An efficient synthesis of terminal allenes from terminal 1-alkynes

Full text of DOI:10.1021/jo802391x

TABLE 1. Optimization of Conditions for the Reaction of 1a with
(CH2O)n, Amine, and CuX
An Efficient Synthesis of Terminal Allenes from
Terminal 1-Alkynes
Jinqiang Kuang and Shengming Ma*
Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, Department of Chemistry, East China Normal
UniVersity, 3663 North Zhongshan Road, Shanghai 200062,
People’s Republic of China, and State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu,
Shanghai 200032, People’s Republic of China
entry
amine (equiv)
catalyst (equiv)
yield of 2a (%)
1
2
3
4
5
6
7
8
i-Pr2NH (1.8)
Cy2NH (1.8)
Cy2NH (1.8)
Cy2NH (1.8)
Cy2NH (1.8)
Cy2NH (1.8)
Cy2NH (1.5)
Cy2NH (2.0)
CuBr (0.5)
CuBr (0.5)
CuCl (0.5)
CuI (0.5)
CuI (0.2)
CuI (0.8)
CuI (0.5)
CuI (0.5)
33
43
26
59
36
54
21
45
masm@mail.sioc.ac.cn
ReceiVed October 26, 2008
propargylic amine from the Mannich-type reaction of terminal
1-alkyne, paraformaldehyde, and i-Pr2NH.4e In addition, re-
cently, Nakamura et al. reported the Pd-catalyzed hydride-
transfer reactions of propargylic diisopropyl or dicyclohexyl
amines for the formation of allenes.5 In this Note, we wish to
report our recent observation that the commercially available
dicyclohexylamine is a superior amine and CuI is a better
mediator for this transformation leading to much higher yields
for the formation of terminal allenes in the presence of different
functional groups, such as mesylate, hydroxyl group, ether,
amide, etc.
1-Decyne was chosen as the model substrate in search of a
better protocol (eq 2). Under the reported conditions,4 the
reaction of 1-decyne with i-Pr2NH and CuBr in dioxane afforded
terminal allene 2a in only 33% yield (entry 1, Table 1). As
expected no reaction was observed with 2-imidazolidone and
2-imidazolidinethione; 1-phenylpiperazine did not work either;
diallyl or dibenzyl amine also failed to promote this reaction.
Amines with one secondary alkyl group such as (1R,2R)-1,2-
diaminocyclohexane, (R)-phenylalanine, benzyl R-naphthylethyl
amine, benzyl isopropyl amine, ethyl isopropyl amine, 2-methyl-
1,4-diazacyclohexane, and N,N-diisopropyl ethylenediamine also
failed or afforded a trace amount of the product.
We have developed a modified method for the synthesis of
terminal allenes from terminal 1-alkyne: The reaction of
1-alkynes with 1.8 equiv of Cy2NH and 2.5 equiv of
paraformaldehyde mediated by CuI (0.5 equiv) in refluxing
dioxane may produce terminal allenes in much higher yields
than the previously reported protocol and many functional
groups such as mesylate, hydroxyl group, ether, amide, etc.
may be tolerated.
Allenes have become more and more important in organic
synthesis,1,2 thus, efficient new methods for the synthesis of
allenes from the commonly used starting materials are highly
desirable.3 Terminal alkynes are readily available organic
compounds and may be efficiently converted to terminal allenes
by reaction with paraformaldehyde in the presence of i-Pr2NH
and CuBr in dioxane.4 However, in many cases the reaction
provides the products in relatively low yields. To further
improve this one-step procedure, we reasoned that the amine
may be crucial for this transformation since the i-Pr2NH used
also provides the “H” for the reduction of the in situ formed
Fortunately, when dicyclohexylamine was used, the yield was
improved to 43% (entry 2, Table 1). Further study led to the
observation that CuI is better than CuBr or CuCl (entries 2 and
3, Table 1) affording 2a in 59% yield. Screening on the amounts
of dicyclohexylamine and CuI indicated that 1.8 equiv of this
amine and 0.5 equiv of CuI are the best (compare entries 4-8,
(1) For monographs, see: (a) The Chemistry of Allenes; Landor, S. R., Ed.;
Academic: London, 1982; Vol. 1. (b) Modern Allene Chemistry; Krause, N.,
Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Vols. 1 and
2. (c) Ma, S. Palladium-Catalyzed Two-or Three-Component Cyclization of
Functionalized Allenes in Palladium in Organic Synthesis; Ed.: Tsuji, J., Ed.;
Springer, Berlin, Germany, 2005; pp 183-210.
