBu
98
85
86
82
1b: R1 =nBu
4
5
1a: R1 =Ph
2c: R2 =iPr
2c: R2 =iPr
3a: R3 =Bn
3a: R3 =Bn
4d: R=Ph
4e: R=p-BrC6H4
60
99
84
83
1c: R1 =p-BrC6H4
6
7
8
1a: R1 =Ph
1a: R1 =Ph
1a: R1 =Ph
2d: R2 =Ph
3b: R3 =allyl
3b: R3 =allyl
3b: R3 =allyl
4 f: R=H
4g: R=OMe
4h: R=CF3
91
76
43
70
60
63
2e: R2 =p-MeO-C6H4
2 f: R2 =p-CF3-C6H4
9
10
1a: R1 =Ph
1a: R1 =Ph
2g: R2 =o-CH3-C6H4
2h: R2 =o-Br-C6H4
3b: R3 =allyl
3b: R3 =allyl
4i: R=Me
4j: R=Br
84
83
32
25
11
12
1a: R1 =Ph
2i
2i
3b: R3 =allyl
3b: R3 =allyl
4k: R=Ph
4l: R=c-hexenyl
80
61
78
74
1d: R1 =c-hexenyl
13
1a: R1 =Ph
3b: R3 =allyl
55
64[c]
2j
4m
4n
14
1a: R1 =Ph
3b: R3 =allyl
63
44
2k
15
16
1a: R1 =Ph
1a: R1 =Ph
2l
2l
3b: R3 =allyl
3a: R3 =Bn
4o: R=allyl
4p: R=Bn
85
84
70
76
[a] Isolated yield of analytically pure product. [b] Enantiomeric excess determined by HPLC using a Chiracel OD-H column (n-heptane/iPrOH). [c] The
ee value was determined after deprotection to give the monodeallylated derivative.
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P. Knochel and N. Gommermann
were successfully utilized. In this study,phenylacetylene
(1a) gave the best selectivities. Branched as well as un-
branched aliphatic aldehydes 2a–c were successfully used as
substrates (entries 1–5). Their reaction with dibenzylamine
(3a) as the amine component led to high enantioselectivities
(82–86% ee). For aromatic aldehydes,it was found that the
presence of either an electron-donating or an electron-with-
drawing substituent in para-position has only a moderate in-
fluence on the reaction enantioselectivity (compare en-
tries 6–8,60–70% ee). However,the yield of product 4h (R
= CF3) was strongly reduced (entry 8,43%) compared with
that of 4 f (R = H) and 4g (R = OMe) (91 and 76%,en-
tries 6–7). A substituent in the ortho-position to the alde-
hyde function has a stronger influence on the enantioselec-
tivity of the reaction,probably due to the steric hindrance.
The use of 2-methylbenzaldehyde (2g) and 2-bromobenzal-
dehyde (2h) furnished products 4i–j with dramatically de-
creased enantiomeric excesses (32 and 25% ee,respective-
ly). Heteroaromatic aldehydes 2i–k were also compatible
and allowed the preparation of propargylamines 4k–n with
moderate to good selectivities (44–78% ee,entries 11–14).
Herein,the use of 3-pyridinecarbaldehyde ( 2k) was leading
to products with remarkably lower enantioselectivities than
the five-membered heterocyclic derivatives 2-benzothienyl-
carbaldehyde (2i) and 3-furancarbaldehyde (2j). Further-
more,ferrocenecarbaldehyde ( 2l) was successfully reacted
with phenylacetylene (1a) and either dibenzylamine (3a) or
diallylamine (3b) leading to products 4p and 4o with 76 and
70% ee,respectively (entries 15 and 16).
value (98 compared with 86% ee). The trimethylsilyl group
as alkyne substituent was found to be optimal for the enan-
tioselectivity of the three-component reaction. Changing
from a trimethylsilyl group to a tert-butyldimethylsilyl group
(compare 5a vs 6 in Scheme 2) is leading to a decreased se-
lectivity (5a: 98% ee; 6: 90% ee). The use of triisopropylsi-
lylacetylene is leading to an almost racemic mixture and
proceeds very sluggishly. Trimethylsilyl-substituted propar-
gylamine 5b was obtained in 99% yield and 97% ee,where-
as the triisopropylsilyl-derivative 7 was obtained with only
31% yield and 4% ee (Scheme 2).
Furthermore,the trimethylsilyl group was easily removed
by treatment of the silylated propargylamines 5 with Bu4NF
in THF or with KOH in MeOH (Scheme 3).
Scheme 3. Preparation of terminal propargylamines 8.
Silylated propargylamines 5 and terminal propargylamines
8 obtained by this method are shown in Table 2. Reaction of
trimethylsilylacetylene (1e) with dibenzylamine (3a) and
various aldehydes 2 in the presence of CuBr and quinap led
to silylated propargylamines 5 in high yields and exception-
ally high enantioselectivities. Various aliphatic and aromatic
aldehydes were successfully used. Unbranched aliphatic al-
dehydes 2a, m, n (R=nPr, nBu, n-pent) provide the expect-
ed propargylamines 5c–e in 88–90% ee and 82–99% yield.
The introduction of a branch in b-position of the aldehyde
(entries 4–5) is leading to an increased selectivity,giving 5 f–
g in 94% ee and 85–94% yield. Further improvement of the
selectivity was achieved using a-branched aldehydes such as
2c und 2p. The propargylamines 5h and 5a were obtained
in 96 and 98% ee,respectively. Aldehydes bearing cyclic ali-
phatic substituents were also successfully used,leading to
propargylamines 5i, 5j and 5b with 92–97% ee. The selec-
tivity increased with the size of the cycloalkyl residue. Cin-
namaldehydes reacted likewise giving propargylamines 5k–l
in 82–84% ee and 82–96% yield. Dihydrocinnamaldehydes
were also reacted successfully leading to propargylamines
5m–o. Functional groups on the aromatic ring such as ester-
and bromo-substituents were well tolerated and no decrease
of the enantioselectivity was observed (entries 13–15,87–
88% ee,73–96%). For aromatic aldehydes,the enantioselec-
tivity was generally lower than for aliphatic aldehydes. The
carbocyclic aldehydes 2d and 2y led to propargylamines
5p–q in 68 and 54% ee,respectively (entries 16–17). Inter-
estingly,thienyl- and benzothienylcarbaldehydes ( 2y–2ab)
gave propargylamines 5r–u with usually high enantioselec-
tivities. A higher selectivity was observed for propargyla-
mines derived from heterocycles with an aldehyde function
in 2-position to sulfur (80 vs 74% ee,entries 18 and 19; 89
vs 82% ee,entries 20 and 21). Most of the silylated propar-
gylamines 5 were transformed further to the terminal prop-
The preparation of terminal propargylamines was then in-
vestigated. The reaction with acetylene itself was investigat-
ed in previous studies in the related addition of alkynes to
enamines.[10] The mono-addition product was found to be
the major product. Unfortunately,it was not possible to
obtain high enantioselectivities using acetylene as alkyne
component. Therefore,we have examined various mono-
protected alkynes in the propargylamine synthesis
(Scheme 2).
Scheme 2. Alkyne protecting groups in the asymmetric propargylamine
synthesis.
As can be seen from Scheme 2,the size of the alkyne sub-
stituent plays a crucial role for the enantioselectivity of the
reaction. Compared with phenylacetylene as in for example
in propargylamine 4q,the introduction of a trimethylsilyl
group in propargylamine 5a led to an increase of the ee
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Enantioselective Synthesis
FULL PAPER
Table 2. Enantioselective three-component one-pot synthesis of silylated propargylamines 5 and desilylation to terminal propargylamines 8.
Entry
Aldehyde 2
Propargylamine 5
Yield [%][a]
ee [%][b]
Propargylamine 8
Yield [%][a]
1
2
3
4
5
6
7
8
2m: nPrCHO
2a: nBuCHO
2n: nPentCHO
2b: iBuCHO
2o: neo-PentCHO
2c: iPrCHO
2p: s-PentCHO
2q: c-PrCHO
2r: c-PentCHO
2s: c-HexCHO
5c: R=nPr
90
82
99
85
94
87
95
98
98
86
90[c]
90[c]
88[d]
94[d]
94[d]
96[c]
98[c]
92[c]
96
8a: R=nPr
98[e]
92[e]
96[e]
99[e]
99[e]
96[e]
98[e]
99[e]
99[e]
93[e]
5d: R=nBu
5e: R=nPent
5 f: R=iBu
5g: R=neo-Pent
5h: R=iPr
5a: R=s-Pent
5i: R=c-Pr
5j: R=c-Pent
5b: R=c-Hex
8b: R=nBu
8c: R=nPent
8d: R=iBu
8e: R=neo-Pent
8 f: R=iPr
8g: R=s-Pent
8h: R=c-Pr
8i: R=c-Pent
8j: R=c-Hex
9
10
97[c]
11
12
2t: PhCH=CH-CHO
2u: Ph2C=CH-CHO
5k: R=H
5l: R=Ph
96
82
82[c]
84[c]
8k: R=H
8l: R=Ph
97[f]
97[f]
13
14
15
2v: Ph
A
5m: R=H
5n: R=Br
5o: R=CO2Et
78
73
96
88[c]
88[c]
87
8m: R=H
8n: R=Br
8o: R=CO2Et
98[e]
98[e]
90[e]
2w: 4-Br-C6H4-(CH2)2CHO
2x: 4-CO2Et-C6H
16
17
18
19
20
21
2d: PhCHO
2y: 2-naphthyl-CHO
2z: 2-thiophen-CHO
2aa: 3-thiophen-CHO
2ab: 2-benzothiophenyl-CHO
2i: 3-benzothiophenyl-CHO
5p: Ar=Ph
98
69
81
85
42
92
68
54
5q: Ar=2-naphthyl
5r: Ar=2-thienyl
5s: Ar=3-thienyl
5t: Ar=2-benzothienyl
5u:Ar=3-benzothienyl
80[c]
74[c]
89
8p:Ar=2-thienyl
8q: Ar=3-thienyl
99[f]
99[f]
82
8r: Ar=3-benzothienyl
93[f]
[a] Isolated yield of analytically pure product. [b] Enantiomeric excess determined by HPLC analysis using Chiracel OD-H column (n-heptane/iPrOH).
[c] The ee was determined after desilylation. [d] The ee was determined after acylation with PhCOCl. [e] Desilylation was carried out with Bu4NF. [f] De-
silylation was carried out with KOH.
argylamines 8 by treatment with either Bu4NF or aq. KOH.
The yields were generally high (90–99%,see Table 2).
These terminal propargylamines can be further functional-
ized by known methods.[11] The synthetic utility of the
method was shown in a short enantioselective synthesis of
(S)-(+)-coniine (9).[12] Coniine is a highly toxic alkaloid in-
ducing curare-type paralysis. It is the main alkaloid of the
Schierling mushroom and used to poison Socrates 399 B.C.
The synthesis is depicted in Scheme 4 and starts with the
preparation of the chiral propargylamine 5c,which was ob-
tained in 90% yield and 90% ee from commercially availa-
ble starting materials. After desilylation giving 8a,the termi-
nal propargylamine was deprotonated with nBuLi
(1.2 equiv) and alkylated with ethylene oxide (3 equiv) in
the presence of BF3·OEt2 (1.2 equiv) under mild conditions
[13]
(À788C,2 h).
Silylation of the alcohol with TIPSCl
Scheme 4. Enantioselective synthesis of (S)-(+)-coniine 9.
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P. Knochel and N. Gommermann
(1.1 equiv) in the presence of DMAP (5 mol%) and imida-
zole (1.5 equiv) in DMF (08C to RT,12 h) led to TIPS-pro-
tected derivative 10 in 70% overall yield. Hydrogenolysis of
the benzyl groups and reduction of the triple bond was read-
ily achieved by hydrogenation (1 atm) of 10 in methanol in
the presence of Pd/C (10 mol%). The silyl-protected amino-
alcohol was desilylated with Bu4NF (THF,RT,12 h) and
subsequently submitted to an intramolecular Mitsunobu re-
15 and 16 (Scheme 7). A drawback of this interesting varia-
tion of the reaction is that no diastereoselectivity was ob-
served in the synthesis of diamines 15 and 16.
action (DEAD (1.1 equiv),PPh (1.1 equiv),THF, À108C to
3
[14]
RT,12 h).
(S)-(+)-coniine (9) was obtained in five steps
with 41% overall yield and 90% ee (see Scheme 4).
Furthermore,the propargylamine synthesis is highly dia-
stereoselective if a chiral amine or aldehyde is used. Thus,
the reaction of the proline-derived methoxymethylpyrroli-
dine (11) with benzaldehyde (2d) or valeraldehyde (2a) and
phenylacetylene (1a) produced the corresponding propar-
gylamines 12a and 12b in yields of 87 and 97% and good
diastereoselectivities of 96:4 and 93:7,respectively. By react-
ing ferrocenecarbaldehyde (2l) with trimethylsilylacteylene
(1e) and amine 11,the corresponding propargylamine 12c
Scheme 7. Propargyldiamines 15 and 16.
Mechanistic investigations show that the enantioselective
propargylamine synthesis displays a strong positive nonlin-
ear effect as discussed previously.[6a] Using the quinap ligand
with only 5% ee,the propargylamine 5a is still obtained
was obtained with
(Scheme 5).
a
diastereoselectivity of >98:2
with 50% ee. Furthermore,the reaction rate and the yield
are approximately linear correlated to the enantiomeric
excess of the ligand (Figure 1).
Scheme 5. Diastereoselective propargylamine synthesis with amine 11.
