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The reduction of (5S)-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene was optimized for diastereoselectivity and overall conversion to (2S,3S,5S)-5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane (2a). A two-step reduction sequence is described wherein the enamine is reduced with a borane-sulfonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a was obtained with 84% diastereoselectivity and an acyclic 1,4 stereoinduction ratio of 14:1. This methodology has been used to produce multikilogram quantities of the diamino alcohol core of Ritonavir and should be general to the synthesis of related diamino hydroxyethylene isosteres.

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Two continuous apparatuses were designed that are capable of safely scaling the highly energetic ozonolysis reaction to multikilogram scale where flow chemistry allowed excellent temperature control and minimized the inventory of the highly unstable ozonide intermediate. First, a continuous stirred tank reactor was developed and proven capable of generating product at a rate of 77 mmol of product per hour while maintaing <46 mmol of ozonide. Then, a larger-scale continuous bubble reactor was designed to deliver 770 mmol of product per hour while maintaing 950 mmol of ozonide present at any given time, and the latter was utilized to deliver 2.5 kg of product. The development of these reactors relied on careful evaluation of the thermal stability and heat of reaction of ozonolysis using computational chemistry and calorimetric measurement. In addition, the reactor design benefited from in situ ATR/FTIR monitoring of the rate of ozonolysis under nonflow conditions which allowed for the flow of substrate to be matched with ozone generation, enabling complete reaction of the alkene with minimal excess of ozone.

Hemicarcerand 1, whose synthesis from t w o tetrol bowls and four pentamethylene ditosylate molecules was templated b y veratrole, was found to bind in solution (one-to-one) eighteen different guests; the crystal structure of 104MeCN is centrosymmetric; hemicarcerand 2, containing four hexamethylenedioxy groups, is also discussed.