A catalytic fluoride-rebound mechanism for C(sp 3 )-CF 3 bond formation

The biological properties of trifluoromethyl compounds have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions. We report the serendipitous discovery of a borane-catalyzed formal C(s...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2017-06, Vol.356 (6344), p.1272-1276
Main Authors: Levin, Mark D, Chen, Tiffany Q, Neubig, Megan E, Hong, Cynthia M, Theulier, Cyril A, Kobylianskii, Ilia J, Janabi, Mustafa, O'Neil, James P, Toste, F Dean
Format: Article
Language:English
Subjects:
Boranes - chemistry
Chemistry Techniques, Synthetic
Chemistry, Pharmaceutical - methods
Fluorides - chemistry
Gold - chemistry
Positron-Emission Tomography
Radioactive Tracers
Radiochemistry - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The biological properties of trifluoromethyl compounds have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions. We report the serendipitous discovery of a borane-catalyzed formal C(sp )-CF reductive elimination from Au(III) that accesses these compounds by a distinct mechanism proceeding via fluoride abstraction, migratory insertion, and C-F reductive elimination to achieve a net C-C bond construction. The parent bis(trifluoromethyl)Au(III) complexes tolerate a surprising breadth of synthetic protocols, enabling the synthesis of complex organic derivatives without cleavage of the Au-C bond. This feature, combined with the "fluoride-rebound" mechanism, was translated into a protocol for the synthesis of F-radiolabeled aliphatic CF -containing compounds, enabling the preparation of potential tracers for use in positron emission tomography.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aan1411