By reacting racemic hydratropaldehyde 13 with dibenzyla-
mine (3a) and trimethylsilylacetylene (1e) without the addi-
tion of the quinap ligand,the corresponding propargylamine
14 is also obtained in good diastereoselectivity (92:8). Addi-
tion of the chiral ligand led to 14 with an increased diaster-
eoselectivity (>99:1) and 64% ee (Scheme 6). The relative
conformation has been determined by X-ray structure analy-
sis.[15]
Figure 1. Influence of the enantiomeric excess on the reaction rate in the
synthesis of 5a.
Interestingly,diines and dialdehydes can also be used in
the propargylamine synthesis leading to propargyldiamines
As can be seen from Figure 1,the reaction rate decreases
with a decreasing enantiomeric excess of the ligand. This is
in accordance with the model of the reservoir effect descri-
bed first by Kagan.[16] According to this model,the Cu/
quinap catalyst forms dimeric species [Cu2quinap2],which is
in good agreement with the previously reported crystal
structure of the [CuBr{(R)-quinap}]2 complex.[10a] The heter-
ochiral complex [Cu2Br2{(R)/(S)-quinap}] seems to react at a
much slower rate than the corresponding homochiral com-
Scheme 6. Diastereoselective propargylamine synthesis with aldehyde 13.
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Enantioselective Synthesis
FULL PAPER
85%,83% ee) as a colourless oil. [a]2D0 = À239 (c=1.00,CHCl 3); 1H
plex [Cu2Br2{(R)/(R)-quinap}]. This explains the strong posi-
tive amplification. Since the minor enantiomer of the ligand
is kept in the more stable and less reactive complex,the
amount of reactive,homochiral copper/quinap complexes
decreases with the % ee of the ligand. The reservoir model
also explains the decrease in the reaction rate with the % ee
of the ligand. Based on these and previous results,we have
suggested a tentative mechanism (see ref. [6a]).
NMR (CDCl3,300 MHz): d=7.44–7.10 (m,15H),3.80 (d,
J=13.7 Hz,
2H),3.51 (t, J=7.4 Hz,1H),3.40 (d,
J=13.8 Hz,2H),1.78–1.56 (m,
2H),1.46–1.23 (m,2H),1.14 (sext,
J=7.2 Hz,2H),0.78 (t, J=7.1 Hz,
3H); 13C NMR (CDCl3,75 MHz): d=139.9,131.8,128.8,128.3,128.2,
127.8,126.8,123.6,88.1,85.2,55.0,52.2,33.6,28.6,22.3,13.5; MS:
m/z
(%): 310 (100) [M +ÀC4H9),218 (3),128 (2),115 (7),91 (57); HRMS
(EI): m/z: calcd for C27H33N: 366.2222; found: 366.2215 [M +ÀH]; IR
(film): n˜ = 3062 (w),3029 (w),2955 (s),2932 (s),1599 (m),1490 (s),
À1
1454 (s),755 (vs),698 cm
(vs); elemental analysis calcd (%) for
The dimeric chiral copper compound 17 forms a complex
with alkyne 1,leading to a side-on complex 18. Aminal 19,
formed by reaction of the aldehyde 2 with the secondary
amine 3,coordinates to the copper complex 18 to give com-
plex 20. Deprotonation of the coordinated alkyne and elimi-
nation of H2O led to complex 21,an end-on copper acety-
lide with a coordinated iminium ion. The addition of the
acetylide to the iminium ion in the coordination sphere of
the chiral copper(i) complex led to chiral propargylamine 4
or 5,respectively,and regenerates the catalyst 17.
C27H33N: C 88.24,H 7.95,N 3.81; found: C 87.85,H 7.84,N 3.73; HPLC
(OD-H,99% n-heptane/1% isopropanol,0.2 mLmin À1): tR =45.4 (+),
53.8 min (À).
N,N-Diallyl-N-[1-(2-bromphenyl)-3-phenyl-2-propynyl]amine (4j): The
reaction was carried out according to GP A with phenylacetylene (1a)
(51 mg,0.50 mmol),2-brombenzaldehyde ( 2h) (93 mg,0.50 mmol) and
diallylamine (3b) (49 mg,0.50 mmol) in the presence of CuBr (3.6 mg,
25.0 mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS 4 Š (250 mg) in
toluene (2 mL) at RT for 5 d. Column chromatographic purification on
silica gel (pentane/Et2O 98:2) yielded propargylamine (À)-4j (151 mg,
0.42 mmol,83%,25%
ee) as a colorless oil. [a]D20
=
À20 (c=1.10,
CHCl3); 1H NMR (300 MHz,CDCl 3): d=7.84–7.80 (m,1H),7.59–7.50
(m,3H),7.36–7.25 (m,4H),7.16 (td,
2H),5.32 (s,1H),5.24 (d,
J=8.9,3.1 Hz,1H),5.99–5.85 (m,
J=9.0 Hz,2H),
J=17.8 Hz,2H),5.12 (d,
Conclusion
3.40–3.33 (m,2H),3.08 (dd, J=14.9,9.0 Hz,2H); 13C NMR (75 MHz,
CDCl3): d=138.0,136.2,133.4,131.8,131.4,129.2,128.3,128.2,126.8,
124.9,123.1,117.2,88.3,85.2,57.2,53.9; MS (70 eV,EI):
m/z (%): 366
The one-pot three-component synthesis of propargylamines
displays a simple and versatile method for the preparation
of this interesting type of structures in asymmetric fashion
with up to 98% ee. The mild reaction conditions and the
broad scope of the reaction illustrates the good synthetic
utility of this method. The reaction is a highly atom econom-
ic process producing only water as a side product. The ap-
plicability of chiral propargylamines in natural product syn-
thesis was successfully shown in the total synthesis of the al-
kaloid (S)-(+)-coniine.
(16) [M +],364 (15),272 (21),271 (97),270 (20),269 (100),211 (13),210
(71),192 (12),191 (25),190 (20),189 (99),188 (14),187 (12),163 (10);
HRMS (EI): m/z: calcd for C21H20BrN: 365.0779; found: 365.0741 [M +];
IR (film): n˜ = 3071 (m),2815 (m),1642 (m),1568 (m),1490 (s),1470 (s),
1441 (s),1027 (m),995 (m),921 (s),754 (vs),690 cm
analysis calcd (%) for C21H20BrN: C 68.86,H 5.50,N 3.82,Br 21.81;
À1
(s); elemental
found: C 68.83,H 5.53,N 3.79,Br 22.21; HPLC (OD-H,99%
n-heptane/
1% isopropanol,0.08 mLmin À1): tR =130.3 (+),140.3 min ( À).
N,N-Diallyl-N-[3-phenyl-1-(3-pyridinyl)-2-propynyl]amine (4n): The re-
action was carried out according to GP A with phenylacteylene (1a)
(51 mg,0.50 mmol),3-pyridinaldehyde ( 2k) (54 mg,0.50 mmol) and dia-
llylamine (3b) (49 mg,0.50 mmol) in the presence of CuBr (3.6 mg,
25.0 mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS 4 Š (250 mg) in
toluene (2 mL) at RT for 5 d. Column chromatographic purification on
silica gel (pentane/Et2O 4:1) yielded propargylamine (À)-4n (91 mg,
0.32 mmol,63%,44% ee) as a yellow oil. [a]2D0 = À69 (c=1.10,CHCl 3);
1H NMR (300 MHz,CDCl 3): d=8.95–8.94 (m,1H),8.56–8.55 (m,1H),
8.01–7.98 (m,1H),7.57–7.54 (m,2H),7.39–7.35 (m,3H),7.32–7.28 (m,
Experimental Section
General considerations: Unless otherwise indicated,all reactions were
carried out under argon and with dried solvents (THF,Et 2O,toluene,di-
chloromethane,pentane,methanol). Reactions were monitored by gas
chromatography (GC,GC-MS) or thin-layer chromatography (TLC)
analysis of hydrolyzed aliquots. For all enantioselective reactions,the rac-
emic mixtures of the products were prepared first and baseline separation
of the two enantiomers were achieved by using HPLC analysis.
1H),5.93–5.80 (m,2H),5.31 (d,
J=14.7 Hz,2H),5.19–5.15 (m,3H),
3.32–3.25 (m,2H),3.08 (dd, J=12.5,6.2 Hz,2H); 13C NMR (75 MHz,
CDCl3): d=150.0,148.7,136.0,135.8,135.0,131.8,128.4,128.3,122.9,
122.8,117.7,88.7,83.7,54.6,53.5; MS (70 eV,EI):
m/z (%): 288 (3) [M +
],287 (11),247 (11),245 (17),210 (44),193 (44),192 (100),191 (25),165
(12),40 (17); HRMS (EI): m/z: calcd for C20H20N2: 288.1626; found [M +
]: 288.1596; IR (film): n˜ = 3080 (m),2819 (m),1643 (m),1575 (m),1490
Experimental procedures and data of the following products have already
been reported: 4b–i, 4k–m, 12a,b;[6a] 5c, 8a, 9, 10. [6b]
(s),1444 (s),1420 (vs),1291 (m),1110 (m),1026 (m),972 (m),922 (s),
À1
Starting materials: The following starting materials were prepared ac-
cording to literature procedures: 3-(4-bromophenyl)propanal (2w),[17]
ethyl 4-(3-oxopropyl)benzoate (2x),[17] 2-benzothienylcarbaldehyde
(2ab),[18] and 4-bromophenylacetylene (1c).[19]
757 (vs),712 (s),691 cm
(s); elemental analysis calcd (%) for C20H20N2:
C 83.30,H 6.99,N 9.71; found: C 82.98,H 6.59,N 9.66; HPLC (OD-H,
99% n-heptane/1% isopropanol,0.2 mLmin À1): tR = 41.8 (À),46.5 min
(+).
N,N-Dibenzyl-5-methyl-1-phenyl-1-hexyn-3-amine (4a)
[a-(N,N-Diallylamino)-g-phenylpropynyl]ferrocene (4o): The reaction
was carried out according to GP A with phenylacetylene (1a) (51 mg,
0.50 mmol),ferrocenecarbaldehyde ( 2l) (107 mg,0.50 mmol) and diallyl-
amine (3b) (49 mg,0.50 mmol) in the presence of CuBr (3.6 mg,
25.0 mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS 4 Š (250 mg) in
toluene (2 mL) at RT for 5 d. Column chromatographic purification on
silica gel (pentane/Et2O 9:1) yielded propargylamine (+)-4o (151 mg,
0.38 mmol,76%,70% ee) as a red oil. [a]2D0 = +240 (c=1.00,CHCl 3);
1H NMR (300 MHz,CDCl 3): d=7.58–7.56 (m,2H),7.39–7.38 (m,3H),
5.94–5.80 (m,2H),5.27 (d, J=17.1 Hz,2H),5.17 (d, J=9.9 Hz,2H),4.91
(s,1H),4.51 (s,1H),4.33 (s,1H),4.23 (s,5H),4.19–4.18 (m,2H),3.26
General procedure A: A dry and argon flushed 10 mL flask,equipped
with a magnetic stirrer and a septum,was charged with copper( i) bro-
mide (3.6 mg,0.025 mmol) and ( R)-quinap (12.1 mg,0.0275 mmol). Dry
toluene (2 mL) was added,the mixture was stirred at RT for 30 min. 4 Š
MS (0.3 g) was added,followed by phenylacetylene
( 1a) (51 mg,
0.5 mmol),valeraldehyde ( 2a) (43 mg,0.5 mmol) and dibenzylamine ( 3a)
(99 mg,0.5 mmol). The reaction mixture was stirred for 48 h at RT. 4 Š
MS was removed by filtration filtered and washed with Et2O. The crude
product was concentrated in vacuo and purified by chromatography on
silica gel (pentane/Et2O 99:1) yielding propargylamine (À)-4a (156 mg,
Chem. Eur. J. 2006, 12,4380 – 4392
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
4385

P. Knochel and N. Gommermann
(dd, J=14.2,5.3 Hz,2H),3.11 (dd,
J=14.2,7.0 Hz,2H);
13C NMR
(%) for C25H36NSi: C 79.51,H 9.34,N 3.71; found: C 79.49,H 9.37,N
3.69. The enantiomeric excess was determined after conversion to 8g.
(75 MHz,CDCl 3): d=136.7,132.5,131.7,128.3,128.0,117.2,87.0,85.8,
85.2,69.2,69.0,68.9,68.2,67.4,53.4,53.3; MS (70 eV,EI):
m/z (%): 395
N,N-Dibenzyl-1-cyclohexyl-3-(trimethylsilyl)-2-propyn-1-amine (5b): The
reaction was carried out according to GP A with trimethylsilylacetylene
(24) [M +],353 (11),300 (32),299 (100),178 (52),177 (18),176 (25),152
(17),151 (10),121 (23),70 (10),68 (11); HRMS (EI):
m/z: calcd for
(1e) (29 mg,0.30 mmol),cyclohexylcarbaldehyde
(
2s) (34 mg,
C25H25FeN: 395.1336; found: 395.1370 [M +]; IR (film): n˜ = 3080 (m),
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 4 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5b (100 mg,0.26 mmol,86%,97% ee) as a colorless solid. M.p. 81–
828C; [a]2D0 =À185 (c=0.89,CHCl 3). 1H NMR (300 MHz,CDCl 3): d=
2960 (m),2929 (m),2815 (m),1728 (s),1489 (s),1444 (m),1288 (s),1106
À1
(s),999 (m),920 (m),756 (vs),691 cm
(s); elemental analysis calcd (%)
for C25H25FeN: C 75.96,H 6.37,N 3.54; found: C 75.55,H 6.70,N 3.02;
HPLC (OD-H,99% n-heptane/1% isopropanol,0.2 mLmin À1): tR
20.6 (À),23.8 min ( +).
