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

Shelp, Russell A.; Walsh, Patrick J.

doi:10.1002/ange.201810061

Cited by 29 publications

(10 citation statements)

References 32 publications

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“…Our team [62][63][64][65][66][67][68][69][70] and other groups [71][72][73][74][75][76][77][78][79][80][81][82][83][84] have been interested in the functionalization of 2-azaallyl anions through an umpolung strategy. Recently, we discovered and developed a unique radical generation approach 85 for the transition-metal-free C(sp 3 )-C(sp 2 ) (Fig.…”

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confidence: 99%

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms

et al. 2021

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Allylation of nucleophiles with highly reactive electrophiles like allyl halides can be conducted without metal catalysts. Less reactive electrophiles, such as allyl esters and carbonates, usually require a transition metal catalyst to facilitate the allylation. Herein, we report a unique transition-metal-free allylation strategy with allyl ether electrophiles. Reaction of a host of allyl ethers with 2-azaallyl anions delivers valuable homoallylic amine derivatives (up to 92%), which are significant in the pharmaceutical industry. Interestingly, no deprotonative isomerization or cyclization of the products were observed. The potential synthetic utility and ease of operation is demonstrated by a gram scale telescoped preparation of a homoallylic amine. In addition, mechanistic studies provide insight into these C(sp3)–C(sp3) bond-forming reactions.

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confidence: 99%

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms

et al. 2021

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“…Instead, 2,5‐dihydro‐1 H ‐imidazole [18] 6 ab was obtained with a 39% yield (Scheme 1b). We hypothesized that this 5‐membered ring arose from a [3+2] cycloaddition between the ketenimine and the semi‐stabilized 2‐azaallyl lithium 5 b , which was also formed in situ under the basic reaction conditions [19,20] . Overall, reports of 1,3‐dipolar cycloaddition with a ketenimine as the dipolarophile remain rather scarce [21–25] .…”

Section: Methodsmentioning

confidence: 99%

“…We hypothesized that this 5-membered ring arose from a [3+2] cycloaddition between the ketenimine and with semi-stabilized 2-azaallyl lithium 5b, which was also formed in situ under the basic reactions conditions. 11,12 Overall, reports of 1,3 dipolar cycloaddition with a ketenimine as the dipolarophile remain rather scarce. [13][14][15] Moreover, [3+2] cycloadditions with non-or semi-stabilized azallylanions 16,17 were mostly developed with olefins as the dipolarophiles.…”

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Base‐Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions

et al. 2021

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Under basic conditions and heat, ynamides can serve as precursor to ketenimines, whose synthetic potential is often hampered by their difficulty of acces. Herein, we report that they can undergo a [3+2] cycloaddition with 2-azaallyl anions, obtained from benzylimines under the same reaction conditions. This reaction between two highly reactive intermediates, both generated in situ from bench stable starting materials, gives access to various nitrogen-rich heterocycles. The reaction usually proceeds with excellent diastereoselectivity, in favor of the cis adduct. Deuteration experiments and DFT calculation helped rationalize the regio and stereo-selectivity of the process as well as the formation of side-products..

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“…BCPs are also useful motifs for organic materials, including rod-like 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] and anionic [21][22][23][24][25] intermediates (Figure 1b). Limitations nonetheless remain, in particular due to the surprisingly harsh reaction conditions often required for these processes, which can restrict functional group tolerance.…”

Section: Introductionmentioning

confidence: 99%

“…22,27 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 valuable insight to support reaction development. [15][16][17]24,25 However, no in-depth theoretical analysis has tackled the origin of the omniphilic reactivity of 1.…”

Section: Introductionmentioning

confidence: 99%

Rationalizing the diverse reactivity of [1.1.1]propellane through sigma-pi-delocalization

Sterling¹,

Dürr²,

Smith³

et al. 2020

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<p>[1.1.1]Propellane has gained increased attention due to its utility as a precursor to bicyclo[1.1.1]pentanes (BCPs) – motifs of high value in pharmaceutical and materials research – by addition of nucleophiles, radicals and electrophiles across its inter-bridgehead C–C bond. However, the origin of this broad reactivity profile is not well-understood. Here, we present a comprehensive computational study that attributes the omniphilicity of [1.1.1]propellane to a moldable, delocalized electron density, characterized by the mixing of the inter-bridgehead C–C bonding and antibonding orbitals. Reactions with anions and radicals are facilitated by stabilization of the adducts through sigma-pi-delocalization of electron density over the cage, while reactions with cations involve charge transfer that relieves Pauli repulsion inside the cage. These results provide a unified framework to rationalize propellane reactivity, opening up opportunities for the exploration of new chemistry of [1.1.1]propellane and related strained systems. </p>

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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.

Cited by 29 publications

References 32 publications

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms

Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms

Base‐Mediated Generation of Ketenimines from Ynamides: [3+2] Annulation with Azaallyl Anions

Rationalizing the diverse reactivity of [1.1.1]propellane through sigma-pi-delocalization

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