Regioselectivity in the ring-opening β-scission of 2-phenyl-1,3-dioxan-2-yl radicals derived from bicyclic benzylidene acetals

Methodology Development and Physical Organic Chemistry: A Powerful Combination for the Advancement of Glycochemistry

“…This limitation is most apparent in the synthesis of the 6-deoxy-β-mannosides, otherwise known as the β-rhamnosides, 67b,69e,86 a class of glycosides that are commonly found, in the form of either enantiomer, in bacterial capsular and lipopolysaccharides. We considered that the use of a 4,6- O -benzylidene protected donor followed by regioselective deoxygenation after β-selective glycosylation, by a modification of either the Hanessian-Hullar 87 or the Roberts’ 88 acetal fragmentation chemistries, would be a suitable way to address this problem. We devised a method based on earlier work 89 for the generation of a benzylidene centered radical by a cascade of reactions beginning with cyclization of a stannane-generated aryl radical onto the sulfur center of a thioester followed by loss of carbon monoxide.…”

“…90 Once the benzylidene radical is accessed it undergoes highly selective contrathermodynamic fragmentation of the primary C6-O6 bond (rather than of the secondary C4-O4 bond), because of a less-strained transition state as explained by Roberts, to bring about the required regioselective deoxygenation. 88 Following cleavage of the chloroacetate ester from 39 the method was applied to the saccharide 40 to give a trisaccharide 41 containing both an α- and a β-D-rhamnopyranoside (Scheme 14). 82 …”

Regioselective Ring Opening of 1,3‐Dioxane‐Type Acetals in Carbohydrates

“…Finally, quenching of this radical leads to the regeneration of the TIPST radical. Although the primary radical seems unstable, calculations have shown that this scission can occur due to a combination of differences in thermodynamic driving forces and charge‐transfer stabilization in the transition state . For a trans ‐decalin‐conformation, such as glucoside 159 , an additional determining factor is its rigid bicyclic conformation.…”

Regioselective synthesis of indole-annulated sulfur heterocycles by tri-n-butyltin hydride-mediated aryl radical cyclization

“…However, there is no report on the radical cyclization containing sulfur heterocycles. We have successfully synthesized quinolone and coumarinannulated [6,6] fused sulfur heterocycles (3a,b) by Bu 3 SnH-mediated radical cyclization where a small amount of β-scission (5) product was formed along with 6-endo cyclization. However, when a highly electron-withdrawing SO 2 group is attached to the radical center, it confers considerable stability (lower energy of the singly occupied molecular orbital [SOMO]) to the intermediate radical and prevents the β-scission with an increase in the product yield.…”