=
7.44–7.42 (m,4H),7.37–7.32 (m,4H),7.28–7.23 (m,2H),3.83 (d,
J=
[a-(N,N-Dibenzylamino)-g-phenylpropynyl]ferrocene (4p): The reaction
was carried out according to GP A with phenylacetylene (1a) (51 mg,
0.50 mmol),ferrocenecarbaldehyde ( 2l) (107 mg,0.50 mmol) and diben-
zylamine (3a) (99 mg,0.50 mmol) in the presence of CuBr (3.6 mg,25.0
mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS 4 Š (250 mg) in tol-
uene (2 mL) at RT for 6 d. Column chromatographic purification on
silica gel (pentane/Et2O 9:1) yielded propargylamine (+)-4p (200 mg,
13.6 Hz,2H),3.39 (d, J=13.6 Hz,2H),3.06 (d, J=10.9 Hz,1H),2.32–
2.28 (m,1H),2.04–2.00 (m,1H),1.73–1.55 (m,4H),1.28–1.07 (m,3H),
0.89–0.67 (m,2H),0.28 (s,9H);
13C NMR (75 MHz,CDCl 3): d=139.8,
128.8,128.2,126.8,103.5,90.1,58.6,54.9,39.5,31.2,30.3,26.6,26.2,25.9,
0.5; MS (70 eV,EI): 307 (27) [ M +ÀcHex],306 (100),91 (34); HRMS
(EI): m/z: calcd for C26H35NSi: 389.2539; found: 389.2506 [M +]; IR
(KBr): n˜ = 2924 (s),2852 (m),2160 (m),1494 (m),1451 (m),1248 (s),
0.40 mmol,81%,76%
ee) as a red oil. [a]2D0 =+43 (c=1.09,CHCl 3);
À1
1006 (m),844 (vs),737 (s),698 cm
(s); elemental analysis calcd (%) for
1H NMR (300 MHz,CDCl 3): d=7.65–7.61 (m,2H),7.44–7.24 (m,13H),
C26H35NSi: C 80.14,H 9.05,N 3.59; found: C 79.90,H 9.07,N 3.54. The
enantiomeric excess was determined after conversion to 8j.
4.80 (s,1H),4.56–4.55 (m,1H),4.35–4.34 (m,1H),4.18–4.16 (m,2H),
4.11 (s,5H),3.83 (d,
J=13.7 Hz,2H),3.59 (d,
J=13.7 Hz,2H);
13C NMR (75 MHz,CDCl 3): d=139.9,131.8,128.7,128.4,128.2,128.0,
126.8,123.6,86.6,86.3,85.4,69.0,68.9,68.8,68.3,67.3,54.3,52.9; MS
N,N-Dibenzyl-1-(trimethylsilyl)-1-heptyn-3-amine (5d): The reaction was
carried out according to GP A with trimethylsilylacetylene (1e) (29 mg,
0.30 mmol),valeraldehyde ( 2a) (26 mg,0.30 mmol) and dibenzylamine
(3a) (59 mg,0.30 mmol) in the presence of CuBr (2.2 mg,15.0 mmol) and
(R)-quinap (7.3 mg,16.5 mmol) and MS 4 Š (150 mg) in toluene (2 mL)
at RT for 5 d. Column chromatographic purification on silica gel (pen-
tane/Et2O 99:1) yielded propargylamine (À)-5d (89 mg,0.25 mmol,82%,
90% ee) as a colorless oil. [a]2D0 =À186 (c=0.69,CHCl 3); 1H NMR
(70 eV,EI): m/z (%): 496 (10),495 (28) [ M +],300 (25),299 (100),121
(13),91 (29); HRMS (EI): m/z: calcd for C33H29FeN: 495.1649; found:
495.1629 [M +]; IR (film): n˜ = 3084 (m),3062 (m),3028 (m),2924 (m),
2833 (m),2806 (m),1490 (s),1443 (vs),1071 (s),1027 (m),755 (m),
698 cmÀ1 (vs); HPLC (OD-H,99%
0.2 mLminÀ1): tR = 24.2 (À),30.0 min ( +).
n-heptane/1% isopropanol,
(300 MHz,CDCl 3): d=7.22–7.00 (m,10H),3.62 (d,
J=13.7 Hz,2H),
N,N-Dibenzyl-4-ethyl-1-phenyl-1-hexyn-3-amine (4q): The reaction was
carried out according to GP A with phenylacetylene (1a) (51 mg,
0.50 mmol),2-ethylbutyraldehyde ( 2p) (50 mg,0.50 mmol) and dibenzyl-
amine (3a) (99 mg,0.50 mmol) in the presence of CuBr (3.6 mg,
25.0 mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS 4 Š (250 mg) in
toluene (2 mL) at RT for 6 d. Column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-4q (175 mg,
3.19 (d, J=13.7 Hz,2H),3.21–3.15 (m,1H),1.59–1.35 (m,2H),1.30–1.10
(m,2H),1.10–0.94 (sext, J=7.3 Hz,2H),0.66 (t, J=7.3 Hz,3H),0.07 (s,
9H); 13C NMR (75 MHz,CDCl 3): d=139.5,128.4,127.7,126.4,104.3,
88.6,54.4,51.9,32.9,28.0,21.8,13.5,0.4; MS (70 eV,EI):
m/z (%): 348
m/z:
(5) [M +ÀCH3],306 (100),214 (4),91 (85),73 (12); HRMS (EI):
calcd for C24H32NSi: 362.2304; found: 362.2333 [M +ÀH]; IR (film): n˜ =
3064 (w),3029 (w),2958 (s),2159 (m),1495 (m),1454 (m),1250 (s),842
0.46 mmol,92%,86%
ee) as
a
colorless oil. [a]2D0 =À246 (c=0.53,
À1
(vs),698 cm
(s); elemental analysis calcd (%) for C24H32NSi: C 79.28,
CHCl3); 1H NMR (300 MHz,CDCl 3): d=7.59–7.56 (m,2H),7.48–7.46
H 9.15,N 3.85; found: C 79.19,H 9.15,N 3.83. The enantiomeric excess
was determined after conversion to 8b.
(m,4H),7.42–7.34 (m,7H),7.31–7.26 (m,2H),3.93 (d,
J=13.8 Hz,2H),
3.51 (d, J=13.8 Hz,2H),3.44 (d,
J=9.8 Hz,1H),1.84–1.69 (m,3H),
N,N-Dibenzyl-1-(trimethylsilyl)-1-octyn-3-amine (5e): The reaction was
carried out according to GP A with trimethylsilylacetylene (1e) (29 mg,
0.30 mmol),hexanal ( 2n) (30 mg,0.30 mmol) and dibenzylamine ( 3a)
(59 mg,0.30 mmol) in the presence of CuBr (2.2 mg,15.0 mmol) and (R)-
quinap (7.3 mg,16.5 mmol) and MS 4 Š (150 mg) in toluene (2 mL) at
RT for 3 d. Column chromatographic purification on silica gel (pentane/
Et2O 99:1) yielded propargylamine (À)-5e (113 mg,0.29 mmol,99%,
88% ee) as a colorless oil. [a]2D0 = À152 (c=0.45,CHCl 3); 1H NMR
1.57–1.37 (m,2H),0.87 (t, J=7.5 Hz,3H),0.66 (t, J=7.5 Hz,3H); 13C
NMR (75 MHz,CDCl 3): d=139.7,131.8,129.1,128.3,128.2,127.8,126.9,
123.8,87.5,86.1,55.3,55.2,41.7,22.3,20.2,10.6,9.0; MS (70 eV,EI):
m/z
(%): 380 (<1) [M +ÀH],311 (22),310 (100),91 (23); HRMS (EI): m/z:
calcd for C28H30N: 380.2378; found: 380.2374 [M +ÀH]; IR (film): n˜
=
3030 (m),2961 (s),2803 (m),1489 (m),1454 (m),754 (vs),746 (vs),698
À1
(vs),690 cm (vs); elemental analysis calcd (%) for C28H30N: C 88.14,H
8.19,N 3.67; found: C 87.96,H 8.18,N 3.65; HPLC (OD-H,100%
n-hep-
(300 MHz,CDCl ): d=7.43–7.40 (m,4H),7.36–7.22 (m,6H),3.83 (d,
J=
3
tane,0.2 mLmin À1): tR =33.7 (+),35.8 min ( À).
13.8 Hz,2H),3.43–3.37 (m,3H),1.77–1.56 (m,2H),1.48–1.11 (m,6H),
0.87 (t, J=7.7 Hz,3H),0.27 (s,9H);
13C NMR (75 MHz,CDCl 3): d=
N,N-Dibenzyl-4-ethyl-1-(trimethylsilyl)-1-hexyn-3-amine (5a): The reac-
tion was carried out according to GP A with trimethylsilylacetylene (1e)
(29 mg,0.30 mmol),2-ethylbutyraldehyde ( 2p) (30 mg,0.30 mmol) and
dibenzylamine (3a) (59 mg,0.30 mmol) in the presence of CuBr (2.2 mg,
15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS 4 Š (150 mg) in
toluene (2 mL) at RT for 6 d. Column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-5a (107 mg,
139.9,128.8,128.2,126.8,104.7,89.0,54.8,52.3,33.5,31.3,25.9,22.5,14.0,
0.4; MS (70 eV,EI): m/z (%): 377 ( <1) [M +],307 (25),306 (100),91
(45); HRMS (EI): m/z: calcd for C25H34NSi: 376.2461; found: 376.2448
[M +ÀH]; IR (film): n˜ = 2957 (s),2933 (s),2159 (m),1494 (m),1454
À1
(m),1250 (s),842 (vs),698 cm
(s); elemental analysis calcd (%) for
C25H34NSi: C 79.51,H 9.34,N 3.71; found: C 79.39,H 9.40,N 3.64. The
enantiomeric excess was determined after conversion to 8c and acylation
with valeroylchloride: HPLC (OD-H,99% n-heptane/1% isopropanol,
0.2 mLminÀ1): tR =22.9 (À),26.0 min ( À).
N,N-Dibenzyl-5-methyl-1-(trimethylsilyl)-1-hexyn-3-amine (5 f): The re-
action was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),isovaleraldehyde ( 2b) (22 mg,0.30 mmol) and
dibenzylamine (3a) (59 mg,0.30 mmol) in the presence of CuBr (2.2 mg,
15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS 4 Š (150 mg) in
toluene (2 mL) at RT for 6 d. Column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-5 f (93 mg,
0.29 mmol,95%,98%
ee) as a colorless oil. [a]2D0 =À199 (c=0.41,
CHCl3); 1H NMR (300 MHz,CDCl 3): d=7.43–7.40 (m,4H),7.36–7.31
(m,4H),7.28–7.23 (m,2H),3.82 (d,
13.5 Hz,2H),3.19 (d, J=10.1 Hz,1H),1.75–1.27 (m,5H),0.81 (t,
7.9 Hz,3H),0.59 (t, J=7.9 Hz,3H),0.29 (s,9H);
J=13.5 Hz,2H),3.37 (d,
J=
J=
13C NMR (75 MHz,
CDCl3): d=139.7,129.1,128.1,126.8,104.0,90.0,55.6,55.0,41.4,22.1,
20.1,10.6,8.9,0.5; MS (70 eV,EI): 362 (1) [
M +ÀCH3],307 (30),306
(100),91 (29); HRMS (EI): m/z: calcd for C25H36NSi: 378.2617; found:
378.2617 [M ++H]; IR (film): n˜ = 2962 (s),2158 (m),1494 (m),1454
À1
(m),1250 (s),842 (vs),747 (m),698 cm
(s); elemental analysis calcd
4386
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
Chem. Eur. J. 2006, 12,4380 – 4392

Enantioselective Synthesis
FULL PAPER
0.26 mmol,85%,94 ee) as a colorless oil. [a]2D0 =À185 (c=0.31,CHCl 3);
1H NMR (600 MHz,CDCl 3): d=7.43–7.41 (m,4H),7.36–7.33 (m,4H),
calcd (%) for C23H29NSi: C 79.48,H 8.41,N 4.03; found: C 79.32,H 8.75,
N 4.04. The enantiomeric excess was determined after conversion to 8h.
7.29–7.25 (m,2H),3.83 (d,
J=14.0 Hz,2H),3.49 (dd,
J=8.5,7.0 Hz,
N,N-Dibenzyl-1-cyclopentyl-3-(trimethylsilyl)-2-propyn-1-amine (5j): The
1H),3.39 (d, J=14.0 Hz,2H),1.93–1.86 (m,1H),1.71–1.66 (m,1H),
1.47–1.42 (m,1H),0.83 (d, J=6.4 Hz,3H),0.68 (d, J=6.4 Hz,3H),0.28
reaction was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),cyclopentylcarbaldehyde
(
2r) (29 mg,
(s,9H); 13C NMR (150 MHz,CDCl ): d=139.8,128.9,128.1,126.8,104.8,
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 6 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5j (110 mg,0.29 mmol,98%,96% ee) as a colorless oil. [a]2D0 =À178
(c=0.5,CHCl 3); 1H NMR (600 MHz,CDCl 3): d=7.44 (d, J=7.8 Hz,
3
88.9,54.8,50.3,42.7,24.5,22.9,21.7,0.4; MS (70 eV,EI): m/z (%): 363
(<1) [M+ ],307 (26),306 (100),91 (78); HRMS (EI):
m/z: calcd for
C24H33NSi: 363.2382,; found: 363.2363 [M +]; IR (film): n˜ = 3029 (m),
2957 (s),2159 (m),1494 (m),1454 (s),1250 (s),989 (m),842 (vs),747 (s),
698 cmÀ1 (vs). The enantiomeric excess was determined after conversion
to 8d and acylation with benzoylchloride: HPLC (OD-H,98% n-hep-
tane/2% isopropanol,0.5 mLmin À1): tR =9.2 (À),10.4 min ( +).
