Synthesis of BCP Benzylamines From 2‐Azaallyl Anions and [1.1.1]Propellane

Abstract

Scheme 2. Gram-scale propellerization and hydrolysis of propellerized product 3n. Scheme 3. Propellerization of ad euterated2 -azaallyl ketimine.

Rationalizing the diverse reactivity of [1.1.1]propellane through σ–π-delocalization

“…This began with a study of anionic addition, for which a number of examples of have been described that access aryl-, alkyl-and aminosubstituted BCPs. [25][26][27][28][29] Given the apparent strain relief associated with this chemistry, it is perhaps surprising that extended reaction times ($16 h) and elevated temperatures (>50 C) are oen required for successful addition. Walsh et al have studied the related addition of dithiane anions, 29 complementing their synthetic work with DFT calculations at the M06-2X level of theory, 73 which revealed carbanion addition to be highly endergonic.…”

“…BCPs are also useful motifs for organic materials, including rodlike one-dimensional polymers, 11 supramolecular spacer units, 12 liquid crystals 13 and FRET sensors. 14 Such applications have stimulated the development of a number of methods to access BCPs in a single step from 1 via radical [15][16][17][18][19][20][21][22][23][24] and anionic [25][26][27][28][29] intermediates (Fig. 1b).…”

“…36 To date, a handful of experimental studies have employed density functional theory (DFT) to investigate the pathways of addition of radicals and anions to [1.1.1]propellane, offering useful insight to support reaction development. 17,18,20,28,29 However, no in-depth theoretical analysis has tackled the origin of the omniphilic reactivity of 1. Here we combine ab initio approaches with electron density difference analysis and Distortion/Interaction Analysis (DIA) [37][38][39] to develop a unied model for the reactivity of [1.1.1]propellane.…”

Saturated Bioisosteres of ortho‐Substituted Benzenes

“…[7] Theo btained analogue showed higher activity,solubility and metabolic stability.Since then, bicyclo-[1.1.1]pentyl-containing derivatives have been playing an important role in both academic and industrial researchthey have already been mentioned in more than one hundred patents. [8,9] Moreover,c ubane and bicyclo [2.2.2]octane have also been validated as saturated bioisosteres for parasubstituted benzenes in bioactive compounds. [10] It is important to mention, that the replacement of the phenyl ring with saturated mimetics is only possible when the phenyl ring in abioactive compound is not involved in specific p-protein interactions (cation-p, p-p,d ipole-p), [11] and acts purely as ar igid linker to hold two substituents in aw elldefined distance.…”

Synthesis of Benzofuran Derivatives through Cascade Radical Cyclization/Intermolecular Coupling of 2‐Azaallyls

“…Recently,w ei ntroduced au nique radical generation strategy [8] fort he transition metal-free C(sp 3 )ÀC(sp 3 )a nd C(sp 3 )ÀC(sp 2 )c oupling reactions between 2-azaallyl radicals [9] and alkyl or aryl radicals (Scheme 2a). [10] Specifically, the single-electron transfer (SET) process between 2-azaallyl anions [8] and aryl iodides or alkyl iodides or bromides led to the generation of the 2-azaallyl radical and aryl or alkyl radicals.T he radical generation relies on the "super electron donor" (SED) feature of 2-azaallyl anions,which initiates the reaction. We hypothesized that the high chemoselectivity in the radical-radical coupling is due to the relative stability of the 2-azaallyl radical, which behaves as apersistent radical.…”