One-pot terminal alkene homologation using a tandem olefin cross-metathesis/allylic carbonate reduction sequence

Article abstract of DOI:10.1039/b709754a

A one-carbon homologation of terminal alkenes has been developed utilizing an olefin cross-metathesis followed by a palladium-mediated allylic carbonate reduction; various substrates were used to demonstrate the scope of the reaction, with yields ranging

Full text of DOI:10.1039/b709754a

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One-pot terminal alkene homologation using a tandem olefin cross-
metathesis/allylic carbonate reduction sequence{
Daniel L. Comins,* Jason M. Dinsmore and Lucas R. Marks
Received (in Bloomington, IN, USA) 27th June 2007, Accepted 16th July 2007
First published as an Advance Article on the web 7th August 2007
DOI: 10.1039/b709754a
there is no report on a conversion of an alkene directly to an allylic
carbonate. However, Grubbs et al. have developed chemistry
where terminal olefins are converted to the corresponding allylic
acetates by cross-metathesis with cis-2-butene-1,4-diol diacetate.3 It
seemed reasonable that a modification of this reaction could be
utilized to make the required allylic carbonate intermediate which
could then be submitted to Tsuji’s conditions to form the desired
terminal alkene. We decided to examine these two reactions in
tandem to produce a one-pot one-carbon alkene homologation. In
addition to being of general use, this methodology will extend the
utility of the well established allylation reactions4 by subsequent
modification of the resulting terminal alkenes 1 to the one-carbon
homologated butenyl derivatives 4 (Scheme 3).
A one-carbon homologation of terminal alkenes has been
developed utilizing an olefin cross-metathesis followed by a
palladium-mediated allylic carbonate reduction; various sub-
strates were used to demonstrate the scope of the reaction, with
yields ranging from 65 to 86%.
One-carbon homologation of a terminal alkene remains a difficult
task in organic synthesis. To date there is no direct method to
accomplish this transformation. A classical three-step sequence
involves hydroboration–oxidation of a terminal alkene, oxidation
to the aldehyde, and subsequent Wittig olefination (Scheme 1).
Scheme 1 Classical sequence for one carbon homologation of alkenes.
Besides being multistep, this sequence is not very functional
group tolerant. In contrast, olefin cross-metathesis (CM) is very
chemoselective and a convenient route to functionalized olefins.1
We envisioned using a CM reaction to provide a functionalized
alkene intermediate which could be easily converted in situ to a
terminal olefin with one additional carbon in the chain.
Tsuji et al.2 reported the conversion of allylic esters, carbonates,
phenyl ethers and chlorides to terminal alkenes utilizing a
palladium-catalyzed reductive cleavage (Scheme 2). Preliminary
results prompted us to target allylic carbonates as intermediates for
our methodology development. To the best of our knowledge
Scheme 3 One-pot terminal alkene homologation reaction.
The investigation commenced by establishing viable cross-
metathesis reaction conditions of terminal alkenes with the allylic
dicarbonate 25 utilizing the Grubbs second-generation catalyst.1,3
The mol percentage of catalyst was varied unveiling a 2% loading
to be optimal. The concentration during the metathesis reaction
was found to be essential to the success of the formation of allylic
carbonate 3. When the concentration approached 1 M, the
product formation was significantly reduced. We observed that the
reaction produced consistent results at a concentration of 0.1 M.
Following the optimized metathesis protocol, the intermediate
carbonate was subjected to various mol percentages of
6
Pd2(dba)3?CHCl3 in the presence of PPh3 and ammonium
formate. Work by Braddock and Wildsmith uncovered that the
success or failure of reactions involving the combination of Grubbs
and Pd catalysts hinged on obtaining the correct ratio between the
two.7 When the ratio exceeded 2 : 1 (Grubbs cat./Pd cat.), the
