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Steric Effects in the Tuning of the Diastereoselectivity of the Intramolecular Free-Radical Cyclization to an Olefin As Exemplified through the Synthesis of a Carba-Pentofuranose Scaffold

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journal contribution
posted on 17.08.2012, 00:00 by Mansoureh Karimiahmadabadi, Sayeh Erfan, Andras Földesi, Jyoti Chattopadhyaya
Two free-radical cyclization reactions with the radical at the chiral C4 of the pentose sugar and the intramolecularly C1-tethered olefin (on radical precursors 8 and 17) gave a new diastereospecific C4–C8 bond in dimethylbicyclo[2.2.1]­heptane 9, whereas the new C4–C7 bond in 7-methyl-2-oxabicyclo[2.2.1]­heptanes 18a/18b gave trans and cis diastereomers, in which the chirality of the C4 center is fully retained as that of the starting material. It has been shown how the chemical nature of the fused carba-pentofuranose scaffolds, dimethylbicyclo[2.2.1]­heptane 9 vis-a-vis 7-methyl-2-oxabicyclo[2.2.1]­heptanes 18a/18b (C7-Me in the former versus 2-O- in the latter), dictates the stereochemical outcome both at the Grignard reaction step as well as in the free-radical ring-closure reaction. The formation of pure 1,8-trans-bicyclo­[2.2.1]­heptane 9 from 8 suggests that the boat-like transition state is favored due to the absence of steric clash of the bulky 1­(S)-O-p-methoxybenzyl (PMB) and 7­(R)-Me substituents (both in the α-face) with that of the 8­(R)-CH2 radical in the β-face. The conversion of 1718a-7­(S) and 18b-7­(R) in 6:4 ratio shows that the participation of both the chair- and the boat-like transition states is likely.