Ambivalent Reactivity Modes of β‐Chlorovinyl Ketones: Electrophilic Lithium [3]Cumulenolates from Soft Vinyl Enolization Strategy

Abstract

The orthogonal arrangement of cumulated double bonds has attracted a great deal of attention from the scientific community since the first allene was prepared by Burton and von Pechmann in 1887. [1] The selection of substituents having a different electronic nature allows the ambivalent reactivity of allenes towards nucleophilic as well as electrophilic reagents with controlled regio-and stereoselectivity. [2,3] Thus, donor/acceptor-substituted allenes have emerged among the most versatile synthetic building blocks in the development of novel carbon-carbon bond-forming reactions (Scheme 1). In contrast, the reactivity behavior of [n]cumulene derivatives, compounds with three or more consecutive double bonds, has not been fully explored because of the difficulty associated with their preparation other than tetrasubstituted [3]cumulene derivatives. [4] While a limited number of acyl-substituted [3]cumulene derivatives are known to be stable [5] and subsequently utilized in the enyne cycloaddition, [6] palladium-catalyzed arylation, [7] Lewis acid catalyzed Diels-Alder reactions, [8] phosphine- [9] and silvercatalyzed [3+2] cycloaddition reactions, [10] the synthesis as well as synthetic utility of donor-substituted [3]cumulene derivatives have yet to be established. [11] Recently, we reported a facile a-vinyl enolization pathway of (E)-b-chlorovinyl ketones in which transient oxy-substituted [3]cumulene derivatives [i.e., cumulenol(ate)s] were postulated as nucleophilic species, reacting either with a protic source [12] or aldehydes [13] (Scheme 2). Drawn by the possibility of investigating the ambivalent reactivity modes of donor-substituted [3]cumulene derivatives, we envisioned a reaction of in situ generated [3]cumulene derivatives with nucleophiles. Herein, we report an electrophilic reactivity mode of oxy-substituted [3]cumulene derivatives in the syntheses of vinyl allenones and 3-methylenepyrrolidines with excellent stereoselectivities.During the course of our investigation into the nucleophilicity of b-chlorovinyl ketones, we observed the formation of the aldol product 2 a as well as the vinyl allenone 3 a under the influence of lithium salts (Table 1). [13] While 3 a was obtained with a low yield of 15 %, we were particularly encouraged by the fact that 3 a, a trisubstituted alkene, was formed stereoselectively. To optimize the formation of 3 a, we Scheme 1. Known and proposed reactivity patterns of functionalized allenes and [3]cumulenes. Scheme 2. Ambivalent reactivity modes of in situ generated oxy-substituted [3]cumulenes.

Domino Staudinger/aza‐Wittig/Mannich Reaction: An Approach to Diversity of Di‐ and Tetrahydropyrrole Scaffolds

“…[11] It is remarkable that isothiocyanates 7 and carbon disulfide 8 react with azides 1 at room temperature, whereas aldehydes, being more reactive carbonylc ompounds, requireh eating. [15] In the discussed reaction, the intramolecular proton transfer (see Scheme 5) ensures the aforementioned polarization as well as increasing the nucleophilicity of the malonate moiety. For intermediate 10,t his is ad isfavored 5-endo-trig process, whereas for the corresponding intermediates in the PPh 3 -initiated reactiono f1 with isothiocyanates 7 or carbon disulfide 8, Scheme5.Proposed mechanism for the formationo fpyrrolidines 2. the rate-limiting step is af avored 5-exo-trig cyclization.…”

“…Nevertheless, it is knownt hat the significant polarization of ad ouble bond raises the possibility of a5 -endo-trig cyclization. [15] In the discussed reaction, the intramolecular proton transfer (see Scheme 5) ensures the aforementioned polarization as well as increasing the nucleophilicity of the malonate moiety.…”

Direct Regioselective [3 + 2]-Cyclization Reactions of Ambivalent Electrophilic/Nucleophilic β-Chlorovinyl Dithianes: Access to Cyclopentene Derivatives

“…In terms of the reactivity modes, these studies allow the ambivalent reactivity of α,β-unsaturated carbonyl compounds toward electrophiles as well as nucleophiles with controlled stereoselectivity (Scheme ). More recently, Oh and co-workers have disclosed the nucleophilic and electrophilic reactivity modes of β-chlorovinyl ketones in the development of novel C–C bond forming reactions . It revealed a soft vinyl enolization strategy of β-chlorovinyl ketones in which oxy-substituted [3]­cumulene derivatives as nucleophilic species reacted with a protic source or aldehydes, and the ambivalent electrophilic reactivity mode with ketimine esters via a formal [3 + 2] cycloaddition pathway…”

Dithiane Induced Cycloaddition/Aromatization Tactic for the Synthesis of Multisubstituted Furans

“…This unique investigation provided a proof of principle for vinylidene dithiane as a reactive acceptor/donor intermediate induced coupling reaction. However, Oh group recently disclosed a mild base-promoted vinylogous aldol-type reaction of β-chlorovinyl ketones through an allenol/cumulenol­(ate) intermediate (Scheme , eq 3) . However, to the best of our knowledge, direct additions of β-chloro-vinyl dithianes to aldehydes are unknown; the synthetic versatility of vinylidene dithiane as a donor allene has scarcely been studied .…”