Mechanistic Duality in Tertiary Amine Additions to Thermally Generated Hexadehydro-Diels–Alder Benzynes

Abstract

Reported here are studies directed at understanding the mechanism of tertiary amine addition to hexade-hydro-Diels-Alder (HDDA)-generated benzynes. Tertiary amines are presumed to engage benzynes by generation of a zwitterionic intermediate. Simple trialkylamines undergo intermolecular protonation by a protic nucleophile to give an aryl ammonium intermediate that is then dealkylated. Amines containing acidified β-protons undergo an intramolecular elimination to give the aniline and an alkene. Finally, aminoalcohols react at either of their N- or O-atoms, depending upon the extent of internal hydrogen bonding.

Reactions of Diaziridines with Benzynes Give N-Arylhydrazones

“…Their reactions with diaziridines were observed to proceed with exclusive regioselectivity for the cases of 8a , 8e , and 8f ; mixtures of constitutional isomers were formed in each of the cases of 8b-d . These selectivities for nucleophilic addition to these benzynes are consistent with those expected either from (i) reported reactions with nucleophiles7 or (ii) the extent and direction of the computed distortion [DFT, Figure 3: 8a-c and f (see SI), 8d, 7a and 8e 7i ]. Distortion analysis has been used quite successfully to account for the strong preference for addition by a nucleophile at the more electrophilic, obtuse sp-center, which has a greater proportion of p-character.…”

Direct observation ofo-benzyne formation in photochemical hexadehydro-Diels–Alder (hν-HDDA) reactions

“…12 Instead of forming cyclohexene derivatives, the HDDA reaction [13][14][15][16] is believed to produce a highly reactive o-benzyne intermediate, and is of much current interest due to its unusual reactivity/mechanism [17][18][19][20][21][22][23][24][25][26][27] and numerous applications in synthetic chemistry. [28][29][30][31][32][33][34][35] A series of reports within the last three years, [36][37][38][39][40][41][42][43] examining the HDDA reaction from a more mechanistic viewpoint, demonstrate the immense versatility of HDDA-generated o-benzynes, including reaction with an alkyne forming a highly reactive benzocyclobutadiene 21 or reaction with electron-decient thioamides giving stabilized ammonium ylides in a new type of [3 + 2]-cycloaddition. 24 These and other examples emphasize the importance of HDDA-generated o-benzynes for the discovery of new reaction pathways.…”

Hexadehydro-Diels–Alder Reaction: Benzyne Generation via Cycloisomerization of Tethered Triynes

“…The mechanism by which tertiary amines trap an HDDA benzyne has been investigated (Figure 14b). 99 Shown here is the reaction of trioctylamine with the tetrayne substrate 122, which gives an ca. 1:1 mixture of products 123a and 124b.…”