Double Duty for Cyanogen Bromide in a Cascade Synthesis of Cyanoepoxides

Abstract

Cyanogen bromide is a versatile reagent used in organic synthesis. Under different conditions, the Br À C bond can be cleaved in a diverse manner (Scheme 1, Modes I-IV). Thus, BrCN was shown to serve as a donor of Br + in reactions with strongly nucleophilic organometallic reagents to provide the corresponding vinyl-or arylbromides (Mode I).[1] In the reaction with vinyltellrium bromide, cyanogen bromide acted as an equivalent of a cyanide anion, and converts vinyltellurium bromide into a vinyltellurium cyanide (Mode II).[2] When reacted with primary or secondary amines or alcohols, cyanogen bromide behaves as an equivalent of CN + , and gives rise to cyanamides or cyanates (Mode III).[3] In the von Braun reaction, BrCN acts as an equivalent of both CN + and Br À by fragmenting tertiary amines into cyanamides and alkylbromides (Mode IV). [4,5] Herein, we report an unprecedented Mode V, in which cyanogen bromide works as an equivalent of Br + and CN À in a one-pot transformation of ketones into cyanoepoxide derivatives (Mode V).Our research group has recently demonstrated that alkynyl bromides can act as equivalents of both Br + and alkynyl anions in a highly efficient, one-pot conversion of ketones into alkynylepoxides.[6] We hypothesized that cyanogen bromide could potentially be involved in a similar transformation as an equivalent of both Br + and CN À (Scheme 2). It was anticipated that a ketone enolate would attack the bromine atom of cyanogen bromide to generate the a-bromoketone 3. Then nucleophilic addition of the formed cyanide to the ketone to give 4, would be followed by the formation of a cyanohydrin anion, which upon intramolecular S N 2 reaction would produce the product cyanoepoxide 2. Thus, cyanogen bromide would act as an equivalent of both Br + and CN À in one cascade transformation. To test the above hypothesis, we examined the reaction of isobutyrophenone (1 a) and cyanogen bromide in the presence of a strong base. It was found that the deprotonation of isobutyrophenone with NaHMDS, and subsequent addition of cyanogen bromide resulted in the formation of cyanoepoxide 2 a in good yield, along with trace amounts of abromoketone 3, and provided support for the proposed path for this transformation.

Mander’s Reagent for the Deoxycyanation of β-Diketones: A Direct Synthesis of Oxoalkenenitriles

“…Interestingly, the 2-methyl diketone 2a was revealed to exist as a tautomeric mixture (~40% enolization) when dissolved in CDCl 3 ( 1 H NMR), 16 which prompted us to explore several reaction systems and reagents for the direct preparation of oxoalkenenitriles from -diketones. Several electrophilic cyanides (e.g., BrCN) 17 or their mixtures with PPh 3 (BrCN, 18 cyanobenzotriazole, 19 tosyl cyanide, or TM-SCN 20 ) were ineffective. However, treatment of -diketone 2a with Mander's reagent in the presence of Et 3 N gave the alkenyl oxonitrile 4a, exclusively in 35% yield (Figure 1c).…”

Base‐Catalyzed NN Bond Cleavage of Hydrazones: Synthesis of α‐Amino Ketones

“…As illustrated in Scheme 3, the reaction scope can be extended to different aldehydes to afford nitriles. [13] Naturally, several benzaldehydes (R 2 = C 6 H 5 , 4-BrC 6 H 4 , 2-BrC 6 H 4 , 4-CH 3 OC 6 H 4 ) reacted well, providing 5 a, 5 b, 5 c, 5 f, and aamino ketone 4a in good yields (Scheme 3, 5 a, 5 b, 5 c, and 5 f). Aromatic heterocycle aldehydes such as 2-thiophenecarboxaldehyde and fused-ring aldehydes including 1-naphthaldehyde were also suitable for the transformations (Scheme 3, 5 d and 5 e).…”

One‐Pot Arylative Epoxidation of Ketones by Employing Amphoteric Bromoperfluoroarenes

“…[4,5] Since the amphoteric reactivity of PFPBr as an equivalent of either Br + or PFP − has been reported (Scheme 1), we hypothesized that it may also serve as a competent reagent for the one-pot cascade epoxidation reaction of ketones (Scheme 2). It was expected that an enolate would abstract Br + from PFPBr to produce an α-bromoketone i and a PFP anion.…”

“…[3] Herein, we present an unprecedented mode III, in which PFPBr functions as an equivalent of both Br + and PFP À in the same transformation: a one-pot arylative epoxidation of ketones into pentafluorophenyloxiranes.Our group has recently reported that alkynyl bromides and cyanogen bromide can act as equivalents of both Br + and alkynyl-or cyanide anions in a highly efficient one-pot conversion of ketones into fully substituted alkynyl or cyanoepoxides. [4,5] As the amphoteric reactivity of PFPBr, as an equivalent of either Br + or PFP À has been established (Scheme 1), we hypothesized that it may also serve as a competent reagent for the one-pot cascade epoxidation of ketones (Scheme 2). It was expected that an enolate would abstract Br + from PFPBr to produce a-bromoketone I and a PFP anion.…”

“…ketones 1 i,j and N-tosylindole-3-yl ketone 1 k, were converted into the corresponding epoxides 2 i-k in good yields (entries [9][10][11]. Importantly, in contrast to the epoxidation reaction with alkynyl bromides [4] and cyanogen bromide, [5] PFPBr smoothly reacted with propiophenone 1 l and butyrophenone 1 m, producing the corresponding trisubstituted oxiranes 2 l,m in good yields and very high diastereoselectivities [7] (entries 12 and 13). It should be mentioned that this reaction is easily scalable, as a 10 mmol scale reaction of propiophenone 1 l with PFPBr resulted in an outcome similar to that for the 0.5 mmol reaction (entry 12).…”