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. 2005 Jun 22;127(24):8644-51.
doi: 10.1021/ja0430346.

Selective synthesis of 5- or 6-aryl octahydrocyclopenta[b]pyrroles from a common precursor through control of competing pathways in a Pd-catalyzed reaction

Joshua E Ney  1 , John P Wolfe
Affiliations

Selective synthesis of 5- or 6-aryl octahydrocyclopenta[b]pyrroles from a common precursor through control of competing pathways in a Pd-catalyzed reaction

Joshua E Ney et al. J Am Chem Soc. .

Abstract

The Pd/phosphine-catalyzed reaction of 1 with aryl bromides leads to the selective synthesis of either 6-aryl octahydrocyclopenta[b]pyrroles (3), the corresponding 5-aryl isomers 5, diarylamine 2, or hexahydrocyclopenta[b]pyrrole 4 depending on the structure of the phosphine ligand. These transformations are effective with a variety of different aryl bromides and provide 3-5 with excellent levels of diastereoselectivity (dr > or = 20:1). The changes in product distribution are believed to derive from the influence of Pd-catalyst structure on the relative rates of reductive elimination, beta-hydride elimination, alkene insertion, and alkene displacement processes in a mechanistically complex reaction. The effect of phosphine ligand structure on product distribution is described in detail, along with analysis of a proposed mechanism for these transformations.

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Figures

Scheme 1
Scheme 1
(a) Conditions: 1.0 equiv 1a, 1.2 equiv 4-Ph(C6H4)Br, 1.4 equiv NaOtBu, 1 mol % Pd2(dba)3, 4 mol % P(o-tol)3, toluene, 110 °C. Isolated yield: 2 (19%), 3 (32%), 4 (5%), 5 (12%) for Ar = 4-methoxyphenyl, Ar1 = 4-(phenyl)phenyl.
Scheme 2
Scheme 2
Scheme 3
Scheme 3
Figure 1
Figure 1
See this image and copyright information in PMC

References

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    1. A portion of this work has been previously communicated. See:Ney JE, Wolfe JP. Angew. Chem. Int. Ed. 2004;43:3605–3608.

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