Author: Smita Mandal

Publisher:

Published: 2024

Total Pages: 0

ISBN-13:

Organofluorine compounds have witnessed significant applications in agrochemical, pharmaceutical industries, and material science. As a result, progress in developing synthetic methods to prepare fluorinated compounds has been rapid. However, general methods for preparing enantioenriched tertiary alkyl fluoride motifs are rare, as such motifs present numerous challenges for both catalysis and stereocontrol. We have demonstrated catalytic asymmetric a-functionalization of a-fluoro acyclic esters by the union of C1-ammonium enolates generated using Lewis base catalyst with pi-(allyl)Ir(III) electrophiles to furnish allylated products with two vicinal stereogenic centers. The configuration of each stereogenic center is controlled independently via a cooperative catalysis platform giving access to the stereodivergent construction of tertiary fluorides. The direct employment of nonstabilized nucleophiles in Pd-catalyzed asymmetric allylic alkylation poses a significant synthetic challenge. We have embraced photoredox/transition metal cooperative catalysis to address this limitation, which offers an alternative approach by unlocking one-electron reaction pathways. However, the control of regioselectivity in such a reaction framework is predominantly determined by the nature of the substituents, where the nucleophile preferentially attacks the allylic carbon with an ‘aryl substituent’. However, access to valuable aliphatic bearing stereocenters is desirable but impossible using existing synthetic protocols. Encouraged by our previous success exploiting substituents on the regioselectivity of nucleophilic attack on pi-(allyl)Pd species, we conceived of a general approach to forge asymmetric C(sp3)-C(sp3) bond formation by leveraging the powerful directing effect of synthetically versatile silicon substituents. Here, the well-established radical precursor 4-alkyl-1,4- dihydropyridine was employed which when irradiated by blue LEDs, generates the desired alkyl radical which then couples with silicon-substituted pi-(allyl)Pd complex to furnish the desired product after reductive elimination.