Electrophilic Fluorocyclization of Allyl Silanes

Abstract

A refreshing cascade: General fluorocyclization reactions will breathe new life into the use of fluorinated hetero‐ and carbocycles as pharmaceuticals and agrochemicals. Allyl silanes have now been shown to undergo fluorination–cyclization with NF reagents to give cis‐ and trans‐substituted fluorinated heterocycles selectively (see scheme). The correct choice of silyl group was critical to prevent competitive fluorodesilylation.

Metal free fluoroamination of allylsilanes: A route to 3-fluoropyrrolidines

“…The use of Selectfluor 1 and NaHCO 3 in acetonitrile at room temperature gave better results and was retained for further investigation. All together, these results highlight clear differences with the corresponding fluoroetherification of silyl-activated homoallylic alcohols [8]. The fluorocyclization of the N-protected homoallylic amines 1a-f was less efficient as competitive fluorodesilylation could not be eradicated or was the predominant reaction pathway, but the level of stereocontrol for the fluoroamination was superior (Table 1).…”

“…Compounds (Z)-1a, (Z)-1b and (Z)-1g were prepared by substituting the corresponding activated alcohols with tosyl amine in DMF. The Z geometry of all precursors was secured through a key ring closing metathesis as previously reported in the literature [8,13,14]. The preparation of (E)-1h began with the known (E)-2,2-dimethyl-5-(triisopropylsilyl)pent-3-enoic acid [8].…”

“…The Z geometry of all precursors was secured through a key ring closing metathesis as previously reported in the literature [8,13,14]. The preparation of (E)-1h began with the known (E)-2,2-dimethyl-5-(triisopropylsilyl)pent-3-enoic acid [8]. This precursor was obtained by crossmetathesis reaction of deconjugated tiglic acid with triisopropylallylsilane followed by methylation under basic condition applying literature procedures [8].…”

“…For this purpose, the triisopropylsilylmethyl and diisopropylphenylsilylmethyl groups were used as activating groups instead of trimethylsilylmethyl. Based on these principles, the fluoroetherification of silyl-activated homoallylic alcohols was performed in the presence of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2]octane bis tetrafluoroborate (Selectfluor 1 ) or N-fluorobenzenesulfonimide (NFSI) and led to a series of fluorinated tetrahydrofurans [8]. The stereochemical outcome of these reactions is consistent with an overall syn addition to the double bond; this stereospecific transformation led to syn-and anticyclized products using E-and Z-allylsilanes respectively.…”

4.07 Electrophilic Cyclization

“…142 The reactions of 5-norbornene-endo-2-carboxylic acid or fluorocyclizations (Scheme 133). 144 The (DHQ) 2 PHAL/Selectfluor combination could induce asymmetry in the cyclization of prochiral allyl silane 510 to produce 511 (70% yield, one diastereomer, 45% ee).…”