π‐Strain‐Induced Electrophilicity in Small Cycloalkynes: A DFT Analysis of the Polar Cycloaddition of Cyclopentyne towards Enol Ethers

Abstract

Small cycloalkynes possess a π‐strain‐induced electrophilicity related to the bending of the C sp 3–Csp–Csp bond angle. For cyclopentyne and benzyne, the electrophilicity index defined in the context of density functional theory gives a coherent rationale for the reactivity of these cycloalkynes, which may act as electrophiles in polar cycloaddition reactions toward enol ethers. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Strain‐Promoted Reactivity of Alkyne‐Containing Cycloparaphenylenes

“…Tw ot rends can be observed regarding the intensity and the position of the Raman active band associated with the alkyne vibration. [42] Aparticularly instructive comparison can be drawn between the smallest known [5]CPPA( Ø1 0.7 , ṽ CC 2202 cm À1 ) [43] and 1 (Ø 10.3-10.8 , ṽ CC 2182 cm À1 ), where the shift to lower wavenumbers is reflecting the significant amount of strain stored in the alkyne unit of 1. [42] Aparticularly instructive comparison can be drawn between the smallest known [5]CPPA( Ø1 0.7 , ṽ CC 2202 cm À1 ) [43] and 1 (Ø 10.3-10.8 , ṽ CC 2182 cm À1 ), where the shift to lower wavenumbers is reflecting the significant amount of strain stored in the alkyne unit of 1.…”

“…[2] Astraightforward way to distort aC Ctriple bond is to incorporate it into asufficiently small cyclic structure,w hich reduces the p-orbital overlap and, in turn, increases its reactivity in synthetic transformations. [3][4][5] This fundamental principle has found widespread application in organic syntheses,a sb est exemplified by its most paradigmatic representative,1 ,2-didehydrobenzene ( Figure 1). [6] Theaptitude of angle-strained alkynes to serve as convenient reactants in selective conversions is thereby decisively governed by the delicate interplay between their stability and reactivity.A ccordingly,i nt he series of strained cycloalkynes-a classical textbook example in organic chemistryparticularly the smaller ring-size members,c yclopentyne, [7] -hexyne, [8] and -heptyne [9] are characterized by their fleeting lifetimes.T his instability impedes their isolation and, thus, these compounds could only be exploited through in situ generation under precisely controlled reaction conditions.…”

“…[6] Theaptitude of angle-strained alkynes to serve as convenient reactants in selective conversions is thereby decisively governed by the delicate interplay between their stability and reactivity.A ccordingly,i nt he series of strained cycloalkynes-a classical textbook example in organic chemistryparticularly the smaller ring-size members,c yclopentyne, [7] -hexyne, [8] and -heptyne [9] are characterized by their fleeting lifetimes.T his instability impedes their isolation and, thus, these compounds could only be exploited through in situ generation under precisely controlled reaction conditions. [3][4][5]10] In contrast, the larger ring size of cyclooctynes-the smallest cycloalkyne that can be isolated [11] -offers an ideal playground to adjust the photophysical and chemical properties by molecular design. Hence,structurally modified versions of the cyclooctyne scaffold, such as DIFO, [12] DIBO, [13] and DIBAC (Figure 1), [14] emerged as promising tools for bioorthogonal chemistry [15] after cyclooctynes were shown to undergo SPAACreactions in biological media.…”

A molecular electron density theory study of the [3 + 2] cycloaddition reaction of nitrones with strained allenes

“…2,5 Note that pseudoradicals are closed-shell species topologically characterised by the presence of at least one V(C) monosynaptic basin integrating less than 1.0e at one carbon atom. 6 Unlike arynes and cyclic alkynes, whose structure and reactivity have been widely studied, [1][2][3]7 highly strained allene species have been studied to a much lesser extent. Since 1966, when Wittig reported, for the rst time, the existence of 1,2-cyclohexadiene (CHDE) 10, 8 the chemistry of this highly strained species has received little attention especially compared to its aryne and alkyne counterparts.…”

Comprehensive DFT Study on Site‐, Regio‐, and Stereoselectivity of Diels–Alder Reactions Leading to 5‐Hydroxybenzofurans

“…[3,4] These conceptual DFT-based descriptors have been successfully applied to interpret reactivity or site-selectivity in different cycloaddition reactions. [5] For the reactions shown in Scheme 1, for instance, we demonstrated that the local electrophilicity (ω k ) and nucleophilicity (N k ) can be used to explain the observed regioselectivity. [6] More recently we studied the regio-and stereoselectivity of the same series of DA reactions using some global reac- and stereochemistry were analyzed in detail.…”