Terminal olefins from aldehydes through enol triflate reduction

Article abstract of DOI:10.1021/jo071151o

(Chemical Equation Presented) The transformation of aldehydes into terminal olefins through reduction of the corresponding enol triflates is described. The method is effective with both linear and α-branched aldehydes.

Full text of DOI:10.1021/jo071151o

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Terminal Olefins from Aldehydes through Enol
Triflate Reduction
Sushil K. Pandey, Andrew E. Greene, and
Jean-Franc¸ois Poisson*
De´partement de Chimie Mole´culaire (SERCO), CNRS,
UMR-5250, ICMG FR-2607, UniVersite´ Joseph Fourier, BP-53,
38041 Grenoble Cedex 9, France
Although olefins have frequently been prepared from ketones
by reduction of the derived enol triflates,5 surprisingly, this
strategy has never, to our knowledge, been previously applied
to aldehydes. In this Note, it is shown that this aldehyde to olefin
conversion is quite general and offers a useful alternative to
existing approaches (eq 2).
jean-francois.poisson@ujf-grenoble.fr
ReceiVed June 4, 2007
A number of aldehydes, linear and R-branched, were selected
to test the breadth of this olefination procedure. The results are
summarized in Table 1. The study began with the methylene-
dioxy derivative 3a, which was used to define the optimum
conditions for enol triflate formation and the subsequent
reduction. The preparation of the enol triflate was first carried
out through treatment of 3a with potassium tert-butoxide in
THF,6 followed by addition of the Comins reagent7 (2-[N,N-
bis(trifluoromethylsulfonyl)amino]-5-chloropyridine). Reduction
of the triflate (3:1 mixture) with Pd(OAc)2(PPh3)2 and tributyl-
ammonium formate8 then produced olefin 4a in 54% overall
yield (method A, entry 1). Notably, no double bond isomer-
ization to form the styryl derivative was observed. The reduction
of the enol triflate with triethylsilane and Pd(PPh3)4 in DMF9
was also efficient, but olefin 4a could not be obtained totally
free of silicon contaminants. The reaction of aldehyde 3a with
triflic anhydride in conjunction with 2,6-di-tert-butyl-4-meth-
ylpyridine (DTBMP)10 in 1,2-dichloroethane at 70 °C for 1 h
also led to the formation of the enol triflate (ca. equimolar E/Z
mixture, 66% isolated yield). The reduction of this triflate using
Pd(OAc)2(PPh3)2 and tributylammonium formate afforded again
the expected olefin 4a in 86% yield (method B, entry 2). While
the overall yield (57%) proved just slightly higher than that
obtained above, the approach is more economical and experi-
mentally convenient. Both the overall yield and the convenience
could be further improved by subjecting the crude triflate
directly to reduction: the crude reaction product, obtained from
3a by treatment with triflic anhydride and DTBMP, followed
by simple filtration through a short plug of silica gel and removal
The transformation of aldehydes into terminal olefins through
reduction of the corresponding enol triflates is described. The
method is effective with both linear and R-branched alde-
hydes.
In the course of our recent synthesis of kainic acid, we
required an efficient procedure for converting a 1-formylethyl
substituent into an isopropenyl group.1 This type of olefination
has often been achieved indirectly via the corresponding alcohol
by using the Sharpless-Grieco methodology,2 which involves
oxidation-thermal decomposition of a derived selenide.3 While
this approach is generally effective, it has at times proven
unsatisfactory, most often with branched and oxidation-sensitive
substrates,4 and indeed failed to yield an acceptable result in
the context of our synthesis. Fortunately, it was discovered that
olefin 2, the penultimate intermediate in our sequence, could
be cleanly secured from aldehyde 1 by reduction of the derived
enol triflate (eq 1).
* To whom correspondence should be addressed. Fax: +33 4 76 51 44 94.
(1) Pandey, S. K.; Orellana, A.; Greene, A. E.; Poisson, J.-F. Org. Lett.
2006, 8, 5665-5668.
(2) (a) Sharpless, K. B.; Young, M. W. J. Org. Chem. 1975, 40, 947-
949. (b) Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Am. Chem. Soc. 1976,
41, 1485-1486.
(3) For examples of this olefination approach from aldehydes, see: (a)
Mash, E. A. J. Org. Chem. 1987, 52, 4143-4146. (b) Kato, N.; Wu, X.;
Tanaka, S.; Takeshita, H. Bull. Chem. Soc. Jpn. 1990, 63, 1729-1734. (c)
Blay, G.; Cardona, L.; Garcia, B.; Lahoz, L.; Pedro, J. R. Eur. J. Org.
Chem. 2000, 2145-2151.
(4) R-Branching generally reduces the rate of nucleophilic substitution
by at least an order of magnitude. See: Smith, M. B.; March, J. March’s
AdVanced Organic Chemistry, 5th ed.; Wiley-Interscience: New York, 2001;
pp 431-432. For an illustration of the rate difference in selenide formation,
see: Takano, S.; Takahashi, M.; Ogasawara, K. J. Am. Chem. Soc. 1980,
102, 4282-4283. For difficulties with oxidation-sensitive substrates, see,
for example: (a) Blay, G.; Cardona, L.; Collado, A. M.; Garcia, B.; Morcillo,
V.; Pedro, J. R. J. Org. Chem. 2004, 69, 7294-7302. (b) Zhou, X.-T.;
Carter, R. G. Angew. Chem., Int. Ed. 2006, 45, 1787-1790.
(5) See, for example: Lambert, T. H.; Danishefsky, S. J. J. Am. Chem.
Soc. 2006, 128, 426-427.
(6) Wada, A.; Nomoto, Y.; Tano, K.; Yamashita, E.; Ito, M. Chem.
Pharm. Bull. 2000, 48, 1391-1394.
(7) Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299-
6302.
(8) Cacchi, S.; Morera, A.; Ortar, G. Tetrahedron Lett. 2001, 57, 9087-
9092.
(9) Scott, W. J.; Stille, J. K. J. Am. Chem. Soc. 1986, 108, 3033-3040.
(10) Stang, P. J.; Treptow, W. Synthesis 1980, 283-284.
10.1021/jo071151o CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/08/2007
J. Org. Chem. 2007, 72, 7769-7770
7769

