41 The 2-azaallyl radical and anions related to the intermediates in these processes were recently isolated and fully characterized (including X-ray crystallographically). 40 Likewise, phenyl allyl ethers react to furnish homoallylic amines.
With hindered alkyl iodides and bromides, such as 1-adamantyl iodide, the 2-azaallyl anion undergoes SET generating the alkyl radical, which again couples with the 2-azaallyl radical. Thus, reaction of 2-azaallyl anions with aryl iodides, 38 bromides or even chlorides (under light irradiation) 39 resulted in SET from the 2-azaallyl anion to the aryl halide to generate an aryl radical and the persistent 40 2-azaallyl radical, which then undergo a radical–radical coupling to afford the arylated product. Recently we discovered that 2-azaallyl anions behave as super electron donors (SEDs) 37 and undergo 1-electron processes with a variety of electrophiles, opening a new reactivity mode and enabling the synthesis of α-branched amines ( Scheme 2b). (d) Applications to synthesis involving trapping of aryl radicals with allenes ultimately affording heterocyclic amines. (c) Dehydrogenative coupling of saturated heterocycles with 2-azaallyl radicals. (b) Single electron reactivity of 2-azaallyl anions with aryl halides and tertiary alkyl iodides via radical intermediates. (a) 2-electron processes such as S N2 and Pd-catalyzed coupling reactions of 2-azaallyl anions. 20,34–36 Hydrolysis of the alkylation, vinylation or arylation products affords α-branched amines with high ee values. Azadiene precursors have also been hydrometallated to generate 2-azaallyl anions for enantioselective transformations. 28–32 A similar approach was use with aryl bromides and alkyl substituted 2-azaallyl anions in the presence of an enantioenriched Pd catalyst 24 or with vinyl bromides and an enantioenriched nickel catalyst 33 for the synthesis of highly enantioenriched benzylic and homoallylic amine derivatives, respectively. 20–27 The 2-azaallyl anions can react with unhindered alkyl halides via S N2, or with aryl halides in the presence of cross-coupling catalysts ( Scheme 2a).
The 2-azaallyl anion is usually generated in situ by deprotonation of aldimines or ketimines under mild conditions and have the advantage of avoiding preformed organometallic reagents. 19 Recent studies have shown the utility of 2-azaallyl anions in a wide range of C(sp 2)–C(sp 3) and C(sp 3)–C(sp 3) coupling reactions via 2-electron processes. (c) Transition-metal-catalyzed α-functionalization of amines with C–C bond-formation.Īlternatively, we and many others, have been interested in an approach involving the inversion of polarity of the imine by generation of 2-azaallyl anions. (b) Transition-metal-catalyzed C–H activation followed by addition to imines. (a) α-Branched amine synthesis via addition of organometallic reagents to imines. 15–18 Although the utility of these reactions is well appreciated, several employ the use of precious metal catalysts.Īpproaches to α-branched amines. Here, both transition-metal-catalyzed processes 14 and photoredox catalyzed radical coupling approaches to form C–C bonds have been successfully introduced ( Scheme 1c). 11–13 The α-functionalization of amines toward the formation of α-branched derivatives has also been developed. A more atom economical method employs transition-metal-catalyzed C–H bond activation followed by addition of the resulting organometallic nucleophile to imines ( Scheme 1b). 7–10 Recent years have witnessed remarkable progress in alternative syntheses of α-branched amines. The traditional approach to α-branched amines involves the addition of organometallic reagents, 5,6 such as Grignard reagents and organolithiums, to imines ( Scheme 1a).
4 As such, their synthesis continues to attract attention, with emphasis on rapid access to new chemical space. Amines with α-branching are important functional groups in bioactive compounds, 1 natural products, 2,3 and medications.
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