title: Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach.
abstract: Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp3)-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellentcis-selectivity was achieved in all cases, except for the THP substrate where minortrans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined.
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom, http://www3.imperial.ac.uk/people/j.bull.
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Affron
authors.affiliation: Department of Chemistry, Imperial College London, South Kensington, London SW7 2AZ, United Kingdom, http://www3.imperial.ac.uk/people/j.bull.
authors.forename: James A
authors.initials: JA
authors.lastname: Bull
keywords: C–H arylation; Homogeneous catalysis; N Heterocycles; O Heterocycles; Palladium