One-pot synthesis of 1,3-disubstituted allenes from 1-alkynes, aldehydes, and morpholine

Article abstract of DOI:10.1021/ja910503k

(Formula Presented) ZnI₂ has been identified as the catalyst for the one-step synthesis of allenes from terminal alkynes and aldehydes with morpholine as the base in toluene. The reaction is believed to proceed via the intermediacy of propargylic amines, which was converted to allenes by a sequential hydride transfer and β-elimination process. The reaction is applicable for both aromatic and aliphatic aldehydes. Functionalities such as halide, hydroxyl, or amine may be tolerated. Copyright

Full text of DOI:10.1021/ja910503k

Published on Web 01/26/2010
One-Pot Synthesis of 1,3-Disubstituted Allenes from 1-Alkynes, Aldehydes, and
Morpholine
Jinqiang Kuang† and Shengming Ma*,†,‡
Shanghai Key Laboratory of Green Chemistry and Chemical Process, Department of Chemistry, East China Normal UniVersity,
3663 North Zhongshan Lu, Shanghai 200062, P. R. China and State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R. China
Received December 13, 2009; E-mail: masm@mail.sioc.ac.cn
During the past 10-15 years, allenes have been shown to be
versatile intermediates in organic synthesis.1,2 In addition to this, many
natural products and pharmaceuticals with an allene moiety have been
identified.3 Thus, synthetic methods for allenes from readily available
organic compounds are of high interest for chemists to use as the
starting materials in their target synthesis.4 Crabbe´ et al. reported the
first CuBr-mediated reaction to form terminal allenes from 1-alkynes
and formaldehyde in the presence of diisopropylamine.5a,b Based on
this, recently we have developed a modified one-step procedure for
converting terminal alkynes to terminal allenes in higher yields by
applying CuI, paraformaldehyde, and dicyclohexylamine.5c However,
it should be noted that the reaction is limited to paraformaldehyde: no
allene was formed when other aldehydes were used. Bertrand et al.
employed a cationic gold(I) complex for the catalytic coupling of
enamines and terminal alkynes to yield a wide range of nonterminal
allenes.6 Wong and Che et al. reported the synthesis of disubstituted
allenes from propargylic amines.7 Thus, a new one-step protocol, which
just involves the easily available aldehydes beyond paraformaldehyde
and terminal alkynes, is highly desirable. Herein, we wish to report
the realization of such a protocol, which uses cost-effective ZnI2 and
morpholine affording 1,3-disubstituted allenes from aromatic or
aliphatic aldehydes and terminal alkynes.8
MeCN; toluene turned out to be the best. Further screening on the
structures of amines led us to find that the most appropriate amine
for the allene forming reaction is morpholine; piperidine is less
effective (Table S2). Then the experimental parameters have been
thoroughly screened to improve the yield (Table S3), and we
observed that the reaction of 1-alkyne with 1.8 equiv of aldehyde,
1.4 equiv of morpholine, and 0.8 equiv of ZnI2 in toluene at 130
°C gave allene 3aa in the highest yield (Table S3, entry 7). Further
study on the concentration effect led us to observe that the reaction
of a 1 mmol scale of 1a in 1, 3, 5, or 7 mL of toluene afforded 3aa
in 37, 56, 65, 61% isolated yields, respectively, which indicates
that the concentration has some influence on the reaction.
After these optimizations, the substrate scope and generality of the
reaction have been investigated and the typical results are summarized
in Table 2: simple terminal alkynes reacted with benzaldehyde or
substituted benzaldehydes bearing p-Cl, p-Br, and p-CF3 functionalities
to afford the corresponding allenes in moderate yields (entries 1-3
and 5-8). Heteromatic aldehyde thiophene-3-carboaldehyde could also
be applied in the transformation, albeit with a relatively lower yield
