Shimizu, Yohei; Shi, Shi-Liang; Usuda, Hiroyuki; Kanai, Motomu; Shibasaki, Masakatsu. Catalytic Asymmetric Total Synthesis of ent-Hyperforin. Angewandte Chemie, International Edition (2010), 49(6), 1103-1106, S1103/1S1103/75. Chiral bisoxazolidinone ligands (BOX ligands) Diels Alder Reaction The Diels Alder Reaction constitutes a very powerful method for the generation of a six membered ring. A wide variety of dienes and dienophiles are possible. Most commonly, the dienophile possesses an electron withdrawing group, as shown in the examples below. MOM ethers as protecting groups for alcohols MOM = Methoxymethyl LDA = lithium diisopropylamide, Diisopropylamine pKa = 36 HMPA = hexamethylphosporamide A polar solvent Isoprene The Claisen Rearrangement Like the Cope Rearrangement, this is an electrocyclic process, categorized as a 3,3-sigmatropic rearrangement Hydroboration-oxidation sequence accomplishes antiMarkovnikov addition of water to the carbon-carbon double bond Link Disiamylborane is a very hindered organoborane, with high selectivity for the terminal position of a terminal double bond. CSA = camphorsulfonic acid, pKa = 1.2 Markovnikov’s Rule The regioselectivity of the Markovnikov Rule is caused, mechanistically, by the tendency to form the more stable carbocation, during the initial electrophilic addition to the double bond, as shown above. The Swern Oxidation Mechanism of the Swern Oxidation Reagents which result in an ‘activated’ form of DMSO Hoveyda-Grubbs 2nd generation catalyst =