Transition-metal-catalyzed rearrangement of 5-alkynals to γ-alkynylketones and 1-cyclopentenylketones

Article abstract of DOI:10.1039/b508278a

The transition-metal-catalyzed rearrangement of 5-alkynals to γ-alkynylketones and 1-cyclopentenylketones was developed using [Rh(P(OPh)₃)₂]BF₄ or Cu(OTf)₂ as a catalyst. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b508278a

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COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Transition-metal-catalyzed rearrangement of 5-alkynals to
c-alkynylketones and 1-cyclopentenylketones{
Ken Tanaka,* Kaori Sasaki, Kenzo Takeishi and Koudai Sugishima
Received (in Cambridge, UK) 13th June 2005, Accepted 1st August 2005
First published as an Advance Article on the web 25th August 2005
DOI: 10.1039/b508278a
of 4-methoxy-4-alkyl-5-alkynals were investigated in the
The transition-metal-catalyzed rearrangement of 5-alkynals
to c-alkynylketones and 1-cyclopentenylketones was developed
using [Rh(P(OPh)3)2]BF4 or Cu(OTf)2 as a catalyst.
presence of 10% [Rh(P(OPh)3)2]BF4 or 10% Cu(OTf)2 at 25 uC
as shown in Table 1.6 Both 6-phenyl- and 6-alkyl-5-
alkynals cleanly afforded the corresponding c-alkynylketones
in good yield (entries 1–4). Although the yields of the ketone
were decreased, 5% Rh or Cu catalyst can be used (entries 1 and 2).
Although the reaction of 6-trimethylsilyl-5-alkynal using
[Rh(P(OPh)3)2]BF4 did not proceed even at elevated
temperature (80 uC), the use of Cu(OTf)2 at 80 uC gave the
desired ketone in low yield (entry 5). The scope of 4-alkyl
substituents was also investigated. Not only methyl, but also
n-propyl and i-propyl substituted 5-alkynals can be used for this
reaction (entries 6 and 7). Interestingly, in the absence of
methoxy group, the intramolecular addition of aldehyde to
alkyne proceeded at 50 uC to give 1-cyclopentenylketones
(entries 8–11).7,8
The transition-metal-catalyzed cyclo-isomerization of alkynyl
carbonyl compounds leading to a variety of cyclic compounds
has been developed though activation of alkynes by p-complexa-
tion to electrophilic transition metal complexes.1–3 However, the
reactions of c-alkynyl carbonyl compounds including 5-alkynals in
the presence of electrophilic transition metal complexes have
been scarcely explored.4 In this Communication, we describe
the transition-metal-catalyzed rearrangement of 5-alkynals to
c-alkynylketones and 1-cyclopentenylketones. The substituents at
the 4-position of 5-alkynals determine the selective formation of
these two different products.
Recently, we reported the intramolecular hydroacylation of
5-alkynals leading to a-alkylidenecyclopentanones using
[Rh(BINAP)]BF4.5,6 When 4-methoxy-4-methyl-5-decynal (1)
was treated with 10% [Rh(BINAP)]BF4 in CH2Cl2 at 25 uC,
a-alkylidenecyclopentanone 2 was obtained in 77% yield. To our
surprise, the reaction of 6-phenyl-5-hexynal 4 provided not the
expected a-alkylidenecyclopentanone 5 but rather gave c-alkynyl-
ketone 6 in 47% yield (eqn 1).
Table 1 Catalytic rearrangement of 5-alkynals to c-alkynylketones
and 1-cyclopentenylketonesa
Entry Substrate
Product
Yield (%)b
ð1Þ
1
R1 5 n-Bu
R1 5 n-Bu
R1 5 Ph
R2 5 Me
R2 5 Me
R2 5 Me
77 (64d)
69 (66d)
71
2c
3
4
R1 5 Cl(CH2)3 R2 5 Me
74
5c
6
R1 5 Me3Si
R1 5 n-Bu
R1 5 n-Bu
R2 5 Me
R2 5 n-Pr
R2 5 i-Pr
24d
43
Various rhodium(I)/phosphine catalysts were examined to
promote the rearrangement of 1 to c-alkynylketone 3. Among
the catalysts examined, the use of cationic rhodium(I)/electron
deficient monodentate phosphine complexes was effective for the
7
57
rearrangement of
1 to 3. Especially, the use of 10%
[Rh(P(OPh)3)2]BF4 gave 3 in 77% yield. Other electrophilic
transition metal complexes, which are frequently used for
activation of alkynes, were also examined. Although the use of
2c,3l–o
3c
8
9
10
11
a
R1 5 n-Bu
R2 5 Me
R3 5 H
62
71
47
43
PdCl2 and PtCl2 led to unidentified mixtures, the use of
3i,j
10% Cu(OTf)2 gave 3 in 69% yield. The reactions of a series
R1 5 n-C6H13 R2 5 n-Bu R3 5 H
R1 5 n-C6H13 R2 5 H
R1 5 n-C10H21 R2 5 H
R3 5 Me
R3 5 H
Department of Applied Chemistry, Graduate School of Engineering,
Tokyo University of Agriculture and Technology, Koganei, Tokyo, 184-
8588, Japan. E-mail: tanaka-k@cc.tuat.ac.jp; Fax: +81 42 388 7037;
Tel: +81 42 388 7037
{ Electronic supplementary information (ESI) available: experimental
details. See http://dx.doi.org/10.1039/b508278a
