We report the first practical use of SF as a fluorinating reagent in organic synthesis. Photoredox catalysis enables the in situ conversion of SF , an inert gas, into an active fluorinating species by using visible light. Under these conditions, deoxyfluorination of allylic alcohols is effected with high chemoselectivity and is tolerant of a wide range of functional groups. Application of the methodology in a continuous-flow setup achieves comparable yields to those obtained with a batch setup, while providing drastically increased material throughput of valuable allylic fluoride products.
Medicinally
relevant diarylamines are prepared through a photoredox-mediated
dual catalytic nickel/ruthenium system from aryl azides and aryl electrophiles.
Photoreduction of the aryl azide is proposed to proceed through an
arylnickel-azide complex, which upon reduction and loss of nitrogen,
generates a nickel(III) species capable of facile reductive elimination
to afford the desired C–N bond formation. A variety of functionalized
(hetero)aryl electrophiles are shown to participate in the coupling,
including iodides, bromides, chlorides, and triflates. The reactions
are simple to set up and are performed under ambient conditions, without
the exclusion of oxygen or moisture.
Three dipeptides bearing alkynes on their side chains (9 (derived from dilysine), 14 (derived from dicysteine) and 17 (derived from diglycine)) were prepared and reacted with W(CO) 3 (dmtc) 2 [dmtc = dimethyldithiocarbamate] to afford, respectively, three metallacyclicpeptides, 18, 19 and 20. The metallacyclicpeptides were characterized by HPLC, ES-MS, and 1 H NMR. The conformational behavior of the alkynes about the tungsten center was assessed using 1 H NMR. It was found that all three metallacyclicpeptides adopt multiple conformations of the alkynes relative to the tungsten. Both 18 and 19 appear to adopt all 8 possible conformations, while 20 adopts a limited number of conformations. The ability of the alkynes to equilibrate between the syn and anti conformations was assessed by examining the alkyne hydrogen resonances using variable temperature 1 H NMR. It was found that the alkyne ligands in 18 and 19 will equilibrate between the syn and anti conformations. The alkyne hydrogen resonances in 18 coalesce to one signal around 343K, while the alkyne hydrogen resonances in 19 do not completely coalesce even by 360K. Complex 18 has a larger ring than complex 19, and the higher temperature of coalescence for 19 is attributed to its smaller ring size. In contrast, complex 20, which has the smallest ring size, cannot equilibrate between the syn and anti conformations, even at elevated temperatures. The results show that cyclic tungsten-bis(alkyne) complexes will form ring systems with ring sizes of approximately 10 atoms, that ring sizes of approximately 10 atoms are rigid, and that rigidity is lost as the ring size is increased.
The use of strong organometallic bases and nucleophiles is commonplace in modern organic synthesis. That they react with a wide range of functional groups requires accurate and precise stoichiometry in reactions that utilize them. For best results, these bases are titrated prior to use, and such titrations can be timeconsuming and variable due to human error near the end point. Herein, we describe an automated method for titrations of multiple commercial organometallic reagents enabled by continuous flow. Through utilizations of continuous monitoring via UV−vis spectroscopy and a feedback loop developed within LabVIEW, titrations with enhanced reproducibility were provided over current batch procedures.
We report the first practical use of SF6 as a fluorinating reagent in organic synthesis. Photoredox catalysis enables the in situ conversion of SF6, an inert gas, into an active fluorinating species by using visible light. Under these conditions, deoxyfluorination of allylic alcohols is effected with high chemoselectivity and is tolerant of a wide range of functional groups. Application of the methodology in a continuous‐flow setup achieves comparable yields to those obtained with a batch setup, while providing drastically increased material throughput of valuable allylic fluoride products.
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