directly from styrene 8 by treatment with TFA, also quantitatively
(Scheme 5).
ꢀ Co(sdmg)3 = Co(III)–N-salicyliminodimethylglycine complex (complex
1 in ref. 23); Mn(dpm)3 = Mn(III)–dipivaloylmethane complex (complex 1
in ref. 24).
** The nature of the N-protecting group is critical for this reaction.
Model N-Bn substrate 11 also gives the expected acetamide quantitatively
on exposure to the Ritter conditions (cf. Scheme 5) whereas its N-Cbz
congener suffers quantitative elimination to a styrene under identical
conditions. Direct application of the Ritter conditions to styrene 9 gave
the acetamide product in just 30% yield after 6 d.
1 S. Scheindlin, Mol. Interventions, 2004, 4, 188–191.
2 W. Zhang and D. P. Curran, Tetrahedron, 2006, 62, 11837–11865.
3 D. G. Hall, Boronic Acids, ed. D. G. Hall, Wiley-VCH, Weinheim, 2005.
4 M. Genov, A. Almor´ın and P. Espinet, Chem.–Eur. J., 2006, 12, 9346–
9352.
5 D. A. Horton, G. T. Bourne and M. L. Smythe, Chem. Rev., 2003, 103,
893–930.
Scheme 5 Step d: Ritter reaction–traceless cleavage (10 → 1) and traceless
cleavage (8 → 2).
6 X. Emonds-Alt, P. Soubrie and R. Steinberg, WO 2000, 064423 (2 Nov
2000).
7 A. Iwashita, N. Tojo, S. Matsuura, S. Yamazaki, K. Kamijo, J. Ishida,
H. Yamamoto, K. Hattori, N. Matsuoka and S. Mutoh, J. Pharmacol.
Exp. Ther., 2004, 310, 425–436.
8 D. J. Turner, R. Ane´mian, P. R. Mackie, D. C. Cupertino, S. G. Yeates,
M. L. Turner and A. C. Spivey, Org. Biomol. Chem., 2007, 5, 1752–1763.
9 G. A. M. Giardina, M. Grugni, R. Rigolio, M. Vassallo, K. Erhard
and C. Farina, Bioorg. Med. Chem. Lett., 1996, 6, 2307–2310.
10 E. J. Corey, G. A. Reichard and S. Sarshar, Bioorg. Med. Chem. Lett.,
1993, 3, 2635–2636.
In summary, efficient syntheses of acetylaminopiperidine 1 (5
steps, 33% yield) and tetrahydropyridine 2 (3 steps, 55% yield)
from bromobenzene have been achieved via a novel route in
which opportunities for material losses by evaporation have been
minimised in the initial immobilisation step and eliminated in
subsequent steps by anchoring to a fluorous phase-tag. The key
elaboration steps, all of which benefit from rapid purification by
fluorous SPE, are Ir-catalysed borylation, Suzuki cross-coupling
and Co-catalysed hydration. Although only a proof-of-concept
study employing cold bromobenzene has been described, we
anticipate that this approach could constitute a general strategy
for the safe preparation of aryl-containing radiolabelled materials
from [14C]-bromobenzene for ADME studies. Its application and
evaluation in this context is in progress.
11 H. Chen, S. Schlecht, T. C. Semple and J. F. Hartwig, Science, 2000,
287, 1995–1997.
12 M. K. Tse, J.-Y. Cho and M. R. Smith, III, Org. Lett., 2001, 3, 2831–
2833.
13 H. Chen and J. F. Hartwig, Angew. Chem., Int. Ed., 1999, 38, 3391–3393.
14 T. Ishiyama, J. Takagi, J. F. Hartwig and N. Miyaura, Angew. Chem.,
Int. Ed., 2002, 41, 3056–3058.
15 J. Takagi, K. Sato, J. F. Hartwig, T. Ishiyama and N. Miyaura,
Tetrahedron Lett., 2002, 43, 5649–5651.
16 A. C. Spivey, C. M. Diaper, H. Adams and A. J. Rudge, J. Org. Chem.,
2000, 65, 5253–5263.
17 J. L. Herde, J. C. Lambert, C. V. Senoff and M. A. Cushing, Inorg.
Synth., 1974, 15, 18–20.
18 R. Uson, L. A. Oro, J. A. Cabeza, H. E. Bryndza and P. Stepro, Inorg.
Synth., 1985, 23, 126–130.
Acknowledgements
Grateful acknowledgement is made to the EPSRC and sanofi-
aventis, Alnwick for financial support.
19 G. A. Chotana, M. A. Rak and M. R. Smith, III, J. Am. Chem. Soc.,
2005, 127, 10539–10544.
20 H. Hata, H. Shinokubo and A. Osuka, J. Am. Chem. Soc., 2005, 127,
Notes and references
8264–8265.
21 J. Uenishi, J.-M. Beau, R. W. Amstrong and Y. Kishi, J. Am. Chem.
Soc., 1987, 109, 4756–4758.
22 S. Talluri and A. Sudalai, Org. Lett., 2005, 7, 855–857.
23 J. Waser and E. M. Carreira, J. Am. Chem. Soc., 2004, 126, 5676–5677.
24 J. Waser and E. M. Carreira, Angew. Chem., Int. Ed., 2004, 43, 4099–
4102.
‡ Preliminary, solution phase studies towards the approach described here
were presented at the 9th International Symposium on the Synthesis and
Applications of Isotopically Labelled Compounds, Edinburgh, 16–20 July
2006, see: A. C. Spivey, L. J. Martin, C. Noban, T. C. Jones, G. J. Ellames
and A. D. Kohler, J. Label. Compd. Radiopharm., 2007, 50, 281–285 and
A. C. Spivey, L. J. Martin, G. J. Ellames and A. D. Kohler, J. Label. Compd.
Radiopharm., 2007, 50, 607–608.
§ Fluorous-tagged germyl bromide 3 is readily prepared in 4 steps (62%
yield overall) from commercial 1H2,2H2-perfluorodecyl iodide (£18/25 g:
www.fluorochem.net) and germanium(II) chloride·1,4-dioxane complex
(£114.50/10 g: www.sigmaaldrich.com), see Supplementary Material
(ESI).
25 J. Waser, B. Gaspar, H. Nambu and E. M. Carreira, J. Am. Chem. Soc.,
2006, 128, 11693–11712.
26 G. A. M. Giardina, M. Grugni, R. Rigolio, M. Vassallo, K. Erhard
and C. Farina, Bioorg. Med. Chem. Lett., 1996, 6, 2307–2310.
27 S. Inoki, K. Kato, S. Isayama and T. Mukaiyama, Chem. Lett., 1990,
1869–1872.
28 P. Magnus and M. R. Fielding, Tetrahedron Lett., 2001, 42, 6633–6636.
29 P. Magnus, A. H. Payne, M. J. Waring, D. A. Scott and V. Lynch,
Tetrahedron Lett., 2000, 41, 9725–9730.
30 H. G. Chen, O. P. Goel and J. Knobelsdorf, Tetrahedron Lett., 1996,
37, 8129–8132.
¶ Diborylation has not previously been noted in these types of reactions,
probably because the borane is invariably employed as the limiting reagent
(with the aryl component often deployed in great excess) or on di-
substituted aryl substrates for which diborylation is precluded on steric
grounds.
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