(4) (a) Rona, P.; Crabbe´, P. J. Am. Chem. Soc. 1969, 91, 3289. (b) Dollat,
J. M.; Luche, J. L.; Crabbe´, P. J. Chem. Soc., Chem. Commun. 1977, 761. (c)
Crabbe´, P.; Fillion, H.; Andre´, D.; Luche, J. L. J. Chem. Soc., Chem. Commun.
1979, 860. (d) Crabbe´, P.; Andre´, D.; Fillion, H. Tetrahedron Lett. 1979, 893.
(e) Searles, S.; Li, Y.; Nassim, B.; Lopes, M.-T. R.; Tran, P. T.; Crabbe´, P.
J. Chem. Soc., Perkin Trans. 1 1984, 747. (f) Ma, S.; Hou, H.; Zhao, S.; Wang,
G. Synthesis 2002, 1643.
(5) (a) Nakamura, H.; Kamakura, T.; Ishiku, M.; Biellmann, J.-F. J. Am.
Chem. Soc. 2004, 126, 5958. (b) Nakamura, H.; Tashiro, S.; Kamakura, T.
Tetrahedron Lett. 2005, 8333. (c) Nakamura, H.; Onagi, S. Tetrahedron Lett.
2006, 2539. (d) Nakamura, H.; Kamakura, T.; Onagi, S. Org. Lett. 2006, 8,
2095. (e) Nakamura, H.; Ishikura, M.; Sugiishi, T.; Kamakura, T.; Biellmann,
J.-F. Org. Biomol. Chem. 2008, 6, 1471.
(2) For reviews, see: (a) Zimmer, R.; Dinesh, C.; Nandanan, E.; Khan, F.
Chem. ReV. 2000, 100, 3067. (b) Ma, S. Chem. ReV. 2005, 105, 2829. (c) Ma,
S. Acc. Chem. Res. 2003, 36, 701. (d) Sydnes, L. Chem. ReV. 2003, 103, 1133.
(e) Marshall, J. Chem. ReV. 2000, 100, 3163. (f) Hashmi, A. S. K. Angew. Chem.,
Int. Ed. 2000, 39, 3590. (g) Bates, R.; Satcharoen, V. Chem. Soc. ReV. 2002,
31, 12. (h) Brandasma, L.; Nedolya, N. A. Synthesis 2004, 735. (i) Tius, M.
Acc. Chem. Res. 2003, 36, 284. (j) Wei, L. L.; Xiong, H.; Hsung, R. P. Acc.
Chem. Res. 2003, 36, 773. (k) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001,
34, 535. (l) Wang, K. K. Chem. ReV. 1996, 96, 207. (m) Ma, S. Aldrichim. Acta
2007, 40, 91.
(3) Brummond, K M.; Deforrest, J. E. Synthesis 2007, 795.
10.1021/jo802391x CCC: $40.75
Published on Web 01/05/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1763–1765 1763

TABLE 2. The Cu(I)-Mediated Reaction of 1-Alkyne,
Paraformaldehyde, and i-Pr2NH or Dicyclohexyl Amine in Dioxane
SCHEME 1
conditions A
conditions B
time yield of time yield of
entry
1: R1
(h)
2a (%)
(h)
2a (%)
1
2
3
4
5
6
7
8
9
CH3(CH2)7 (1a)
CH3(CH2)9 (1b)
p-C6H4C6H4 (1c)
MsO(CH2)7 (1d)
2.7
2.5
1.9
2.3
1.5
2.9
2.0
3.0
1.9
2.3
2.2
42
36
59
30
53
59
40
32
33
35
27
2.7
2.5
2.2
2.3
1.5
2.9
3.0
3.0
1.9
2.3
2.2
66 (2a)
60 (2b)
70 (2c)
53 (2d)
81 (2e)
98 (2f)
74 (2g)
72 (2h)
52 (2i)
65 (2j)
42 (2k)
PhCH2OCH2 (1e)
magnesium bromide with p-phenylphenyl iodide with Pd(PPh3)4
as the catalyst.7 Alkyne 1d was prepared by the tosylation of
8-nonyn-1-ol.8 Alkynes 1e and 1f were prepared by the reaction
of the corresponding benzyl alcohols with propargyl bromide in
DMSO at room temperature with KOH as the base and in THF at
50 °C with NaOH as the base, respectively.9 Homopropargyl
alcohols 1g, 1h, and 1j were prepared by the Zn-promoted Barbier-
type reaction of the related aldehydes with propargyl bromide under
solvent-free conditions at room temperature.10 Homopropargyl
alcohol 1i was obtained by the reaction of 2-chlorobenzaldehyde
with the Grignard reagent of propargyl bromide in Et2O.11 Terminal
alkyne 1k was prepared by the reaction of 2-hydroxytosylamide
with propargyl bromide, using K2CO3 (2 equiv)-TBAB (0.5 equiv)
as the base in THF at room temperature.12 The 13CNMR data are
H-decoupled.
