Bond energy enabled amine distinguishing strategy: chemo-, regioselective 1,3-diamination of (trifluoromethyl)alkenes with different amines by two C(sp³)–F bond cleavages

Abstract

The methods to distinguish different amines are rarely investigated. In this manuscript, a bond energy enabled amines distinguishing strategy is reported. With (trifluoromethyl)alkenes as linchpins, a chemo-, regioselective three-component defluorinative...

Combining Hydrodefluorination and Defluorophosphorylation for Chemo- and Stereoselective Synthesis of gem-Fluorophosphine Alkenes

“…Apparently, the latter would be more challenging due to the inherent complexity and uncontrollability that arises from the diverse reaction pathways during the integration of multiple molecules, which could result in an unideal distribution of products . Against this background, Zhu’s group reported a sequential ipso -/γ-selective defluorinative 1,3-amination of trifluoromethyl alkenes using two identical or different amines . Zhou and co-workers described a one-pot, two-step, three-component defluorinative annulation of trifluoromethyl alkenes, alkenes, and sodium sulfinates under photocatalysis .…”

“…On the basis of these control experiments and previous reports, we proposed a plausible reaction mechanism (Scheme ). − Initially, the carbonyl-containing trifluoromethyl alkenes react with reductive PhSiH 3 to realize hydrodefluorination through an S N 2′-type nucleophilic process and a simultaneous carbonyl reduction, leading to gem -difluorinated alkene B (pathway a). Subsequently, phosphoryl anion D selectively adds to the highly electrophilic α-position in gem -difluoroalkenes, followed by β-fluorine elimination to deliver the desired product 3 .…”

“…Subsequently, the previously reported ipso -/γ-selective defluorinative pathway could be ruled out, because the reaction of trifluoromethyl enone 1a with phosphine oxide 2a did not produce the coupled intermediate 8 under the standard conditions (Scheme S1-C). In addition, the carbonyl group was found to be vital for tuning the reactivity of the C­(sp 3 )-F bond, since the use of unactivated CF 3 -substituted alkene 9 as a substrate only resulted in the formation of direct defluorophosphorylated compound 11 in 35% yield (Scheme S1-D). We believed that the presence of an electron-deficient carbonyl moiety on the double bond of a trifluoromethyl alkene could reduce its electronic bias, thereby causing the stronger nucleophile PhSiH 3 to undergo hydrodefluorination preferentially over defluorophosphorylation with diarylphosphine oxides .…”

DBN-Mediated Addition Reaction of α-(Trifluoromethyl)styrenes with Diazoles, Triazoles, Tetrazoles, and Primary, Secondary, and Secondary Cyclic Amines

“…The reaction of α-(trifluoromethyl)­styrenes with nitrogen nucleophiles via the S N 2′ type of defluorinative addition/elimination process is a classical method for the synthesis of nitrogen-containing gem -difluoroalkenes (Scheme a) . More recently, the groups of Zhu and Jiang have extensively investigated the reactions of α-(trifluoromethyl)­styrenes with nitrogen nucleophiles such as indoles, carbazoles, pyrroles, and diamines (Scheme b–d) . A variety of nitrogen-containing monofluoroalkenes were synthesized via a sequential ipso /γ-selective defluorinative amination pathway.…”

“…Inspired by Zhu’s works, we subsequently investigated the defluorinations of α-(trifluoromethyl)­styrenes with different nitrogen nucleophiles under the optimized reaction conditions (Table , entry 23). Unfortunately, most N-heterocycles and alkyl amines were poor substrates and the defluorinative amination reaction could not take place, except for 2a and 2b .…”