A one pot, metathesis-hydrogenation sequence for the selective formation of carbon-carbon bonds

Article abstract of DOI:10.1039/b510420c

A combination of homogeneous hydrogenation and metathesis reactions allows highly efficient, stepwise chemo- and stereo-selective formation of three separate 2,7-diaminosuberic acid derivatives in a single pot without isolation of intermediates. The Royal

Full text of DOI:10.1039/b510420c

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COMMUNICATION
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A one pot, metathesis–hydrogenation sequence for the selective
formation of carbon–carbon bonds{
Andrea J. Robinson,*a Jomana Elaridi,a Jim Patelb and W. Roy Jacksonb
Received (in Cambridge, UK) 22nd July 2005, Accepted 7th September 2005
First published as an Advance Article on the web 4th October 2005
DOI: 10.1039/b510420c
cross-metathesis selectivity and did not affect the mechanistic
course of the reaction sequence. An equimolar mixture of olefins 1,
2 and 3 was subjected to the catalytic sequence outlined below and
in Table 1. Olefin 1, a derivative of allylglycine, readily underwent
homodimerisation with first (20 mol%) and second generation
Grubbs’ catalysts2 (5 mol%) to form an unsaturated dicarba bridge
4. Under these reaction conditions, the more sterically hindered
olefin 2 and the electronically compromised olefin 3 were
unreactive. The resultant alkene 4 was then hydrogenated in the
presence of Rh(I)(PPh3)3Cl (Wilkinson’s catalyst)3 to afford the
saturated dicarba bridge 5. Again, olefins 2 and 3 were unreactive
under these conditions. Both the metathesis and hydrogenation
reactions proceeded under mild experimental conditions with
quantitative, unambiguous conversion to give the first suberic acid
derivative 5 as shown by NMR and MS analysis (Scheme 1).
The next reaction in the sequence involved the activation of
the dormant prenyl olefin 2 via cross-metathesis with 2-butene
(butenolysis) to generate a more reactive crotylglycine derivative 6
(Scheme 1). The mixture of 2, 3 and 5 was exposed to an
atmosphere of 2-butene (15 psi) in the presence of 5 mol% second
generation Grubbs’ catalyst to afford the expected crotylglycine
derivative 6 with quantitative conversion. Interestingly, exposure
of 2 to 20 mol% of second generation Grubbs’ catalyst under an
atmosphere of ethylene (15 psi) resulted in only poor conversions
to the allylglycine analogue of 6 (,32%). We postulated that this
result may be due to the unstable nature of the in situ generated
ruthenium–methylidene intermediate at elevated temperature4 or
A combination of homogeneous hydrogenation and metathesis
reactions allows highly efficient, stepwise chemo- and stereo-
selective formation of three separate 2,7-diaminosuberic acid
derivatives in a single pot without isolation of intermediates.
The selective formation of C–C bonds in complex molecules is one
of the major challenges in organic chemistry. Olefin metathesis
provides an efficient methodology for C–C bond synthesis1 and
in this communication we demonstrate the application of this
technology for the formation of three identical dicarba bridges by
selective and successive formation of three diaminosuberic acid
derivatives.
Towards this end, a metathesis triplet 1, 2, 3 has been developed
to facilitate the controlled formation of the three dicarba bridges
(Table 1). The method involves cross-metathesis of reactive olefins
to form a new olefin followed by hydrogenation to form the
saturated bridge. The differing olefin substitution in the molecules
provides tuneable reactivity towards homogeneous metathesis
and hydrogenation catalysts. Three different N-acyl protecting
groups were employed to facilitate unambiguous assessment of
aSchool of Chemistry, Monash University, Clayton 3800, Victoria,
Australia. E-mail: andrea.robinson@sci.monash.edu.au;
Fax: 61 03 9905 4597; Tel: 61 03 9905 4553
bCentre for Green Chemistry, Monash University, Clayton 3800,
Victoria, Australia
{ Electronic supplementary information (ESI) available: Spectral data for