General Procedure for the Synthesis of Allenes (2a-k).
(CH2O)n (0.5 mmol), CuI (0.1 mmol), dioxane (1 mL), alkyne (0.2
mmol), and amine (0.36 mmol) were added sequentially into an
oven-dried reaction tube equipped with a reflux condenser under
an argon atmosphere. The resulting mixture was stirred under reflux.
When the reaction was complete as monitored by TLC, it was
cooled to rt. Water (5 mL) and ether (10 mL) were added and then
the aqueous solution was separated and extracted with ether (3 ×
5 mL). The organic layer was then washed with brine and dried
over anhydrous Na2SO4. Evaporation and column chromatography
on silica gel (eluent: petroleum ether or petroleum ether/Et2O)
afforded the terminal allene.
p-O2NC6H4CH2OCH2 (1f)
p-EtC6H4CH(OH)CH2 (1g)
p-ClC6H4CH(OH)CH2 (1h)
o-ClC6H4CH(OH)CH2 (1i)
p-BrC6H4CH(OH)CH2 (1j)
HOCH2C(Me)2NTsCH2 (1k)
10
11
a Isolated yield.
Table 1). Thus, we defined the reaction of 1-alkyne with 2.5
equiv of paraformaldehyde, 1.8 equiv of dicyclohexylamine, and
CuI (0.5 equiv) in dioxane as the standard (conditions B).
With the standard conditions B, the scope and generality of
this new procedure were studied and the results are summarized
in Table 2. For alkyl or p-phenylphenyl-substituted terminal
alkynes, the reaction afforded the corresponding allenes 2a-c
in 60-70% isolated yields (entries 1-3, Table 2). The reaction
of the terminal alkyne with a methanesulfonate functionality
1d afforded allene 2d in 53% isolated yield (entry 4, Table 2).
Terminal alkynes with a benzyl ether functionality are high
yielding (entry 5 and 6, Table 2). The reaction of homoprop-
argylic alcohols yielded ꢀ-allenols6 2g-j in 52-74% isolated
yields (entry 7-10, Table 2). Finally the terminal homoprop-
argylic tosylamide with a free hydroxyl group was converted
to the corresponding allene 2k in 42% yield (entry 11, Table
2). In all cases the modified protocol afforded the allenes in
higher yields (compare conditions A with B in Table 2).
Three examples of large-scale reactions also have been
demonstrated (Scheme 1).
In conclusion, we have developed a modified one-step
procedure for converting terminal alkynes to terminal allenes
by applying 0.5 equiv of CuI, 1.8 equiv of dicyclohexylamine,
and 2.5 equiv of paraformaldehyde. Due to the increasing
importance of allenes in organic chemistry and the commercial
availability of all the reagents, this method will be of interest
for organic chemists since many functional groups such as
mesylate, hydroxyl group, ether, amide, etc. may be tolerated.
Further studies in this area are being actively pursued in this
laboratory.
(1) Synthesis of undeca-1,2-diene (2a). Conditions A: The
reaction of dec-1-yne (27.9 mg, 0.20 mmol), paraformaldehyde
(15.3 mg, 0.51 mmol), diisopropylamine (37.0 mg, 0.37 mmol),
and CuBr (14.4 mg, 0.10 mmol) in dioxane (1 mL) afforded 2a4e
(12.9 mg, 42%) as a liquid (eluent: petroleum ether): 1H NMR (300
MHz, CDCl3) δ 5.15-5.04 (m, 1 H), 4.70-4.60 (m, 2 H),
2.05-1.93 (m, 2 H), 1.47-1.18 (m, 12 H), 0.88 (t, J ) 6.6 Hz, 3
H); 13C NMR (75 MHz, CDCl3) δ 208.5, 90.1, 74.5, 31.9, 29.5,
29.3, 29.2, 29.1, 28.3, 22.7, 14.1; MS (EI) m/z 152 (M+, 0.04),
137 (M+ - CH3, 1.87), 54 (100); IR (neat) 1957, 1466, 1378, 841
cm-1
.
