ChemInform Abstract: A Catalytic Diastereoselective Formal [5 + 2] Cycloaddition Approach to Azepino[1,2‐a]indoles: Putative Donor‐Acceptor Cyclobutanes as Reactive Intermediates.

Abstract

Alkyl‐substituted terminal double bonds [e.

Influence of Ring Strain and Bond Polarization on the Ring Expansion of Phosphorus Homocycles

“…A 31 P NMR spectrum of the reaction mixture containing equimolar amounts of i PrNC and [4F][OTf] (Scheme 9c) showed signals due to unreacted [4F] + , 10, t BuPF 2 (δ 31 P = 228.0 ppm, δ 19 F = −109.8 ppm, 1 J PF = 1180 Hz), 66 2, [11] + , and one unidentified set of resonances (Figure 7c). The identity of [11] + was established on the basis of its AGMX spin system, the most telling feature of which was the 16-line pattern for the quaternary phosphorus center due to coupling to one fluorine ( 1 J PF = 1201 Hz) and three unique phosphorus environments ( 1 J PP = 513 Hz, 2 J PP = 13 Hz, 3 J PP = 63 Hz). A 19 F NMR assay showed the expected eight-line pattern ( 1 J PF = 1201 Hz, 2 J PP = 48 Hz, 3 J PP = 16 Hz).…”

“…4 In contrast, derivatives functionalized with vicinal donor−acceptor groups (III and IV, Scheme 1, top) have polarized bonds and, consistent with expectation of a lower barrier for C−C heterolysis, a rich ring-opening and expansion chemistry exists for the archetypal organic frameworks III and IV that is inaccessible to I and II. For example, while cyclopropane and cyclobutane are both unreactive toward dipolar substrates, a vast array of cycloaddition reaction have been reported between donor−acceptor functionalized cycloalkanes and 1,2-dipoles (e.g., nitriles, 5−8 nitrosyls, 9,10 ketones, 11 aldehydes 12 ), permitting the rapid assembly of complex four-, five-, and six-membered heterocycles. 3,13 In these reactions, donor−acceptor functionalized strained cycloalkanes behave as masked dipoles whose reactivity is analogous to that of canonical dipoles like the azide anion.…”

Calcium-Catalyzed Formal [5 + 2] Cycloadditions of Alkylidene β-Ketoesters with Olefins: Chemodivergent Synthesis of Highly Functionalized Cyclohepta[b]indole Derivatives

“…Previously reported [4 + 3] cycloaddition reactions utilized in situ generated highly reactive intermediates such as indolyl carbocations, 13a,d,e,h oxyallyl cations, 13f and metal carbe- Toward this end, we sought an approach to the cyclohepta- [b]indole core inspired by our report on the formal [5 + 2] cycloaddition of N-indolyl alkylidene β-amide esters with substitued olefins and to form azepino[1,2-a]indoles (Scheme 1). 15 The Lewis-acid-catalyzed reaction proceeds through a putative cyclobutane intermediate (via formal [2 + 2] cycloaddition) that undergoes Friedel−Crafts-type ring-opening cyclization to form the azepinoindole. Choice of the Lewis acid catalyst determines the extent of the [5 + 2] vs [2 + 2] pathways.…”

“…Alkylidene 2a, which is readily accessible in two steps from commercially available 1-methylindole-2-carboxylic acid, was selected as the model substrate (Table 1). To probe the formal [5 + 2] reaction, 15 α-methylstyrene (3a) was chosen as the reactive partner. Given its effectiveness in the azepinoindole system, 10 mol % of Sc(OTf) 3 was initially screened, providing 51% yield of 4aa as a complex keto−enol mixture when the reaction was performed at room temperature in CH 2 Cl 2 (entry 1).…”

“…It is important to note that the cyclobutane was never detected under any of the reaction conditions, which is in sharp contrast with the azepino system. 15 To ensure that the catalysis is due to the calcium−additive complex and not from its individual components, a series of control reactions were conducted. Performing the reaction without the additive, n-Bu 4 NPF 6 , afforded no desired product (entry 13).…”