Table 2 Relative yields and ee values of products 15 and 16 from
asymmetric cyclopropanation of alkenes 13 and 14
63, 117; (d) D. R. Boyd and T. Bugg, Org. Biomol. Chem., 2006,
4, 181.
2 (a) D. R. Boyd, N. D. Sharma, M. R. J. Dorrity, M. V. Hand, R.
A. S. McMordie, J. F. Malone, H. P. Porter, J. Chima, H. Dalton
and G. N. Sheldrake, J. Chem. Soc., Perkin Trans. 1, 1993, 1065;
(b) D. R. Boyd, N. D. Sharma, L. V. Modyanova, J. G. Carroll,
J. F. Malone, C. C. R. Allen, J. T. G. Hamilton, D. T. Gibson, R.
E. Parales and H. Dalton, Can. J. Chem., 2002, 80, 589.
3 N. Misawa, K. Shindo, H. Takahashi, H. Suenaga, K. Iguchi, H.
Okazaki, S. Harayama and K. Furukawa, Tetrahedron, 2002, 58,
9605.
Product
Yield (%)
% ee
Ligand
Alkene
6F
6F
8F
8F
a
13
14
13
14
15
16
15
16
91a
90b
95a
97b
88
91
92
95
b
Relative to product 17. Relative to product 18.
4 D. R. Boyd, N. D. Sharma, G. P. Coen, F. Hempenstall, V.
Ljubez, J. F. Malone, C. C. R. Allen and J. T. G. Hamilton,
Org. Biomol. Chem., 2008, DOI: 10.1039/b810235j.
5 D. R. Boyd, N. D. Sharma, J. G. Carroll, C. C. R. Allen, D. A.
Clarke and D. T. Gibson, Chem. Commun., 1999, 1201.
6 K. Shindo, Y. Ohnishi, H.-K. Chun, H. Takahashi, M. Hayashi,
A. Saito, K. Iguchi, K. Furukawa, S. Harayama, S. Horinouchi
and N. Misawa, Biosci., Biotechnol., Biochem., 2001, 65, 2472.
7 D. R. Boyd, N. D. Sharma, F. Hempenstall, M. A. Kennedy, J. F.
Malone, S. M. Resnick and D. T. Gibson, J. Org. Chem., 1999, 64,
4005.
cyclopropanation of alkenes 13 and 14, to give products 15
and 16 with high de (80–94%) and ee (88–95%) values. These
results are comparable to the best reported using other types
of chiral 2,20-bipyridines obtained by alternative synthetic
methods.13
The results in Tables 1 and 2 show that the new chiral 2,20-
bipyridines 2F, 6F, 7F and 8F obtained by the chemoenzy-
matic route are particularly useful in Cu(I)-catalysed reactions
of alkenes to yield benzoate esters of chiral allylic alcohols and
cyclopropanes with ee values up to 95–97%. This new route to
chiral ligands has the additional advantage of synthetic versa-
tility. Thus, for example, the addition of further chiral centres
is possible via epoxidation or cis-dihydroxylation of the re-
maining alkene bonds in cis-dihydrodiols 2B, 3B, 5B and
bipyridine 5F.
8 A. V. Malkov, M. Bella, V. Langer and P. Kocovsky
2000, 2, 3047.
´ , Org. Lett.,
9 (a) D. R. Boyd, A. Drake, J. Gawronski, M. Kwit, J. F. Malone
and N. D. Sharma, J. Am. Chem. Soc., 2005, 127, 4308; (b) D. R.
Boyd, N. D. Sharma, G. N. Coen, P. Gray, J. F. Malone and J.
Gawronski, Chem.–Eur. J., 2007, 13, 5804–5811; (c) M. Kwit,
N. D. Sharma, D. R. Boyd and J. Gawronski, Chem.–Eur. J., 2007,
13, 5812–5821; (d) M. Kwit, N. D. Sharma, D. R. Boyd and J.
Gawronski, Chirality, 2008, 20, 609–620.
10 Crystal data for 2F: C24H28N2O4, M = 408.5, monoclinic, a =
10.103(4), b = 7.746(2), c = 13.929(4) A, b = 93.59(2)1,
U = 1088.0(6) A3, space group P21 (no. 4), Z = 2, T = 293(2)
The potential of the 2,20-bipyridines 3F and 5F, obtained
using the same chemoenzymatic method, and the correspond-
ing mono- and di-N-oxide derivatives of 2,20-bipyridines 2F,
3F, 5F–8F as chiral ligands for these and other types of
catalytic asymmetric synthesis is currently under investigation.
