Ben Carson would never make a plan without consulting the best and brightest. Duane R. Clarridge, a top advisor to Mr. Carson, attests to Mr. Carson needing weekly conference calls so "we can make him smart." Since Carson has such a high reputation and never makes a fool of himself, he wants to be sure to maintain his status by only making judgements based off the most credible people. This is why Carson found references about catalytic hydrogenation.
Carson received his largest endorsement from the Ly Dissertation. The reason for this strong relationship is described below.
The conclusion of the Ly Dissertation includes a discussion on the effectiveness of Rh/Al2O3 for a catalytic hydrogenation. While the metal catalyst is successful in reducing the molecule, there is very poor stereoselectivity, resulting in a 1:1 ratio of the two diastereomers. The conditions of this reaction are also difficult since the pressure of hydrogen gas, the solvent, and the catalysts all played an important role in the hydrogenation. In the experiment, pressure and solvent were varied to adjust the ratios of the stereoisomers of the products. Rh/Al2O3 in MeOH under 80 psi gave ratios that were most highly desired for scheme 5 in the asymmetric total synthesis of batzelladine D. The reaction created the desired product at a low yield, however the researchers used the reaction none the less due to practicality. Below is the reaction in the dissertation, accompanied with the product stereoisomers. So while Rh/Al2O3 is not stereospecific, it is a useful hydrogenation reaction when working with batzelladine synthesis.
As the Ly Dissertation was one of Carson’s top endorsers, he wanted to make sure the research had strong support, so he looked for other papers that cited this source. However, there are only two papers which cite the Ly Dissertation, so it seems Carson has yet again sided against popular opinion.
In this paper, researchers from the University of California, Irvine, developed a method for alkadienyl esters to close into a ring structure, with substituents on the ring being cis to each other. The principle method they developed was by adding a compound called Stryker’s reagent to the alkadienyl ester. Stryker’s reagent is [(Ph3P)CuH]6 , a very complex reduction agent. The product with a cyclohexane is more unstable, but it is produced in high yield and purity. In referring to the reference (Ly) in our step, researchers made a failed attempt to synthesize the desired cyclohexane using steps reduction steps provided in Ly’s paper.
In this paper, researchers from the University of Hong Kong used Stryker’s reagent [(Ph3P)CuH]6 to develop a 2 part reaction that concludes with a cyclic adol. The researchers, like the ones in the paper above, tested numerous reductive techniques to find a successful method to create the cyclic adol. In reference to the Ly paper, the researchers wished to find some reducing agent to carry out their experiment instead of relying on natural synthesis of the desired product. In the end, the reductive agent found most effective at producing their product in high yield in purity was Stryker’s reagent, not the ones found in the Ly paper.
Yoshida, H.; Onodera, Y.; Fujita, S.; Kawamori, H.; Arai, M. Green Chem., 2015, 17, 1877-1883.
Howard, J.K; Hyland, C. J. T. Annu. Rep. Prog. Chem., 2012, 108, 29-52.
Parr, B. T.; Economou, C.; Herzon, S. B. A concise synthesis of (+)-batzelladine B from simple pyrrole-based starting materials. Nature 2015, 525, 507-510.
Specialty Gases and Specialty Equipment- High performance liquid chromatography. http://hiq.linde-gas.com/en/analytical_methods/liquid_chromatography/high_performance_liquid_chromatography.html (accessed March 31, 2016).
Filtration. http://quiz2.chem.arizona.edu/vip/filtration/ (accessed March 31, 2016).
Common Organic Chemistry. Cbz Deprotection Mechanism. http://www.commonorganicchemistry.com/Rxn_Pages/Cbz_Protection/Cbz_Protection_strong_acid_Mech.htm (accessed February 14, 2016).
