Browsing by Author "Arhin, Grace"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    1, 3-Dipolar cycloaddition reactions of selected 1,3-dipoles with 7-isopropylidenenorbornadiene and follow-up thermolytic cleavage: Acomputational study
    (Elsevier Inc., 2019-08-08) Arhin, Grace; Adams, Anita Houston; Opoku, Ernest; Tia, Richard; Adei, Evans
    The mechanism, regio-, stereo-, and enantio-selectivities of the 1,3-dipolar cycloaddition reactions of7-isopropylidenenorbornadiene (DENBD) with nitrones and azides to form pharmaceutically relevantisoxazolidine and triazole analogues have been studied computationally at the M06/6-31G(d), 6-31G(d,p), 6-311G(d,p), 6e311þþG(d,p) and M06-2X/6-31G(d) levels of theory. In the reactions of DENBDwith phenyl nitrones, the cycloaddition steps have low activation barriers, with the highest being 16 kcal/mol; and the Diels-Alder cycloreversion steps have generally high barriers, with the lowest being 20 kcal/mol, suggesting that the isolable products in these reactions are the bicyclic isoxazolidine cycloadductsand not the thermolytic products. This is in contrast to the reactions of DENBD with phenyl azide wherethe isolable products are predicted to be the thermolytic products since the Diels-Alder cycloreversionsteps had relatively lower activation barriers. Electron-donating substituents on the dipolarophile sub-strate favour attack of the nitrone on the least hindered side of the DENBD substrate while electron-withdrawing substituents on the dipolarophile substrate favour attack on the more hindered side ofthe DENBD, indicating that site-selectivity is affected by nature of substituents. Global reactivity indicescalculations are in good agreement with the activation barriers obtained. Analysis of the electrophilic(PþKÞand nucleophilic (P KÞParr functions at the reactive centres reveal that the cycloaddition occursbetween atoms with the largest Mulliken and NBO atomic spin densities which agrees well with theenergetic trends and the experimental product outcomes.
  • Thumbnail Image
    Item
    Site‑, enantio‑ and stereo‑selectivities of the 1,3‑dipolar cycloaddition reactions of oxanorbornadiene with C,N‑disubstituted nitrones and dimethyl nitrilimines: a DFT mechanistic study
    (Springer-Verlag GmbH Germany, 2020-01-01) Opoku, Ernest; Arhin, Grace; Pipim, George Baffour; Adams, Anita Houston; Tia, Richard; et. al
    1,3-Dipolar cycloaddition of nitrones to oxanorbornadienes is an important method for the enantioselective synthesis of highly substituted 5-membered heterocycles such as furans and isoxazolidines, which have high utility in the chemical and pharmaceutical industries. The mechanism of the reaction and the effects of substituents on the (3 + 2) cycloaddition reactions (32CA) of C,N-dialkyl nitrones with a series of substituted oxanorbornadienes have been studied with focus on the site-selectivity (attack on the more substituted double bond of the oxanorbornadiene derivatives versus attack on the less substituted double bond), enantioselectivity and stereo-selectivity using density functional theory calculations at the M06/6-311++G(d,p) of theory. The results showed that the addition step to form the bicyclic isoxazolidines cycloadducts has generally low barriers compared to the cycloreversion step which converts the cycloadducts into furans and monocyclic isoxazolidines. Generally, electron-withdrawing substituents favour the nitrone attack on the highly substituted double bond, while electron-donating substituents favour the attack on less substituted double bond. The R enantiomers are generally favoured over the S enantiomers, and exo stereo-isomers are generally favoured over the endo stereo-isomers, irrespective of substituents.