compounds 4–12. See http://dx.doi.org/10.1039/b510420c
Scheme 1 Reagents and conditions: (i) 20 mol% first generation Grubbs’ catalyst, DCM, 50 uC, 18 h; (ii) Rh(I)(PPh3)3Cl, 15 psi H2, RT, THF:tBuOH
(1:1), 14 h; (iii) 5 mol% second generation Grubbs’ catalyst, 15 psi C4H8, DCM, 50 uC, 17 h; (iv) 5 mol% second generation Grubbs’ catalyst, DCM, 50 uC,
17 h; (v) [(COD)Rh(I)(S,S)-Et-DuPHOS]OTf, 75 psi H2, RT, MeOH, 2 h, .99% ee.
5544 | Chem. Commun., 2005, 5544–5545
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unfavourable competition between the rising concentration of
terminal olefins and 2 for binding to the ruthenium catalyst.5
Exposure to an atmosphere of 2-butene overcame this problem,
facilitating catalysis via the more stable ruthenium–ethylidene
intermediate. The newly formed disubstituted olefin 6 was then
readily homodimerised to the expected unsaturated dimer 7 with
5 mol% of second generation Grubbs’ catalyst (Scheme 1). Exposure
of the newly formed olefin to a hydrogen atmosphere and
Wilkinson’s catalyst resulted in quantitative conversion to the
saturated dicarba bridge 8. Once again, the sterically and electro-
nically compromised olefin 3 remained a spectator over the three
reactions used to form the second diaminosuberic acid derivative.
The remaining acrylate-type olefin 3 was then used to form the
final dicarba bridge. A double activation sequence needed to be
employed to render this remaining olefin reactive to homo-
dimerisation. This was achieved through the use of asymmetric
hydrogenation and cross-metathesis. Homogeneous hydrogena-
tion of dienamide 36 using chiral (S,S)-Rh(I)-Et-DuPHOS (Burk’s
catalyst)7 gave (S)-configured prenylglycine derivative
9 in
excellent enantioselectivity (.99% ee), chemoselectivity and
conversion.8 No evidence of over-reduction of the C4 carbon–
carbon double bond was observed. The resulting prenyl olefin 9
was then converted to the crotylglycine analogue 10 via butenolysis
(Scheme 1). Exposure of this olefin 10 to the previously described
cross-metathesis and hydrogenation conditions then led to the
formation of the final dicarba bond and the third diaminosuberic
acid derivative 11 via alkene intermediate 12 (Scheme 1). The
product mixture resulting from the nine homogeneous catalytic
transformations was separated by column chromatography to
afford diamidosuberic acid esters 5, 8 and 11 in 70, 81 and
73% yields respectively. Significantly, no other byproducts were
isolated which demonstrates the high chemoselectivity exhibited by
each catalytic step.
The homogeneous catalytic methodology described in this
communication could find widespread use in peptidomimetics and
total product synthesis where multiple C–C bonds and/or rings
need to be selectively constructed. This methodology is currently
being applied to the preparation of several biologically active and
naturally occurring cyclic molecules and peptides.
We acknowledge the provision of an Australian Postgraduate
Research Award (to J.E.) and thank the Australian Research
Council for financial assistance.
Notes and references
1 (a) A. K. Chatterjee, T-L. Choi, D. P. Sanders and R. H. Grubbs, J. Am.
Chem. Soc., 2003, 125, 11360–11370; (b) S. J. Connon and S. Blechert,
Angew. Chem., Int. Ed., 2003, 42, 1900–1923.
2 J. Louie, C. W. Bielawski and R. H. Grubbs, J. Am. Chem. Soc., 2001,
123, 11312–11313.
3 J. A. Osborn, F. H. Jardine, J. F. Young and G. Wilkinson, J. Chem.
Soc. A, 1966, 1711–1736.
4 P. Schwab, R. H. Grubbs and J. W. Ziller, J. Am. Chem. Soc., 1998, 118,
100–110.
5 K. A. Burdett, L. D. Harris, P. Margl, B. R. Maughon, T. Mokhtar-
Zadeh, P. C. Saucier and E. P. Wasserman, Organometallics, 2004, 23,
2027–2047.
6 E. Teoh, E. M. Campi, W. R. Jackson and A. Robinson, Chem.
Commun., 2002, 978–979.
7 M. J. Burk, J. E. Feaster, W. A. Nugent and R. L. Harlow, J. Am. Chem.
Soc., 1993, 115, 10125–10138.
8 Enantioselectively was measured using a chiral GC column (50CP2/
XE60-SVALSAPEA); [a]22D +58.2u.
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