The reaction was conducted using [Rh(P(OPh)3)2]BF4 (0.050 mmol),
5-alkynal (0.50 mmol), and solvent (2.0 mL) at 25 uC (CH2Cl2,
entries 1–4, 6, and 7), 50 uC {(CH2Cl)2, entries 8–11}, or 80 uC
{(CH2Cl)2, entry 5} for 15–110 h. Isolated yield. Cu(OTf)2 was
used as a catalyst in CH3CN. d 5% Catalysts were used.
b
c
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ð3Þ
ð4Þ
In conclusion, we have developed the catalytic rearrangement
of 5-alkynals to c-alkynyl ketones and 1-cyclopentenyl
ketones using [Rh(P(OPh)3)2]BF4 or Cu(OTf)2 as a catalyst.
The substituents at the 4-position of 5-alkynals play an
important role for the selection of two different rearrangement
pathways.
Scheme 1
Although no reaction was observed when 4-methoxy-5-decynal
was treated with 10% [Rh(P(OPh)3)2]BF4 at 25 uC, we anticipated
that exchange reaction between formyl hydrogen and propargylic
hydrogen might occur instead of exchange reaction between
formyl hydrogen and the propargylic alkyl group. Indeed, the
exchange reaction between formyl deuterium and propargylic
hydrogen proceeded slowly in the reaction of 1-deuterium-4-
methoxy-5-decynal (eqn. 2).
We thank Prof. Gregory C. Fu (Massachusetts Institute of
Technology) for his helpful encouragement.
Notes and references
1 For metal-catalyzed cyclo-isomerization of alkynyl ketones, see:
A. V. Kel’in and V. Gevorgyan, J. Org. Chem., 2002, 67, 95 and
references therein.
Scheme 1 depicts a possible mechanism of these rearrangements.
We believe that the coordination of an electrophilic transition
metal complex would induce an attack of a carbonyl oxygen to an
alkyne through an endo pathway leading to vinylmetal complex
A.9 In the case of 4-methoxy-5-alkynals (R2 5 OMe), exchange
reaction between alkyl group (R3) and formyl hydrogen
proceeds via the oxygen-stabilized cationic intermediate B to form
c-alkynyl ketone and regenerates the transition metal complex. On
the other hand, in the case of 5-alkynals (R2 5 H), a methathesis
reaction proceeds via the cationic intermediate C to form
1-cyclopentenylketones.7,8
2 (a) For metal-catalyzed cyclo-isomerization of a-alkynyl carbonyl
compounds, see: T. Yao, X. Zhang and R. C. Larock, J. Am. Chem.
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T. M. Frost, Angew. Chem. Int. Ed., 2000, 39, 2285; (c) Y. Fukuda,
H. Shiragami, K. Utimoto and H. Nozaki, J. Org. Chem., 1991, 56, 5816.
3 (a) For metal-catalyzed cyclo-isomerization of b-alkynyl carbonyl
compounds, see: A. S. K. Hashmi, J. P. Weyrauch, W. Frey and
J. W. Bats, Org. Lett., 2004, 6, 4391; (b) J. Zhu, A. R. Germain and
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ð2Þ
Consistent with these pathways, the reactions of 1-deuterium-5-
alkynals led to stereospecific incorporation of deuterium in the
propargylic position of c-alkynyl ketone and the vinylic
position of 1-cyclopentenyl ketone (eqn 3 and 4). Furthermore,
through a crossover experiment, we have established that
this transfer proceeds intramolecularly. Deuterium crossover
was not observed in the reaction of a 1 : 1 mixture of a
4 Carbocyclization of alkynes tethered to b-dicarbonyl nucleophiles, see: (a)
S. T. Staben, J. J. Kennedy-Smith and F. D. Toste, Angew. Chem. Int.
Ed., 2004, 43, 5350; (b) F. E. McDonald and T. C. Olson, Tetrahedron
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5 K. Takeishi, K. Sugishima, K. Sasaki and K. Tanaka, Chem. Eur. J.,
2004, 10, 5681.
deuterated-5-alkynal and
[Rh(P(OPh)3)2]BF4 (eqn 4).
a
nondeuterated-5-alkynal with
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6 For rhodium-catalyzed intramolecular hydroacylation of 3-methoxy-4-
alkynals, see: (a) K. Tanaka and G. C. Fu, J. Am. Chem. Soc., 2003, 125,
8078; (b) K. Tanaka and G. C. Fu, J. Am. Chem. Soc., 2002, 124,
10296.
8 (a) For a Ag(I)-catalyzed reaction, see: J. U. Rhee and M. J. Krische,
Org. Lett., 2005, 7, 2493; (b) For a Yb(OTf)3-catalyzed reaction,
see: M. Curini, F. Epifano, F. Maltese and O. Rosati, Synlett, 2003,
552.
7 For reactions using stoichiometric lewis acids, see: (a) G. S. Viswanathan
and C.-J. Li, Tetrahedron Lett., 2002, 43, 1613; (b) A. Hayashi,
M. Yamaguchi and M. Hirama, Synlett, 1995, 195.
9 Synthesis of seven-membered ring glycals via endo-selective alkynol cyclo-
isomerization, see: E. Alcazar, J. M. Pletcher and F. E. McDonald, Org.
Lett., 2004, 6, 3877.
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