4H),7.34 (t, J=7.8 Hz,4H),7.29–7.25 (m,2H),3.87 (d,
J=13.7 Hz,
2H),3.38 (d, J=13.8 Hz,2H),3.06 (d, J=10.6 Hz,1H),2.28–2.22 (m,
1H),1.90–1.82 (m,2H),1.54–1.36 (m,5H),1.31–1.25 (m,1H),0.29 (s,
9H); 13C NMR (150 MHz,CDCl 3): d=139.9,128.9,128.1,126.8,104.3,
N,N-Dibenzyl-5,5-dimethyl-1-(trimethylsilyl)-1-hexyn-3-amine (5g): The
reaction was carried out according to GP A with trimethylsilylacetylene
89.0,57.7,54.9,42.6,30.9,30.2,25.0,24.9,0.4; MS (70 eV,EI):
m/z: 375
m/z: calcd for
(1e) (29 mg,0.30 mmol)3,3-,dimethylbutyraldehyde
(
2o) (26 mg,
(<1) [M +],307 (26),306 (100),91 (53); HRMS (EI):
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 6 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5g (106 mg,0.28 mmol,94%,94% ee) as a colorless oil. [a]2D0 =À182
(c=0.47,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.44–7.40 (m,4H),
C25H32NSi: 374.2304; found: 374.2289 [M +ÀH]; IR (film): n˜ = 2957 (s),
2868 (m),2158 (m),1494 (m),1454 (m),1250 (s),842 (vs),747 (m),
698 cmÀ1 (s); elemental analysis calcd (%) for C25H32NSi: C 79.51,H
9.34,N 3.71; found: C 80.05,H 9.38,N 3.76; HPLC (OD-H,100%
n-hep-
tane,0.2 mLmin À1): tR =22.1 (À),25.0 min ( +).
(1E)-N,N-Dibenzyl-1-phenyl-5-(trimethylsilyl)-1-penten-4-yn-3-amine
(5k): The reaction was carried out according to GP A with trimethylsily-
7.36–7.23 (m,6H),3.81 (d,
J=13.7 Hz,2H),3.47 (dd,
J=8.1,4.0 Hz,
1H),3.40 (d, J=13.8 Hz,2H),1.78–1.62 (m,2H),0.84 (s,9H),0.26 (s,
9H); 3C NMR (75 MHz,CDCl 3): d=139.7,128.9,128.1,126.8,105.8,
88.9,54.9,48.9,48.6,30.6,29.7,0.3; MS (70 eV,EI): m/z (%): 377 (
lacetylene (1e) (29 mg,0.30 mmol),cinnamaldehyde
(
2t) (40 mg,
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 5 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5k (118 mg,0.29 mmol,96%,82% ee) as a colorless oil. [a]2D0 =À13
(c=0.70,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.46–7.24 (m,15H),
<1)
m/z: calcd for
[M +],307 (23),306 (100),91 (43); HRMS (EI):
C25H34NSi: 376.2461; found: 376.2491 [M +ÀH]; IR (film): n˜ = 2957 (s),
À1
2158 (m),1454 (m),1367 (m),1250 (s),842 (vs),745 cm
(s). The enan-
tiomeric excess was determined after conversion to 8e and acylation with
benzoylchloride: HPLC (OD-H,98%
n-heptane/2% isopropanol,
6.91 (dd, J=16.1,2.0 Hz,1H),6.24 (dd,
J=16.1,4.0 Hz,1H),4.34 (dd,
J=13.6 Hz,2H),3.50 (d, J=13.6 Hz,2H),
0.3 mLminÀ1): tR =14.2 (À),15.7 min ( +).
J=4.0,2.0 Hz,1H),3.88 (d,
N,N-Dibenzyl-4-methyl-1-(trimethylsilyl)-1-pentyn-3-amine (5h): The re-
action was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),isobutyraldehyde ( 2c) (22 mg,0.30 mmol) and
dibenzylamine (3a) (59 mg,0.30 mmol) in the presence of CuBr (2.2 mg,
15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS 4 Š (150 mg) in
toluene (2 mL) at RT for 3 d. Column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-5h (91 mg,
0.35 (s,9H); 13C NMR (75 MHz,CDCl 3): d=139.6,136.8,132.6,128.8,
128.5,128.3,128.2,127.5,126.9,126.6,101.2,92.6,54.8,54.5,0.4; MS
(70 eV,EI): m/z: 409 (8) [M +],408 (10),336 (12),319 (25),318 (85),306
(19),213 (31),97 (18),92 (11),91 (100),73 (32); HRMS (EI):
m/z: calcd
for C28H31NSi: 409.2226; found: 409.2251 [M +]; IR (film): n˜ = 3028 (m),
2959 (m),2160 (m),1494 (s),1454 (m),1250 (s),968 (m),842 (s),866
À1
(vs),746 (s),697 cm
(vs); elemental analysis calcd (%) for C28H31NSi:
0.26 mmol,87%,96%
ee) as
a
colorless oil. [a]2D0 =À275 (c=0.44,
C 82.10,H 7.63,N 3.42; found: C 82.23,H 8.14,N 3.43. The enantiomeric
excess was determined after conversion to 8k.
CHCl3); 1H NMR (300 MHz,CDCl 3): d=7.45–7.42 (m,4H),7.37–7.36
(m,6H),3.84 (d, J=13.6 Hz,2H),3.39 (d, J=13.6 Hz,2H),2.94 (d, J=
N,N-Dibenzyl-1,1-diphenyl-5-(trimethylsilyl)-1-penten-4-yn-3-amine (5l):
The reaction was carried out according to GP A with trimethylsilylacety-
lene (1e) (29 mg,0.30 mmol), b-phenylcinnamaldehyde (2u) (62 mg,
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 3 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
10.5 Hz,1H),1.96–1.86 (m,1H),1.03 (d,
6.2 Hz,3H),0.29 (s,9H);
J=6.3 Hz,3H),1.00 (d, J=
13C NMR (75 MHz,CDCl 3): d=139.8,128.9,
128.2,126.8,103.6,89.9,59.9,55.0,30.5,20.8,19.9,0.4; MS (70 eV,EI):
m/z: 307 (27) [M +ÀiPr],306 (100),91 (34); HRMS (EI): m/z: calcd for
C23H30NSi: 348.2148; found: 348.2166 [M +ÀH]; IR (film): n˜ = 2959 (s),
2158 (m),1494 (m),1454 (s),1249 (vs),1019 (s),842 (vs),746 (s),
698 cmÀ1 (vs); elemental analysis calcd (%) for C23H30NSi: C 79.02,H
8.94,N 4.01; found: C 79.10,H 9.17,N 3.83. The enantiomeric excess was
determined after conversion to 8 f.
(+)-5l (119 mg,0.25 mmol,82%,84%
ee) as a colorless oil. [a]2D0 =+46
(c=0.43,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.31–7.13 (m,20H),
6.17 (d, J=9.3 Hz,1H),4.26 (d,
J=9.3 Hz,1H),3.86 (d,
J=13.6 Hz,
2H),3.60 (d, J=13.7 Hz,2H),0.27 (s,9H); 13C NMR (75 MHz,CDCl 3):
d=144.3,142.3,139.4,138.7,129.7,128.9,128.1,128.0,127.9,127.7,127.5,
N,N-Dibenzyl-1-cyclopropyl-3-(trimethylsilyl)-2-propyn-1-amine (5i): The
reaction was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),cyclopropylcarbaldehyde
(
2q) (21 mg,
127.2,126.7,125.8,103.6,90.3,55.1,51.9,0.3; MS (70 eV,EI):
m/z: 485
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 6 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5i (102 mg,0.29 mmol,98%,92% ee) as a colorless oil. [a]2D0 =À163
(c=0.42,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.47–7.42 (m,4H),
7.37–7.23 (m,6H),3.98 (d, J=13.8 Hz,2H),3.45–3.39 (m,3H),1.14–1.04
(m,1H),0.59–0.37 (m,3H),0.28–0.26 (m,1H),0.27 (s,9H);
(75 MHz,CDCl 3): d=140.1,128.8,128.1,126.8,101.4,90.1,55.8,55.0,
13.3,3.6,1.7,0.4; MS (70 eV,EI):
m/z: 347 (3) [M +],307 (27),306 (100),
(16) [M +],413 (14),412 (26),408 (11),395 (19),394 (56),318 (12),306
(15),298 (15),290 (19),289 (68),215 (14),167 (16),92 (12),91 (100),73
(60); HRMS (EI): m/z: calcd for C34H35NSi: 485.2539; found: 485.2500
[M +]; IR (film): n˜ = 3029 (m),2959 (m),2158 (m),1494 (s),1445 (m),
À1
1250 (s),843 (vs),748 (s),698 cm
(vs); elemental analysis calcd (%) for
C34H35NSi: C 84.07,H 7.20,N 2.88; found: C 84.08,H 7.78,N 2.82. The
enantiomeric excess was determined after conversion to 8l.
13C NMR
N,N-Dibenzyl-5-phenyl-1-(trimethylsilyl)-1-pentyn-3-amine (5m): The re-
action was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),dihydrocinnamaldehyde
(
2v) (40 mg,
91 (56),73 (10); HRMS (EI): m/z: calcd for C23H29NSi: 347.2069; found:
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 3 d. Column chromatographic
347.2034 [M +]; IR (film): n˜ = 2959 (m),2160 (m),1494 (m),1454 (m),
À1
1250 (s),1026 (m),842 (vs),747 (m),698 cm
(s); elemental analysis
Chem. Eur. J. 2006, 12,4380 – 4392
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
4387

P. Knochel and N. Gommermann
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5m (96 mg,0.23 mmol,78%,88% ee) as a colorless oil. [a]2D0 =À114
(c=0.38,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.44–7.14 (m,13H),
7.09–7.06 (m,2H),3.88 (d, J=13.6 Hz,2H),3.50 (d, J=7.6 Hz,1H),3.45
(d, J=13.6 Hz,2H),2.85–2.75 (m,1H),2.69–2.59 (m,1H),2.12–1.88 (m,
2H),0.28 (s,9H); 13C NMR (75 MHz,CDCl 3): d=141.9,139.7,128.9,
128.4,128.3,128.2,126.9,125.7,104.2,89.6,55.0,52.2,35.6,32.6,0.4; MS
(70 eV,EI): m/z: 411 (<1) [M +],307 (25),306 (100),91 (60); HRMS
(EI): m/z: calcd for C28H33NSi: 411.2382; found: 411.2406 [M +]; IR
195 (11),91 (61),83 (11),73 (13); HRMS (EI): m/z: calcd for C30H31NSi:
433.2226; found: 433.2240 [M +]; IR (KBr): n˜ = 3436 (m br),3063 (m),
3029 (m),2960 (m),2834 (m),2808 (m),2164 (w),1495 (m),1454 (m),
À1
1250 (s),1121 (m),1007 (m),843 (vs),816 (m),762 (m),744 (s),697 cm
(s); HPLC (OD-H,100% n-heptane,0.2 mLmin À1): tR =34.2 (À),
38.7 min (+).
N,N-Dibenzyl-1-(2-thienyl)-3-(trimethylsilyl)-2-propyn-1-amine (5r): The
reaction was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),2-thiophencarbaldehyde
(
2z) (34 mg,
(film): n˜ = 3027 (m),2956 (m),2158 (m),1495 (s),1454 (s),1250 (s),842
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (S)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 7 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
À1
(vs),746 (s),698 cm
(vs); elemental analysis calcd (%) for C28H33NSi:
C 81.69,H 8.08,N 3.40; found: C 81.92,H 8.56,N 3.37. The enantiomeric
excess was determined after conversion to 8m.
(+)-5r (95 mg,0.24 mmol,81%,80%
ee) as a colorless solid. M.p. 90–
N,N-Dibenzyl-5-(4-bromphenyl)-1-(trimethylsilyl)-1-pentyn-3-amine (5n):
The reaction was carried out according to GP A with trimethylsilylacety-
lene (1e) (29 mg,0.30 mmol),3-(4-bromophenyl)propanal ( 2w) (64 mg,
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 2 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(À)-5n (107 mg,0.22 mmol,73%,88% ee) as a colorless oil. [a]2D0 =À76
(c=0.28,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.41–7.25 (m,12H),
918C; [a]2D0 =+84 (c=0.33,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=
7.52–7.49 (m,4H),7.35 (t, J=7.5 Hz,4H),7.29–7.24 (m,4H),6.96 (dd,
J=5.3,3.6 Hz,1H),4.86 (s,1H),3.86 (d,
J=13.6 Hz,2H),3.47 (d, J=
13.6 Hz,2H),0.35 (s,9H); 13C NMR (75 MHz,CDCl 3): d=144.4,139.2,
128.7,128.2,127.1,126.2,126.0,125.4,100.3,91.8,54.4,52.9,0.3; MS
(70 eV,EI): m/z (%): 389 (30) [M +],298 (27),194 (17),193 (100),165
(50),91 (50); HRMS (EI): m/z: calcd for C24H27NSSi: 389.1633; found:
389.1625 [M +]; IR (KBr): n˜ = 3436 (m br),3028 (w),2957 (w),2835
(w),2167 (w),1495 (w),1454 (w),1249 (m),987 (m),854 (s),752 (m),
698 cmÀ1 (vs). The enantiomeric excess was determined after conversion
to 8p.
