We next examined the scope of the reduction with respect to
the ketone substrate. A variety of aryl alkyl- and dialkyl
ketones were reduced, as summarized in Table 4. The ketones
were reduced in good yields and with generally useful enantio-
induction. In particular, phenethynyl methyl ketone 7h was
reduced to the corresponding alcohol 8h in 70% ee (Table 4,
entry 8), which compares favourably with reduction of the
same substrate using Alpine-Borane and the CBS catalyst
(78% ee15 and 71% ee,16 respectively). Pinacolone 7i was
reduced to 8i in 62% ee (Table 4, entry 9), again comparing
favourably with literature precedent.17
(k) P. A. Chase and D. W. Stephan, Angew. Chem., Int. Ed.,
2008, 47, 7433–7437; (l) J. D. Masuda, W. W. Schoeller,
B. B. Donnadieu and G. Bertrand, J. Am. Chem. Soc., 2007, 129,
14180–14181; (m) C. A. Dyker and G. Bertrand, Science, 2008,
321, 1050–1051; (n) Y. Wang, Y. Xie, P. Wei, R. B. King,
H. F. Schaefer III, P. v. R. Schleyer and G. H. Robinson, Science,
2008, 321, 1069–1071; (o) Y. Wang, B. Quillian, P. Wei, Y. Xie,
C. S. Wannere, R. B. King, H. F. Schaefer III, P. v. R. Schleyer
and G. H. Robinson, J. Am. Chem. Soc., 2008, 130, 3298–3299.
7 (a) S. H. Ueng, M. M. Brahmi, E. Derat, L. Fensterbank,
E. Lacote, M. Malacria and D. P. Curran, J. Am. Chem. Soc.,
2008, 130, 10082–10083; (b) see also J. C. Walton, Angew.
Chem., Int. Ed., 2009, 48, 1726–1728; (c) S. H. Ueng,
A. Solovyev, X. Yuan, S. J. Geib, L. Fensterbank, E. Lacote,
M. Malacria, M. Newcomb, J. C. Walton and D. P. Curran, J. Am.
Chem. Soc., 2009, 131, 11256–11262; (d) J. Monot, M. M. Brahmi,
S. H. Ueng, C. Robert, M. Desage-El Murr, D. P. Curran,
M. Malacria, L. Fensterbank and E. Lacote, Org. Lett., 2009,
11, 4914–4917; (e) Q. Chu, M. M. Brahmi, A. Solovyev,
S. H. Ueng, D. P. Curran, M. Malacria, L. Fensterbank and
E. Lacote, Chem.–Eur. J., 2009, 15, 12937.
In summary, we have synthesised a range of chiral and
achiral NHC–borane and –organoborane complexes, and
shown, in the first example of asymmetric synthesis using
structurally well-defined chiral NHC–main group complexes,
their potential in the asymmetric reduction of ketones. Work
in our laboratory is ongoing to identify more effective chiral
NHCs to apply the methodology to other CQX18 systems and
to develop a catalytic, asymmetric variant of the reaction, and
these studies will be described in due course.
8 A recent report on the asymmetric conjugate borylation of
a,b-unsaturated carbonyl systems notably invokes an NHC–boron
intermediate: K. S. Lee, A. R. Zhugralin and A. H. Hoveyda,
J. Am. Chem. Soc., 2009, 131, 7253–7255.
9 There is a single report of the use of IMesꢀInH3 in the reduction of
acetophenone, although the extreme reactivity and difficulty of
preparing and handling the indium hydride precursors may
discourage their widespread use; C. D. Abernethy, M. L. Cole,
A. J. Davies and C. Jones, Tetrahedron Lett., 2000, 41, 7567–7570.
10 THIBO is an acronym derived from the IUPAC name for the
tricyclic core: tetrahydroimidazo[4,3-b:5,1-b0]bis[1,3]oxazol-4-ium.
HIBDIO is an acronym derived from the IUPAC name for the
heptacyclic core: 2,3,10,14,21,22-hexahydroimidazo[4,3-b:5,1-b0]-
bis(3aS,8aR)-8,8a-dihydro-3aH-indeno[1,3]oxazol-11-ium.
11 (a) F. Glorius, G. Altenhoff, R. Goddard and C. W. Lehman,
Chem. Commun., 2002, 2704–2705; (b) G. Altenhoff, R. Goddard,
C. W. Lehmann and F. Glorius, J. Am. Chem. Soc., 2004, 126,
15195–15201.
We thank the EPSRC for
a studentship to D.M.
(EP/C531922/1) and an Advanced Research Fellowship to
D.M.L. (GR/S52100/02).
Notes and references
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14 It should be noted that, although apparently dramatic, a switch
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difference of only 0.8 kcal molꢁ1, whereas the switch reported by
Jørgensen,13 83% ee to 85% ee at room temperature, corresponds
to a much greater energy difference of 3 kcal molꢁ1
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18 For a recent example of an organoborane-mediated reduction of
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ꢂc
This journal is The Royal Society of Chemistry 2010
2476 | Chem. Commun., 2010, 46, 2474–2476