palladium chemistry did not work perhaps due to complexation of
the PCy3 to the palladium catalyst; a Grubbs cat./Pd cat. loading
ratio of 1 : 2.5 proved to be optimal. After numerous solvent
Scheme 2 Tsuji’s reduction of allylic compounds.
Department of Chemistry, North Carolina State University, Raleigh,
NC, USA. E-mail: Daniel_Comins@ncsu.edu; Fax: 01 919 515-9371;
Tel: 01 919 515-2911
{ Electronic supplementary information (ESI) available: Experimental
procedures, characterization of all new compounds, and copies of their 1H
and 13C NMR spectra. See DOI: 10.1039/b709754a
4170 | Chem. Commun., 2007, 4170–4171
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homologation of homoallylic alcohol derivatives prepared by
allylation of the corresponding aldehydes. Attempts at accessing
these products in the absence of a silyl protecting group were met
with limited success. Entries 4, 6 and 7 show the accomplishment
of the reaction in the presence of more complex substrates.
A typical procedure is as follows: the terminal alkene and bis-
carbonate 2 (2 equiv.) were dissolved in CH2Cl2 and degassed.
Grubbs second-generation catalyst (2%) was added and the
mixture was heated at reflux for 1 d.8 The solution of the in situ
formed allylic carbonate was then cooled to rt, and PPh3 (20%),
Pd2(dba)3?CHCl3 (5%), and ammonium formate (2 equiv.) were
added. The mixture was heated at reflux for 1 d and then filtered.
The product was purified by silica gel chromatography.
Table 1 One-pot homologation of terminal alkenes
Entrya
Substrate 1
Product 4
Yieldb (%)
86
1
2
3
85
83
In summary, we have developed a one-pot one-carbon alkene
homologation from an existing terminal alkene, a process that
should be of considerable synthetic utility.
4
76
We express appreciation to the National Institutes of Health
(Grant GM 34442) for financial support of this research. J. M. D.
also thanks the Burroughs–Wellcome Fellowship Fund for a
second year graduate assistantship.
5
6
66
66
Notes and references
1 (a) T. W. Funk, J. Efskind and R. H. Grubbs, Org. Lett., 2005, 7, 187; (b)
A. K. Chatterjee, T.-L. Choi, D. P. Sanders and R. H. Grubbs, J. Am.
Chem. Soc., 2003, 125, 11360. Reviews: (c) S. J. Connon and S. Blechert,
Angew. Chem., Int. Ed., 2003, 42, 1900–1923; (d) A. H. Hoveyda,
D. G. Gillingham, J. J. Van Veldhuizen, O. Kataoka, S. B. Garber,
J. S. Kingsbury and J. P. A. Harrity, Org. Biomol. Chem., 2004, 2, 8–23.
2 J. Tsuji, I. Shimizu and I. Minami, Chem. Lett., 1984, 1017.
3 (a) R. H. Grubbs, E. L. Dias and S. Nguyen, J. Am. Chem. Soc., 1997,
119, 3887; (b) D. J. O’Leary, H. E. Blackwell, R. A. Washenfelder and
R. H. Grubbs, Tetrahedron Lett., 1998, 39, 7427; (c) H. E. Blackwell,
D. J. O’Leary, A. K. Chatterjee, R. A. Washenfelder, D. A. Bussmann
and R. H. Grubbs, J. Am. Chem. Soc., 2000, 122, 58.
7
65
4 For recent reviews of allylmetal additions, see: (a) S. E. Denmark and
J. Fu, Chem. Rev., 2003, 103, 2763; (b) S. E. Denmark and
N. G. Almstead, in Modern Carbonyl Chemistry, ed. J. Otera, Wiley-
VCH, Weinheim, Germany, 2000, ch. 10; (c) S. R. Chemler and
W. R. Rousch, in Modern Carbonyl Chemistry, ed. J. Otera, Wiley-VCH,
Weinheim, Germany, 2000, ch. 11.
a
b
Reactions were carried out on a 0.1–1.0 mmol scale. Yield of
pure isolated product.
5 K. Burgess, Tetrahedron Lett., 1985, 26, 3049.
6 (a) I. Shimizu, A. Yamamoto, M. Oshima and F. Ozawa,
Organometallics, 1991, 10, 1221; (b) F. Ozawa, A. Yamamoto,
M. Oshima, T. Sakamoto, Y. Maruyama and I. Shimizu, Bull. Chem.
Soc. Jpn., 2000, 73, 453.
7 D. C. Braddock and A. J. Wildsmith, Tetrahedron Lett., 2001, 42, 3239.
8 The reaction is followed by TLC until the starting alkene 1 has been
completely consumed.
studies, it was determined that methylene chloride could be used as
the solvent for both reactions, eliminating the need for exchanging
solvents.
The results of this study are summarized in Table 1 with product
yields ranging from 65 to 86%. Entries 1–3 and 5 demonstrate
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Chem. Commun., 2007, 4170–4171 | 4171