6.88 (d, J=8.3 Hz,2H),3.85 (d,
J=13.8 Hz,2H),3.44 (dd,
J=7.1,
1.0 Hz,1H),3.42 (d, J=13.8 Hz,2H),2.76–2.53 (m,2H),2.06–1.83 (m,
2H),0.27 (s,9H); 13C NMR (75 MHz,CDCl 3): d=140.7,139.6,131.2,
130.2,128.9,128.2,126.9,119.4,103.9,89.7,55.0,51.7,35.3,31.8,0.4; MS
(70 eV,EI): m/z: 489 (<1) [M +],307 (26),306 (100),91 (54); HRMS
(EI): m/z: calcd for C28H32BrNSi: 489.1487; found: 489.1441 [M +]; IR
N,N-Dibenzyl-1-(3-thienyl)-3-(trimethylsilyl)-2-propyn-1-amine (5s): The
reaction was carried out according to GP A with trimethylsilylacetylene
(1e) (29 mg,0.30 mmol),3-thiophencarbaldehyde
(
2aa) (34 mg,
(film): n˜ = 2956 (m),2158 (m),1488 (s),1454 (m),1250 (s),1072 (m),
0.30 mmol) and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence
of CuBr (2.2 mg,15.0 mmol) and (S)-quinap (7.3 mg,16.5 mmol) and MS
4 Š (150 mg) in toluene (2 mL) at RT for 7 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
À1
1012 (m),843 (vs),747 (m),698 cm
(s). The enantiomeric excess was
determined after conversion to 8n.
Ethyl 4-[3-(dibenzylamino)-5-(trimethylsilyl)-4-pentynyl]-benzoate (5o):
(+)-5s (99 mg,0.26 mmol,85%,74%
ee) as a colorless solid. M.p. 75–
The reaction was carried out according to GP A with trimethylsilylacety-
768C; [a]2D0 =+69 (c=0.60,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=
lene (1e) (29 mg,0.30 mmol),ethyl 4-(3-oxopropyl)benzoate
(
2x)
7.45–7.42 (m,5H),7.37–7.24 (m,8H),4.69 (s,1H),3.78 (d,
J=13.6 Hz,
(62 mg,0.30 mmol) and dibenzylamine ( 3a) (59 mg,0.30 mmol) in the
presence of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,16.5 mmol)
and MS 4 Š (150 mg) in toluene (2 mL) at RT for 2 d. Column chromato-
graphic purification on silica gel (pentane/Et2O 9:1) yielded propargyl-
2H),3.45 (d, J=13.6 Hz,2H),0.35 (s,9H); 13C NMR (75 MHz,CDCl 3):
d=140.8,139.5,128.8,128.2,127.4,127.0,125.6,123.2,101.4,91.4,54.5,
52.8,0.4; MS (70 eV,EI): m/z (%): 389 (47) [M +],316 (15),306 (21),299
(15),298 (59),196 (53),195 (12),194 (33),193 (92),179 (12),166 (13),
amine (À)-5o (140 mg,0.29 mmol,96%,87%
ee) as a colorless oil.
[a]2D0 =À72 (c=0.72,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.89 (d,
165 (88),153 (11),92 (11),91 (100); HRMS (EI):
m/z: calcd for
C24H27NSSi: 389.1633; found: 389.1624 [M +]; IR (KBr): n˜ = 3436 (m),
2834 (w),2168 (w),1495 (w),1454 (w),1249 (m),844 (vs),757 (s),
700 cmÀ1 (s). The enantiomeric excess was determined after conversion
to 8q.
J=8.4 Hz,2H),7.42–7.22 (m,10H),7.09 (d,
J=8.0 Hz,2H),4.39 (q, J=
6.9 Hz,2H),3.86 (d, J=13.6 Hz,2H),3.45 (d, J=7.3 Hz,1H),3.43 (d,
J=13.7 Hz,2H),2.88–2.78 (m,1H),2.72–2.62 (m,1H),2.10–1.87 (m,
2H),1.42 (t, J=6.9 Hz,3H),0.28 (s,9H);
d=166.6,147.2,139.5,129.6,128.9,128.3,128.2,128.0,126.9,103.8,89.8,
13C NMR (75 MHz,CDCl 3):
N-[1-(1-Benzothien-2-yl)-3-(trimethylsilyl)-2-propynyl]-N,N-dibenzyl-
amine (5t): The reaction was carried out according to GP A with trime-
thylsilylacetylene (1e) (29 mg,0.30 mmol),2-benzothiophencarbaldehyde
(2ab) (49 mg,0.30 mmol) and dibenzylamine ( 3a) (59 mg,0.30 mmol) in
the presence of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,
16.5 mmol) and MS 4 Š (150 mg) in toluene (2 mL) at RT for 7 d.
Column chromatographic purification on silica gel (pentane/Et2O 99:1)
60.7,55.0,51.9,35.1,32.6,14.4,0.4; MS (70 eV,EI):
m/z: 483 (<1) [M +],
307 (26),306 (100),91 (45); HRMS (EI): m/z: calcd for C31H37NO2Si:
483.2594; found: 483.2627 [M +]; IR (film): n˜ = 2957 (m),2158 (m),1719
(vs),1454 (m),1276 (vs),1250 (s),1178 (m),1107 (s),843 (s),748 (s),
699 cmÀ1 (s); elemental analysis calcd (%) for C31H37NO2Si: C 76.97,H
7.71,N 2.90; found: C 76.66,H 7.73,N 2.77; HPLC (OD-H,99%
n-hep-
tane/1% isopropanol,0.3 mLmin À1): tR =16.9 (À),26.8 min ( +).
yielded propargylamine (À)-5t (55 mg,0.13 mmol,42%,89%
ee) as a
yellow solid. M.p. 112–1138C; [a]2D0 =À14 (c=0.29,CHCl 3); 1H NMR
N,N-Dibenzyl-1-(2-naphthyl)-3-(trimethylsilyl)-2-propyn-1-amine
(5q):
(300 MHz,CDCl 3): d=7.80–7.77 (m,1H),7.71–7.68 (m,1H),7.51–7.49
The reaction was carried out according to GP A with trimethylsilylacety-
lene (1e) (29 mg,0.30 mmol),2-naphthaldehyde ( 2y) (47 mg,0.30 mmol)
and dibenzylamine (3a) (59 mg,0.30 mmol) in the presence of CuBr
(2.2 mg,15.0 mmol) and (S)-quinap (7.3 mg,16.5 mmol) and MS 4 Š
(150 mg) in toluene (2 mL) at RT for 7 d. Column chromatographic puri-
fication on silica gel (pentane/Et2O 99:1) yielded propargylamine (+)-5q
(m,4H),7.45–7.44 (m,1H),7.36–7.21 (m,8H),4.90 (d,
3.87 (d, J=13.7 Hz,2H),3.45 (d, J=13.7 Hz,2H),0.35 (s,9H);
NMR (75 MHz,CDCl 3): d=145.5,140.3,139.3,139.0,128.8,128.3,128.2,
127.1,124.0,123.3,122.7,122.3,99.6,92.5,54.5,53.4,0.3; MS (70 eV,EI):
m/z (%): 439 (12) [M +],281 (13),244 (29),243 (100),215 (21),207 (39),
J=1.4 Hz,1H),
13C
203 (19),91 (49); HRMS (EI): m/z: calcd for C28H29NSSi: 439.1790;
(45 mg,0.11 mmol,35%,54%
ee) as a colorless solid. M.p. 98–998C;
found: 439.1816 [M +]; IR (KBr): n˜ = 3027 (w),2835 (w),2165 (w),1494
[a]2D0 =+2 (c=0.25,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=8.17 (s,
1H),7.91–7.84 (m,3H),7.74 (dd, J=8.8,1.8 Hz,1H),7.51–7.44 (m,6H),
À1
(m),1454 (m),1249 (s),990 (m),981 (m),854 (vs),749 (s),698 cm
(s);
HPLC (OD-H,100% n-heptane,0.2 mLmin À1): tR =29.2 (À),31.3 min
(+).
7.35 (t, J=8.0 Hz,4H),7.29–7.24 (m,2H),4.89 (s,1H),3.79 (d,
J=
13.3 Hz,2H),3.50 (d, J=13.3 Hz,2H),0.42 (s,9H); 13C NMR (75 MHz,
CDCl3): d=139.5,136.4,133.0,132.9,128.9,128.3,128.1,127.8,127.5,
127.2,127.0,126.4,125.9,125.8,100.9,93.5,56.4,54.5,0.4; MS (70 eV,
EI): m/z (%): 434 (11),433 (31) [ M +],360 (13),343 (11),342 (33),307
(16),306 (62),238 (40),237 (100),223 (11),209 (50),197 (35),196 (49),
N-[1-(1-Benzothien-3-yl)-3-(trimethylsilyl)-2-propynyl]-N,N-dibenzyl-
amine (5u): The reaction was carried out according to GP A with trime-
thylsilylacetylene (1e) (29 mg,0.30 mmol),3-benzothiophencarbaldehyde
(2i) (49 mg,0.30 mmol) and dibenzylamine ( 3a) (59 mg,0.30 mmol) in
4388
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
Chem. Eur. J. 2006, 12,4380 – 4392

Enantioselective Synthesis
FULL PAPER
the presence of CuBr (2.2 mg,15.0 mmol) and (R)-quinap (7.3 mg,
16.5 mmol) and MS 4 Š (150 mg) in toluene (2 mL) at RT for 7 d.
Column chromatographic purification on silica gel (pentane/Et2O 99:1)
1.3 Hz,1H),1.83–1.73 (m,1H),1.71–1.63 (m,1H),1.50–1.33 (m,2H),
1.25–1.17 (m,2H),0.87 (t, J=7.3 Hz,3H); 13C NMR (150 MHz,CDCl 3):
d=139.7,128.8,128.2,126.9,82.2,72.4,54.7,51.5,33.4,28.4,22.2,13.9;
yielded propargylamine (À)-5u (121 mg,0.28 mmol,92%,82%
ee) as a
MS (70 eV,EI): m/z (%):290 (1) [M +ÀH],235 (22),234 (98),181 (11),
92 (100),65 (10); HRMS (EI): m/z: calcd for C21H25N: 290.1909; found:
yellow solid. M.p. 132–1338C; [a]2D0 =À128 (c=0.77,CHCl 3); 1H NMR
(300 MHz,CDCl 3): d=7.81 (s,1H),7.70 (s,1H),7.23–7.14 (m,12H),
290.1885 [M +ÀH]; IR (film): n˜ = 3302 (m),2956 (s),2934 (s),2860 (m),
À1
7.10 (d, J=7.2 Hz,1H),4.89 (s,1H),3.70 (d,
J=12.3 Hz,2H),0.28 (s,9H);
13C NMR (75 MHz,CDCl 3): d=140.5,
138.7,137.2,133.2,129.1,127.8,126.8,125.9,123.9,123.2,123.1,122.2,
J=12.3 Hz,2H),3.35 (d,
1494 (m),1454 (s),746 (s),698 cm
(vs); elemental analysis calcd (%)
for C21H25N: C 86.55,H 8.65,N 4.81; found: C 86.84,H 8.80,N 4.97;
HPLC (OD-H,100% n-heptane,0.8 mLmin À1): tR =11.3 (+),12.9 min
(À).
100.2,92.0,54.5,51.9,0.0; MS (70 eV,EI):
244 (28),243 (100),215 (25),203 (13),196 (17 [
m/z (%): 439 (18),348 (10),
M +]),91 (51); HRMS
N,N-Dibenzyl-1-octyn-3-amine (8c): The reaction was carried out accord-
(EI): m/z: calcd for C28H29NSSi: 439.1790; found: 439.1787 [M +]; IR
(KBr): n˜ = 3027 (m),2955 (m),2838 (m),2164 (w),1495 (m),1454 (m),
1248 (s),1106 (m),1054 (m),981 (m),954 (m),845 (vs),751 (s),738 (s),
700 cmÀ1 (s); HPLC (OD-H,100% n-heptane,0.2 mLmin À1): tR =31.7
(À),39.7 min ( +).
ing to GP
B
with propargylamine (À)-5e (113 mg,0.29 mmol) and
Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for 15 min. Standard
workup and column chromatographic purification on silica gel (pentane/
Et2O 99:1) yielded propargylamine (À)-8c (84 mg,0.28 mmol,95%) as a
1
colorless oil. [a]2D0 =À115 (c=0.41,CHCl ); H NMR (600 MHz,CDCl 3):
3
N,N-Dibenzyl-1-(tert-butyldimethylsilyl)-4-ethyl-1-hexyn-3-amine
The reaction was carried out according to GP A with tert-butyldimethylsi-
lylacetylene (70 mg,0.50 mmol),2-ethylbutyraldehyde 2p) (50 mg,
(6):
d=7.44 (d, J=7.2 Hz,4H),7.35 (t, J=7.2 Hz,4H),7.29–7.26 (m,2H),
3.87 (d, J=13.7 Hz,2H),3.44 (d, J=13.7 Hz,2H),3.44–3.43 (m,1H),
2.35 (d, J=2.3 Hz,1H),1.80–1.74 (m,1H),1.70–1.64 (m,1H),1.49–1.37
(
0.50 mmol) and dibenzylamine (3a) (99 mg,0.50 mmol) in the presence
of CuBr (3.6 mg,25.0 mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS
4 Š (250 mg) in toluene (2 mL) at RT for 7 d. Column chromatographic
purification on silica gel (pentane/Et2O 99:1) yielded propargylamine
(m,2H),1.30 (sext,
J=7.2 Hz,2H),1.20–1.15 (m,2H),0.88 (t,
J=
7.2 Hz,3H); 13C NMR (150 MHz,CDCl 3): d=139.7,128.8,128.2,126.9,
82.2,72.4,54.7,51.4,33.6,31.3,25.9,22.5,14.0; MS (70 eV,EI):
m/z (%):
305 (<1) [M +],235 (18),234 (93),91 (100); HRMS (EI): m/z: calcd for
(À)-6 (88 mg,0.21 mmol,42%,90%
ee) as a colorless oil. [a]2D0 =À192
C22H27N: 305.2143; found: 305.2165 [M +]; IR (film): n˜ = 3304 (m),2954
(c=0.26,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.43–7.19 (m,10H),
3.83 (d, J=13.8 Hz,2H),3.40 (d, J=13.8 Hz,2H),3.20 (d, J=10.3 Hz,
(s),2933 (s),1495 (m),1454 (s),746 (s),698 cm
calcd (%) for C22H27N: C 86.51,H 8.91,N 4.59; found: C 86.31,H 8.99,
N 4.55.
