on the hydroxyketone products shows that there is much
potential for further elaboration and it is our hope that these
conditions for accomplishing the acyloin reaction will become
widely used.
We would like to thank the EPSRC/Pharma Organic
Synthetic Chemistry Studentships program for supporting this
project and both EPSRC and AstraZeneca for financial
support.
Notes and references
Scheme 5
z Interestingly, control experiments on diester 7a under traditional
acyloin conditions, Na–xylene, gave very low yields of the acyloin
product.
this reaction was garnered when we quenched the acyloin
reaction of 7d directly with allyl bromide, thus forming 15
(which is a handle for further derivatisation by alkene migration,
metathesis or oxidative cleavage) in 72% yield; as expected,
the aromatic group attached to the enediolate had again
controlled the regiochemistry of the alkylation in the same
sense as that observed for protonation (compare 8d with 15).
Finally, we sought to exemplify the utility of the a-hydroxy
ketones that had been prepared in this sequence, and so
using 8d as an example, subjected it to a range of different
derivatisation reactions (see 16–19, Scheme 6).10 Clearly, there
is much scope for transformations into stereochemically
defined diols together with short sequences which enable the
formation of aromatic heterocycles (18, 19z)11 with control
of regiochemistry stemming directly from the outcome of the
acyloin coupling.
y Compound 8j was formed as a 1 : 1 mixture of diastereoisomers.
z The structures of 13 and 19 were proven by X-ray crystallography.
1 See for example, (a) R. A. Holton, H. B. Kim, C. Somoza,
F. Liang, R. J. Biediger, P. D. Boatman, M. Smith, C. C. Shindo
and S. Kim, J. Am. Chem. Soc., 1994, 116, 1599; (b) H. B. Sik Yun,
Y. K. Ma, K. Byoung-Mog, K. Hong-Gi, L. Hyang-Bok,
B. Kyung-Sook and K. Sung-Uk, J. Antibiot., 2000, 53, 248;
(c) C. I. Viturro, J. R. de la Fuente and M. S. Maier, J. Nat.
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2 For recent references see, (a) D. Enders and A. Hensler, Adv.
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J. S. Johnson, J. Org. Chem., 2010, 75, 3317; (d) S. E. Denmark
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C. A. Rose, S. Gundala, K. Zeitler and S. J. Connon, J. Org.
Chem., 2011, 76, 347; (f) M. Y. Jin, S. M. Kim, H. Han, D. H. Ryu
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3 T. Saito, A. Kimishima and T. Nakata, Heterocycles, 2006, 70,
177.
4 (a) Typical homogeneous conditions use ammonia as a solvent.
For a review see: J. J. Bloomfield, D. C. Owsley and J. M. Nelke,
Org. React., 1976, 23, 259; (b) R. Karaman and J. L. Fry,
Tetrahedron Lett., 1989, 30, 4931.
To conclude, we have shown that LiDBB promotes the
acyloin reaction at low temperatures and allows electron
transfer in solution. Moreover, the use of a rigid (and reusable)
linker between two ester groups facilitates crossed acyloin
coupling with very high efficiency. The introduction of an
aromatic substituent on the enediolate intermediate allows the
formation of a single regioisomer of the product, and also
enantiopure hydroxyl ketones can be produced by the diastereo-
selective protonation of chiral substrates. A snapshot of the
various derivatisation reactions that can be accomplished
5 T. S. Daynard, P. S. Eby and J. H. Hutchinson, Can. J. Chem.,
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6 For representative references on the use of LiDBB see:
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7 A. G. M. Barrett, C. R. A. Godfrey, D. M. Hollinshead,
P. A. Prokopiou, D. H. R. Barton, R. B. Boar, L. Joukhadar,
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8 Diol 5 was prepared from norbornene in one step (KMnO4, 78%
yield), see: K. B. Wiberg and K. A. Saegebarth, J. Am. Chem. Soc.,
1956, 79, 2822.
9 See: F. Machrouhi, J. Namy and H. Kagan, Tetrahedron Lett.,
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10 (a) J. Broeker, M. Knollmueller and P. Gaertner, Tetrahedron:
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P. Singh, Tetrahedron, 2006, 62, 4018; (c) F. A. Davis, M. S. Haque
and R. M. Przeslawski, J. Org. Chem., 1988, 54, 2021.
11 (a) O. R. S. John, N. M. Killeen, D. A. Knowles, S. C. Yau,
M. C. Bagley and N. C. O. Tomkinson, Org. Lett., 2007, 9, 4009;
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´
sar and
¨
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Scheme 6
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 5849–5851 5851