(entry 4). Moreover, aliphatic aldehydes may also be used, although a
longer time or a higher temperature is needed (entries 10 and 11).
Based on our experience in this area, we chose 1-decyne, benzal-
dehyde, and morpholine as the starting point: with FeCl3 or MgI2, the
formation of allene 3aa was not observed (entries 1 and 2, Table 1).
After extensive screening, it is fortunate to observe that when CdI2
was used, allene 3aa was formed in 36% yield (entry 3, Table 1)!
Further screening led to the observation that cheaper ZnI2 may play
the same role affording 3aa in a slightly higher yield (entry 4, Table
1). ZnX2 (Cl or Br) is not effective; Zn(OTf)2 afforded 3aa in 19%
NMR yield after 4.8 h.
Table 2. ZnI2-Promoted Reaction of Various 1-Alkynes with
Aldehydes in the Presence of Morpholinea
time
(h)
yield of
3 (%)
entry
R1 (1); R2 (2)
b
CH3(CH2)7 (1a); Ph (2a)
1a; p-ClC6H4 (2b)
7.2
6.7
6.8
13.7
9.7
8.5
8.5
9.0
9.2
22
65 (3aa)
52 (3ab)
53 (3ac)
30 (3ad)
57 (3ba)
53 (3bb)
55 (3bc)
58 (3be)
51 (3ca)
56 (3df)
42 (3dg)
1
2
3
4
5
6
7
8
9
Table 1. Attempted One-Step Synthesis of Allene 3aa from
1a; p-BrC6H4 (2c)
1-Decyne and Benzaldehydea
1a; 3-thienyl (2d)
CH3(CH2)9 (1b); 2a
b
b
1b; p-ClC6H4 (2b)
1b; p-BrC6H4 (2c)
1b; p-F3CC6H4 (2e)
p-O2NC6H4CH2O(CH2)2 (1c); 2a
p-O2NC6H4CH2OCH2 (1d); i-Pr (2f)
p-O2NC6H4CH2OCH2 (1d); n-Bu (2g)
b c
,
10
11
b c d
,
,
6
yield of 3aa
(%)/time (h)
yield of 3aa
(%)/time (h)
entry
cat.
entry
cat.
a The reactions were carried out in 1.0 mmol scale in 3 mL of
toluene. b The reactions were carried out in 1.0 mmol scale in 5 mL of
toluene. c The reaction was carried out in a reaction tube sealed with a
screw cap. d The reaction was carried out at 150 °C.
b
1
2
3
FeCl3
MgI2
CdI2
0/20
0/2
36 /2.6
4
5
6
ZnI2
ZnCl2
ZnBr2
38 /2.6
c
16 /5.5
b
c
17 /5.5
a The reactions were carried out in 0.3 mmol scale in 0.9 mL of
toluene. b Isolated yield. c NMR yield.
As we know, 2,3-allenols and 2,3-allenyl amines are usful in organic
synthesis.1,2 4-Substituted 2,3-allenyl alcohols or amines4c,9,10 could
also be obtained as a mixture of ∼1:1 diastereoisomers through this
protocol: the reaction of terminal propargylic alcohols (4a-c) with
benzaldehyde afforded the corresponding 2,3-allenols 5a-c in 52-62%
isolated yields; the reaction of terminal propargylic tosylamide 6 with
Encouraged by these results, we started to study the solvent effect
(Table S1): no product was formed in MeNO2, CHCl3, DCE, or
† East China Normal University.
‡ Chinese Academy of Sciences.
9
1786 J. AM. CHEM. SOC. 2010, 132, 1786–1787
10.1021/ja910503k  2010 American Chemical Society

C O M M U N I C A T I O N S
benzaldehyde or i-PrCHO afforded the corresponding 2,3-allenyl
tosylamides 7a and 7f in 59% and 49% isolated yields, respectively
(Scheme 1).
understand this transformation, and the reaction pathway outlined
in Scheme 2 should be considered a mechanistic framework.
In conclusion, we have established an efficient ZnI2-mediated
protocol for one-pot synthesis of 1,3-disubstituted allenes from
1-alkynes, aldehydes, and morpholine. Although the mechanism
needs further attention, due to the easy availability of all the reagents
used and potential of the allene products,1-3 this reaction will be
of high interest to the scientific community. Further investigations
in this area are being pursued in our laboratory.
Scheme 1
Acknowledgment. Financial support from the National Basic
Research Program of China (No. 2009CB825300) is greatly
appreciated. We thank Mrs. S. Li, J. Chen, and B. Wan in this
group for reproducing some of the results presented in manuscript.
Supporting Information Available: Spectroscopic data and general
procedure. This material is available free of charge via the Internet at
http://pubs.acs.org.
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Scheme 2
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