(vs); elemental analysis
À1
1H),1.76–1.59 (m,3H),1.47–1.28 (m,2H),1.06 (s,9H),0.81 (t,
7.5 Hz,3H),0.61 (t, J=7.5 Hz,3H),0.22 (s,3H),0.21 (s,3H);
J=
13C NMR
N,N-Dibenzyl-5-methyl-1-hexyn-3-amine (8d): The reaction was carried
out according to GP B with propargylamine (À)-5 f (93 mg,0.26 mmol)
and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for 15 min.
Standard workup and column chromatographic purification on silica gel
(pentane/Et2O 99:1) yielded propargylamine (À)-8d (75 mg,0.26 mmol,
(75 MHz,CDCl 3): d=139.7,129.1,128.1,126.8,104.5,88.0,55.6,55.1,
41.6,26.2,26.0,22.1,20.2,16.6,10.6,9.0,
À4.2, À4.9; MS (70 eV,EI): m/z
(%): 419 (<1) [M +],350 (12),349 (49),348 (94),97 (13),92 (15),91
(100),83 (13),73 (21),59 (12),57 (11),42 (13); HRMS (EI):
m/z: calcd
for C28H41NSi: 419.3008; found: 419.3038 [M +]; IR (film): n˜ = 2957 (vs),
99%) as
a
colorless oil. [a]D20 =À165 (c=0.45,CHCl 3); 1H NMR
2930 (vs),2857 (s),2158 (m),1495 (m),1470 (m),1454 (s),1249 (s),834
(600 MHz,CDCl 3): d=7.43 (d, J=7.3 Hz,4H),7.35 (t, J=7.3 Hz,4H),
À1
(s),826 (s),747 (s),698 cm
(s); elemental analysis calcd (%) for
7.29–7.26 (m,2H),3.86 (d,
1H),3.42 (d, J=13.8 Hz,2H),2.35 (d,
J=13.8 Hz,2H),3.51 (td,
J=7.7,2.5 Hz,
C28H41NSi: C 80.13,H 9.85,N 3.34; found: C 79.63,H 10.22,N 3.17. The
enantiomeric excess was determined after conversion to 8g.
J=2.2 Hz,1H),1.91–1.87 (m,
1H),1.72–1.68 (m,1H),1.52–1.48 (m,1H),0.83 (d,
J=6.3 Hz,3H),0.70
N,N-Dibenzyl-1-cyclohexyl-3-[tri-tert-butylsilyl]-2-propyn-1-amine
The reaction was carried out according to GP A with triisopropylsilylace-
tylene (91 mg,0.50 mmol),2-ethylbutyraldehyde ( 2p) (50 mg,0.50 mmol)
and dibenzylamine (3a) (99 mg,0.50 mmol) in the presence of CuBr
(3.6 mg,25.0 mmol) and (R)-quinap (12.1 mg,27.5 mmol) and MS 4 Š
(250 mg) in toluene (2 mL) at RT for 6 d. Column chromatographic puri-
fication on silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-7
(7):
(d, J=6.3 Hz,3H); 13C NMR (150 MHz,CDCl 3): d=139.7,128.9,128.2,
126.9,82.3,72.3,54.8,49.4,42.8,24.5,22.7,21.8; MS (70 eV,EI):
m/z
m/z:
=
(%): 291 (<1) [M +],235 (18),234 (100),91 (89); HRMS (EI):
calcd for C21H24N: 290.1909; found: 290.1885 [M +ÀH]; IR (film): n˜
À1
3302 (m),2955 (s),2934 (s),1495 (m),1454 (s),746 (s),698 cm
(vs).
N,N-Dibenzyl-5,5-dimethyl-1-hexyn-3-amine (8e): The reaction was car-
ried out according to GP
with propargylamine (À)-5g (106 mg,
B
(73 mg,0.15 mmol,31%,4%
ee) as a colorless oil. [a]2D0 =À8 (c=0.40,
0.28 mmol) and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for
15 min. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-8e (85 mg,
0.28 mmol,99%) as a colorless oil. [ a]2D0 =À175 (c=0.65,CHCl 3); 1H
NMR (600 MHz,CDCl 3): d=7.43–7.40 (m,4H),7.33–7.30 (m,4H),
7.26–7.22 (m,2H),3.81 (d, J=13.8 Hz,2H),3.48–3.44 (m,1H),3.40 (d,
J=13.8 Hz,2H),2.34 (d, J=2.3 Hz,1H),1.76 (dd, J=13.6,7.7 Hz,1H),
CHCl3); 1H NMR (300 MHz,CDCl 3): d=7.43–7.19 (m,10H),3.86 (d,
J=13.7 Hz,2H),3.46 (d, J=13.6 Hz,2H),3.10 (d, J=10.4 Hz,1H),2.31
(d, J=13.3 Hz,1H),2.07 (d, J=13.3 Hz,1H),1.74–1.59 (m,4H),1.35–
1.27 (m,3H),1.18 (s,21H),0.87–0.74 (m,2H);
CDCl3): d=139.9,128.8,128.2,126.8,105.2,85.7,58.6,55.0,39.7,31.3,
13C NMR (75 MHz,
30.3,29.7,29.4,26.6,25.9,18.8,18.5,11.4; MS (70 eV,EI):
m/z (%): 472
(<1) [M +ÀH],319 (24),390 (100),91 (28); HRMS (EI): m/z: calcd for
C32H46NSi: 472.3400; found: 472.3418 [M +ÀH]; IR (film): n˜ = 2940 (vs),
2864 (s),2156 (w),1452 (m),1003 (m),883 (m),746 (m),698 (s),
676 cmÀ1 (m); elemental analysis calcd (%) for C32H46NSi: C 81.12,H
10.00,N 2.96; found: C 80.75,H 9.84; N 2.73. The enantiomeric excess
was determined after conversion to 8j.
1.67 (dd, J=13.5,4.0 Hz,1H),0.82 (s,9H);
13C NMR (150 MHz,
CDCl3): d=139.6,128.9,128.2,126.9,83.3,72.4,54.8,48.7,48.1,30.7,
29.6; MS (70 eV,EI): m/z (%): 305 (<1) [M +],235 (12),234 (71),91
(100),58 (12),44 (36); HRMS (EI): m/z: calcd for C22H26N: 304.2065;
found: 304.2076 [M +ÀH]; IR (film): n˜ = 3304 (m),2956 (s),1495 (m),
1454 (s),1368 (m),746 (s),698 cm À1 (vs).
N,N-Dibenzyl-1-heptyn-3-amine (8b)
N,N-Dibenzyl-4-methyl-1-pentyn-3-amine (8 f): The reaction was carried
out according to GP B with propargylamine (À)-5h (91 mg,0.26 mmol)
and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for 15 min.
Standard workup and column chromatographic purification on silica gel
(pentane/Et2O 99:1) yielded propargylamine (À)-8 f (71 mg,0.25 mmol,
General procedure B: Propargylamine (À)-5d (89 mg,0.25 mmol) was
dissolved in dry THF (3 mL) and cooled to 08C. Bu4NF (0.10 mL,
0.10 mmol) in THF (3 mL) was added dropwise and the reaction was stir-
red for 15 min. The reaction mixture was quenched with water (25 mL)
and extracted with Et2O (3”20 mL). After evaporation of the solvent
and column chromatographic purification on silica gel (pentane/Et2O
99:1),propargylamine ( À)-8b (69 mg,0.24 mmol,95%) was obtained as
98%) as
a
colorless oil. [a]D20 =À231 (c=0.76,CHCl 3); 1H NMR
(300 MHz,CDCl 3): d=7.46–7.24 (m,10H),3.87 (d,
J=13.7 Hz,2H),
3.42 (d, J=13.7 Hz,2H),2.95 (d, J=10.8 Hz,1H),2.38 (s,1H),2.02–1.90
(m,1H),1.04 (t, J=6.7 Hz,6H); 13C NMR (75 MHz,CDCl 3): d=139.6,
128.8,128.2,126.9,81.2,73.2,58.9,54.9,30.5,20.8,19.8; MS (70 eV,EI):
m/z: 235 (18),234 (100) [ M +ÀiPr],91 (16); HRMS (EI): m/z: calcd for
a
colorless oil. [a]2D0 =À190 (c=0.87,CHCl 3); 1H NMR (600 MHz,
CDCl3): d=7.41 (d, J=7.7 Hz,4H),7.33 (t, J=7.3 Hz,4H),7.25 (t, J=
7.3 Hz,2H),3.85 (d, =13.8 Hz,2H),3.46–3.40 (m,3H),2.33 (d,
J=
Chem. Eur. J. 2006, 12,4380 – 4392
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
4389

P. Knochel and N. Gommermann
C20H22N: 276.1752; found: 276.1720 [M +ÀH]; IR (film): n˜ = 2959 (m),
emental analysis calcd (%) for C23H27N: C 87.02,H 8.57,N 4.41; found:
C 86.74,H 8.37,N 4.32; HPLC (OD-H,100% n-heptane,0.2 mLmin À1):
tR = 31.7 (À),36.0 min ( +).
À1
1495 (m),1454 (m),746 (m),698 cm
(vs); elemental analysis calcd (%)
for C20H22N: C 86.59,H 8.36,N 5.05; found: C 86.25,H 8.20,N 4.98;
HPLC (OD-H,100% n-heptane,0.2 mLmin À1): tR =29.7 (À),34.9 min
(+).
(1E)-N,N-Dibenzyl-1-phenyl-1-penten-4-yn-3-amine (8k)
General procedure C: Propargylamine (+)-5k (118 mg,0.29 mmol) was
dissolved in MeOH (5 mL). KOH (0.4 mL,1.0 m in MeOH,0.40 mmol)
was added and the reaction mixture was stirred at RT for 12 h. The reac-
tion mixture was quenched with water (25 mL) and extracted with Et2O
(3”20 mL). After evaporation of the solvent and column chromatograph-
ic purification on silica gel (pentane/Et2O 99:1),propargylamine ( +)-8k
(93 mg,0.28 mmol,95%) was obtained as a colorless oil. [ a]2D0 =+41 (c=
0.77,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.47–7.25 (m,15H),6.95
N,N-Dibenzyl-4-ethyl-1-hexyn-3-amine (8g): The reaction was carried
out according to GP B with propargylamine (À)-5a (107 mg,0.29 mmol)
and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for 15 min.
Standard workup and column chromatographic purification on silica gel
(pentane/Et2O 99:1) yielded propargylamine (À)-8g (87 mg,0.28 mmol,
98%) as
a
colorless oil. [a]D20 =À252 (c=0.47,CHCl 3); 1H NMR
(300 MHz,CDCl 3): d=7.43–7.41 (m,4H),7.37–7.32 (m,4H),7.29–7.24
(m,2H),3.84 (d, J=13.7 Hz,2H),3.40 (d, J=13.7 Hz,2H),3.21 (dd, J=
(dd, J=15.9,1.7 Hz,1H),6.26 (dd,
1H),3.91 (d, J=13.9 Hz,2H),3.52 (d,
J=15.9,4.4 Hz,1H),4.37–3.36 (m,
J=13.9 Hz,2H),2.63 (d, J=
10.1,2.3 Hz,1H),2.38 (d,
(m,2H),0.81 (t,
J=2.3 Hz,1H),1.79–1.62 (m,3H),1.50–1.28
J=7.3 Hz,3H); 13C NMR
2.1 Hz,1H); 13C NMR (75 MHz,CDCl 3): d=139.5,136.6,132.7,128.8,
128.5,128.3,128.0,127.6,127.0,126.6,79.0,75.6,54.7,53.6; MS (70 eV,
EI): m/z: 337 (12) [M +],336 (24),246 (44),142 (16),141 (68),115 (31),
J=7.3 Hz,3H),0.60 (t,
(75 MHz,CDCl ): d=139.6,129.0,128.2,126.9,81.3,73.3,55.0,54.6,41.4,
3
21.9,19.9,10.4,8.9; MS (70 eV,EI):
m/z: 235 (20),234 (100) [ M +
ÀHÀethylpropyl],91 (74); HRMS (EI):
m/z: calcd for C22H26N:
92 (11),91 (100),65 (11); HRMS (EI): m/z: calcd for C25H23N: 337.1830;
304.2065; found: 304.2075 [M +ÀH]; IR (film): n˜ = 3302 (m),2963 (s),
found: 337.1853 [M +]; IR (film): n˜ = 3291 (s),3281 (s),3024 (m),2839
À1
À1
2937 (m),1495 (m),1454 (m),748 (m),698 cm
(s); elemental analysis
(m),1494 (m),1453 (m),967 (s),745 (s),698 cm
(vs); elemental analy-
calcd (%) for C22H26N: C 86.51,H 8.91,N 4.59; found: C 86.45,H 9.07,
N 4.57; HPLC (OD-H,100% n-heptane,0.2 mLmin À1): tR =28.4 (À),
31.9 min (+).
sis calcd (%) for C25H23N: C 88.98,H 6.87,N 4.15; found: C 88.64,H
7.12,N 4.08; HPLC (OD-H,99%
n-heptane/1% isopropanol,
0.15 mLminÀ1): tR = 35.0 (À),46.3 min ( +).
