{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":48,"searchCount":0},"additional":{"submitter":["Park H"],"funding":["NIGMS NIH HHS"],"pagination":["755-762"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6289870"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["10(7)"],"pubmed_abstract":["The development of a Pd(II)-catalysed enantioselective fluorination of C(sp3)-H bonds would offer a new approach to making chiral organofluorines. However, such a strategy is particularly challenging because of the difficulty in differentiating prochiral C(sp3)-H bonds through Pd(II)-insertion, as well as the sluggish reductive elimination involving Pd-F bonds. Here, we report the development of a Pd(II)-catalysed enantioselective C(sp3)-H fluorination using a chiral transient directing group strategy. In this work, a bulky, amino amide transient directing group was developed to control the stereochemistry of the C-H insertion step and selectively promote the C(sp3)-F reductive elimination pathway from the Pd(IV)-F intermediate. Stereochemical analysis revealed that while the desired C(sp3)-F formation proceeds via an inner-sphere pathway with retention of configuration, the undesired C(sp3)-O formation occurs through an SN2-type mechanism. Elucidation of the dual mechanism allows us to rationalize the profound ligand effect on controlling reductive elimination selectivity from high-valent Pd species."],"journal":["Nature chemistry"],"pubmed_title":["Controlling Pd(IV) reductive elimination pathways enables Pd(II)-catalysed enantioselective C(sp3)-H fluorination."],"pmcid":["PMC6289870"],"funding_grant_id":["R01 GM084019"],"pubmed_authors":["Yu JQ","Park H","Hong K","Verma P"],"view_count":["48"],"additional_accession":[]},"is_claimable":false,"name":"Controlling Pd(IV) reductive elimination pathways enables Pd(II)-catalysed enantioselective C(sp3)-H fluorination.","description":"The development of a Pd(II)-catalysed enantioselective fluorination of C(sp3)-H bonds would offer a new approach to making chiral organofluorines. However, such a strategy is particularly challenging because of the difficulty in differentiating prochiral C(sp3)-H bonds through Pd(II)-insertion, as well as the sluggish reductive elimination involving Pd-F bonds. Here, we report the development of a Pd(II)-catalysed enantioselective C(sp3)-H fluorination using a chiral transient directing group strategy. In this work, a bulky, amino amide transient directing group was developed to control the stereochemistry of the C-H insertion step and selectively promote the C(sp3)-F reductive elimination pathway from the Pd(IV)-F intermediate. Stereochemical analysis revealed that while the desired C(sp3)-F formation proceeds via an inner-sphere pathway with retention of configuration, the undesired C(sp3)-O formation occurs through an SN2-type mechanism. Elucidation of the dual mechanism allows us to rationalize the profound ligand effect on controlling reductive elimination selectivity from high-valent Pd species.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Jul","modification":"2020-10-31T08:09:03Z","creation":"2019-03-27T00:11:55Z"},"accession":"S-EPMC6289870","cross_references":{"pubmed":["29892027"],"doi":["10.1038/s41557-018-0048-1"]}}