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Enantioselective, Noncovalent, Substrate‐Directable Heck–Matsuda and Oxidative Heck Arylations of Unactivated Five‐Membered Carbocyclic Olefins
Author(s) -
de Oliveira Juliana Manso,
Angnes Ricardo Almir,
Khan Ismat Ullah,
Polo Ellen Christine,
Heerdt Gabriel,
Servilha Bruno M.,
Menezes da Silva Vitor H.,
Braga Ataualpa A. C.,
Correia Carlos Roque Duarte
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201801910
Subject(s) - enantioselective synthesis , substrate (aquarium) , oxidative phosphorylation , heck reaction , chemistry , stereochemistry , organic chemistry , catalysis , palladium , biology , biochemistry , ecology
Highly diastereo‐ and enantioselective, noncovalent, substrate‐directable Heck desymmetrizations of cyclopentenyl olefins containing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97 %, diastereoselectivity up to >20:1, and enantiomeric excesses of up to 99 %. Noncovalent directing effects were shown to be prevalent in both Heck–Matsuda and oxidative Heck reactions, allowing the preferential formation of cis ‐substituted aryl cyclopentenes containing two stereocenters, including quaternary stereocenters. These results further validate the internal out‐of‐coordination‐sphere ion–dipole interaction concept directing the reaction diastereoselectivity to the cis ‐Heck product. This approach is complementary to existing methods using bis‐phosphine monoxide ligands to give the opposite trans ‐diastereoisomer. The applicability of the method is showcased by the straightforward synthesis of a potent phosphodiesterase 4 inhibitor in a diastereo‐ and enantioselective manner. The reaction is operationally simple and has broad scope with regard to the nature of the arenediazonium salt and boronic acid employed. The mechanism and origin of stereoselectivity were investigated with control experiments and DFT calculations that fully supported the stabilizing internal out‐of‐coordination‐sphere ion–dipole interaction between the resident functional group and cationic palladium.