N,N-Dibenzyl-1-cyclopropyl-2-propyn-1-amine (8h): The reaction was
carried out according to GP B with propargylamine (À)-5i (102 mg,
0.29 mmol) and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for
15 min. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-8h (80 mg,
0.29 mmol,99%) as a colorless oil. [ a]2D0 =À138 (c=0.40,CHCl 3); 1H
NMR (300 MHz,CDCl 3): d=7.33 (d, J=7.1 Hz,4H),7.23 (t, J=7.8 Hz,
N,N-Dibenzyl-1,1-diphenyl-1-penten-4-yn-3-amine (8l): The reaction was
carried out according to GP C with propargylamine (+)-5l (119 mg,
0.25 mmol) and KOH (0.40 mL,0.40 mmol) in MeOH (3 mL) at RT for
12 h. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (+)-8l (101 mg,
0.25 mmol,98%) as a colorless oil. [ a]2D0 =+47 (c=0.27,CHCl 3); 1H
NMR (300 MHz,CDCl 3): d=7.31–7.11 (m,20H),6.20 (d,
J=9.3 Hz,
4H),7.18–7.13 (m,2H),3.89 (d,
2H),3.24 (dd, J=5.7,2.1 Hz,1H),2.21 (d, J=2.1 Hz,1H),1.06–0.98 (m,
1H),0.49–0.30 (m,3H),0.19–0.13 (m,1H);
13C NMR (75 MHz,CDCl 3):
J=13.8 Hz,2H),3.34 (d, J=13.8 Hz,
1H),4.29 (dd, J=9.3,2.2 Hz,1H),3.89 (d, J=13.8 Hz,2H),3.62 (d, J=
13.8 Hz,2H),2.46 (d, J=2.2 Hz,1H); 13C NMR (75 MHz,CDCl 3): d=
144.6,142.2,139.3,138.6,129.6,128.8,128.1,128.0,127.7,127.6,127.3,
d=139.9,128.7,128.2,126.8,79.4,73.2,55.1,55.0,13.5,3.7,2.0; MS
126.8,125.3,112.3,81.6,73.5,55.1,50.9; MS (70 eV,EI):
m/z: 413 (16)
(70 eV,EI): m/z: 275 (2) [M +],234 (37),91 (100),77 (13),65 (11);
HRMS (EI): m/z: calcd for C20H21N: 275.1674; found: 275.1655 [M +]; IR
(film): n˜ = 3299 (m),3027 (m),1495 (m),1454 (m),1027 (m),746 (s),
[M +],412 (20),323 (23),322 (86),218 (20),217 (83),218 (18),215 (39),
202 (45),139 (28),91 (100); HRMS (EI):
m/z: calcd for C31H37N:
413.2143; found: 413.2103 [M +]; IR (film): n˜ = 3292 (m),3028 (m),1494
698 cmÀ1 (vs); HPLC (OD-H,99%
n-heptane/1% isopropanol,
À1
(m),1454 (m),1444 (m),748 (m),697 cm
(vs); elemental analysis calcd
0.2 mLminÀ1): tR =20.5 (À),22.9 min ( +).
(%) for C31H37N: C 90.03,H 6.58,N 3.39; found: C 90.34,H 6.65,N 3.23;
HPLC (OD-H,99% n-heptane/1% isopropanol,0.15 mLmin À1): tR =37.4
(À),40.5 min ( +).
N,N-Dibenzyl-1-cyclopentyl-2-propyn-1-amine (8i): The reaction was car-
ried out according to GP
B
with propargylamine (À)-5j (110 mg,
0.29 mmol) and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for
15 min. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-8i (87 mg,0.2
9 mmol,99%) as a colorless oil. [ a]2D0 =À138 (c=0.57,CHCl 3); 1H NMR
N,N-Dibenzyl-5-phenyl-1-pentyn-3-amine (8m): The reaction was carried
out according to GP B with propargylamine (À)-5m (96 mg,0.23 mmol)
and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for 15 min.
Standard workup and column chromatographic purification on silica gel
(pentane/Et2O 99:1) yielded propargylamine (À)-8m (75 mg,0.22 mmol,
(300 MHz,CDCl ): d=7.45–7.42 (m,4H),7.37–7.24 (m,6H),3.89 (d,
J=
3
97%) as
a
colorless oil. [a]D20 =À83 (c=0.46,CHCl 3); 1H NMR
13.8 Hz,2H),3.40 (d, J=13.8 Hz,2H),3.09 (dd, J=10.6,2.3 Hz,1H),
2.34 (d, J=2.3 Hz,1H),2.36–2.20 (m,1H),1.93–1.81 (m,2H),1.56–1.22
(m,6H); 13C NMR (75 MHz,CDCl 3): d=139.7,128.9,128.2,126.9,81.8,
(300 MHz,CDCl 3): d=7.45–7.15 (m,13H),7.09–7.07 (m,2H),3.91 (d,
J=13.8 Hz,2H),3.52 (dd, J=8.0,2.2 Hz,1H),3.48 (d, J=13.8 Hz,2H),
72.4,56.9,54.9,42.6,30.8,30.2,24.9,24.8; MS (70 eV,EI):
m/z: 303 (<1)
m/z: calcd for
2.87–2.77 (m,1H),2.72–2.62 (m,1H),2.39 (d,
J=2.2 Hz,1H),2.16–1.93
[M +],235 (15),234 (82),91 (100),43 (25); HRMS (EI):
(m,2H); 13C NMR (75 MHz,CDCl ): d=141.7,139.5,128.9,128.3,128.3,
3
C22H25N: 303.1987; found: 303.2011 [M +]; IR (film): n˜ = 3301 (m),2955
128.2,126.9,125.7,81.7,72.9,54.9,51.2,35.5,32.5; MS (70 eV,EI):
m/z:
m/z: calcd for
(s),1495 (m),1453 (m),747 (s),698 cm À1 (vs).
339 (1) [M +],235 (18),234 (100),91 (94); HRMS (EI):
C25H25N: 339.1987; found: 339.1975 [M +]; IR (film): n˜ = 3295 (m),3027
N,N-Dibenzyl-1-cyclohexyl-2-propyn-1-amine (8j): The reaction was car-
À1
(m),1495 (s),1454 (s),746 (s),698 cm
(vs); elemental analysis calcd
ried out according to GP
B
with propargylamine (À)-5b (100 mg,
(%) for C25H25N: C 88.45,H 7.42,N 4.13; found: C 88.30,H 7.47,N 4.01;
HPLC (OD-H,99% n-heptane/1% isopropanol,0.15 mLmin À1): tR =38.6
(+),42.5 min ( À).
0.26 mmol) and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for
15 min. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-8j (78 mg,
0.25 mmol,95%) as a colorless solid. M.p. 75–76 8C; [a]2D0 =À157 (c=
0.35,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=7.44–7.41 (m,4H),7.36–
N,N-Dibenzyl-5-(4-bromphenyl)-1-pentyn-3-amine (8n): The reaction
was carried out according to GP B with propargylamine (À)-5n (107 mg,
0.22 mmol) and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for
15 min. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-8n (92 mg,
0.22 mmol,99%) as a colorless oil. [ a]2D0 =À54 (c=0.41,CHCl 3); 1H
7.31 (m,4H),7.27–7.23 (m,2H),3.85 (d,
13.7 Hz,2H),3.07 (dd,
J=13.7 Hz,2H),3.41 (d, J=
J=2.2 Hz,1H),
J=10.6,2.2 Hz,1H),2.37 (d,
2.35–2.28 (m,1H),2.06–2.00 (m,1H),1.72–1.59 (m,4H),1.31–1.07 (m,
3H),0.91–0.72 (m,2H); 13C NMR (75 MHz,CDCl 3): d=139.7,128.8,
128.2,126.8,81.0,73.4,57.6,54.8,39.5,31.2,30.2,26.5,26.1,25.9; MS
NMR (300 MHz,CDCl ): d=7.41–7.25 (m,12H)6, .89 (d, J=8.2 Hz,2H),
3
(70 eV,EI): m/z: 235 (21),234 (100) [ M +Àc-Hex],91 (88); HRMS (EI):
3.87 (d, J=14.0 Hz,2H),3.45 (d,
J=14.0 Hz,2H),3.43 (dd,
J=7.4,
m/z: calcd for C23H27N: 317.2143; found: 317.2139 [M +]; IR (KBr): n˜ =
2.1 Hz,1H),2.77–2.56 (m,2H),2.38 (d,
J=2.2 Hz,1H),2.09–1.87 (m,
À1
3302 (s),2926 (vs),2851 (s),1495 (m),1448 (m),746 (s),698 cm
(s); el-
2H); 13C NMR (75 MHz,CDCl 3): d=140.5,139.4,131.3,130.1,128.9,
4390
www.chemeurj.org
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
Chem. Eur. J. 2006, 12,4380 – 4392

Enantioselective Synthesis
FULL PAPER
128.3,127.0,119.5,81.5,73.0,55.0,50.8,35.3,31.8; MS (70 eV,EI):
m/z:
367.1395; found: 367.1382 [M +]; IR (film): n˜ = 3274 (vs),3026 (m),2836
(m),1453 (m),1428 (m),1368 (m),1099 (m),755 (s),737 (s),701 (s),674
(m),658 cm À1 (m).
417 (<1) [M +],235 (19),234 (100),91 (79); HRMS (EI): m/z: calcd for
C25H24BrN: 417.1092; found: 417.1044 [M +]; IR (film): n˜ = 3296 (m),
3028 (m),2931 (m),2835 (m),1488 (vs),1454 (s),1072 (s),1012(s),747
(s),698 cm
47.8 (À),67.2 min ( +).
(R)-1-Ferrocenyl-1-[(S)-2-methoxymethyl-1-pyrrolidinyl]-3-trimethylsilyl-
2-propyne (12c): Prepared according to GP A from trimethylsilylacety-
À1
(vs); HPLC (OD-H,100% n-heptane,0.5 mLmin À1): tR =
lene (1e) (982 mg,10.0 mmol),ferrocenecarbaldehyde
(
2l) (2.14 g,
Ethyl 4-[3-(dibenzylamino)-4-pentynyl]benzoate (8o): The reaction was
carried out according to GP B with propargylamine (À)-5o (140 mg,
0.29 mmol) and Bu4NF (0.10 mL,0.10 mmol) in THF (3 mL) at 0 8C for
15 min. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 9:1) yielded propargylamine (À)-8o (108 mg,
0.26 mmol,91%) as a colorless oil. [ a]2D0 =À83 (c=0.81,CHCl 3); 1H
NMR (300 MHz,CDCl 3): d=7.89 (d, J=8.2 Hz,2H),7.42–7.24 (m,
10.0 mmol),(2 S)-2-(methoxymethyl)pyrrolidine (1.15 g,10.0 mmol),
CuBr (72 mg,0.50 mmol),MS 4 Š (5.0 g) in toluene (20 mL) at RT for 5
d. Standard workup and column chromatographic purification on silica
gel (pentane/Et2O 9:1) afforded 12c as a red oil (3.03 g,7.40 mmol,
74%). [a]2D0 =+181.9 (c=1.56,CHCl 3); 1H NMR (300 MHz,CDCl 3): d=
4.72 (s,1H),4.43 (s,1H),4.20 (s,1H),4.16 (s,5H),4.08 (s,2H),3.39 (s,
3H),3.38 (dd, J=9.2 Hz,5.9 Hz,1H),3.28 (dd,
J=9.2 Hz,6.3 Hz,1H),
10H),7.09 (d, J=8.5 Hz,2H),4.39 (q,
13.6 Hz,2H),3.50–3.46 (m,1H),3.45 (d,
J=7.1 Hz,2H),3.88 (d,
J=13.6 Hz,2H),2.88–2.78 (m,
J=
3.11–3.07 (m,1H),2.66–2.61 (m,2H),1.86–1.80 (m,1H),1.67–1.56 (m,
3H),0.24 (s,9H); 13C NMR (75 MHz,CDCl 3): d=103.0,88.8,86.1,76.6,
76.2,68.6,68.3,67.8,67.1,59.5,58.7,53.9,48.1,26.3,22.5,0.12; MS (EI,
70 eV): m/z (%): 410 (10) [M +ÀH],409 (31),296 (33),295 (100);
HRMS: m/z: calcd for C22H31FeNOSi: 409.1524; found: 409.1544; IR
(KBr): n˜ = 3096 (m),2960 (s),2873 (s),2825 (m),2161 (m),1449 (m),
1249 (s),1106 (vs),999 (s),842 cm À1 (vs).