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TABLE 1. Conversion of Aldehydes to Olefins
example, could be converted in good yield into dodecene 4e
(entry 7). There was no double bond migration to an internal
position under the reduction conditions, a phenomenon often
encountered with palladium(II) catalysts.11 Only when the
reaction mixture was allowed to react for a longer time and/or
at a higher temperature did the formation of double bond isomers
occur. The olefin from aldehyde 3f showed a greater pro-
pensity for double bond isomerization; however, reduction of
the crude triflate with the palladium catalyst and tributylam-
monium formate at 35 °C for 30 min afforded the unconjugated
olefin 4f in 65% yield with less than 3% isomerized product
(entry 8).
The case of kainic acid (eq 1) is interesting in that the
aldehyde precursor 1 bears multiple functional groups. Triflic
anhydride and DTBMP did not cleanly produce the intermediate
enol triflate, most likely due to incompatibility with the N-Boc
protecting group.12 The use of KHMDS and Comins’ reagent,
however, led to clean formation of the enol triflate in the
presence of the Boc and two methoxycarbonyl groups. The
reduction of the triflate could, in this case, be carried out with
triethylsilane as the hydride source due to the relatively polar
nature of the product.
In conclusion, a simple method that permits rapid transforma-
tion of an aldehyde, branched or linear, into a terminal alkene
has been developed. The method proceeds in useful yields, is
comparatively economical, and avoids the use of toxic selenium
derivatives.
Experimental Section
General experimental procedure, method C: To a stirred solution
of aldehyde 3 (1.0 mmol) and 2,6-di-tert-butyl-4-methylpyridine
(1.2 mmol) in 1,2-dichloroethane (4.0 mL) under argon is added
triflic anhydride (1.1 mmol), and the resulting solution is heated at
70 °C for 1 h. After being allowed to cool to room temperature,
the reaction mixture is filtered through a short plug of silica gel,
the filtrate is concentrated under reduced pressure, and DMF (2.0
mL), Pd(OAc)2(PPh3)2 (0.05 mmol), NBu3 (3.0 mmol), and formic
acid (2.0 mmol) are added. The reaction mixture is stirred at 35 °C
for approximately 30 min and then processed in the usual way,
and the crude reaction product is purified by flash chromatography
on silica gel to provide olefin 4.
a Method A: (i) tert-BuOK, Comins’ reagent, THF; (ii) Pd(OAc)2(PPh3)2,
HCO2H, NBu3, DMF. Method B: (i) Tf2O, DTBMP, ClCH2CH2Cl; (ii)
Pd(OAc)2(PPh3)2, HCO2H, NBu3, DMF. Method C: same as B, but no
triflate purification. b Overall yield. c Method C provided the olefin in ca.
85% purity. d Contains a small amount (<3%) of â-methylstyrene.
of volatiles, on reduction with Pd(OAc)2(PPh3)2 and tributyl-
ammonium formate provided olefin 4a, now in 63% yield
(method C, entry 3). This simple and rapid protocol (triflate
formation 1 h, reduction 0.5 h, no intermediate purification)
was used, except for entry 5, with the other aldehydes in Table
1.
From the aliphatic R-branched aldehyde 3b, the olefin 4b
was obtained in good yield, despite the volatility of the product
(entry 4). With aldehyde 3c, the olefin formed by using method
C was inseparable from a small amount (ca. 15%) of a byproduct
produced during enol triflate formation. In this case, application
of method A allowed isolation of the pure diene 4c in 53%
overall yield (entry 5). R-Methylstyrene 4d could be obtained
with no sign of polymerization in 65% yield from the pheny-
lacetaldehyde derivative 3d (entry 6).
Acknowledgment. We thank Professor P. Dumy (UJF) for
his interest in our work and Dr C. Fehr (Ferminish) for a
generous gift of aldehyde 3c. Financial support from the CNRS
and the Universite´ Joseph Fourier (UMR 5250, FR 2607) is
gratefully acknowledged.
Supporting Information Available: Characterization data and
1H and 13C NMR spectra for compounds (4a-f); experimental
procedures for methods A and B. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO071151O
(11) See, for example: (a) Danishefsky, S.; O’Neill, B. T.; Taniyama,
E.; Vaughan, K. Tetrahedron Lett. 1984, 25, 4199-4202. (b) Whang, K.;
Cooke, R. J.; Okay, G.; Cha, J. K. J. Am. Chem. Soc. 1990, 112, 8985-
8987.
(12) Under the reaction conditions (but at 25 °C), N-Boc-pyrrolidine and
N-Boc-proline methyl ester each rapidly underwent decomposition.
This olefination method, while probably more useful for the
synthesis of disubstituted olefins, can also be applied to straight-
chain aldehydes to produce linear alkenes. Dodecenal 3e, for
7770 J. Org. Chem., Vol. 72, No. 20, 2007