Efficient Synthesis and Ring‐Opening Reactions of Monofluorinated Epoxides Derived from α‐Fluorosulfoximines

Abstract

Monofluorinated epoxides were successfully prepared through the O-cyclization reaction between a-fluorosulfoximines and ketones. The obtained fluoroepoxides were found to readily undergo an interesting ring-opening process (involving both a C À F bond cleavage and another C À F bond formation) in the presence of titanium tetrafluoride or pyridinium poly(hydrogen fluoride) to afford afluorinated ketones. The later process constitutes a formal catalytic 1,2-fluorine shift reaction.Keywords: epoxides; fluorine; fluorine shift; ringopening; sulfoximines Due to the high electronegativity and small size of the fluorine atom, the replacement of hydrogen atom(s) by fluorine in organic compounds often results in a profound change in their physical, chemical and biological properties.[1] As a consequence, over the past decade, organofluorine compounds have found broad applications in both life sciences and materials science.[2] To date, many endeavours have been made to develop new efficient synthetic methods for the selective introduction of fluorine atom(s) or fluorinated moieties into organic molecules.[2] Although epoxides are highly useful building blocks in organic synthesis, the reports on the preparation and synthetic utilizations of monofluorinated epoxides are scarce. [3][4][5] Monofluorinated epoxides are usually prepared by the epoxidation of monofluoroolefins, [3] the treatment of fluorohalohydrins with a base, [4] or the Darzens reaction between a ketone and dibromo(tertbutyldimethylsililyl)fluoromethane [5] (or ethyl dibromofluoroacetate [6] ). Fluorinated epoxides are known to be relatively unstable, and tend to undergo a variety of ring-opening reactions with nucleophiles.[3c,7,9] When monofluoroepoxides were treated with fluoride ion, a-fluorinated carbonyl compounds were obtained through a ringopening process involving both a C À F bond cleavage and another C À F bond formation. [3a,8] This type of transformation also proceeded smoothly in the presence of triethylamine-tris(hydrogen fluoride) [9] or boron trifluoride [10] . Futhermore, the acid-catalyzed isomerizations of polyfluorinated epoxides into the corresponding ketones have been previously documented. [7] As part of our efforts to develop new synthetic approaches for organofluorine compounds, [11] we recently developed some unique synthetic methods for the preparation of di-and monofluorinated compounds by using fluorinated sulfoximine reagents. [12,13] In particular, the a-difluoromethylsulfoximine was used as a novel and efficient difluorocarbene reagent, [12] and the a-fluorosulfoximines could readily react with simple nitrones to give monofluoroalkenes with excellent Z/E stereocontrol. [13] In this paper, we wish to report another interesting synthetic application of fluorinated sulfoximines, that is, the efficient synthesis of a-monofluorinated epoxides derived from a-fluorosulfoximines and ketones, and the subsequent ringopening reaction of the monofluoroepoxides by using TiF 4 or pyridinium poly(hydrogen fluoride) (Olahs reage...

Stereoselective Carbonyl Olefination with Fluorosulfoximines: Facile Access to Z or E Terminal Monofluoroalkenes

“…To our delight, when 1 b with an electron-donating TBS substituent was used, its reaction with 2 s proceeded smoothly to afford olefin 3 s in moderate yield with high E selectivity (entry 2). In the case of 1 c, the formation of the corresponding monofluoroepoxide was detected, [16] whereas in the case of 1 d, the product of addition to the carbonyl group was obtained as reported previously. Reactions with either N-tosyl or N-TBS-substituted S-phenylsulfoximine (substrates 1 c and 1 d) failed to produce the olefination product (Table 1, entries 3 and 4).…”

Brønsted acid-catalyzed 1,2-fluorine migration with fluoroepoxides

“…However, it has been reported that many simple fluoroepoxides are rather sensitive to moisture and can readily decompose during the purification, 8,10 and we also found that the stability of the fluoroepoxides derived from fluorosulfoximines and aryl ketones is closely linked with the electronic nature of the functionalities on aryl groups (Table 1). Although strongly electron-deficient fluoroepoxides can be easily purified by silica gel column chromatography, attempts to purify the tetrasubstituted electron-neutral fluoroepoxides with moderate stability by using silica gel column chromatography resulted in ring-opening products (a mixture of 1,2-fluorine migration product 5 and a considerable amount of defluorination products).…”

“…8 Through this fluorine migration reaction, many structurally diverse α-fluorinated ketones can be efficiently constructed. 8 Through this fluorine migration reaction, many structurally diverse α-fluorinated ketones can be efficiently constructed.…”

“…In previous investigations, 8 we found that in contrast to cyclopropyl-substituted fluoroepoxides 1, unpurified simple fluoroepoxides 4 are difficult to subject to an efficient 1,2-fluorine migration reaction in the absence of external fluorinating agents due to the influence of impurities (such as ketone, fluorosulfoximine, and sulfinamide) introduced during their preparation from fluorosulfoximines and ketones. 9 To develop Scheme 1 Fluorine migration reactions.…”

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“…2 Since 2008, N,N-dimethyl α-fluoromethyl sulfoximinium salts (by research groups led by Shibata 4,5 and Prakash 6 ), N-tosyl racemic α-fluoro sulfoximines (by Hu's group [7][8][9] ), and other α-fluoro sulfoximines (by Magnier's group 10 ) have been exploited for fluoroalkylation reactions. Inspired by recent developments in the synthesis of chiral fluorinated molecules, they envisioned several conceptually new chiral fluoroalkylation reagent controlled diastereoselective and enantioselective nucleophilic reactions by taking advantage of the stereogenic center of sulfur in sulfoxi m ines.…”