1H),2.74–2.63 (m,1H),2.39 (d, J=2.2 Hz,1H),2.13–1.90 (m,2H),1.42
(t, J=7.1 Hz,3H); 13C NMR (75 MHz,CDCl 3): d=166.6,147.0,139.4,
129.6,128.9,128.3,128.1,127.0,88.6,81.5,73.1,60.7,55.0,51.0,35.1,32.5,
14.4; MS (70 eV,EI): m/z: 411 (2) [M +],235 (19),234 (100),91 (83);
HRMS (EI): m/z: calcd for C28H29NO2: 411.2198; found: 411.2233 [M +];
IR (film): n˜ = 3295 (m),2936 (m),1716 (vs),1611 (m),1454 (m),1367
(m),1277 (vs),1178 (m),1107 (s),747 (m),699 cm
sis calcd (%) for C28H29NO2: C 81.72,H 7.10,N 3.40; found: C 81.60,H
7.19,N 3.29.
N,N-Dibenzyl-4-phenyl-1-pentyn-3-amine (14): Prepared according to GP
A from trimethylsilylacetylene (1e) (196 mg,2.00 mmol),phenyl propio-
naldehyde (268 mg,2.00 mmol),dibenzylamine ( 3a) (394 mg,2.00 mmol),
CuBr (14.2 mg,0.10 mmol) and MS 4 Š (1.0 g) in toluene (4 mL) at RT
for 4 d. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) afforded 14 as a white solid (363 mg,
À1 (s); elemental analy-
N,N-Dibenzyl-1-(2-thienyl)-2-propyn-1-amine (8p): The reaction was car-
ried out according to GP
C with propargylamine (+)-5r (95 mg,
1
0.24 mmol) and KOH (0.40 mL,0.40 mmol) in MeOH (3 mL) at RT for
12 h. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (+)-8p (76 mg,
0.24 mmol,99%) as a colorless oil. [ a]2D0 =+32 (c=0.50,CHCl 3); 1H
NMR (300 MHz,CDCl 3): d=7.53–7.51 (m,4H),7.37 (t, J=7.5 Hz,4H),
7.30–7.25 (m,4H),6.97 (dd, J=4.8,3.6 Hz,1H),4.90 (s br,1H),3.90 (d,
J=13.8 Hz,2H),3.51 (d, J=13.8 Hz,2H),2.64 (d, J=2.3 Hz,1H); 13C
NMR (75 MHz,CDCl 3): d=144.0,139.0,128.7,128.3,127.1,126.2,126.1,
0.88 mmol,44%). The dr 92:8 was determined by H NMR analysis. M.p.
79–818C; 1H NMR (300 MHz,CDCl 3): d=7.31–7.28 (m,3H),7.23–7.19
(m,6H),7.00–6.91 (m,6H),3.77 (d,
11.3 Hz,1H),3.32 (d, J=13.6 Hz,2H),3.14–3.02 (m,1H),1.34 (d,
6.8 Hz,3H),0.33 (s,9H);
129.0,128.9,128.2,128.0,127.9,126.7,126.1,103.3,90.6,58.5,54.5,42.7,
J=13.6 Hz,2H),3.53 (d,
J=
J=
13C NMR (75 MHz,CDCl 3): d=144.1,139.2,
21.2,0.4; MS (70 eV,EI): m/z (%): 396 (1) [M +ÀCH3],307 (28),306
(100),91 (32); HRMS (EI): m/z: calcd for C28H32NSi: 410.2304; found:
410.2329 [M +ÀH]; IR (KBr): n˜ = 2958 (w),2806 (w),2158 (w),1495
125.5,78.4,74.8,54.4,52.1; MS (70 eV,EI):
m/z (%): 317 (22) [M +],226
(32),121 (100); HRMS (EI): m/z: calcd for C21H19NS: 317.1238; found:
(w),1453 (w),1247 (m),1005 (m),838 (s),748 (s),698 cm
À1 (vs); elemen-
317.1255 [M +]; IR (film): n˜ = 3294 (m),3028 (m),2834 (m),2810 (m),
tal analysis calcd for C28H33NSi: C 81.69,H 8.08,N 3.40; found: C 81.99,
H 7.87,N 3.32.
N4,N4,N13,N13-Tetrabenzyl-5,11-hexadecadiyne-4,13-diamine (15): Pre-
pared according to GP A from 1,7-octadiyne (106 mg, 1.00 mmol), butyr-
À1
1495 (m),1454 (m),1232 (m),1116 (m),745 (m),698 (vs),665 cm
(m);
=
HPLC (OD-H,98% n-heptane/2% isopropanol,0.2 mLmin À1): tR
21.0 (À),23.0 min ( +).
N,N-Dibenzyl-1-(3-thienyl)-2-propyn-1-amine (8q): The reaction was car-
ried out according to GP with propargylamine (+)-5s (99 mg,
aldehyde (2m) (144 mg,2.00 mmol),dibenzylamine
(
3a) (394 mg,
C
2.00 mmol),CuBr (14.2 mg,0.10 mmol) and MS 4 Š (1.0 g) in toluene
(4 mL) at RT for 7 d. Standard workup and column chromatographic pu-
rification on silica gel (pentane/Et2O 99:1) afforded 15 (372 mg,
0.26 mmol) and KOH (0.40 mL,0.40 mmol) in MeOH (3 mL) at RT for
12 h. Standard workup and column chromatographic purification on
silica gel (pentane/Et2O 99:1) yielded propargylamine (+)-8q (74 mg,
0.26 mmol,99%) as a colorless oil. [ a]2D0 =+22 (c=0.52,CHCl 3); 1H
NMR (300 MHz,CDCl 3): d=7.43–7.37 (m,5H),7.32–7.18 (m,8H),4.67
(s br,1H),3.75 (d, J=13.6 Hz,2H),3.42 (d, J=13.6 Hz,2H),2.55 (d,
J=2.2 Hz,1H); 13C NMR (75 MHz,CDCl 3): d=140.5,139.4,128.8,
0.61 mmol,61%)as a colorless oil. 1H NMR (300 MHz,CDCl ): d=7.40–
3
7.37 (m,8H),7.31–7.18 (m,12H),3.81 (d,
J=14.0 Hz,4H),3.40 (d, J=
14.0 Hz,4H),3.39–3.36 (m,2H),2.39–2.37 (m,2H),1.81–1.37 (m,12H),
0.78 (t, J=7.2 Hz,6H); 13C NMR (75 MHz,CDCl 3): d=140.1,128.8,
128.1,126.7,84.4,78.5,54.9,51.5,36.4,28.4,19.6,18.3,13.7; MS (70 eV,
EI): m/z (%): 608 (<1) [M +],566 (13),565 (29),370 (12),92 (12),91
(100); HRMS (EI): m/z: calcd for C44H52N2: 608.4130; found: 608.4106
128.3,127.4,127.0,125.7,123.2,79.3,74.5,54.4,52.0; MS (70 eV,EI):
m/z
(%): 317 (22) [M +],226 (31),196 (48),122 (20),120 (100),92 (12),91
(84); HRMS (EI): m/z: calcd for C21H19NS: 317.1238; found: 317.1232
[M +]; IR (film): n˜ = 3294 (s),3028 (m),2809 (m),1494 (s),1454 (s),
1284 (m),1116 (m),1074 (m),842 (m),790 (s),753 (s),741 (s),698 (vs),
[M +]; IR (KBr): n˜ = 3028 (m),2956 (s),2935 (s),2871 (m),1494 (s),
À1
1454 (s),747 (s),698 cm
(vs); elemental analysis calcd (%) for
C44H52N2: C 86.79,H 8.61,N 4.60; found: C 87.04,H 8.59,N 4.52.
660 cmÀ1 (m); HPLC (OD-H,98%
n-heptane/2% isopropanol,
N,N-Diallyl-N-(1-{4-[1-(diallylamino)-3-phenyl-2-propynyl]-phenyl}-3-
phenyl-2-propynyl)amine (16): Prepared according to GP A from phenyl-
acetylene (1a) (408 mg,4.00 mmol),terephthalaldehyde (268 mg,
0.2 mLminÀ1): tR =20.6 (À),23.5 min ( +).
N-[1-(1-Benzothien-3-yl)-2-propynyl]-N,N-dibenzylamine (8r): The reac-
tion was carried out according to GP C with propargylamine (À)-5u
(121 mg,0.28 mmol) and KOH (0.40 mL,0.40 mmol) in MeOH (3 mL) at
RT for 12 h. Standard workup and column chromatographic purification
2.00 mmol),diallylamine
( 3b) (388 mg,4.00 mmol),CuBr (28.7 mg,
0.20 mmol) and MS 4 Š (2.0 g) in toluene (6 mL) at RT for 1 d and at
608C for 18 h. Standard workup and column chromatographic purifica-
on silica gel (pentane/Et2O 99:1) yielded propargylamine (À)-8r (95 mg,
tion on silica gel (pentane/Et2O 24:1) afforded 16 (718 mg,1.45 mmol,
1
1
0.26 mmol,92%) as a yellow oil. [ a]2D0 =À119 (c=0.82,CHCl ); H NMR
72%)as a yellow solid. M.p. 738C; H NMR (300 MHz,CDCl ): d=7.68–
3
3
(600 MHz,CDCl 3): d=7.70 (m,1H),7.67 (m,1H),7.63 (s,1H),7.24–
7.47 (m,4H),7.56–7.52 (m,4H),7.37–7.32 (m,6H),5.94–5.81 (m,4H),
5.31–5.26 (m,4H),5.16–5.13 (m,4H),5.11 (s,2H),3.33–3.27 (m,4H),
3.10–3.03 (m,4H); 13C NMR (75 MHz,CDCl 3): d=138.5,136.5,131.8,
7.20 (m,10H),7.16–7.14 (m,2H),4.92 (s,1H),3.73 (d,
J=13.1 Hz,2H),
3.37 (d, J=13.1 Hz,2H),2.61 (s,1H); 13C NMR (150 MHz,CDCl 3): d=
141.3,139.4,137.9,133.7,129.9,128.6,127.6,126.7,124.8,124.1,123.8,
123.0,79.0,75.8,55.2,51.8; MS (70 eV,EI):
(16),172 (19),171 (100),91 (33); HRMS (EI): m/z: calcd for C25H21NS:
128.3,128.1,128.0,123.3,117.3,87.8,85.5,56.4,53.6; MS (70 eV,EI):
m/z
m/z (%): 367 (10) [M +],196
(%): 496 (10) [M +],455 (13),401 (29),400 (100),399 (11),358 (12),318
(11),305 (25),304 (50),210 (26),41 (28); HRMS (EI):
m/z: calcd for
Chem. Eur. J. 2006, 12,4380 – 4392
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
4391

P. Knochel and N. Gommermann
C36H36N2: 496.2878; found: 496.2878 [M +]; IR (KBr): n˜ = 3079 (m),
Int. Ed. 2001, 40,2534; e) L. Shi,Y.-Q. Tu,M. Wang,F.-M. Zhang,
C.-A. Fan, Org. Lett. 2004, 6,1001; f) C. M. Wei,C.-J. Li, J. Am.
2817 (m),1643 (m),1490 (s),1443 (m),1417 (m),995 (m),972 (m),920
À1
(s),755 (vs),690 cm
(s); elemental analysis calcd (%) for C36H36N2: C
Chem. Soc. 2002, 124,5638; g) C. M. Wei,Z. G. Li,C.-J. Li,
Org.
87.05,H 7.31,N 5.64; found: C 87.01,H 7.43,N 5.51.
Lett. 2003, 5,4473; h) Z. Li,C.-J. Li, Org. Lett. 2004, 6,4997; i) J. F.
Traverse,A. H. Hoveyda,M. L. Snapper, Org. Lett. 2003, 5,3273;
j) for the preparation of chiral propargylic alcohols see: D. E.
Frantz,R. Faessler,E. M. Carreira, J. Am. Chem. Soc. 2000, 122,
1806.
Acknowledgements
[8] a) J. M. Valk,G. A. Whitlock,T. P. Layzell,J. M. Brown,
Tetrahe-
dron: Asymmetry 1995, 6,2593; b) E. Fernandez,K. Maeda,M. W.
Hooper,J. M. Brown, Chem. Eur. J. 2000, 6,1840.
We thank the Fonds der Chemischen Industrie and Merck Research Lab-
oratories (MSD) for financial support. We thank the DFG (SPP 1118
“Sekundäre Wechselwirkungen als Steuerungsprinzip zur gerichteten
Funktionalisierung reaktionsträger Substrate”) for a fellowship for N.G.
and Chemetall GmbH (Frankfurt) and BASF AG (Ludwigshafen) for
generous gift of chemicals.
[9] P. J. Kocienski, Protective Groups,Thieme,Stuttgart,3rd ed.,
2003.
[10] a) C. Koradin,K. Polborn,P. Knochel,
Angew. Chem. 2002, 114,
2651; Angew. Chem. Int. Ed. 2002, 41,2535; b) C. Koradin,N. Gom-
mermann,P. Knochel, Chem. Eur. J. 2003, 9,2797.
[11] a) K. Sonogashira in Comprehensive Organic Synthesis, Vol. 3 (Eds.:
B. M. Trost,I. Fleming,G. Pattenden),Pergamon Press,New York,
1991; b) K. Sonogashira,Y. Tohda,N. Hagihara, Tetrahedron Lett.
1975,4467; c) for an excellent review,see: R. R. Tykwinski, Angew.
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[12] a) F. Bois,D. Gardette,J.-C. Gramain, Tetrahedron Lett. 2000, 41,
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Received: October 7,2005
Published online: March 24,2006
4392
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