ChemComm
Communication
these enol ethers to undergo a versatile selection of transforma-
tions leading to a range of skeletally distinct products.
Chiral Pd-Phox catalysts offer an effective route to enantio-
enriched pyran derivatives via a kinetic resolution process.
These compounds have versatile functionality that can be easily
manipulated towards a range of new compounds with high
enantiocontrol.
Notes and references
1 S. J. Meek and J. P. A. Harrity, Tetrahedron, 2007, 63, 3081.
2 (a) D. R. Carbery, N. D. Miller and J. P. A. Harrity, Chem. Commun.,
2002, 1546; (b) D. R. Carbery, S. Reignier, J. W. Myatt, N. D. Miller
and J. P. A. Harrity, Angew. Chem., Int. Ed., 2002, 41, 2584;
(c) D. R. Carbery, S. Reignier, N. D. Miller, H. Adams and
J. P. A. Harrity, J. Org. Chem., 2003, 68, 4392; (d) S. J. Meek,
F. Pradaux, E. H. Demont and J. P. A. Harrity, Org. Lett., 2006,
8, 5597; (e) S. J. Meek, F. Pradaux, E. H. Demont and J. P. A. Harrity,
J. Org. Chem., 2007, 72, 3467; ( f ) S. J. Meek, E. H. Demont and
J. P. A. Harrity, Tetrahedron Lett., 2007, 48, 4165.
3 For an elegant application of this chemistry in the synthesis of
hydrolytically stable glycoside mimics see: A. Deleuze, C. Menozzi,
M. Sollogoub and P. Sina¨y, Angew. Chem., Int. Ed., 2004, 43, 6680.
4 J. C. R. Brioche, T. A. Barker, D. J. Whatrup, M. D. Barker and
J. P. A. Harrity, Org. Lett., 2010, 12, 4832.
5 (a) B. M. Trost, T. A. Runge and L. N. Jungheim, J. Am. Chem. Soc.,
1980, 102, 2840; (b) J. Tsuji, Y. Kobayashi, H. Kataoka and
T. Takahashi, Tetrahedron Lett., 1980, 21, 1475; (c) P. Langer and
E. Holtz, Angew. Chem., Int. Ed., 2000, 39, 3086.
6 (a) J. M. J. Williams, Synlett, 1996, 705; (b) G. Helmchen, J. Organomet.
Chem., 1999, 576, 203; (c) G. Helmchen and A. Pfaltz, Acc. Chem. Res.,
2000, 33, 336; (d) A. Pfaltz and W. J. Drury III, Proc. Natl. Acad. Sci.
U. S. A., 2004, 101, 5723.
Scheme 4 Stereoselective transformations of enantioenriched (E,Z)-1.
Conditions for the synthesis of; 12: (i) 10 eq. Et3SiH; (ii) 3 eq. TFA, CH2Cl2,
À78 1C, 45 min; 13: mW, 300 W, DMF, 180 1C, 20 min; (E)-14: 1% RuCl3,
1.5 eq. oxone,
4 eq. NaHCO3 CH3CN/H2O (3/1); 2: 5% Pd(dba)2,
6% (Æ)-But-Phox, DMSO, 80 1C, 3 h.
nucleophilic addition to p-allyl palladium complexes bearing
Phox-ligands proceeds at the carbon atom trans-to the phosphine
moiety.9 Based on the assumption that the oxidative insertion event
follows a similar pathway (i.e. reverse reaction), we propose that, in
the case of substrates bearing a trans allylic substituent, complexa-
tion and oxidative insertion at the (S)-enantiomer via I would
proceed to generate the favoured exo-diastereomer II. An analogous
insertion mode in substrates bearing a (Z)-allylic ether (III) would
however form a p-allyl complex with the alkyl group in the anti-
position, engendering a steric clash with the face-on presudoequa-
torial P–Ph moiety in IV.10 This may be better accommodated by
reaction through the (R)-substrate (V - VI). DFT studies aimed at
providing a better understanding of the underpinning reasons for
these selectivities are underway and will be reported in due course.
In order to demonstrate the synthetic potential of these
enantioenriched allylic ethers in organic synthesis, we opted
to perform a series of transformations on substrate (E,Z)-1.
Specifically, Pd-catalyzed [1,3]-rearrangement of (E,Z)-1 using
7 For pioneering studies on the use of Phox-ligands in enantio-
selective Pd-catalyzed allylic substitution see: (a) J. Sprinz and
G. Helmchen, Tetrahedron Lett., 1993, 34, 1769; (b) P. von Matt
and A. Pfaltz, Angew. Chem., Int. Ed. Engl., 1993, 32, 566; (c) G. J.
Dawson, C. G. Frost, J. M. J. Williams and S. J. Coote, Tetrahedron
Lett., 1993, 34, 3149.
8 Enantioselectivities were determined by chiral HPLC. For details of
these measurements and assignment of stereochemical configu-
ration see ESI†.
9 J. Sprinz, M. Kiefer, G. Helmchen, M. Reggelin, G. Huttner,
O. Walter and L. Zsolnai, Tetrahedron Lett., 1994, 35, 1523.
racemic ligand delivered cyclohexanone 2 in high ee. Further- 10 G. Helmchen, J. Organomet. Chem., 1999, 576, 203.
11 Pd-catalysed cyclisations also offer stereoselective routes to pyrans:
more, chemoselective reduction of the enol ether provided cis-
´
´
B. Alcaide, P. Almendros, T. Martınez del Campo, M. T. Quiros,
2,6-disubstituted pyran 12 in high yield.11 Thermally promoted
E. Soriano and J. L. Marco-Contelles, Chem.–Eur. J., 2013, 19, 14233.
[3,3]-rearrangement delivered the corresponding cyclooctenone 12 (E,E)-1 underwent a Claisen rearrangement to provide the trans-2,3-
cis-13 with excellent stereocontrol.12 Finally, selective oxidative
cleavage of the enol ether olefin provided lactone (E)-14. There-
disubstituted cyclooctenone in 86% yield, 85% ee (99% es). The
stereochemistry of trans-13 was established by X-ray crystallography.
The stereochemistry of cis-13 was inferred by comparison to trans-
fore, the reactions shown in Scheme 4 highlight the potential of
13, see ESI† for details.
This journal is ©The Royal Society of Chemistry 2014
Chem. Commun., 2014, 50, 2735--2737 | 2737