Subsequent treatment with lithium hexamethyldisilazide (LiHMDS) and TMSCl gave the TMS-protected silyl enol ether, which was immediately subjected to an acetic acid- (HOAc) pyridine- (Py) buffered Rubottom oxidation before acidic hydrolysis to afford 2S-hydroxymutilin. This highly optimized sequence features two important aspects. First, the authors originally generated the silyl enol ether using triethylamine, which gave a mixture of the desired kinetic product, (shown below) the undesired thermodynamic product, and hydrolysis back to mutilin. The authors blamed the formation of the acidic triethylammonium (pKa = 10.6) byproduct for the undesired side products and remedied this by using the LiHMDS to exclusively form the desired kinetic product with no acid-catalyzed side reactions due to the significantly lower acidity of the protonated product (pKa = 26). Second, while oxidation occurred from the desired convex face of the silyl enol ether, the authors saw a significant number of overoxidation products that they attributed to the stability of the oxocarbenium ion intermediate under sodium bicarbonate buffered conditions. They hypothesized that the increased lifetime of the intermediate species would allow for over oxidation to occur. After a significant amount of optimization, it was found that an HOAc/Py buffer trapped the oxocarbenium intermediate and prevented overoxidation to exclusively give 2S-hydroxymutilin after hydrolysis of the silyl protecting groups. Ovalicin, fumagillin, and their derivatives exhibit strong anti-angiogenesis properties and have seen numerous total syntheses since their isolation. Corey and Dittami reported the first total synthesis of racemic ovalicin in 1985 followed by two asymmetric syntheses reported in 1994 by Samadi and Corey which featured a chiral pool strategy from L-quebrachitol and an asymmetric dihydroxylation, respectively. In 2010, Yadav and coworkers reported a route that intercepted the Samadi route from the chiral pool starting material D-ribose. A standard Rubottom oxidation gives a single stereoisomer due to substrate control and represents the key stereogenic step in the route to the Samadi ketone. Once synthesized, the Samadi ketone could be elaborated to (−)-ovalicin through known steps. Velutinol A was first synthesized by Isaka and coworkers. The authors show that the high regioselectivity of this reaction is directed by the hydroxyl group syn to the ring-fusion proton. Reactions where the stereochemistry of the hydroxyl group is inverted saw lower regioselectivity, and removal of the hydroxyl group gave the exclusive formation of the other regioisomer. It is likely that the close proximity of the hydroxyl group in the syn isomer acidifies the ring-fusion proton