Conditions B: The reaction of dec-1-yne (27.8 mg, 0.20 mmol),
paraformaldehyde (15.0 mg, 0.50 mmol), dicyclohexylamine (65.5
(7) Negishi, E.-I.; Kotora, M.; Xu, C. J. Org. Chem. 1997, 62, 8957.
(8) (a) Ma, D.; Lu, X. Tetrahedron 1990, 46, 6319. (b) Taylor, E. C.; Macor,
J. E.; French, L. G. J. Org. Chem. 1991, 56, 1807.
Experimental Section
(9) Boger, D. L.; Palanki, M. S. S. J. Am. Chem. Soc. 1992, 114, 9318.
(10) Wang, J.; Jia, X.; Meng, T.; Xin, L. Synthesis 2005, 2838.
(11) (a) Speicher, A.; Bomm, V.; Eicher, T. J. Prakt. Chem. 1996, 338, 558.
(b) Hashmi, A. S. K.; Ruppert, T. L.; Kno¨fel, T.; Bats, J. W. J. Org. Chem.
1997, 62, 7295. (c) Ma, S.; Yu, S.; Yin, S. J. Org. Chem. 2003, 68, 8996.
(12) Ozaki, S.; Matsushita, H.; Ohmori, H. J. Chem. Soc., Perkin Trans. 1
1993, 2339.
Starting alkynes 1a and 1b are commercial available from Sigma-
Aldrich; Compound 1c was prepared by the coupling of acetylenyl
(6) (a) Ma, S.; Gao, W. Synlett 2002, 65. (b) Ma, S.; Gao, W. J. Org. Chem.
2002, 67, 6104. (c) Cheng, X.; Jiang, X.; Yu, Y.; Ma, S. J. Org. Chem. 2008,
73, 8960.
1764 J. Org. Chem. Vol. 74, No. 4, 2009

mg, 0.36 mmol), and CuI (19.1 mg, 0.10 mmol) in dioxane (1 mL)
afforded 2a (20.2 mg, 66%).
2 H), 2.50-2.41 (m, 2 H), 2.12 (s, 1 H), 1.24 (t, J ) 7.5 Hz, 3 H);
13C NMR (75 MHz, CDCl3) δ 209.4, 143.6, 140.9, 127.9, 125.8,
86.2, 74.9, 73.5, 38.3, 28.5, 15.6.
(2) Synthesis of 1-(4-Ethylphenyl)penta-3,4-dien-1-ol (2g). Into
a 50-mL three-necked flask equipped with a reflux condenser were
added 0.453 g (15.1 mmol) of paraformaldehyde, 0.571 g (3.0
mmol) of CuI, 9 mL of dioxane, 1.062 g (6.1 mmol) of 1g, and
1.955 g (10.8 mmol) of dicyclohexylamine sequentially. The
resulting mixture was gently refluxed with stirring. After 2.5 h as
monitored by TLC, the resulting mixture was then cooled to room
temperature and filtered. The filtrate was concentrated under vacuum
to a gummy residue and then diluted with 5 mL of water followed
by the addition of 10 mL of ether. The resulting mixture was then
acidified with 1 N hydrochloric acid to pH 1-2. The organic layer
was separated and the aqueous solution was extracted with ether
(3 × 10 mL). The combined organic layer was washed with small
portions of water until pH 6-7. The organic layer was then washed
with brine and dried over anhydrous Na2SO4. Evaporation and
column chromatography on silica gel (eluent: petroleum ether/Et2O)
Acknowledgment. Financial support from the Major State
BasicResearchDevelopmentProgram(GrantNo.2006CB806105)
and National Natural Science Foundation of China (No.
20732005) is greatly appreciated.
Note Added after ASAP Publication. There were errors in
the Supporting Information file published ASAP January 5,
2009; the corrected version was published January 22, 2009.
Supporting Information Available: Typical experimental
procedure and analytical data for all new products not listed in
1
the text and H and 13C NMR spectra of all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
afforded the terminal allene 2g6c (0.824 g, 72%): H NMR (300
1
MHz, CDCl3) δ 7.29 (d, J ) 8.1 Hz, 2 H), 7.19 (d, J ) 8.1 Hz, 2
H), 5.18-5.06 (m, 1 H), 4.78-4.68 (m, 3 H), 2.65 (q, J ) 7.5 Hz,
JO802391X
J. Org. Chem. Vol. 74, No. 4, 2009 1765