Aza-Michael Access to Fluoroalkylidene Analogues of Biomolecules

Abstract

The synthesis of fluoroaminosulfones derived from piperidine and nucleic bases followed by the study of their chemical behavior in the modified Julia reaction are described. The resulting aminosulfones open a straightforward access to a series of new fluorinated biomolecules including a potent DPP-II inhibitor and acyclonucleoside analogues as potential enzyme inhibitors.

Good Partnership between Sulfur and Fluorine: Sulfur-Based Fluorination and Fluoroalkylation Reagents for Organic Synthesis

“…Julia–Kocienski Reaction. The Julia–Kocienski reaction is an important method to convert the carbonyl compounds into alkenes in one step, which has found many applications in the synthesis of both internal and terminal monofluoroalkenes. ,− Mechanically, these reactions commences with the nucleophilic addition of the α-monofluorinated sulfone anion to a carbonyl compound followed by a Smiles rearrangement, and concludes with the formation of a fluorinated CC double bond, which links the nonfluorinated and monofluorinated motifs together in one molecule. Two key issues in direct monofluoroolefination are the incorporation of a fluorine atom into the α-position of heteroaromatic or electron-deficient aromatic sulfones and the control of the stereoselectivity of the olefination reaction.…”

Synthesis of Fluorine‐Containing 3,3‐Disubstituted Oxetanes and Alkylidene Oxetanes

“…The addition of freshly distilled pyrrolidine to unsaturated sulfone 5e in the presence of a catalytic amount of tetra-n-butylammonium fluoride (TBAF; 20 mol-%) in THF proceeded smoothly [35] to give oxetane 8f in 87 % yield. A single crystal was obtained that allowed structural confirmation by X-ray crystallography (see the Supporting information).…”

Synthesis of Monofluoroalkenes: A Leap Forward

“…Since 2011, the Lequeux group has studied the synthesis of fluoroallylamines. [65][66][67][68][69] To access this class of compound, a Julia-Kocienski olefination was used as the key step. In most cases, good yields were obtained, but a lack of stereoselectivity was observed (Scheme 49).…”