In conclusion, this preliminary study has demonstrated that
enantiopure cis-dihydrodiol bioproducts derived from aza-
arene substrates containing several functionalities can be
converted in three steps to a new range of 2,20-bipyridines.
Several new 2,20-bipyridines have already proved to be useful
ligands for asymmetric allylic oxidation and cyclopropanation
of alkenes. The synthetic versatility of these and other cis-
dihydrodiol metabolites from mono- and polycyclic azaarenes
should generate many new 2,20-bipyridine ligands with appli-
cations to a much wider range of catalytic asymmetric syn-
thesis reactions.
K, Mo-Ka radiation, l = 0.71073 A, F(000) = 436, Dx
=
1.247 g cmꢀ3, m = 0.085 mmꢀ1, Bruker P4 diffractometer, o scans,
4.01 o 2y o 60.01, measured/independent reflections: 4399/3383,
Rint = 0.031, direct methods solution, full-matrix least squares
refinement on Fo2, anisotropic displacement parameters for non-
hydrogen atoms; all hydrogen atoms located in a difference Fourier
synthesis but included at positions calculated from the geometry of
the molecule using the riding model, with isotropic vibration
parameters. R1 = 0.058 for 2058 data with I 4 2s(I), 276
parameters, oR2 = 0.168 (all data), GoF = 1.02, Drmin,max
=
ꢀ0.20/0.30 e Aꢀ3. CCDC reference number 698751. The molecule
has a transoid-conformation with respect to the pyridine rings. The
N–C–C–N torsion angle is ꢀ176.51. Data can be obtained from
ESI or free of charge from The Cambridge Crystallographic Data
11 For reviews in this area, see: (a) J. Eames and M. Watkinson,
Angew. Chem., Int. Ed., 2001, 40, 3567; (b) M. B. Andrus and J. C.
Lashley, Tetrahedron, 2002, 58, 845; (c) J. Bayardon, D. Sinou, M.
Guala and G. Desimoni, Tetrahedron: Asymmetry, 2004, 15, 3195;
(d) J. S. Clark, M. R. Clark, J. Clough, A. J. Blake and C. Wilson,
Tetrahedron Lett., 2004, 45, 9447.
12 (a) M. B. Andrus and Z. Zhou, J. Am. Chem. Soc., 2002, 124, 8806;
(b) S. K. Ginotra and V. K. Singh, Org. Biomol. Chem., 2006, 4,
4370; (c) A. V. Malkov, I. R. Baxendale, M. Bella, V. Langer, J.
Fawcett, D. R. Russell, D. J. Mansfield, M. Valko and P.
Kocovsky, Organometallics, 2001, 11, 3427; (d) A. V. Malkov, D.
4-Chloroquinoline has similarly been found to yield a useful
cis-dihydrodiol metabolite. This has in turn been used as an
enantiopure building block in the production of chiral metal–
organic frameworks (MOFs).14
We thank CenTACat (to LS), ESF (to TB), DEL/CAST (to
DM), and Science Foundation Ireland (Grant No. 04/IN3/
B581, to NDS) for funding and Dr John Blacker for his help
and advice during the initial phase of the programme.
Pernazza, M. Bell, M. Bella, A. Massa, F. Teply´ , P. Meghani and
P. Kocovsky, J. Org. Chem., 2003, 68, 4727; (e) M. P. A. Lyle and
´
P. Wilson, Org. Biomol. Chem., 2006, 4, 41.
13 (a) K. Ito, S. Tabuchi and T. Katsuki, Synlett, 1992, 575; (b) K. Ito
and T. Katsuki, Tetrahedron Lett., 1993, 34, 2661; (c) M. P. A. Lyle
and P. D. Wilson, Org. Lett., 2004, 6, 855; (d) M. P. A. Lyle, N. D.
Draper and P. Wilson, Org. Biomol. Chem., 2006, 4, 877.
14 L. Sbircea, N. D. Sharma, W. Clegg, R. W. Harrington, P. N.
Horton, M. B. Hursthouse, D. C. Apperley, D. R. Boyd and S. L.
James, Chem. Commun., 2008, DOI: 10.1039/b812366g.
Notes and references
1 (a) D. R. Boyd and G. N. Sheldrake, Nat. Prod. Rep., 1998, 15,
309; (b) T. Hudlicky, D. Gonzalez and D. T. Gibson, Aldrichimica
Acta, 1999, 32, 35; (c) R. A. Johnson, Org. React. (N. Y.), 2004,
ꢁc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 5535–5537 | 5537